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Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Previous studies have documented that angiotensin converting enzyme (ACE) inhibitors consistently reduce albuminuria and retard the progression of diabetic nephropathy. However, the involvement of angiotensin II in diabetic nephropathy is not fully understood. In this study we compared the effects of CS-866, a new angiotensin II type 1 receptor antagonist, to that of an ACE inhibitor, temocapril hydrochloride, on the development and progression of diabetic nephropathy using Otsuka Long-Evans Tokushima fatty rats, a type II diabetes mellitus model animal. High doses of CS-866 or temocapril treatment were found to significantly improve urinary protein and β2-microglobulin excretions in diabetic rats. In electron microscopic analysis, loss of glomerular anionic sites, one of the causes of glomerular hyperpermeability in diabetic nephropathy, was found to be significantly prevented by CS-866 treatment. Light microscopic examinations revealed that both treatments ameliorated glomerular sclerosis and tubulointerstitial injury in diabetic rats. Furthermore, high doses of CS-866 or temocapril treatment significantly reduced the positive stainings for transforming growth factor-β (TGF-β), vascular endothelial growth factor, and type IV collagen in glomeruli of diabetic rats. These results indicate that intrarenal angiotensin II type 1 receptor activation plays a dominant role in the development and progression of diabetic nephropathy. Our study suggests that CS-866 represents a valuable new drug for the treatment of diabetic patients with nephropathy.

Male rats received daily intraperitoneal injections of cadmium sulfate (2.0 mg/kg) for 3, 6, and 8 days (cadmium-treated groups) or physiological saline for 8 days (control group). The thoracic aortae from both groups were used for electron microscopy and immunocytochemistry for big endothelin (ET)-1, ET-1 and ET-converting enzyme (ECE)-1, and the blood plasma and homogenized thoracic aortae were prepared for assays of big ET-1 and ET-1 concentrations. A remarkable increase in the number of Weibel-Palade (WP) bodies, enhanced immunoreactivities for ET-1 and ECE-1 along the endothelium, and elevated concentrations of ET-1 in the blood plasma as well as in homogenized thoracic aortae were observed in the cadmium-treated groups. However, immunoreactivity for big ET-1 and the plasma and aortic tissue concentrations of big ET-1 did not show any significant changes between the control and cadmium-treated groups. By immunoelectron microscopy, immunoreactivities for ET-1 and ECE-1 were much more pronounced in the increased WP bodies. Since WP bodies are involved in the extracellular release of ET-1 in the manner of a regulated pathway, these findings indicate that cadmium administration induces the enhanced release of ET-1, which is actively processed by ECE-1 in the WP bodies.

A total of 548 upper limbs (276 right and 272 left hands) from Japanese cadavers were dissected. The arrangements of extensor indicis proprius, extensor digitorum communis (EDC), and extensor digiti minimi tendons and the intertendinous connections were studied. The most common pattern of extensor tendons was as follows: the index finger had a single EDC tendon, the middle finger had a single EDC tendon, the ring finger had a single EDC tendon, and the small finger had a single EDC tendon or a single common EDC tendon distributed to the ring and small finger. A single extensor indicis proprius tendon ran along the ulnar side of the EDC, and the extensor digiti minimi tendon consisted of 2 slips. Intertendinous connections were classified into 3 types: type 1 with a filamentous band, type 2 with a fibrous band, and type 3 with a tendinous band subdivided to r-shaped and y-shaped. The most common patterns were type 1 in the second intermetacarpal space (IMCS), type 3r in the third IMCS, and type 3y in the fourth IMCS.

