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=THE AMERICAN JOURNAL OF ANATOMY=
 
=THE AMERICAN JOURNAL OF ANATOMY=
  
 +
EDITORIAL BOARD
  
THE AMERICAN JOURNAL
+
CHARLES R. BAUDEEN, University nf Wisco>ni)i.
  
OF
+
HENRY H. DONALDSON, Wistar Institute of Aiiatotiiy
  
ANATOMY
+
THOMAS DWIGHT, Harvard University
  
 +
JOSEPH MARSHALL FLINT, University of California.
  
 +
SIMON H. GAGE, Cornell University
  
EDITORIAI. BOARD
+
G. CARL HUBER, University of Michigan.
  
 +
GEORGE S. HUNTINGTON, Columbia University.
  
 +
FRANKLIN P. MALL, Johns Hopkins University
  
CHARLES R. BAUDEEN,  
+
J. PLAYFAIR McMURRICH,
  
Universitij nf Wisco>ni)i.  
+
University of Jfic/iiyaii.  
HENRY H. DONALDSON,
 
  
Wisiar Institute of Aiiatotiiy .  
+
CHARLES S. MINOT, Harvard University.
THOMAS DWIGHT,  
 
  
Harvard Univemitij.  
+
GEORGE A. PIERSOL, University of Pennsylvania.
JOSEPH MARSHALL FLINT,  
 
  
University of California.  
+
HENRY McE. KNOWER, Secuetary, Johns Hopkins University.
SIMON H. GAGE,
 
  
Cornell Universitij.
 
G. CARL HUBER,
 
  
University of Jlichiyan.
+
VOLUME V 1906
  
 +
THE AMERICAN JOURNAL OF ANATOMY BALTIMORE, MD., U. S. A.
  
 +
BALTIMORE, MD., V- 8. A.
  
GEORGE S. HUNTINGTON,
+
==CONTENTS OF VOL V==
  
Columbia University.  
+
===No. 1. December 1, 1905===
FRANKLIN P. MALL,  
 
  
Johns Hopkins University .  
+
I. John Warken. The Development of the Paraj^hysis and the Pineal liegion in Nectiinis Maculatus = 1 With 23 text figures.
J. PLAYFAIR McMURRICH,
 
  
University of Jfic/iiyaii.  
+
II. {{Ref-Bell1905}} With 3 plates and 5 text figures.
CHARLES S. MINOT,
 
  
Harvard University.  
+
III. Jeremiah 8. Ferguson. The Veins of the Adrenal.  G3 With 3 text figures.
GEORGE A. PIERSOL,
 
  
University of Pennsylvania.  
+
IV. George Walker. The Blood Vessels of the Prostate Gland 73 With 3 colored plates.
  
HENRY McE. KNOWER, Secuetaky,
+
V. {{Ref-Allen1905}} 9 With 1 double plate and G text figures.
  
Johns Hopkins University.  
+
VI. {{Ref-Lewis1905a}} With 8 text figures.
  
 +
VII. {{Ref-Lewis1905b}} With 1 text figure.
  
 +
===No. 2. May 31, 1906===
  
VOLUME V
+
{{Ref-Harrison1906}} With 5 figures.
J 906
 
  
 +
IX. Ai.i!i:i;t C. Eyclesiiymi:!; .-iiid James Meredith Wilson. The (lastnilation and I'iinbrvo Formation in Amia Calva 13;i With I (lonl.lc plalcs.
  
 +
{{Ref-McClure1906}} With 1 single and 4 double plates and 27 text figures.
  
THE AMERICAN JOURNAL OF ANATOMY
 
BALTIMORE, MD., U. S. A.
 
  
 +
LIST OF MEMBERS OF ASSOCIATION OF AMERICAN ANATOMISTS XXII-XXXII
  
 +
===No. 3. July 25, 1906===
  
 +
XI. {{Ref-Mall1906liver}} With 74 figures and 7 tables.
  
Zf)t fviiUnvoaii Company
+
XII. Albert C. Eycleshy'mer. The Development of Clnoma tophores in Necturus 309 With 7 figures.
  
BALTIMORE, MD., V- 8. A.  
+
XIII. Sidney Klein, S. M., ]\L D. On the Nature of the Granule Cells of Paneth in the Intestinal Glands of Mammals 315 With 5 figures.
  
 +
XIV. {{Ref-EdwardsHahn1906}} With 15 text figures.
  
 +
===No. 4. September 1, 1906===
  
/a ^»
+
XV. Robert Bennett Bean. Some Racial Peculiarities of the Negro Brain ... 353 With 16 fig-ures, 12 charts, and 7 tables.
  
 +
XVI. {{Ref-Mall1906bone}} With (1 text figures and 7 tables.
  
 +
XVII. {{Ref-Bremer1906}} With 16 text figures.
  
CONTENTS OF VOL V
+
XVIII. Charles R. Stockard. The Development of the Mouth and Gills in Bdellostoma Stouti 481-517 With 36 figures.
  
 +
XIX. PROCEEDIXGS OF THE AS80CIATI0X OF AMERICAN ANATOMISTS. NINETEENTH SESSION, August 6-10, 1905. TWENTIETH SESSION, Decemher 27, 28, and 29, 1905 I-XX
  
  
No. 1. December 1, 1905.
 
  
I. John Warken. The Developnicnt of the Paraj^hysis and
+
==The Development Of The Paraphysis And The Pineal Region In Necturus Maculatus==
  
the Pineal liegion in Nectiinis Maculatus .... 1
+
By
With 23 text figures.
 
  
II. E. T. Bell. The Development of the Thymus ... 39
+
John Warren.
With 3 plates and 5 text figures.  
 
  
III. Jeremiah 8. Ferguson. The A^eins of the Adrenal. . G3
+
Demonstrator of Anatomy, the Anatomical Laboratory, Harvard Medical
  
With 3 text figures.  
+
School.
  
IV. George Walker. The Blood Vessels of the Prostate
+
With 23 Text Figures.
  
Gland 73
+
The presence of the paraphysis in Necturns was noted by Prof. C. S. Minot in his article " On the Morphology of the Pineal Region, based on its Development in x'Vcanthias " (38), and a brief description of certain stages given. C. L. Herrick (15, PI. YIII, Fig. 1, 3, 4) gives a brief account of the adult paraphj'sis, and shows it in the above figures, vvlicre it is named " Preparaphysis." Osbom (31, PI. IV) shows th-e paraphysis in an adult brain in comparison with the brains of other amphibia. Kingsbury (21) describes briefly the adult paraphysis as well as a few of the earlier stages, and also gives an account of the epi))hysis and the plexuses. I have found, however, no detailed account of all the stages in the development of the paraphysis and the pineal region. This term is used here in the same sense as in Minot's article, quoted above.
  
With 3 colored plates.  
+
The greater part of the specimens studied for this article were taken from the Embryological Collection of the Harvard Medical School, and the numbers of each section used are given. Other specimens were prepared specially for this purpose. In some cases where the plane of section was uneven, two or more sections were used in drawing the figures ill order to show all the structures, which should appear in the uK^dian line.
  
V. Bennet M. Allen. The Emhryonic Development of the  
+
Fig. 1 is a median sagittal section through the brain of an einl)ryo of 8-9 mm. I am indebted to a colleague for the drawing of this section, as this stage is wanting in the collection. In the roof of the fore brain three arches are seen. From before backward these are the j)aia|)liysal arch, P. A., the post- velar arch, P. V. A., and the epiphysal arch, Ep. A. The first two are separated by the velum transversum. V, which marks the limit between the two subdivisions .of the fore brain. Hence the paraphysal arch belongs to the telencephalon, the other two to the
  
Pete-Cords and Sex-Cords of Chrysemys 79
+
2 Paraphysis and the Pineal Ees^ion in Necturns Maenlatus
  
Witli 1 doul)]e plate and G text figures.  
+
dieneephalon. The epiphysal are]i is homided l)y two angles, which represent the position of the future supra and posterior commissures. The velum transversum is a simple infolding of the brain roof, and consists of two distinct layers, one caudad and one cephalad, the space between them being filled by a loose mesenchymal tissue, which later contains numerous blood vessels. This figure is practically identical with Minot's figure of acanthias of the same stage (28, Fig. 1), and is, therefore, of great importance in showing the homologies of these parts in elasmobranchs and amphibians. It is probable, as Minot states, that these arches occur in most of the vertebrate series.
  
VI. Frederic T. Lewis. The Development of the Lymphatic
+
The term post-velar arch, introduced by Minot (28), is much better for purposes of description than the terms " zirbelpolster " of German writers, and the " dorsal sack " or " postparaphysis " of American authors.
  
System in Pabbits 95
 
  
With 8 text fi,gures.
 
  
VII. Frederic T. Lewis. The Development of the Veins in
 
  
the Limbs of Rabbit Embryos 113
 
  
With 1 text figure.
 
  
No. 2. May 31, 1906.
 
  
A'lTI. Poss Granvtllk IIarhison. Further Experiments on the
+
Fig. 1. Embryo of 8-9 mm. Sagittal section, X 63 diams.
  
Development of Peripheral Nerves 131
+
Fig. 2. Embryo of 10 mm. Harvard Embryological Collection, Sagittal Series, No. 269, Section 39, X 63 diams.
  
With 5 figures.
 
  
  
 +
Fig. 2 represents the roof of the dieneephalon and telencephalon of an embryo of 10 mm. The two layers of the velum are nearer together and in the region of the epiphysal arch are seen the first signs of the epiphysis, E. This structure is a small rounded diverticulum, which arises from the cephalic end of the arch. It is hollow and opens into the cavity of the fore brain.
  
iv Contciils
+
Fig. 3 is a similar section of an embryo of 12 mm. The velum is a trifle longer and the epiphysis a little larger than in the preceding figure. Immediately cephalad to the velum a very small evagination in the paraphysal arch can be seen, P. This is the first sign of the paraphysis, and it appears distinctly later than the epiphysis. The latter overlaps its short stalk both caudad and cephalad, and at this stage the stalk is still hollow, though its cavity was obliterated in this section.
  
IX. Ai.i!i:i;t C. Eyclesiiymi:!; .-iiid James Meredith Wilson.
 
The (lastnilation and I'iinbrvo Formation in Amia
 
  
C'alva 13;i
+
Fig. 4 is a section of an embryo of 13 mm. The velum is again a little longer and its caudal layer is now distinctly thinner than its cephalic layer. The paraphysis is now a well-marked narrow diverticulum extending dorsad from the paraphysal arch parallel to the velum. The paraphysal arch just cephalad to the opening of the paraphysis has been
  
With I (lonl.lc plalcs.
 
  
X. Charles F. W. McClure. A Contribution to the Anatomy
+
Fig. 3. Embryo of 12 mm. Harvard Embryological Collection, Sagittal Series, No. 49, Section 58, X 63 diams.
and Development of the Venous System of Didelpliys
 
Marsiii)ialis (L.)-— I'iH-t II. Development .... lOo
 
Willi 1 single and 4 double plates and 27 text fi2:ures.  
 
  
LIST OF MEMBERS OF ASSOCIATION OF AMERICAN ANATOMISTS XXII-XXXII
+
Fig. 4. Embryo of 13 mm. Harvard Embryological Collection, Sagittal Series, No. 598, Sections 71 and 75, X 63 diams.
  
 +
forced downward to a slight degree, as there is relatively more space between it and the ectoderm than in the previous figures. The epiphysis is about the same size as in Fig. 3, and its opening into the brain is clearly seen.
  
 +
Fig. 5 is a section of an embryo of 12A mm., which is, however, further advanced than that of Fig. 4. The velum, the post-velar arch, and the epiphy.sis are about the same, but the paraphysis is distinctly longer, and
  
No. 3. July 25, 190G.
 
  
XL Franklin P. Mall. A Study of the Structural Unit of
 
  
the Liver ^ 227
 
  
With 74 fio-ures and 7 tables.
 
  
 +
Fig. 5. Embryo of 12.4 mm. Harvard Embryological Collection, Sagittal Series, No. 675, Section 57, X 63 diams.
  
 +
Fig. 6. Same as Fig. 5, X about 120 diams.
  
XII. Albert C. Eycleshy'mer. The Development of Clnoma
+
has become a narrow tube. The brain roof cephalad to it has descended still more into the cavity of the telencephalon and the opening of the paraphysis is much nearer the tip of the velum. Fig. 6 is the same section as Fig. 5, only drawn on a higher scale to show the histological details. The walls of the paraphysis and "velum consist of a single layer of cells, with large oval nuclei and without very distinct cell boundaries.
tophores in Necturus 309
 
  
With 7 figures.
 
  
XIII. Sidney Klein, S. M., ]\L D. On the X^ature of the
+
These cells are, of course, continuous with tliose which form the brain wall in this region. The same is true of the epiphysis, but the walls seem thicker, as the organ has been cut somewhat obliquely. Close to the paraphysis two vessels can be seen, a larger one cephalad and a much smaller one caudad, _ F<?6'. The vessels lie in intimate relation to this structure, and it is important to note their relation at this early stage, because as development progresses the relation between paraphysis and blood vessels becomes more and more intimate.
  
Granule Cells of Paneth in the Intestinal Glands of  
+
Fig. 7 is a section of an embryo of 15 mm. The most striking feature here is the increase in size of the paraphysis. which has become a long tube with a lumen extending its entire length, and at its distal end a lateral diverticulum has appeared. The roof of the fore brain has now descended to such a degree that the opening of the paraphysis is on a level with the tip of the velum. The velum itself has lost its cephalic layer, and consists of one .layer only, which, however, is much longer than the velum in Fig. 5. If Figs 4, 5, and 7 are compared it will be seen that
  
Mammals 315
 
  
AVith .5 figures.
 
  
XIV. Charles L. Edwards and Clarence W. LTahn. Some
 
  
Phases of the Gastrulation of the Horned Toad, Phrynosoma Cornutum Harlan 331
+
Fig. 7. Embryo of 15 mm. Harvard Embryological Collection, Sagittal Series. No. 79, Sections 85 and 89, X 63 diams.
  
With 15 text figures.  
+
the distal end of the paraphysis is practically at the same distance from the ectoderm in each case. As the paraphysis has developed during those stages into a long tube, its growth must have occurred by a downward extension of the neighboring parts into the cavity of the fore brain. This is practically the same process described by Minot in Acanthias. It is also shown by the great increase in distance between the roof of the telencephalon and the ectoderm from Fig. 4 to Fig. 7. The opening of the paraphysis in Fig. 3 is nearly on a level with tlie base of the velum, and as the down growth of the parts takes place the opening of the paraphysis and the paraphysal arch descend, apparently pushing the cephalic layer of the velum ahead of them. Therefore the single layer of the velum in Fig. 7 really corresponds to the original caudal layer, plus the cephalic layer, which has been forced down ahead of the opening of the paraphysis.
  
No. 4. September 1, 1906.
+
In stud5ing Fig. 7 it might seem as if the posterior wall of the paraphysis corresponded to the cephalic layer of the velum. This, however, is
  
XV. Robert Bennett Bean. Some Racial Peculiarities of
 
  
the Negro Brain ... 353
+
not tlie case, as can be seen in a wax reconstruction of the parts, Fig. S. This is a reconstruction of the brain of an embryo of 14.5 mm. The tops of the hemispheres, H, have been removed to give a clear view of the paraphysis, P, which otherwise would be more or less covered in by them. The paraphysis appears as a straight tube in the median line and caudad to it is seen a broad partition, V , extending the whole width of the diencephalon. This is the velum, consisting of one layer only, which represents the tw^o originally distinct cephalic and caudal layers. The down grow^th of the parts in order to provide room for the development of the paraphysis has formed a deep angle in the roof of the fore brain. This
  
With 16 fig-ures, 12 charts, and 7 tables.
 
  
  
  
Contents ' v
+
Fig. 8. Wax model of brain of embryo of 14.5 mm. Harvard Embryological Collection, Sagittal Series, X 120 times.
  
XVT. Franklin P. Mall. On Ossification Centers in Human
+
angle is bounded caudad by the velum and cephalad or ventrad by the narrow roof of the telencephalon (paraphysal arch) immediately cephalad to the paraphysis. As the hemispheres develop, they grow at first in a dorsal direction and occupy the space left by the formation of this angle, so that the paraphysis is practically buried between the hemispheres in front and the velum behind. Fig. 10. The growth of the paraph3^sis must, therefore, be regarded as liaving an important effect on the development of the fore brain at this stage.
  
Embryos Less Than One Hnndred Days Old 433
+
Up to this stage the development of the velum has been in a ventral direction towards the floor of the fore brain, but now it begins to grow in quite a ditferent direction. In Fig. 7 a distinct bulging of the velum is
 +
seen, which is extending candad at ncarl}- a right angle to its previous line of growth. If the roof of the telencephalon be closely examined a slight bulging will be seen just cephalad to the opening of the paraphysis. These two outgrowths into the fore brain mark the beginning of the choroid plexuses, which, therefore, have in their origin a very intimate and definite relation to the opening of the paraphysis, one arising caudad and the other cephalad to it. The epiphysis at this stage has increased considerably in size, and the cavity in its stalk is now permanently obliterated. The body of the organ overlaps the stalk a little behind, and is beginning to grow well forward of it. The posterior commissure, P. C, appears here for the first time, a distinct interval in the roof of the brain lying between it and the stalk of the epiphysis.
  
With (i text figures and 7 tables.
 
  
XVII. J. L. Bremer. Description of a 4-inm. Human Embryo. 459
 
With 16 text figures.
 
  
XVIII. Charles R. Stockard. The Development of tlio Mouth
 
  
and Gills in Bdellostoma Stouti 481-517
 
  
With 36 figures.  
+
Fig. 9. Embryo of 17.5 mm. Harvard Embryological Collection, Series, No. 540, Sections 113-115, X 63 diams.
  
XIX. PROCEEDIXGS OF THE AS80CIATI0X OF
 
AMERICAN ANATOMISTS. NINETEENTH SESSION, August 6-10, 1905. TWENTIETH SESSION,
 
Decemher 27, 28, and 29, 1905 I-XX
 
  
  
  
THE DEVELOPMENT OF THE PARAPHYSIS AND THE
+
Fig. 9 is a section through the brain of an embryo of 17.5 mm. The paraphysis has increased in length, and from its distal end, which is somewhat enlarged, small tubules are given off. The whole tube is tipped somewhat forward. The choroid plexus is now well developed, and consists of two distinct parts, one dorsal and one ventral. The dorsal part corresponds to the velum, which has grown caudad as far as the mid brain and has absorbed a large part of the post-velar arch. The ventral part is developed from the original paraphysal arch, and is growing towards the floor of the fore brain. Burckhardt (3) refers to these plexuses as " plexus medius " and " plexus inferioris," respectively, and Mrs. Gage (13), who studied them in Diemyctylus, where the anatomical conditions closely resemble those of JSTecturus, names them the " diaplexus " and " prosoplexus." Prof. Minot has suggested the terms diencephalic
PINEAL REGION IN NECTURUS MACULATUS. '
 
  
BY
+
plexus for the dorsal part, and tel encephalic plexus for the ventral part, and I shall use these terms, as they express more clearly the exact origin of each plexus.
  
JOHN WARREN.  
+
The diencephalic plexus, V. Plx., appears as a large wedge-shaped mass covered by a thin layer of cells, and consisting of a loose connective tissue in the interstices of which numerous blood corpuscles can be seen. The telencephalic plexus, Tel. Plx., has the same general characteristics as the diencephalic. The epiphysis has become flattened and more elongated, and is attached by a narrow stalk to the brain wall. The supra commissure, S. C, is seen just cephalad to the stalk of the epiphysis, which is prolonged forward above it. I was unable to obtain any sagittal series between 15 and 17.5 mm., but in a transverse series of 16.5 mm. the first traces of this commissure can just be made out. and therefore it
  
Demonstrator of Anatomy, the Anatomical Laboratory, Harvard Medical
 
  
School.
 
  
With 23 Text Figures.
 
  
The presence of the paraphysis in Necturns was noted by Prof. C. S.  
+
Fig. 10. Wax model of brain of embryo of 18 mm. Harvard Embryological Collection, Frontal Series, No. 850, X about 75 diams.
Minot in his article " On the Morphology of the Pineal Region, based on
 
its Development in x'Vcanthias " (38), and a brief description of certain
 
stages given. C. L. Herrick (15, PI. YIII, Fig. 1, 3, 4) gives a brief
 
account of the adult paraphj'sis, and shows it in the above figures, vvlicre
 
it is named " Preparaphysis." Osbom (31, PI. IV) shows th-e paraphysis in an adult brain in comparison with the brains of other amphibia. Kingsbury (21) describes briefly the adult paraphysis as well
 
as a few of the earlier stages, and also gives an account of the epi))hysis
 
and the plexuses. I have found, however, no detailed account of all the
 
stages in the development of the paraphysis and the pineal region. This
 
term is used here in the same sense as in Minot's article, quoted above.  
 
  
The greater part of the specimens studied for this article were taken
 
from the Embryological Collection of the Harvard Medical School, and
 
the numbers of each section used are given. Other specimens were prepared specially for this purpose. In some cases where the plane of section was uneven, two or more sections were used in drawing the figures
 
ill order to show all the structures, which should appear in the uK^dian
 
line.
 
  
Fig. 1 is a median sagittal section through the brain of an einl)ryo of
 
8-9 mm. I am indebted to a colleague for the drawing of this section,
 
as this stage is wanting in the collection. In the roof of the fore brain
 
three arches are seen. From before backward these are the j)aia|)liysal
 
arch, P. A., the post- velar arch, P. V. A., and the epiphysal arch, Ep. A.
 
The first two are separated by the velum transversum. V, which marks
 
the limit between the two subdivisions .of the fore brain. Hence the
 
paraphysal arch belongs to the telencephalon, the other two to the
 
  
AMERICAN' JOUIJNAL OF ANATOMY. VOL. V.  
+
probably appears between 16 mm. and 17 mm. as a rule, but at these early stages there is a good deal of variation in the development of all these parts. The posterior commissure is rather larger than in the previous stage.
  
1
+
Fig. 10 is the drawing of the model of the brain of an embryo of 18 ram. This model is intended to show the circulation of the paraphysis at this stage. The distal end of the paraphysis, P, is surrounded by a venous circle, from either side of which veins, Ves., run outward and backward just caudad to the hemispheres, H, to terminate in the internal jugular vein, I. J. V. This vein is passing backward external to the fifth, V, and seventh, VII, cranial nerves. Fig. 6 showed the intimate relation of the paraphysis to these vessels at 12.4 mm., and when the sections of this series were followed out it was found that here the vessels surrounded the tip of the paraphysis. It seems that as the paraphysis develops it forces its way into the veins lying over this part of the fore brain, and the tnbnles, as they are given off at la.ter stages, force their way into these veins, Fig. 15, forming the sinusoidal type of circulation described by Minot (29) and Lewis (25). From the venous circle shown in Fig. 10 smaller vessels run down along the sides of the paraphysis and anastomose with the vessels of the choroid plexuses. A vessel also runs back to the epiphysis, and a larger one forward between the hemispheres. The circulation of this region appears at this stage to be mostly venous, as I could trace the arteries only to their point of entrance in the anlage of the skull, and the return circulation probably occurs by means of a minute capillary network over the surface of tlie brain.
  
 +
Fig. 11 is a section through the brain of an embryo of 26 mm. The
  
  
2 Paraphysis and the Pineal Ees^ion in Necturns Maenlatus
 
  
dieneephalon. The epiphysal are]i is homided l)y two angles, which represent the position of the future supra and posterior commissures. The
 
velum transversum is a simple infolding of the brain roof, and consists
 
of two distinct layers, one caudad and one cephalad, the space between
 
them being filled by a loose mesenchymal tissue, which later contains
 
numerous blood vessels. This figure is practically identical with Minot's
 
figure of acanthias of the same stage (28, Fig. 1), and is, therefore, of
 
great importance in showing the homologies of these parts in elasmobranchs and amphibians. It is probable, as Minot states, that these
 
arches occur in most of the vertebrate series.
 
  
The term post-velar arch, introduced by Minot (28), is much better
+
Fig. 11. Embryo of 26 mm. Harvard Embryological Collection, Sagittal Series, No. 377, Sections 125 and 126, X 63 diams.
for purposes of description than the terms " zirbelpolster " of German
 
writers, and the " dorsal sack " or " postparaphysis " of American authors.  
 
  
  
  
 +
paraphysis here is much more developed. It inclines somewliat forward, and from its wide central lumen a number of tubules are given oif in every direction. The epiphysis and the commissures show but little change. The striking feature of this figure is the great development of the plexuses. The diencephalic plexus, D. Pl.r.. has grown through the mid-brain nearly to the hind-brain, and the telencephalic plexus, Tel. Fix., has grown downwards into the depths of the cavity of the fore brain towards the infundibular recess.
  
 +
Fig. 12 is a transverse section of an embryo of 26 mm., corresponding approximately to the line A-B, Fig. 11. The section passes through the epiphysis, E, and the supra commissure, S. C, just beneath it. Then through the diencephalic plexus, D. Fix., and that part of the cavity of the diencephalon between this plexus and the roof, T>ien. The section then passes through the paraphysis at a point where two small tubules are given off, then through the telencephalic plexus, Te2. Plx.. the telen
  
Dien
 
  
  
 +
FiG. 12. Embryo of 26 mm. Harvard Embryological Collection, Transverse Series, No. 376, Section 89, X 63 diams. (See line A-B, Fig. 11.)
  
Fig. 1.  
+
cephaloii, Teh. the lateral ventricles, L. V., and the foramina of Munro, F. M. In this section the plexuses of tlie hemispheres, L. Plx., are seen. They arise on either side of the origin of the telencephalic plexus, and
  
  
  
Fig. 2.  
+
Fig. 13. Embryo of 26 mm. Harvard Embryological Collection, Frontal Series, No. 378, Section 138, X 63 diams. (See line C-D, Fig. 11.)
  
 +
pass outward at right angles to it through the foramina o£ Munro into the lateral ventricles.
  
 +
Fig. 13 is a frontal section through an embryo of 2Q mm., corresponding closely to the line C-D, Fig. 11. The section passes through the paraphyses, P, and a large lateral tubule, and then through the entire length
  
Fig. 1. Embryo of 8-9 mm. Sagittal section, X 63 diams.
 
  
Fig. 2. Embryo of 10 mm. Harvard Embryological Collection, Sagittal
 
Series, No. 269, Section 39, X 63 diams.
 
  
  
 +
Fig. 14. Same Series as Fig. 13. Section 108. (See line E-F, Fig. 11.)
  
Fig. 2 represents the roof of the dieneephalon and telencephalon of
+
of the diencephalic plexus, D. Fix., the distal end of which is here enlarged and has reached to the hind brain, H. B. Fig. 14 is of the same
an embryo of 10 mm. The two layers of the velum are nearer together
 
and in the region of the epiphysal arch are seen the first signs of the
 
epiphysis, E. This structure is a small rounded diverticulum, which
 
arises from the cephalic end of the arch. It is hollow and opens into
 
the cavity of the fore brain.
 
  
Fig. 3 is a similar section of an embryo of 12 mm. The velum is a
 
trifle longer and the epiphysis a little larger than in the preceding figure.
 
Immediately cephalad to the velum a very small evagination in the
 
paraphysal arch can be seen, P. This is the first sign of the paraphysis,
 
and it appears distinctly later than the epiphysis. The latter overlaps
 
its short stalk both caudad and cephalad, and at this stage the stalk is
 
still hollow, though its cavity was obliterated in this section.
 
  
  
 +
Fig. 15. Same as Fig. 11. X about 150 diams.
  
John Warren 3
+
series as Fig. 13, and corresponds approximately to the line E-F, Fig. 11. It passes through the telencephalic plexus, Tel. Fix., the plexus of the
 +
hemispheres. L. Plx., and the lateral ventricles, L. V. It shows clearly how the plexuses of the hemispheres arise from the telencephalic plexus and pass at first outward and then forward through the foramina of Munro towards the cephalic extremity of the lateral ventricles.
  
Fig. 4 is a section of an embryo of 13 mm. The velum is again a  
+
Fig.- 15 is a high power drawing of Fig. 11, magnified 150 diams. The wall of the paraphysis consists of a single layer of cells with large oval nuclei, and these cells are continuous with the cells covering the choroid plexuses, but the latter are flatter and form a thinner layer. On either side of the paraphysis two large vessels are seen, ves., the epithelial cells of which lie directly against the wall of the paraphysis. The little tubules seem to be forcing their way into these vessels, which are branches of the vessels seen in Fig. 6 and Fig. 10. The vessels also pass down into the choroid plexuses. Fig. 16 is a section of an embryo of 31.4 mm.
little longer and its caudal layer is now distinctly thinner than its cephalic
 
layer. The paraphysis is now a well-marked narrow diverticulum extending dorsad from the paraphysal arch parallel to the velum. The  
 
paraphysal arch just cephalad to the opening of the paraphysis has been
 
  
  
  
  
Tel.  
+
Fig. 16. Embryo of 31.4 mm. Harvard Embryological Collection, Sagittal Series, No. 537, Sections 119-122, X 63 dlams.
  
  
  
 +
The general arrangement is practically the same as in Fig. 11, except that all the parts have progressed somewhat in their development. The distal end of the paraphysis has begun to grow distinctly more cephalad, and the whole structure is much larger than at 26 mm. The choroid plexuses are more extensive, and from the diencephalic plexus a prolongation is extending downwards towards the telencephalic plexus. This latter has pretty well filled up the depths of the third ventricle, and from it prolongations dip down into the recesses in the floor of the fore brain. The two commissures are practically the same as they were at 26 mm., and
  
Fig. 3.
 
  
  
 +
12 Paraph vsis and the I'iiieal Heo-ion in Noetiiriis Maeulatus
  
Pig. 4.
 
  
  
 +
though the epiphysis is a little larger it has been displaced considerably candad, as this part of these sections was unluckily somewhat injured.
  
Fig. 3. Embryo of 12 mm. Harvard Embryological Collection, Sagittal
+
Fig. IT is a section through the brain of an adult necturus. This drawing is magnified 38 diams. only, as it was too large to draw on the same scale as the preceding figures. The paraphysis, P. forms a very complex structure extending far forward above and between the hemispheres. It consists in a general Avay of a proximal and a distal part. The former is broad and thick, and oxtends forward and upward. It then turns forward at quite a marked angle to form the distal part, which is narrow and. tapering. The central canal in the proximal part is very large and irregiilar, but in the distal portion much narrower. From all parts of this canal a large number of tubules are given off, which extend in every direction, and between which lies a confused mass of bloodvessels. One sees here a large vessel ventrad to the organ, and a smaller dorsad to it. the same relations as appear at 12.4 mm., Fig. 6. From these vessels branches pass into the choroid plexuses.
Series, No. 49, Section 58, X 63 diams.  
 
  
Fig. 4. Embryo of 13 mm. Harvard Embryological Collection, Sagittal
+
Fig. 18 is a transverse . section of an adult brain corresponding approximately to the line A-B, Fig. 17. This is drawn on the same scale as most of the preceding figures, 63 diams. The paraphysis, P, is seen in the median line between the hemispheres. It shows a distinct central eavit}', with many tubules running out in every direction, between which is a mass of blood-vessels of all sizes. Below a portion of the telencephalic plexus aiu1 the ])l(\\-us of the hemispheres are seen.
Series, No. 598, Sections 71 and 75, X 63 diams.  
 
  
forced downward to a slight degree, as there is relatively more space
 
between it and the ectoderm than in the previous figures. The epiphysis
 
is about the same size as in Fig. 3, and its opening into the brain is
 
clearly seen.
 
  
Fig. 5 is a section of an embryo of 12A mm., which is, however, further
 
advanced than that of Fig. 4. The velum, the post-velar arch, and the
 
epiphy.sis are about the same, but the paraphysis is distinctly longer, and
 
  
  
 +
Via. 17. Brain of adult necturus. Sag-ittal Section, x 38 diams.
  
  
  
Fig. 5. Embryo of 12.4 mm. Harvard Embryological Collection, Sagittal
+
Fig. is. Brain of adult necturus. Transverse section, X 63 diams. (See line A-B. Fig. 17.)
Series, No. 675, Section 57, X 63 diams.  
 
  
Fig. 6. Same as Fig. 5, X about 120 diams.
 
  
has become a narrow tube. The brain roof cephalad to it has descended
 
still more into the cavity of the telencephalon and the opening of the
 
paraphysis is much nearer the tip of the velum. Fig. 6 is the same
 
section as Fig. 5, only drawn on a higher scale to show the histological
 
details. The walls of the paraphysis and "velum consist of a single layer
 
of cells, with large oval nuclei and without very distinct cell boundaries.
 
  
 +
14 Paraphysis and the Pineal Eegion in Nectunis Maciilatus
  
 +
Fig. 19 is from a wax recoustruction of tlie adult paraphysis on a scale of 120 diams., made from the same series as Fig. 18. The angle between the proximal and distal parts is quite striking, and is much more marked in Ichthyophis (Burckhardt, 4, Fig. 1), but of course this division into proximal and distal parts is really a purely arbitrary one. This model gives a good idea of the complex structure of the organ. The tubules are of all shapes and sizes, often convoluted and anastomosing with each other. The spaces between them, which the vessels occupy, are quite large and striking.
  
4 rai;i])li\si> and the Pineal Kegion in Necturus Maculatus
 
  
These cells are, of course, continuous with tliose which form the brain
 
wall in this region. The same is true of the epiphysis, but the walls seem
 
thicker, as the organ has been cut somewhat obliquely. Close to the
 
paraphysis two vessels can be seen, a larger one cephalad and a much
 
smaller one caudad, _ F<?6'. The vessels lie in intimate relation to this
 
structure, and it is important to note their relation at this early stage,
 
because as development progresses the relation between paraphysis and
 
blood vessels becomes more and more intimate.
 
  
Fig. 7 is a section of an embryo of 15 mm. The most striking feature
 
here is the increase in size of the paraphysis. which has become a long
 
tube with a lumen extending its entire length, and at its distal end a lateral diverticulum has appeared. The roof of the fore brain has now
 
descended to such a degree that the opening of the paraphysis is on a level
 
with the tip of the velum. The velum itself has lost its cephalic layer,
 
and consists of one .layer only, which, however, is much longer than the
 
velum in Fig. 5. If Figs 4, 5, and 7 are compared it will be seen that
 
  
 +
Fig. 19. Wax model of paraphysis of adult necturus, same series as Fig. 18, X about 120 diams.
  
  
  
Tel.  
+
Pig, 20 represents a small portion of the paraphysis of Fig. 17, magnified 560 diams., and shows clearly the relation of the tubules to the vessels. In the centre of the figure is a tubule, T, dividing into two branches, T^ T-. Surrounding these tubules on every side are sinusoids, si., whose flat endothelial cells are seen lying directly against the epithelial wall of the tubules with no connective tissue between them. We find here in order first a sinusoid, then a tubulcj then another sinusoid and another tubule, and finally a sinusoid. The wall of the tubules consists of a single layer of cells with large oval nuclei and very indistinct cell boundaries. The nuclei contain masses of granules arranged very irregu
  
  
 +
Joljn Warren
  
Fig. 7. Embryo of 15 mm. Harvard Embryological Collection, Sagittal
 
Series. No. 79, Sections 85 and 89, X 63 diams.
 
  
the distal end of the paraphysis is practically at the same distance from
 
the ectoderm in each case. As the paraphysis has developed during those
 
stages into a long tube, its growth must have occurred by a downward
 
extension of the neighboring parts into the cavity of the fore brain. This
 
is practically the same process described by Minot in Acanthias. It is
 
also shown by the great increase in distance between the roof of the
 
telencephalon and the ectoderm from Fig. 4 to Fig. 7. The opening of
 
the paraphysis in Fig. 3 is nearly on a level with tlie base of the velum,
 
and as the down growth of the parts takes place the opening of the paraphysis and the paraphysal arch descend, apparently pushing the cephalic
 
layer of the velum ahead of them. Therefore the single layer of the
 
velum in Fig. 7 really corresponds to the original caudal layer, plus the
 
cephalic layer, which has been forced down ahead of the opening of the
 
paraphysis.
 
  
In stud5''ing Fig. 7 it might seem as if the posterior wall of the paraphysis corresponded to the cephalic layer of the velum. This, however, is  
+
larly. There can be no question abont the glandular nature of the paraphysis, and its circulation is evidently sinusoidal.
  
 +
The choroid plexus, Ch. Fix., Fig. 17, appears as a confused mass of
  
  
John Warren 5
 
  
not tlie case, as can be seen in a wax reconstruction of the parts, Fig. S.
 
This is a reconstruction of the brain of an embryo of 14.5 mm. The tops
 
of the hemispheres, H, have been removed to give a clear view of the
 
paraphysis, P, which otherwise would be more or less covered in by them.
 
The paraphysis appears as a straight tube in the median line and caudad
 
to it is seen a broad partition, V , extending the whole width of the diencephalon. This is the velum, consisting of one layer only, which represents the tw^o originally distinct cephalic and caudal layers. The down
 
grow^th of the parts in order to provide room for the development of the
 
paraphysis has formed a deep angle in the roof of the fore brain. This
 
  
 +
Fig. 20. Small portion of adult paraphysls, same section as Fig. 17, X 560 diams.
  
 +
vessels covered by a thin layer of cells. This mass completely fills up the cavity of the fore and mid brains, and may in some cases appear in the hind brain, Fig. 23, though there seems to be considerable variation
  
  
Fig. 8. Wax model of brain of embryo of 14.5 mm. Harvard Embryological Collection, Sagittal Series, X 120 times.
 
  
angle is bounded caudad by the velum and cephalad or ventrad by the
 
narrow roof of the telencephalon (paraphysal arch) immediately
 
cephalad to the paraphysis. As the hemispheres develop, they grow at
 
first in a dorsal direction and occupy the space left by the formation of
 
this angle, so that the paraphysis is practically buried between the hemispheres in front and the velum behind. Fig. 10. The growth of the
 
paraph3^sis must, therefore, be regarded as liaving an important effect on
 
the development of the fore brain at this stage.
 
  
Up to this stage the development of the velum has been in a ventral
+
Fig. 21. Wax model of epiphysis of adult necturus. X 280 diams.
direction towards the floor of the fore brain, but now it begins to grow in
 
quite a ditferent direction. In Fig. 7 a distinct bulging of the velum is
 
  
 +
in the caudad development of this part of the ple.xus. Tlie two parts of the plexus overlap each other, and are also closely interlaced.
  
 +
The epiphysis, E. is still attached to the brain by a very narrow stalk. The body overlaps the stalk somewhat behind, and then is prolonged forward as an oval flattened body above the roof of the diencephalon, and its cavity seems to be divided more or less into compartments. Fig. :H represents a wax reconstrnction of an adult epiphysis seen from ^above. It is irregularly triangular in shape with a broad base and a blunt apex. Its surface is grooved more or less by vessels which lie against its Avails. Fig. 22 is the same model with the top removed. The interior is more or less subdivided by incomplete septa. At its apex there is a small cavity
  
6 Paraphysis and tlio Pineal Pogion in Xeclurus 'Maculatus
 
  
seen, which is extending candad at ncarl}- a right angle to its previous
 
line of growth. If the roof of the telencephalon be closely examined a
 
slight bulging will be seen just cephalad to the opening of the paraphysis.
 
These two outgrowths into the fore brain mark the beginning of the
 
choroid plexuses, which, therefore, have in their origin a very intimate
 
and definite relation to the opening of the paraphysis, one arising caudad
 
and the other cephalad to it. The epiphysis at this stage has increased
 
considerably in size, and the cavity in its stalk is now permanently obliterated. The body of the organ overlaps the stalk a little behind, and is
 
beginning to grow well forward of it. The posterior commissure, P. C,
 
appears here for the first time, a distinct interval in the roof of the brain
 
lying between it and the stalk of the epiphysis.
 
