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Biomedical subjects

I Narama

Publications and source records attributed to I Narama.

At least 37 records · Page 2Linked to original sources

Glomus tumor in a dog.

A mass of glomus tumor was found on the skin of the right foreleg of a ten-year old male mongrel dog. Histologically the mass contained some vasculatures and sheet-like proliferation of epithelioid tumor cells. Some blood vessels were rimmed by the tumor cells, which had a round to ovoid nucleus and plump eosinophilic cytoplasm. Immunohistochemically, smooth muscle actin and vimentin were demonstrated in the tumor cells. By electron microscopic examination, actin-like filaments with dense bodies were observed in the cytoplasm of the tumor cells. This is the first case report of a canine glomus tumor.

Actins↗

Degenerative axonal swellings in the trigeminal ganglia of cattle.

We examined the acidophilic oval structures which were frequently encountered in the trigeminal ganglia of cattle that clinically showed trigeminal disturbance. Histopathologically, these structures were composed of numerous fine granules and were generally located near the neuronal cell bodies. They were demonstrated in silver preparations and, using neuron-specific enolase, tau and ubiquitin antibodies. Electron microscopy revealed an accumulation of large membranous vesicles thought to be derived from the smooth endoplasmic reticulum of axons, a few degenerative mitochondria and non-membrane-bound osmiophilic debris. Such pathological alterations were consistent with degenerative axonal changes or enlargements, although the pathogenesis was not clear. It should be emphasized that such axonal degeneration is frequently observed as a nonspecific reaction in the trigeminal ganglia in various diseases that cause trigeminal failure in cattle.

Animals↗

Peripheral neuropathy in the spontaneously diabetic WBN/Kob rat.

We report that the morphological characteristics of the peripheral 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.

Animals↗

Non-functional pituitary chromophobe adenoma in a calf.

A 5-month-old male calf showed neurological signs, including circling, in-co-ordination, depression, blindness and eventual recumbency. On necropsy, a mass measuring 3.5 x 4.5 x 5 cm was found at the base of the brain, at the level of the pituitary gland. The hypothalamus and optic nerves were compressed by the dorsally expanding mass. Non-functional pituitary chromophobe adenoma was diagnosed from histochemical, immunohistochemical and electron microscopical findings.

Adenoma, Chromophobe↗

Transformation of grayanotoxin III to 10-epi-grayanotoxin III. Its X-ray crystallographic analysis and acute toxicity in mice.

Grayanotoxin (GTX) III, a tetracyclic diterpenoid, is the main toxic component obtained from the leaves of Leucothoe grayana MAX. In this paper, we report the correlation between toxicity and C10 stereostructure of GTX-III. 10-epi-GTX-III was derived from GTX-III in four steps. Oxidation of the GTX-II-3,6,14,16-tetraacetate with formic acid/hydrogen peroxide in chloroform gave 10,20-epoxy derivation in high yield. Reduction of the 10,20-epoxyacetate with LiAlH4 in tetrahydrofuran gave the two products, 10-epi-GTX-III and 10,20-epoxy-GTX-II. The absolute structure of the 10-epi-GTX-III was deduced from the results of X-ray crystallographic analysis. Dosage level of acute toxicity of 10-epi-GTX-III in mice was estimated at about half of natural GTX-III.

Animals↗

Morphogenesis of degenerative changes predisposing dogs to rupture of the cranial cruciate ligament.

The cranial cruciate ligaments (CCL) of 13 dogs with clinical signs of CCL rupture and those of 22 clinically healthy young beagle dogs for laboratory use were examined histopathologically and immunohistopathologically. The most constant changes at an early stage of degenerating ligament tissue in affected dogs were nuclear enlargement and perinuclear halo formation of fibrocytes followed by chondroid metaplasia. These changes were also frequent in apparently healthy young beagles kept under laboratory conditions. PAS and alcian blue positive substance accumulated around activated fibrocytes and within perinuclear halos. S-100 protein was also positive in these cells preceding the morphological change of chondroid metaplasia. Increased mitotic figures and Ki-67 positive cells showed the proliferating nature of these cells at a later stage. Alteration of extracellular matrices from dense collagen fiber type to those of cartilage tissue seemed to predispose dogs to rupture of the CCL along with a degradation in collagen fiber of the primary bundles. Collagen fiber bundles with a parallel fibrillar array never formed in the CCL with degraded primary bundles, whereas activated fibrocytes constantly underwent chondroid metaplasia. The pathogenic mechanism underlying chondroid metaplasia was thought to be nonspecific and attributable to an essential property of activated fibrocytes in the mature tendon tissue.

Animals↗

Mitochondrial abnormalities of muscle tissue in mice with juvenile visceral steatosis associated with systemic carnitine deficiency.

