Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Forty-three patients with hematopoietic disease were treated with intensive chemotherapy and radiotherapy, followed by allogeneic bone marrow transplantation (BMT) from 28 HLA-identical and 10 one to two antigen haploidentical sibling donors and autologous BMT (5 cases). Of these cases, there were 21 with acute nonlymphocytic leukemia (ANLL), 5 with acute lymphocytic leukemia (ALL), 6 with chronic myelocytic leukemia (CML), 2 with Hodgkin's disease (HD), 8 with severe-form aplastic anemia (SAA) and 1 with thalassemia. Complications of BMT were evaluated including acute graft-versus-host disease (GVHD), interstitial pneumonia (IP), veno-occlusive liver disease (VOD), abnormalities of liver function (LF), and alteration of hepatitis B virus (HBV) markers. In thirty-three patients who were followed up for more than 3 months, we found that the incidence of moderate to severe acute GVHD (9.1%) and IP (two cases, 4.7%) were low. No VOD occurred in our series. During the follow-up period, 27 out of 35 patients (77%) had high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, even up to 1000 U/liter; however, only one patient succumbed to a hepatitis-related complication. Previous hepatic damage from HBV infection before BMT does not appear to increase the risk of posttransplant morbidity and mortality.
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PMID:Complications of bone marrow transplantation in Chinese. 232 72

1-Nitronaphthalene is a mutagenic particulate of diesel exhaust which causes acute liver and lung toxicity in rodents. The studies presented here describe morphological changes in the lung and liver at several time intervals following a single injection of 1-nitronaphthalene (100 mg/kg, i.p.) in male Sprague-Dawley rats using transmission and scanning electron microscopy. Although both the lungs and liver are injured by 1-nitronaphthalene, the lungs appear to be the primary target organ. Within 4 h of treatment, all 1-nitronaphthalene treated animals exhibited respiratory distress characterized by labored breathing, severe gasping and chromodacryorrhea. The primary ultrastructural alteration were hydropic changes in the non-ciliated bronchiolar (Clara) cells of the distal-most bronchioles of the lung. These were apparent as early as 1 h after 1-nitronaphthalene injection, while adjacent ciliated cells showed no alterations. Over a 24 h period, the bronchioles showed progressive ultrastructural changes leading to necrosis and exfoliation of both ciliated and Clara cells. Interstitial pneumonitis and edema were observed in all animals treated with 1-nitronaphthalene, and was usually associated with bronchioles containing necrotic epithelium. In the liver, ultrastructural changes were observed in the centrilobular hepatocytes at 8 h and consisted of cytomegaly, loss of continuous inner membrane and reduced matrix density of the mitochondria. At 48 h, cellular damage to centrilobular hepatocytes was severe and nearly all mitochondria were damaged. Elevated levels of alanine aminotransferase, aspartate aminotransferase and bilirubin were detected in the serum of animals treated with 1-nitronaphthalene at 8-48 h. In conclusion, 1-nitronaphthalene is a pulmonary toxicant with a unique progression of injury, which primarily damages Clara cells followed by ciliated cells. This disparity is likely due to a difference in the bioactivation of 1-nitronaphthalene. Furthermore, this systemic toxicant also has injurious effects on the centrilobular region of the liver which precedes lung injury.
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PMID:An ultrastructural evaluation of acute 1-nitronaphthalene induced hepatic and pulmonary toxicity in the rat. 902 Mar 98

Four groups of 12 pregnant Wistar rats each were fed with rations containing 0, 0.01, 0.015 and 0.02% of monocrotaline (MCT) from day 6 to 21 of gestation. Liver weights of the dams from the three experimental groups were significantly lower than those from the control group. Serum levels of aspartate aminotransferase; alkaline phosphatase; lactate dehydrogenase; gamma glutamyltransferase, urea and creatinine were significantly higher in dams from MCT 0.02% group. The weights of the placenta, fetuses and fetal lungs of the 0.02% MCT group were significantly lower than those of the control group. A mild to moderate interstitial pneumonia and liver lesions were observed in dams ingesting 0.02% of MCT. These results showed the toxicity of MCT to the females that ingested 0.02% and their fetuses. Because there was no differences on the weight gains and food and water consumption of the dams it is suggested that this toxic effects in the fetuses was caused by the diffusion of MCT through the placenta. No significant differences were observed in the frequency of skeletal and visceral malformation or anomalies between the control and treated groups suggesting that MCT had no teratogenic effect.
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PMID:Fetotoxicity and reproductive effects of monocrotaline in pregnant rats. 1068 74

