Susceptibility of laboratory and wild rodents to Rattus or Apodemus-type hantaviruses.

Adult Wistar rats (Rattus norvegicus), Apodemus agrarius, Meriones unguiculatus, Clethrionomys rufocanus, and Apodemus argenteus were inoculated with Rattus-type (SR-11, KI-262, and TB-314) or Apodemus-type (Hantaan 76-118) hantaviruses. Production of serum antibody to the inoculated virus (IAHA titres of 1:32 to 1:4 096) was obsersved in all rodent species 10 weeks after virus inoculation. Rattus-type virus was detected in some organs of all the rodent species employed except of Apodemus agrarius.

Pulmonary corpora amylacea contain surfactant apoprotein.

The case of a 53-year-old female with interstitial pneumonitis is described with special regard to biochemical characterization of pulmonary corpora amylacea which were found in the lung specimen obtained by bronchial biopsy from the patient. The main protein component in bronchoalveolar lavage (BAL) fluid of the patient was albumin, but proteins in the precipitate fraction of BAL fluid, where the corpora amylacea were recovered, predominantly consisted of 36 kD protein which was stained with the monoclonal antibody PE 10 to human pulmonary surfactant apoprotein by immunoblot. Histologically the pulmonary corpora amylacea were stained with eosin and PAS.

Clinico-pathological studies of LEC rats with hereditary hepatitis and hepatoma in the acute phase of hepatitis.

The LEC rat, which suffers from hereditary hepatitis, was examined for elucidation of its clinicopathological characteristics during development of the acute phase of hepatitis by quantitative analyses of histological observations of the liver in combination with laboratory data on various serum enzymes. The progression of acute hepatitis in the LEC rat was observed to begin insidiously early in life, i.e.

Characterization of phospholipids accumulated in pulmonary-surfactant compartments of rats intratracheally exposed to silica.

Phospholipids in the lung fractions, i.e. alveolar free cells, extracellular pulmonary surfactant, intracellular pulmonary surfactant (lamellar bodies) and microsomal fractions, of rats were examined 28 days after intratracheal injection of silica (40 mg/kg).

[Combined immunodeficiency in LEC (Long Evans Cinnamon) rats with spontaneous hepatitis].

We investigated LEC rats immunopathologically which spontaneously developed hepatitis to find out the genesis, in comparison with non-hepatitis LEA (Long Evans Agouti) rats. 1) Wet weights of the spleen and thymus of 6-week old LEC rats were significantly lighter than those of LEA rats of the same age. 2) Serum IgG (Immunoglobulin G) in LEC rats remained markedly low after the age of two months and IgG antibody formation to SRBC (Sheep Red Blood Cell) as detected by plaque assay was also significantly suppressed.

[Pathogenesis of spontaneous hepatitis in an inbred strain of LEC (Long Evans cinnamon) rats].

We have reported an inbred strain LEC rats with high frequency of spontaneous hepatitis. In this paper, we study a possible involvement of hepatitis virus, hereditary background, and correlation between serum IgG level and onset of hepatitis in LEC rats. Neither electron microscopy nor indirect immunofluorescent test could detect hepatitis virus article or antigen.

[Establishment of an inbred strain of LEC (Long Evans Cinnamon) rats with spontaneous hepatitis].

At the Center for Experimental Plants and Animals, Hokkaido University, two inbred strains, Long Evans Cinnamon (LEC) and Long Evans Agouti (LEA), which were selected for coat colour, were isolated from a closed colony of Long Evans rats. While the two inbred strains were maintained by sibmating, only LEC rats, over 24-generation, spontaneously developed acute hepatitis with sudden appearance of systemic jaundice at around four months after birth. The frequency of acute hepatitis was 80 to 90% and the disease in nearly 80% of these rats were progressive and they died within two weeks after onset, with their clinical course and histopathological findings similar to those of human fulminant hepatitis.

Hereditary hepatitis in LEC rats: accumulation of abnormally high ploid nuclei.

