Distribution of adrenomedullin-containing perivascular nerves in the rat mesenteric artery.

Distribution of adrenomedullin (AM)-containing perivascular nerve fibers was studied in rat mesenteric arteries. Many fibers containing AM-like immunoreactivity (LI) were observed in the adventitia. AM-LI fibers were abolished by cold storage denervation or capsaicin but not 6-hydroxydopamine. Double immunostainings showed colocalization of AM-LI with calcitonin gene-related peptide (CGRP)-LI. The dorsal root ganglia had many AM-positive cells and AM mRNA detected by RT-PCR. Electron microscopy study revealed high proportions of immunogold labeling for AM and colocalization of both AM-LI and CGRP-LI in unmyelinated nerve axons. These results suggest that AM-containing perivascular nerves are distributed in the rat mesenteric artery.

Immunochemical studies of microsomal membranes of rat preneoplastic and neoplastic hepatocytes.

Heterogenous rabbit antisera were prepared against microsomal proteins of hyperplastic hepatic nodules (HPN) induced by chemicals, and were utilized to assess the antigenic differences of microsomal polypeptides within a normal liver, HPN, and hepatocellular carcinomas (HCC), utilizing immunodetection of antigens separated electrophoretically and transferred to nitrocellulose. Although most antigens were common to all microsomes, differences (increase or decrease) were noted in some polypeptides not only between the normal liver and HPN, but also between HPN and HCC. On the other hand, monoclonal antibodies against epoxide hydrolase (EH), which was initially found as the PN antigen, reacted to a single polypeptide with a molecular weight of 49,000 in all the microsomes. These results suggested that there is little molecular modification of EH during hepatic carcinogenesis.

[An autopsy case of colonic carcinoid with marked leukocytosis].

A 45-year-old man with right hypochondralgia and marked leukocytosis was found to have Borrmann type II carcinoma of the sigmoid colon and its metastasis to the liver. The peripheral leukocyte count gradually increased up to 150 X 10(3)/mm3 according to the tumor enlargement. The patient died of hepatic insufficiency, and autopsy revealed carcinoid of the colon and its metastasis to the liver. Leukemoid reaction has been reported in various kinds of malignancies. However, the present case seems to be of particular interest because of the rare association with carcinoid and marked leukocytosis of more than 100 X 10(3)/mm3 without any evidence of infection.

Healing of focal injury in the rat liver.

The healing process of focal hepatic injury produced by thrusting a liquid nitrogen-cooled or fire-heated needle in rat liver was investigated by light and electron microscopy and autoradiography. Twenty-four hours after the injury, necrotic areas were sharply demarcated from the surrounding normal hepatic tissue, and their margin was infiltrated with monocytes, macrophages, neutrophils, and platelets. Following the inflammatory infiltration, Ito cells, cholangiolar cells, and capillary endothelial cells proliferated in the peripheral areas of the necrosis. In accordance with the proliferation of Ito cells, collagen fibers markedly increased. Autoradiography demonstrated that cells proliferating in necrotic areas were predominantly Ito cells, and that hepatocytes adjacent to the damaged sites showed DNA synthesis. Necrotic and fibrotic areas were gradually decreased in size; and by 2 weeks, damaged sites were restored to almost normal histologic appearance, occasional scars remaining. The results of this study indicate that small focal hepatic injury is repaired locally by a mechanism resembling that of wound healing, and that Ito cells play an important role in that process.

[Merkel cell tumor of the skin].

A skin tumor of a 66-year-old female was examined morphologically and immunohistochemically in relation to its histogenetic aspect. The tumor was located within the dermis and composed of compact round cells with scanty cytoplasm. Electron-microscopic study revealed the presence of dense-cored granules within the cytoplasm. Thus the tumor was thought to derive from Merkel cells. The tumor cells were positive for keratin and negative for S-100 protein by immunohistochemistry. Therefore, we posit that the tumor cells did probably not originate from the neural crest, but rather from epidermal immature cells.

Initiation of focal hyperplastic hepatic lesions by transplacental administration of ethylnitrosourea in rats of F1 generation, and no transmission of the effect to F2 and F3 generations.

Administration of ethylnitrosourea (ENU) to pregnant rats in the late stage of gestation has been known to have a mainly neurocarcinogenic action on the progeny. However, when transplacental administration of ENU was combined in postnatal life with a brief dietary exposure to 2-acetylaminofluorene (2-AAF) and a two-thirds partial hepatectomy, numerous focal hyperplastic lesions of gamma-glutamyltranspeptidase (GGT)-positive hepatocytes emerged in the liver of the progeny. On the other hand, rats of F2 generation born of F1 parents and F3 rats born of F2 parents showed no increase in the incidence of hepatic lesions after treatment with the same dietary regimen. It was suggested that direct interaction between fetal liver cells and the carcinogen is important for occurrence of initiated hepatocytes and that the initiation effect on rat liver by ENU does not persist in the descendants of F2 and F3 generations.

Laboratory and histological similarities between Wilson's disease and rats with copper toxicity.

Rats were injected intraperitoneally with copper-lactate daily for over 160 days (total dose of 30 mg copper in each animal). At 120 to 160 days of copper administration, animals developed symptoms similar to those of Wilson's disease, i.e., kidney functional disturbances, proteinuria, aminoaciduria, decreased blood ceruloplasmin oxidase activity and increased urinary copper excretion. Cirrhosis was found in some animals. Tubular necrosis of the kidneys, liver fibrosis and tigrolysis of thalamic nerve cells were also found. Copper depositions were observed in liver parenchymal cells, renal tubular epithels, thalamus glia cells and on the Descemet's membrane of the cornea. The similarities between induced copper- intoxication in rats and Wilson's disease are discussed.

Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis.

Rats and rabbits parenterally treated with a large daily dose of ferric nitrilotriacetate manifested diabetic symptoms such as hypergycemia, glycosuria, ketonemia, and ketonuria after approximately 60 days fo treatment. The blood insulin response to oral glucose loading was poor. Heavy iron deposits were found in liver parenchymal cells and in pancreatic exocrine cells, although some iron was deposited in the macrophages and reticuloendothelial cells of the organs. Faint iron staining was found in some pancreatic islet cells, with a reduction in beta granules and weak zinc staining. Cirrhotic liver changes and skin pigment deposition were not observed. Repeated blood withdrawals from ferric-nitrilotriacetate-treated animals resulted in disappearance of hypergycmia, glycosuria, ketonemia, and ketonuria; disappearance of iron from the liver and pancreas; and restoration of islet beta granules to the control level.