Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of mice to 1000 ppm of vinyl chloride (VC), 6 hr/day, 5 days/week, caused some acute deaths with toxic hepatitis and marked tubular necrosis of the renal cortex. Starting the sixth month, mice exposed to 1000, 250, or 50 ppm of VC became lethargic, lost weight quickly, and died. Only a few mice exposed to 50 ppm survived for 12 months. Pulmonary macrophage count was elevated in some mice. There was a high incidence of bronchiolo-alveolar adenoma, mammary gland tumors including ductular adenocarcinoma, squamous and anaplastic cell carcinomas with metastasis to the lung, and hemangiosarcoma in the liver, and, to a lesser extent, in some other organs. The incidence of these tumors quickly increased, and the severity was in direct proportion to the levels of VC and the length of exposure. Malignant lymphoma involving various organs was observed in a few mice. Rats were more resistant to the toxic effects of VC. Exposure to 1000 ppm slightly depressed the body weight of the females. Exposures of 250 or 1000 ppm caused a number of deaths and hemangiosarcoma in the liver starting the ninth month. Most rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Hemangiosarcoma occasionally occurred in other tissues of one or two rats exposed to 50 ppm or higher level of VC. Exposure of mice to 55 ppm of vinylidene chloride (VDC) also caused a few acute deaths and a few hepatic hemangiosarcomas. Inflammatory, degenerative, and mitotic changes occurred in the liver. No mouse exposed to VDC developed any mammary gland tumors. Several mice had bronchioloalveolar adenoma. Exposure of rats to 55 ppm of VDC slightly depressed the body weight. Hemangiosarcoma occurred in the mesenteric lymph node or subcutaneous tissue in two rats.
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PMID:Inhalation toxicity of vinyl chloride and vinylidene chloride. 56 2

A 39-year-old male with bleeding esophageal varices due to portal hypertension was observed. The patient had taken an arsenical preparation during a period of 12 yr because of psoriasis and subsequently developed keratotic changes of the palms and soles of his feet and an epithelioma of the scrotum. Physical examination was unremarkable except for splenomegaly and skin lesions. Liver function tests were normal; a needle biopsy of the liver (right lobe) showed nonspecific changes. Combined hepatic and umbilicoportal catheterization revealed, on splenography and portography, huge esophageal varices and patent portal vein; dilation, distortion, and cut-off of many intrahepatic portal branches were found. A marked gradient existed between the free portal venous pressure (25 mm Hg) and the wedged hepatic venous pressure (9.5 mm Hg). Hepatic blood flow, portal PO2, cardiac output, cardiac index, and blOOD volume were within normal range. Arteriographies did not reveal arteriovenous shunts in the splanchnic or splenic vessels. A splenorenal shunt were performed and a wedged biopsy of the liver (left lobe) revealed nonspecific changes. Three years later the patient had not experienced any episode of hemorrhage or hepatic encephalopathy but developed an epithelioma of the tongue. No known cause could be incriminated in the pathogenesis of the portal hypertension. However, there was unequivocal chronic arsenic intoxication. Toxic hepatitis, cirrhosis, noncirrhotic portal hypertension, and hemangiosarcoma of the liver have been reported with the intake of arsenicals. Thus, it is suggested that in this patient, presinusoidal portal hypertension was secondary to chronic arsenical intake associated with marked intrahepatic vascular changes seen on portography.