  
  
 +
Fig. 22. Same as Fig. 21, with top of epiphysis removed.
  
 +
1)0unded behind by a partial septum, then comes a large chamber, which divides into two passages running back towards the angles at the base. Between these two passages appears a comparatively solid area, interrupted, hoAvever. to some extent by small spaces, aa^IucIi communicaio Avith each other and the larger chambers. This solid area lies over tbe stalk of the organ. The sujDra commissure appears to be comparatively small,
  
Hyp.
 
  
  
  
OCh.  
+
Fig. 23. Brain of adult necturus. Viewed from above. X 7 diams.
  
 +
while the posterior is large and forms a deep groove in the roof of tlie brain. Fig. 23 is a vioAv of the brain of an adult necturus shoAving the relative positions of paraphysis and epiphysis. The tufted extremity of the diencephalic plexus can be seen in the fourth ventricle.
  
 +
If Fig. 1, the embryo of 8-9 mm., is compared Avith Fig. 17, the adult, one sees that the paraphysal arch has been Avholly taken up in the formation of the telencephalic plexus, the plexus of the hemispheres, and
  
A.C.
 
  
  
 +
John Warren 17
  
Fig. 9. Embryo of 17.5 mm. Harvard Embryological Collection,  
+
the paraphysis. The velum and the greater part of the post-velar arch have been absorbed in the formation of the diencephalic plexus. A portion of this arch, however, persists and forms that part of the roof of the diencephalon between the diencephalic plexus and the supra commissure. The epiphysal arch has formed the epiphysis.
Series, No. 540, Sections 113-115, X 63 diams.  
 
  
 +
The paraphysis is a structure common to all vertebrates either in the adult or embryonic condition (Selenka, 34, Francotte, 11), but previous observations on mammals leave much to be desired. It always arises from the telencephalon cephalad to the velum transversum, and its opening is placed between and dorsad to the foramina of Munro as emphasized by Dexter (5).
  
 +
In the cyclostomes, Ammocoetes (Kupffer, 24), and Petromyzon (Burckhardt, 3), the paraphysis appears as a small sac-like diverticulum lying ventrad and close to the enlarged distal end of the epiphysis. In elasmobranchs, Minot (28) and Locy (27) found that the paraphysis in Acanthias appears at quite a late stage as a small outgrowth from the paraphysal arch and, owing to the small size of the post-velar arch and the compression of the velum, it comes to lie immediately cephalad to the epiphysis. In ganoids, Kupffer found in Accipenser that the paraphysis appears first as a small outgrowth which later becomes a somewhat sacculated vesicle (23, Fig. 19). Hill (18) and Eycleshymer and Davis (9) studied the paraphysis in Amia. Here it begins as a simple vesicle, which increases rapidly in size and gives off diverticuli from its central cavity. In teleosts (Burckhardt, 3) the paraphysis appears late and remains in a rudimentary condition. In the dipnoi, Burckhardt (3) describes the paraphysis in Protopterus as a wide outgrowth giving off small . diverticuli.
  
Sagittal
+
In amphibia the organ becomes highly differentiated and its appearance in the adult brain is very striking. It appears as an elongated body lying above and between the hemispheres, and extending cephalad for a varjdng distance in various forms. Fig. 23. Osborn (31, PI. 4) shows a view of the brains of Siredon, Necturus, Proteus, and Siren. The paraphysis has the same general form in each of these, but it is somewhat larger in Necturus. The paraphysis of Triton and Ichthyophis (Burckhardt, 4) has the same characteristics. In the latter the paraphysis appears in sagittal section as a hammer-shaped organ extending forward above the hemispheres. (4, Fig. 1). In Rana the paraphysis has the same position as in Necturus, but is smaller. On removing the top of the skull in Necturus the paraphysis is seen lying beneath the pia surrounded by the blood-vessels which cover this part of the brain. It appears to the naked eye so vascular and also in sections so intimately related to the 2
  
  
  
Fig. 9 is a section through the brain of an embryo of 17.5 mm. The
+
18 Paraphysis and the Pineal Pegion in Necturns Maculatus
paraphysis has increased in length, and from its distal end, which is
 
somewhat enlarged, small tubules are given off. The whole tube is tipped
 
somewhat forward. The choroid plexus is now well developed, and consists of two distinct parts, one dorsal and one ventral. The dorsal part
 
corresponds to the velum, which has grown caudad as far as the mid brain
 
and has absorbed a large part of the post-velar arch. The ventral part is
 
developed from the original paraphysal arch, and is growing towards the
 
floor of the fore brain. Burckhardt (3) refers to these plexuses as
 
" plexus medius " and " plexus inferioris," respectively, and Mrs. Gage
 
(13), who studied them in Diemyctylus, where the anatomical conditions
 
closely resemble those of JSTecturus, names them the " diaplexus " and
 
" prosoplexus." Prof. Minot has suggested the terms diencephalic
 
  
 +
choroid plexus that it is not astonishing that it was at first regarded as a portion of this plexus. According to Minot (28) the paraphysis of Eana is characterized by the character of its epithelium, its tubular structure and its apparently sinusoidal circulation. This is practically similar to the conditions found in Necturus.
  
 +
In ^lenopoma Sorenscn (36) describes the paraph3'sis as a solid vascular mass, and in Ichthyophis Burckhardt (3) describes it as an elaborately folded structure of a glandular character. In Amblystoma, Eycleshymer (8) shows that the organ gives off tubules and has a digitated appearance. In Diemyctylus (Mrs. Gage, 13), in an embryo of 10 mm. the paraphysis closely resembles that of Necturus at 18 mm. (Minot, 28, Fig. 13), and in the adult it is a long tube giving off many tubules in close relation to vessels.
  
John Warren 7
+
Herrick (15) calls the paraphysis of an adult Necturus the " preparaphysis " and says it consists of an irregular central chamber with complicated diverticuli in close relation to vessels. This description corresponds closely with Fig. 17. The model of the adult paraphysis, Fig. 19, shows the complicated arrangement of the tubules, many of which anastamose with each other, and the spaces between the tubules are filled by blood-vessels.
  
plexus for the dorsal part, and tel encephalic plexus for the ventral part,
+
Fig. 6 shows how the paraphysis at 12.5 mm. is beginning to invade a large vessel lying over it on the surface of the brain. This vessel at this point is much enlarged. Fig. 10 shows this relation much clearer and also that these vessels in relation to the paraphysis are tributaries of the internal jugular vein. Fig. 15 shows the relation of the paraphysis to these vessels at 26 mm. and that the vessels pass into the choroid plexuses both dorsad and ventrad to the organ. The little tubules can be seen growing out into the vessels. Fig. 17 shows how these relations between vessels and tubules in the adult become much more intimate, and the vessels corresponding to those in Fig. 15 are seen passing into the choroid plexuses dorsad as well as ventrad to the paraphysis. Schobel (33), who studied the circulation in the brain of certain amphibia, of which Necturus was one, shows that in the adult two large vessels pass outward just caudad to the hemispheres to empt}'^ eventually in the internal jugular vein. These vessels surround the paraphysis and anastomose with two or three large vessels running forward between the hemispheres. This is practically the same arrangement shown in the model in Fig. 10. He does not mention the paraphysis but refers to it as a large venous plexus. Eex (32) also has studied the veins in the amphibian brain, and his preparations are practically the same as Schobel's. He refers to the paraphysis as the " nodus chorioideus " and says that it is a sort
and I shall use these terms, as they express more clearly the exact origin
 
of each plexus.  
 
  
The diencephalic plexus, V. Plx., appears as a large wedge-shaped mass
 
covered by a thin layer of cells, and consisting of a loose connective tissue
 
in the interstices of which numerous blood corpuscles can be seen. The
 
telencephalic plexus, Tel. Plx., has the same general characteristics as
 
the diencephalic. The epiphysis has become flattened and more elongated, and is attached by a narrow stalk to the brain wall. The supra
 
commissure, S. C, is seen just cephalad to the stalk of the epiphysis,
 
which is prolonged forward above it. I was unable to obtain any sagittal
 
series between 15 and 17.5 mm., but in a transverse series of 16.5 mm. the
 
first traces of this commissure can just be made out. and therefore it
 
  
  
 +
John Warren 19
  
 +
of meeting point for the veins of the fore and mid brains. He shows beautifully in his injections how veins pass both dorsad and ventrad to the paraphj'sis to enter the plexuses, and how closely these vessels are related to the tubules of this structure. Mrs. Gage shows practically the same arrangement in Diemyctylus
  
Fig. 10. Wax model of brain of embryo of 18 mm. Harvard Embryological Collection, Frontal Series, No. 850, X about 75 diams.  
+
As regards the arteries Schobel shows that they are much smaller than the veins, and describes a small vessel passing caudad to the hemispheres to pass eventually into the plexuses. The intercrescence of the tubules of the adult paraphysis and the veins is shown clearly in Fig. 30, each vessel and tubule lying back to back with no connective tissue between them. In view of all these facts it seems evident that the circulation of the paraphysis is sinusoidal. According to the above descriptions, the development of the paraphysis into a complicated, glandular organ, which is also very vascular, seems to be a striking characteristic of the amphibia.
  
 +
In lacertilia the paraphysis of Anguis fragilis has been studied by Francotte and of Lacerta vivipara by Francotte (10, 11, 12) and Burckhardt (3). The latter shows the paraphysis in an embryo of 13 mm. as a narrow tube with a slightly expanded distal extremity, much as that of ISTecturus of 15 mm. Francotte describes the paraphysis of Lacerta vivipara as a long tube giving off a mass of tubules which lies under the parietal eye, and resembles the epiphysis of birds (11, Fig. 14; 12, Fig. 24). In Anguis (10, Figs. 15 and 19) the paraphysis forms a long narrow sack, with somewhat convoluted walls, which curves back over the post-velar arch to end in close relation to the parietal eye.
  
 +
The conditions in the lizard are essentially the same (10, Fig, 31). In Phrynosoma coronata Sorensen (35, Fig. 2) describes the paraphysis as a long, narrow tube, immediately cephalad to the epiphysis.
  
probably appears between 16 mm. and 17 mm. as a rule, but at these early
+
In the ophidia Leydig (26, Fig. 6) shows the paraphysis of an embryo of Vivipara urcini near birth as a large, wide tube with no convolutions or diverticuli and practically the same conditons in a young " Eingelnatter" and Tropidonatus natrix (26, Figs. 5 and 2).
stages there is a good deal of variation in the development of all these
 
parts. The posterior commissure is rather larger than in the previous
 
stage.  
 
  
Fig. 10 is the drawing of the model of the brain of an embryo of
+
Among the chelonia Voelzkow (39) has described the paraphysis in Chelone imbricata as at first a wide tube much convoluted, which later decreases somewhat in size. (Figs. 21 and 22.) Its distal end inclines caudad close to the epiphysis. In Chelone mydas Humphrey (20, Fig. 7, PI. II) shows the paraphysis as a long tubular structure, giving off small tubules, and in an embryo of Chelydra it appears as a large, wide sack, from which tubules arise. It is in closer relation to the epiphysis than in Chelone mydas or imbricata.
18 ram. This model is intended to show the circulation of the paraphysis  
 
at this stage. The distal end of the paraphysis, P, is surrounded by a  
 
venous circle, from either side of which veins, Ves., run outward and backward just caudad to the hemispheres, H, to terminate in the internal
 
jugular vein, I. J. V. This vein is passing backward external to the fifth,  
 
V, and seventh, VII, cranial nerves. Fig. 6 showed the intimate relation  
 
of the paraphysis to these vessels at 12.4 mm., and when the sections of
 
this series were followed out it was found that here the vessels surrounded the tip of the paraphysis. It seems that as the paraphysis devel
 
  
 +
In Cistudo Herrick shows a model of Sorensen (15, Fig. 5, PI. VI) of the paraphysis, which is a wide tube with convoluted walls and tubules.
  
S Parapliv.sis and the Pineal Region in Nectnms Maculatus
 
  
ops it forces its way into the veins lying over this part of the fore brain,
 
and the tnbnles, as they are given off at la.ter stages, force their way into
 
these veins, Fig. 15, forming the sinusoidal type of circulation described
 
by Minot (29) and Lewis (25). From the venous circle shown in Fig. 10
 
smaller vessels run down along the sides of the paraphysis and anastomose with the vessels of the choroid plexuses. A vessel also runs back to
 
the epiphysis, and a larger one forward between the hemispheres. The
 
circulation of this region appears at this stage to be mostly venous, as I
 
could trace the arteries only to their point of entrance in the anlage of
 
the skull, and the return circulation probably occurs by means of a
 
minute capillary network over the surface of tlie brain.
 
  
Fig. 11 is a section through the brain of an embryo of 26 mm. The
+
20 Paraphysis and the Pineal Region in Necturus Maculatus
  
 +
In the crocodilia Voelzkow (39) has described the paraphysis of Crocodilus madagascarensis grand and Caiman niger spix. In the former the paraphysis is at first a wide tube which becomes convoluted and much longer and narrower. In the latter the paraphysis forms a larger tube and the convolutions and tubules are more complicated. In both cases the organ reaches its greatest development in embryonic life and retrogrades later, though more so in the crocodile. He was unable, however, to follow the development in the caiman as far as in the crocodile. Owing to the thickenings in the brain wall the organ is crowded somewhat caudad against the post-velar arch.
  
 +
In birds the paraphysis is relatively rudimentary. Burckhardt (3) shows the paraphysis in an embryo of the crow as a small diverticulum not unlike that of Petromyzon. Dexter (5) worked out in detail the development of the organ in the common fowl, and showed that it appeared at first as a small diverticulum. The walls become much thickened and in a chicken of 10 days it is a small, oval structure, about 150 fx in its greatest diameter, with very thick walls (5, Fig. 5). Selenka (34) has described the paraphysis in the oppossum, but as far as I am aware little is known of the development of the paraphysis in mammals, though Francotte (11) has observed it in human embryo of twelve weeks.
  
 +
From the cyclostomes to the amphibia the paraphysis shows a steadily progressive development, and the various forms through which it passes, from the simple diverticulum of Petromyzon to the elaborate gland of the urodela, are illustrated in a general way by the stages of its development in Necturus. In the vertebrates above the amphibia the paraphysis retrogrades and practically retraces its steps through the reptilia and birds to mammals, reaching in the chick essentially the same form in which it started in Petromyzon. Its development, therefore, may be indicated by a curve, which ascends steadily from the cyclostomes, reaches its height in urodela, and descends through the reptilia and birds to mammals.
  
Fig. 11. Embryo of 26 mm. Harvard Embryological Collection, Sagittal
+
The epiphysis is present in nearly all vertebrates. It is stated to be absent in the alligator (Sorensen, 36 and 37), and in the caiman and crocodile (Voelzkow, 39) and in Torpedo (d'Erchia, 7).
Series, No. 377, Sections 125 and 126, X 63 diams.  
 
  
 +
The epiphysis of Necturus as compared with the paraphysis is relatively poorly developed and in this respect resembles the epiphysis of other urodela (Mrs. Gage, 13). In Diemyctylus Mrs. Gage found that the epiphysis was entirely cut off from the brain and that its cavity was nearly obliterated. In Ichthyophis (Burckhardt, 1 and 4) the epiphysis is a small, pear-shaped organ attached to the brain by a narrow solid stalk. Herrick (15) in Menopoma, describes the epiphysis as an irreg
  
  
paraphysis here is much more developed. It inclines somewliat forward,
+
John Warren 21
and from its wide central lumen a number of tubules are given oif in
 
every direction. The epiphysis and the commissures show but little
 
change. The striking feature of this figure is the great development of
 
the plexuses. The diencephalic plexus, D. Pl.r.. has grown through the
 
mid-brain nearly to the hind-brain, and the telencephalic plexus, Tel.
 
Fix., has grown downwards into the depths of the cavity of the fore brain
 
towards the infundibular recess.
 
  
Fig. 12 is a transverse section of an embryo of 26 mm., corresponding
+
ular number of vesicles attached to the brain by a narrow opening. According to Kingsbury (21) the structure in Necturus consists of an aggregation of closed vesicles, forming an oval, flattened body, and there is no connection with the brain. The cavity of the epiphysis communicates through its stalk with the cavity of the diencephalon up to 15 mm., when the cavity in the stalk becomes obliterated. The stalk persists and was present in all the adult brains which I examined, but in some cases it was so small that it could easily be overlooked. The reconstruction of an adult epiphysis. Fig. 22, shows that the cavity of the organ forms a large chamber subdivided to a certain extent by incomplete septa. A much more solid area is seen towards the caudal extremity, which is placed just over the stalk. The same characteristics I have observed in another model made from a different brain. One gets the idea that the epiphysis consists of a series of vesicles in studying sagittal sections a little to one side of the median line, as for instance in Fig. 17, where the epiphysis was displaced a little to one side.
approximately to the line A-B, Fig. 11. The section passes through the  
 
epiphysis, E, and the supra commissure, S. C, just beneath it. Then
 
through the diencephalic plexus, D. Fix., and that part of the cavity of  
 
the diencephalon between this plexus and the roof, T>ien. The section
 
  
 +
. There has been such a vast amount written on the origin of the epiphysis and the pineal or parietal eye and their homologies that it seems superfluous to add anything more here. In a very general way, however, there seems to be some sort of proportion in the relative development of the paraphysis, epiphysis, and the parietal eye. In urodela where there is no parietal eye and a small epiphysis, the paraphysis reaches its highest degree of development. In those forms where the paraphysis is rudimentary or relatively slightly developed the parietal eye is present or else the epiphysis is relatively highly developed. Compare, for example, the figures of Burckhardt (3) of Petromyzon, Minot (28) of Acanthias, Burckhardt (3) of Trout, Leydig (26) and Voelzkow (38) of reptilia, and Dexter (5) of the fowl. Rana, however, seems to be a marked exception to this statement, as there the paraphysis, epiphysis, and pineal eye are all present and well developed, and the same may be said for Lacerta (Francotte, 10 and 11) and Sphenodon (Dendy, 6). As the paraphysis and epiphysis are glandular structures they have probably some sort of compensatory function and where one is highly developed the other is relatively rudimentary or even absent. Compare in this respect also Torpedo with Acanthias and the crocodile and alligator with the chick.
  
 +
As a rule the stalk of the epiphysis is placed immediately caudad to the supra commissure, in all cases I believe, except in the toad, where there is a distinct interval between it and this commissure (Sorenson, 36). In Necturus there is an interval in the roof of the brain between the stalk and the posterior commissure. This portion of the roof of the brain was
  
John Warrcu 9
 
  
then passes through the paraphysis at a point where two small tubules are
 
given off, then through the telencephalic plexus, Te2. Plx.. the telen
 
  
 +
22 Paraphysis and the Pineal Eegion in Necturus Macnlatus
  
 +
described by Kupffer (23) as the " schaltstlick," and according to him it is best developed in amphibia. Burckhardt (3) maintains that it occurs in all vertebrates from Pctromyzon np, but according to Kupffer it is absent in Accipenser (23, Fig. 19), and it is also wanting in Acanthias (Minot, 28, Pig. 10) and in the fowl (Dexter, 5, Fig. 9).
  
FiG. 12. Embryo of 26 mm. Harvard Embryological Collection, Transverse Series, No. 376, Section 89, X 63 diams. (See line A-B, Fig. 11.)
+
The velum transversum is probably characteristic of all vertebrates. Minot (28). In Petromyzon the velum appears as a small transverse fold, and the post-velar arch is well marked. The plexus development is, however, very slight. In elasmobranchs the velum of Acanthias forms a long, narrow, transverse fold, and the post-velar arch is so small that the origin of the velum seems to be close to the supra commissure. The caudal layer of the velum is distinctly thinner than the cephalic (Minot, 28, Fig. 6). This is also seen in Torpedo (d'Erchia, 7, Fig. 12), and in Necturus, Fig. 6. The velum later on has the character of a choroid plexus, but the plexus of the hemispheres is very rudimentary (Minot, 28). In Notidanus Burckhardt (3) shows a long, narrow velum, a short post-velar arch, and a small telencephalic plexus. The plexus of the hemispheres, however, is absent.
  
cephaloii, Teh. the lateral ventricles, L. V., and the foramina of Munro,
+
In Accipenser (Kupffer, 23, Fig. 19) the velum is long, well developed and folded to a certain extent, and the post-velar arch is quite extensive. In ganoids (Studnicka, 38) the membranous roof of the brain serves as the tela choroidea of higher types. In this class of vertebrates according to Burckhardt (3) the plexus of the hemispheres is lacking, but the telencephalic plexus is well developed, and in teleosts the former is also wanting, but the latter present in a reduced form.
F. M. In this section the plexuses of tlie hemispheres, L. Plx., are seen.
 
They arise on either side of the origin of the telencephalic plexus, and  
 
  
 +
In amphibia all the plexuses are highly developed, and in J^ecturus they are of marked extent (Kingsbury, 21). The velum in Necturus appears at first as a transverse fold in the roof of the brain separating the diencephalon from the telencephalon. This fold develops at first ventrad and then caudad through the mid brain as far as the hind brain. This great growth of the velum forms the diencephalic plexus. The post-velar arch, which at first is wide and well marked, is practically absorbed by the overgrowth of the velum, and a small portion only persists in the roof of the diencephalon between the origin of the diencephalic plexus and the supra commissure. Fig. 17. The telencephalic plexus develops from the paraphysal arch immediately cephalad to the paraphysis, the opening of which therefore is surrounded by these two plexuses. They fill up the cavity of the third ventricle and mid brain, and the diencephalic plexus may appear in the hind brain (Osl>orn, 29). This seems to vary in different cases, and in the majority of brains which I was able to examine the extremity of this plexus did not actually extend
  
  
  
jRi-TT
+
John Warren 23
  
 +
into the hind brain. In- Fig. 33, however, this extremity appears as a marked tuft in the fourth ventricle. The plexuses of the hemispheres arise on either side from the origin of the telencephalie plexus and pass into the lateral ventricles, extending nearly to their cephalic extremities.
  
 +
In Lacerta vivipara (Francotte, 12, Fig. 24) the post- velar arch has been much com})ressed from before backward so as to form a deep narrow angle. At the apex of the angle the folds of the diencephalic plexus are seen. The velum is smooth and apparently is not included in the formation of the plexus. In Anguis fragilis (Francotte, 10, Figs. 19 and 15), the post-velar arch does not seem to be so much compressed, and the plexus formation somewhat greater. As he says, however, the development of those parts in Lacerta is practically the same as in Anguis. According to Burckhardt the telencephalie plexus is much reduced in size, consisting merely of small folds, but the plexus of the hemispheres is well developed (Burckhardt, 3).
  
Fig. 13. Embryo of 26 mm. Harvard Embryological Collection, Frontal
+
In the turtles Humphrey (20) found that the velum of Chelydra is but slightly developed, and no diencephalic plexus is formed. All the other plexuses are telencephalie in origin.
Series, No. 378, Section 138, X 63 diams. (See line C-D, Fig. 11.)
 
  
pass outward at right angles to it through the foramina o£ Munro into the  
+
Herrick (15, Fig. 5, PI. VI), shows in Cistudo a well-developed telencephalie plexus and a diencephalic plexus represented by many folds in the caudal layer of the velum and the post-velar arch. In Chelone imbricata Yoelzkow (39, Figs. 19 and 22) shows at first a well marked velum and a wide post-velar arch. In later stages the velum and practically all the arch are thrown into folds to form the diencephalic plexus. The telencephalie plexus is also well developed. In the serpents much the same arrangement can be seen. The velum (Leydig, 26, Figs. 2, 5, and 6) forms a prominent fold, and it and the post-velar arch form a very vascular plexus. In the crocodilia (Voelzkow, 39, Figs. 7, 11, 13, 15), the velum and the post-velar arch are at first well marked, but the parts later become so compressed from before backward that the arch forms a deep acute angle in the depths of which plexus foldings are seen. The caudal layers of the velum, however, takes no part in the plexus formation. In birds, Dexter (5) found that the velum of the fowl is small and the post-velar arch broad at first. This becomes compressed so as to form an acute angle much as in the crocodilia. The cephalic limb of this angle and all the velum is converted into the choroid plexus. In birds the plexus of the hemispheres is very well developed, but the telencephalie plexus is practically absent.
lateral ventricles.  
 
  
Fig. 13 is a frontal section through an embryo of 2Q mm., corresponding
+
In fishes the plexus development is quite simple, in many cases being merely the thin membranous roof of the third ventricle; in others, however, this is much folded and vascular (Sorensen, 35). In certain forms
  
  
  
10
+
24 Paraphysis and tfio Pineal Eegion in Necturus Maculatus
  
 +
there is a telenccphalic plexus, but the plexus of the hemispheres is absent or rudimentary (Burckhardt, 3). In amphibia there is a great overgrowth of all the plexuses, especially of the diencephalic plexus, which here reaches its highest development. In reptilia the plexus of the hemispheres is well developed, but the telencephalic plexus is reduced in size (Burckhardt, 3), and the diencephalic much more so. In birds the plexus of the hemispheres is highly developed, the telencephalic plexus practically absent, and the diencephalic plexus, while very similar to that of reptilia, approaches nearer to the tela choroidea of higher mammalia.
  
 +
Osborn first named the supra-commissure and worked out its homologies. According to him (30) the urodela are distinguished from the anura by the frequent extensive development of this commissure, which is large in Amphiuma, smaller in Necturus, and much reduced in Eana. It appears in Necturus a little later than the posterior commissure, as is usual in most cases, as far as I am aware, except in Ammocoetes, where it appears shortly before the posterior commissure (Kupffer, 24, Fig. 5). It is found in all the chief types of vertebrates, and is usually smaller than the posterior (Minot, 28). It is developed from the diencephalon, while the posterior belongs to the cephalic limit of the mid brain.
  
Paraphysis aud the Pineal Kegion in Necturus Maculatus
+
Conclusions.
  
 +
1. The paraphysis appears first in an embryo of 12 mm. It is developed from the telencephalon immediately cephalad to the velum transversum as a small diverticulum, which becomes eventually a complicated gland with anastomosing tubules. The gland is very vascular, and has a sinusoidal circulation.
  
 +
2. The epiphysis appears first in an embryo of 9-10 mm., and is developed from the diencephalon. It is always attached to the brain by a small solid stalk, and the cavity is partially subdivided by incomplete septa.
  
closely to the line C-D, Fig. 11. The section passes through the paraphyses, P, and a large lateral tubule, and then through the entire length
+
3. The velum transversum grows at first ventrad and then caudad as far as the hind brain, forming in this way the diencephalic portion of the choroid plexus. The post-velar arch, which is at first quite extensive, is almost entirely absorbed in this extensive growth of the v.elum.
  
 +
4. The telencephalic plexus arises from the roof of the telencephalon, and fills up the depths of the cavity of the third ventricle. The opening of the paraphysis is surrounded by these two plexuses.
  
 +
5. The plexus of the hemispheres arises at a right angle from the telencephalic plexiis just cephalad and ventrad to the opening of the paraphysis.
  
  
Fig. 14. Same Series as Fig. 13. Section 108. (See line E-F, Fig. 11.)
 
  
of the diencephalic plexus, D. Fix., the distal end of which is here enlarged and has reached to the hind brain, H. B. Fig. 14 is of the same
+
John Warren 25
  
,Tf,s-.  
+
6. The supra-commissure appears first at 16-17 mm. It lies immediately cephalad to the stalk of the epiphysis and is comparatively small.
  
 +
7. The posterior commissure appears first at 15 mm., and there is a marked interval in the roof of the diencephalon between it and the epiphysis.
  
 +
I wish in conclusion to express my acknowledgments to Prof. Minot for his kind advise and interest in the preparation of this article.
  
M.  
+
BIBLIOGRAPHY.
  
 +
The following are the principal articles consulted, but of course do not form a complete bibliography of this subject:
  
 +
1. BuRCKHAKDT, R. — Die Zirbel von Ichthyophis Glutinosus und Protopterus
  
 +
Annectens. Anat. Anz., Bd. VI.
  
 +
2. Die Homologien des Zwischenhirndaches bei Reptilien und Vogeln.
  
 +
Anat. Anz., Bd. IX, 320-324.
  
D.PIX
+
3. Der Bauplan des Wirbeltiergehirns. Morpholog. Arbeiten, IV
  
  
  
o??,:
+
Bd., 2 Heft, 131.
  
 +
4. Untersuchungen am Gehirn und Geruchsorgan von Triton und
  
 +
Ichthyophis. Zeitschr. f. Wiss. Zoologie, Bd. 52.
  
^ m
+
5. Dexter, F. — The Development of the Paraphysis in the Common Fowl.
  
 +
American Journ. Anat., Vol. II, No. 1, 13-24.
  
 +
6. Dendy, a. — On the Development of the Pineal Eye and Adjacent Organs
  
<£5S^ferffiICi^!^^^;
+
in Sphenodon (Hatteria). Quart. Journal Micros. Soc, Vol. 42, 111.
  
 +
7. D'Ebchia, F. — Contributo alio studio della volta del cervello intermedio
  
 +
e della regione parafisaria in embrioni di Pesci e di Mammiferi. Monitore Zoologico, VII, 118 e 201.
  
 +
8. Eycleshymer, a. C. — Paraphysis and Epiphysis in Amblystoma. Anat.
  
Tel.Plx. .^1-^^
+
Anz., Bd. VII.
  
 +
9. Eycleshymer, A. C, and Davis, B. M. — The Early Development of the
  
 +
Paraphysis and Epiphysis in Amia. Journal of Comp. Neurology, Vol. 7.
  
 +
10. Francotte, p. — Recherches sur le developpement de L'epiphyse. Arch.
  
Fig. 15. Same as Fig. 11. X about 150 diams.  
+
de biologie, T. VIII.
  
series as Fig. 13, and corresponds approximately to the line E-F, Fig. 11.  
+
11. Note sur I'ceil parietal, l'epiphyse, la paraphyse et les plexus
It passes through the telencephalic plexus, Tel. Fix., the plexus of the
 
  
 +
choroides du troisieme Ventricule. Bull, de I'acad, royale, etc., d. Belg., 3 Serie, T. 27.
  
 +
12. Contribution a I'tHude de I'oeil parietal, de l'epiphyse chez les
  
John Warren
+
Lacertiliens.
  
 +
13. Gage, S. P. — The Brain of Diemyctylus Viridescens. Wilder Quart. Cent.
  
 +
Book, 1898.
  
11
+
14. Gaupp, E. — Zirbel, Parietalorgan und Paraphysis. Ergebn. Anat. Entwick. Ges., VII, 208-285.
  
 +
15. Hebbick, C. L. — Topography and Histology of the Brain of certain Rep tiles. Journ. of Comp. Neurology, Vol. I, 37; Vol. Ill, 77-104, 119-138.
  
 +
16. Topography and Histology of certain Ganoid Fishes. Journ. of
  
hemispheres. L. Plx., and the lateral ventricles, L. V. It shows clearly
+
Comp. Neurology, Vol. I, 162.
how the plexuses of the hemispheres arise from the telencephalic plexus
 
and pass at first outward and then forward through the foramina of
 
Munro towards the cephalic extremity of the lateral ventricles.  
 
  
Fig.- 15 is a high power drawing of Fig. 11, magnified 150 diams.
 
The wall of the paraphysis consists of a single layer of cells with large
 
oval nuclei, and these cells are continuous with the cells covering the
 
choroid plexuses, but the latter are flatter and form a thinner layer. On
 
either side of the paraphysis two large vessels are seen, ves., the epithelial
 
cells of which lie directly against the wall of the paraphysis. The little
 
tubules seem to be forcing their way into these vessels, which are branches
 
of the vessels seen in Fig. 6 and Fig. 10. The vessels also pass down into
 
the choroid plexuses. Fig. 16 is a section of an embryo of 31.4 mm.
 
  
  
 +
26 Paraphysis and the Pineal Kegion in Nectun;s Macnlatus
  
 +
17. Hkkuick, C. L. — Embryological Notes on the Brain of a Snake. Journ.
  
HB.  
+
Neurology, Vol. I, lGO-176. IS. Hill, C. L. — The Epiphysis in Teleosts and Amia. Journ. of Morphology.
  
 +
Vol. IX, 237-268.
  
 +
19. His, W. — Zur allgemeinen Morphologie des Gehirns. His. Archiv, 1892,
  
OCh.  
+
346-383.
  
 +
20. Humphrey, O. D. — On the Brain of the Snapping Turtle. Journ. of Comp.
  
 +
Neurology, Vol. IV, 73-108.
  
Hyp.  
+
21. Kingsbury, B. F. — The Brain of Necturus Maculatus. Journ. of Comp.
  
 +
Neurology, Vol. V.
  
 +
22. The Encephalic Evaginations in Ganoids. Journ. of Comp. Neurology, Vol. VII.
  
Fig. 16. Embryo of 31.4 mm. Harvard Embryological Collection, Sagittal
+
23. KxiPFFER, C. V. — Studien zur vergleichenden Entwicklungsgeschichte des
Series, No. 537, Sections 119-122, X 63 dlams.  
 
  
 +
Kopfes der Kranioten. Hefte I.
  
 +
24. Derselbe. Hefte II.
  
The general arrangement is practically the same as in Fig. 11, except that
+
25. Lewis, F. T. The Question of Sinusoids. Anat. Anx., Bd. XXV, No. 11.
all the parts have progressed somewhat in their development. The distal
 
end of the paraphysis has begun to grow distinctly more cephalad, and the
 
whole structure is much larger than at 26 mm. The choroid plexuses are
 
more extensive, and from the diencephalic plexus a prolongation is extending downwards towards the telencephalic plexus. This latter has
 
pretty well filled up the depths of the third ventricle, and from it prolongations dip down into the recesses in the floor of the fore brain. The
 
two commissures are practically the same as they were at 26 mm., and
 
  
 +
26. Leydig, F. — Zirbel und Jacobsonsche Organe einiger Reptilien. Archiv f.
  
 +
Mikrosk. Anatomie, Bd. 50.
  
12 Paraph vsis and the I'iiieal Heo-ion in Noetiiriis Maeulatus
+
27. LocY, W. A. — Contribution to the Structure of the Vertebrate Head.
  
 +
Journ. of Morphology, XI.
  
 +
28. MiNOT, C. S. — On the Morphology of the Pineal Region, based on its
  
though the epiphysis is a little larger it has been displaced considerably
+
Development In Acanthias. American Journ. of Anatomy, Vol. I, No. 1, 81-98.
candad, as this part of these sections was unluckily somewhat injured.  
 
  
Fig. IT is a section through the
+
29. On a Hitherto Unrecognized Form of Blood Circulation without
brain of an adult necturus. This
 
drawing is magnified 38 diams. only,
 
as it was too large to draw on the
 
same scale as the preceding figures.
 
The paraphysis, P. forms a very
 
complex structure extending far forward above and between the hemispheres. It consists in a general Avay
 
of a proximal and a distal part. The
 
former is broad and thick, and oxtends forward and upward. It then
 
turns forward at quite a marked
 
angle to form the distal part, which
 
is narrow and. tapering. The central
 
canal in the proximal part is very
 
large and irregiilar, but in the distal
 
portion much narrower. From all
 
parts of this canal a large number of
 
tubules are given off, which extend
 
in every direction, and between
 
which lies a confused mass of bloodvessels. One sees here a large vessel
 
ventrad to the organ, and a smaller
 
dorsad to it. the same relations as
 
appear at 12.4 mm., Fig. 6. From
 
these vessels branches pass into the
 
choroid plexuses.
 
  
Fig. 18 is a transverse . section of
+
Capillaries in Organs of Vertebrates. Pro. Boston Soc. Nat. Hist., Vol. 29, No. 10, S. 185-215.
an adult brain corresponding approximately to the line A-B, Fig. 17.  
 
This is drawn on the same scale as
 
most of the preceding figures, 63
 
diams. The paraphysis, P, is seen in
 
the median line between the hemispheres. It shows a distinct central
 
eavit}', with many tubules running out in every direction, between which
 
is a mass of blood-vessels of all sizes. Below a portion of the telencephalic plexus aiu1 the ])l(\\-us of the hemispheres are seen.  
 
  
 +
30. OsBORN, H. F. — Preliminary Observations on the Brain of Menopoma.
  
 +
Proceed. Phil. Acad., 1884.
  
 +
31. Contribution to the Internal Structure of the Amphibian Brain.
  
Via. 17. Brain of adult necturus.  
+
Journ. of Morphology, Vol. II, 51-86.
Sag-ittal Section, x 38 diams.  
 
  
 +
32. Rex, H. — Beitrage zur Morphologie der Hirnvenen der Amphibien. Morph.
  
 +
Jahrb., XIX, 295-311.
  
John Warroii
+
33. ScHOBEL, Jos. — Ueber die Blutgefasse des Cerebrospinalen Nervensystems
  
 +
der Urodelen. Archiv f. Wissen. Mikros., Bd. XX, 87-91.
  
 +
34. Selenka, E. — Das Stirnorgan der Wirbelthiere. Biolog. Centralbl., Bd. X,
  
13
+
323-326.
  
 +
35. Sorensen, a. D. — The Roof of the Diencephalon. Journ. of Comp. Neu rology, III, 50-53.
  
 +
36. Comparative Study of the Epiphysis and the Roof of the Diencephalon. Journal Comp. Neurology, IV, 153-170.
  
 +
37. Continuation of above. Vol. IV, 153-170.
  
Fig. is. Brain of adult necturus. Transverse section, X 63 diams. (See
+
38. Studenicka, F. Cii. — Beitrage zur Anatomie und Entwicklungsgeschichte
line A-B. Fig. 17.)
 
  
 +
des Vorderhirns der Cranioten.
  
 +
39. VoELZKOw, A. — Epiphysis und Paraphysis bei Krokodilien und Schild krot>en. Abhand. der SenchenbiXrgischen Naturforschenden Gesellschaft, Bd. XXVII, Heft. II.
  
14 Paraphysis and the Pineal Eegion in Nectunis Maciilatus
 
  
Fig. 19 is from a wax recoustruction of tlie adult paraphysis on a
 
scale of 120 diams., made from the same series as Fig. 18. The angle
 
between the proximal and distal parts is quite striking, and is much more
 
marked in Ichthyophis (Burckhardt, 4, Fig. 1), but of course this division
 
into proximal and distal parts is really a purely arbitrary one. This
 
model gives a good idea of the complex structure of the organ. The
 
tubules are of all shapes and sizes, often convoluted and anastomosing
 
with each other. The spaces between them, which the vessels occupy, are
 
quite large and striking.
 
  
 +
John Warren
  
  
  
Fig. 19. Wax model of paraphysis of adult necturus, same series as Fig.
+
27
18, X about 120 diams.
 
  
  
  
Pig, 20 represents a small portion of the paraphysis of Fig. 17, magnified 560 diams., and shows clearly the relation of the tubules to the
+
ABBREVIATIONS.
vessels. In the centre of the figure is a tubule, T, dividing into two
 
branches, T^ T-. Surrounding these tubules on every side are sinusoids,
 
si., whose flat endothelial cells are seen lying directly against the epithelial
 
wall of the tubules with no connective tissue between them. We find
 
here in order first a sinusoid, then a tubulcj then another sinusoid and
 
another tubule, and finally a sinusoid. The wall of the tubules consists
 
of a single layer of cells with large oval nuclei and very indistinct cell
 
boundaries. The nuclei contain masses of granules arranged very irregu
 
  
  
Joljn Warren
 
  
 +
A. C. — Anterior commissure. L. Y. Ch. Fix. — Choroid plexus. M. B Dien. — Diencephalon. 0. C D. Flex. — Diencephalic plexus. Tel. Plx. i?.— Epiphysis. Tel. Ep. A. — Epiphysal arch. F. C F. B. — Fore-brain. P. T- A. —
  
 +
F. M. — Foramen of Munro. ■ P. A. H. — Hemisphere. F.
  
larly. There can be no question abont the glandular nature of the paraphysis, and its circulation is evidently sinusoidal.  
+
H-JB.— Hind brain. S.C.
  