Acute toxicity of bis (tributyltin) oxide in the sweat glands in the rat footpad was investigated by electron microscopy and an energy-dispersive X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg bis (tributyltin) oxide. After 6–8 h, swelling of mitochondria appeared in the secretory cells of the sweat glands. After 12 h, the secretory cells began to show intracytoplasmic edema. After 16–20 h, secretory cells in some sweat glands showed marked hydropic degeneration with swollen cytoplasm. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria of the affected secretory cells. Mitochondria dysfunction due to the toxic effects of bis (tributyltin) oxide induced changes in the secretory cells of rat sweat glands. After 24–48 h, the secretory portion of the sweat glands contained three types of cells: degenerating dark cells, regenerating cells carrying injured mitochondria, and light cells which were morphologically very similar to the cells in the transitional portion of the sweat gland. These light cells appeared to differentiate into active secretory cells after settling down in the secretory portion. Based on these observations, we concluded that the cells in the transitional portion could play an important role at least as reserve cells against secretory cell toxicity. In association with the regenerating process of the damaged secretory portions, increased mitotic activities were seen in different areas of all the dermal sweat ducts. The above-mentioned morphological observations for cell damage and subsequent regeneration and renewal of secretory cells in sweat gland intoxication have not been reported so far.

We investigated the morphological characteristics of cervical nerve roots in 38 cadavers. The cadavers consisted of 20 males and 18 females with a mean age of 75 years (range : 44 to 93 years). The morphological correlation between the ventral nerve root and dorsal nerve root was classified into three types.Type I in which one anterior root joins one dorsal root. Type II in which two anterior roots join one dorsal root. Type III in which two anterior roots become one again and joins one dorsal root. The results of macroscopic investigation from C3 to C8 nerve roots in 38 cadavers were as follows : TypeI was mainly found in 261 roots (82.9%), typeII in 37 roots (11.7%), and type III in 17 roots (5.4%). In the lower cervical spine such as C6 and C7, type II and III were more frequently found than those of the upper cervical level.

This report describes a rare case of absence of the celiac trunk, which was encountered in a Japanese female cadaver in the dissecting room at Kurume University School of Medicine in 1993. In this case, the left gastric, the splenic, the common hepatic and the superior mesenteric arteries arose independently in that order from the abdominal aorta. In addition, the left aberrant hepatic artery arose from the left gastric artery. This anomalous case belongs to type 5 (Typus primitivus) of Morita's classification (1935), and is the fifth case of this kind of vascular variation to be reported in Japan.

Toxic effects of bis (tributyltin) oxide (TBTO) on the rat exocrine pancreas were studied with an electron microscope and X-ray microanalyzer. To measure tin concentrations in the blood, atomic absorption spectrophotometry was carried out. Adult male Wistar rats received an intramuscular injection of TBTO (0.5 ml/kg). At 2 h after injection, a marked swelling of mitochondria and an enlargement of the cisterns of the rough endoplasmic reticulum appeared in the pancreatic acinar cells. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria. Heterogeneous zymogen granules with an electron dense core and a pale central zone increased in number in the acinar cells between 4 and 8 h after TBTO treatment. By 24 h after TBTO injection, the acinar cells had been ultrastructurally restored. Atomic absorption analyses showed that blood tin concentrations peaked at approximately 1 h after TBTO injection and then progressively declined, reaching the zero level at 12 h after injection. The effects of TBTO on the synthesis and secretion of zymogen granules were investigated with and without caerulein as a stimulant of secretion. Data obtained from these experiments indicated that TBTO inhibited both the synthesis and secretion of zymogen granules. The inhibition of the protein synthesis and secretion might be caused partly by mitochondrial dysfunctions due to the toxic effects of TBTO.

The epithelial downgrowth arises in the presumptive foliate papilla region of the tongue approximately at prenatal day 22, and the distal portion of the primary epithelial cell cords transforms to the bifurcated serous gland and excretory duct between prenatal day 30 and postnatal day 2. The excretory ducts extend upward through the primary epithelial cell cords at rather random intervals and are open to the tongue surface between postnatal days 1 and 2. In this process, successive connections between the adjacent ascending excretory ducts occur mainly due to desquamation of the keratinized lining cells of the ducts, resulting in the formation of the foliate gutter. Taste bud primordia appear in the primary epithelial cell cords by nerve penetration through the basal lamina from prenatal day 30 and nearly fully formed taste buds facing the ascending excretory ducts have been already observed before the foliate gutter formation is completed. In the differentiation process of chemoreceptor (type III) cells from less-differentiated basal (type IV) cells, subsurface cisterns of endoplasmic reticulum are occasionally present where nerve endings make contact. Since subsurface cisterns have been considered to be involved in reciprocal or efferent synaptic transmission, it is reasonable to consider that these morphological specializations may take a role in neurotrophic signals for differentiation of the chemoreceptor cells.