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PMID:Noncirrhotic presinusoidal portal hypertension associated with chronic arsenical intoxication. 112 3

Male and female B6C3F1 mice from 12 National Toxicology Program (NTP) 2-yr carcinogenesis studies were found to be infected with Helicobacter hepaticus. Many of the male mice from 9 of these studies had an associated hepatitis (affected studies). Helicobacter hepaticus has been reported to be associated with an increased incidence of hepatitis and hepatocellular neoplasms in the A/JCr male mouse. We attempted to determine if the data from the Helicobacter-affected NTP B6C3F1 mouse studies were compromised and unsuitable for cancer hazard identification. The incidences of neoplasms of the liver (both hepatocellular and hemangiosarcoma) but not of other organs in control male B6C3F1 mice were increased in affected studies as compared with control males from unaffected studies. The increased incidence of hepatocellular neoplasms was observed in those males exhibiting H. hepaticus-associated hepatitis. Other observations further differentiated control male mice from affected and unaffected studies. H-ras codon 61 CAA to AAA mutations were less common in liver neoplasms from males from affected studies as compared with historical and study controls. In addition, increases in cell proliferation rates and apoptosis were observed in the livers of male mice with H. hepaticus-associated hepatitis. These data support the hypothesis that the increased incidence of liver neoplasms is associated with H. hepaticus and that hepatitis may be important in the pathogenesis. Therefore, interpretation of carcinogenic effects in the liver of B6C3F1 mice may be confounded if there is H. hepaticus-associated hepatitis.
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PMID:Impact of Helicobacter hepaticus infection in B6C3F1 mice from twelve National Toxicology Program two-year carcinogenesis studies. 978 46

The results of liver cytology and corresponding biopsy specimens submitted to the Pathology Department at Angell Memorial Animal Hospital during 1998 were retrospectively reviewed to objectively assess the diagnostic value of liver cytology. A "corresponding" biopsy was defined as a biopsy specimen obtained within 1 day of the cytology specimen. Fifty-six cases were reviewed, including 25 from dogs and 31 from cats. Results were in complete agreement in 34 cases, in partial agreement in 11 cases, and in disagreement in 11 cases. Agreement occurred most often in cases of fatty change (10 cases) and neoplasia (7 cases of lymphoma and 3 cases of epithelial tumor). Disagreement was most common in cases of hepatitis (6 cases) in which inflammation was not seen in cytologic specimens. Other causes for disagreement included fibrosis (2 cases), and 1 case each of amyloidosis, hemangiosarcoma, and lymphoma. Three cytologic specimens were considered suggestive of hepatitis because of leukocytosis in the background, although clinicians were advised to compare cytologic observation to CBC results. Cytologic evaluation of the liver was useful for determining disease processes, especially when disease distribution was diffuse.
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PMID:Comparison of liver cytology and biopsy diagnoses in dogs and cats: 56 cases. 1202 29

Cobalt sulfate is used in the electroplating and electro chemical industries. It is also used as a coloring agent for ceramics and as a drying agent in inks, paints, varnishes, and linoleum. Cobalt sulfate may be added to animal feed as a mineral supplement and has been used as a top dressing on pasture lands. Cobalt sulfate was nominated by the National Cancer Institute for study based on a lack of information on the toxicity of soluble salts. Male and female F344/N rats and B6C3F1 mice were exposed to cobalt sulfate heptahydrate (approximately 99% pure) by inhalation for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium. The results of prechronic inhalation toxicity studies were reported previously (Bucher et al., 1990; NTP, 1991). 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate heptahydrate 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights Survival of exposed males and females was similar to that of the chamber controls. Mean body weights of exposed male and female rats were similar to those of the chamber controls throughout the study. Pathology Findings The incidences and severities of proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were markedly greater in all exposed groups of male and female rats than in the chamber controls. The incidences of alveolar epithelial hyperplasia in all groups of exposed males and in females exposed to 3.0 mg/m3 were significantly greater than those in the chamber control groups, as were the incidences of squamous metaplasia in 1.0 mg/m3 females