The choroid plexus, Ch. Fix., Fig. 17, appears as a confused mass of
+
Hyp. — Hypophysis. Si.
  
 +
I. J. V. — Internal jugular vein. T.
  
 +
L. Fix. — Choroid plexus of lateral Tes.
  
 +
ventricle. ^'
  
Fig. 20. Small portion of adult paraphysls, same section as Fig. 17, X 560
 
diams.
 
  
vessels covered by a thin layer of cells. This mass completely fills up
 
the cavity of the fore and mid brains, and may in some cases appear in
 
the hind brain, Fig. 23, though there seems to be considerable variation
 
  
 +
Lateral ventricle. Mid-brain. Optic commissure. -Telencephalic plexus. -Telencephalon. -Posterior commissure. Post-velar arch. Paraphysal arch. Paraphysis. -Superior commissure. Sinusoid. •Tubule. ■Vessel. -Velum transversum.
  
  
  
Fig. 21. Wax model of epiphysis of adult necturus. X 280 diams.  
+
THE DEVELOPMENT OF THE THYMUS.
  
in the caudad development of this part of the ple.xus. Tlie two parts
+
BY
of the plexus overlap each other, and are also closely interlaced.
 
  
The epiphysis, E. is still attached to the brain by a very narrow stalk.  
+
E. T. BELL, B. S., M. D.
The body overlaps the stalk somewhat behind, and then is prolonged
 
forward as an oval flattened body above the roof of the diencephalon, and
 
  
 +
Instructor in Anatomy, University of Missouri.
  
 +
With 3 Plates and 5 Text Figures.
  
16
+
This paper is intended mainly as a contribution to our knowledge of the histogenesis of the thymus in mammals. Special attention is given to the origin and development of the corpuscles of Hassall, since their mode of formation has never been satisfactorily described in mammals and their significance in all forms is in dispute. An attempt is also made to show in detail the changes that occur during the transformation of the thymus from the epithelial to the lymphoid condition.
  
 +
This work was begun at the suggestion of Dr. D. D. Lewis at the University of Chicago. The greater part of it has been done at the University of Missouri. Special acknowledgments are due Dr. C. M. Jackson for valuable criticism and suggestions. T wish also to thank Mr. Charles H. Miller of the University of Chicago for his kindness in sending me material.
  
 +
Material and Methods.
  
PiiTajiln'sis and tlic Pineal Rogig^i in Xccturus Maculatns
+
As material for the greater part of my work, I. have used pig embryos from 8 mm. to full term (26 cm. to 30 cm.). These are especially suitable for such work since they may be procured in abundance from the large packing houses at almost any stage of development. For special purposes I have studied a few specimens from human foetuses, and from the cat, rat, and guinea pig. The smaller pigs used (8 mm. to 27 mm.') belong to the collection in the anatomical laboratory at the University of Missouri. These were stained in bulk with alum-cochineal and mounted in serial sections. In the later stages, which were prepared specially for this work, tbe ventral half of the cervical and anterior thoracic regions was usually out out and embedded from pigs from 3 cm. to 8 cm. On specimens from 8 cm. to 30 cm.. I dissected out the thymus and used sucb parts as were desired.
  
 +
^ The crown-rump measurement is used in all cases.
  
 +
AMERICAN .TOCTRNAL OF ANATOMY. VOI,. V.
  
its cavity seems to be divided more or less into compartments. Fig. :H
 
represents a wax reconstrnction of an adult epiphysis seen from ^above.
 
It is irregularly triangular in shape with a broad base and a blunt apex.
 
Its surface is grooved more or less by vessels which lie against its Avails.
 
Fig. 22 is the same model with the top removed. The interior is more
 
or less subdivided by incomplete septa. At its apex there is a small cavity
 
  
  
 +
30 Tlie Development of the Thymus
  
 +
All pig material was fixed in Zenker's fluid, embedded in paraffin, and mounted in serial sections from 3 ju, to 10 /x thick. Except those of the young stages (8 mm. to 27 mm.) the sections were stained on the slide. Most of them were stained with hsematoxylin or iron-hgematoxylin and counterstained with Congo red. For special purposes many other stains were used.
  
Fig. 22. Same as Fig. 21, with top of epiphysis removed.  
+
To demonstrate the delicate protoplasmic threads of the syncytium during the later stages of the lymphoid transformation, I stained by the iron-haematoxylin method but omitted the final decolorization in ironalum. Protoplasm is stained deep black; nuclear structure is poorly shown, but the finest cytoplasmic processes may be seen.
  
1)0unded behind by a partial septum, then comes a large chamber, which
+
For the demonstration of connective tissue fibrillae in the syncytium, I found the method recommended by Jackson (13, S. 39) most satisfactory.
divides into two passages running back towards the angles at the base.
 
Between these two passages appears a comparatively solid area, interrupted, hoAvever. to some extent by small spaces, aa^IucIi communicaio Avith
 
each other and the larger chambers. This solid area lies over tbe stalk
 
of the organ. The sujDra commissure appears to be comparatively small,
 
  
 +
Text Fig. 2.
  
 +
Text Figure 1. Cranial view of third gill pouch (thymic anlage) ; X 33; pig embryo, 11 mm.; ec, ectoderm; I, lumen; nt, nodulus thymicus; ph, connection to pharynx; s p, sinus prsecervicalis.
  
 +
Text Figure 2. Ventral view of thymic anlage; X 33; pig embryo, 15 mm.; ec, ectoderm; I, lumen; n t, nodulus thymicus; ph, connection to pharynx; s p, sinus prsecervicalis.
  
Fig. 23. Brain of adult necturus. Viewed from above. X 7 diams.  
+
To determine the relation of the blood-vessels to the corpuscles of Hassall, I put a young kitten under deep anesthesia and injected a large quantity of a strong aqueous solution of Prussian blue into the aorta through the common carotid artery. The heart continues to beat even after an amount of fluid twice as great as the total volume of the blood has been injected. An injection made in this way is under a slightly increased blood pressure and easily reaches the finest capillaries. There is therefore a thorough injection with little danger of rupturing delicate blood-vessels.
  
while the posterior is large and forms a deep groove in the roof of tlie
+
Organogenesis. My observations on this phase of development are not sufficiently complete to warrant a full discussion. A brief survey may however prepare the way for a better understanding of the histogenesis. The text figures show the shape in outline of the third gill pouch and thymic anlage
brain. Fig. 23 is a vioAv of the brain of an adult necturus shoAving the
 
relative positions of paraphysis and epiphysis. The tufted extremity
 
of the diencephalic plexus can be seen in the fourth ventricle.
 
  
If Fig. 1, the embryo of 8-9 mm., is compared Avith Fig. 17, the adult,
 
one sees that the paraphysal arch has been Avholly taken up in the
 
formation of the telencephalic plexus, the plexus of the hemispheres, and
 
  
  
  
John Warren 17
+
E. T. Bell 31
  
the paraphysis. The velum and the greater part of the post-velar arch
+
from 11 mm. to 27 mm. . They are graphic reconstructions. Since this pouch is nearly all converted into thymus it may be regarded as the thymic anlage from a very early stage.
have been absorbed in the formation of the diencephalic plexus. A
 
portion of this arch, however, persists and forms that part of the roof
 
of the diencephalon between the diencephalic plexus and the supra commissure. The epiphysal arch has formed the epiphysis.  
 
  
The paraphysis is a structure common to all vertebrates either in the  
+
At 11 mm. (Text Figure 1), the pouch is a hollow epithelial tube directed from without ventrally and mesially. The lumen (l) is large and communicates freely with the pharynx. On the dorso-lateral aspect of the pouch is a solid epithelial mass (n t) distinctly different in structure from the rest of the pouch. This is the nodulus thymicus (Kastschenko, 14) and will be referred to by that term. This structure has been described by Stieda (26), Prenant ' (22), and others as the anlage of the carotid gland.
adult or embryonic condition (Selenka, 34, Francotte, 11), but previous
 
observations on mammals leave much to be desired. It always arises from
 
the telencephalon cephalad to the velum transversum, and its opening
 
is placed between and dorsad to the foramina of Munro as emphasized
 
by Dexter (5).  
 
  
In the cyclostomes, Ammocoetes (Kupffer, 24), and Petromyzon
+
It was evidently mistaken by Minot ' in a 12-mm. pig for the anlage of the entire thymus. It may be seen as early as the 8 mm. stage budding off from the cranio-lateral aspect of the pouch. Immediately behind the nodulus thymicus, but not connected to it at this stage is the inner blind extremity of the sinus prsecervicalis (s p). These become fused at 12 mm. or 13 mm.
(Burckhardt, 3), the paraphysis appears as a small sac-like diverticulum
 
lying ventrad and close to the enlarged distal end of the epiphysis. In
 
elasmobranchs, Minot (28) and Locy (27) found that the paraphysis
 
in Acanthias appears at quite a late stage as a small outgrowth from  
 
the paraphysal arch and, owing to the small size of the post-velar arch
 
and the compression of the velum, it comes to lie immediately cephalad to
 
the epiphysis. In ganoids, Kupffer found in Accipenser that the paraphysis appears first as a small outgrowth which later becomes a somewhat
 
sacculated vesicle (23, Fig. 19). Hill (18) and Eycleshymer and Davis
 
(9) studied the paraphysis in Amia. Here it begins as a simple vesicle,
 
which increases rapidly in size and gives off diverticuli from its central
 
cavity. In teleosts (Burckhardt, 3) the paraphysis appears late and
 
remains in a rudimentary condition. In the dipnoi, Burckhardt (3) describes the paraphysis in Protopterus as a wide outgrowth giving off small .  
 
diverticuli.  
 
  
In amphibia the organ becomes highly differentiated and its appearance in the adult brain is very striking. It appears as an elongated body
+
At 15 mm. (Text Figure 2) the thymic anlage is more elongated. It now projects ventrally and medianwards, its free end lying immediately caudad to the median thyroid anlage and just craniad to the pericardium. Its lumen (Z) is still in communication with the pharynx. The sinus prsecervicalis {s p) is drawn out, its lumen being smaller and longer. It is now fused to the outer two-thirds of the posterior aspect of the nodulus thymicus (n t).
lying above and between the hemispheres, and extending cephalad for
 
a varjdng distance in various forms. Fig. 23. Osborn (31, PI. 4) shows
 
a view of the brains of Siredon, Necturus, Proteus, and Siren. The
 
paraphysis has the same general form in each of these, but it is somewhat
 
larger in Necturus. The paraphysis of Triton and Ichthyophis (Burckhardt, 4) has the same characteristics. In the latter the paraphysis appears in sagittal section as a hammer-shaped organ extending forward
 
above the hemispheres. (4, Fig. 1). In Rana the paraphysis has the
 
same position as in Necturus, but is smaller. On removing the top of the  
 
skull in Necturus the paraphysis is seen lying beneath the pia surrounded
 
by the blood-vessels which cover this part of the brain. It appears to the
 
naked eye so vascular and also in sections so intimately related to the
 
2
 
  
 +
At 18 mm. (Text Figure 3) the anlage is growing rapidly in a caudal direction and just entering the thoracic cavity. It is connected to the pharynx by a delicate epithelial cord. There is still a lumen in its caudal part. The sinus praecervicalis has lost its connection to the nodulus thymicus." The outer part of its lumen has disappeared and it seems about to lose its connection with the ectoderm.
  
 +
At 20 mm. (Text Figure 4) the thymus extends well into the thoracic cavity. Its thoracic segment (t h) has increased considerably in size and is united to the gland of the opposite side.
  
18 Paraphysis and the Pineal Pegion in Necturns Maculatus
+
The nodulus thymicus still forms the greater part of the head. The anlage has no connection with the pharynx or the epidermis. There is
  
choroid plexus that it is not astonishing that it was at first regarded as
+
"Prenant is said to have since abandoned this idea and accepted Kastschenko's view. (v. Ebner in Kolliker's Gewebelehre des Menschen. Aufl. 6, Bd. 3, 1, S. 340.)
a portion of this plexus. According to Minot (28) the paraphysis of
 
Eana is characterized by the character of its epithelium, its tubular structure and its apparently sinusoidal circulation. This is practically similar
 
to the conditions found in Necturus.  
 
  
In ^lenopoma Sorenscn (36) describes the paraph3'sis as a solid vascular mass, and in Ichthyophis Burckhardt (3) describes it as an
+
^Laboratory Text of Embryology, p. 191; also p. 209 and Fig. 124.
elaborately folded structure of a glandular character. In Amblystoma,  
 
Eycleshymer (8) shows that the organ gives off tubules and has a digitated appearance. In Diemyctylus (Mrs. Gage, 13), in an embryo of
 
10 mm. the paraphysis closely resembles that of Necturus at 18 mm.
 
(Minot, 28, Fig. 13), and in the adult it is a long tube giving off many
 
tubules in close relation to vessels.  
 
  
Herrick (15) calls the paraphysis of an adult Necturus the " preparaphysis " and says it consists of an irregular central chamber with
+
On the opposite side in this specimen, .these structures were fused over a
complicated diverticuli in close relation to vessels. This description
+
very small area.
corresponds closely with Fig. 17. The model of the adult paraphysis,  
 
Fig. 19, shows the complicated arrangement of the tubules, many of
 
which anastamose with each other, and the spaces between the tubules
 
are filled by blood-vessels.  
 
  
Fig. 6 shows how the paraphysis at 12.5 mm. is beginning to invade a
 
large vessel lying over it on the surface of the brain. This vessel at this
 
point is much enlarged. Fig. 10 shows this relation much clearer and
 
also that these vessels in relation to the paraphysis are tributaries of the
 
internal jugular vein. Fig. 15 shows the relation of the paraphysis to
 
these vessels at 26 mm. and that the vessels pass into the choroid plexuses
 
both dorsad and ventrad to the organ. The little tubules can be seen growing out into the vessels. Fig. 17 shows how these relations between vessels
 
and tubules in the adult become much more intimate, and the vessels
 
corresponding to those in Fig. 15 are seen passing into the choroid plexuses dorsad as well as ventrad to the paraphysis. Schobel (33), who
 
studied the circulation in the brain of certain amphibia, of which
 
Necturus was one, shows that in the adult two large vessels pass outward
 
just caudad to the hemispheres to empt}'^ eventually in the internal
 
jugular vein. These vessels surround the paraphysis and anastomose
 
with two or three large vessels running forward between the hemispheres.
 
This is practically the same arrangement shown in the model in Fig. 10.
 
He does not mention the paraphysis but refers to it as a large venous
 
plexus. Eex (32) also has studied the veins in the amphibian brain,
 
and his preparations are practically the same as Schobel's. He refers
 
to the paraphysis as the " nodus chorioideus " and says that it is a sort
 
  
  
 +
32
  
John Warren 19
 
  
of meeting point for the veins of the fore and mid brains. He shows
 
beautifully in his injections how veins pass both dorsad and ventrad to
 
the paraphj'sis to enter the plexuses, and how closely these vessels are
 
related to the tubules of this structure. Mrs. Gage shows practically the
 
same arrangement in Diemyctylus
 
  
As regards the arteries Schobel shows that they are much smaller than
+
The Development of the Thymus
the veins, and describes a small vessel passing caudad to the hemispheres
 
to pass eventually into the plexuses. The intercrescence of the tubules
 
of the adult paraphysis and the veins is shown clearly in Fig. 30, each
 
vessel and tubule lying back to back with no connective tissue between
 
them. In view of all these facts it seems evident that the circulation of
 
the paraphysis is sinusoidal. According to the above descriptions, the
 
development of the paraphysis into a complicated, glandular organ, which
 
is also very vascular, seems to be a striking characteristic of the amphibia.
 
  
In lacertilia the paraphysis of Anguis fragilis has been studied by
 
Francotte and of Lacerta vivipara by Francotte (10, 11, 12) and
 
Burckhardt (3). The latter shows the paraphysis in an embryo of
 
13 mm. as a narrow tube with a slightly expanded distal extremity,
 
much as that of ISTecturus of 15 mm. Francotte describes the paraphysis
 
of Lacerta vivipara as a long tube giving off a mass of tubules which
 
lies under the parietal eye, and resembles the epiphysis of birds (11, Fig.
 
14; 12, Fig. 24). In Anguis (10, Figs. 15 and 19) the paraphysis forms
 
a long narrow sack, with somewhat convoluted walls, which curves back
 
over the post-velar arch to end in close relation to the parietal eye.
 
  
The conditions in the lizard are essentially the same (10, Fig, 31).
 
In Phrynosoma coronata Sorensen (35, Fig. 2) describes the paraphysis
 
as a long, narrow tube, immediately cephalad to the epiphysis.
 
  
In the ophidia Leydig (26, Fig. 6) shows the paraphysis of an embryo
+
now an elongated mass of thymic tissue extending upwards behind the nodiilus thymicus, and fused with it. Its upper pointed extremity curves outwards around the hypoglossal nerve. This is the " thymus superficialis " (t s) of Kastschenko and is regarded by him as being formed from the sinus praecervicalis. Kastschenko describes this elongated portion as being always separate from the rest of the head, being connected only by connective tissue. In my preparations it is clearly continuous with the rest of the anlage, and seems to have formed by growing out from it. The presence of a lumen in its lower end favors Kast
of Vivipara urcini near birth as a large, wide tube with no convolutions
 
or diverticuli and practically the same conditons in a young " Eingelnatter" and Tropidonatus natrix (26, Figs. 5 and 2).  
 
  
Among the chelonia Voelzkow (39) has described the paraphysis in
 
Chelone imbricata as at first a wide tube much convoluted, which later
 
decreases somewhat in size. (Figs. 21 and 22.) Its distal end inclines
 
caudad close to the epiphysis. In Chelone mydas Humphrey (20, Fig. 7,
 
PI. II) shows the paraphysis as a long tubular structure, giving off small
 
tubules, and in an embryo of Chelydra it appears as a large, wide sack,
 
from which tubules arise. It is in closer relation to the epiphysis than
 
in Chelone mydas or imbricata.
 
  
In Cistudo Herrick shows a model of Sorensen (15, Fig. 5, PI. VI)
+
.ec
of the paraphysis, which is a wide tube with convoluted walls and tubules.  
 
  
  
  
20 Paraphysis and the Pineal Region in Necturus Maculatus
 
  
In the crocodilia Voelzkow (39) has described the paraphysis of
 
Crocodilus madagascarensis grand and Caiman niger spix. In the former
 
the paraphysis is at first a wide tube which becomes convoluted and much
 
longer and narrower. In the latter the paraphysis forms a larger tube
 
and the convolutions and tubules are more complicated. In both cases
 
the organ reaches its greatest development in embryonic life and retrogrades later, though more so in the crocodile. He was unable, however,
 
to follow the development in the caiman as far as in the crocodile.
 
Owing to the thickenings in the brain wall the organ is crowded somewhat caudad against the post-velar arch.
 
  
In birds the paraphysis is relatively rudimentary. Burckhardt (3)
+
Text Fig. 3.
shows the paraphysis in an embryo of the crow as a small diverticulum
 
not unlike that of Petromyzon. Dexter (5) worked out in detail the
 
development of the organ in the common fowl, and showed that it appeared at first as a small diverticulum. The walls become much thickened and in a chicken of 10 days it is a small, oval structure, about 150 fx
 
in its greatest diameter, with very thick walls (5, Fig. 5). Selenka (34)
 
has described the paraphysis in the oppossum, but as far as I am aware
 
little is known of the development of the paraphysis in mammals, though
 
Francotte (11) has observed it in human embryo of twelve weeks.  
 
  
From the cyclostomes to the amphibia the paraphysis shows a steadily
 
progressive development, and the various forms through which it passes,
 
from the simple diverticulum of Petromyzon to the elaborate gland of
 
the urodela, are illustrated in a general way by the stages of its development in Necturus. In the vertebrates above the amphibia the paraphysis
 
retrogrades and practically retraces its steps through the reptilia and
 
birds to mammals, reaching in the chick essentially the same form in
 
which it started in Petromyzon. Its development, therefore, may be
 
indicated by a curve, which ascends steadily from the cyclostomes, reaches
 
its height in urodela, and descends through the reptilia and birds to
 
mammals.
 
  
The epiphysis is present in nearly all vertebrates. It is stated to be
 
absent in the alligator (Sorensen, 36 and 37), and in the caiman and
 
crocodile (Voelzkow, 39) and in Torpedo (d'Erchia, 7).
 
  
The epiphysis of Necturus as compared with the paraphysis is relatively
+
Text Fig. 4.
poorly developed and in this respect resembles the epiphysis of other
 
urodela (Mrs. Gage, 13). In Diemyctylus Mrs. Gage found that the
 
epiphysis was entirely cut off from the brain and that its cavity was
 
nearly obliterated. In Ichthyophis (Burckhardt, 1 and 4) the epiphysis
 
is a small, pear-shaped organ attached to the brain by a narrow solid
 
stalk. Herrick (15) in Menopoma, describes the epiphysis as an irreg
 
  
  
John Warren 21
 
  
ular number of vesicles attached to the brain by a narrow opening. According to Kingsbury (21) the structure in Necturus consists of an
+
Text Figure 3. Ventral view of thymic anlage; X 33; pig embryo, 18 mm.; ec, ectoderm; I, lumen; nt, nodulus thymicus; ph, connection to pharynx; s p, sinus praecervicalis.
aggregation of closed vesicles, forming an oval, flattened body, and there
 
is no connection with the brain. The cavity of the epiphysis communicates through its stalk with the cavity of the diencephalon up to 15 mm.,  
 
when the cavity in the stalk becomes obliterated. The stalk persists and
 
was present in all the adult brains which I examined, but in some cases
 
it was so small that it could easily be overlooked. The reconstruction
 
of an adult epiphysis. Fig. 22, shows that the cavity of the organ forms
 
a large chamber subdivided to a certain extent by incomplete septa. A
 
much more solid area is seen towards the caudal extremity, which is
 
placed just over the stalk. The same characteristics I have observed in
 
another model made from a different brain. One gets the idea that the
 
epiphysis consists of a series of vesicles in studying sagittal sections a
 
little to one side of the median line, as for instance in Fig. 17, where the
 
epiphysis was displaced a little to one side.  
 
  
. There has been such a vast amount written on the origin of the
+
Text Figure 4. Ventral view of thymic anlage; X 33; pig embryo, 20 mm.; f, area fused with gland of opposite side; I, lumen; nt, nodulus thymicus; th, thoracic segment; t s, thymus superficialis.
epiphysis and the pineal or parietal eye and their homologies that it seems
 
superfluous to add anything more here. In a very general way, however,
 
there seems to be some sort of proportion in the relative development of
 
the paraphysis, epiphysis, and the parietal eye. In urodela where there
 
is no parietal eye and a small epiphysis, the paraphysis reaches its highest
 
degree of development. In those forms where the paraphysis is rudimentary or relatively slightly developed the parietal eye is present or
 
else the epiphysis is relatively highly developed. Compare, for example,
 
the figures of Burckhardt (3) of Petromyzon, Minot (28) of Acanthias,  
 
Burckhardt (3) of Trout, Leydig (26) and Voelzkow (38) of reptilia,  
 
and Dexter (5) of the fowl. Rana, however, seems to be a marked exception to this statement, as there the paraphysis, epiphysis, and pineal
 
eye are all present and well developed, and the same may be said for
 
Lacerta (Francotte, 10 and 11) and Sphenodon (Dendy, 6). As the
 
paraphysis and epiphysis are glandular structures they have probably
 
some sort of compensatory function and where one is highly developed
 
the other is relatively rudimentary or even absent. Compare in this
 
respect also Torpedo with Acanthias and the crocodile and alligator with
 
the chick.  
 
  
As a rule the stalk of the epiphysis is placed immediately caudad to the
+
schenko's view, for there is no lumen in the head at 18 mm. in my preparations. On the other hand the separation from the head at the 18 mm. stage favors the idea that the sinus prsecervicalis degenerates. I have not studied a sufficient number of specimens at this transition stage to enable me to decide this point, though I believe the ectoderm takes no part in the formation of the thymic anlage. Kastschenko's results are opposed by nearly all other students of this problem, but his work should not be discarded before the development of the thymus superficialis in the pig has been accurately determined.
supra commissure, in all cases I believe, except in the toad, where there
 
is a distinct interval between it and this commissure (Sorenson, 36).
 
In Necturus there is an interval in the roof of the brain between the stalk
 
and the posterior commissure. This portion of the roof of the brain was
 
  
 +
At 27 mm. (Text Figure 5) the thymus is much longer and extends
  
  
22 Paraphysis and the Pineal Eegion in Necturus Macnlatus
 
  
described by Kupffer (23) as the " schaltstlick," and according to him it
+
E. T. Bell
is best developed in amphibia. Burckhardt (3) maintains that it occurs
 
in all vertebrates from Pctromyzon np, but according to Kupffer it is
 
absent in Accipenser (23, Fig. 19), and it is also wanting in Acanthias
 
(Minot, 28, Pig. 10) and in the fowl (Dexter, 5, Fig. 9).  
 
  
The velum transversum is probably characteristic of all vertebrates.
 
Minot (28). In Petromyzon the velum appears as a small transverse
 
fold, and the post-velar arch is well marked. The plexus development
 
is, however, very slight. In elasmobranchs the velum of Acanthias
 
forms a long, narrow, transverse fold, and the post-velar arch is so small
 
that the origin of the velum seems to be close to the supra commissure.
 
The caudal layer of the velum is distinctly thinner than the cephalic
 
(Minot, 28, Fig. 6). This is also seen in Torpedo (d'Erchia, 7, Fig.
 
12), and in Necturus, Fig. 6. The velum later on has the character of
 
a choroid plexus, but the plexus of the hemispheres is very rudimentary
 
(Minot, 28). In Notidanus Burckhardt (3) shows a long, narrow velum,
 
a short post-velar arch, and a small telencephalic plexus. The plexus
 
of the hemispheres, however, is absent.
 
  
In Accipenser (Kupffer, 23, Fig. 19) the velum is long, well developed
 
and folded to a certain extent, and the post-velar arch is quite extensive.
 
In ganoids (Studnicka, 38) the membranous roof of the brain serves as
 
the tela choroidea of higher types. In this class of vertebrates according
 
to Burckhardt (3) the plexus of the hemispheres is lacking, but the
 
telencephalic plexus is well developed, and in teleosts the former is also
 
wanting, but the latter present in a reduced form.
 
  
In amphibia all the plexuses are highly developed, and in J^ecturus
+
33
they are of marked extent (Kingsbury, 21). The velum in Necturus
 
appears at first as a transverse fold in the roof of the brain separating
 
the diencephalon from the telencephalon. This fold develops at first
 
ventrad and then caudad through the mid brain as far as the hind brain.
 
This great growth of the velum forms the diencephalic plexus. The
 
post-velar arch, which at first is wide and well marked, is practically
 
absorbed by the overgrowth of the velum, and a small portion only
 
persists in the roof of the diencephalon between the origin of the diencephalic plexus and the supra commissure. Fig. 17. The telencephalic
 
plexus develops from the paraphysal arch immediately cephalad to the
 
paraphysis, the opening of which therefore is surrounded by these two
 
plexuses. They fill up the cavity of the third ventricle and mid brain,
 
and the diencephalic plexus may appear in the hind brain (Osl>orn, 29).
 
This seems to vary in different cases, and in the majority of brains which
 
I was able to examine the extremity of this plexus did not actually extend
 
  
  
  
John Warren 23
+
well down into the thoracic cavity in relation to the base of the heart where it has fused with the gland of the opposite side. Buds are now beginning to form through the greater part of its extent. Traces of the original lumen (I) may still be seen in several places. The "thymus superficialis " is bent around the twelfth nerve. A delicate cord of thymic
  
into the hind brain. In- Fig. 33, however, this extremity appears as a
 
marked tuft in the fourth ventricle. The plexuses of the hemispheres
 
arise on either side from the origin of the telencephalie plexus and pass
 
into the lateral ventricles, extending nearly to their cephalic extremities.
 
  
In Lacerta vivipara (Francotte, 12, Fig. 24) the post- velar arch has
 
been much com})ressed from before backward so as to form a deep narrow
 
angle. At the apex of the angle the folds of the diencephalic plexus are
 
seen. The velum is smooth and apparently is not included in the
 
formation of the plexus. In Anguis fragilis (Francotte, 10, Figs. 19
 
and 15), the post-velar arch does not seem to be so much compressed,
 
and the plexus formation somewhat greater. As he says, however, the
 
development of those parts in Lacerta is practically the same as in Anguis.
 
According to Burckhardt the telencephalie plexus is much reduced
 
in size, consisting merely of small folds, but the plexus of the hemispheres is well developed (Burckhardt, 3).
 
  
In the turtles Humphrey (20) found that the velum of Chelydra is
 
but slightly developed, and no diencephalic plexus is formed. All the
 
other plexuses are telencephalie in origin.
 
  
Herrick (15, Fig. 5, PI. VI), shows in Cistudo a well-developed telencephalie plexus and a diencephalic plexus represented by many folds in
+
Text Fig. 5.
the caudal layer of the velum and the post-velar arch. In Chelone imbricata Yoelzkow (39, Figs. 19 and 22) shows at first a well marked
 
velum and a wide post-velar arch. In later stages the velum and practically all the arch are thrown into folds to form the diencephalic plexus.
 
The telencephalie plexus is also well developed. In the serpents much
 
the same arrangement can be seen. The velum (Leydig, 26, Figs.
 
2, 5, and 6) forms a prominent fold, and it and the post-velar arch
 
form a very vascular plexus. In the crocodilia (Voelzkow, 39, Figs.
 
7, 11, 13, 15), the velum and the post-velar arch are at first well
 
marked, but the parts later become so compressed from before backward that the arch forms a deep acute angle in the depths of which plexus
 
foldings are seen. The caudal layers of the velum, however, takes no part
 
in the plexus formation. In birds, Dexter (5) found that the velum of
 
the fowl is small and the post-velar arch broad at first. This becomes
 
compressed so as to form an acute angle much as in the crocodilia. The
 
cephalic limb of this angle and all the velum is converted into the choroid
 
plexus. In birds the plexus of the hemispheres is very well developed,
 
but the telencephalie plexus is practically absent.  
 
  
In fishes the plexus development is quite simple, in many cases being
+
Text Figxjre 5. Ventral view of thymic anlage; X 33; pig embryo, 27 mm.; /. area fused with gland of opposite side; 1, lumen; nt, nodulus thymicus; th, thoracic segment; t s, thymus superficialis.
merely the thin membranous roof of the third ventricle; in others, however, this is much folded and vascular (Sorensen, 35). In certain forms
 
  
 +
tissue fused with the l)ack of the nodulus thymicus connects the thymus superficialis to the rest of the head.
  
 +
From about 3 cm. until toward the end of fcetal life the thymus shows the two constrictions, described by Prenant (22) (for the sheep) as the intermediary and the cervico-thoracic cords. These cords connect three 3
  
24 Paraphysis and tfio Pineal Eegion in Necturus Maculatus
 
  
there is a telenccphalic plexus, but the plexus of the hemispheres is
 
absent or rudimentary (Burckhardt, 3). In amphibia there is a great
 
overgrowth of all the plexuses, especially of the diencephalic plexus,
 
which here reaches its highest development. In reptilia the plexus of the
 
hemispheres is well developed, but the telencephalic plexus is reduced
 
in size (Burckhardt, 3), and the diencephalic much more so. In birds
 
the plexus of the hemispheres is highly developed, the telencephalic
 
plexus practically absent, and the diencephalic plexus, while very similar
 
to that of reptilia, approaches nearer to the tela choroidea of higher
 
mammalia.
 
  
Osborn first named the supra-commissure and worked out its homologies. According to him (30) the urodela are distinguished from the
+
3-i Tlic Development of the Tliynius
anura by the frequent extensive development of this commissure, which
 
is large in Amphiuma, smaller in Necturus, and much reduced in Eana.
 
It appears in Necturus a little later than the posterior commissure, as
 
is usual in most cases, as far as I am aware, except in Ammocoetes, where
 
it appears shortly before the posterior commissure (Kupffer, 24, Fig. 5).
 
It is found in all the chief types of vertebrates, and is usually smaller
 
than the posterior (Minot, 28). It is developed from the diencephalon,
 
while the posterior belongs to the cephalic limit of the mid brain.
 
  
Conclusions.  
+
enlargements which we may call the head, the luid-t-ervical segment, and the thoracic segment. I will consider each part separately. The thoracic segment develops rapidly, spreading out ahove and in front of the heart. The glands of the two sides fuse completely in this region. The lymphoid transformation is noticeable at 3.5 cm. and well advanced at 4.5 cm. The medulla begins to form at 8 cm. The cervico-thoracic cord is at first very narrow but soon thickens and joins the cord of the opposite side. At full term they form a sharp constriction, 3 mm. to 4 mm. wide and 5 mm. to 6 mm. long, situated at the superior aperture of the thorax, and connecting the mid-cervical and thoracic segments. The histological changes take place here later than in the enlargements.
  
1. The paraphysis appears first in an embryo of 12 mm. It is developed from the telencephalon immediately cephalad to the velum transversum as a small diverticulum, which becomes eventually a complicated
+
The mid-cervical segment develops like the thoracic segment but somewhat more slowly. Budding, lymphoid transformation, and formation of the medulla all begin here a little later than in the head and thoracic segment. Its caudal end is slightly in advance of its cranial end. The intermediary cord is well marked at 4 cm. It soon becomes very attenuated, having at 6 cm. in many places a diameter of only 15 fx. Prenant suggests that this drawing out of the gland is caused by the rapid growth of the neck. Later it increases in size and at full term is noticeable only as a very slight constriction between the head and the mid-cervical segment. The histological changes are much later here than in other parts of the gland.
gland with anastomosing tubules. The gland is very vascular, and has a
 
sinusoidal circulation.  
 
  
2. The epiphysis appears first in an embryo of 9-10 mm., and is developed from the diencephalon. It is always attached to the brain by a  
+
The greater part of the head in the early stages is formed by the nodulus thymicus. This body grows slowly, attaining a diameter in crosssection of .5 mm. at 8 cm. Its cross-sectional area at 8 cm. is about onethird that of the rest of the head of the thymus. At this stage the nodulus thymicus is a rounded body lying on the inner aspect of the head in relation to the carotid artery. A small area of its outer surface is fused with the lymphoid tissue of the thymus. Its histological structure has been fully described by Prenant (22). From the earliest stages, it consists of cords of epithelial cells separated by blood capillaries. At 8 cm. the thymus superficialis (Kastschenko) is a large body lying craniad and dorsal to the rest of the head but connected to it at its caudal extremity.
small solid stalk, and the cavity is partially subdivided by incomplete
 
septa.  
 
  
3. The velum transversum grows at first ventrad and then caudad as
+
I have no observations on the head of the thymus between 8 cm. and full term, having overlooked it in collecting my material. In a full term pig (30 cm.), the cervical part of the thymus is in two distinct parts. The postero-ventral part, representing part of the head, the intermediary cord, and the mid-cervical segment, is about 3 cm. long and 1 cm. wide. It extends from the upper border of the thyroid cartilage to the thorax, and with the corresponding part of the opposite gland encloses the
far as the hind brain, forming in this way the diencephalic portion of  
 
the choroid plexus. The post-velar arch, which is at first quite extensive,  
 
is almost entirely absorbed in this extensive growth of the v.elum.
 
  
4. The telencephalic plexus arises from the roof of the telencephalon,
 
and fills up the depths of the cavity of the third ventricle. The opening
 
of the paraphysis is surrounded by these two plexuses.
 
  
5. The plexus of the hemispheres arises at a right angle from the
 
telencephalic plexiis just cephalad and ventrad to the opening of the
 
paraphysis.
 
  
 +
E. T. Bell 35
  
 +
trachea, thyroid, and lower ]iait of the larynx. A slight narrowing at the junction of the upper and middle thirds indicates the position of the intermediary cord. The antero-dorsal part^ the thymus superficialis, is rounded in cross-section, tapei-rrfg- to a point behind. Its anterior end is about 7 mm. in diameter and loops around the twelfth nerve as in the earliest stages. A lobule hangs over ventral to the nerve, a thin cord being dorsal to it. The posterior end of the thymus superficialis extends to the cricoid cartilage dorsal to the postero-ventral part of the gland. It is united to this part of the gland by a very delicate band of thymic tissue. I did not find the nodulus thymicus at full term. It has either moved away from the head or degenerated.
  
John Warren 25
+
The duct of the thymus is the lumen of the third gill pouch. A glance at the Text Figures will show its development. It is broken up into segments and finally obliterated. I could find no traces of it at 3.7 cm. or later. On the theory of the exclusively endodermal origin of the thymus. I cannot explain the absence of a lumen in the head at IS mm. and its presence at 20 mm. and 27 mm. unless it be due to individual variation in different specimens.
  
6. The supra-commissure appears first at 16-17 mm. It lies immediately cephalad to the stalk of the epiphysis and is comparatively small.  
+
It appears from the foregoing that in the pig the exclusively endodermal origin of the thymus from the third gill [loueh is probable, but a slight participation by the ectoderm has not been satisfactorily excluded. Kastschenko's conclusions, however, as to the ectodermal origin of the thymus are imwarranted by his recorded observations. Prenant, after his careful work (on the sheep), was not sure that a small mass of ectoderm did not enter into the formation of the head. Practically all other investigators of this problem maintain that tlie ectoderm takes no part in the formation of the thymus. The epithelial l)ody (nodulus thymicus) developing in connection witli tlie head of the thymus from the third gill pouch does not form the carotid gland. Kastschenko's description of the origin of the carotid gland in mammals from the adventitia of the internal carotid is now accepted by the majority of anatomists, and it therefore has nothing to do with the thymus in oi'igin.
  
7. The posterior commissure appears first at 15 mm., and there is a
+
TiiK Hist<)L()(;y of tiik FrLLY-F()i;.Mi:i) Thymus.
marked interval in the roof of the diencephalon between it and the
 
epiphysis.  
 
  
I wish in conclusion to express my acknowledgments to Prof. Minot
+
Before taking u\) tlic histogenesis, I shall bi'iclly (.-(Uisider the histology of the gland as shown in a 24-cni. embryo. At this stage ihe gland nuiy be regarded as fully formed. As is well known, tlie thymic lobule consists of a cortical and a medidlary portion, — the medulla of all the lobules being united by the medullary cord. The cortex consists of a delicate reticulum with its spaces well filled by cells, usually lymphocytes. The reticulum may be regarded as composed of small branched anastom
for his kind advise and interest in the preparation of this article.  
 
  
BIBLIOGRAPHY.
 
  
The following are the principal articles consulted, but of course do not
+
36 The Development of the Thymus
form a complete bibliography of this subject:
 
  
1. BuRCKHAKDT, R. — Die Zirbel von Ichthyophis Glutinosus und Protopterus
+
osing cells, though of eourse no cell houndaries are distinguishable. The nuclei are poor in chromatin, rounded, and usually 4.5 /a to 5.5 /x in diameter. The amount of cytoplasm around the nuclei and connecting them is usually very small. At some nodes there is a greater amount of cytoplasm giving the appearance of a large reticulum cell. In connection with the lilood-vessels, which are numerous in the cortex, are often found branched cells with pale nuclei and cytoplasm that stains more intensely than that of the rest of the reticulum. By a modification of Mallory's method used by Jackson (13, S. 39), I have been able to demonstrate numerous fibrillEe in the reticulum. In some cortical areas at this stage there are a great many erythroblasts. Masses of free erythrocytes are often found, usually near a comparatively large vessel, but such cells occur singly anywhere in the cortex.
  