The toxic effects of bis (tributyltin) oxide (TBTO) on the rat liver were studied with an electron microscope and the accumulation sites of tin were determined with an X-ray microanalyzer. The activities of serum enzymes and the concentration of serum bilirubin were also analyzed. Male Wistar rats received an intramuscular injection of 0.5 ml/kg of TBTO. Marked swelling of the mitochondria appeared in the hepatocytes 4 h after injection of TBTO. Cytoplasmic vacuoles, which contained degenerated mitochondria, gradually increased in number in these hepatocytes. This in turn may have caused a decrease in the volume of hepatic cell cords and an enlargement of sinusoids in the entire hepatic lobule. However, fine structures of intrahepatic bile ducts were not altered. By X-ray microanalysis, tin peaks were preferentially obtained from swollen mitochondria of the hepatocytes. By polarographic analysis of the respiratory responses of mitochondria, it was demonstrated that rates of state 4 respiration and respiratory control ratio were significantly disturbed in TBTO-treated rats in comparison with those of controls. The activities of AST (aspartate aminotransferase) and ALT (alanine aminotransferase) were significantly increased after TBTO treatment, but those of ALP (alkaline phosphatase), LAP (leucine aminopeptidase) and total bilirubin were not changed. These results indicated that parenterally administered TBTO accumulated in the liver cell mitochondria and disturbed oxidative phosphorylation. Mitochondrial dysfunction might induce severe damage of the hepatocytes. Four days after injection of TBTO, hepatic structures and chemical indices were almost restored by the regeneration of hepatocytes.

The role of the submandibular glands in the excretion of parenterally administered bis (tributyltin) oxide (TBTO) was studied. Fine structural alterations of the submandibular glands were observed with an electron microscope. Accumulation sites of TBTO were determined with an X-ray microanalyzer and tin concentrations in saliva and blood were measured by atomic absorption spectrophotometry.

Fiber type differentiation as revealed by myosin ATPase activities and the immunological analysis of myosin light chains (MLC) by the Western blotting method were done on the postnatal rat soleus and extensor digitorum longus (EDL) muscles. In the soleus, type 1 (slow-twitch) muscle fibers gradually increase in percentage after postnatal day 10, and, in the EDL, the differentiation of type 2A and 2B (fast-twitch) muscle fibers is also pronounced between postnatal days 10 and 15. The present immunological analysis of MLC indicates that the antigenicity of LclS becomes more intense with a rapid decrease in anti-genicity of Lc2F from postnatal day 7 in the soleus, while the antigenicity of LclF becomes noticeable during the same period in the EDL. These results suggest that the differentiation of slow-twitch fibers is mainly due to that of Lc1S in the soleus and the differentiation of fast-twitch fibers is mainly due to that of Lc1F in the EDL

Effects of cadmium on the fetal and postnatal rat hepatocytes were studied with an electron microscope and an X-ray microanalyzer. Pregnant and lactating Wistar rat dams at 15 and 21 days of pregnancy and at 3 days after delivery received intraperitoneal injections of cadmium sulfate (1 mg/kg body weight) for 3 days. On the day following the last injection, the livers were isolated from the fetal and suckling rats and provided for electron microscopy. The livers from the untreated fetal and newborn rats served as control. Large bile canaliculi, which were formed by five or more hepatocytes, were frequently observed in the cadmium-treated perinatal rat livers. The intercellular space between each adjacent hepatocyte was widened. By X-ray microanalysis, cadmium peaks were preferentially detected out from intramitochondrial granules of the cadmium-treated hepatocytes. By morphometric analysis, the increase both in the mitochondria volume and in the number of intramitochondrial granules was evident in the cadmium-treated hepatocytes when compared to those of control. These data suggest the preferential accumulation of cadmium in mitochondria of the hepatocytes interferes with the morphogenesis of the perinatal rat liver.

