Genshiro Ide

Effects of bis (tri-n-butyltin) oxide on endocrine and lymphoid organs of male rats.

A total of 160 Sprague‐Dawley rats averaging in body weight, were used for hlstopathological and biochemical studies of toxicity of bis (tri‐n‐butyltin) oxide (TBTO). Short‐term effects and long‐term effects were examined. LD50 of TBTO by gastric tubing was 197 mg/kg. The effects of a single dose of TBTO were transient, and rapid recovery followed. TBTO at a a single dose of 100 mg/kg, or a total dose of 390 to 780 mg/kg In 13 weeks, or 780 to 1,560 mg/kg in 26 weeks, caused adrenal hypertrophy, flattening of the thyroid epithelium and atrophy of the thymus and lymph nodes. A single or repeated administration induced swelling and vacuolatlon of aldehyde‐fuchsin‐posltive cells in the adenohypophysls. The lmmunohistochemlcal stainability of the cytoplasm of ACTH‐cells was markedly depressed 24 hours after TBTO treatment, and that of the cytoplasm of TSH‐cells was enhanced. Analogous an inverse relationship was also manifested in the hormonal levels of serum: levels of Cortisol were elevated, while those of T‐4 and TSH were depressed.

HEPATIC MICROCIRCULATION OF LIVER CIRRHOSIS STUDIED BY CORROSION CAST/SCANNING ELECTRON MICROSCOPE EXAMINATION

Changes of hepatic microcirculations in 22 autopsy cases of liver cirrhosis were analyzed by corrosion cast/scanning electron microscope (SEM) examination. By this method, the site of arterioportal (A‐P) communication in liver cirrhosis was clearly demonstrated between proliferated portal venules and arterial capillaries. The communications were observed at the same site as in the normal liver and were not at larger arterial and portal vein branches. The findings indicate that the increase of A‐P communication in liver cirrhosis may be called “capillary shunting”. On the basis of the findings, it was postulated that the A‐P shunt could not assist in the development of portal hypertension by the transmission of high arterial pressure to the portal vein but could only compensate for decreased portal flow and/or elevate the oxygen concentration in the sinusoids to improve the hypoxic state of the liver parenchyma. It was also demonstrated that the arterial capillarization of the interstitial septa in micronodular wide septal cirrhosis was more prominent than that in macronodular thin septal cirrhosis. A grade of portal vein reduction and compensatory arterialization in a fibrous septum have been regarded as an index to estimate the advancement of liver cirrhosis. Therefere, if alcoholic micronodular cirrhosis could change into macronodular, the process should have occurred at least before the establishment of micronodular wide septal cirrhosis.

Immunohistochemical studies on myoepithelial changes in breast tumors.

Specific rabbit antisera directed against human uterine myosin were prepared and used for immunohistochemical studies on myoepithelial cells (MECs) in some breast tumors. In Abroadenomas, MECs were observed confined to the periductal portions but not in the stroma. In infiltrating duct carcinomas, MECs were also present as a distinctive periductal layer. Moreover, they were also seen in the infiltrating area, either associated with a small nest of carcinoma cells or freely in the stroma. Larger nests of medullary carcinomas usually were not accompanied by any layer of MECs. No MECs were detected in lobular carcinomas as far as the infiltrating area was concerned. It is suggested from these results that the behavior of MECs is significantly different, depending upon the types of breast tumors. It also appears that the present method may be useful for further analysis of the origin and growth pattern in various breast tumors.

POTENTIATION OF LARGE INTESTINAL TUMORIGENICITY OF CYCASIN DERIVATIVE BY HIGH–FAT DIET AND LACTOBACILLUS IN GERMFREE MICE

Large intestinal tumorigenesis was investigated in germ free (GF) mice following the administration of methylazoxymethanol (MAM) acetate, lard, and lactobacillus arabinosus. Twelve weekly doses of 0.3 mg/10 g MAM acetate given to groups of male weanling, germfree ICR mice, fed either low‐fat (LF) chow alone, or chow with added lard (HF). Additional groups of mice, on the low‐fat diet, were monocontaminated with lactobacillus arabinosus (GA) and they and their GF controls were given 12 weekly doses of 0.2 mg/10 g of MAM acetate. The HF and LF groups were sacrificed after 123 days, and the GA and GF groups after 214 days. Serial sections of the entire large intestine of the MAM acetate‐treated mice revealed many more sessile polyps in the mice maintained on the high‐fat diet. In the mice monocontaminated with lactobacillus, numerous tumors were found, of which 25 percent were invasive. In addition, the polyps found in these animals were generally considerably larger than the polyps found in the GF mice. Atypia occurred in the large intestinal mucosa in all groups. Lard enhanced the large intestinal polypogenesis induced by MAM acetate in germfree mice. Gnotobiosis potentiated the formation of sessile polyps, and carcinogenesis.

NIEMANN-PICK DISEASE ASSOCIATED WITH LIVER DISORDERS

We report a case of Niemann‐Pick disease (NPD) with accumulation of sphingomyelin in reticuloendothelial system (RES), hepatocellular giant cell transformation (GCT), cirrhosis, and multiple hepatocellular adenomata in a 19‐month‐old girl. GCT, but no NP‐cells, were seen at age 3 months by biopsy. Cirrhosis and hepatocellular adenomata were demonstrated in the liver at 19 months of age. Cytoplasmic, probably locally synthesized, globules of alpha‐1‐antitrypsin (A‐l‐AT) were accumulated in the hepatocellular adenomata. A‐l‐AT and alpha‐fetoprotein (AFP) were present in the serum.