Annectens. Anat. Anz., Bd. VI.  
+
In the medulla, the syncytial character of the stroma is much more pronounced. The cytoplasm is much more abundant than in the cortex, and the spaces are smaller and not so numerous. There is not so much room for lymphocytes as in the cortex, hence the lighter color of the medulla in stained preparations. The nuclei of the syncytium are either pale or dark, both types showing wide variations in size. By Jackson's method (13, S. 39), fibrilla3 may be readily demonstrated in the syncytium. In Plate I, Fig. 6, is shown the arrangement of these fibrillse (s f) in the medulla at 24 cm. They often may be traced into the areas which are forming the concentric corpuscles. In some parts of the medulla the fibrillae are very numerous ; in a few places, entirely absent. In both cortex and medulla eosinophile cells are often found. These occur in groups in the interlobular tissue around the blood-vessels, around some of the corpuscles of Hassall, and singly in the reticulum. These have been described by Schaffer (24). Free erythrocytes a.re rarely found in the medulla. In the medulla are also found the corpuscles of Hassall. Since the structure of these bodies depends largely upon their age, it may be better understood from the consideration of their development.
  
2. Die Homologien des Zwischenhirndaches bei Reptilien und Vogeln.  
+
The Lymphoid Transformation.'
  
Anat. Anz., Bd. IX, 320-324.
+
Kolliker, in 79, first advanced the idea that the leucocytes are formed directly from the epithelial cells of the thymic anlage. According to Minot (in human embryology, p. 878), "he records for the rabbit that between the twentieth and twenty-third days the cells of the thymus become smaller and their outlines disappear, so that the organ appears to
  
3. Der Bauplan des Wirbeltiergehirns. Morpholog. Arbeiten, IV
+
° This term will be used to include those changes that occur in the thymus during its passage from an epithelial to a characteristic lymphoid structure.
  
  
  
Bd., 2 Heft, 131.  
+
,E. T. Bell 37
  
4. Untersuchungen am Gehirn und Geruchsorgan von Triton und
+
bo ail atiuiiiulaticni of small round nuclei. At about the same period blood-vessels and eonneetive tissue grow into the epithelial anlage."
  
Ichthyophis. Zeitschr. f. Wiss. Zoologie, Bd. 52.  
+
His {I'i 1)). 80, and Stieda (26), 81, claimed that the corpuscles of Hassall are the only remnants of the epithelial anlage, that the lymphocytes, reticulum, etc., are of mesenchymal origin.
  
5. Dexter, F. The Development of the Paraphysis in the Common Fowl.  
+
Maurer (17 a), 86, described the leucocytes as arising directly from the cells of the epithelial anlage in the thymus of teleosts. In the amphibian thymus (17 b), 88, he thinks that the leucocytes are probably of mesenchymal origin. He was unwilling to conclude that they arose from the epithelium because he could not find transition forms. In lizards (17 c), 99, he records that even before the separation of the epithelial anlage of the thymus from the pharynx, changes begin. The peripheral cells are closely crowded together and show many mitoses. There arises between the central cells, or is formed in vacuoles in their protoplasm, a fluid which accumulates until the nuclei surrounded by a thin zone of protoplasm are connected only by protoplasmic threads. A loose medulla is thus formed which looks like a cellular reticulum. The cortex is still solid. The lymphocytes are formed from the epithelial cells; none come from without. Later, blood-vessels and connective tissue grow in. He believes that the reticulum is of mesenchymal origin in all forms. Maurer (17 d), 02, still holds that in amphibians the lymphocytes are probably of mesenchymal origin.
  
American Journ. Anat., Vol. II, No. 1, 13-24.  
+
Plermann et Tourneux (11), 87, find that in man and other mammals the epithelial anlage of the thymus is gradually converted into leucocytes and reticulum cells. Vacuoles appear during the transformation which seem to be formed by the absorption of large cells. In a sheep embryo of 130 mm., the clear epithelial cells have all disappeared, giving rise to small round cells and reticulum cells. Prolongations of connective tissue, each containing a blood-vessel, grow into the anlage during the transformation. They are not sure that all the thymic elements are epithelial in origin, being especially in doubt about the origin of some of the reticulum cells.
  
6. Dendy, a. — On the Development of the Pineal Eye and Adjacent Organs
+
Gulland (8), 91, describes the development of the tonsil in the rabbit. Leucocytes first appear in the connective tissue around the thymus. Later they appear in the connective tissue around the tonsil. They infiltrate the tonsillar epithelium. Fo leucocytes are of epithelial origin. After studying the tonsil he examined the thymus in a few specimens and concluded that the same process of leucocyte infiltration occurred there. He does not give the details of their infiltration, and did not see any of the transition forms of nuclei in the thymus at that period.
  
in Sphenodon (Hatteria). Quart. Journal Micros. Soc, Vol. 42, 111.
+
Prenant (22), 94, made a careful study of the development of the
  
7. D'Ebchia, F. — Contributo alio studio della volta del cervello intermedio
 
  
e della regione parafisaria in embrioni di Pesci e di Mammiferi.
 
Monitore Zoologico, VII, 118 e 201.
 
  
8. Eycleshymer, a. C. — Paraphysis and Epiphysis in Amblystoma. Anat.
+
38 The Drvi'lopincnt ol' the 'riiynius
  
Anz., Bd. VII.  
+
thynuis in sheep embrvos. His results are as follows. At 25 mm. the gland is composed of distinct polyhedral cells with nuclei of only one kind. A few mitoses and an occasional direct division are to be seen. At 20 mm. mitoses are numerous (oi^e nucleus in fifty). jSTuclei are regularly rounded or elliptical and some small nuclei occur juxtaposed to large nuclei. At 28 mm. many mitoses are present and irregular spaces have appeared. These spaces are not blood-vessels nor parts of the thymic duet but vacuoles. Some nuclei, noticeably small and darkly colored, lie close to the large, clear nuclei and seem to be budded off from them. Some nuclei (rare) are broken into three or four chromatic bodies. Embryos of 40 mm. have undergone in great part the lymphoid transformation. All transitions are found between the large, pale elliptical nuclei of clear reticular structure and the small, deeply colored rounded nuclei whose sap is strongly stained. These last are certainly lymphocytes and constitute an immense majority of the cellular elements. Large, clear nuclei are found Joined to small dark ones — nuclear couples.
  
9. Eycleshymer, A. C, and Davis, B. M. — The Early Development of the  
+
At 85 mm. the medulla appears; the cortex corresponds to the entire thymic mass of preceding stages. The cortex contains a great many lymphocytes separated by islands and rows of pale nuclei. There are about thirty lymphocytes to one pale nucleus. Mitoses are numerous in the cortex. In the medulla at this stage, the large clear, and small dark, nuclei are about equal in number, and mitoses are rarer than in the cortex. In later embryonic stages a clear peripheral zone is present where cell proliferation takes place. Mitoses are now more numerous in the medulla than in the cortex. It is probable that a certain number of the epithelial cells persist as reticulum cells in the fully-formed organ.
  
Paraphysis and Epiphysis in Amia. Journal of Comp. Neurology,
+
J. Beard (3 a), 94, (3 b), 99, thinks that the function of the thymus is to form the first leucocytes. He finds that in the skate the epithelial cells are converted early into lymphocytes which emigrate into the blood. There are many breaks in the gland where the lymphocytes escape in masses. The thymus is the only source of leucocytes until the other lymphoid organs are formed.
Vol. 7.  
 
  
10. Francotte, p. — Recherches sur le developpement de L'epiphyse. Arch.  
+
Ver Eecke (28), 99, finds that in the frog the epithelial thymus is invaded by lymphocytes and connective tissue. The epithelial cells are not destroyed but merely dispersed by the mesenchymal elements. He calls the resulting tissue lympho-epithelial. This idea of the commingling of the two tissues had already been advanced by Eettcrer.
  
de biologie, T. VIII.  
+
Xusbaum and Prymak (20), 01, on teleosts, agree with j\Iaurer that the lymphocytes are of epithelial origin but disagree on the details of their formation. They find that the epithelial anlage is at first composed of cells with distinct lioundaries. It is not different from the epithelium
  
11. Note sur I'ceil parietal, l'epiphyse, la paraphyse et les plexus
 
  
choroides du troisieme Ventricule. Bull, de I'acad, royale, etc., d.
 
Belg., 3 Serie, T. 27.
 
  
12. Contribution a I'tHude de I'oeil parietal, de l'epiphyse chez les
+
E. T. Bell 39
  
Lacertiliens.  
+
of the pharynx. Before any blood-vessels or connective tissue have invaded the organ, changes begin in. the central part. These changes consist in the breaking up of the cytoplasm so that the cells become branched and connected by delicate processes. These processes finally break apart leaving a nucleus surrounded by a thin layer of protoplasm — a lymphocyte. The peripheral epithelial layer multiplies rapidly, forming nuclei somewhat smaller and darker than their own. These nuclei become gradually changed into the nuclei of lymphocytes and break away from the other cells. All transitions are present between the large, clear epithelial nuclei and the lymphocytes. Blood-vessels and connective tissue grow in from the outside.
  
13. Gage, S. P. — The Brain of Diemyctylus Viridescens. Wilder Quart. Cent.  
+
It appears from a survey of the literature that, of those who have studied the origin of lymphocytes in the mamalian thymus. His, Stieda, and Gulland have advocated the idea that they invade the gland from without, and that the original epithelial anlage persists only as remnants, the corpuscles of Hassall. They also consider the stroma of mesenchymal origin. On the other hand, Kolliker, Hermann and Tourneux, and Prenant, have described the lymphocytes as derived directly from the epithelial cells of the anlage. Hermann and Tourneux and Prenant ascribed a similar origin to part of the reticulum.
  
Book, 1898.  
+
Xeither His, Stieda, nor Gulland made a detailed histological study of the changes that take place in the thymus during the transformation. They did not see the vacuolization of the cytoplasm, the changes in the epithelial nuclei, etc. — processes wdiich undoubtedly occur. Gulland made nearly all his observations on the tonsil and then from a superficial examination of the thymus concluded that the process is the same there. The conclusions of these men are therefore not to be compared on this point with those obtained by the thorough and careful work of Prenant.
  
14. Gaupp, E. — Zirbel, Parietalorgan und Paraphysis. Ergebn. Anat. Entwick.
+
On amphibians, Maurer hesitatingly agrees with His, and Yer Eecke accepts the mesenchymal origin of the leucocytes ; while on fishes Maurer, Beard, and Nusbaum and Prymak believe in the epithelial origin of lymphocytes. Maurer's work on reptiles is in agreement with his work on teleosts.
Ges., VII, 208-285.  
 
  
15. Hebbick, C. L. — Topography and Histology of the Brain of certain Rep
+
As to the origin of leucocytes in the lymphoid organs of tlie alimentary canal, opinion is divided. Eetterer, v. Davidoff, Rudinger, Klaatsch, and others have described the leucocytes as arising from epithelium and being invaded by mesenchymal elements forming adenoid tissue. Stohr, Gulland, Tomarkin, and others describe them as penetrating the epithelium from without.
tiles. Journ. of Comp. Neurology, Vol. I, 37; Vol. Ill, 77-104, 119-138.  
 
  
16. Topography and Histology of certain Ganoid Fishes. Journ. of
+
I shall now discuss my own observations on the lymphoid transformation in the thymus of the pig. From a very early stage (11 mm.), the
  
Comp. Neurology, Vol. I, 162.
 
  
  
 +
40 The Development of the Thymus
  
26 Paraphysis and the Pineal Kegion in Nectun;s Macnlatus
+
t'pithelium of the third gill pouch is a syncytium. No cell boundaries exist. The nuclei, large and irregular in shape, are embedded in a common mass of cytoplasm. In the thymus at 20 mm. I find a syncytium of dense cytoplasm embedded in which are large nuclei of irregular shape and size. No distinct types of nuclei are present yet; all stain with medium intensity. A few mitoses are to be seen.
  
17. Hkkuick, C. L. — Embryological Notes on the Brain of a Snake. Journ.  
+
In a section of the mid-cervical segment at 3.7 cm. (Plate I, Fig. 1), I find evidence that the lymphoid transformation has begun. The syncytium is composed of coarsely reticulated cytoplasm much looser in texture than that of the preceding stage. It contains a few irregular spaces (s s) which are evidently of the nature of vacuoles. These may be formed, as Maurer suggests, by liquefaction of the cytoplasm. There is no reason to suppose that cells degenerate and form them as Hermann and Tourneux believed. Three types of nuclei may be distinguished; large pale nuclei (Ipn) large dark nuclei (I dn), and small dark nuclei (lymphoblasts) (Ih). Transition forms occur between these types. The large dark nuclei are intermediate forms between the pale nuclei and the lymphoblasts. A few mitoses (m) occur. No blood-vessels are present inside the anlage but they may be seen between the buds just outside. At this stage, the head and the thoracic segment have areas that are somewhat farther advanced than this. The intermediary and cervico-thoracic cords show no changes.
  
Neurology, Vol. I, lGO-176.
+
At a later stage than the above (Plate I, Fig. 2), in the thoracic segment of a 4.5-cm. pig, jthe spaces of the syncytium (s s) have increased greatly in number and size. The anlage is now a cellular reticulum. The large pale nuclei are somewhat less numerous than the dark nuclei and many have become angular, adapting themselves to the nodes of the syncytium. They contain less chromatin than in the preceding stage. Large dark nuclei and lymphoblasts are present; the lymphoblasts are much more numerous than in the preceding stage. A very few small dark nuclei are completely separated from the syncytium. These are lymphocytes. There are no lymphocytes in the connective tissue around the thymus or in the blood at this stage. I did not examine the tonsil or spleen at any stage. A few small blood-vessels are to be seen; their walls consist of endothelium only. There are more mitoses than at the preceding stage, but none happened to be present in the area shown in the figure. During mitosis, at all stages of development, except the early epithelial condition, the chromosomes are so closely packed that it is very difficult to distinguish them individually.
IS. Hill, C. L. The Epiphysis in Teleosts and Amia. Journ. of Morphology.  
 
  
Vol. IX, 237-268.  
+
In a section through the mid-cervical segment of a 7-cm. pig (Plate I, Fig. 5), we see a stage somewhat later than the one shown in
  
19. His, W. — Zur allgemeinen Morphologie des Gehirns. His. Archiv, 1892,
 
  
346-383.
 
  
20. Humphrey, O. D. — On the Brain of the Snapping Turtle. Journ. of Comp.  
+
E. T. Bell 41
  
Neurology, Vol. IV, 73-108.  
+
Fig. 2. In various jiarts of the section lymphocytes (I) are completely formed. Tlie great majority of the small round nuclei are in the lymphoblast (l h) condition, i. e.,thcy are not yet completely separated from the syncytium. There are a few lymphocytes outside the thymus in the interlobular tissue in this region; around the head and the thoracic segment at 7 cm. they are numerous, these parts being in a later stage of transformation. I have never seen lymphocytes outside the thyfnus, where there were none inside it ; but they appear outside shortly after they are formed here. Those formed next the interlobular septa seem to pass out very early. Of course the lymphoblasts, which are distinguishable from the lymphocytes only by being imbedded in the syncytium, are to be seen in the thymus long before any appear outside.
  
21. Kingsbury, B. F. — The Brain of Necturus Maculatus. Journ. of Comp.  
+
At the stage shown in Fig. 5, a great many nuclei are in mitosis. I have not seen at any stage, the amitoses and nuclear couples described by Prenant for the sheep. In some parts of the section comparatively large solid epithelial areas occur. These are found as often in the central as in the peripheral part. Many of the pale nuclei are smaller than those shown in Fig. 2. The blood-vessels are somewhat larger and more numerous than those at 4.5 cm.
  
Neurology, Vol. V.  
+
It is to be noted that the epithelial anlage does not at any stage become converted entirely into small round cells as many observers have stated. Distinctly pale angular reticular nuclei can always be seen.
  
22. The Encephalic Evaginations in Ganoids. Journ. of Comp. Neurology, Vol. VII.  
+
In the mid-cervical segment at 8.5 cm. (Plate I, Fig. 4), a great many lymphocytes (/) are formed. These lie between the persisting epithelial cells which are now arranged in irregular cords and islands. In these epithelial masses, lymphoblasts may still be seen indicating that the formation of lymphocytes is still in progTCss. Many of the pale nuclei are now small. The heavy hsematoxylin stain in this case makes the nuclei darker than they would appear with an ordinary stain. A few nuclei are in mitosis.
  
23. KxiPFFER, C. V. — Studien zur vergleichenden Entwicklungsgeschichte des
+
This figure shows also the first appearance of the medulla {ind). The medulla is formed directly, as shown in the figure, from persisting parts of the epithelial syncytium. Certain centrally situated masses of this syncytium undergo changes of such a nature that they stain readily with cytoplasmic stains such as Congo red. In sections stained with hematoxylin and Congo red, the medulla is first recognized as a l)rightly colored area situated usually about the center of the lobule. Tlicse epithelial masses that give rise to the medulla seem to increase in size about the time of the change in staining capacity. The first differentiation of the medulla is chemical rather than morphological, for there are other persisting epithelial masses even larger than it in the same section
  
Kopfes der Kranioten. Hefte I.
 
  
24. Derselbe. Hefte II.
 
  
25. Lewis, F. T. — The Question of Sinusoids. Anat. Anx., Bd. XXV, No. 11.
+
42 The Development of the Thymus
  
26. Leydig, F. — Zirbel und Jacobsonsche Organe einiger Reptilien. Archiv f.  
+
that do not react in the same way with the cytophismic stains. The meduna appears in the head and the thoracic segment at 7.5 cm. to 8 cm. All the gland except this small central area forms the cortex. Bloodvessels now reach 'all parts of the gland, but are still few in number. I cannot distinguish any wall except the endothelium on those actually inside the gland.
  
Mikrosk. Anatomie, Bd. 50.  
+
In a 9.5-cm. pig, the medulla is larger. It contains pale nuclei of various sizes, large dark nuclei, and lymphoblasts. Its spaces are smaller than those of the cortex. The early stages in the formation of the corpuscles of Hassall appear as soon as the medulla begins to form. The epithelial cords in the cortex have become less conspicuous, but are still forming lymphocytes. A few nuclei are in mitosis. Many blood capillaries may now be seen penetrating the gland from the periphery. These vessels run in the epithelial masses and have a wall of large endothelial cells which gives them the appearance of radiating cords. When these vessels first appear, as at this stage, they have only an endothelial wall. The blood-vessels grow in as small capillaries which, after their entrance, increase in size and branch ; they do not break in as large vessels surrounded by mesenchymal tissue. I am fairly sure that aside from the endothelial cells few or no mesenchymal cells come into the thymus. Around the greater part of the periphery of the gland is a solid zone of syncytium two or three nuclei deep which is in transformation like the epithelial cords inside. This zone, described by Prenant as a zone of proliferation, grows rapidly, as the frequent mitoses indicate. Its inner boundary is forming lymphocytes and reticulum cells.
  
27. LocY, W. A. — Contribution to the Structure of the Vertebrate Head.  
+
In a 14-cm. pig, the lymphoid transformation is practically at an end except in the medulla. The peripheral zone of proliferation has disappeared. The cortex has about the same structure as at 24 cm., as previously described. In the medulla, lymphoblasts, large pale nuclei, and the large dark intermediate types are still present. There are a few mitoses here. It is very probable therefore that the formation of lymphocytes is still in progress in the medulla. The medulla at 2-i cm. shows a similar structure except that there are fewer lymphoblasts. These facts persuade me to regard the medulla as a center for lymphocyte formation at least as late as birth. Connective tissue fibrillae begin to appear in the gland along the large blood-vessels and the interlolmlar septa as early as 10.5 cm. They are only a little farther in at 16 cm. ; but near full term they are present in nearly all parts of the stroma. (See Plate I, Fig. 6.)
  
Journ. of Morphology, XI.
+
The above account may be summarized as follows: In the pig the epithelial syncytium of the thymic anlage becomes loosened up by the
  
28. MiNOT, C. S. — On the Morphology of the Pineal Region, based on its
 
  
Development In Acanthias. American Journ. of Anatomy, Vol. I,
 
No. 1, 81-98.
 
  
29. On a Hitherto Unrecognized Form of Blood Circulation without
+
E. T. Bell 43
  
Capillaries in Organs of Vertebrates. Pro. Boston Soc. Nat. Hist.,
+
formation of vacuoles in it. These vacuoles increase in number and size, converting the anlage into a cellular reticulum. While this vacuolization is in progress, the nuclei, which at first are of one kind with a medium amount of chromatin, ditferentiate into large clear, large dark, and small dark (lymphoblast) forms. The large dark nuclei probably divide by mitosis and form the lymphoblasts. The lymphoblasts gradually break loose from the syncytium, passing into its spaces and becoming lymphocytes. Shortly after lymphocytes begin to be formed, some of them pass out of the gland into the surrounding connective tissue. The lymphoid transformation begins in embryos of 2.5 cm. to 3 cm. and continues in the cortex until 13 cm. or 13 cm. In the medulla it is not complete at birth. Since the thymus increases greatly in size during this period the epithelial syncytium must grow rapidly. Lymphocytes are constantly being formed at the expense of the growing syncytium. A peripheral zone of proliferation is present from about 8 cm. to 13 cm. The medulla is formed as a chemical differentiation of certain centrally situated areas of the epithelial syncytium. The histological changes occur earlier in the head and thoracic segment than in the mid-cervical segment and very much earlier than in the cords. The reticulum of both cortex and medulla is practically all of e])ithelial origin. Some branched cells around the blood-vessels in the cortex may be of mesenchymal origin.
Vol. 29, No. 10, S. 185-215.  
 
  
30. OsBORN, H. F. — Preliminary Observations on the Brain of Menopoma.
+
My reasons for regarding tlie lymphocytes as of epithelial origin are as follows :
  
Proceed. Phil. Acad., 1884.  
+
A. The lympholilasts are true epithelial nuclei, because (1) there are numerous transition forms between them and the large dark nuclei which later cannot l)e regarded as invading lymphocytes; (3) they are closely embedded in the syncytium and show no evidence of having eaten their way through the protoplasm; (3) they are present from a very early stage and increase in number as development proceeds; (4) they are present before blood-vessels invade the gland and have no constant relation to blood-vessels or to the surface of the gland that indicates an invasion from either of these directions; (5) they are present before lymphocytes appear in the connective-tissue around the thymus.
  
31. Contribution to the Internal Structure of the Amphibian Brain.  
+
B. Some observers admit tliat the small dark nuclei (lymphoblasts) are of epithelial origin but do not admit that tlicy form lym])hocytes. The considerations that lead me to bciicNc tliat the lymphoblasts do form the lymphocytes are: (1) the small dark nuclei (lymphoblasts) show every possible relation to the syncytium from being completely embedded in it to lying free in the syncytial s]")aces. A comparison with later stages shows tb.at tliis appearance is not due to poor fixation oi- to the
  
Journ. of Morphology, Vol. II, 51-86.
 
  
32. Rex, H. — Beitrage zur Morphologie der Hirnvenen der Amphibien. Morph.
 
  
Jahrb., XIX, 295-311.
+
44 'V\\v ncvclopnioiit of tlio M'hymns
  
33. ScHOBEL, Jos. — Ueber die Blutgefasse des Cerebrospinalen Nervensystems
+
adherence of the nuclei to the reticuhini ; (?) the first free niiclci often appear in the center of the gland whoi tlicrc are no other free nuclei in the periphery at that level; (3) there is good evidence that lymphocytes emigrate from the thymns in large numbers. If we examine the thymus of a 7-cm. pig in serial sections we find that the lymphoid transformation is less advanced in the mid-cervical segment than in the head. In the mid-cervical segment there are a few lymphocytes in the interlobular tissue. In the lower end of the head where there are more lymphocytes inside the gland, lymphocytes pack the interlobular tissue and form a thin zone around the periphery of the gland. In the middle of the head where the transformation is far advanced, lymphocytes pack the interlobular tissue and form a thick zone around the entire gland. Indeed, in some sections, there are more l3T3iphocytes in the zone outside than are present inside the gland. If this zone of lymphocytes be passing into the gland, it is not easy to understand why it is formed from Avithin outwards, and why it is thickest where the greatest number of lymphoc3ies are already present inside. No satisfactory suggestion has yet been made as to why lymphocytes should thus suddenly pour into the thymus at a time when if present at all elsewhere they are rare. They do not come to break up the thymic epithelium, for that is already a reticulum before free cells are present (Fig. 3, Plate I). Where lymphocytes invade intestinal epithelium as in the tonsil they eat paths through it leaving spaces. The epithelial reticulum of the thymus is not formed in that way. On the other hand it is not difficult to believe that this zone of lymphocytes is formed l^y cells passing out the periphery of the thymus and that the gland thus contributes a great number of lymphocytes to the organism; (4) I have not been able to find lymphocytes in the connectivetissue around the th}Tuus before they are present inside. An invasion by way of the blood-vessels may be excluded, since the thick zone of lymphocytes formed around the gland shows that these cells either enter or leave it through the preiphery.
  
der Urodelen. Archiv f. Wissen. Mikros., Bd. XX, 87-91.  
+
The Corpuscles of Hassall.
  
34. Selenka, E. — Das Stirnorgan der Wirbelthiere. Biolog. Centralbl., Bd. X,
+
These bodies were first mentioned by Hassall ( 10 ) in 46, He speaks of them as being composed of mother cells which enclose the newlyformed daughter cells and nuclei. He thought the central mass was formed by the outer enclosing layers. He found bodies which lie regarded of the same nature in fibrous coagulations in the heart.
  
323-326.  
+
Virchow (29), 51, in a discussion of endogenous cell formation, compares Hassall's corpuscles to carcinoma pearls. He had about the same
  
35. Sorensen, a. D. — The Roof of the Diencephalon. Journ. of Comp. Neu
 
rology, III, 50-53.
 
  
36. Comparative Study of the Epiphysis and the Roof of the Diencephalon. Journal Comp. Neurology, IV, 153-170.
 
  
37. Continuation of above. Vol. IV, 153-170.  
+
E. T. Bell 45
  
38. Studenicka, F. Cii. — Beitrage zur Anatomie und Entwicklungsgeschichte
+
conception of the nature of the corpuscles as Hassall. This oft-quoted comparison was therefore not based upon a deep insight into their nature.
  
des Vorderhirns der Cranioten.  
+
Giinzburg (9), 57, did not advance beyond Hassall's conception that the central mass is formed by the peripheral layers.
  
39. VoELZKOw, A. — Epiphysis und Paraphysis bei Krokodilien und Schild
+
Paulitzky (21), 63, described the center of the corpuscles as homogeneous or granular. They sometimes contain an elliptical nucleus, sometimes fat droplets. The larger ones have in the center several nuclei' or cell-like forms. The central part is formed from masses of epithelial cells. Connective tissue cells grow around them and are transformed into epithelial cells forming the peripheral part of the corpuscle.
krot>en. Abhand. der SenchenbiXrgischen Naturforschenden Gesellschaft, Bd. XXVII, Heft. II.  
 
  
 +
The term "concentric corpuscles" was introduced by Ecker (6), who described them as arising directly from gland cells by fatty metamorphosis. He distinguished (1) simple corpuscles, round vesicles with thick concentric hulls, containing inside a fatty opalescent mass, and (2) compound corpuscles, which consist of several vesicles with a common hull. The peripheral layers of a corpuscle consist of flattened cells.
  
 +
His (13 a, 12 b), 60, 80, described the corpuscles as consisting of an outer striated shell, probably composed of nucleated cells, and containing lymphocyte-like cells inside. He supposed them to be the original cells of the epithelial anlage which become entangled in the reticulum in some way. Their rapid growth in their narrow confines causes the concentric form.
  
John Warren
+
Cornil et Eanvier (5), 69, considered the corpuscles as arising from the endothelium of blood-vessels and compared them to the spheres of their " Sarcome angiolithique."
  
 +
This suggestion of a vascular origin, made by Cornil et Eanvier, was elaborated by Afanassiew (la), 77.
  
 +
Afanassiew held that the corpuscles of Hassall arise from the endothelium of the smaller veins and capillaries. The endothelial cells increase in size, become cubical, and later fill the lumen of the vessel. During the proliferation of the endothelium, the blood-vessels break up into segments which are now nearly solid cords. These cords are at first connected to each other and to blood-vessels, but they soon break apart. The surest proof that the corpuscles are of vascular origin is that erythrocytes may be found inside them. Vascular injections, however, do not go into a corpuscle except in a very early stage, since the lumen is soon obliterated by the endothelial plugs. The corpuscles are formed entirely by the endothelial cells. Afanassiew worked on embryos of man, the rabbit, and the calf.
  
27
+
Stieda (26), 81, in sheep embryos, describes the epithelial mass of the
  
  
  
ABBREVIATIONS.
+
4G Tlie Dcv('lf)|)tn(Mit of the Tli\nms
  
 +
thymic aulage as being broken up by ingrowing adenoid tissue. From 50 mm. to 60 mm., there arc no hirge epithelial ceils; but later at 100 mm. ho iinds in the adenoid tissue large cells 9 /a to 15 /x in diameter, isolated or united in groups, Avhose protoplasm colors light-red with carmine. These large cells have a concentric structure. Some of them are enclosed bv large cells whose cytoplasm does not color with carmine, giving rise to a yellowish mass of irregular form and stratified appearance. In older embryos (250 mm.), the cellular masses are numerous but the large colored cells are rare. The yellowish masses are groups of the large cells which have undergone a transformation like that of the stratum corneum of the epidermis. Stieda considers the large colored cells which form the corpuscles as remnants of the epithelial anlage, although he admits that for a long period during development he found no trace of them. He explains the formation of the corpuscles in accordance with Cohnheim's hypothesis that most tumors arise from unused tissue remnants.
  
 +
Ammann (2) 82, made most of his observations on human foetuses. He describes the corpuscles as arising from connective tissue. The corpuscles are cellular in structure and are formed of one, two, or three central cells around which a variable number of cells, increasing with age, are arranged like the coats of an onion. The corpuscles are formed from reticulum cells and leucocytes. Growth consists in the apposition of cells from without. The life of a corpuscle consists usually of four stages : (1) Stadium der Transparenz ; (3) Stadium der colloidcn Entartung; (3) Stadium der Verkalkung; (4) Stadium des Zerfalls. The nucleus of a reticulum cell or leucocyte increases in size at the expense of the cell body. Its increase in size establishes the concentric form. The corpuscle undergoes colloid and usually calcareous degeneration. Fat droplets, cholesterin crystals, and colloid granules are found together in the degenerating corpuscles. Breaking up in this way makes absorption possible. No epithelial remnants are to be observed. Xo erythrocytes are found in the corpuscles.
  
A. C. — Anterior commissure. L. Y.
+
In four cases of atrophic thymus gland wliich yet contained lymphoid tissue Ammann found corpuscles in all stages of development. He also found that the corpuscles are formed most rapidly when the thymus is at the height of its development. From these facts he concluded that they are not connected with the involution of the thymus as Afanassiew thought. He thought that their formation is due to a physiological decrease in the intensity of growth of the medulla, due to the rapid growth of the cortex.
Ch. Fix. — Choroid plexus. M. B
 
Dien. — Diencephalon. 0. C
 
D. Flex. — Diencephalic plexus. Tel. Plx.
 
i?.— Epiphysis. Tel.
 
Ep. A. — Epiphysal arch. F. C
 
F. B. — Fore-brain. P. T- A. —
 
  
F. M. — Foramen of Munro. ■ P. A.
+
Watney (31), 83, agreed with Ammann that the corpuscles arise from connective tissue cells.
H. — Hemisphere. F.  
 
  
H-JB.— Hind brain. S.C.
 
  
Hyp. — Hypophysis. Si.
 
  
I. J. V. — Internal jugular vein. T.  
+
E. T. Bell 47
  
L. Fix. Choroid plexus of lateral Tes.  
+
Monguidi (18), 85, distinguished true and false concentric corpuscles • the latter being onl}- sections of blood-vessels.
  
ventricle. ^'
+
Hermann et Tourneux (11), 87, gave a description of the structure and formation of the concentric corpuscles about like that given by Ammann except that they regard the reticulum cells from which the corpuscles develop as of epithelial origin.
  
 +
Gulland (8), 91, regarded the corpuscles as epithelial remnants and compared them to the epithelial pearls of the tonsil.
  
 +
Maurer (17 c), 99, described the corpuscles as epithelial in origin. His description of their formation is however different from that of His. All the cells of the epithelial anlage at first assume a lymphoid character. Later, some of these cells reassume their epithelial nature and then form the corpuscles. His conclusions for teleosts and amphibians are similar to the above results which he obtained from the lizard.
  
Lateral ventricle.  
+
Yer Eecke (28), 99, for the frog, describes the leucocytes and connective tissue cells as invading the thymic anlage and separating the epithelial cells. The epithelial cells, separated by the mesenchymal elements, lie at first in groups or singly. They go through a cycle of two phases, a stage of growth, and a stage of involution. In the former stage, they increase to three or four times their original size and their cytoplasm differentiates into circular layers like the coats of an onion. The majority are monocellular. Some cells grow together making a more complex multicellular type. There are some intermediate forms, cells with a dense dark protoplasmic body, indistinct striations, and a nucleus partly or completely hidden in a precocious degeneration. In the stage of involution, which sets in early, the cytoplasm degenerates by the formation of vacuoles containing a hyaline liquid. The liquefaction may be in the form of a diffuse vacuolization, a large central vacuole, or a peripheral vacuole circular in section. The nucleus loses its affinity for stains, becomes deformed, breaks up, and finally disappears. The corpuscles are finally absorbed. They never contain erythrocytes. The cells do not degenerate to form a corpuscle. The liquefaction forms an internal secretion which is forced out by the muscle tissue in the reticulum.
Mid-brain.  
 
Optic commissure.  
 
-Telencephalic plexus.  
 
-Telencephalon.  
 
-Posterior commissure.  
 
Post-velar arch.  
 
Paraphysal arch.  
 
Paraphysis.  
 
-Superior commissure.  
 
Sinusoid.  
 
•Tubule.  
 
■Vessel.  
 
-Velum transversum.  
 
  
 +
Entirely different results on amphibians are reported by Nusbaum and Machowski (19), 02. These investigators revive the old idea of Afanassiew, accepting his results except that they think the adventitia as well as the endothelium of the blood-vessels takes part in the formation of the corpuscles. They find erythrocytes in the corpuscles. These erythrocytes either gradually shrivel and disappear, or they are absorbed by leucocytes or endothelial cells. The leucocytes after digesting the hemoglobin of the erythrocytes become eosinophile cells which are numerous in the thymus.
  
  
THE DEVELOPMENT OF THE THYMUS.
 
  
BY
+
48 The Development of the Thymus
  
E. T. BELL, B. S., M. D.  
+
Wallisch (30), 03, measured the volume of the human thymus and of the corpuscles of Hassali at various stages. He finds that the total volume of the corpuscles of a 7-mo. embryo is 4.6 mm./ and of those of a 6-mo. child, 174.6 mm." The total volume of the thymus of a 78-mm. embryo, when it has already been partly transformed into adenoid tissue is only 6.8 mm.^ Since there is no evidence that the cells of the corpuscles multiply, he concludes that they cannot be regarded merely as remnants of the original epithelial anlage.
  
Instructor in Anatomy, University of Missouri.  
+
Disregarding the crude observations of the earliest investigators, there remain three distinct theories of the formation of the corpuscles of Hassali.
  
With 3 Plates and 5 Text Figures.  
+
1. The epithelial anlage of the thymus is broken up by the invading mesenchymal elements. The separated masses of epithelial cells undergo further changes mainly of a degenerative nature to form the corpuscles. This was the belief of His and KoUiker. According to this interpretation, the corpuscles are to be regarded as remnants that have nothing further to do with the gland. Stieda, Maurer, and Ver Eecke held this view in a modified form. Stieda regarded the cells forming the corpuscles as epithelial remnants but admitted that they go through a stage in which, for a time, they lose their epithelial character. This is substantially the same as ]\Iaurer's view. He thinks that the cells of the epithelial anlage all become lymphoid, and that some of them afterwards reassume their epithelial nature and form the corpuscles. Yer Eecke regards the corpuscles as epithelial remnants but thinks that they are glandular in nature, not mere useless remains.
  
This paper is intended mainly as a contribution to our knowledge of
+
2. The corpuscles are formed from the proliferating walls of bloodvessels. This idea was suggested by Cornil and Eanvier and elaborated by Afanassiew. Nusbaum and Machowski accept Afanassiew's view except that they believe the adventitia of the blood-vessels as well as their endothelium takes part in the formation of a corpuscle. These investigators thought that the formation of the corpuscles is connected with the involution of the thymus.
the histogenesis of the thymus in mammals. Special attention is given
 
to the origin and development of the corpuscles of Hassall, since their
 
mode of formation has never been satisfactorily described in mammals
 
and their significance in all forms is in dispute. An attempt is also
 
made to show in detail the changes that occur during the transformation
 
of the thymus from the epithelial to the lymphoid condition.  
 
  
This work was begun at the suggestion of Dr. D. D. Lewis at the  
+
3. The corpuscles are formed from reticulum cells of the medulla and grow by apposition of the surrounding cells. This view was advanced by Ammann. Ammann thought that the reticulum is of connective tissue origin. He also believed that leucocytes formed the central part at least of some corpuscles. Hermann and Tourneux accepted Ammann's results, except that they ascribed an epithelial origin to the reticulum. (I do not know whether they accepted the origin from leucocytes described by Ammann.) Ammann thought that the corpuscles formed because of a physiological decrease in the rate of growth in the medulla.
University of Chicago. The greater part of it has been done at the
 
University of Missouri. Special acknowledgments are due Dr. C. M.  
 
Jackson for valuable criticism and suggestions. T wish also to thank
 
Mr. Charles H. Miller of the University of Chicago for his kindness in  
 
sending me material.  
 
  
Material and Methods.
 
  
As material for the greater part of my work, I. have used pig embryos
 
from 8 mm. to full term (26 cm. to 30 cm.). These are especially suitable for such work since they may be procured in abundance from the
 
large packing houses at almost any stage of development. For special
 
purposes I have studied a few specimens from human foetuses, and from
 
the cat, rat, and guinea pig. The smaller pigs used (8 mm. to 27 mm.')
 
belong to the collection in the anatomical laboratory at the University of
 
Missouri. These were stained in bulk with alum-cochineal and mounted
 
in serial sections. In the later stages, which were prepared specially for
 
this work, tbe ventral half of the cervical and anterior thoracic regions
 
was usually out out and embedded from pigs from 3 cm. to 8 cm. On
 
specimens from 8 cm. to 30 cm.. I dissected out the thymus and used sucb
 
parts as were desired.
 
  
^ The crown-rump measurement is used in all cases.  
+
E. T. Bell 49
  
AMERICAN .TOCTRNAL OF ANATOMY. VOI,. V.  
+
l\Iy own observations on tlie development of tlie eorpuseles of Hassall in pi_o- embrvos. will now be considered. The medulla, as previouslv described, begins to form from the epithelial syncvtium usually near the center of the lobule. It is first recognized by its more marked reaction with cytoplasmic stains such as Congo red. Shortly after the medulla begins to form, the earliest stages of the corpuscles may be observed. - A few corpuscles have appeared at 9.5 cm. I did not find them earlier. They are all formed from the epithelial syncytium of the medulla.
  
 +
Before beginning this discussion I will explain the use of ray terms. By a corpuscle of Hassall, I mean a modified area of the epithelial syncytium of the medulla, containing at some period of its development, one or more nuclei, and whose cytoplasm has been in part or entirely transformed into colloid. The term colloid is applied to various substances probably of widely different chemical nature, but is fairly adapted to our imperfect knowledge. I shall use the term here in the restricted sense employed by Ziegler," i. e., hyaline substances of epithelial origin, that do not give the reactions of mucin.
  
