Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To learn the toxicity of xenogeneic tumor-specific immune ribonucleic acid (I-RNA), experimental and clinical studies were carried out. Experimentally, doses of 30 mg/kg, 15 mg/kg, 7.5 mg/kg or 3.75 mg/kg of xenogeneic I-RNA extracted from lymphoid tissues of rabbits sensitized with 105,000 Xg sediments of human gastric carcinoma tissue were injected intraperitoneally into Wistar rats once a day for 30 days. During the period of the study, changes of physiological and biochemical values were examined. In addition, pathological study was made for each organ after the I-RNA administration. There was no death during the study. In the groups of high dose administration, there were poor increase in the body weight, elevation of GOT, GPT and LDH, findings of vacuolar degeneration of hepatic cells, and increase of mesangial matrix and polynuclear glomerulus. Throughout the experiment, the groups given 7.5 mg/kg and 3.75 mg/kg of I-RNA showed no significant difference from control groups. Clinically, 31 cases treated with passive immunotherapy with allogeneic lymphocytes, preincubated with xenogeneic I-RNA, were examined retrospectively for the difference in hematological and biochemical data before and after the therapy. One case showed a transient mild febrile reaction after the therapy. There was no significant difference in hematological and biochemical data. Pathological findings in 3 autopsies after the treatment were reported.
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PMID:Experimental and clinical studies on toxicity of xenogeneic tumor-specific immune ribonucleic acid. 49 51

Simian hemorrhagic fever (SHF) virus and a new strain of Ebola virus were isolated concurrently in recently imported cynomolgus monkeys (Macaca fascicularis) being maintained in a quarantine facility. Ebola virus had never been isolated in the U.S. previously and was presumed to be highly pathogenic for humans. A chronology of events including measures taken to address the public health concerns is presented. The clinicopathologic features of the disease were abrupt anorexia, splenomegaly, marked elevations of lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, with less prominent elevations of blood urea nitrogen, creatinine, and other serum chemistry parameters. Histologically, fibrin deposition, hemorrhage, and necrosis of lymphoid cells and reticular mononuclear phagocytes were present in the spleens of SHF and of Ebola virus-infected animals. Intravascular fibrin thrombi and hemorrhage were also present in the renal medulla and multifocally in the gastrointestinal tract. Necrosis of lymphoid and epithelial cells was occasionally noted in the gastrointestinal tract. The histopathologic findings considered specific for Ebola virus infection include hepatocellular necrosis, necrosis of the zona glomerulosa of the adrenal cortex, and interstitial pneumonia, all of which were generally associated with the presence of 1 to 4 mu intracytoplasmic amphophilic inclusion bodies. The disease spread within rooms despite discontinuation of all direct contact with animals, and droplet or aerosol transmission was suspected. Antibody to Ebola virus developed in animal handlers but no clinical disease was noted, suggesting a less virulent strain of virus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combined simian hemorrhagic fever and Ebola virus infection in cynomolgus monkeys. 131 46

The immunotoxicity, hepatotoxicity, and nephrotoxicity of subacute exposure to carbon tetrachloride (CCl4) were evaluated in young adult (8-9 weeks old) male Fischer 344 rats dosed by gavage with CCl4 for 10 consecutive days at 0, 5, 10, 20 or 40 mg/kg/day. Two days following the last treatment rats were evaluated for alterations in immune function by monitoring the following: body and lymphoid organ weights; mitogen and mixed leukocyte reaction lymphoproliferative responses; natural killer cell activity; and cytotoxic T lymphocyte responses. A separate group of similarly dosed rats was immunized with sheep red blood cells (SRBC) on Day 9 of dosing, and the primary antibody response was assessed 4 days later. Hepatic and renal toxicity were assessed 2 days after the last treatment by monitoring organ weights, serum indicators of hepatic and renal damage, and hepatic cytochrome P450 levels, as well as by histological evaluation. Significant increases in relative liver weights were observed in rats dosed at 40 mg/kg/day. Histologically, these livers displayed mild to moderate vacuolar degeneration and minimal to mild hepatocellular necrosis. In addition, serum levels of aspartate aminotransferase and alanine aminotransferase were elevated at this dosage, as well as at 20 mg/kg/day. There were no renal effects observed at these dosages of CCl4. In addition, no consistent alterations were observed in the immune parameters examined in these same animals nor in the rats immunized with SRBC. Furthermore, there was no difference in the antibody response to SRBC in another set of rats dosed at 40, 80 or 160 mg/kg/day CCl4. These results indicate that CCl4 is not immunotoxic in the rat at dosages that produce overt hepatotoxicity.
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PMID:Immunotoxicologic assessment of subacute exposure of rats to carbon tetrachloride with comparison to hepatotoxicity and nephrotoxicity. 183 55