Osteogenesis bioassay and immunohistochemical and radioisotopic studies of parotin, parotid gland extract, and subunit

Bioassay data support the hypothesis that the salivary gland participates in endocrine regulation of the development and maintenance of connective tissues. Epiphyseal cartilages become dystrophic in young growing rats after the resection of all major salivary glands. A subunit obtained from parotin, an extract of bovine parotid glands, contains the active agent for the presumed endocrine function of the salivary gland. Daily injections of 3 mg/rat of parotin or the subunit allow normal epiphyseal endochondral osteogenesis in salivary gland-deprived rats. The active agent appears to be secreted by the salivary acinar cells and resorbed through the striated ducts. Pancreatic islets and striated ducts of salivary glands share immunohistochemical activities for insulin, glucagon, and the subunit of parotin. Hyperglycemia and hypocholesterolemia occur in intact rats given 5 mg/day of parotin for 30 days. Together these data suggest endocrine functions of the salivary gland and possible interactions between the pancreatic islet and salivary gland.

Osteogenesis bioassay and immunohistochemical and radioisotopic studies of a subunit of parotin, a parotid gland extract

Bioassay data support the hypothesis that salivary glands participate in endocrine regulation of the development and maintenance of connective tissues. Resection of all three major salivary glands damages epiphyseal cartilages in young growing rats. A subunit obtained from parotin, an extract of bovine parotid glands, contains the active agent for the presumed endocrine function of salivary glands. Daily injections of 3 mg/rat of parotin or the subunit allow normal epiphyseal endochondral osteogenesis in salivary gland-deprived rats. The active agent appears to be secreted by the salivary acinar cells and resorbed through the striated ducts. Pancreatic islets and striated ducts of salivary glands share immunohistochemical activities for insulin, glucagon, and the subunit of parotin. Hyperglycemia and hypocholesterolemia occurred in intact rats given 1 to 5 mg/day of parotin for 30 days. These data together suggest endocrine function of the salivary glands and possible interactions between the pancreatic islets and salivary glands.

HISTOPATHOLOGICAL STUDIES ON MESENCHYMAL TISSUES OF RAT TREATED WITH EXTRACTS FROM PAROTID GLANDS

Publisher Summary This chapter presents an experiment on mesenchymal tissues of a rat treated with extracts from parotid glands. In this experiment, about 20 S.D. strain male rats, which were four weeks old, were divided into four groups. Various methods were performed on these rats. A strong positive reaction was observed by immunofluorescence and the HRP-labelled antibody method at the striated epithelium of the duct of parotid glands, but a negative reaction was observed at the other part of epithelium of the duct. In the subacute experiment, the groups of asial treated with parotin or subunit injections showed similar findings to the group of control in the epiphyseal cartilage cell at the zone of proliferation and columns. Bone formation was regular. In the group of asial treated with saline, cartilage cells of the proliferative zone were degenerative, atrophic, and necrosis. The cell arrangement was irregular at the zone of columns.

Promoting effect of basic lead acetate administration on the tumorigenesis of lung in N-nitrosodimethylamine-treated mice

Lead compounds are frequent environmental contaminations and some of them have been found to be carcinogenic for animals, although epidemiological studies have not been considered to provide sufficient evidence that exposure to lead or lead compounds causes cancer in humans. There re only a few reports on the promoting effect of lead on chemical carcinogenesis in vivo. By the concurrent administration of lead compounds and certain organic carcinogens to rats or hamsters, the cocarcinogenic activity of lead has been found in the kidney of rats or the lung of hamsters. In this report the promoting effect of posttreatment with basic lead acetate (BLA) on the development of lung tumors in strain dd mice exposed to N-nitrosodimethylamine (NDMA) was examined. The concentration of lead and the activity of {gamma}-glutamyltranspeptidase ({gamma}-GTP) in the lung during the carcinogenicity experiment were also measured.

Promoting effects of bile acid to intestinal tumorigenesis in gnotobiotic ICR mice.

Gnotobiotes were produced by administrating Lactobacillus plantarum IAM 1041 in ICR strain male germfree mice which were fed by ordinary or high fat diet. Both groups were orally administered 0.3 mg/10 g of body weight (B. W.) of methylazoxymethanol (MAM) acetate. The oral administration of 0.3 mg/10 g/B.W. once a week for 11 consecutive weeks caused a total of 68 adenomatous polyps in the large intestine (an average of 11.4/mouse) of gnotobiotic high fat diet mice and a total of 32 adenomatous polyps (an average of 5.3/mouse) of the ordinary diet mice. There were no malignancies in either of the groups. Bile acids in the feces showed higher values in the high fat diet group than in the ordinary group. Bile acids are a factor which promotes the appearance of intestinal tumors. It was also assumed that the L. plantarum promoted the activation of β‐glucuronidase and alcohol dehydrogenase in the liver and intestine. ACTA PATHOL. JPN. 35: 1427–1433, 1985.