 +
Colloid in the corpuscles of Hassall does not usually appear as solid masses in its early formation, but as fibers, granules, or sheets which are separated by more or less cytoplasm that is not yet changed. This stage I have called, "colloid in formation" (c f). It later assumes a more solid homogeneous appearance which I call solid colloid (c s). Often the solid colloid stains intensely with cyto])lasmic stains. I call this kind solid deeply-staining colloid (c .*? d). In later stages, the colloid often loses its affinity for cytoplasmic stains, staining a very pale color or not staining at all. I call this variety old colloid (o c).
  
30 Tlie Development of the Thymus
+
According to their mode of development, the corpuscles of Hassall may be classified as follows :
  
All pig material was fixed in Zenker's fluid, embedded in paraffin, and
+
A. Concentric Corpuscles.
mounted in serial sections from 3 ju, to 10 /x thick. Except those of the
 
young stages (8 mm. to 27 mm.) the sections were stained on the slide.
 
Most of them were stained with hsematoxylin or iron-hgematoxylin and
 
counterstained with Congo red. For special purposes many other stains
 
were used.  
 
  
To demonstrate the delicate protoplasmic threads of the syncytium
+
a. Simple.
during the later stages of the lymphoid transformation, I stained by the
 
iron-haematoxylin method but omitted the final decolorization in ironalum. Protoplasm is stained deep black; nuclear structure is poorly
 
shown, but the finest cytoplasmic processes may be seen.  
 
  
For the demonstration of connective tissue fibrillae in the syncytium,
+
1. Ordinary type.
I found the method recommended by Jackson (13, S. 39) most satisfactory.  
 
  
Text Fig. 2.  
+
2. Epithelioid type.
  
Text Figure 1. Cranial view of third gill pouch (thymic anlage) ; X 33;
+
3. Cystic ty.pe.
pig embryo, 11 mm.; ec, ectoderm; I, lumen; nt, nodulus thymicus; ph, connection to pharynx; s p, sinus prsecervicalis.  
 
  
Text Figure 2. Ventral view of thymic anlage; X 33; pig embryo, 15 mm.;
+
b. Compound.
ec, ectoderm; I, lumen; n t, nodulus thymicus; ph, connection to pharynx;
 
s p, sinus prsecervicalis.  
 
  
To determine the relation of the blood-vessels to the corpuscles of
+
B. Irregular Corpuscles.
Hassall, I put a young kitten under deep anesthesia and injected a large
 
quantity of a strong aqueous solution of Prussian blue into the aorta
 
through the common carotid artery. The heart continues to beat even
 
after an amount of fluid twice as great as the total volume of the blood
 
has been injected. An injection made in this way is under a slightly
 
increased blood pressure and easily reaches the finest capillaries. There
 
is therefore a thorough injection with little danger of rupturing delicate
 
blood-vessels.  
 
  
Organogenesis.
+
a. Compact type.
My observations on this phase of development are not sufficiently complete to warrant a full discussion. A brief survey may however prepare
 
the way for a better understanding of the histogenesis. The text figures
 
show the shape in outline of the third gill pouch and thymic anlage
 
  
 +
b. Eeticular type.
  
 +
Gen. Pathology, 10th ed., Warthin's translation, p. 205.
  
  
E. T. Bell 31
+
50 Tlie Development of the Thymus
  
from 11 mm. to 27 mm. . They are graphic reconstructions. Since this
+
A. The concentric corpuscles inchule those that from their earliest appearance are concentric in structure. Adopting Ecker's classification, I distinguis^i simple concentric corpuscles and compound concentric corpuscles.
pouch is nearly all converted into thymus it may be regarded as the
 
thymic anlage from a very early stage.  
 
  
At 11 mm. (Text Figure 1), the pouch is a hollow epithelial tube directed from without ventrally and mesially. The lumen (l) is large
+
(a) Three types of simple concentric corpuscles are to be considered. (1) The ordinary type is far more numerous than any other. The earliest recognizable stage is shown in Plate II, Fig. 11. A nucleus (n) of the syncytium of the medulla has enlarged to perhaps twice its ordinary volume and has lost the ability to stain in the characteristic way with ha?matoxylin. Its sap is clear and a few reddish stained granules represent its chromatin. x\round it in the cytoplasm is an indistinct uneven layer of colloid (c /). The colloid is not yet solid and is being formed in concentric fibers or sheets. A slightly later stage is shown in Plate II, Fig. 14 and Fig. 15 (left side of figure). Some of the colloid (c s) next to the nucleus is now solid. The next stage is shown in Plate II, Fig. 15 (right side of figure). These corpuscles show a thick layer of colloid (c s d) that stains intensely with Congo red. Just outside the deeply staining colloid, colloid in formation may be seen. The nuclei are clear, and have become smaller and irregular in outline. The colloid seems to be pressing upon them and obliterating them. The colloid transformation gradually involves the adjacent c3^toplasm of the syncytium until other nuclei are involved. The corpuscle has now reached the condition shown in Plate II, Fig. 12. The central area (o c) is solid, the nucleus having disappeared entirely. Another (n') is nearly obliterated by the colloid. Part of the central area {o c) no longer stains intensely, and it is breaking loose by the formation of a concentric space. Several nuclei are surrounded by colloid in formation. Their long axes are nearly in a tangential direction. These nuclei are clear but only moderately swollen.
and communicates freely with the pharynx. On the dorso-lateral aspect
 
of the pouch is a solid epithelial mass (n t) distinctly different in structure from the rest of the pouch. This is the nodulus thymicus
 
(Kastschenko, 14) and will be referred to by that term. This structure
 
has been described by Stieda (26), Prenant ' (22), and others as the  
 
anlage of the carotid gland.  
 
  
It was evidently mistaken by Minot ' in a 12-mm. pig for the anlage of  
+
In the further development of the corpuscle (Plate III, Fig. 17 and Plate II, Fig. 7), the central area {c s d) increases in size. The nuclei involved in this area become obliterated probably by the pressure of the colloid and are no longer distinguishable. This central area usually splits off and may break up into many smaller masses. The peripheral part of the corpuscle increases by extension of the colloid formation into the adjacent part of the syncytium. This extension takes place in the early stages by direct progressive involvement of the immediately adjacent cytoplasm; in later stages (Fig. 7), by the formation of concentric lamellae which cut ofl' unchanged areas of cytoplasm. The lamelhp increase in size and number, the cytoplasm included between them is changed into colloid. They finally become closely packed, giving the characteristic and
the entire thymus. It may be seen as early as the 8 mm. stage budding
 
off from the cranio-lateral aspect of the pouch. Immediately behind the
 
nodulus thymicus, but not connected to it at this stage is the inner blind
 
extremity of the sinus prsecervicalis (s p). These become fused at
 
12 mm. or 13 mm.
 
  
At 15 mm. (Text Figure 2) the thymic anlage is more elongated. It
 
now projects ventrally and medianwards, its free end lying immediately
 
caudad to the median thyroid anlage and just craniad to the pericardium.
 
Its lumen (Z) is still in communication with the pharynx. The sinus
 
prsecervicalis {s p) is drawn out, its lumen being smaller and longer.
 
It is now fused to the outer two-thirds of the posterior aspect of the
 
nodulus thymicus (n t).
 
  
At 18 mm. (Text Figure 3) the anlage is growing rapidly in a caudal
 
direction and just entering the thoracic cavity. It is connected to the
 
pharynx by a delicate epithelial cord. There is still a lumen in its caudal
 
part. The sinus praecervicalis has lost its connection to the nodulus
 
thymicus." The outer part of its lumen has disappeared and it seems
 
about to lose its connection with the ectoderm.
 
  
At 20 mm. (Text Figure 4) the thymus extends well into the thoracic
+
E. T. Bell 51
cavity. Its thoracic segment (t h) has increased considerably in size and
 
is united to the gland of the opposite side.  
 
  
The nodulus thymicus still forms the greater part of the head. The  
+
well-kncnvn onion-like structure found in the fully-formed eorpusele. The nuclei that are enclosed between the lamells! gradually lose their chromatin and become flattened out. They do not swell and are not obliterated. It seems that swelling occurs only in nuclei that are surrounded by deeply staining colloid, and that this change is preparatory to their obliteration by or transformation into colloid. The amount of the corpuscle that breaks up to form the softer center is very variable. The size of the center usually seems to increase with the age of the corpuscle.
anlage has no connection with the pharynx or the epidermis. There is
 
  
"Prenant is said to have since abandoned this idea and accepted Kastschenko's view. (v. Ebner in Kolliker's Gewebelehre des Menschen. Aufl.
+
Plate III, Fig. 21, shows a variation from the ordinary concentric type. The central nucleus (n) stains reddish but is not enlarged. Most of the other nuclei are unchanged. All the colloid (c /") is in the early fibrous and granular stage.
6, Bd. 3, 1, S. 340.)  
 
  
^Laboratory Text of Embryology, p. 191; also p. 209 and Fig. 124.  
+
From 20 cm. to full term nmny corpuscles show masses of calcareous material in or near the center. This material rarely appears in younger corpuscles (Plate III, Fig. 17, cl). It stains a violet blue with Delafield's ha?matoxylin.
  
* On the opposite side in this specimen, .these structures were fused over a
+
The majority of the corpuscles of Hassall belong to the ordinary type of simple concentric cor])uscles described above. It is very clear that they have nothing to do with blood-vessels. They never contain erythrocytes nor anything resembling them. Earely a lymphoblast or leucocyte is found inside the corpuscle. These seem to be usually involved in the corpuscle like ordinary stronui nuclei during the formation of the lamellae. (Their occurrence in other types will be discussed later.) It is also clear that these corpuscles arise from the syncytium of the medulla. They are epithelial in origin, since the entire stroma of the gland is derived from epithelium, but they are certainly not remnants of the original epithelial anlage. Xeither are they forjned from lymphoidlike elements that reassume their epithelial nature as Maurer described for the lizard.
very small area.  
 
  
 +
Some of Ammann's observations are in accord with my results. The swelling of the nucleus was noted by Ammann as tlu; first step toward the formation of the corpuscle. It should he noted, however, that rarely a corpuscle begins to form as a mass of colloid out in the cytoplasm and involves nuclei secondarily. I cannot distiiiguish his " Stadium der Transparenz " for I cannot be sure that a corpuscle is beginning to form until some colloid is present. The formation of the colloid is associated with the swelling of the nucleus. His other three stages, "Stadium der coUoiden Entartung," " Stadium der Yerkalkung," and " Stadium des Zerfalls " are easily seen. I have never seen corpuscles begin in leucocytes as x\mmann described. His statement thnt the corpuscle grows by apposition of reticulum cells is true in a modified sense. He thought that
  
  
32
 
  
 +
52 Tln' I )L'V('lo[)iiu'iit of []]{' 'I'liymus
  
 +
the outer ])art of a {•or])nscle is formed of reticuhim cells that have moved up and thittened themselves out around it. The description just given shows ihat tlie coi'puscles are iieNcr composed of distinct cells, and that the increase in size is due to an extension outward of tlie colloid foi'mation and not to a moving in of the adjacent tissue.
  
The Development of the Thymus
+
The concentric form of this type of corpuscle is due at first to its l)eing formed around a spherical or ellipsoidal nucleus. The swelling of this nucleus creates a centrifugal pressure in the adjacent cytoplasm. Before or during its transformation into colloid, the cytoplasm also increases in quantity\ That the cytoplasm increases in quantity is shown hy the fact that the nuclei are fewer in the corpuscle than in any adjacent area of the syncytium of equal size. This centrifugal pressure presses the newly formed colloid into concentric lamellae. It at first turns the long axes of the nuclei tangentially. and later flattens them and makes them concave toward the center.
  
 +
3. The epithelioid type of corpuscle is characterized by large areas of cytoplasm so marked off by colloid lamella? as to give the appearance of a mass of large epithelial cells. They may contain only one nucleus embedded in a well-defined area of cytoplasm (Plate III, Figs. 18 and 20). These correspond to the monocellular corpuscles that have been described for lizards and amphibians. They are rare in the pig. I have not been able to trace these very far, as they soon become indistinguishable from other forms. The only difference I have noted is that the outer colloid lamellae begin to form early, causing the peculiar appearance of a large epithelial cell. Again the epithelioid type may present an appearance such as shown in Plate I, Fig. 3. These do not seem to be formed around any special nucleus. The outer colloid lamella? form before any center has been established, niarking off large cytoplasmic areas that may look like large cells. The centrifugal pressure of expansion caused by the great increase of cytoplasm in this area determines the concentric form in these corpuscles. Pure epithelioid corpuscles are very rare, but epithelioid areas in other corpuscles are not uncommon. The occurrence of epithelioid areas in corpuscles of the ordinary type shows that it is due to variations in a fundamentally similar process.
  
 +
3. In the cystic type of corpuscle, the central part, instead of becoming transformed into colloid, undergoes early liquefaction, forming vacuoles. The central nucleus does not increase in size as in the ordinary type, but shrivels up and disappears. The corpuscle begins by the formation of outer colloid lamellae-^the central mass is not changed into colloid. In Plate II, Fig. 10, the central area (/; m) is undergoing a diffuse liquefaction. The nucleus (iv) is colorless and shrunken. In Plate TI.
  
now an elongated mass of thymic tissue extending upwards behind the
 
nodiilus thymicus, and fused with it. Its upper pointed extremity curves
 
outwards around the hypoglossal nerve. This is the " thymus superficialis " (t s) of Kastschenko and is regarded by him as being formed
 
from the sinus praecervicalis. Kastschenko describes this elongated
 
portion as being always separate from the rest of the head, being connected only by connective tissue. In my preparations it is clearly continuous with the rest of the anlage, and seems to have formed by growing
 
out from it. The presence of a lumen in its lower end favors Kast
 
  
  
.ec
+
E. T. Bell 53
  
 +
Fig. 8 (right side of figure), the central area has fonned two lai-ge vacuoles (v). On the left side of the same figure, a concentric vacuole (v) has formed, separating off a central spherical nucleated mass of protoplasm. The nucleus of this mass of protoplasm is shrunken and the cytoplasm shows many small vacuoles. The corpuscle shown in Plate II, Fig. 9, is probably a later stage of the form just described. The central protoplasmic mass has become converted into an ellipsoidal pale bo'dy (pm). The small circular body in this shriveled mass is probably the nucleus. Some corpuscles like the one shown in Fig. 9 are found in wdiich the central mass has entirely disappeared. The further growth of corpuscles of this type seems to be by formation of colloid lamella? as in the ordinary type. They soon become indistinguishable from other forms.
  
 +
The cystic type of corpuscle is rare in the pig. This evidently corresponds to the form in amphibia that misled Nusbaum and Machowski into reviving Afanassiew's theory. The central masses, in Figs. 8 and 9, might readily be mistaken for red corpuscles in animals in which these cells are nucleated. But the red cells of the blood of the pig are not nucleated at this stage. I have traced a number of these corpuscles (as well as those of other types) in serial sections and have never seen any indications of a connection to blood-vessels. Nusbaum and Machowski (19), (Fig. 1, c, S. 116) show a corpuscle which is similar to jny Fig. 9. It will 1)0 noted that the central space in neither of these figures is lined by endothelium. The early form of corpuscle shown by Nusbaum and Machowski (Fig. 1, d, S. 116) is very probably a normal bloodvessel with cubical endothelium. I have often found such vessels with cubical endothelium in the interlobular tissue of the pig's thymus at 10 cm. to 12 cm. They probably may be found at other stages also. In the thymus of a kitten, injected l)y the intra-vitam Prussian blue method previously described, the majority of the corpuscles were found to be in early stages. The injection did not penetrate any corpuscle. I had a somewhat better opportunity to study the relations of the corpuscles to the blood-vessels in a 14 cm. human embryo. Here the vessels of the thymus were all very much distended with blood and the corpuscles were in early stages. No blood cells were found in the corpuscles.
  
 +
(b) Compound concentric corpuscles are formed whenever two or more simple concentric corpuscles begin to form so close together that they come in contact during their later growth. An early stage of such a corpuscle is shown in Plate II, Fig. 15. The colloid lamellae are formed around each center until they come in contact; they are tlien formed around both centers. In Plate III, Fig. 22, a compound concentric cor
  
  
Text Fig. 3.
+
5-t Tlio D(>\('l()|)in('iit of the Tliyiinis
  
 +
piisclc is shown. 'I'lici'c aiT three siiiiph' coiu'cntric corpuscles in it — one of them (the h>\vcst in the liyiii-c) in a very early stage. Several lamella' ai'c common lo the older cor|)uscles, and one is common to all three. This ari'an<i'ement of the lamella' is a mechanical efTect of the tension in the cytoplasm, due to the ccntrifug^al pressure from the two centers. The size of the separate centers in a compound corpuscle depends upon the stage they have reached when they come in contact. If a compound coi'puscle he formed hy the union of two simple corpuscles in an early stage, as in Plate 111, Fig. 19, all indications of its compound nature are soon lost. A corpuscle originally compound may, then, in later stages, hecome indistinguishal)Ie fi'om simple corjniscles. The simple corpuscles uniting to form a compound concentric cor]niscle may be of any of the types previously described.
  
 +
B. Irregular Corpuscles.
  
Text Fig. 4.  
+
This grou]) includes those corpuscles which are not at first concentric. Concentric areas may appear later. According to the classification previously given, I distinguish a compact type and a reticular type.
  
 +
(a) The compact type (Plate III, Fig. 16) first appears as a compact area of syncytium of irregular shape. It is recognizable l)y the colloid it contains. The nuclei are not noticeably increased in size and have no regular arrangement. Their chromatin still stains dark with nuclear stains. The colloid (c f) is not yet solid. The corpuscle has no distinct center. These corpuscles grow by direct colloid transformation of the adjacent syncytium. No distinct lamella^ are formed. The colloid may remain in the fibrous condition shown in the figure (c f) or it may become solid, but it never reaches the deeply staining condition unless a concentric area be established.
  
 +
A later stage of this tyi)e is shown in Plate III, Fig. 23. The corpuscle is sharply marked off from the syncytium. Some of its colloid is solid. A concentric area (cs) is beginning to form. The nuclei are not markedly different from those of the adjacent syncytium. These corpuscles may become large and branched. Often one or more concentric areas are developed after the corpuscle has attained considerable size. By the growth of these concentric areas, irregidar corpuscles may become converted into concentric corpuscles.
  
Text Figure 3. Ventral view of thymic anlage; X 33; pig embryo, 18 mm.;
+
(b) The reticular type is produced by colloid formation in the ordinary reticulum of the medulla. In the types previously described, the spaces of the reticulum are \isually obliterated as the colloid formation advances; but in this form the spaces persist as a part of the corpuscle. Pure reticular corpuscles vary greatly in size, sometimes involving only
ec, ectoderm; I, lumen; nt, nodulus thymicus; ph, connection to pharynx;
 
s p, sinus praecervicalis.
 
  
Text Figure 4. Ventral view of thymic anlage; X 33; pig embryo, 20 mm.;
 
f, area fused with gland of opposite side; I, lumen; nt, nodulus thymicus;
 
th, thoracic segment; t s, thymus superficialis.
 
  
schenko's view, for there is no lumen in the head at 18 mm. in my preparations. On the other hand the separation from the head at the 18 mm.
 
stage favors the idea that the sinus prsecervicalis degenerates. I have not
 
studied a sufficient number of specimens at this transition stage to
 
enable me to decide this point, though I believe the ectoderm takes no
 
part in the formation of the thymic anlage. Kastschenko's results are
 
opposed by nearly all other students of this problem, but his work should
 
not be discarded before the development of the thymus superficialis in
 
the pig has been accurately determined.
 
  
At 27 mm. (Text Figure 5) the thymus is much longer and extends
+
E. 'W Bell ■ 55
  
 +
one node of the syncytium. Thev are never concentric, and never form lamellae. Eeticnlar areas often occur in other forms of corpuscles. In tiiis way leucocytes are often involved in tlic corpuscle, since they lie in the spaces of the reticulum. Lymphocytes often get into a corpuscle in the lymphohlast condition, heing cut off hy tlio formation of lamellae outside tliem (Plate III, Fig. 22). The Icui'Dcytes shut in the cor])uscle in this way during development uuiy not degenerate. They probably persist and help to remove the corpuscle in its final stages of degeneration.
  
 +
The amount of expansion of the cyt()i)lasm before or during the colloid transformation is probably small in the irregular reticular corpuscles, since it does not obliterate the spaces of the syncytium. In the compact type, the spaces of the syncytium are obliterated and there is evidence of some expansive force (note the arrangenunit of the nuclei in the upper part of Fig. 23, Plate III). In the figure referred to, the number of nuclei in any part of the corpuscle is less than in an equal area of the adjacent reticulum. These facts indicate that there is an expansion of the cytoplasm. That this expansive force does not produce a concentric form is due primarily to the fact that there is no expansion of a nucleus and distinct center of formation as is present in concentric corpuscles of the ordinary type. The absence of the onion-like structure in irregular corpuscles is due to the fact that the colloid is not laid down in lanielUw
  
E. T. Bell
+
Significance of the corpuscles of Hassall. It has been shown in the preceding pages that the corpuscles of Hassall in the pig are not epithelial remnants, and also that they are not formed from blood-vessels. There is no evidence connecting their development with the involution of the thymus, for they begin to form before the lymphoid transformation is complete and are most numerous when the thymus is at the height of its development. I have not been al)le to see the decrease in the rate of growth of the medulla described by Amnumn, and even if such did occur it is difficult to understand how it could cause the formation of a corpuscle.
  
 +
The above theories are, therefore, inconsistent with the facts of development in the pig. It seems to me that the formation of a corpuscle is not to be regarded as a ]u-ocess of degeneration. The fact that the formation of colloid is an essential feature in the development of every corpuscle is a strong argument that it is a form of secretion such as occurs in its neighl)oring branchial derivative, the thyroid. The fact that the corpuscles differentiate in an aj^parently uniform syncytium is further evidence airainst a theory of degeneration. Since the lymphocyte-forming fuiu-tion of tbc tliymus is probaI)ly secondary, it is not
  
  
33
 
  
 +
56 The Dov(^lopin(<Tit of tlio Thymus
  
 +
unreasonable to suppose that its primitive fimetion was the formation of a colloid secretion such as occurs in the thyroid, and that the corpuscles are abortive expressions of this primitive function/
  
well down into the thoracic cavity in relation to the base of the heart
+
Giant Cells.
where it has fused with the gland of the opposite side. Buds are now
 
beginning to form through the greater part of its extent. Traces of the
 
original lumen (I) may still be seen in several places. The "thymus
 
superficialis " is bent around the twelfth nerve. A delicate cord of thymic
 
  
 +
Polykaryocytes may often 1)0 seen in the medulla. Tliese bodies develop froui the syncylium of the uieilulla. They are first noticeable as groups of small s])herieal nuclei in a solid area of the syncytium. Tliese nuclei stain with merlium intensity and are all very similar in size and color. The area containing this group of nuclei becomes a well-defined node of the reticulum and persists as such. A polykaryocyte is, therefore, a large node of the reticulum containing a number of small nuclei very similar in appearance. These cells often occur in groups. They are entirely distinct from the corpuscles. They are evidently similar to the polykaryocytes found in bone marrow and other lymphoid tissues.
  
 +
Summary.
  
 +
The following is a resume of the development of the thymus in the pig :
  
Text Fig. 5.  
+
The thymus of the pig is probably developed entirely from the endoderm of the third gill pouch.
  
Text Figxjre 5. Ventral view of thymic anlage; X 33; pig embryo, 27 mm.;
+
By a gradual process of vacuolization and liquefaction of the cytoplasm, the epithelial syncytium of the thymic anlage is converted into a cellular reticulum.
/. area fused with gland of opposite side; 1, lumen; nt, nodulus thymicus;
 
th, thoracic segment; t s, thymus superficialis.  
 
  
tissue fused with the l)ack of the nodulus thymicus connects the thymus
+
From the first appearance of vacuolization, three types of nuclei are present: large pale nuclei; small dark nuclei (lymphoblasts), and large dark intermediate forms.
superficialis to the rest of the head.  
 
  
From about 3 cm. until toward the end of fcetal life the thymus shows
+
The lymphoblasts gradually break loose from the cellular reticulum, moving into its spaces and forming lymphocytes. Mitoses are most numerous at the period of the most rapid formation of lymphocytes. The medulla continues to form lymphocytes at least as late as birth.
the two constrictions, described by Prenant (22) (for the sheep) as the
 
intermediary and the cervico-thoracic cords. These cords connect three
 
3
 
  
 +
Lymphocytes appear in the connective tissue aromul tlu> th.ynuis shortly after they are formed ; and lymphoblasts, wdiich are distinguishable from lymphocytes only by being embedded in the syncytium, arc present in the thymus a long period before lymphocytes are found anywhere in the neighborhood of the thymus.
  
 +
The celhdar reticulum of the earlier stages persists in a modified form as the reticulum of both cortex and medulla. It retains more cytoplasm
  
3-i Tlic Development of the Tliynius
+
' Ver Eecke (28) believes that the corpuscles in amphibians are of a glandular nature.
  
enlargements which we may call the head, the luid-t-ervical segment, and
 
the thoracic segment. I will consider each part separately. The thoracic
 
segment develops rapidly, spreading out ahove and in front of the heart.
 
The glands of the two sides fuse completely in this region. The lymphoid
 
transformation is noticeable at 3.5 cm. and well advanced at 4.5 cm. The
 
medulla begins to form at 8 cm. The cervico-thoracic cord is at first
 
very narrow but soon thickens and joins the cord of the opposite side.
 
At full term they form a sharp constriction, 3 mm. to 4 mm. wide and
 
5 mm. to 6 mm. long, situated at the superior aperture of the thorax,
 
and connecting the mid-cervical and thoracic segments. The histological
 
changes take place here later than in the enlargements.
 
  
The mid-cervical segment develops like the thoracic segment but somewhat more slowly. Budding, lymphoid transformation, and formation
 
of the medulla all begin here a little later than in the head and thoracic
 
segment. Its caudal end is slightly in advance of its cranial end. The
 
intermediary cord is well marked at 4 cm. It soon becomes very attenuated, having at 6 cm. in many places a diameter of only 15 fx. Prenant
 
suggests that this drawing out of the gland is caused by the rapid growth
 
of the neck. Later it increases in size and at full term is noticeable only
 
as a very slight constriction between the head and the mid-cervical
 
segment. The histological changes are much later here than in other
 
parts of the gland.
 
  
The greater part of the head in the early stages is formed by the
+
E. T. Bell 57
nodulus thymicus. This body grows slowly, attaining a diameter in crosssection of .5 mm. at 8 cm. Its cross-sectional area at 8 cm. is about onethird that of the rest of the head of the thymus. At this stage the nodulus
 
thymicus is a rounded body lying on the inner aspect of the head in relation to the carotid artery. A small area of its outer surface is fused
 
with the lymphoid tissue of the thymus. Its histological structure has
 
been fully described by Prenant (22). From the earliest stages, it
 
consists of cords of epithelial cells separated by blood capillaries. At
 
8 cm. the thymus superficialis (Kastschenko) is a large body lying craniad
 
and dorsal to the rest of the head but connected to it at its caudal
 
extremity.  
 
  
I have no observations on the head of the thymus between 8 cm. and  
+
in tlio inedulla. Practically all the reticnhira of both cortex and nie(liilla. as well as the lymphocytes, are, therefore, of epithelial origin.
full term, having overlooked it in collecting my material. In a full term
 
pig (30 cm.), the cervical part of the thymus is in two distinct parts.
 
The postero-ventral part, representing part of the head, the intermediary
 
cord, and the mid-cervical segment, is about 3 cm. long and 1 cm. wide.  
 
It extends from the upper border of the thyroid cartilage to the thorax,
 
and with the corresponding part of the opposite gland encloses the
 
  
 +
The {■oi-])iisclos of Hassall develop from the syncytium and arc, therefore, epithelial in origin. They are, however, not to be considered as remnants of the original epithelial anlage.
  
 +
In development various types of corpuscles are distinguished. Tlie ordinary typo of concentric corpuscles first appears as an enlarged clear nucleus around which colloid is being formed. Before or during the formation of colloid, the cytoplasm increases in quantity, filling the spaces of the reticulum and producing a centrifugal pressure which shapes the newly-formed colloid into concentric lamellse and flattens the neighboring nuclei, making them concave toward the center. The central nuclei usually become obliterated.
  
E. T. Bell 35
+
The epithelioid type is distinguished by its resemblance to large epithelial cells, this appearance being due to the formation of colloid lamella" around largo areas of clear cytoplasm. The central part of the corpuscle usually remains unchanged until after some of the colloid lamellfE are formed.
  
trachea, thyroid, and lower ]iait of the larynx. A slight narrowing at
+
The cystic type differs from the ordinary type only in that the central part undergoes vacuolization instead of colloid transformation. Those with concentric vacuoles may simulate blood-vessels containing nucleated red cells. Corpuscles never contain erythrocytes; neither can they be injected at any stage of development. Serial sections also show tliat there is no connection to blood-vessels at any stage.
the junction of the upper and middle thirds indicates the position of the
 
intermediary cord. The antero-dorsal part^ the thymus superficialis, is
 
rounded in cross-section, tapei-rrfg- to a point behind. Its anterior end is
 
about 7 mm. in diameter and loops around the twelfth nerve as in the
 
earliest stages. A lobule hangs over ventral to the nerve, a thin cord
 
being dorsal to it. The posterior end of the thymus superficialis extends
 
to the cricoid cartilage dorsal to the postero-ventral part of the gland.  
 
It is united to this part of the gland by a very delicate band of thymic
 
tissue. I did not find the nodulus thymicus at full term. It has either
 
moved away from the head or degenerated.  
 
  
The duct of the thymus is the lumen of the third gill pouch. A
+
Compound concentric corpuscles are formed by the union of two or more simple concentric corpuscles during development.
glance at the Text Figures will show its development. It is broken up
 
into segments and finally obliterated. I could find no traces of it at
 
3.7 cm. or later. On the theory of the exclusively endodermal origin of
 
the thymus. I cannot explain the absence of a lumen in the head at
 
IS mm. and its presence at 20 mm. and 27 mm. unless it be due to
 
individual variation in different specimens.  
 
  
It appears from the foregoing that in the pig the exclusively endodermal origin of the thymus from the third gill [loueh is probable, but
+
Irregular corpuscles are not concentric ' in arrangement, and are formed in the syncytium in an irregular manner. In the compact type of irregular corpuscles, concentric areas may form.
a slight participation by the ectoderm has not been satisfactorily excluded.
 
Kastschenko's conclusions, however, as to the ectodermal origin of the
 
thymus are imwarranted by his recorded observations. Prenant, after
 
his careful work (on the sheep), was not sure that a small mass of ectoderm did not enter into the formation of the head. Practically all other
 
investigators of this problem maintain that tlie ectoderm takes no part
 
in the formation of the thymus. The epithelial l)ody (nodulus thymicus)
 
developing in connection witli tlie head of the thymus from the third
 
gill pouch does not form the carotid gland. Kastschenko's description of
 
the origin of the carotid gland in mammals from the adventitia of the
 
internal carotid is now accepted by the majority of anatomists, and it
 
therefore has nothing to do with the thymus in oi'igin.  
 
  
TiiK Hist<)L()(;y of tiik FrLLY-F()i;.Mi:i) Thymus.  
+
The formation of colloid is an essential feature in the development of every corpuscle, and is not to be considered as a process of degeneration.
  
Before taking u\) tlic histogenesis, I shall bi'iclly (.-(Uisider the histology
+
Since the conclusion of my work and after my manuscript was given to the publishers, two articles dealing with the thymus have appeared.
of the gland as shown in a 24-cni. embryo. At this stage ihe gland nuiy
 
be regarded as fully formed. As is well known, tlie thymic lobule consists of a cortical and a medidlary portion, — the medulla of all the
 
lobules being united by the medullary cord. The cortex consists of a
 
delicate reticulum with its spaces well filled by cells, usually lymphocytes.
 
The reticulum may be regarded as composed of small branched anastom
 
  
 +
Ph. Stohr (Ueber die Thymus, Sitzungsberichte der phys.-med. Gesellschaft zu Wiirzburg, June 8, 1905) believes that the thymus first epithelial in nature becomes converted entirely into small cells of lymphoid appearance. Later the large reticulum cells are formed from these by enlargement. The corpuscles of Hassall are formed by the massing together and enlargement of these lymphoid-like cells. The small round cells of the gland are epithelial in origin but are to be regarded not as lymphocytes but as epithelial cells. The thymus is not a source of lymphocytes.
  
36 The Development of the Thymus
 
  
osing cells, though of eourse no cell houndaries are distinguishable. The
 
nuclei are poor in chromatin, rounded, and usually 4.5 /a to 5.5 /x in
 
diameter. The amount of cytoplasm around the nuclei and connecting
 
them is usually very small. At some nodes there is a greater amount of
 
cytoplasm giving the appearance of a large reticulum cell. In connection
 
with the lilood-vessels, which are numerous in the cortex, are often found
 
branched cells with pale nuclei and cytoplasm that stains more intensely
 
than that of the rest of the reticulum. By a modification of Mallory's
 
method used by Jackson (13, S. 39), I have been able to demonstrate
 
numerous fibrillEe in the reticulum. In some cortical areas at this
 
stage there are a great many erythroblasts. Masses of free erythrocytes
 
are often found, usually near a comparatively large vessel, but such cells
 
occur singly anywhere in the cortex.
 
  
In the medulla, the syncytial character of the stroma is much more
+
58 J'lu^ Devolopmont nf the Tliymiis
pronounced. The cytoplasm is much more abundant than in the cortex,
 
and the spaces are smaller and not so numerous. There is not so much
 
room for lymphocytes as in the cortex, hence the lighter color of the
 
medulla in stained preparations. The nuclei of the syncytium are either
 
pale or dark, both types showing wide variations in size. By Jackson's
 
method (13, S. 39), fibrilla3 may be readily demonstrated in the syncytium. In Plate I, Fig. 6, is shown the arrangement of these fibrillse
 
(s f) in the medulla at 24 cm. They often may be traced into the
 
areas which are forming the concentric corpuscles. In some parts of the
 
medulla the fibrillae are very numerous ; in a few places, entirely absent.
 
In both cortex and medulla eosinophile cells are often found. These
 
occur in groups in the interlobular tissue around the blood-vessels, around
 
some of the corpuscles of Hassall, and singly in the reticulum. These
 
have been described by Schaffer (24). Free erythrocytes a.re rarely found
 
in the medulla. In the medulla are also found the corpuscles of Hassall.
 
Since the structure of these bodies depends largely upon their age, it may
 
be better understood from the consideration of their development.
 
  
The Lymphoid Transformation.'  
+
The author apparently believes that none of the small rounrt cells leave the gland though he admits that lymphocytes enter. But as mentioned above the zone of connective tissue immediately around the head at 7 cm. may contain even more lymphocytes than are present inside the gland at that time If these are all entering the gland then it is probable that most of the small round cells are really lymphocytes. This conception then does not simplify the problem but is only a theoretical compromise between the two views a'i to the origin of the lymphocytes.
  
Kolliker, in 79, first advanced the idea that the leucocytes are formed  
+
J. Aug. Hammar (Zur Histogenese und Involution der Thymusdriise, Anat. Anz. Bd. XXVII, June 17, 1905) regards the reticulum as formed from the epithelial anlage but thinks the evidence at hand insufficient to decide the question as to the origin of the lymphocytes. He finds lymphocytes outside the thymus in many animals (man, cat, chick, frog) before any are present inside the gland. The corpuscles of Hassall develop from the epithelial reticulum and undergo hyaline (colloid?) degeneration.
directly from the epithelial cells of the thymic anlage. According to
 
Minot (in human embryology, p. 878), "he records for the rabbit that
 
between the twentieth and twenty-third days the cells of the thymus become smaller and their outlines disappear, so that the organ appears to
 
  
° This term will be used to include those changes that occur in the thymus
+
My description of the formation of the corpuscles of Hassall differs essentially from Hammar's, in that I believe the formation of the corpuscle consists in the expansion of the cytoplasm of the syncytium and its conversion into colloid. Hammar did not recognize " colloid in formation," though he speaks of the coarse fibrillar structure of the protoplasm. He -did not describe such corpuscles as are shown in Fig. 7, Plate II.
during its passage from an epithelial to a characteristic lymphoid structure.  
 
  
 +
The considerations presented above in favor of the epithelial origin of the lymphocytes seem to me much stronger than those given by Hammar. His statements as to the presence of lymphocytes around the thymus before they are present inside are to be taken with some reservation inasmuch as he mentions small round cells separate from the syncytium earlier, but regards ihem as degenerating epithelial cells (S. 65). His figure from the human foetus (Fig. 18, S. 66) does not seem to be strong support for his statement. Certainly many lymphocytes are present in the pig thymus when the reticulum is broken up as much as shown in the figure referred to. It is also to be borne in mind that the different parts of the thymus undergo the lymphoid transformation at different times and that a single section may therefore be misleading.
  
 +
LITERATURE.
  
,E. T. Bell 37
+
la. Afanassiew, B. — Ueber die concentrischen Korper der Thymus. Archiv
  
bo ail atiuiiiulaticni of small round nuclei. At about the same period
+
f. mikr. Anat., Bd. XIV, 1877. lb. Weitere Untersuchungen iiber den Bau und die Entwickelung
blood-vessels and eonneetive tissue grow into the epithelial anlage."
 
  
His {I'i 1)). 80, and Stieda (26), 81, claimed that the corpuscles of
+
der Thymus und der Wintcrschlafdriise der Saugethiere. Archiv f.
Hassall are the only remnants of the epithelial anlage, that the lymphocytes, reticulum, etc., are of mesenchymal origin.  
 
  
Maurer (17 a), 86, described the leucocytes as arising directly from the
+
mikr. Anat., Bd. XIV, 1877. 2. Ammann, a. — Beitrage zur Anatomic der Thymusdriise. Basel, 1882. 3a. Beard. The development and probable function of the thymus. Anat.
cells of the epithelial anlage in the thymus of teleosts. In the amphibian
 
thymus (17 b), 88, he thinks that the leucocytes are probably of mesenchymal origin. He was unwilling to conclude that they arose from the
 
epithelium because he could not find transition forms. In lizards (17 c),  
 
99, he records that even before the separation of the epithelial anlage of
 
the thymus from the pharynx, changes begin. The peripheral cells are
 
closely crowded together and show many mitoses. There arises between
 
the central cells, or is formed in vacuoles in their protoplasm, a fluid which
 
accumulates until the nuclei surrounded by a thin zone of protoplasm are
 
connected only by protoplasmic threads. A loose medulla is thus formed
 
which looks like a cellular reticulum. The cortex is still solid. The  
 
lymphocytes are formed from the epithelial cells; none come from without. Later, blood-vessels and connective tissue grow in. He believes
 
that the reticulum is of mesenchymal origin in all forms. Maurer
 
(17 d), 02, still holds that in amphibians the lymphocytes are probably
 
of mesenchymal origin.  
 
  
Plermann et Tourneux (11), 87, find that in man and other mammals
+
Anz., Bd. IX, 1894. 3b. The true function of the thymus. Lancet, 1899.
the epithelial anlage of the thymus is gradually converted into leucocytes
 
and reticulum cells. Vacuoles appear during the transformation which
 
seem to be formed by the absorption of large cells. In a sheep embryo
 
of 130 mm., the clear epithelial cells have all disappeared, giving rise
 
to small round cells and reticulum cells. Prolongations of connective
 
tissue, each containing a blood-vessel, grow into the anlage during the
 
transformation. They are not sure that all the thymic elements are
 
epithelial in origin, being especially in doubt about the origin of some of
 
the reticulum cells.  
 
