Minoru Tsuchitani

A new diabetic strain of rat (WBN/Kob):

A new, spontaneously occurring diabetic syndrome has been observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. The main clinical sign, glycosuria, was first detected at about 60 weeks of age, and thereafter some animals developed hyperlipidaemia and gradual emaciation. Prior to the onset of glucosuria, male rats showed impaired glucose tolerance after a glucose load at 21 weeks of age. The histopathologic lesions of the pancreas in the diabetic males consisted of multifocal fibrosis, decrease in number and size of islets and atrophy of exocrine tissue. Multifocal inflammatory foci of varying stages were the main pancreatic lesion in prediabetic male rats. This inflammatory change was detected even in 12-week-old rats and tended to occur around the islets. Therefore focal fibrosis and the decrease in the number and size of islets were considered to result from post-inflammatory scarring. The maturity-onset of this syndrome and the impaired glucose tolerance in younger animals suggested that diabetes mellitus of this rat strain is insulin-independent type II. However, the histological lesions of the pancreas were somewhat different from previous reports of both type I and II diabetes mellitus in man and animals.

CARCINOGENICITY TEST OF 50 HZ SINUSOIDAL MAGNETIC FIELDS IN RATS

Male and female F344 rats, 48 per exposure group, were sham exposed (Group A) or exposed to 0.5 (Group B) and 5 mT (Group C) magnetic fields for two years. Animals were exposed from 5-109 weeks of age in SPF conditions according to the OECD test guideline No. 451. Average exposure was 22.6 hr/day. No significant differences in body weight and food consumption were observed between the sham and exposed groups. At the end of the exposure period, survival rates of the male rats were 73, 83, and 79%, and those of the females, 77, 79, and 75% for Groups A, B, and C, respectively, with no significant differences between groups. Differential counts of leukocytes were measured at the 52nd, 78th, and 104th weeks of exposure and no significant differences were observed between the exposure groups. All survivors were euthanized on schedule, and all the organs and tissues suspected of tumoral lesions were examined histopathologically. Incidences of mononuclear cell leukemia in the male and the female rats were 5, 4, 4 and 8, 6, 7 for Groups A, B and C, respectively; incidences of malignant lymphoma in the female rats were 0, 1 and 1. Neither significant increases nor acceleration of incidence of leukemia were observed. Incidences of brain and intracranial tumors did not increase in the exposed groups. Incidences of both benign and malignant neoplasms showed no significant difference between the exposed and sham exposed groups with one exception: fibroma of the subcutis in the male rats, which was considered not to be a statistically significant when evaluated with respect to the historical control data in our laboratory.

Histopathology of Incidental Findings in Beagles Used in Toxicity Studies

The purpose of our publication is to widely communicate the pictures of spontaneous findings occurring in beagles. Spontaneous arteritis occurs commonly in beagles. Frequent sites of arteritis are the heart, spleen, pancreas, epididymis and spinal cord. Morphological similarities between spontaneous and drug-induced arterial lesions may cause confusion when evaluating vascular toxicity of chemicals such as vasodilating agents. Focal and minimal inflammatory lesions are occasionally seen in the lung and may be associated with aspiration of food particles or of unknown causes. A cystic change with copious mucin production occurs occasionally in the mucosal epithelium of the gall bladder. Nesidioblastosis is seen rarely in the pancreas of beagles. C-cell complex and lymphocytic thyroiditis are common thyroid lesions. Spontaneous focal hypospermatogenesis and lobular Sertoli-cell-only seminiferous tubules occurring frequently in beagles must be distinguished from drug-induced damage of the seminiferous tubules in toxicity studies. The morphological differences of the female genital system in each cycle need to be understood; therefore, we present the normal features of the cyclic changes of the female genital organs. Further, we provide more information on spontaneous findings in beagles for exact diagnoses in toxicity studies.

Histopathology of Incidental Findings in Cynomolgus Monkeys (Macaca Fascicularis) Used in Toxicity Studies

The purpose of our publication is to widely communicate pictures of spontaneous findings occurring in cynomolgus monkeys. Focal lymphoplasmacytic infiltration is commonly seen in the general organs. The frequency and severity of these lesions may be influenced by the administration of drugs with an effect on the immune system. Lymphoplasmacytic infiltration in the lamina propria of the stomach is also frequently seen in cynomolgus monkeys, and it is caused mainly by a Helicobacter pylori infection. Various degrees of brown pigments are observed in various organs, and it is possible to distinguish the material of the pigments by its morphological features and site. A focal/segmental glomerular lesion is occasionally seen in a section of the kidney, and the minimal lesion has no influence on the urinalysis. We showed the common glomerular lesions in HE-stained sections, as well as in PAM- or PAS-stained sections, for understanding the details. Young and pubertal monkeys are usually used in toxicity studies; therefore, understanding various maturation stages of the genital system is important. In particular, the female genital system needs to be understood in the morphology, because their cyclic changes are different from other laboratory animals. Thus, we present the normal features of the cyclic changes of the female genital organs. Furthermore, we provide more information on spontaneous findings in cynomolgus monkeys for exact diagnoses in toxicity studies.

Peripheral neuropathy in the spontaneously diabetic WBN/Kob rat

Abstract We report that the morphological characteristics of the periperhal neuropathy in WBN/Kob rat, a diabetic animal model that develops persistent diabetes, were primary segmental demyelination and secondary axonal degeneration. These findings are similar to those in human patients with diabetes mellitus and unlike those in rodents with streptozotosin-induced diabetes. However, these changes were also indistinguishable from those of age-dependent neuropathy. In the spontaneous peripheral motor neuropathy of rats, pressure neuropathy from housing in wire-mesh cages has also been reported to be indistinguishable from the peripheral neuropathy in plantar nerve or tibial nerve. Therefore, we examined phrenic nerves that were free from the pressure of body weight in rats and described the changes with light and electron microscopy. The morphological changes of the nerve fibers consisted of myelin blebbing or distention, and early remyelination. The changes were seen with age. On morphometric analysis, a marked reduction of fiber occupancy was observed in WBN/Kob rats over 23 months old. The present study demonstrated that the peripheral neuropathy of WBN/Kob rats is myelinopathy. Since the phrenic nerve was not affected by pressure neuropathy anatomically, this study indicates that the peripheral neuropathy of WBN/Kob rats is not pressure neuropathy.