The LEC (Long-Evans with a cinnamon-like coat color) rat is a new mutant strain with hereditary hepatitis. The rate of DNA synthesis, the relative amounts of binucleated cells, and the polyploidizations of LEC hepatocytes have been analyzed. Markedly high polyploidy, such as 32n and 64n, were detected after manifestation of hepatitis; however, no aneuploidy was detected.

Accumulation of abnormally high ploid nuclei in the liver of LEC rats developing spontaneous hepatitis.

Enlarged hepatocytes with huge nuclei were found in LEC rats with hereditary hepatitis. Flow cytometric analysis of the DNA content of nuclei from jaundiced LEC rats revealed the presence of very high polyploids, such as 32n and 64n. At the age of 12 weeks, before the onset of hepatitis, 8n polyploid nuclei were more frequent in LEC rats than in LEA rats, a sibling line of LEC rats.

Spontaneous hepatitis in Long-Evans rats. A potential animal model for fulminant hepatitis in man.

Spontaneous hepatitis associated with severe jaundice occurred in 90% of an inbred strain of Long-Evans rats. The rapidly progressive syndrome was characterized by abrupt onset, hyperbilirubinemia and increased serum levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, associated with massive and multifocal necrosis of the liver. This strain should provide a useful animal model for analysis of the pathogenesis of fulminant hepatitis in humans.

High susceptibility to hepatocellular carcinoma development in LEC rats with hereditary hepatitis.

A remarkably high incidence of hepatocellular carcinomas was observed in long-surviving LEC rats with hereditary hepatitis. Among the 60 LEC rats examined between 12 and 28 months of age from F29 and F30, 55 (92%) developed putative preneoplastic and neoplastic lesions such as hyperplastic foci and nodules, and hepatocellular carcinomas. Of these, hepatocellular carcinomas were observed with a high frequency (46/55; 84%).

Elevation of serum alpha-fetoprotein and proliferation of oval cells in the livers of LEC rats.

Alpha-fetoprotein (AFP) in the sera of 35 LEC (Long-Evans with a cinnamon-like coat color) rats between 7 and 25 weeks of age was evaluated by enzyme-linked immunosorbent assay (ELISA). Elevation of serum AFP and proliferation of oval cells in the liver were observed in most LEC rats, which suffered from acute hepatitis. On the other hand, the serum AFP level was within the normal range before the onset of hepatitis.

Hereditary hepatitis of LEC rats is controlled by a single autosomal recessive gene.

The natural history of hereditary hepatitis in long-survived LEC rats was reported. Among 56 (female: male, 28:28) LEC rats of F30, 16 (8:8) (29%) died of fulminant hepatitis approximately four months after birth. The remaining 40 (20:20) rats that survived more than one year developed chronic hepatitis and subsequent hepatic lesions including hepatocellular carcinomas.

A transplantable cell line derived from spontaneous hepatocellular carcinoma of the hereditary hepatitis LEC rat.

A serially transplantable rat hepatocellular carcinoma (HCC) line was established. The primary spontaneous HCC which developed in a 506-day-old male hereditary hepatitis LEC rat was inoculated into young LEC rats. Only this HCC of 18 primary HCCs was successful in serial transplantation.

Spontaneous occurrence of placental glutathione S-transferase-positive foci in the livers of LEC rats.

Spontaneous occurrence of placental glutathione S-transferase (GST-P)-positive foci was observed in the livers of 5-month-old LEC rats. Quantitative studies revealed that GST-P foci appeared after the onset of hepatitis. The number and size of GST-P foci increased with age and more foci were induced in males than in females.

Induction of a novel Ca2+-dependent protease in preneoplastic and neoplastic liver tissues during rat liver carcinogenesis.