Adult wild-trapped opossums were infected with Leishmania donovani (Khartoum strain, WR 378) and evaluated as an animal model of visceral leishmaniasis. All infected opossums died within 32 days. Loss of body fat, hepatomegaly, and petechiae of skin and abdominal musculature were seen at necropsy. Microscopically, numerous amastigote-laden macrophages were seen in histologic sections of liver, spleen, and lymph nodes; fewer parasite-laden macrophages were in the bronchial-associated lymphoid tissues and renal glomeruli. Hematological findings included thrombocytopenia (terminal), neutropenia, and lymphopenia. Blood lymphocyte blastogenesis in response to concanavalin A and phytohemagglutinin was decreased markedly at day 24 post-infection (PI). Serum antibodies (1:40 dilution) to promastigotes of L. donovani were detected in five of eight infected opossums tested on days 10 and 24 PI. Total bilirubin concentrations and alanine aminotransferase and aspartate aminotransferase activities were increased after day 25 PI. Activated partial thromboplastin times and one-stage prothrombin times were prolonged before death. Concurrently, factors V, VIII, and XII activities were decreased.
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PMID:Experimental visceral leishmaniasis in the opossum. 276 21

Rabbits were given T-2 mycotoxin orally at 0, 0.25, 0.5, and 0.75 mg/kg of body weight/day for 21 days. Only rabbits in the 0.75 mg/kg/day group (4 of 5 rabbits) died. Alveolar macrophages were harvested on day 22 and used for in vitro phagocytosis of killed Aspergillus fumigatus conidia. Cultures included sera from untreated rabbits or rabbits treated with T-2. Phagocytosis was significantly (P less than 0.01) reduced in cultures that used serum from rabbits treated with 0.5 mg of T-2/kg/day and alveolar macrophages from untreated rabbits or rabbits treated with T-2. There was little reduction in phagocytosis when alveolar macrophages from rabbits treated with T-2 and normal serum were used. Ingestion of 0.5 mg of T-2 toxin/kg/day significantly (P less than 0.05) reduced weight gain, serum alkaline phosphatase activity, serum sorbitol dehydrogenase activity, and serum bacteriostasis. Similar changes were found in the 0.75 mg/kg/day group, as well as a significant (P less than 0.05) reduction in PCV, total WBC, and differential leukocyte counts. Neutrophil counts decreased, but not significantly (0.05 less than P less than 0.10). Significant changes were not detected in alanine transaminase activity, aspartate transaminase activity, blood urea nitrogen concentration, or complement hemolytic activity. Histopathologic changes consisting of centrilobular hepatocellular swelling, mild portal and periportal fibrosis and lymphocyte necrosis within secondary lymphoid tissues developed in most rabbits treated with T-2. Thymic atrophy, bile duct reduplication, and lymphocyte depletion of secondary lymphoid tissues developed in the group given 0.75 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of T-2 mycotoxin ingestion on phagocytosis of Aspergillus fumigatus conidia by rabbit alveolar macrophages and on hematologic, serum biochemical, and pathologic changes in rabbits. 305 39

The acute toxicity of helenalin, a sesquiterpene lactone isolated from Helenium microcephalum, was examined in male BDF1 mice. The 14-day LD50 for a single ip dose of helenalin in male mice was 43 mg/kg. A single ip injection of 25 mg helenalin/kg increased serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea nitrogen (BUN), and sorbitol dehydrogenase within 6 hr of treatment. Multiple helenalin exposures, ip injection of 25 mg helenalin/kg for 3 days, increased differential polymorphonuclear leukocyte counts and decreased lymphocyte counts. Serum ALT, BUN, and cholesterol levels were also increased by multiple helenalin exposures at 25 mg helenalin/kg/day. Helenalin significantly reduced liver, thymus, and spleen relative weights and histologic evaluation revealed substantial effects of multiple helenalin exposures on lymphocytes of the thymus, spleen, and mesenteric lymph nodes. No helenalin-induced histologic changes were observed in the liver or kidney. Multiple helenalin exposures (25 mg/kg/day) significantly inhibited hepatic microsomal enzyme activities (aminopyrine demethylase and aniline hydroxylase) and decreased microsomal cytochromes P-450 and b5 contents. Three concurrent days of diethyl maleate (DEM) pretreatment (3.7 mmol DEM/kg, 0.5 hr before helenalin treatment) significantly increased the toxicity of helenalin exposure. The present studies indicate that the hepatic microsomal drug metabolizing system and lymphoid organs are particularly vulnerable to the effects of helenalin. In addition, helenalin toxicity is increased by DEM pretreatments which have been shown to decrease glutathione concentrations.
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PMID:Acute toxicity of helenalin in BDF1 mice. 335 17