A mouse with juvenile visceral steatosis (the JVS mouse) has been recognized as a novel animal model for systemic carnitine deficiency. We examined cardiac, skeletal and smooth muscle cells in JVS and control mice by light and electron microscopy. Cardiac and skeletal muscle cells of these mice at 4 weeks of age exhibited a ragged-red appearance after trichrome staining. Electron microscopy, demonstrated increased numbers of mitochondria and lipid droplets in the cells. Compression or distortion of the myofibril bundles, primarily due to the increased number of mitochondria, suggests the possible existence of a functional disturbance of the cardiac and skeletal muscle. In the urinary bladder, only one or two large lipid droplets and slightly increased number of mitochondria were recognized in the perinuclear region of the smooth muscle cells. At 8 weeks of age, the mouse enzyme histochemistry specific for mitochondria, such as cytochrome c oxidase and succinic dehydrogenase, and oil red O staining, confirmed further increases in the number of mitochondria and lipid droplets in the heart. However, the accumulation of these organelles in the skeletal and smooth muscle cells was no greater than that noted in JVS mice at 4 weeks of age. In the cardiac muscle cells, autolysosomes or autophagic vacuoles containing electron-dense membranous, lamellar or whorled structures closely associated with mitochondria and pseudoinclusion bodies in the nucleus were recognized, and bundles of myofibrils were buried under numerous mitochondria, suggesting the existence of disturbed contractile function in the heart of JVS mice. These results indicate that this murine strain associated with systemic carnitine deficiency exhibits a generalized mitochondrial abnormality in the muscle system especially in the heart.

Animals↗

Enhancement of tumor growth under short light/dark cycle in mouse lung.

We examined whether a change in daily light/dark cycle affected DNA synthesis and tumor growth in mouse lung. Both CD-1 and A/J mice, which were treated with urethane and maintained under the short light/dark cycle (6 h light, 6 h dark), developed significantly larger sizes of lung tumors than the mice maintained under the standard light/dark cycle (12 h light, 12 h dark), indicating that short and frequent light/dark cycles enhanced tumor growth. When 3H-labeled thymidine was injected and incorporated radioactivity in the lung tissue was measured, two peaks of DNA synthesis in the lung were observed in a day under the short light/dark cycle, and both peaks were during light periods, while only one peak was observed during the dark period under the standard light/dark cycle. Although the level of [3H]thymidine incorporation into the lung tissue in the short light/dark cycle is lower than that in the standard cycle, frequent or unbalanced DNA synthesis may have promoted the growth of lung tumors.

Adenoma↗

The presence of giant granules in the juxtaglomerular cells of beige rats may affect plasma renin activity and blood pressure.

Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder, characterized histopathologically by giant granules in various cells. Since little is known about the juxtaglomerular (JG) cells of CHS, the present study was undertaken as a morphological investigation of the JG cell of Beige rats, which were found to be a new animal model of CHS. In addition, we measured the blood pressure and plasma renin activity. The blood pressure of Beige rats is similar to that of DA rats, the mother strain of Beige rats. However, the plasma renin activity of Beige rats increases with age, whereas that of DA rats decreases. Morphologically, JG cells of Beige rats gave no evidence of hyperplasia and hypertrophy. The most conspicuous change was a small number of giant JG granules. Ultrastructurally, JG granules of Beige rats were large, irregular, and varied in size at 2 months of age, but no age-dependent changes were detected. These results suggested that giant JG granule formation slightly increases renin release with age, but does not affect blood pressure.

Animals↗

Histological and topographical characteristics of canine granulomatous leptomeningitis.

Histological and topographical characteristics of granulomatous leptomeningitis were studied in 14 laboratory beagle dogs (12 males, two females), 8 to 19 months old. The dogs, which were either saline-treated controls or drug-treated animals in four different toxicity studies, remained clinically normal during the experimental period, and granulomatous leptomeningitis was identified as an incidental finding by routine histopathological examination. There were no macroscopical lesions in the brain or other organs. Microscopical lesions of the central nervous system were of three types, namely (1) a diffuse inflammatory type, characterized by diffuse infiltration of macrophages, (2) a granulomatous type, characterized by non-caseating granulomas, or (3) a fibrotic type, featuring dense connective tissue. Each of the 14 cases fell into one of three disease phases, early, fulminating and healing. In the early phase, only diffuse inflammatory-type lesions were seen. In the fulminating phase, all three types of lesion were present. In the healing phase, discrete granulomas were relatively few and fibrosis was prominent.

Animals↗

Chediak-Higashi syndrome in rats: light and electron microscopical characterization of abnormal granules in beige rats.

Chediak-Higashi syndrome (CHS) is a rare disease occurring in several animal species. Recently, mutant beige rats with CHS were found among DA strain rats in Japan. In the present study, histological examination of beige rats revealed giant granules in the hepatocytes, renal proximal tubules, submandibular ducts, thyroid follicular cells, granulocytes, mast cells, melanocytes, retinal pigment epithelial cells and globular leucocytes. Ultrastructurally, these granules varied from enlarged lysosomes, which were amorphous, granular or filamentous, to giant mast cell granules, crystalloid granules of eosinophils and slightly enlarged neutrophil granules. These findings bore many similarities to those in the beige mouse, which is a well known animal model for CHS, but some differences were apparent. Thus the giant granules of beige rats were larger and more easy to observe than those in beige mice. The study indicated that the beige rat may prove useful as an animal model for CHS.