Cadmium toxicity to the cornea of pregnant rats was studied using the electron microscope and x-ray microanalyzer. In in-vivo experiments, severe corneal edema occurred in pregnant dams that received intraperitoneal injections of cadmium sulphate for 4 days during gestation, but not in nonpregnant rats. Prominent swelling of mitochondria and the occurrence of intra- and inter-cellular vacuoles in the corneal endothelium were observed only in pregnant dams. In in-vitro experiments, electron-dense deposits consiting of cadmium-oxine complexes were preferentially found in swollen mitochondria of the endothelial cells. Cadmium peaks were obtained from these deposits with x-ray microanalysis. These data suggest that the corneal edema observed after administration of cadmium may imply the disturbance of pump function and barrier function of the corneal endothelium due to the primary toxic effects of this metal on mitochondria.

The authors conducted a study in which they applied the spinal cord compression-decompression model in rabbits to investigate the morphological changes and histopathological findings in the deformed spinal cord over a long-term period after performing decompressive surgery. Throughout the experimental period, mangnetic resonance (MR) images were obtained frequently; after obtaining a final MR image, the spinal cord was dissected and underwent histological examination. Immediately after decompressive surgery, axial T1-wieighted MR imaging revealed an increase in the cross-sectional area of the spinal cord during the 1st and 2nd weeks. The spinal cord area achieved a peak at an average of 5.9 weeks after decompressive surgery, when it displayed isointensity on T1- and high-intensity on T2-weighted images. The main histological findings were spongy changes in the white matter, which persisted for 4 months postsurgery. There was a significant correlation between the presurgical spinal cord area and the postsurgical decreased number of motor neuron cells. Based on the MR imaging and histopathological studies, although the deformed spinal cord that underwent compression for 3 months was immediately restored morphologically after decompressive surgery, the change in quality in the spinal cord persisted at least 4 months.

This report describes two arterial anomaly cases in the celiaco-mesenteric region, which were encountered in two Japanese male cadavers in the dissecting room at Kurume University School of Medicine in 1999. In these cases, the usual celiac trunks were not identified, and the hepato-mesenteric and the gastro-splenic trunks were independently arising from the abdominal aorta. Moreover, in the first case, the common hepatic artery passed ventral side of the portal vein and divided into the hepatic proper and the gastroduodenal arteries. This type of arterial anomaly belongs to the Type V of Adachi's classification and the Type IV' of Morita's classification. In the second case, the common hepatic artery passed dorsal side of the portal vein and divided into the hepatic proper and the gastroduodenal arteries. This type of arterial anomaly belongs to the Type VI of Adachi's classification and the Type IV' of Morita's classification.

This report describes an arterial anomaly case in the celiaco-mesenteric region, which was encountered in a Japanese male cadaver in the dissecting room at Kurume University School of Medicine in 1999. In this case, the usual celiac trunk was not identified, and the hepato-spleno-mesenteric and the gastro-phrenic trunks were independently arising from the abdominal aorta. In addition, the common hepatic artery divided into the left hepatic, the right hepatic, and the gastroduodenal arteries simultaneously, then, the accessory gastric artery arose from the left hepatic artery. This type of arteral anomaly belongs to the Type III of Adachi's classification and the Type II of Morita's classification.