Glycogen accumulation in the renal tubular cells of spontaneously occurring diabetic WBN/Kob rats

Cytoplasmic and nuclear accumulation of glycogen granules in the kidney cells of 72 male WBN/Kob rats with a long-term diabetic condition was studied histologically and by electron microscopy. The incidence and degree of the accumulation showed good correlation with the blood glucose concentration. In the kidneys, there was evidence of two types of lesion, cytoplasmic glycogen accumulation in the distal convoluted tubules and nuclear accumulation in the ascending thick segment of Henles loops. Electron microscopically, the cytoplasmic glycogen accumulation was often associated with an increased number of lysosomal bodies containing lamellar bodies. Glycogen bodies, the halo of which was thought to be identical with that of nuclear bodies, were frequently observed in the nuclei containing the glycogen granules. These morphological and topographical differences between the two types of lesion were considered suggestive of different pathogenetic mechanisms for glycogen accumulation in the kidney cells.

A Novel Immunohistochemical Marker of Normal and Neoplastic Melanocytes in Formalin-fixed, Paraffin-embedded Tissues of Albino Rats

In albino rats, spontaneous occurrence of melanocytic tumors is rare, with diagnosis difficult. This study evaluated immunoreactivity for PNL2 in normal and neoplastic melanocytes in formalin-fixed and paraffin-embedded tissues of albino rats. The samples consisted of 11 (1.57%) amelanotic melanomas in 700 rats (2 studies), 23 non-melanocytic tumors, and a wide variety of normal tissues. In normal albino rats, PNL2 stained the melanocytes in the iris and choroid of the eyeball and the hair bulb and basal cell layers of the epidermis of the whole body. In amelanotic melanoma, the tumor cells consisted of spindle cells with eosinophilic cytoplasm without melanin granules. PNL2 consistently stained cytoplasm in all amelanotic melanoma cells. In contrast, the nonmelanocytic tumor cells were not labeled. Electron microscopically, neoplastic, and normal melanocytes showed numerous cytoplasmic premelanosomes (stage II melanosome). In conclusion, PNL2 is direct against a fixative-and decalcific-resistant melanocyte-associated antigen, and has high specificity against normal and neoplastic melanocytes of albino rats.

Cadmium-Induced Dental Lesions in Ovariectomized Rats

The effects of cadmium chloride on both incisor and molar teeth of ovariectomized female rats were studied histopathologically. The rats were injected intravenously with the compound at doses of 1.0 and 2.0 mg/kg, 5 days/wk. Six rats per group were sacrificed at 4, 8, and 13 wk. Discoloration of the incisors was observed in the rats of the 2.0-mg/kg group from 8 wk. Histopathologic examination of the incisor demonstrated decreased iron-containing pigment in ameloblasts and destruction of the enamel organ. These changes were accompanied with accumulation of cadmium and loss of iron in the teeth. Necrosis of the dental pulp occurred from the coronal end of both the incisor and molar teeth extended to the apical, deep portion of the teeth. The dental pulp of the molar teeth, which is shorter than that of the incisor, was mildly affected by cadmium intoxication. These findings suggested that intradental ischemia due to cadmium toxicity may have contributed to the development of the pulpal necrosis.

The morphogenesis of a papillomatous gastric polyp in the crab-eating monkey (Macaca fascicularis)

The histopathology of gastric papillomas in 17 crab-eating monkeys from Indonesia and Malaysia was investigated. The changes in the affected mucosa consisted of papillomatous proliferation with accidental heterotopia, desquamation or necrosis of the epithelium associated with eggs or adults of the small nematode Nochtia nochti, inflammatory cell infiltration and haemorrhage or oedema and fibrosis. The primary pathogenic effect of this parasite was due to its irritant action on the gastric mucosa. Hyper-regeneration, with a downward shift of the proliferating zone in the gastric gland and an inflammatory process, appeared to play a significant role in the morphogenesis of this lesion. It is concluded that the gastric papilloma associated with Nochtia nochti in the monkey is a parasitic inflammatory polyp.

Eosinophilic Substance is ''Not Amyloid'' in the Mouse Nasal Septum

An eosinophilic substance (ES) is usually observed in the mouse nasal septum and increases in volume with aging. It has been described as amyloid in textbooks and one report. However, it has been described as “not amyloid” in other reports because there was a negative reaction to Congo red. In this study, the ES was investigated histopathologically and electron microscopically to determine whether it was amyloid or not. The ES was only observed at the interstitium of clear HE-stained nasal glands in the septum, in which 2 kinds of glands were present (dark and clear stained by HE). The volume of the ES was small in young mice and large in older ones. Neither nasal gland degeneration nor inflammation resulted, even if a large amount of the ES was observed. The ES reacted negatively to Congo red but was strongly positive to periodic acid–Schiff reaction with prior diastase treatment. In the electron microscope observation, the ES consisted of amorphous material and collagen, but no nonbranching fibrils. Similar amorphous material was also observed in the nasal gland epithelial cells and was connected to the material in the rough endoplasmic reticulum. The above-mentioned findings indicated that the ES was not amyloid and suggested the ES might consist of not only collagen but also complex carbohydrate, which was produced by the nasal gland epithelial cells.