Acid Phosphatase↗

Distemper skin lesions in a dog.

Skin lesions were studied in a 3-year-old male Maltese dog with distemper. Hyperkeratosis and parakeratosis with vesicles and pustule formation were the outstanding features of the skin lesions around the eye, nose, and mouth. Multinucleated syncytial giant cells together with nuclear and cytoplasmic inclusion bodies containing viral particles and viral antigen were scattered in the epidermis, and epidermal appendages. These findings suggest a direct viral attack on the skin.

Animals↗

Corneal dermoid in two laboratory beagle dogs.

Two male laboratory beagle dogs used in toxicity studies, one 7 months old and the other 9 months old, showed the evidence of corneal dermoid. Grossly, the dermoid was observed in both cases as hair growth from the cornea. In one case, the hairs had been removed from the cornea, but regrowth was observed about 70 days later. Histopathologically, melanocytes, melanin granules, hairs, hair bulbs, adipose tissue and sebaceous and sweat glands were observed in the corneal epithelium and propria. According to the information obtained from 4 breeders, the incidence of corneal dermoid was extremely rare in laboratory beagle dogs.

Animals↗

Cutaneous papillomatosis associated with papillomavirus infection in a dog.

A 7-year-old female Kerry blue terrier dog developed 20 cutaneous nodules, up to 4 mm in diameter, over the body. Light and electron microscopy demonstrated that they were virus-associated inverted papillomas and they are described because canine skin viral papillomas have not been frequently reported.

Animals↗

Hodgkin's-like lymphoma in a dog.

This is the first reported case of canine Hodgkin's-like lymphoma in Japan. Tumor growth involved the lymph nodes and multiple visceral organs. Histopathological examination revealed that the tumor consisted of a large number of typical Reed-Sternberg cells with symmetrically arranged nuclei, the so-called "mirror-image" cells, intermingled with various numbers of inflammatory cells and globule leucocytes.

Animals↗

Bone lesions of multiple myeloma in three dogs.

Three cases of canine multiple myeloma that showed monoclonal IgA gammopathy and bone lesions were examined. One dog was associated with Bence-Jones proteinuria as well. Radiographic examination revealed extensive skeletal involvement of flat bones such as scapula, pelvic bone, costa, and epiphysis of long bones where the hematopoiesis was active throughout the life. Histopathologically, small osteolytic lesions occurred from periosteum and Haversian canal as well as endosteum, and larger lesions were formed by gradual expansion or fusion of small lesions. Osteolytic lesions did not necessarily involve tumor growth, explaining the inconsistent confirmation of tumor cells in biopsy specimens for diagnosis of multiple myeloma and suggesting the possible mechanism for osteolysis by some other humoral factors.

Animals↗

Granulomatous leptomeningitis in beagle dogs.

A granulomatous leptomeningitis was seen in seven laboratory Beagle dogs (four males, three females), 14 to 15 months old, that had been used as control or experimental subjects in a toxicologic study. The dogs were clinically normal during the experimental period. Microscopic lesions were characterized by typical noncaseating granulomas in leptomeninges and slight scattered perivascular cuffing in gray and white matter throughout the central nervous system, with no site of predilection. Although no microorganisms could be found by ordinary light microscopic examination, there was a positive reaction for Escherichia coli antigen in the cytoplasm of macrophages, which corresponded to periodic acid-Schiff-positive, calcium-negative, and iron-negative materials in the granulomas and cuffs. Electron microscopic examination revealed that these materials were large phagolysosomes indicative of abnormal lysosomal function. These findings indicate that at least some cases of canine granulomatous leptomeningitis could be very likely caused by E. coli and represent an entity distinct from classical canine granulomatous meningoencephalitis.

Animals↗

[Teratological study of trandolapril (RU44570) in rats].

A teratogenicity study was performed in Sprague-Dawley rats treated orally with trandolapril (RU44570) at the dosage levels of 3, 30 and 300 mg/kg/day from day 7 to day 17 of pregnancy. In each group, 24 or 25 female rats were sacrificed on day 20 of pregnancy for the examination of their fetuses, and 14 or 15 female rats were allowed to litter naturally for the postnatal examination of their offspring. Clinical symptoms and mortality attributable to administration of RU44570 were not observed in the dams (P). Body weight gain and food consumption were slightly depressed in the 300 mg/kg dosage group comparing with those of control group. However, RU44570 showed no adverse effect on the fetal mortality, prenatal development or teratogenicity of the fetuses. Incidence of dilatation of renal pelvis was slightly increased in fetuses in the 300 mg/kg dosage group comparing with that of the control group. However, the offspring in each treated group showed similar incidence of this abnormality to that of the control group in more advanced age. Therefore, these changes were considered to be reversible. No adverse effects on the postnatal development of the offspring containing reproductive ability were detected. The results suggest that non-effective dose level of RU44570 is 30 mg/kg for dams, 30 mg/kg for fetuses and 300 mg/kg for development in offspring, respectively.

Abnormalities, Drug-Induced↗