We previously reported the chronological appearance of adenohypophysial cells in freshwater teleosts using an immunocytochemical technique. The present study investigated the chronological appearance of adenohypophysial cells in the ayu, which is spawned and has its early development in brackish water, and the results were compared with those obtained in freshwater and seawater teleosts, as well as in other vertebrates. In the adult teleostean adenohypophysis, seven or eight types of secretory cells have been distinguished, each of which produce different hormones: prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), gonadotropic hormones (GTH I and GTH II), adrenocorticotropic hormone (ACTH), melanophore stimulating hormone (MSH) and somatolactin (SL). In the pituitary of adult ayu, seven distinct types of glandular cells (PRL, GH, TSH, GTH, ACTH, MSH and SL cells) were identified. Chronologically, a few immunoreactive (ir)-PRL and ir-GH cells appeared in the ventral side of the pituitary one day before hatching. Then, just after hatching, ir-GTH cells were observed in the central to dorsal portion; ir-ACTH cells were found distributed in the anterior portion and some ir-MSH and a few ir-SL cells were seen in the posterior portion of the pituitary. Finally, a small number of ir-TSH cells were identified 50 days after hatching. These results differed from those obtained in other fishes previously reported with regard to the times of appearance of the PRL and GH cells. PRL cells appeared first, followed by GH cells in the freshwater teleosts, PRL and GH cells appeared at the same time in the brackishwater teleosts, while GH cells appeared first and PRL cells appeared last in the seawater teleosts. These results reflect the fact that PRL plays a major role in osmoregulation among freshwater teleosts, as compared with GH, which plays a similar role in seawater teleosts. It seems that both PRL and GH may play important roles in osmoregulation in brackishwater fish.

This study is based on the dissections of 645 pelvic halves of Japanese cadavers. The branching of the internal iliac artery was classified according to Adachi's classification (1928), and the data was compared with previous reports. Type I was predominant in this, as well as, in previous studies. During the course of the present study, some branching forms were different from the types in Adachi's classification. Therefore, this classification was modified into 5 types and 19 groups. Type I-Group 1 was most frequently observed in the modified Adachi's classification, however, the frequency was less than 50% (46.8%). To clarify the basic branching pattern of the original internal iliac artery and to simplify the classification for medical purposes, a new classification system was designed. The superior gluteal, inferior gluteal and internal pudendal arteries were defined as the major branches of the internal iliac artery, and the umbilical artery was excluded from this group. The branching of the internal iliac artery was classified into 4 groups. Almost 80% of the present specimens were included in Group A of the new classification, namely, the internal iliac artery dividing into two major branches, the superior gluteal artery and the common trunk of the inferior gluteal and internal pudendal arteries. This type of branching seemed to be the basic branching pattern for the original internal iliac artery.

This report describes a rare case of the right-sided aortic arch with the right subclavian artery as the last branch, which was encountered in a Japanese male cadaver in the dissecting room at Kurume University School of Medicine in 1995. In this subject, the ascending aorta arose from the left ventricle and ascended obliquely, curving forward and to the right, and became the right-sided aortic arch. The aortic arch passed upwards, reaching a summit at the level of the third thoracic vertebral body, then curved dorsally. The left brachiocephalic, the right common carotid and the right subclavian arteries came off the aortic arch in that order. After the right subclavian artery, the aortic arch dilated and formed the aortic diverticulum behind the trachea and the esophagus. The right thoracic aorta, a continuation of the aortic arch, descended to the right of the vertebral column. This case is a type M anomaly according to the Adachi-Williams-Nakagawa's classification, and is the twelfth case with this type of vascular variation to be reported in Japan.

Male rats received daily intraperitoneal injections of cadmium sulphate (2.0 mg/kg) for 3 (Cd-3 group), 6 (Cd-6 group) and 8 days (Cd-8 group). The blood samples were prepared for endothelin (ET)-1 assay, and the thoracic aorta was investigated by both electron microscopy and immunoelectron microscopy using anti ET-1 sera. The plasma ET-1 concentrations of both Cd-6 and Cd-8 groups increased significantly in a cumulative dose-dependent manner. The cadmium-treated rat aorta showed an increase in the number of Weibel-Palade (WP) bodies in endothelial cells, and degranulation and exocytosis of WP bodies occurred exclusively in the Cd-8 group. Immunoreaction for ET-1 was localized preferentially in WP bodies of both cadmium-treated and control groups, and in the rough endoplasmic reticulum of the cadmium-treated groups only. Reactivity was also found on the WP bodies undergoing exocytosis in the Cd-8 group. Cadmium intoxication induces an increase in number of ET-1-storing WP bodies in the rat aorta endothelium. The enhancement of extracellular release of their contents by exocytosis results in elevation of the plasma ET-1 concentration.