and atypical alveolar epithelial hyperplasia in 3.0 mg/m3 females. In 3.0 mg/m3 males, the combined incidence of alveolar/ bronchiolar neoplasms (adenoma and/or carcinoma) was significantly greater than in the chamber controls. In female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were significantly greater than those in the chamber control group and exceeded the NTP historical control ranges. A squamous cell carcinoma was observed in one 1.0 mg/m3 and one 3.0 mg/m3 female. The incidences of benign, complex, or malignant pheochromocytoma (combined) in 1.0 mg/m3 males and in 3.0 mg/m3 females were significantly greater than those in the chamber controls and exceeded the historical control ranges. Hyperplasia of the lateral wall of the nose, atrophy of the olfactory epithelium, and squamous metaplasia of the epiglottis were observed in all exposed groups of males and females, and the severities of these lesions increased with increasing exposure concentration. The incidences of squamous metaplasia of the lateral wall of the nose and metaplasia of the olfactory epithelium were increased in 3.0 mg/m3 males and females. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate heptahydrate 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights Survival of exposed males and females was similar to that of the chamber controls. Mean body weights of 3.0 mg/m3 male mice were less than those of the chamber controls from week 96 until the end of the study. The mean body weights of all exposed groups of female mice were generally greater than those of the chamber controls from week 20 until the end of the study. Pathology Findings The incidences of diffuse histiocytic cell infiltration in 3.0 mg/m3 males and of focal histiocytic cell infil tration in 3.0 mg/m3 females were significantly greater than those in the chamber controls. The incidences of alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were significantly greater than those in the chamber control groups. The combined incidences of alveolar/bronchiolar adenoma or carcinoma and the incidences of alveolar/bronchiolar carcinoma in 3.0 mg/m3 males and females and the incidence of alveolar/bronchiolar adenoma in 3.0 mg/m3 females exceeded the NTP historical crical control ranges for inhalation studies. The incidences of atrophy of the olfactory epithelium in 1.0 and 3.0 mg/m3 males and females and hyper plasia of the olfactory epithelium in 3.0 mg/m3 males and females were significantly greater than in the chamber controls. Squamous metaplasia of the larynx was observed in all exposed groups of males and females. Male mice had a pattern of nonneoplastic liver lesions along with silver-staining helical organisms within the liver, characteristic of an infection with Helico bacter hepaticus. In NTP studies with H. hepaticus- associated hepatitis, increased incidences of hemangiosarcoma were seen in the liver of male mice. In this study of cobalt sulfate heptahydrate, incidences of hemangiosarcoma were increased in exposed groups of male mice. Because of the above association, interpretation of the increased incidences of hemangiosarcoma in the livers of male mice was confounded. Incidences of lesions at other sites in this study of cobalt sulfate heptahydrate were not considered to have been significantly impacted by the infection with H. hepaticus or its associated hepatitis. GENETIC TOXICOLOGY: Cobalt sulfate heptahydrate was mutagenic in S. typhimurium strain TA100 with and without liver S9 metabolic activation enzymes; no mutagenic activity was detected in strain TA98 or TA1535, with or without S9. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity of cobalt sulfate heptahydrate in male F344/N rats based on increased incidences of alveolar/bronchiolar neoplasms. Marginal increases in incidences of pheochromocytomas of the adrenal medulla may have been related to exposure to cobalt sulfate heptahydrate. There was clear evidence of carcinogenic activity in female F344/N rats based on increased incidences of alveolar/bronchiolar neo-plasms and pheochromocytomas of the adrenal medulla in groups exposed to cobalt sulfate heptahydrate. There was clear evidence of carcinogenic activity of cobalt sulfate heptahydrate in male and female B6C3F1 mice based on increased incidences of alveolar/bronchiolar neoplasms. Exposure to cobalt sulfate heptahydrate caused a spectrum of inflammatory, fibrotic, and proliferative lesions in the respiratory tract of male and female rats and mice. Synonyms: Bieberite; cobalt(II) sulfate (1:1) heptahydrate; cobalt monosulfate heptahydrate; cobalt(II) sulphate heptahydrate; sulfuric acid, cobalt(2+) salt (1:1) heptahydrate
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PMID:NTP Toxicology and Carcinogenesis Studies of Cobalt Sulfate Heptahydrate (CAS No. 10026-24-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1257 2