The activity of a novel Ca2+-dependent protease in preneoplastic and neoplastic tissues of male Fisher 344 rat liver was examined during experimental liver carcinogenesis. This protease activity is significantly high in hyperplastic nodules and hepatocellular carcinomas which were induced by the method of Solt and Farber. Taken together with our previous report on the promoter-specific induction of this protease, the results suggest the possible importance of this protease in the promotion stage of liver carcinogenesis.

New mutation causing hereditary hepatitis in the laboratory rat.

A new mutant causing hereditary hepatitis associated with severe jaundice has been discovered in the LEC strain of rats. Hepatitis appears suddenly in adult rats three to four months after birth. The clinical signs of hepatitis are characterized by severe jaundice, subcutaneous bleeding, oliguria, and loss of body weight.

Immunohistochemical studies on the expression of pulmonary surfactant apoproteins in human lung carcinomas using monoclonal antibodies.

To reevaluate the expression of pulmonary surfactant apoproteins in lung carcinomas, cancerous tissues from 47 cases were immunohistochemically examined by the avidin-biotin peroxidase complex method using monoclonal antibodies. These antibodies recognized apoproteins in type II pneumocytes in normal and in hyperplastic alveoli and nonciliated columnal cells (Clara cells) in terminal bronchioles of noncancerous tissues. Cancer cells positive for surfactant apoproteins were observed in 11 out of 33 adenocarcinomas, including 1 case of bronchioloalveolar carcinoma.

Induction of a novel Ca2+-dependent serine protease in rat liver treated with various promoters of liver carcinogenesis.

The induction of a novel Ca2+-dependent protease in rat liver treated with various liver promoters, as well as its increase in preneoplastic lesions during liver carcinogenesis, was demonstrated. Six groups of male Fischer 344 rats (150 g body weight) were fed separately diets containing one of the following promoters: 0.05% phenobarbital (PB), 0.

A case of adrenal tumor producing renin, aldosterone, and sex steroid hormones.

A 27-year-old woman with an adrenal tumor that produced renin and aldosterone, associated with hypertension and adrenogenital syndrome, is described. Severe hypertension, cardiomegaly, a low serum potassium level, clinical symptoms of adrenogenital syndrome, and a left upper abdominal tumor also were found. Endocrinological studies showed that plasma and urinary levels of sex steroid hormones such as dehydroepiandrosterone, androsterone, and testosterone were markedly increased.

Immunohistochemical study of human pulmonary surfactant apoproteins with monoclonal antibodies. Pathologic application for hyaline membrane disease.

Three monoclonal antibodies, PC6, PE10, and PE12, were used for immunohistochemical studies of human lungs by immunoperoxidase staining. Monoclonal antibodies PC6 and PE10 against pulmonary surfactant apoproteins stained faint granules in the cytoplasm of some alveolar wall cells in adult lung. These stained cells appeared to be alveolar Type II cells.

Induction of a novel Ca2+-dependent chymotrypsin-like serine protease by tumor promoters in rat livers.

Induction of a microsomal Ca2+-dependent serine protease by hepatic tumor promoters was studied. Male F344 rats were fed a diet containing one of the following promoting agents: phenobarbital (CAS: 50-06-6), dichlorophenyltrichloroethane (CAS: 50-29-3), butylated hydroxytoluene, ethyl-alpha-chlorophenoxyisobutyrate (CAS: 128-95-0), or 17-alpha-ethynylestradiol (CAS: 57-63-6) or a nonpromoting agent, diphenylhydantoin (CAS: 57-41-0), for 1 week. By treatment with promoters, the protease activity in the microsomal fraction was increased to threefold to fivefold that of control, whereas only a slight increase of activity was found after diphenylhydantoin treatment.

[Two cases of paragangliomas of the cauda equina--case reports and review of the literature].

Paragangliomas are tumors arising in the paraganglia and rarely occurring in the cauda equina. We report two cases of paraganglioma arising in this region. The tumors exhibited a typical "Zellballen" pattern, and immunohistochemical studies were positive for neuron-specific enolase, but negative for S-100 protein and glial fibrillary acidic protein.