The neovascularization of the rabbit phallus at ages between prenatal days 15 and 21 was investigated by light- and electron microscopy, computer-aided light microscopic reconstruction, and immunocytochemistry. The phalli are embedded by an abundance of mesenchymal cells, which are in contact with the neighboring ones or with the endothelial lining of growing capillaries. They often form solid cell cords that eventually make contact with the growing capillaries. The computer-aided reconstruction of the serial light micrographs reveals that these cell cords are involved in connecting the adjacent capillaries. The incorporation of such mesenchymal cell projections into the endothelial lining, occasionally conjugated with simple attachment devices, is frequently observed by transmission and scanning electron microscopy. The contact areas between the mesenchymal and endothelial cells show immunoreactions of fibronectin. These results indicate the successive transformation of mesenchymal cells to endothelial cells of the growing capillaries. As endothelial cells of the growing capillaries show mitotic proliferation, such vasoformative mesenchymal cells seem to be involved in the acceleration of the neocapillarization of the rabbit phallus. Fibronectin actively produced in the mesenchymal cells may participate in their migration and the mechanical linkage with the endothelial cells.

The toxic effects of cadmium on the thyroid gland of pregnant rats were studied with an electron microscope and an X-ray microanalyzer. Serum levels of thyroid hormones (T3 and T4) were also analyzed. Deterioration of the rough-surfaced endoplasmic reticulum occurred in the thyroid follicular epithelium on the fifth day of cadmium treatment. Large intracellular vacuoles, which arose from dilated cisternae of the rough-surfaced endoplasmic reticulum, were fused together, and marked swelling of the mitochondria was also noted. Thyroglobulin-secreting granules at the apical cytoplasm were decreased in number. By energy dispersive X-ray microanalysis, cadmium peaks were preferentially obtained from swollen mitochondria in the follicular epithelial cells. Serum levels of T3 and T4 were significantly decreased in cadmium-treated rats dams when compared to those of controls. In the present experiment, cycloheximide also caused degenerative changes in the rough-surfaced endoplasmic reticulum and the disappearance of thyroglobulin-secreting granules. Cycloheximide is a known inhibitor of protein synthesis on cytosolic ribosomes. These results indicated that accumulated cadmium in the mitochondria of thyroid follicular epithelial cells might disturb the oxidative phosphorylation of this organelle and the loss of energy supply possibly caused the inhibition of the synthesis and release of thyroid hormones.

Corneal edema induced by bis (tributyltin) oxide (TBTO) was studied with an electron microscope and the accumulation sites of tin were determined with an X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg TBTO. After time intervals of 2, 4, 6, 8, 10, 12 h after injection, corneas were isolated and provided for electron microscopy. Corneas from untreated rats served as controls. Marked swelling of mitochondria in the corneal endothelial cells occurred at 4 h after TBTO injection. The corneal edema appeared in the endothelial layer and the stroma at 6 h after injection. By X-ray microanalysis, Sn peaks were obtained from swollen mitochondria in the endothelial cells. At 12 h after TBTO injection, edematous swelling of the corneal tissue became more advanced. These results indicated that parenterally administered TBTO accumulated in the mitochondria of corneal endothelial cells. The direct toxic effects of TBTO on the mitochondria might cause the interference with active pump function of endothelial cells and induced the corneal edema.