One of the main difficulties in studying dengue virus infection in humans and in developing a vaccine is the absence of a suitable animal model which develops the full spectrum of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome. It is our proposal to present morphological aspects of an animal model which shows many similarities with the dengue infection in humans. BALB/c mice were intraperitoneally infected with non-neuroadapted dengue virus serotype 2 (DENV-2). Histopathological and morphometrical analyses of liver tissue revealed focal alterations along the infection, reaching wide-ranging portal and centrolobular veins congestion and sinusoidal cell death. Additional ultrastructural observations demonstrated multifocal endothelial injury, platelet recruitment, and alterated hepatocytes. Dengue virus antigen was detected in hepatocytes and in the capillar endothelium of the central lobular vein area. Liver function tests showed high levels of aspartate transaminase and alanine transaminase enzyme activity. Lung tissue showed interstitial pneumonia and mononuclear cells, interseptal oedema, hyperplasia, and hypertrophy of the bronchiolar epithelial cells. DENV-2 led to a transient inflammatory process, but caused focal alterations of the blood-exchange barrier. Viremia was observed from 2nd to 11th day p.i. by isolation of DENV-2 in C6/36 mosquito cell line inoculated with the supernatant of macerated liver, lung, kidney, and cerebellum tissues of the infected mice.
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PMID:Morphological studies in a model for dengue-2 virus infection in mice. 1729 87

Because of its excellent optical performance and electrical properties, TiO2 has a wide range of applications in many fields. It is often considered to be physiologically inert to humans. However, some recent studies have reported that nano-sized TiO2 may generate potential harm to the environment and humans. In this paper the in vivo acute toxicity of nano-sized TiO2 particles to adult mice was investigated. Mice were injected with different dosages of nano-sized TiO2 (0, 324, 648, 972, 1296, 1944 or 2592 mg kg(-1)). The effects of particles on serum biochemical levels were evaluated at various time points (24 h, 48 h, 7 days and 14 days). Tissues (spleen, heart, lung, kidney and liver) were collected for titanium content analysis and histopathological examination. Treated mice showed signs of acute toxicity such as passive behavior, loss of appetite, tremor and lethargy. Slightly elevated levels of the enzymes alanine aminotransferase and aspartate aminotransferase were found from the biochemical tests of serum whereas blood urea nitrogen was not significantly affected (P < 0.05). The accumulation of TiO2 was highest in spleen (P < 0.05). TiO2 was also deposited in liver, kidney and lung. Histopathological examinations showed that some TiO2 particles had entered the spleen and caused the lesion of spleen. Thrombosis was found in the pulmonary vascular system, which could be induced by the blocking of blood vessels with TiO2 particles. Moreover, hepatocellular necrosis and apoptosis, hepatic fibrosis, renal glomerulus swelling and interstitial pneumonia associated with alveolar septal thickening were also observed in high-dose groups.
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PMID:In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection. 1915 10

To study the clinical features and associated risk factors of interstitial lung disease (ILD) in clinically amyopathic dermatomyositis (CADM) in Chinese patients. Forty-one Chinese Han patients with a diagnosis of CADM in West China Hospital from August 2008 to 2011 were retrospectively analyzed. The prevalence of ILD in CADM patients is 60.98 %, in which 26.83 % for acute/subacute interstitial pneumonia (A/SIP) and 34.15 % for chronic interstitial pneumonia (CIP). Mortality of A/SIP is 63.64 %, with a 6-month survival rate of 54.50 %. Levels of erythrocyte sedimentation rate, serum ferritin, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, hydroxybutyric dehydrogenase, and immunoglobulin A (IgA) are higher in CADM-ILD patients than CADM patients without ILD. Levels of serum ALB and lymphocyte count in peripheral blood are significant lower in A/SIP than in CIP group. Sign of ground glass opacities in high-resolution computed tomography (HRCT) images is more common in A/SIP group, and diffusion function is worse in these patients compared with CIP group. The prevalence of ILD in Chinese CADM patients is strikingly high, and A/SIP is a major cause of death in CADM patients. Laboratory findings combined with HRCT examination and pulmonary function tests can provide valuable predictive information of ILD or A/SIP in CADM patients.
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PMID:Interstitial lung disease in clinically amyopathic dermatomyositis (CADM) patients: a retrospective study of 41 Chinese Han patients. 2314 53

Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group.
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PMID:Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial. 2429 16

Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection.
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PMID:Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure. 2499 Apr 81