  
Gulland (8), 91, describes the development of the tonsil in the rabbit.
+
4. Born, G.— Ueber die Derivate der embryonalen Schlundbogen und
Leucocytes first appear in the connective tissue around the thymus. Later
 
they appear in the connective tissue around the tonsil. They infiltrate
 
the tonsillar epithelium. Fo leucocytes are of epithelial origin. After
 
studying the tonsil he examined the thymus in a few specimens and
 
concluded that the same process of leucocyte infiltration occurred there.  
 
He does not give the details of their infiltration, and did not see any of
 
the transition forms of nuclei in the thymus at that period.  
 
  
Prenant (22), 94, made a careful study of the development of the
+
Schlundspalten bei Saugethieren. Archiv f. mikr. Anat., Bd. XXII, 1883.
  
 +
5. CoRNiL et Ranvier. — Manuel d'histologie pathologique. Paris, 1869, p.
  
 +
135 (cited from Ammann).
  
38 The Drvi'lopincnt ol' the 'riiynius
 
  
thynuis in sheep embrvos. His results are as follows. At 25 mm. the
 
gland is composed of distinct polyhedral cells with nuclei of only one
 
kind. A few mitoses and an occasional direct division are to be seen. At
 
20 mm. mitoses are numerous (oi^e nucleus in fifty). jSTuclei are regularly rounded or elliptical and some small nuclei occur juxtaposed to
 
large nuclei. At 28 mm. many mitoses are present and irregular spaces
 
have appeared. These spaces are not blood-vessels nor parts of the
 
thymic duet but vacuoles. Some nuclei, noticeably small and darkly
 
colored, lie close to the large, clear nuclei and seem to be budded off from
 
them. Some nuclei (rare) are broken into three or four chromatic
 
bodies. Embryos of 40 mm. have undergone in great part the lymphoid
 
transformation. All transitions are found between the large, pale elliptical nuclei of clear reticular structure and the small, deeply colored
 
rounded nuclei whose sap is strongly stained. These last are certainly
 
lymphocytes and constitute an immense majority of the cellular elements.
 
Large, clear nuclei are found Joined to small dark ones — nuclear couples.
 
  
At 85 mm. the medulla appears; the cortex corresponds to the entire
+
E. T. Bell 59
thymic mass of preceding stages. The cortex contains a great many
 
lymphocytes separated by islands and rows of pale nuclei. There are
 
about thirty lymphocytes to one pale nucleus. Mitoses are numerous in
 
the cortex. In the medulla at this stage, the large clear, and small dark,
 
nuclei are about equal in number, and mitoses are rarer than in the
 
cortex. In later embryonic stages a clear peripheral zone is present
 
where cell proliferation takes place. Mitoses are now more numerous in
 
the medulla than in the cortex. It is probable that a certain number of
 
the epithelial cells persist as reticulum cells in the fully-formed organ.  
 
  
J. Beard (3 a), 94, (3 b), 99, thinks that the function of the thymus
+
6. EcKER. — Art. " Blutgefassdrusen," Wagner's Handw. der Phys., Ill (cited
is to form the first leucocytes. He finds that in the skate the epithelial
 
cells are converted early into lymphocytes which emigrate into the blood.  
 
There are many breaks in the gland where the lymphocytes escape in
 
masses. The thymus is the only source of leucocytes until the other
 
lymphoid organs are formed.  
 
  
Ver Eecke (28), 99, finds that in the frog the epithelial thymus is
+
from Ammann).
invaded by lymphocytes and connective tissue. The epithelial cells are
 
not destroyed but merely dispersed by the mesenchymal elements. He
 
calls the resulting tissue lympho-epithelial. This idea of the commingling of the two tissues had already been advanced by Eettcrer.  
 
  
Xusbaum and Prymak (20), 01, on teleosts, agree with j\Iaurer that
+
7. Priedleben, a. — Die Physiol, der Thymusdriise. Frankfurt, 1858.
the lymphocytes are of epithelial origin but disagree on the details of their
 
formation. They find that the epithelial anlage is at first composed of
 
cells with distinct lioundaries. It is not different from the epithelium
 
  
 +
8. GULLAND. — The Development of adenoid tissue with special reference
  
 +
to the tonsil and thymus. Laboratory Reports issued by the Royal College Phys., Edinburgh, Vol. Ill, 1891.
  
E. T. Bell 39
+
9. GiJNZBURG. — Ueber die geschichteten Korper der Thymus. Zeitschr. f.
  
of the pharynx. Before any blood-vessels or connective tissue have invaded the organ, changes begin in. the central part. These changes consist in the breaking up of the cytoplasm so that the cells become
+
klin. Med., Bd. VI, 1857, S. 456 (cited from Henle und Meissner. Bericht iiber die Fortschritte der Anat. u. Physiol.).
branched and connected by delicate processes. These processes finally
 
break apart leaving a nucleus surrounded by a thin layer of protoplasm —
 
a lymphocyte. The peripheral epithelial layer multiplies rapidly, forming
 
nuclei somewhat smaller and darker than their own. These nuclei become gradually changed into the nuclei of lymphocytes and break away
 
from the other cells. All transitions are present between the large, clear
 
epithelial nuclei and the lymphocytes. Blood-vessels and connective
 
tissue grow in from the outside.  
 
  
It appears from a survey of the literature that, of those who have
+
10. Hassall. — The microscropical anatomy of the human body in health and
studied the origin of lymphocytes in the mamalian thymus. His, Stieda,
 
and Gulland have advocated the idea that they invade the gland from
 
without, and that the original epithelial anlage persists only as remnants,
 
the corpuscles of Hassall. They also consider the stroma of mesenchymal
 
origin. On the other hand, Kolliker, Hermann and Tourneux, and Prenant, have described the lymphocytes as derived directly from the epithelial
 
cells of the anlage. Hermann and Tourneux and Prenant ascribed a
 
similar origin to part of the reticulum.
 
  
Xeither His, Stieda, nor Gulland made a detailed histological study
+
disease. London, 1846 (cited from Ammann).
of the changes that take place in the thymus during the transformation.  
 
They did not see the vacuolization of the cytoplasm, the changes in the
 
epithelial nuclei, etc. — processes wdiich undoubtedly occur. Gulland
 
made nearly all his observations on the tonsil and then from a superficial
 
examination of the thymus concluded that the process is the same there.
 
The conclusions of these men are therefore not to be compared on this
 
point with those obtained by the thorough and careful work of Prenant.  
 
  
On amphibians, Maurer hesitatingly agrees with His, and Yer Eecke
+
11. Hermann et Tourneux. — Article thymus, Diet, encycl. des Sciences Medi cales. Troisieme Serie, 17, 1887. 12a. His, W.— Zeitschrift f. wiss. Zoologie, Bd. X, S. 348. Leipzig, 1860. 12b. Anatomic menschlicher Embryonen. Leipzig, 1880, S. 56.
accepts the mesenchymal origin of the leucocytes ; while on fishes Maurer,  
 
Beard, and Nusbaum and Prymak believe in the epithelial origin of
 
lymphocytes. Maurer's work on reptiles is in agreement with his work
 
on teleosts.  
 
  
As to the origin of leucocytes in the lymphoid organs of tlie alimentary
+
13. Jackson, C. M. — Zur Histologie und Histogenese des Knochenmarkes.
canal, opinion is divided. Eetterer, v. Davidoff, Rudinger, Klaatsch,
 
and others have described the leucocytes as arising from epithelium and
 
being invaded by mesenchymal elements forming adenoid tissue. Stohr,
 
Gulland, Tomarkin, and others describe them as penetrating the epithelium from without.  
 
  
I shall now discuss my own observations on the lymphoid transformation in the thymus of the pig. From a very early stage (11 mm.), the
+
Archiv f. Anat. und Physiol., Anat. Abth., 1904.
  
 +
14. Kastschenko. — Das Schicksal der embryonalen Schlundspalten bei
  
 +
Saugethieren. Archiv f. mikr. Anat., Bd. XXX, 1887.
  
40 The Development of the Thymus  
+
15. Klein. — Neuere Arbeiten iiber die Glandula Thymus. Centralbl. f. allg.
  
t'pithelium of the third gill pouch is a syncytium. No cell boundaries
+
Pathol, u. pathol. Anat., 1898.
exist. The nuclei, large and irregular in shape, are embedded in a common mass of cytoplasm. In the thymus at 20 mm. I find a syncytium
 
of dense cytoplasm embedded in which are large nuclei of irregular shape
 
and size. No distinct types of nuclei are present yet; all stain with
 
medium intensity. A few mitoses are to be seen.  
 
  
In a section of the mid-cervical segment at 3.7 cm. (Plate I, Fig. 1),
+
16. Langerhans und Savei.iew. — Beitrage zur Physiologic der Brustdriise.
I find evidence that the lymphoid transformation has begun. The syncytium is composed of coarsely reticulated cytoplasm much looser in
 
texture than that of the preceding stage. It contains a few irregular
 
spaces (s s) which are evidently of the nature of vacuoles. These may
 
be formed, as Maurer suggests, by liquefaction of the cytoplasm. There
 
is no reason to suppose that cells degenerate and form them as Hermann
 
and Tourneux believed. Three types of nuclei may be distinguished;
 
large pale nuclei (Ipn) large dark nuclei (I dn), and small dark nuclei
 
(lymphoblasts) (Ih). Transition forms occur between these types.
 
The large dark nuclei are intermediate forms between the pale nuclei
 
and the lymphoblasts. A few mitoses (m) occur. No blood-vessels are
 
present inside the anlage but they may be seen between the buds just
 
outside. At this stage, the head and the thoracic segment have areas
 
that are somewhat farther advanced than this. The intermediary and
 
cervico-thoracic cords show no changes.  
 
  
At a later stage than the above (Plate I, Fig. 2), in the thoracic
+
Virchow's Archiv, Bd. 134, 1S93. 17a. Maurer. — Schilddriise und Thymus der Teleostier. Morph. Jahrb.. Bd.
segment of a 4.5-cm. pig, jthe spaces of the syncytium (s s) have increased greatly in number and size. The anlage is now a cellular reticulum. The large pale nuclei are somewhat less numerous than the
 
dark nuclei and many have become angular, adapting themselves to the
 
nodes of the syncytium. They contain less chromatin than in the
 
preceding stage. Large dark nuclei and lymphoblasts are present; the
 
lymphoblasts are much more numerous than in the preceding stage. A
 
very few small dark nuclei are completely separated from the syncytium.  
 
These are lymphocytes. There are no lymphocytes in the connective
 
tissue around the thymus or in the blood at this stage. I did not
 
examine the tonsil or spleen at any stage. A few small blood-vessels are
 
to be seen; their walls consist of endothelium only. There are more
 
mitoses than at the preceding stage, but none happened to be present in
 
the area shown in the figure. During mitosis, at all stages of development, except the early epithelial condition, the chromosomes are so
 
closely packed that it is very difficult to distinguish them individually.  
 
  
In a section through the mid-cervical segment of a 7-cm. pig
+
XI, 1886. 17b. Schilddriise, Thymus, und Kiemenreste bei Amphibien. Morph.
(Plate I, Fig. 5), we see a stage somewhat later than the one shown in
 
  
 +
Jahrb., Bd. XIII, 1888. 17c. Schilddriise, Thymus, und andere Schlundspaltenderivate bei der
  
 +
Eidechse. Morph. Jahrb., Bd. XXVII, 1899. 17d. In Hertwig's Handbuch der Entwickelungslehre der Wirbelthiere,
  
E. T. Bell 41
+
Lief. 6-8, S. 131 ff., 1902.
  
Fig. 2. In various jiarts of the section lymphocytes (I) are completely
+
18. MoNGUiui. — Sulla glandula timo. Parma, 1885 (cited from Prenant).
formed. Tlie great majority of the small round nuclei are in the lymphoblast (l h) condition, i. e.,thcy are not yet completely separated from the
 
syncytium. There are a few lymphocytes outside the thymus in the
 
interlobular tissue in this region; around the head and the thoracic
 
segment at 7 cm. they are numerous, these parts being in a later stage
 
of transformation. I have never seen lymphocytes outside the thyfnus,
 
where there were none inside it ; but they appear outside shortly after they
 
are formed here. Those formed next the interlobular septa seem to pass
 
out very early. Of course the lymphoblasts, which are distinguishable
 
from the lymphocytes only by being imbedded in the syncytium, are to
 
be seen in the thymus long before any appear outside.  
 
  
At the stage shown in Fig. 5, a great many nuclei are in mitosis. I
+
19. NusBAUM, J., und Maciiowski. — Die Bildung der concentrischen Korper chen und die phagocytotischen Vorgange bei der Involution der Amphibienthymus, etc. Anat. Anz., Bd. XXI, 1902.
have not seen at any stage, the amitoses and nuclear couples described
 
by Prenant for the sheep. In some parts of the section comparatively
 
large solid epithelial areas occur. These are found as often in the
 
central as in the peripheral part. Many of the pale nuclei are smaller
 
than those shown in Fig. 2. The blood-vessels are somewhat larger and
 
more numerous than those at 4.5 cm.  
 
  
It is to be noted that the epithelial anlage does not at any stage become
+
20. NusBAUM, J., und Prymak, T.— Zur Entwickelungsgeschichte der lym phoiden Elemente der Thymus bei den Knochenfischen. Anat. Anz., Bd. XIX, 1901.
converted entirely into small round cells as many observers have stated.  
 
Distinctly pale angular reticular nuclei can always be seen.  
 
  
In the mid-cervical segment at 8.5 cm. (Plate I, Fig. 4), a great many
+
21. Paulitzky. — Disquis. de stratis glandulse thymi corpusculis. Habilita tionsschr., Halis, 1S63 (cited from Henle und Meissner's Bericht iiber die Fortschritte der Anat. und Physiol.).
lymphocytes (/) are formed. These lie between the persisting epithelial
 
cells which are now arranged in irregular cords and islands. In these
 
epithelial masses, lymphoblasts may still be seen indicating that the
 
formation of lymphocytes is still in progTCss. Many of the pale nuclei
 
are now small. The heavy hsematoxylin stain in this case makes the
 
nuclei darker than they would appear with an ordinary stain. A few
 
nuclei are in mitosis.  
 
  
This figure shows also the first appearance of the medulla {ind). The
+
22. Prenant. — Developpement organique et histologique du thymus, de la
medulla is formed directly, as shown in the figure, from persisting parts
 
of the epithelial syncytium. Certain centrally situated masses of this
 
syncytium undergo changes of such a nature that they stain readily with
 
cytoplasmic stains such as Congo red. In sections stained with hematoxylin and Congo red, the medulla is first recognized as a l)rightly
 
colored area situated usually about the center of the lobule. Tlicse
 
epithelial masses that give rise to the medulla seem to increase in size
 
about the time of the change in staining capacity. The first differentiation of the medulla is chemical rather than morphological, for there are
 
other persisting epithelial masses even larger than it in the same section
 
  
 +
glande thyroide, et de la glande carotidienne. La Cellule, Tome X, 1894.
  
 +
23. Prymak. T. — Beitrage zur Kenntnis des feineren Baues und der Involu tion der Thymusdriise bei den Teleostieren. Anat. Anz., Bd. XXI, 1902.
  
42 The Development of the Thymus
 
  
that do not react in the same way with the cytophismic stains. The
 
meduna appears in the head and the thoracic segment at 7.5 cm. to 8 cm.
 
All the gland except this small central area forms the cortex. Bloodvessels now reach 'all parts of the gland, but are still few in number. I
 
cannot distinguish any wall except the endothelium on those actually
 
inside the gland.
 
  
In a 9.5-cm. pig, the medulla is larger. It contains pale nuclei of
+
60 'I'lio Dovclnpmont of the T'hynms
various sizes, large dark nuclei, and lymphoblasts. Its spaces are smaller
 
than those of the cortex. The early stages in the formation of the corpuscles of Hassall appear as soon as the medulla begins to form. The
 
epithelial cords in the cortex have become less conspicuous, but are still
 
forming lymphocytes. A few nuclei are in mitosis. Many blood capillaries may now be seen penetrating the gland from the periphery.
 
These vessels run in the epithelial masses and have a wall of large
 
endothelial cells which gives them the appearance of radiating cords.
 
When these vessels first appear, as at this stage, they have only an
 
endothelial wall. The blood-vessels grow in as small capillaries which,
 
after their entrance, increase in size and branch ; they do not break in as
 
large vessels surrounded by mesenchymal tissue. I am fairly sure that
 
aside from the endothelial cells few or no mesenchymal cells come into
 
the thymus. Around the greater part of the periphery of the gland is
 
a solid zone of syncytium two or three nuclei deep which is in transformation like the epithelial cords inside. This zone, described by Prenant as a zone of proliferation, grows rapidly, as the frequent mitoses
 
indicate. Its inner boundary is forming lymphocytes and reticulum cells.
 
  
In a 14-cm. pig, the lymphoid transformation is practically at an end
+
24. SciiAKFER, J. — Ueber den feirieren Bau der Thymus und deren Beziehung^
except in the medulla. The peripheral zone of proliferation has disappeared. The cortex has about the same structure as at 24 cm., as
 
previously described. In the medulla, lymphoblasts, large pale nuclei,
 
and the large dark intermediate types are still present. There are a few
 
mitoses here. It is very probable therefore that the formation of lymphocytes is still in progress in the medulla. The medulla at 2-i cm.
 
shows a similar structure except that there are fewer lymphoblasts. These
 
facts persuade me to regard the medulla as a center for lymphocyte
 
formation at least as late as birth. Connective tissue fibrillae begin to
 
appear in the gland along the large blood-vessels and the interlolmlar
 
septa as early as 10.5 cm. They are only a little farther in at 16 cm. ;
 
but near full term they are present in nearly all parts of the stroma.
 
(See Plate I, Fig. 6.)
 
  
The above account may be summarized as follows: In the pig the
+
zur Blutbildung. Sitzungsber. d. K. Acad. d. Wissensch. Math.naturw. Kl. Wien., Bd. CII, Abt. Ill, 1893.
epithelial syncytium of the thymic anlage becomes loosened up by the
 
  
 +
25. SciiEnEL, J. — Zellvermehrung in der Thymusdriise. Archiv f. mikr.
  
 +
Anat., Bd. XXIV.
  
E. T. Bell 43
+
26. Stieda, L. — Untersuchungen uber die Entwickelung der Glandula Thy mus, Glandula Thyroidea, und Glandula Carotica. Leipzig, 1881 (cited from Hermann et Tourneux).
  
formation of vacuoles in it. These vacuoles increase in number and
+
27. Sx'LTAN.^Beitrag zur Involution der Thymusdriise. Virchow's Archiv,
size, converting the anlage into a cellular reticulum. While this vacuolization is in progress, the nuclei, which at first are of one kind with a
 
medium amount of chromatin, ditferentiate into large clear, large dark,
 
and small dark (lymphoblast) forms. The large dark nuclei probably
 
divide by mitosis and form the lymphoblasts. The lymphoblasts gradually break loose from the syncytium, passing into its spaces and becoming
 
lymphocytes. Shortly after lymphocytes begin to be formed, some of
 
them pass out of the gland into the surrounding connective tissue. The
 
lymphoid transformation begins in embryos of 2.5 cm. to 3 cm. and continues in the cortex until 13 cm. or 13 cm. In the medulla it is not complete at birth. Since the thymus increases greatly in size during this
 
period the epithelial syncytium must grow rapidly. Lymphocytes are
 
constantly being formed at the expense of the growing syncytium. A
 
peripheral zone of proliferation is present from about 8 cm. to 13 cm.
 
The medulla is formed as a chemical differentiation of certain centrally
 
situated areas of the epithelial syncytium. The histological changes
 
occur earlier in the head and thoracic segment than in the mid-cervical
 
segment and very much earlier than in the cords. The reticulum of both
 
cortex and medulla is practically all of e])ithelial origin. Some branched
 
cells around the blood-vessels in the cortex may be of mesenchymal
 
origin.
 
  
My reasons for regarding tlie lymphocytes as of epithelial origin are
+
Bd. 144, 189G.
as follows :
 
  
A. The lympholilasts are true epithelial nuclei, because (1) there are
+
28. Vek Eecke. — Structure et modifications fonctionelles du thymus de la
numerous transition forms between them and the large dark nuclei which
 
later cannot l)e regarded as invading lymphocytes; (3) they are closely
 
embedded in the syncytium and show no evidence of having eaten their
 
way through the protoplasm; (3) they are present from a very early
 
stage and increase in number as development proceeds; (4) they are
 
present before blood-vessels invade the gland and have no constant relation to blood-vessels or to the surface of the gland that indicates an invasion from either of these directions; (5) they are present before lymphocytes appear in the connective-tissue around the thymus.
 
  
B. Some observers admit tliat the small dark nuclei (lymphoblasts)
+
grenouille. Bulletin de I'Acadc'mie royale de MC'dicine de Belgique, 1899.
are of epithelial origin but do not admit that tlicy form lym])hocytes.  
 
The considerations that lead me to bciicNc tliat the lymphoblasts do form
 
the lymphocytes are: (1) the small dark nuclei (lymphoblasts) show
 
every possible relation to the syncytium from being completely embedded
 
in it to lying free in the syncytial s]")aces. A comparison with later
 
stages shows tb.at tliis appearance is not due to poor fixation oi- to the
 
  
 +
29. ViKciiow, R. — Kritisches iiber den oberschlesischen Typhus. Archiv, Bd.
  
 +
3, 1851, S. 222.
  
44 'V\\v ncvclopnioiit of tlio M'hymns
+
30. Wallisch. — Zur Bedeutung der Hassall'schen Korperchen. Archiv f.
  
adherence of the nuclei to the reticuhini ; (?) the first free niiclci often
+
mikr. Anat., 1903.
appear in the center of the gland whoi tlicrc are no other free nuclei in
 
the periphery at that level; (3) there is good evidence that lymphocytes
 
emigrate from the thymns in large numbers. If we examine the thymus
 
of a 7-cm. pig in serial sections we find that the lymphoid transformation
 
is less advanced in the mid-cervical segment than in the head. In the
 
mid-cervical segment there are a few lymphocytes in the interlobular
 
tissue. In the lower end of the head where there are more lymphocytes
 
inside the gland, lymphocytes pack the interlobular tissue and form a
 
thin zone around the periphery of the gland. In the middle of the head
 
where the transformation is far advanced, lymphocytes pack the interlobular tissue and form a thick zone around the entire gland. Indeed,
 
in some sections, there are more l3T3iphocytes in the zone outside than
 
are present inside the gland. If this zone of lymphocytes be passing into
 
the gland, it is not easy to understand why it is formed from Avithin outwards, and why it is thickest where the greatest number of lymphoc3ies
 
are already present inside. No satisfactory suggestion has yet been made
 
as to why lymphocytes should thus suddenly pour into the thymus at a
 
time when if present at all elsewhere they are rare. They do not come
 
to break up the thymic epithelium, for that is already a reticulum before
 
free cells are present (Fig. 3, Plate I). Where lymphocytes invade
 
intestinal epithelium as in the tonsil they eat paths through it leaving
 
spaces. The epithelial reticulum of the thymus is not formed in that
 
way. On the other hand it is not difficult to believe that this zone of
 
lymphocytes is formed l^y cells passing out the periphery of the thymus
 
and that the gland thus contributes a great number of lymphocytes to the
 
organism; (4) I have not been able to find lymphocytes in the connectivetissue around the th}Tuus before they are present inside. An invasion by
 
way of the blood-vessels may be excluded, since the thick zone of lymphocytes formed around the gland shows that these cells either enter or leave
 
it through the preiphery.  
 
  
The Corpuscles of Hassall.  
+
31. Watxey. — The minute anatomy of the thymus. Philos. Transact, of the
  
These bodies were first mentioned by Hassall ( 10 ) in 46, He speaks
+
Royal Society of London, Vol. 173, Part III, 1883 (cited from Prenant).
of them as being composed of mother cells which enclose the newlyformed daughter cells and nuclei. He thought the central mass was
 
formed by the outer enclosing layers. He found bodies which lie regarded
 
of the same nature in fibrous coagulations in the heart.  
 
  
Virchow (29), 51, in a discussion of endogenous cell formation, compares Hassall's corpuscles to carcinoma pearls. He had about the same
+
EXPLANATION OF PLATES.
  
 +
All the figures were drawn with Leitz obj. 1/12, oc. 4, and camera lucida. The magnification after the reduction of the plates is about 1060 diameters. All drawings were made from transverse sections of the mid-cervical segment of the thymus unless they are otherwise indicated.
  
 +
The following abbreviations designate the structures indicated in all the figures :
  
E. T. Bell 45
+
c f — colloid in formation. I p n — -large pale nucleus.
  
conception of the nature of the corpuscles as Hassall. This oft-quoted
+
cl — -calcareous deposit. m — nucleus in mitosis,
comparison was therefore not based upon a deep insight into their nature.  
 
  
Giinzburg (9), 57, did not advance beyond Hassall's conception that
+
c s — solid colloid. vid — beginning of medulla,
the central mass is formed by the peripheral layers.  
 
  
Paulitzky (21), 63, described the center of the corpuscles as homogeneous or granular. They sometimes contain an elliptical nucleus, sometimes fat droplets. The larger ones have in the center several nuclei' or
+
c s d — solid colloid that stains n — nucleus.
cell-like forms. The central part is formed from masses of epithelial
 
cells. Connective tissue cells grow around them and are transformed into
 
epithelial cells forming the peripheral part of the corpuscle.  
 
  
The term "concentric corpuscles" was introduced by Ecker (6), who
+
deeply. o c — old colloid.
described them as arising directly from gland cells by fatty metamorphosis. He distinguished (1) simple corpuscles, round vesicles with
 
thick concentric hulls, containing inside a fatty opalescent mass, and (2)
 
compound corpuscles, which consist of several vesicles with a common
 
hull. The peripheral layers of a corpuscle consist of flattened cells.  
 
  
His (13 a, 12 b), 60, 80, described the corpuscles as consisting of an
+
e — erythrocyte. p m — protoplasmic mass.
outer striated shell, probably composed of nucleated cells, and containing lymphocyte-like cells inside. He supposed them to be the original
 
cells of the epithelial anlage which become entangled in the reticulum in
 
some way. Their rapid growth in their narrow confines causes the concentric form.  
 
  
Cornil et Eanvier (5), 69, considered the corpuscles as arising from
+
end — -endothelial nucleus. sf — fibril in syncytium.
the endothelium of blood-vessels and compared them to the spheres of their
 
" Sarcome angiolithique."
 
  
This suggestion of a vascular origin, made by Cornil et Eanvier, was
+
I — lymphocyte. ss — space in syncytium.
elaborated by Afanassiew (la), 77.  
 
  
Afanassiew held that the corpuscles of Hassall arise from the endothelium of the smaller veins and capillaries. The endothelial cells increase in size, become cubical, and later fill the lumen of the vessel.  
+
Z& — lymphoblast. v — vacuole. I d n — large dark nucleus.
During the proliferation of the endothelium, the blood-vessels break up
 
into segments which are now nearly solid cords. These cords are at first
 
connected to each other and to blood-vessels, but they soon break apart.
 
The surest proof that the corpuscles are of vascular origin is that erythrocytes may be found inside them. Vascular injections, however, do
 
not go into a corpuscle except in a very early stage, since the lumen is
 
soon obliterated by the endothelial plugs. The corpuscles are formed
 
entirely by the endothelial cells. Afanassiew worked on embryos of man,
 
the rabbit, and the calf.  
 
  
Stieda (26), 81, in sheep embryos, describes the epithelial mass of the
+
Plate I.
  
 +
Fig. 1. From a 3.7-cm. pig embryo. Stained with iron-lijematoxylin and Congo red. Vacuolization of the cytoplasm and differentiation of the nuclei have begun.
  
 +
Fig. 2. From the thoracic segment of a 4.5-cm. pig embryo. Stained with iron-haematoxylin and Congo red. A cellular reticulum is now formed. Large pale nuclei, lymphoblasts, and the large dark intermediate forms are present.
  
4G Tlie Dcv('lf)|)tn(Mit of the Tli\nms
+
Fig. 3. Epithelioid type of concentric corpuscle. From a 16-cm. pig embryo. Stained with hajmatoxylin and Congo red. Colloid lamellae (c s d)
  
thymic aulage as being broken up by ingrowing adenoid tissue. From
 
50 mm. to 60 mm., there arc no hirge epithelial ceils; but later at 100 mm.
 
ho iinds in the adenoid tissue large cells 9 /a to 15 /x in diameter, isolated
 
or united in groups, Avhose protoplasm colors light-red with carmine.
 
These large cells have a concentric structure. Some of them are enclosed
 
bv large cells whose cytoplasm does not color with carmine, giving rise to
 
a yellowish mass of irregular form and stratified appearance. In older
 
embryos (250 mm.), the cellular masses are numerous but the large
 
colored cells are rare. The yellowish masses are groups of the large cells
 
which have undergone a transformation like that of the stratum corneum
 
of the epidermis. Stieda considers the large colored cells which form
 
the corpuscles as remnants of the epithelial anlage, although he admits
 
that for a long period during development he found no trace of them.
 
He explains the formation of the corpuscles in accordance with Cohnheim's hypothesis that most tumors arise from unused tissue remnants.
 
  
Ammann (2) 82, made most of his observations on human foetuses.
 
He describes the corpuscles as arising from connective tissue. The corpuscles are cellular in structure and are formed of one, two, or three central cells around which a variable number of cells, increasing with age,
 
are arranged like the coats of an onion. The corpuscles are formed from
 
reticulum cells and leucocytes. Growth consists in the apposition of cells
 
from without. The life of a corpuscle consists usually of four stages :
 
(1) Stadium der Transparenz ; (3) Stadium der colloidcn Entartung;
 
(3) Stadium der Verkalkung; (4) Stadium des Zerfalls. The nucleus
 
of a reticulum cell or leucocyte increases in size at the expense of the
 
cell body. Its increase in size establishes the concentric form. The
 
corpuscle undergoes colloid and usually calcareous degeneration. Fat
 
droplets, cholesterin crystals, and colloid granules are found together in
 
the degenerating corpuscles. Breaking up in this way makes absorption
 
possible. No epithelial remnants are to be observed. Xo erythrocytes
 
are found in the corpuscles.
 
  
In four cases of atrophic thymus gland wliich yet contained lymphoid
+
E. T. Bell 61
tissue Ammann found corpuscles in all stages of development. He also
 
found that the corpuscles are formed most rapidly when the thymus is
 
at the height of its development. From these facts he concluded that
 
they are not connected with the involution of the thymus as Afanassiew
 
thought. He thought that their formation is due to a physiological decrease in the intensity of growth of the medulla, due to the rapid growth
 
of the cortex.  
 
  
Watney (31), 83, agreed with Ammann that the corpuscles arise from
+
separate large areas of cleai- cytoplasm, causing the appearance of large epithelial cells. Colloid is being formed between the lamellae and around several nuclei.
connective tissue cells.  
 
  
 +
Fit;. 4. From a 8.5-cm. pig embryo. Stained with iron-hsematoxylin (not decolorized). The medulla has appeared. Lymphocytes are present between the epithelial cords.
  
 +
Fig. 5. From a 7-cm. pig embryo. Stained with iron-htematoxylin and Congo red. A few lymphocytes have been formed. In the cellular reticulum are large pale nuclei, lymphoblasts, and large dark intermediate nuclei. The nuclei in mitosis are very compact.
  
E. T. Bell 47
+
Fig. 6. From the medulla of a 24-cm. pig embryo. Stained with Jackson's modification of Mallory's method (ref. in text). Many fibrilte are seen in the syncytium.
  
Monguidi (18), 85, distinguished true and false concentric corpuscles — •
+
Plate II.
the latter being onl}- sections of blood-vessels.  
 
  
Hermann et Tourneux (11), 87, gave a description of the structure
+
Fig. 7. Ordinary type of simple concentric corpuscle. From a 16.5-cm. pig embryo. Stained with hsematoxylin and Congo red. The corpuscle is well advanced in development. Concentric lamellag of colloid have been formed. The cytoplasm between the lamellse is in an early stage of colloid transformation. Colloid fibers cut transversely appear as dots. The nuclei are becoming flattened by the pressure of expansion. The central mass stains irregularly and all traces of the nuclei in that region are gone.
and formation of the concentric corpuscles about like that given by
 
Ammann except that they regard the reticulum cells from which the
 
corpuscles develop as of epithelial origin.  
 
  
Gulland (8), 91, regarded the corpuscles as epithelial remnants and  
+
Fig. 8. Two cystic concentric corpuscles. From a 16-cm. pig embryo. Stained with iron-hgematoxylin and Congo red. On the left, a nucleated mass of protoplasm has been separated off by the formation of a vacuole annular in section. This might be mistaken for a blood-vessel containing a nucleated red cell. In this central protoplasmic mass the nucleus is shrunken and the cytoplasm vacuolated. In the small corpuscle on the right, two large vacuoles have formed.
compared them to the epithelial pearls of the tonsil.  
 
  
Maurer (17 c), 99, described the corpuscles as epithelial in origin.  
+
Fig. 9. Cystic concentric corpuscle. From a 14-cm. pig embryo. Stained with hsematoxylin and Congo red. The central protoplasmic mass is pale and shrunken. The small circular body in it probably is the remains of the nucleus. Colloid lamellae are forming. Colloid fibers cut transversely appear as dots.
His description of their formation is however different from that of His.  
 
All the cells of the epithelial anlage at first assume a lymphoid character.  
 
Later, some of these cells reassume their epithelial nature and then form
 
the corpuscles. His conclusions for teleosts and amphibians are similar
 
to the above results which he obtained from the lizard.  
 
  
Yer Eecke (28), 99, for the frog, describes the leucocytes and connective tissue cells as invading the thymic anlage and separating the epithelial cells. The epithelial cells, separated by the mesenchymal elements,
+
Fig. 10. Cystic concentric corpuscle. From a 10.5-cm. pig embryo. Stained with hsematoxylin and Congo red. The center contains no colloid and seems to be softening. The nucleus is shrunken.
lie at first in groups or singly. They go through a cycle of two phases,
 
a stage of growth, and a stage of involution. In the former stage, they
 
increase to three or four times their original size and their cytoplasm
 
differentiates into circular layers like the coats of an onion. The majority
 
are monocellular. Some cells grow together making a more complex
 
multicellular type. There are some intermediate forms, cells with a dense
 
dark protoplasmic body, indistinct striations, and a nucleus partly or
 
completely hidden in a precocious degeneration. In the stage of involution, which sets in early, the cytoplasm degenerates by the formation
 
of vacuoles containing a hyaline liquid. The liquefaction may be in the
 
form of a diffuse vacuolization, a large central vacuole, or a peripheral
 
vacuole circular in section. The nucleus loses its affinity for stains, becomes deformed, breaks up, and finally disappears. The corpuscles are
 
finally absorbed. They never contain erythrocytes. The cells do not degenerate to form a corpuscle. The liquefaction forms an internal secretion which is forced out by the muscle tissue in the reticulum.  
 
  
Entirely different results on amphibians are reported by Nusbaum and
+
Fig. 11. Ordinary concentric corpuscle in a very early stage. From a l{j.5-cm. pig embryo. Stained with iron-ha'matoxylin and Congo red. The nucleus is enlarged and colloid is forming around it. A few colloid fibers may be seen in the cytoplasm for some distance from the central nucleus.
Machowski (19), 02. These investigators revive the old idea of Afanassiew, accepting his results except that they think the adventitia as well
 
as the endothelium of the blood-vessels takes part in the formation of the
 
corpuscles. They find erythrocytes in the corpuscles. These erythrocytes
 
either gradually shrivel and disappear, or they are absorbed by leucocytes
 
or endothelial cells. The leucocytes after digesting the hemoglobin of the
 
erythrocytes become eosinophile cells which are numerous in the thymus.  
 
  
 +
Fig. 12. Ordinary concentric corpuscle. Several nuclei are involved. From a 10.5-cm. pig embryo. Stained with hsematoxylin and Congo red. The deeply-staining colloid has completely obliterated the central nucleus (in the region o c), and nearly obliterated another («'). Some of the colloid now stains pale (o c).
  
 +
Fig. 13. Ordinary concentric corpuscle. . From a 10.5-cm. pig. Stained with hiematoxylin and Congo red. The central nucleus is being obliterated
  
48 The Development of the Thymus
 
  
Wallisch (30), 03, measured the volume of the human thymus and of
 
the corpuscles of Hassali at various stages. He finds that the total volume
 
of the corpuscles of a 7-mo. embryo is 4.6 mm./ and of those of a 6-mo.
 
child, 174.6 mm." The total volume of the thymus of a 78-mm. embryo,
 
when it has already been partly transformed into adenoid tissue is only
 
6.8 mm.^ Since there is no evidence that the cells of the corpuscles
 
multiply, he concludes that they cannot be regarded merely as remnants
 
of the original epithelial anlage.
 
  
Disregarding the crude observations of the earliest investigators, there
+
(52 The I)i'V('l()})iiHiit nf the Tlivnius
remain three distinct theories of the formation of the corpuscles of
 
Hassali.
 
  
1. The epithelial anlage of the thymus is broken up by the invading
+
by the deeply-staiuing colloid. The neighboring nuclei are beginning to show the effect of the centrifugal pressure.
mesenchymal elements. The separated masses of epithelial cells undergo
 
further changes mainly of a degenerative nature to form the corpuscles.
 
This was the belief of His and KoUiker. According to this interpretation,
 
the corpuscles are to be regarded as remnants that have nothing further to
 
do with the gland. Stieda, Maurer, and Ver Eecke held this view in a
 
modified form. Stieda regarded the cells forming the corpuscles as
 
epithelial remnants but admitted that they go through a stage in which,
 
for a time, they lose their epithelial character. This is substantially the
 
same as ]\Iaurer's view. He thinks that the cells of the epithelial anlage
 
all become lymphoid, and that some of them afterwards reassume their
 
epithelial nature and form the corpuscles. Yer Eecke regards the corpuscles as epithelial remnants but thinks that they are glandular in nature,
 
not mere useless remains.  
 
  
2. The corpuscles are formed from the proliferating walls of bloodvessels. This idea was suggested by Cornil and Eanvier and elaborated by
+
Fig. 14. Ordinary concentric corpuscle in an early stage. From a 10.5-cm. pig. Stained with haematoxylin and Congo red. A band of deeply-staining colloid has been formed. Just outside this is colloid in formation.
Afanassiew. Nusbaum and Machowski accept Afanassiew's view except
 
that they believe the adventitia of the blood-vessels as well as their endothelium takes part in the formation of a corpuscle. These investigators
 
thought that the formation of the corpuscles is connected with the involution of the thymus.  
 
  
3. The corpuscles are formed from reticulum cells of the medulla
+
Fig. 15. Two simple concentric corpuscles which would have formed a compound concentric corpuscle. From a 10.5-cm. pig. Stained with haematoxylin and Congo red. The left corpuscle is a little more advanced than Fig. 11. The right corpuscle shows a large area of deeply-staining colloid which has pressed the nucleus into a small Irregular shape.
and grow by apposition of the surrounding cells. This view was advanced
 
by Ammann. Ammann thought that the reticulum is of connective tissue
 
origin. He also believed that leucocytes formed the central part at least
 
of some corpuscles. Hermann and Tourneux accepted Ammann's results,
 
except that they ascribed an epithelial origin to the reticulum. (I do not
 
know whether they accepted the origin from leucocytes described by
 
Ammann.) Ammann thought that the corpuscles formed because of a  
 
physiological decrease in the rate of growth in the medulla.  
 
  
 +
Plate III.
  
 +
Fig. 16. Compact irregular corpuscle In an early stage. From a 14-cm. pig embryo. Stained with haematoxylin and Congo red. The colloid is not yet solid. The nuclei are not essentially different from those of the adjacent syncytium.
  