The luminal, fractured, and basal surfaces of the duct and acini in the rat Harderian gland were examined by scanning electron microscopy. The acinar endpiece is alveolar in shape and bifurcated, and the duct is also bifurcated. Therefore, the rat Harderian gland may be morphologically classified as a compound alveolar gland. Myoepithelial cells consisting of elongated cell bodies and long, bifurcating processes grasp the acinus in the form of a dilicate network. In the fractured surface, the glandular cells of the acinus are columnar in shape. A round nucleus is situated in the basal portion of the cytoplasm and a large number of secretory vacuoles are observed throughout the cytoplasm. The luminal surface of the glandular cell presents a bulged appernce, polygonal in shape, with short, randomly distributed microvilli. Domed protrusions and round pits are observed on the glandular surface. The excretory duct appears as a main trunk with numerous short branches. In the fractured surface, the excretory duct consisted of stratified coumnar or cuboidal cells. The luminal surface of the duct epithelial cell appears flat, polygonal in shape, and is provided with short microvilli rondomly distributed over the body of the cell.

The wound healing of the rabbit colonic mucosa after experimental excision was observed with the electron microscope. Between 5 and 7 days, considerable numbers of undifferentiated mesenchymal cells (group I), differentiating muscle cells (group II) and histiocyte-like cells (group III) appear in the regions where the muscularis mucosae is re-establishing. Our electron micrographs indicate that group I cells are stem cells which differentiate to group II cells involved in muscle regeneration or to group III cells involved in phagocytosis. The mitotic proliferation of pre-existing smooth-muscle cells at the ulcer margin does not seem to be the major reason for the re-establishment of the muscular layer. Multinucleated cells occurring in this healing mucosa are considered to be formed by successive fusions between the group III cells and to play a role in enclosure of cell debris such as fragments of elastin.

In the late prenatal stage, the rabbit corpora cavernosa penis (cavernous bodies) are occupied by a large number of mesenchymal cells actively proliferating by mitosis. Most profiles of the cavernous sinuses show growing capillaries consisting of immature endothelial cells and enclosing a narrow lumen. Such growing capillaries are often associated with the mesenchymal cells that contact with each other and eventually with the endothelial cells. Between 1 and 7 postnatal days, the capillary network develops extensively and the maturation of the capillaries results in a flattened endothelium with a continuous basal lamina. The mesenchymal cells are also associated with the helicine arterial sprouts at this time period. No endothelial mitotic figures were observed within the growing capillaries in pre- and postnatal specimens examined. Single pulse labeling with 3H-thymidine in the postnatal rabbits demonstrates that the labeled endothelial cells of the growing capillaries increase in number at 48 hours after injection compared with those at 24 hours, whereas the labeled mesenchymal cells inversely decrease in number. These findings indicate that the incorporation of the mesenchymal cells as vesselforming cells into the growing capillaries accelerates the neovascularization in the rabbit cavernous bodies.

Dynamic changes of rat corneal epithelium and stroma after alkali burning were observed with the electron microscope. The neovascularization process in the stroma was almost the same as that observed after burning by heat. Reversible changes of the epithelial cells occurred throughout the course of wound healing. Approximately 10 days after burning, cells in deeper layers of the epithelium showed temporary changes such as increased in number of mitochondria and formation of lamellar cytoplasmic infoldings. These changes gradually disappeared while the reconstruction of regular arrangement of the collagen lamellae in the stroma was established. As it is widely accepted that such iofoldings play a role in active transport, dynamic changes of the epithelial cells in the present study indicate that reabsorption of the corneal edema is accomplished by both the corneal endothelium and the corneal epithelium.

Fetal rabbit skin between 10 and 26 days of gestation was observed by light and electron microscopy. The present study indicates that rapid epidermal differentiation, including the epidermal downgrowths as primordia of the hair follicles, is induced by aggregation of mesenchymal cells associated with growing capillaries beneath the epidermis. In addition, the transformation of these mesenchymal cells to vasoformative cells for rapid capillary growth is further evidenced by this study. Glycogen-storing cells in the periderm are most numerous between 15 and 18 days of gestation, but disappear almost completely by 20 days when a capillary network develops beneath the epidermis.This may imply an active involvement of the periderm in glucose uptake from the amniotic fluid during early developmental stages of the skin.