Ten dogs were inoculated with Ehrlichia platys (E. platys) from an acutely infected dog. Two dogs were necropsied on each of days 7, 14, 21, 28, and 35 post-inoculation, and tissues were collected and either fixed in formalin or frozen for light microscopic examination of lesions or E. platys antigen localization in tissues. Serum antibody titers to E. platys and serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities were also determined. The significant light microscopic findings were lymph node follicular hyperplasia and crescent-shaped hemorrhages in the splenic periarteriolar lymphoid sheaths beginning day 7 post-inoculation. There was significant megakaryocyte hyperplasia of bone marrow on days 28 and 35 post-inoculation. Ehrlichia platys antigen was in macrophages at 14 days post-inoculation which corresponded to the initial decline in platelet numbers. Initial thrombocytopenia and splenic crescent-shaped hemorrhages were temporally related, however the degree of lesion development and prominence were not related to subsequent platelet numbers.
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PMID:Acute Ehrlichia platys infection in the dog. 367 11

A lethal syndrome characterized clinically by growth retardation, progressive acrodermatitis, chronic pyoderma and paronychia, diarrhea, pneumonia, and abnormal behavior was observed in 17 related Bull Terrier pups. Median survival time was 7 months. Laboratory evaluation revealed non-degenerative neutrophilia, consistently low activities of serum alkaline phosphatase and alanine transaminase, and frequently, hypercholesterolemia. Lymphocyte blastogenic responses were decreased and there was dysgammaglobulinemia in pups in which quantitative studies of immunoglobulins were made. The mean of plasma zinc concentrations in 5 affected pups was significantly lower than the mean of age- and breed-matched controls. Pathologic findings included parakeratosis, hyperkeratosis, and superficial bacterial infections of the skin. There was severe reduction of lymphocytes in T-lymphocyte areas of lymphoid tissue. Bronchopneumonia and dilatation of the cerebral ventricles were found in most affected pups. Family studies indicated that the syndrome is inherited as an autosomal recessive trait. In spite of its similarities to lethal trait A46 in Black Pied Danish cattle and acrodermatitis enteropathica in man, oral or parenteral treatment with zinc failed to ameliorate the clinical signs of the syndrome.
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PMID:Lethal acrodermatitis in bull terriers. 371 Aug 72

4-Fluoro-3-nitroaniline (4-F-3-NA), an intermediate used in the production of commercial hair dyes, was administered daily for 90 days via po intubation to Charles River CD rats at doses of 40, 120, or 360 mg/kg to determine its subchronic toxicology. All animals receiving 360 mg/kg died prior to termination of the study. The principal effect to rats of 4-F-3-NA exposure was alteration of the hematopoietic system characteristic of hemolytic anemia. Hematocrit, hemoglobin concentration, and erythrocyte count were decreased and reticulocytes increased in a dose-related pattern in both male and female animals. Histopathological change consistent with hemolytic anemia was observed in the bone marrow (erythroid hyperplasia), kidneys (deposition of biliverdin and pigment-laden macrophages in the tubules), liver (pigmented Kupffer cells), and spleen (increased hematopoiesis) in males and females. Heinz bodies and an increase in methemoglobinemia were not observed in this study. In the testes, aspermia and testicular degeneration were seen in isolated tubules, but these changes were significant only at the high dose. Additional pathologic changes noted at the high dose included colloid depletion and follicular cell hypertrophy of the thyroid gland, hypertrophy of the zone fasciculata in the adrenal glands, and lymphoid cell depletion in mesenteric lymph nodes. The calcification of the myocardium and coronary arteries was considered metastatic in nature, secondary to kidney damage. Serum ALT and BUN were elevated in males and AP was elevated in females from the high dose group. Glycosuria, bilirubinuria, and urobilinogenuria were also increased in both sexes at this dose.
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PMID:Subchronic oral toxicology of 4-fluoro-3-nitroaniline in the rat. 671 Apr 91

The correlation between histological features of liver biopsy specimens before interferon (IFN) treatment and the clinical effect of IFN administration on chronic hepatitis C was investigated. The changes in the biopsy specimens were graded on the basis of different histological features. The degree of portal fibrosis adversely affected the rate of normalization of ALT levels in the patients treated with IFN. During IFN treatment, the group of chronic hepatitis C patients who showed marked piecemeal necrosis and less lymphoid follicle formation in the liver specimens, showed abnormal ALT values even after disappearance of hepatitis C virus RNA in the sera, suggesting that functions of IFN other than antiviral effect, including enhancing interaction between lymphocytes and hepatocytes, sometimes induce exacerbation of hepatitis.
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PMID:[Correlation between histological features of liver biopsy specimens and clinical effect of interferon on patients with chronic hepatitis C]. 752 16


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