E. T. Bell 49
+
Fig. 17. Ordinary concentric corpuscle. From a 12-cm. pig embryo. Stained with haematoxylin and Congo red. There is a large, central, deeplystaining colloid mass in which calcareous deposits (c?) have been made. The neighboring nuclei show the effects of the centrifugal pressui-e.
  
l\Iy own observations on tlie development of tlie eorpuseles of Hassall
+
Fig. is. Epithelioid concentric corpuscle in an early stage. From a 10.5cm. pig embryo. Stained with haematoxylin and Congo red. The outer colloid lamella marks off a nucleated mass of cytoplasm resembling a large cell. The nucleus is undergoing the same changes as occur in the central nucleus of an ordinary concentric corpuscle.
in pi_o- embrvos. will now be considered. The medulla, as previouslv described, begins to form from the epithelial syncvtium usually near the
 
center of the lobule. It is first recognized by its more marked reaction
 
with cytoplasmic stains such as Congo red. Shortly after the medulla
 
begins to form, the earliest stages of the corpuscles may be observed. - A
 
few corpuscles have appeared at 9.5 cm. I did not find them earlier.
 
They are all formed from the epithelial syncytium of the medulla.  
 
  
Before beginning this discussion I will explain the use of ray terms.  
+
Fig. 19. Compound concentric corpuscle. From a 10.5-cm. pig embryo. Stained with haematoxylin and Congo red. This would have soon lost all evidence of its compound nature.
By a corpuscle of Hassall, I mean a modified area of the epithelial syncytium of the medulla, containing at some period of its development, one
 
or more nuclei, and whose cytoplasm has been in part or entirely transformed into colloid. The term colloid is applied to various substances
 
probably of widely different chemical nature, but is fairly adapted to our
 
imperfect knowledge. I shall use the term here in the restricted sense
 
employed by Ziegler," i. e., hyaline substances of epithelial origin, that do
 
not give the reactions of mucin.  
 
  
Colloid in the corpuscles of Hassall does not usually appear as solid
+
Fig. 20. Epithelioid concentric corpuscle. From a 10.5-cm. pig embryo. Stained with hematoxylin and Congo red. Some colloid is forming outside the circular area. Solid deeply-staining colloid is forming.
masses in its early formation, but as fibers, granules, or sheets which are
 
separated by more or less cytoplasm that is not yet changed. This stage
 
I have called, "colloid in formation" (c f). It later assumes a more
 
solid homogeneous appearance which I call solid colloid (c s). Often
 
the solid colloid stains intensely with cyto])lasmic stains. I call this
 
kind solid deeply-staining colloid (c .*? d). In later stages, the colloid
 
often loses its affinity for cytoplasmic stains, staining a very pale color or
 
not staining at all. I call this variety old colloid (o c).  
 
  
According to their mode of development, the corpuscles of Hassall may
+
Fig. 21. Ordinary concentric corpuscle, showing a variation from the usual type. From a 16.5-cm. pig embryo. Stained with iron-haematoxylin and Congo red. The central nucleus is reddish but not enlarged. No solid colloid has been formed.
be classified as follows :
 
  
A. Concentric Corpuscles.  
+
Fig. 22. Compound concentric corpuscle. From a lG.5-cm. pig embryo. Three centers are present. The pale colloid in the upper part is probably older than the deeply-staining variety. In the lower part of the figure, a young corpuscle is shown.
  
a. Simple.  
+
Fig. 23. Compact irregular corpuscle. From a 16-cm. pig embryo. Stained with haematoxylin and Congo red. Some of the colloid is solid. No definite center is present but one is beginning to form (c s) . The nuclei are not markedly different from those of the adjacent syncytium.
  
1. Ordinary type.
 
  
2. Epithelioid type.
 
  
3. Cystic ty.pe.  
+
THE DEVELOPMENT OF THE THYMUS. E. T. BELL.
  
b. Compound.
 
  
B. Irregular Corpuscles.
 
  
a. Compact type.
+
Idn
  
b. Eeticular type.
 
  
*Gen. Pathology, 10th ed., Warthin's translation, p. 205.
 
  
 +
f'^
  
  
50 Tlie Development of the Thymus
 
  
A. The concentric corpuscles inchule those that from their earliest
 
appearance are concentric in structure. Adopting Ecker's classification,
 
I distinguis^i simple concentric corpuscles and compound concentric
 
corpuscles.
 
  
(a) Three types of simple concentric corpuscles are to be considered.
 
(1) The ordinary type is far more numerous than any other. The earliest recognizable stage is shown in Plate II, Fig. 11. A nucleus (n)
 
of the syncytium of the medulla has enlarged to perhaps twice its ordinary
 
volume and has lost the ability to stain in the characteristic way with
 
ha?matoxylin. Its sap is clear and a few reddish stained granules represent its chromatin. x\round it in the cytoplasm is an indistinct uneven
 
layer of colloid (c /). The colloid is not yet solid and is being formed
 
in concentric fibers or sheets. A slightly later stage is shown in Plate II,
 
Fig. 14 and Fig. 15 (left side of figure). Some of the colloid (c s)
 
next to the nucleus is now solid. The next stage is shown in Plate II,
 
Fig. 15 (right side of figure). These corpuscles show a thick layer of
 
colloid (c s d) that stains intensely with Congo red. Just outside the
 
deeply staining colloid, colloid in formation may be seen. The nuclei
 
are clear, and have become smaller and irregular in outline. The colloid
 
seems to be pressing upon them and obliterating them. The colloid
 
transformation gradually involves the adjacent c3^toplasm of the syncytium until other nuclei are involved. The corpuscle has now reached
 
the condition shown in Plate II, Fig. 12. The central area (o c) is
 
solid, the nucleus having disappeared entirely. Another (n') is nearly obliterated by the colloid. Part of the central area {o c) no longer stains
 
intensely, and it is breaking loose by the formation of a concentric space.
 
Several nuclei are surrounded by colloid in formation. Their long axes
 
are nearly in a tangential direction. These nuclei are clear but only
 
moderately swollen.
 
  
In the further development of the corpuscle (Plate III, Fig. 17 and
 
Plate II, Fig. 7), the central area {c s d) increases in size. The nuclei
 
involved in this area become obliterated probably by the pressure of the
 
colloid and are no longer distinguishable. This central area usually splits
 
off and may break up into many smaller masses. The peripheral part of
 
the corpuscle increases by extension of the colloid formation into the
 
adjacent part of the syncytium. This extension takes place in the early
 
stages by direct progressive involvement of the immediately adjacent cytoplasm; in later stages (Fig. 7), by the formation of concentric lamellae
 
which cut ofl' unchanged areas of cytoplasm. The lamelhp increase in
 
size and number, the cytoplasm included between them is changed into
 
colloid. They finally become closely packed, giving the characteristic and
 
  
 +
//-«
  
  
E. T. Bell 51
 
  
well-kncnvn onion-like structure found in the fully-formed eorpusele.
 
The nuclei that are enclosed between the lamells! gradually lose their
 
chromatin and become flattened out. They do not swell and are not
 
obliterated. It seems that swelling occurs only in nuclei that are surrounded by deeply staining colloid, and that this change is preparatory to
 
their obliteration by or transformation into colloid. The amount of the
 
corpuscle that breaks up to form the softer center is very variable. The
 
size of the center usually seems to increase with the age of the corpuscle.
 
  
Plate III, Fig. 21, shows a variation from the ordinary concentric
 
type. The central nucleus (n) stains reddish but is not enlarged. Most
 
of the other nuclei are unchanged. All the colloid (c /") is in the early
 
fibrous and granular stage.
 
  
From 20 cm. to full term nmny corpuscles show masses of calcareous
 
material in or near the center. This material rarely appears in younger
 
corpuscles (Plate III, Fig. 17, cl). It stains a violet blue with Delafield's ha?matoxylin.
 
  
The majority of the corpuscles of Hassall belong to the ordinary type
+
-V)
of simple concentric cor])uscles described above. It is very clear that
 
they have nothing to do with blood-vessels. They never contain erythrocytes nor anything resembling them. Earely a lymphoblast or leucocyte is found inside the corpuscle. These seem to be usually involved in
 
the corpuscle like ordinary stronui nuclei during the formation of the
 
lamellae. (Their occurrence in other types will be discussed later.) It
 
is also clear that these corpuscles arise from the syncytium of the
 
medulla. They are epithelial in origin, since the entire stroma of
 
the gland is derived from epithelium, but they are certainly not remnants
 
of the original epithelial anlage. Xeither are they forjned from lymphoidlike elements that reassume their epithelial nature as Maurer described
 
for the lizard.
 
  
Some of Ammann's observations are in accord with my results. The
 
swelling of the nucleus was noted by Ammann as tlu; first step toward the
 
formation of the corpuscle. It should he noted, however, that rarely a
 
corpuscle begins to form as a mass of colloid out in the cytoplasm and
 
involves nuclei secondarily. I cannot distiiiguish his " Stadium der
 
Transparenz " for I cannot be sure that a corpuscle is beginning to form
 
until some colloid is present. The formation of the colloid is associated
 
with the swelling of the nucleus. His other three stages, "Stadium der
 
coUoiden Entartung," " Stadium der Yerkalkung," and " Stadium des
 
Zerfalls " are easily seen. I have never seen corpuscles begin in leucocytes
 
as x\mmann described. His statement thnt the corpuscle grows by apposition of reticulum cells is true in a modified sense. He thought that
 
  
  
  
52 Tln' I )L'V('lo[)iiu'iit of []]{' 'I'liymus
 
  
the outer ])art of a {•or])nscle is formed of reticuhim cells that have moved
 
up and thittened themselves out around it. The description just given
 
shows ihat tlie coi'puscles are iieNcr composed of distinct cells, and that
 
the increase in size is due to an extension outward of tlie colloid foi'mation
 
and not to a moving in of the adjacent tissue.
 
  
The concentric form of this type of corpuscle is due at first to its l)eing
 
formed around a spherical or ellipsoidal nucleus. The swelling of this
 
nucleus creates a centrifugal pressure in the adjacent cytoplasm. Before
 
or during its transformation into colloid, the cytoplasm also increases in
 
quantity\ That the cytoplasm increases in quantity is shown hy the fact
 
that the nuclei are fewer in the corpuscle than in any adjacent area of
 
the syncytium of equal size. This centrifugal pressure presses the newly
 
formed colloid into concentric lamellae. It at first turns the long axes of
 
the nuclei tangentially. and later flattens them and makes them concave
 
toward the center.
 
  
3. The epithelioid type of corpuscle is characterized by large areas of
 
cytoplasm so marked off by colloid lamella? as to give the appearance of a
 
mass of large epithelial cells. They may contain only one nucleus embedded in a well-defined area of cytoplasm (Plate III, Figs. 18 and 20).
 
These correspond to the monocellular corpuscles that have been described
 
for lizards and amphibians. They are rare in the pig. I have not been
 
able to trace these very far, as they soon become indistinguishable from
 
other forms. The only difference I have noted is that the outer colloid
 
lamellae begin to form early, causing the peculiar appearance of a large
 
epithelial cell. Again the epithelioid type may present an appearance
 
such as shown in Plate I, Fig. 3. These do not seem to be formed around
 
any special nucleus. The outer colloid lamella? form before any center
 
has been established, niarking off large cytoplasmic areas that may look
 
like large cells. The centrifugal pressure of expansion caused by the
 
great increase of cytoplasm in this area determines the concentric form
 
in these corpuscles. Pure epithelioid corpuscles are very rare, but epithelioid areas in other corpuscles are not uncommon. The occurrence of
 
epithelioid areas in corpuscles of the ordinary type shows that it is due
 
to variations in a fundamentally similar process.
 
  
3. In the cystic type of corpuscle, the central part, instead of becoming
 
transformed into colloid, undergoes early liquefaction, forming vacuoles.
 
The central nucleus does not increase in size as in the ordinary type, but
 
shrivels up and disappears. The corpuscle begins by the formation of
 
outer colloid lamellae-^the central mass is not changed into colloid.
 
In Plate II, Fig. 10, the central area (/; m) is undergoing a diffuse
 
liquefaction. The nucleus (iv) is colorless and shrunken. In Plate TI.
 
  
  
  
E. T. Bell 53
 
  
Fig. 8 (right side of figure), the central area has fonned two lai-ge vacuoles (v). On the left side of the same figure, a concentric vacuole (v)
 
has formed, separating off a central spherical nucleated mass of protoplasm. The nucleus of this mass of protoplasm is shrunken and the
 
cytoplasm shows many small vacuoles. The corpuscle shown in Plate II,
 
Fig. 9, is probably a later stage of the form just described. The central
 
protoplasmic mass has become converted into an ellipsoidal pale bo'dy
 
(pm). The small circular body in this shriveled mass is probably the
 
nucleus. Some corpuscles like the one shown in Fig. 9 are found in
 
wdiich the central mass has entirely disappeared. The further growth
 
of corpuscles of this type seems to be by formation of colloid lamella? as
 
in the ordinary type. They soon become indistinguishable from other
 
forms.
 
  
The cystic type of corpuscle is rare in the pig. This evidently corresponds to the form in amphibia that misled Nusbaum and Machowski
+
f
into reviving Afanassiew's theory. The central masses, in Figs. 8 and 9,
 
might readily be mistaken for red corpuscles in animals in which these
 
cells are nucleated. But the red cells of the blood of the pig are not
 
nucleated at this stage. I have traced a number of these corpuscles (as
 
well as those of other types) in serial sections and have never seen any
 
indications of a connection to blood-vessels. Nusbaum and Machowski (19), (Fig. 1, c, S. 116) show a corpuscle which is similar to jny
 
Fig. 9. It will 1)0 noted that the central space in neither of these figures
 
is lined by endothelium. The early form of corpuscle shown by Nusbaum and Machowski (Fig. 1, d, S. 116) is very probably a normal bloodvessel with cubical endothelium. I have often found such vessels with
 
cubical endothelium in the interlobular tissue of the pig's thymus at 10
 
cm. to 12 cm. They probably may be found at other stages also. In the
 
thymus of a kitten, injected l)y the intra-vitam Prussian blue method previously described, the majority of the corpuscles were found to be in
 
early stages. The injection did not penetrate any corpuscle. I had a
 
somewhat better opportunity to study the relations of the corpuscles to
 
the blood-vessels in a 14 cm. human embryo. Here the vessels of the
 
thymus were all very much distended with blood and the corpuscles were
 
in early stages. No blood cells were found in the corpuscles.
 
  
(b) Compound concentric corpuscles are formed whenever two or more
 
simple concentric corpuscles begin to form so close together that they
 
come in contact during their later growth. An early stage of such a
 
corpuscle is shown in Plate II, Fig. 15. The colloid lamellae are formed
 
around each center until they come in contact; they are tlien formed
 
around both centers. In Plate III, Fig. 22, a compound concentric cor
 
  
  
5-t Tlio D(>\('l()|)in('iit of the Tliyiinis
+
^^^ Idn
  
piisclc is shown. 'I'lici'c aiT three siiiiph' coiu'cntric corpuscles in it —
 
one of them (the h>\vcst in the liyiii-c) in a very early stage. Several
 
lamella' ai'c common lo the older cor|)uscles, and one is common to all
 
three. This ari'an<i'ement of the lamella' is a mechanical efTect of the
 
tension in the cytoplasm, due to the ccntrifug^al pressure from the two
 
centers. The size of the separate centers in a compound corpuscle depends upon the stage they have reached when they come in contact. If
 
a compound coi'puscle he formed hy the union of two simple corpuscles
 
in an early stage, as in Plate 111, Fig. 19, all indications of its compound nature are soon lost. A corpuscle originally compound may, then,
 
in later stages, hecome indistinguishal)Ie fi'om simple corjniscles. The
 
simple corpuscles uniting to form a compound concentric cor]niscle may
 
be of any of the types previously described.
 
  
B. Irregular Corpuscles.
 
  
This grou]) includes those corpuscles which are not at first concentric.
 
Concentric areas may appear later. According to the classification previously given, I distinguish a compact type and a reticular type.
 
  
(a) The compact type (Plate III, Fig. 16) first appears as a compact
 
area of syncytium of irregular shape. It is recognizable l)y the colloid
 
it contains. The nuclei are not noticeably increased in size and have no
 
regular arrangement. Their chromatin still stains dark with nuclear
 
stains. The colloid (c f) is not yet solid. The corpuscle has no distinct
 
center. These corpuscles grow by direct colloid transformation of the
 
adjacent syncytium. No distinct lamella^ are formed. The colloid may
 
remain in the fibrous condition shown in the figure (c f) or it may
 
become solid, but it never reaches the deeply staining condition unless a
 
concentric area be established.
 
  
A later stage of this tyi)e is shown in Plate III, Fig. 23. The corpuscle is sharply marked off from the syncytium. Some of its colloid is
 
solid. A concentric area (cs) is beginning to form. The nuclei are
 
not markedly different from those of the adjacent syncytium. These
 
corpuscles may become large and branched. Often one or more concentric areas are developed after the corpuscle has attained considerable
 
size. By the growth of these concentric areas, irregidar corpuscles may
 
become converted into concentric corpuscles.
 
  
(b) The reticular type is produced by colloid formation in the ordinary reticulum of the medulla. In the types previously described, the
 
spaces of the reticulum are \isually obliterated as the colloid formation
 
advances; but in this form the spaces persist as a part of the corpuscle.
 
Pure reticular corpuscles vary greatly in size, sometimes involving only
 
  
  
  
E. 'W Bell ■ 55
+
-f»i
  
one node of the syncytium. Thev are never concentric, and never form
 
lamellae. Eeticnlar areas often occur in other forms of corpuscles. In
 
tiiis way leucocytes are often involved in tlic corpuscle, since they lie in
 
the spaces of the reticulum. Lymphocytes often get into a corpuscle in
 
the lymphohlast condition, heing cut off hy tlio formation of lamellae
 
outside tliem (Plate III, Fig. 22). The Icui'Dcytes shut in the cor])uscle in this way during development uuiy not degenerate. They probably persist and help to remove the corpuscle in its final stages of degeneration.
 
  
The amount of expansion of the cyt()i)lasm before or during the colloid
+
J^'\ i
transformation is probably small in the irregular reticular corpuscles,
 
since it does not obliterate the spaces of the syncytium. In the compact
 
type, the spaces of the syncytium are obliterated and there is evidence
 
of some expansive force (note the arrangenunit of the nuclei in the
 
upper part of Fig. 23, Plate III). In the figure referred to, the number
 
of nuclei in any part of the corpuscle is less than in an equal area of the
 
adjacent reticulum. These facts indicate that there is an expansion of
 
the cytoplasm. That this expansive force does not produce a concentric
 
form is due primarily to the fact that there is no expansion of a nucleus
 
and distinct center of formation as is present in concentric corpuscles of
 
the ordinary type. The absence of the onion-like structure in irregular
 
corpuscles is due to the fact that the colloid is not laid down in lanielUw
 
  
Significance of the corpuscles of Hassall. It has been shown in the
 
preceding pages that the corpuscles of Hassall in the pig are not epithelial remnants, and also that they are not formed from blood-vessels.
 
There is no evidence connecting their development with the involution
 
of the thymus, for they begin to form before the lymphoid transformation is complete and are most numerous when the thymus is at the height
 
of its development. I have not been al)le to see the decrease in the rate
 
of growth of the medulla described by Amnumn, and even if such did
 
occur it is difficult to understand how it could cause the formation of a
 
corpuscle.
 
  
The above theories are, therefore, inconsistent with the facts of development in the pig. It seems to me that the formation of a corpuscle is
 
not to be regarded as a ]u-ocess of degeneration. The fact that the formation of colloid is an essential feature in the development of every
 
corpuscle is a strong argument that it is a form of secretion such as
 
occurs in its neighl)oring branchial derivative, the thyroid. The fact
 
that the corpuscles differentiate in an aj^parently uniform syncytium is
 
further evidence airainst a theory of degeneration. Since the lymphocyte-forming fuiu-tion of tbc tliymus is probaI)ly secondary, it is not
 
  
 +
1 ss
  
  
56 The Dov(^lopin(<Tit of tlio Thymus
 
  
unreasonable to suppose that its primitive fimetion was the formation
+
%
of a colloid secretion such as occurs in the thyroid, and that the corpuscles
 
are abortive expressions of this primitive function/
 
  
Giant Cells.
 
  
Polykaryocytes may often 1)0 seen in the medulla. Tliese bodies develop froui the syncylium of the uieilulla. They are first noticeable as
 
groups of small s])herieal nuclei in a solid area of the syncytium. Tliese
 
nuclei stain with merlium intensity and are all very similar in size and
 
color. The area containing this group of nuclei becomes a well-defined
 
node of the reticulum and persists as such. A polykaryocyte is, therefore, a large node of the reticulum containing a number of small nuclei
 
very similar in appearance. These cells often occur in groups. They
 
are entirely distinct from the corpuscles. They are evidently similar
 
to the polykaryocytes found in bone marrow and other lymphoid tissues.
 
  
Summary.
 
  
The following is a resume of the development of the thymus in the
 
pig :
 
  
The thymus of the pig is probably developed entirely from the endoderm of the third gill pouch.
 
  
By a gradual process of vacuolization and liquefaction of the cytoplasm, the epithelial syncytium of the thymic anlage is converted into a
 
cellular reticulum.
 
  
From the first appearance of vacuolization, three types of nuclei are
 
present: large pale nuclei; small dark nuclei (lymphoblasts), and large
 
dark intermediate forms.
 
  
The lymphoblasts gradually break loose from the cellular reticulum,
 
moving into its spaces and forming lymphocytes. Mitoses are most numerous at the period of the most rapid formation of lymphocytes. The
 
medulla continues to form lymphocytes at least as late as birth.
 
  
Lymphocytes appear in the connective tissue aromul tlu> th.ynuis
+
u
shortly after they are formed ; and lymphoblasts, wdiich are distinguishable from lymphocytes only by being embedded in the syncytium, arc
 
present in the thymus a long period before lymphocytes are found anywhere in the neighborhood of the thymus.
 
  
The celhdar reticulum of the earlier stages persists in a modified form
 
as the reticulum of both cortex and medulla. It retains more cytoplasm
 
  
' Ver Eecke (28) believes that the corpuscles in amphibians are of a
 
glandular nature.
 
  
  
 +
t
  
E. T. Bell 57
 
  
in tlio inedulla. Practically all the reticnhira of both cortex and nie(liilla. as well as the lymphocytes, are, therefore, of epithelial origin.
 
  
The {■oi-])iisclos of Hassall develop from the syncytium and arc, therefore, epithelial in origin. They are, however, not to be considered as
 
remnants of the original epithelial anlage.
 
  
In development various types of corpuscles are distinguished. Tlie
 
ordinary typo of concentric corpuscles first appears as an enlarged clear
 
nucleus around which colloid is being formed. Before or during the
 
formation of colloid, the cytoplasm increases in quantity, filling the
 
spaces of the reticulum and producing a centrifugal pressure which
 
shapes the newly-formed colloid into concentric lamellse and flattens the
 
neighboring nuclei, making them concave toward the center. The central nuclei usually become obliterated.
 
  
The epithelioid type is distinguished by its resemblance to large epithelial cells, this appearance being due to the formation of colloid
 
lamella" around largo areas of clear cytoplasm. The central part of the
 
corpuscle usually remains unchanged until after some of the colloid
 
lamellfE are formed.
 
  
The cystic type differs from the ordinary type only in that the central
 
part undergoes vacuolization instead of colloid transformation. Those
 
with concentric vacuoles may simulate blood-vessels containing nucleated
 
red cells. Corpuscles never contain erythrocytes; neither can they be
 
injected at any stage of development. Serial sections also show tliat
 
there is no connection to blood-vessels at any stage.
 
  
Compound concentric corpuscles are formed by the union of two or
 
more simple concentric corpuscles during development.
 
  
Irregular corpuscles are not concentric ' in arrangement, and are
 
formed in the syncytium in an irregular manner. In the compact type
 
of irregular corpuscles, concentric areas may form.
 
  
The formation of colloid is an essential feature in the development of
 
every corpuscle, and is not to be considered as a process of degeneration.
 
  
Since the conclusion of my work and after my manuscript was given to the
 
publishers, two articles dealing with the thymus have appeared.
 
  
Ph. Stohr (Ueber die Thymus, Sitzungsberichte der phys.-med. Gesellschaft
 
zu Wiirzburg, June 8, 1905) believes that the thymus first epithelial in nature
 
becomes converted entirely into small cells of lymphoid appearance. Later
 
the large reticulum cells are formed from these by enlargement. The corpuscles of Hassall are formed by the massing together and enlargement of
 
these lymphoid-like cells. The small round cells of the gland are epithelial
 
in origin but are to be regarded not as lymphocytes but as epithelial cells.
 
The thymus is not a source of lymphocytes.
 
  
 +
Ijlil.
  
  
58 ''J'lu^ Devolopmont nf the Tliymiis
 
  
The author apparently believes that none of the small rounrt cells leave
 
the gland though he admits that lymphocytes enter. But as mentioned above
 
the zone of connective tissue immediately around the head at 7 cm. may
 
contain even more lymphocytes than are present inside the gland at that time
 
If these are all entering the gland then it is probable that most of the small
 
round cells are really lymphocytes. This conception then does not simplify
 
the problem but is only a theoretical compromise between the two views a'i
 
to the origin of the lymphocytes.
 
  
J. Aug. Hammar (Zur Histogenese und Involution der Thymusdriise, Anat.
 
Anz. Bd. XXVII, June 17, 1905) regards the reticulum as formed from the
 
epithelial anlage but thinks the evidence at hand insufficient to decide the
 
question as to the origin of the lymphocytes. He finds lymphocytes outside
 
the thymus in many animals (man, cat, chick, frog) before any are present
 
inside the gland. The corpuscles of Hassall develop from the epithelial
 
reticulum and undergo hyaline (colloid?) degeneration.
 
  
My description of the formation of the corpuscles of Hassall differs essentially from Hammar's, in that I believe the formation of the corpuscle consists
 
in the expansion of the cytoplasm of the syncytium and its conversion into
 
colloid. Hammar did not recognize " colloid in formation," though he speaks
 
of the coarse fibrillar structure of the protoplasm. He -did not describe such
 
corpuscles as are shown in Fig. 7, Plate II.
 
  
The considerations presented above in favor of the epithelial origin of the
+
3 ?rt
lymphocytes seem to me much stronger than those given by Hammar. His
 
statements as to the presence of lymphocytes around the thymus before they
 
are present inside are to be taken with some reservation inasmuch as he
 
mentions small round cells separate from the syncytium earlier, but regards
 
ihem as degenerating epithelial cells (S. 65). His figure from the human
 
foetus (Fig. 18, S. 66) does not seem to be strong support for his statement.
 
Certainly many lymphocytes are present in the pig thymus when the reticulum is broken up as much as shown in the figure referred to. It is also to
 
be borne in mind that the different parts of the thymus undergo the lymphoid
 
transformation at different times and that a single section may therefore be
 
misleading.
 
  
LITERATURE.
 
  
la. Afanassiew, B. — Ueber die concentrischen Korper der Thymus. Archiv
 
  
f. mikr. Anat., Bd. XIV, 1877.
 
lb. Weitere Untersuchungen iiber den Bau und die Entwickelung
 
  
der Thymus und der Wintcrschlafdriise der Saugethiere. Archiv f.
 
  
mikr. Anat., Bd. XIV, 1877.
 
2. Ammann, a. — Beitrage zur Anatomic der Thymusdriise. Basel, 1882.
 
3a. Beard. — The development and probable function of the thymus. Anat.
 
  
Anz., Bd. IX, 1894.
+
lb
3b. The true function of the thymus. Lancet, 1899.
 
  
4. Born, G.— Ueber die Derivate der embryonalen Schlundbogen und
 
  
Schlundspalten bei Saugethieren. Archiv f. mikr. Anat., Bd. XXII,
 
1883.
 
  
5. CoRNiL et Ranvier. — Manuel d'histologie pathologique. Paris, 1869, p.
+
B^9'^'^'
  
135 (cited from Ammann).
 
  
  
 +
'm
  
E. T. Bell 59
 
  
6. EcKER. — Art. " Blutgefassdrusen," Wagner's Handw. der Phys., Ill (cited
 
  
from Ammann).
+
//)
  
7. Priedleben, a. — Die Physiol, der Thymusdriise. Frankfurt, 1858.
 
  
8. GULLAND. — The Development of adenoid tissue with special reference
 
  
to the tonsil and thymus. Laboratory Reports issued by the Royal
+
^4ii'
College Phys., Edinburgh, Vol. Ill, 1891.
 
  
9. GiJNZBURG. — Ueber die geschichteten Korper der Thymus. Zeitschr. f.
 
  
klin. Med., Bd. VI, 1857, S. 456 (cited from Henle und Meissner.
 
Bericht iiber die Fortschritte der Anat. u. Physiol.).
 
  
10. Hassall. — The microscropical anatomy of the human body in health and
 
  
disease. London, 1846 (cited from Ammann).
 
  
11. Hermann et Tourneux. — Article thymus, Diet, encycl. des Sciences Medi
 
cales. Troisieme Serie, 17, 1887.
 
12a. His, W.— Zeitschrift f. wiss. Zoologie, Bd. X, S. 348. Leipzig, 1860.
 
12b. Anatomic menschlicher Embryonen. Leipzig, 1880, S. 56.
 
  
13. Jackson, C. M. — Zur Histologie und Histogenese des Knochenmarkes.
+
4
  
Archiv f. Anat. und Physiol., Anat. Abth., 1904.
 
  
14. Kastschenko. — Das Schicksal der embryonalen Schlundspalten bei
 
  
Saugethieren. Archiv f. mikr. Anat., Bd. XXX, 1887.
+
/i-^/i
  
15. Klein. — Neuere Arbeiten iiber die Glandula Thymus. Centralbl. f. allg.
 
  
Pathol, u. pathol. Anat., 1898.
 
  
16. Langerhans und Savei.iew. — Beitrage zur Physiologic der Brustdriise.
+
f
  
Virchow's Archiv, Bd. 134, 1S93.
 
17a. Maurer. — Schilddriise und Thymus der Teleostier. Morph. Jahrb.. Bd.
 
  
XI, 1886.
 
17b. Schilddriise, Thymus, und Kiemenreste bei Amphibien. Morph.
 
  
Jahrb., Bd. XIII, 1888.
 
17c. Schilddriise, Thymus, und andere Schlundspaltenderivate bei der
 
  
Eidechse. Morph. Jahrb., Bd. XXVII, 1899.
 
17d. In Hertwig's Handbuch der Entwickelungslehre der Wirbelthiere,
 
  
Lief. 6-8, S. 131 ff., 1902.
 
  
18. MoNGUiui. — Sulla glandula timo. Parma, 1885 (cited from Prenant).
 
  
19. NusBAUM, J., und Maciiowski. — Die Bildung der concentrischen Korper
 
chen und die phagocytotischen Vorgange bei der Involution der
 
Amphibienthymus, etc. Anat. Anz., Bd. XXI, 1902.
 
  
20. NusBAUM, J., und Prymak, T.— Zur Entwickelungsgeschichte der lym
 
phoiden Elemente der Thymus bei den Knochenfischen. Anat. Anz.,
 
Bd. XIX, 1901.
 
  
21. Paulitzky. — Disquis. de stratis glandulse thymi corpusculis. Habilita
+
^5^'
tionsschr., Halis, 1S63 (cited from Henle und Meissner's Bericht iiber
 
die Fortschritte der Anat. und Physiol.).
 
  
22. Prenant. — Developpement organique et histologique du thymus, de la
 
  
glande thyroide, et de la glande carotidienne. La Cellule, Tome X,
 
1894.
 
  
23. Prymak. T. — Beitrage zur Kenntnis des feineren Baues und der Involu
+
.■#^?
tion der Thymusdriise bei den Teleostieren. Anat. Anz., Bd. XXI,
 
1902.  
 
  
  
  
60 'I'lio Dovclnpmont of the T'hynms
 
  
24. SciiAKFER, J. — Ueber den feirieren Bau der Thymus und deren Beziehung^
+
//>;*
  
zur Blutbildung. Sitzungsber. d. K. Acad. d. Wissensch. Math.naturw. Kl. Wien., Bd. CII, Abt. Ill, 1893.
 
  
25. SciiEnEL, J. — Zellvermehrung in der Thymusdriise. Archiv f. mikr.
 
  
Anat., Bd. XXIV.
+
5 ' ^P>i
  
26. Stieda, L. — Untersuchungen uber die Entwickelung der Glandula Thy
 
mus, Glandula Thyroidea, und Glandula Carotica. Leipzig, 1881
 
(cited from Hermann et Tourneux).
 
  
27. Sx'LTAN.^Beitrag zur Involution der Thymusdriise. Virchow's Archiv,
 
  
Bd. 144, 189G.
 
  
28. Vek Eecke. — Structure et modifications fonctionelles du thymus de la
 
  
grenouille. Bulletin de I'Acadc'mie royale de MC'dicine de Belgique,
 
1899.
 
  
29. ViKciiow, R. — Kritisches iiber den oberschlesischen Typhus. Archiv, Bd.
 
  
3, 1851, S. 222.
 
  
30. Wallisch. — Zur Bedeutung der Hassall'schen Korperchen. Archiv f.
 
  
mikr. Anat., 1903.
 
  
31. Watxey. — The minute anatomy of the thymus. Philos. Transact, of the
+
AMERICAN JOURNAL OF ANATOMY--VOL V.
  
Royal Society of London, Vol. 173, Part III, 1883 (cited from Prenant).
 
  
EXPLANATION OF PLATES.
 
  
All the figures were drawn with Leitz obj. 1/12, oc. 4, and camera lucida.
+
E. T. BELL, DEL.
The magnification after the reduction of the plates is about 1060 diameters.
 
All drawings were made from transverse sections of the mid-cervical segment of the thymus unless they are otherwise indicated.  
 
  
The following abbreviations designate the structures indicated in all the
 
figures :
 
  
c f — colloid in formation. I p n — -large pale nucleus.
 
  
cl — -calcareous deposit. m — nucleus in mitosis,
+
THE DEVELOPMENT OF THE THYMUS. E. T. BELL.
  
c s — solid colloid. vid — beginning of medulla,
 
  
c s d — solid colloid that stains n — nucleus.
 
  
deeply. o c — old colloid.
 
  
e — erythrocyte. p m — protoplasmic mass.
+
12
  
end — -endothelial nucleus. sf — fibril in syncytium.
 
  
I — lymphocyte. ss — space in syncytium.
 
  
Z& — lymphoblast. v — vacuole.
+
^^®\r
I d n — large dark nucleus.
 
  
Plate I.
 
  
Fig. 1. From a 3.7-cm. pig embryo. Stained with iron-lijematoxylin and
 
Congo red. Vacuolization of the cytoplasm and differentiation of the nuclei
 
have begun.
 
  
Fig. 2. From the thoracic segment of a 4.5-cm. pig embryo. Stained with
 
iron-haematoxylin and Congo red. A cellular reticulum is now formed. Large
 
pale nuclei, lymphoblasts, and the large dark intermediate forms are present.
 
  
Fig. 3. Epithelioid type of concentric corpuscle. From a 16-cm. pig embryo. Stained with hajmatoxylin and Congo red. Colloid lamellae (c s d)
+
AMERICAN JOURNAL OF ANATOMY--VOL V.
  
  
  
E. T. Bell 61
+
E. T. BELL, DEL.
  
separate large areas of cleai- cytoplasm, causing the appearance of large
 
epithelial cells. Colloid is being formed between the lamellae and around
 
several nuclei.
 
  
Fit;. 4. From a 8.5-cm. pig embryo. Stained with iron-hsematoxylin (not
 
decolorized). The medulla has appeared. Lymphocytes are present between
 
the epithelial cords.
 
  
Fig. 5. From a 7-cm. pig embryo. Stained with iron-htematoxylin and
+
THE DEVELOPMENT OF THE THYMUS. E. T. BELL.
Congo red. A few lymphocytes have been formed. In the cellular reticulum
 
are large pale nuclei, lymphoblasts, and large dark intermediate nuclei. The
 
nuclei in mitosis are very compact.  
 
  
Fig. 6. From the medulla of a 24-cm. pig embryo. Stained with Jackson's
 
modification of Mallory's method (ref. in text). Many fibrilte are seen in
 
the syncytium.
 
  
Plate II.
 
  
Fig. 7. Ordinary type of simple concentric corpuscle. From a 16.5-cm.
 
pig embryo. Stained with hsematoxylin and Congo red. The corpuscle is
 
well advanced in development. Concentric lamellag of colloid have been
 
formed. The cytoplasm between the lamellse is in an early stage of colloid
 
transformation. Colloid fibers cut transversely appear as dots. The nuclei
 
are becoming flattened by the pressure of expansion. The central mass stains
 
irregularly and all traces of the nuclei in that region are gone.
 
  
Fig. 8. Two cystic concentric corpuscles. From a 16-cm. pig embryo.
+
rsil
Stained with iron-hgematoxylin and Congo red. On the left, a nucleated
 
mass of protoplasm has been separated off by the formation of a vacuole
 
annular in section. This might be mistaken for a blood-vessel containing a
 
nucleated red cell. In this central protoplasmic mass the nucleus is shrunken
 
and the cytoplasm vacuolated. In the small corpuscle on the right, two large
 
vacuoles have formed.
 
  
Fig. 9. Cystic concentric corpuscle. From a 14-cm. pig embryo. Stained
 
with hsematoxylin and Congo red. The central protoplasmic mass is pale
 
and shrunken. The small circular body in it probably is the remains of
 
the nucleus. Colloid lamellae are forming. Colloid fibers cut transversely
 
appear as dots.
 
  
Fig. 10. Cystic concentric corpuscle. From a 10.5-cm. pig embryo.
 
Stained with hsematoxylin and Congo red. The center contains no colloid
 
and seems to be softening. The nucleus is shrunken.
 
  
Fig. 11. Ordinary concentric corpuscle in a very early stage. From a
+
rsil .,
l{j.5-cm. pig embryo. Stained with iron-ha'matoxylin and Congo red. The
 
nucleus is enlarged and colloid is forming around it. A few colloid fibers
 
may be seen in the cytoplasm for some distance from the central nucleus.  
 
  
Fig. 12. Ordinary concentric corpuscle. Several nuclei are involved.
 
From a 10.5-cm. pig embryo. Stained with hsematoxylin and Congo red. The
 
deeply-staining colloid has completely obliterated the central nucleus (in the
 
region o c), and nearly obliterated another («'). Some of the colloid now
 
stains pale (o c).
 
  
Fig. 13. Ordinary concentric corpuscle. . From a 10.5-cm. pig. Stained
 
with hiematoxylin and Congo red. The central nucleus is being obliterated
 
  
 +
AMERICAN JOURNAL OF ANATOMY--VOL V.
  
  
(52 The I)i'V('l()})iiHiit nf the Tlivnius
 
  
by the deeply-staiuing colloid. The neighboring nuclei are beginning to
+
E. T. BELL, DEL.
show the effect of the centrifugal pressure.  
 
  
Fig. 14. Ordinary concentric corpuscle in an early stage. From a 10.5-cm.
 
pig. Stained with haematoxylin and Congo red. A band of deeply-staining
 
colloid has been formed. Just outside this is colloid in formation.
 
  
Fig. 15. Two simple concentric corpuscles which would have formed a
 
compound concentric corpuscle. From a 10.5-cm. pig. Stained with haematoxylin and Congo red. The left corpuscle is a little more advanced than
 
Fig. 11. The right corpuscle shows a large area of deeply-staining colloid
 
which has pressed the nucleus into a small Irregular shape.
 
  
Plate III.  
+
THE YEIXS OF THE ADEE^AL.
  