The traumatic cataract was experimentally induced in the lens of a Japanese monkey and observed with the electron microscope. The purpose of this study was to shed some light on the origin of the cataract caused by various factors. The clinical examinations of the experimental animal showed the opacity of the posterior subcapsular cortex. Electronmicroscopic investigations revealed that lens fibers within the opaque region increased in number of mitochondrion, rough surfaced endoplasmic reticulum and other organelles when compared with those in the clinically normal region of the lens. Furthermore, the intercellular space in the opaque region increased to such an extent that large extracellular vacuoles were formed. Many of these lens fibers became swollen and decreased the interdigitation. Some swollen cells showed sparse arrangement of their cytoplasmic filaments. These morphological changes showed an acceleration of water absorption of the lens fibers from a relatively early stage of the traumatic contusion cataract. The increase in number of mitochondrion in such swollen (hydropic) fibers may play an important role in this process. The present experiment suggests that the appearance of so-called hydropic cells is an initial change in the cataractous lens.

The organ of Corti in human fetuses aged 5 and 7 months, respectively, was observed with the scanning and transmission electron microscope (SEM and TEM). By SEM observation, bulbous cytoplasmic structures protruding from the apical surface of the outer and inner hair cells were observed as was the case in SEM reports by others. By TEM observation, it was revealed that these structures are cytoplasmic projections from the so-called cuticular notch which, in adults, houses the basal body and is a site for synthesis of auditory stereocilia and a single kinocilium. The stria vascularis was examined only in the 5 month specimen. The cytoplasm of the differentiating marginal cells is characterized by the presence of thick walled tubular membranes. The observation suggests that this tubular system may represent "a particular site" for secretion of some ions into the endolymph in the fetal condition.

Schlemm's canal (Sinus venous sclerae) of human fetuses and postnatal monkeys (Macaca fuscata) were observed with the light and electron microscope.Between the 21st and 24th week of gestation of the fetuses, many branches of Schlemm's vascular plexus at the sclerocorneal junction, which is immatured form of Schlemm's canal, were connected to each other by young fibroblasts invading from the surrounding connective tissue. Our observations indicate that the main pathway of aqueous humor across endothelium of the canal is converted from “intercellular” into “intracellular” (transported by vacuoles and pores) in these stages.In the postnatal monkeys, large vacuoles were observed in the differentiating endothelium at the inner wall of the canal. Our electron micrographs indicate that these vacuoles are formed by a successive fusion of adjacent pinocytotic vesicles in the endothelial cells and take an important role for aqueous humor transport.

A remarkable increase in number of endothelial specific granules was observed in the rabbit umbilical veins between 2 and 5 days after birth. Electron microscopy indicated that the granules were segregated in the Golgi complex of the endothelial cells and released into the vascular lumen during the postnatal obliteration stage of this vessel. Incubation of the postnatal vessels in Ringer solution containing a histamine-releasing compound induced remarkable morphological alterations of these cytoplasmic components; a reduction of their osmiophilia, swelling with a widened space separating the granular matrix from the limiting membrane, fusion to each other and expulsion of their contents into the vascular lumen, as in mast cell degranulation by this drug, were noted. High-performance liquid chromatography of the homogenized vessels demonstrated appreciable concentrations of histamine in the postnatal samples. There was a correlation between the histamine concentration and the quantity of granules in the respective postnatal samples. The present study strongly suggests that the granules are reservoirs of histamine and have an important role in the obliteration of this vessel.

The corneal neovascularization was observed in adult rats after the application of heat. The new capillaries are formed in associated with the tips of the limbal vessels by transformation of young f ibroblasts to endothelial cells. The present observations have no inconsistencies with the previous hypothesis that the corneal edema is a “necessary condition” for the neovascularization. However, the study indicates that aggregation of abundant young f ibroblasts in the limbal region by mesenchymal reaction is “also necessary” for the neovascularization. New capillaries in the corneal stroma are sinusoidal type similar in structure to hepatic capillaries. Free passage of blood cells and plasma across the wall is frequent. Significance of mast cells for the corneal neovascularization was discus-sed. They may play a role for the venous edema as well as the connective tissue remodelling.