Fig. 16. Compact irregular corpuscle In an early stage. From a 14-cm.
+
BY
pig embryo. Stained with haematoxylin and Congo red. The colloid is not
 
yet solid. The nuclei are not essentially different from those of the adjacent
 
syncytium.
 
  
Fig. 17. Ordinary concentric corpuscle. From a 12-cm. pig embryo.  
+
JEREMIAH S. FERGUSON, M. Sc, M. D.
Stained with haematoxylin and Congo red. There is a large, central, deeplystaining colloid mass in which calcareous deposits (c?) have been made.  
 
The neighboring nuclei show the effects of the centrifugal pressui-e.  
 
  
Fig. is. Epithelioid concentric corpuscle in an early stage. From a 10.5cm. pig embryo. Stained with haematoxylin and Congo red. The outer colloid lamella marks off a nucleated mass of cytoplasm resembling a large cell.
+
From the Histological Laboratory of Cornell University Medical College.
The nucleus is undergoing the same changes as occur in the central nucleus
 
of an ordinary concentric corpuscle.  
 
  
Fig. 19. Compound concentric corpuscle. From a 10.5-cm. pig embryo.
+
Neio York, N. Y.
Stained with haematoxylin and Congo red. This would have soon lost all
 
evidence of its compound nature.  
 
  
Fig. 20. Epithelioid concentric corpuscle. From a 10.5-cm. pig embryo.
+
With 3 Text Figures.
Stained with hematoxylin and Congo red. Some colloid is forming outside
 
the circular area. Solid deeply-staining colloid is forming.  
 
  
Fig. 21. Ordinary concentric corpuscle, showing a variation from the  
+
Within the past decade our knowledge of the functions of the adrenal glands, and of their relations to the rest of the economy, has been greatly enhanced l)y many careful cliomical and physiological researches. Tlie recent studies of Aichel (1), Wiesel (2, 3), Soulie (4), and others have placed the early development of the organ upon a fairly certain basis. These advances in the physiology and embryology of the organ have not as yet been accompanied by corresponding advances in our appreciation of its minute anatomy. Hence this branch of the subject is, at the present time, one of unusual interest.
usual type. From a 16.5-cm. pig embryo. Stained with iron-haematoxylin
 
and Congo red. The central nucleus is reddish but not enlarged. No solid
 
colloid has been formed.  
 
  
Fig. 22. Compound concentric corpuscle. From a lG.5-cm. pig embryo.
+
The intimate relation of the parenchyma of the adrenal to its bloodvessels, as shown by the general tendency to regard the organ as a true gland whose secretion enters its blood-vessels and leaves the organ through its efferent veins, makes it specially important that these vessels should be carefully studied and their structure and distribution accurately recorded.
Three centers are present. The pale colloid in the upper part is probably
 
older than the deeply-staining variety. In the lower part of the figure, a
 
young corpuscle is shown.  
 
  
Fig. 23. Compact irregular corpuscle. From a 16-cm. pig embryo. Stained
+
The exhaustive study of Flint (5), on the course of the adrenal vessels, based as it was upon carefully prepared reconstructions, leaves little to be desired along this line. The writer is, however, unable to find in the literature any reference to the minute structure of the veins of the adrenal, with the notable exception of Minot's (6) article on sinusoids.
with haematoxylin and Congo red. Some of the colloid is solid. No definite
 
center is present but one is beginning to form (c s) . The nuclei are not
 
markedly different from those of the adjacent syncytium.  
 
  
 +
To be sure Pfaundler (7) mentioned the occurrence, in the medulla of the adrenal, of venous vessels whose only wall consisted of endothelium. Gottschau (8) also, though omitting their description, has figured similar vessels in his Plate XVIII, Fig. 1. But as to the structure of the larger blood-vessels of the adrenal glands the literature seems to be entirely barren.
  
 +
The architecture of the arterial walls does not appear to offer any distinctive peculiarities, the tissues of which they consist being arranged in a manner precisely similar to that which characterizes the arteries of American Journal of Anatomy. — Vol. V.
  
THE DEVELOPMENT OF THE THYMUS.
 
E. T. BELL.
 
  
  
 +
64 The N'ein.s oi' the Adrenal
  
Idn
+
similar size occnrriiiii- in olliei' or<ians. 'I'lie veins, liowever, j^resent distinct and remarkable peeidiarilies which it is the iiur))()se oi' the present |>a|)ci- to describe.
  
 +
Methods (iiid Mafcr'ud. — The tissue used for this stud}^ has included specimens of the adrenal from twenty-one human adults, together with the casual examination of fetal adrenals of the pig and of man. The adrenals of other mammals, e. g., nionke}^ dog, cat, rabbit, and guineapig, have also been more or less carefiilly studied.
  
 +
These tissues have been fixed and hardened with many reagents, among which are Zenker's solution, formol. Miiller-formol, alcohol, corrosive acetic mixture, Tellyesniczky's fluid, and Flemming's solution. The stains used were hematein by various methods, acid hematein, iron hematein, etc., and for counter stains eosin, orange. Van Clieson's picrofuchsin, Weigert's elastic tissue stain, Mann's methyl blue-eosin mixture, Congo-red, and Ehrlich's triacid mixture. A combination of Mann's hematein, Weigert's elastic tissue stain and A'an Gieson's picro-fuchsin, gave the best results for the differentiation of the muscular and connective tissues. This method was applied as follows, and may be used after any of the above fixatives.
  
f'^  
+
1. Stain 10-12 minutes in Mann's hematein or in Bohmer's hematoxylin, until somewhat overstained. 2. Wash well in water. 3. Stain 10-20 minutes in recently prepared resorcin-fuchsin solution after the method of Weigert (9). -1. Wash in water. 5. Stain 1-3 minutes in the freshly prepared picric acid-acid fuchsin solution of A^an Gieson (10). 6. Wash and dehydrate in 95 per cent, or in absolute alcohol. 7. Clear, and mount.
  
 +
Types of Adrenal Veins. — The efferent veins of the adrenals arise in the medulla of the organ by the union of the broad capillaries of the medulla and the adjacent zone of the cortex. These capillaries form broad thin-walled vessels which have been described by Minot (6) as sinnsoids. They converge toward the middle of the medulla, where they pass into somewhat larger vessels, which, for convenience, may be termed small central veins. These veins tend toward the hilum, are relatively short, and by union with one another soon form thicker-walled vessels which may be described as large central veins. These large veins pass toward the hilum, near which, they unite to form a large efferent vessel, the suprarenal vein. This last vein makes its exit from the hilum of the organ and enters either the vena cava inferior, as is the rule on the right side, or the renal vein, as frequently occurs on the left.'
  
 +
From this brief review of the course of these vessels it will l)e seen thai four distinct venous types have been enumerated, and it is the purpose
  
  
  
 +
Jeremiah S. Ferguson 65
  
//-«
+
of the writer to show that these types exhibit well-defined structural peculiarities.
  
 +
Observations. — The sinusoids, after the careful description by Minot (6), will require but brief mention. These vessels possess the wall of a capillary and the lumen of a venule. A number of such vessels may be seen in Fig. 1, in the central portion of the medulla, on either side of the group of central veins. Their wall consists of nucleated endothelial plates which rest directly upon the parenchymal cells. Their lumen is several times the diameter of the- medullary capillaries. They are dis > >
  
  
Line 3,140: Line 1,617:
  
  
-V)
 
  
  
 +
Fig. 1. A group of vessels from the central portion of tlie medulla of the human suprarenal gland, a, sinusoids; h. small central veins. Fixation, 5 per cent formalin; stain, Mayer's hematein; thickness, 8// ; photomicrograph, X 100.
  
 +
tinguished from the small central veins by the absence of connective tissue from the wall of the sinusoids.
  
 +
The small central veins are of the type shown in Fig. 1. The wall of these vessels consists of two coats, endothelial and connective tissue. The latter is always relatively thin, though the vessels possess a very considerable lumen. Venules of this type of structure. Fig. 1, collect the blood from the sinusoids of the medulla. Frequently, however, the sinusoids open directly into the small central veins and venules, the connective tissue of the venous wall being occasionally continued for a very short distance upon the endothelium of the sinusoid. 5
  
  
  
 +
66
  
  
  
 +
The Veins of the Adrenal
  
  
  
f
+
The connective tissue of the small central veins is richly supplied with elastic fibers, which are disposed in oblique nnd circular directions,
  
  
  
^^^ Idn
 
  
 +
Fig. 2. The medulla ol a suprarenal gland of man, showing a group of large central veins. The middle and lowermost veins are in transection, the uppermost vessel in longitudinal section. The series of sections shows that this last vessel is a branch of that in the middle of the figure. Fixation, Zenker's fluid; stain, hematein and methyl-blue, Mann's method; thickness, 10 // ; photomicrograph, X GO.
  
 +
occasional elastic fibers are also longitudinal. The typical small central veins contain no muscle. As they ap]iroach tlieir termination in the
  
  
  
 +
JciTiniah S. i^\'rgiL-'on 67
  
 +
large central veins a few smooth nnisole fibers are found, but these are always disposed in a longitudinal direction. As soon as longitudinal muscle fibers appear in apprcciahh' uiiinl)ors the venous wall acquires the type of the succeeding variety, ihc large central vein.
  
 +
In the large central veins, as in the small, but two coats can be readily distino-uished. The inner coat, or intima, in these vessels consists of a lining endothelium, which rests upon a very thin membrane of delicate connective tissue, containing numy elastic fibers.
  
 +
The outer coat, or adventitia, is also a vei-y thin m(!ml)rane of fibroelastic tissue, but its fibrous Ijiindlos are coarser than those of the intima, and its clastic fibers form a very close network. The outer portion of this coat contains a few longitudinal smooth muscle tibers. The great majority of these fibers, however, ai'c arranged in the form of longitudinal ridges which project into the adjacent medullary tissue. From one to live of these muscular ridges occur in the circumference of the vein (Fig. 2 and 3). Except at those points at which the muscle occurs, the venous wall is extremely thin (Fig. 3). The muscular ridges are frequently so large as to materially obstruct the lumen of the vessel (e. g., the middle vessel in Fig. 2, also the uppermost vessel, which is cut in v(!ry neirly longitudinal section), and they form so noticcuible a peculiarity that their presence may be considered charactei-istic of this type of vessel. The writer has never failed to find these peculiar muscular ridges more or less highly developed in each of the human adrenals which he has examined : he believes them to be constantly present. They are less highly developed in the suprarenal vessels of the lower mammals, but even there they may frequently be demonstrated.
  
*-f»i
+
The muscle fibers of the larger ridges are an-anged in bundh^s which are enveloped in fibro-elastic septa of connective tissue. All of the muscle fibers in these bundles are longitudinally disposed. This arrangement is well shown in Fig. 3, in which a hii'ge central vein is seen in transection at a point near the entrance of a large branch. p]xamination of sections somewhat higher in the series shoAvs the union of these two vessels.
  
 +
In the section photographed, tlu; l)raiicli has been longitudinally cut. The fine dai'k lines shown in the figure are bauds of elastic fibers which are enveloped in delicate white fibrous tissue inclosing the cut ends of the bundles of smooth muscle. The tendency to form longitudinal ridges is shown in this figure by the irregular disti-ibufion of the muscle, one side of the vessel, in both the parent stem and the branch, beirig almost devoid of muscle fibers. The muscular character' of these ridges is beyond doubt.
  
  
J^'\ i
 
  
 +
G8
  
  
1 ss
 
  
 +
The Veins of the Adrenal
  
  
%
 
  
  
 +
Fig 3 Large central veins from the medulla of the human suprarenal gland The figure shows the distribution of the elastic tissue and the bundles of smooth muscle which are seen in transection in the larger vein and m longitudinal section in the smaller ones below. The series shows thes. latter vessels to be branches of the former, the section being selected to show a plane near the point of division. The smaller vessels are jeiy obliquely cut and the muscle is distinctly longitudinal. Fixation Zfnker s fluid; stain, Mann's hematein, Weigert's elastic tissue, and Van Gieson s picro-fuchsin; thickness, 10 a; photomicrograph, X 37.
  
  
  
 +
Jeremiah S, Eerguson 69
  
 +
The writer has observed that the formation of such heavy ridges as those shown in Fig. 3, nearly always occurs at those points where the vessel branches. It is possible that, as in the case of the somewhat similar ridges in the veins of the erectile tissues (see Kolliker's Handbuch der Gewebelehre, 6te Aufl., 1902, pages 486 and 487), these muscular protuberances may to some extent serve the purpose of valves.
  
 +
As the large central veins approach the hilum of the organ they form still larger vessels which partake of the structure of the suprarenal vein. The point of transition from the one type to the other is variable, occasionally the type of the large central veins is continued to the exit of the suprarenal vein at the hilum of the organ. More frequently the primary branches of the suprarenal vein may be traced for a considerable distance into the medulla of the organ, still retaining the type of structure found in the larger vessel.
  
 +
The suprarenal vein presents three coats, intima, media, and adventitia. The tunica intima, in addition to its endothelial lining, possesses a thin membrane of very delicate connective tissue in which occasional branched connective tissue cells may be distinguished; such cells are, however, very scanty. This coat also contains a delicate network of elastic fibers.
  
u
+
The tunica media of the suprarenal vein is extremely thin, rarely ever does it exceed in thickness the tunica intima. It consists chiefly of fibro-elastic tissue, the elastic fibers forming quite a dense network. Few muscle fibers occur in this coat, nowhere are they found in sufficient numbers to form a definite layer, as in veins of similar size in other organs. Some of the muscle fibers are circularly disposed, but many of them are longitudinal.
  
 +
The tunica adventitia is by far the thickest of. the three coats and forms two-thirds to five-sixths of the entire vascular wall. It consists chiefly of smooth muscle fibers, all of which are longitudinally disposed. These smooth muscle fibers form characteristic coarse bundles which are distributed around the entire circumference of the vessel. The largest of these bundles may occasionally form projecting ridges as in the smaller veins, but as a rule the muscular tissue is more evenly distributed than in the central veins. Each of the muscle bundles is enveloped in a perimysial sheath of connective tissue, which blends with that of the tunica media. These adventitial sheaths possess a dense network of elastic fibers, in fact the greater part of the elastic tissue in the vascular wall is frequently found in the adventitia. On its outer surface the tunica adventitia is continuous with the capsule of the adrenal or with the adjacent connective tissue.
  
 +
This peculiar type of vessel is not strictly confined to the suprarenal
  
  
t
 
  
 +
•70 'JMu' W'ins of tlie Adiviial
  
 +
gland, but occurs, more or less typically developed, in many of the large abdominal veins, notably in the renal veins and vena cava, into which the suprarenal veins empty. But UQwhere is this peculiar venous type more strikingly developed, nowhere is the adventitia relatively so much thicker than the media, nowhere is a greater proportion of the smooth muscle of the venous wall longitudinally disposed, nowhere is there relatively less circular muscle, than in the suprarenal vein. Eealizing the intimate relation of the parenchyma of the organ to its blood-vessels, and adopting, if we may, the accepted physiological function of the adrenal — the formation of an internal secretion, a powerful vaso-constrictor which is poured into the blood within the capillaries and veins of the organ — ^the peculiar longitudinal arrangement of the muscular tissue, the valve-like protuberances at the junctions of the venous vessels, the absence of circular muscle from the walls of the veins of all sizes, and the general appearance of these vessels which are so remarkably different from the veins of most other organs, become, to say the least, extremely significant of a close structural relation, physiologically speaking, to the presence of an astringent secretion in the outflowing blood current.
  
 +
In this connection, one further observation is of importance. In the periadrenal connective tissue are numbers of small veins which return the abundant blood supply of the tissues of this region, most of them emptying into the phrenic veins. Many of these veins do not differ from the similar veins of other parts, but in many others the writer has observed that the muscle tissue is almost entirely disposed in a longitudinal direction, a condition which is quite the reverse of that found in the adipose and areolar tissues of other portions of the body.
  
 +
The writer also finds that many of the small veins of the adrenal, instead of opening into the central veins as is usually the case, pursue a less frequent course, penetrating the cortex and capsule of the organ, and emptying into the small veins of the surrounding connective tissue. The frequency with which this condition was associated with the occurrence of longitudinal muscle fibers in the periadrenal veins, suggests a more than casual relationship between the two conditions.
  
 +
Summary.
  
 +
In conclusion, the above facts may be summarized as follows:
  
 +
1. The efferent blood-vessels of the adrenals form four successive vascular types, the sinusoids, the small central vein, the large central vein, and the suprarenal vein.
  
 +
2. Each of these types presents distinctive characteristics.
  
  
  
 +
Jeremiah S. Ferguson 71
  
Ijlil.  
+
3. In all four tA^pes circular muscle is either absent or noticably deficient.
  
 +
4. In the large central veins prominent and characteristic muscular ridges are constantly present, and are frequently in relation with those points at which the branches of these vessels enter.
  
 +
5. These peculiarities of structure may possibly bear a close physiological relation to the function of the adrenal as a gland that forms an internal secretion which has been shown to be a powerful vaso-constrictor and stimulant of smooth or involuntary muscle.
  
 +
BIBLIOGRAPHY.
  
 +
1. AicHEL.— Munch, med. Wochenschr., 1900, XLVII, 1228; and Arch. f. mik.
  
 +
Anat, 1900, LVI, 1.
  
3 ?rt
+
2. WiESEL.— Anat. Hefte. 1901, XVI, 115.
  
 +
3. Ibid., 1902, XIX, 481.
  
 +
4. SouLiE.— J. de I'anat. et de la physiol., 1903, XXXIX, 197, 390, 634.
  
 +
5. Flint. — Contrib. -dedicated to W. H. Welch, Baltimore, 1900, 153; also in
  
 +
Johns Hop. Hosp. Rep., 1900, IX, 153.
  
 +
6. MiNOT.— Proc. Post. Soc. Nat. Hist., 1900, XXIX, 185.
  
lb
+
7. Pfaundler. — Sitz. d. Akad. d. Wissensch., Wien, 1892, CI, 515.
  
 +
8. GoTTSCHAU.— Arch. f. Anat., 1883, 412.
  
 +
9. Weigert.— Centralbl. f. allg. Path. u. path. Anat., 1898, IX, 289. 10. Freeborn.— Proc. N. Y. Path. Soc, 1893, 73.
  
B^9'^'^'
 
  
  
 +
THE BLOOD VESSELS OF THE PEOSTATE GLAND.
  
'm
+
BY
  
 +
GEORGE WALKER, M. D.
  
 +
Associate m Surgery, Johns Hopkins University. From the Anatomical Laboratory, Johns Hopkins University. With 2 Colored Plates.
  
//)
+
As the structures of the body are being more and more carefully investigated it is found that organs are composed of like structural units, which when repeated a number of times form the whole organ. In general these units are formed by the glandular structures, the blood-vessels, or by both, as is the case in the liver.
  
 +
Some eight years ago, at the suggestion of Dr. Mall, I undertook the study of the prostate gland, with the hope of finding structural units in it. In this search I was successful. Since then my work has been continued in the laboratories of Professor Born ^ of Breslau and Professor Spalteholz ^ of Leipzig, and although this communication is several years late in appearing, it should in reality have preceded those that were published in 1899.
  
 +
In the present study for the most part the prostate glands of dogs were used. Several cadavers were injected and the gross blood supply was studied in part from these. After the animals had been killed by chloroform, the aorta was exposed just above the bifurcation and injected with various substances. A preliminary washing out of the blood-vessels with salt solution was practised in a few of the first injections, but this was soon discarded as it did not seem to enhance the value of the method.
  
^4ii'
+
Carmine gelatine, followed by ultramarine-blue gelatine, as an injecting mass, gave the most satisfactory results. About 250 cc. of the carmine gelatine were injected first, the injection being stopped as soon as all of the tissues had acquired a maximum carmine hue. This was followed by the injection of ultramarine-blue gelatine, which was kept up until no more of the material would pass in. The carmine gelatine
  
 +
^Walker. George: Ueber die Lymphgefasse der Prostata beim Hunde. Arch, fiir Anatomie, 1899.
  
 +
= Walker, George: Beitrag zur Kenntnlss der Anatomie und Physiologie der Prostata, etc. Ibid., 1899. American Joukxal of Anatomy. — Vor-. V.
  
  
  
 +
74 Tlif lUood Vessels of the Prostate Cilaiicl
  
4
+
filled the arteries, capillaries, and veins ; the blue passed into the arteries and arterioles, displacing the gelatine and filling them, but was stopped at the capillaries because the nltramarine-blue granules were too large to enter them. In a specimen thus prepared the arteries appear blue, and the capillaries and veins red. This is shown in Figure 1, with colors reversed, in order to present the conventional appearance. As it was impossible to get a perfectly complete injection in one specimen, several of the best were selected and the gaps filled in, with the results as shown in Figure 1. One section, however, is remarkably beautiful and presents a picture very closely resembling that seen in this figure.
  
 +
In order to map out the complete network of arteries surrounding a separate lobule, I injected them with Prussian blue, then opened the urethra, and injected carmine gelatine into a prostatic duct through a very fine blunt hypodermic needle. A specimen made in this way is shown in Figure 2 where the ducts are represented in brown. The capillaries were studied in a specimen which had been completely injected with carmine gelatine. A very thin section of this was stained with iron hematoxylin, and is shown in Figure 3. The basement membrane is artificially tinted with yellow so as to make it visible.
  
 +
The technique of the injecting is rendered difficult by the fact that the situation of the gland in the pelvis is somewhat remote. In all, about
  
/i-^/i
+
75 dogs were used before a complete circulation cycle could be seen. Cinnabar, lampblack, and various other substances were tried, but they did not prove as good as the combination of carmine gelatine followed by ultramarine-blue gelatine.
  
 +
When the ordinary directions for preparing carmine gelatine were followed, it always proved difficult to get a perfectly transparent substance. The trouble is connected with the neutralization of the ammonia by the acetic acid. The gelatine should be rendered practically neutral, but if the reaction is carried the least bit too far, the solution becomes cloudy. Sometimes two drops of the acetic acid are sufficient to make turbid a whole litre of the prepared carmine. After a good many trials, the following method was adopted : Take 10 cc. of the ordinary laboratory ammonia and dilute with 40 cc. of distilled water, then determine by titration the exact amount of the laboratory acetic acid which will neutralize it. After this determination has been made, 10 grms. of pure carmine are rubbed up with 50 cc. of distilled water; then 25 cc. of the ordinarj^ ammonia are measured, and a few drops at a time are poured into the carmine mixture which is kept constantly rubbed up. This process is very closely watched, and the ammonia is gradually added until the carmine is completely dissolved, and the mixture becomes
  
  
f
 
  
 +
George Walker 75
  
 +
translucent and assumes .a dark red color. Tlie amount of ammonia used is determined by referring to the vessel in which the 25 cc. have been measured. The gelatine in whatever proportion it is required — according as a thin or thick solution is desired — is dissolved in the distilled water, and the carmine solution is added to it. We then calculate how mucli acetic acid will be required for the amount of ammonia w^hich has been used; this is measured and added, drop l)y drop, to the mixture which is constantly stirred. A sufficient quantity of water is then added to bring the amount up to a litre. I found that in this way I could always obtain a beautifully clear gelatine and was never annoyod by the failures and uncertainties belonging to tlie other method.
  
 +
Akteries. .
  
 +
The prostate gland derives its arterial supply from the internal iliac arteries by means of four branches; the superior vesical, the inferior vesical, a small branch from the inferior hemorrhoidal, and a small terminal branch from the internal pudic artery. These vessels will be found illustrated in my paper published in 1899. The superior vesical, a branch from the internal iliac, which is given off high up, divides before reaching the bladder, into two fair-sized branches ; the lower and smaller branch extends downward and supplies the vesical third of the prostate ; this branch is sometimes called the middle vesical artery. The inferior vesical, which is a large branch, is practically the main blood vessel of the prostate gland, and should be called the prostatic artery for, in the majority of instances, it does not send any branches to the bladder. The major part of the gland is supplied by this vessel; it courses along the vesicorectal fascia and meets the prostate at its lower border, where it usually divides into seven branches, four of these enveloping the anterior, and three the posterior surface. The posterior are about one-half the size of the anterior lu'anchcs. These vessels are situated in the capsule of the gland and envelop it as the fingers of one's hand would do in clasping a round object. From these trunks a numljer of smaller ones are given off, so that a very close arterial network is formed over the surface of the gland. The ])ranch from the inferior liemorrhoidal is not constant; in fact, it appears to be more often absent than present. When it is seen, it occurs as one or two small branches wbicli ]uQci llic prostate in its urethral half, and extend over the surface as line vessels which anastomose with the vesica] artery. The internal ])iulic branch is fairly constant. It extends along Ibc membranous urotlira and ])lunges directly into the prostatic substance usually without giving off any l)ranclies to the surface.
  
  
  
 +
7G The Blood Vessels of the Prostate Gland
  
 +
A slight anastomosis is occasionally seen. The vessels supplying the two sides of the gland are distinct. The only anastomosis across the median line is by way of the venous channels around the urethra.
  
^5^'
+
From the large superficial branches above described, smaller ones are given off at right angles, and pierce the gland in places corresponding to the divisions of the lobules (Art. Fig. 1). Here they penetrate the fibrous-tissue septa, and extend to the urethra, becoming smaller and smaller, however, as they approach it, so that in this region they are seen as very delicate terminal vessels. As they pass down, they give off branches which penetrate into the lobule and finally divide into myriads of capillaries which pass around the alveoli, and come in very close relationship with the secreting cells. From these cells they are separated simply by a delicate basement membrane composed of fine fibrils. From the superficial vessels branches are given off which enter the lobule directly, that is, they do not pass first into the fibrous-tissue septa {8up. Br. Fig. 1). On the anterior surface there are usually two branches which do not give off as many smaller ones as the rest, and consequently remain larger and extend over to the middle line, where they dip into the median fissure and supply the median side of the lobules (Med. Br. Fig. 1).
  
 +
The arrangement on the posterior surface corresponds to that seen on the anterior surface, in so far as the supply of the lobules is concerned. On the posterior surface toward the bladder one vessel penetrates the substance of the gland and runs directly to the caput gallinaceum (Art. Col. Sem. Fig. 1). Here it divides into a fine network and supplies the erectile tissue of the organ. Before this vessel reaches the eminence a small trunk is given off which extends to the ejaculatory duct (Ai-t. duct. ej. Fig. 1). The branch supplying the caput gallinaceum is usually derived from the pudic; sometimes it comes from the inferior vesical.
  
 +
The arterial supply in the connective tissue toward the urethra is much poorer than in the secreting portion. Here the vessels terminate in fine branches, relatively somewhat sparsely scattered. The arterial arrangement is shown on the red side of Figure 1.
  
.■#^?
+
Capillaries.
  
 +
The capillaries form a very complete and elaborate network around the alveoli of the lobule. Here, as is seen in Figure 3, they surround an alveolus in a more or less circular manner, and upon these vessels the cells rest almost directly, being separated only by the very delicate connective-tissue basement membrane. From this outside capillary, a folding in is seen, which forms a definite loop (Cap. L. Fig. 3.) This at
  
  
  
//>;*
+
George Walker 77
  
 +
first sight might appear to end blindly, but a more careful study reveals the two branches, which sometimes appear winding around each otlier, and presenting enlarged club-shaped ends. The cells rest on these as they do on the circular portion. Under the low power, the epithelial cells appear to be in direct contact with the capillaries, and it is only by the aid of the oil immersion that a very delicate connective-tissue basement membrane is seen. This is shown artificially colored as B. M. Fig, 3. This membrane contains a few elastic fibers.
  
 +
Veins.
  
5 ' ^P>i
+
On the surface of the gland are veins corresponding to the arteries which lie in the capsule. As a rule they merge into two main trunks corresponding to the vesical arteries; occasionally several small branches pass off into the middle hemorrhoidal vein.
  
 +
The superficial veins do not drain the blood from the whole gland, but only from the outer fourth, as is shown in Fig. 1. From the inner threefourths of the gland the blood passes towards the centre, and into the large venous sinuses which are a continuation of the corpora spongiosa. (Co. 8p. Fig. 1). These immediately surround the urethra. The large venous trunks which collect the blood from the gland do not lie on the same plane as the arteries, but are situated in the fibrous septa some little distance removed from them. These run, as do the arteries, on the outside of the lobule, and are interlobular, not intralobular. For the venous return from the caput gallinaceum there is no distinct vessel corresponding with the artery, but there are anastemoses with the spongy plexus.
  
 +
The venous plexus around the urethra is, as before stated, a continuation of the corpora spongiosa. The blood from this region passes away into the internal pudic vein. Occasionally two or three small veins drain the tissues from this region, pass out of the prostate and run along the membranous urethra and off into the vesicorectal fascia.
  
 +
There is an anastomosis of the veins in the prostate and bladder where these organs come together, and also on the outside through the superior vesical veins. There is, of course, an anastomosis of the urethral veins through the corpora spongiosa plexus.
  
 +
SUMMAEY.
  
 +
The prostate gland is supplied with blood by branches of the internal iliac arteries, viz., the superior vesicals, inferior vesicals, inferior hemorrlioidals, and internal pudics; the main blood supply comes from the inferior vesicals.
  
  
  
 +
78 The Jilood Vessels of I lie Tr. .slate 11 land
  
 +
Branelies of llieso envelop iho siirfaec! of tlie <ilnii(l and f^ivo ofT smallcMon(>s, wliieli iieiielratc between tlie lohnles in (he fihrons-tissuc septa.
  
AMERICAN JOURNAL OF ANATOMY--VOL V.  
+
The caiiilhii-ies are separated iVom I he ciiilhclial cells only by a very lliiii haseiiieiil iiieiiibraiie.
  
 +
'I'here are siipei-llcial vcins correspond iiiii' with the arteries.
  
 +
I'\)i- the Older superficial fourth of the gland the return flow is towards (lie siirfaei'. 'I'he inner three-fourths are drained by veins wliieb enijjiy into the venous plexus immediately aronnd the nretlira.
  
E. T. BELL, DEL.  
+
The lobule is formed primarily by the individual gland dnets as shown in Figure 2. The main arteries surround this lobnle wliicb they penetrate at many points. The veins leave the lobule mainly at its peripheral 5ind central (urethral) ends as shown in Fig. ].
  
 +
EXPLANATION OF PLATP^S I AND II.
  
 +
Fid. 1 is Irom a section of a prostate gland of a dog injected with carmine gelatine and ultramarine-blue gelatine. The arteries in the section were blue, the veins and capillaries red. The section was cut free hand, about r.O// in thickness, and cleared both in glycerine and in creosote. In the figure this artery is red and this vein blue. Ar^., Arteries; Art. Col. Ficm.. Artery of the colliculus seminal is; Art. duct, cj.. Artery of the ejeculatory duct; Col. Scni., Colliculus s(>niinalis; V. J'L, Venous plexus around the urethra.
  
THE DEVELOPMENT OF THE THYMUS.  
+
Fio. 2. Lobule of prostate from a gland which had been injected with uHramarine-golatine blue into the artery, and with carmine gelatine into the prostatic duct. Pr. duct., Opening of the prostatic duct into the urethra; Gl. Tis., Gland tissues distended with carmine gelatine; Art., Surrounding artery. In this figure the artery is represented in red and the ducts in brown.
E. T. BELL.  
 
  
 +
Fig. 3. Very thin section from Ihe i)rostate gland of a dog. Capillaries in red, injected with carmine gelatine. Section stained with iron h;rmatoxylin, with artificial yellow tinting of basement membrane. Oil immersion with one inch eye-piece amplification. Cap., Capillaries; B. M., Basement membrane; 07. Ep., Glandular epithelium; Cap. L., Capillary loop.
  
  
  
12
+
BLOOD VESSELS OF PROSTATE GLAND
  
 +
GEORGE WALKER
  
  
^^®\r
 
  
 +
PLATE
  
  
  
AMERICAN JOURNAL OF ANATOMY--VOL V.
 
  
 +
a) CO
  
  
E. T. BELL, DEL.
 
  
 +
Q
  
  
THE DEVELOPMENT OF THE THYMUS.
 
E. T. BELL.
 
  
 +
AMERICAN JOURNAL OF ANATOMY — VOL. V
  
  
  
rsil
+
BLOOD VESSELS OF PROSTATE GLAND
  
 +
GEORGE WALKER
  
  
rsil .,
 
  
 +
PLATE II
  
  
AMERICAN JOURNAL OF ANATOMY--VOL V.
 
  
 +
GI.Tis.
  
  
E. T. BELL, DEL.
 
  
 +
Art
  
  
THE YEIXS OF THE ADEE^AL.
 
  
BY
 
  
JEREMIAH S. FERGUSON, M. Sc, M. D.
+
PKDuct
  
From the Histological Laboratory of Cornell University Medical College.  
+
Fig. 2
  
Neio York, N. Y.
 
  
With 3 Text Figures.
 
  
Within the past decade our knowledge of the functions of the adrenal
 
glands, and of their relations to the rest of the economy, has been greatly
 
enhanced l)y many careful cliomical and physiological researches. Tlie
 
recent studies of Aichel (1), Wiesel (2, 3), Soulie (4), and others have
 
placed the early development of the organ upon a fairly certain basis.
 
These advances in the physiology and embryology of the organ have not
 
as yet been accompanied by corresponding advances in our appreciation
 
of its minute anatomy. Hence this branch of the subject is, at the
 
present time, one of unusual interest.
 
  
The intimate relation of the parenchyma of the adrenal to its bloodvessels, as shown by the general tendency to regard the organ as a true
+
Cq1>.L,
gland whose secretion enters its blood-vessels and leaves the organ
 
through its efferent veins, makes it specially important that these vessels
 
should be carefully studied and their structure and distribution accurately
 
recorded.
 
  
The exhaustive study of Flint (5), on the course of the adrenal vessels,
 
based as it was upon carefully prepared reconstructions, leaves little to
 
be desired along this line. The writer is, however, unable to find in the
 
literature any reference to the minute structure of the veins of the adrenal,
 
with the notable exception of Minot's (6) article on sinusoids.
 
  
To be sure Pfaundler (7) mentioned the occurrence, in the medulla of
 
the adrenal, of venous vessels whose only wall consisted of endothelium.
 
Gottschau (8) also, though omitting their description, has figured similar
 
vessels in his Plate XVIII, Fig. 1. But as to the structure of the larger
 
blood-vessels of the adrenal glands the literature seems to be entirely
 
barren.
 
  
The architecture of the arterial walls does not appear to offer any
+
NCap.
distinctive peculiarities, the tissues of which they consist being arranged
 
in a manner precisely similar to that which characterizes the arteries of
 
American Journal of Anatomy. — Vol. V.  
 
  
  
  
64 The N'ein.s oi' the Adrenal
+
Krcj. 3
  
similar size occnrriiiii- in olliei' or<ians. 'I'lie veins, liowever, j^resent
 
distinct and remarkable peeidiarilies which it is the iiur))()se oi' the
 
present |>a|)ci- to describe.
 
  
Methods (iiid Mafcr'ud. — The tissue used for this stud}^ has included
 
specimens of the adrenal from twenty-one human adults, together with the
 
casual examination of fetal adrenals of the pig and of man. The
 
adrenals of other mammals, e. g., nionke}^ dog, cat, rabbit, and guineapig, have also been more or less carefiilly studied.
 
  
These tissues have been fixed and hardened with many reagents, among
+
AMERICAN JOURNAL OF AN ATOM Y--VO L. V
which are Zenker's solution, formol. Miiller-formol, alcohol, corrosive
 
acetic mixture, Tellyesniczky's fluid, and Flemming's solution. The
 
stains used were hematein by various methods, acid hematein, iron
 
hematein, etc., and for counter stains eosin, orange. Van Clieson's picrofuchsin, Weigert's elastic tissue stain, Mann's methyl blue-eosin mixture,
 
Congo-red, and Ehrlich's triacid mixture. A combination of Mann's
 
hematein, Weigert's elastic tissue stain and A'an Gieson's picro-fuchsin,
 
gave the best results for the differentiation of the muscular and connective tissues. This method was applied as follows, and may be used
 
after any of the above fixatives.  
 
  
1. Stain 10-12 minutes in Mann's hematein or in Bohmer's hematoxylin, until somewhat overstained. 2. Wash well in water. 3. Stain
 
10-20 minutes in recently prepared resorcin-fuchsin solution after the
 
method of Weigert (9). -1. Wash in water. 5. Stain 1-3 minutes in
 
the freshly prepared picric acid-acid fuchsin solution of A^an Gieson
 
(10). 6. Wash and dehydrate in 95 per cent, or in absolute alcohol.
 
7. Clear, and mount.
 
  
Types of Adrenal Veins. — The efferent veins of the adrenals arise in
 
the medulla of the organ by the union of the broad capillaries of the
 
medulla and the adjacent zone of the cortex. These capillaries form
 
broad thin-walled vessels which have been described by Minot (6) as
 
sinnsoids. They converge toward the middle of the medulla, where they
 
pass into somewhat larger vessels, which, for convenience, may be termed
 
small central veins. These veins tend toward the hilum, are relatively
 
short, and by union with one another soon form thicker-walled vessels
 
which may be described as large central veins. These large veins pass
 
toward the hilum, near which, they unite to form a large efferent vessel,
 
the suprarenal vein. This last vein makes its exit from the hilum of the
 
organ and enters either the vena cava inferior, as is the rule on the right
 
side, or the renal vein, as frequently occurs on the left.'
 
  
From this brief review of the course of these vessels it will l)e seen thai
+
THE EMBKYONIC DEVELOPMENT OP THE EETE-CORDS AND SEX-COEDS OF CHRYSEMYS.
four distinct venous types have been enumerated, and it is the purpose
 
  
 +
BY
  
 +
BENNET M. ALLEN,
  
Jeremiah S. Ferguson 65
+
Instructor in Yertehrate Anatomy, University of Wisconsin.
  
of the writer to show that these types exhibit well-defined structural
+
With 1 Double Plate akd 6 Text Figures.
peculiarities.  
 
  
Observations. — The sinusoids, after the careful description by Minot
+
A glance at the diagrams on the next page will at once serve to show the great difference of opinion that has prevailed in regard to the origin of the sex-cords and rete-cords of the Sauropsida. In fact, it is hard to conceive of any possible manner of origin that has not been held to be correct by some well-known embryologist.
(6), will require but brief mention. These vessels possess the wall of a
 
capillary and the lumen of a venule. A number of such vessels may be
 
seen in Fig. 1, in the central portion of the medulla, on either side of the  
 
group of central veins. Their wall consists of nucleated endothelial
 
plates which rest directly upon the parenchymal cells. Their lumen is
 
several times the diameter of the- medullary capillaries. They are dis
 
> >
 
  
 +
The Chelonia have remained almost untouched in the study of this problem. Only one work has appeared upon the rete-cords (Von Moller, 98), while no work has been published upon the subject of the sex-cords.
  
 +
Von ]\Ioller studied two turtles, one a specimen of Emys lutaria of 2.5 cm. plastron length, and the other Clemmys leprosa of 4.9 cm. plastron length. He observed no connection between the testis and Wolffian body. This caused him to remark :
  
 +
" Dieser Befund wird hochst auffallig, wenn mann bedenkt dass die Beobachtungen an Amphibien zeigen dass die Verbindungen zwischen Hoden und Wolffschen Gauge schon dann angelegt und vollendet werden, wenn die iibrigen Organe sich noch in der Entwickelung befinden, und wenn das Junge in der Eischale, respective in Uterus eingeschlossen ist. Die zwei von mir untersuchten Schildkroten hatten dagegen schon seit Monaten die Eischale verloren, und doch war bei ihnen noch kein einzige Verbindung zwischen Hoden und Wolffschen Gauge vorhanden, obwohl Anlagen dieser Verbindungen sich bereits vorfanden."
  
 +
It is quite unfortunate that he considered these stages to be early enough for his purpose, since my work has shown the rete-cords to be formed at a relatively early stage of development in Chrysemys.