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)

As part of a study of the pathology and pathogenesis of bovine ephemeral fever virus infection 44 cattle were infected by the intravenous injection of virulent virus. Thirty-eight animals responded clinically and detailed haematological and serological data were obtained from 10 of them. Inappetence was the only clinical sign observed before the onset of fever. The temperature response was characteristically biphasic, with the second peak occurring 12 to 24 hours after the first. The only consistent haematological response was an increase in the numbers of circulating neutrophils with a concurrent decline in the numbers of mononuclear leucocytes. There were no detectable changes in plasma or blood volume, packed cell volume, red cell count, haemoglobin concentration, serum calcium, magnesium, phosphorus and creatinine concentrations, or aspartate aminotransferase activity. Viraemia was demonstrated on either the first or second day of clinical disease and lasted for at most 48 hours. Low levels of neutralising antibody could be detected within one or two days after the cessation of viraemia. Six antibody-free animals did not respond clinically to injection with virulent virus, and did not develop detectable viraemia or a serum neutralising antibody response.
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PMID:Clinical response of cattle to experimental infection with bovine ephemeral fever virus. 230 90

We measured levels of virus in sequential specimens from 137 patients with Lassa fever. The probability of fatal disease increased significantly with the level of viremia measured either on admission or during the course of illness. The odds ratio of death in patients with viremia greater than 10 TCID50/ml was 3.7 (90% confidence interval, 1.9-7.2). The same ratio in patients with viremia greater than 10 TCID50/ml and with levels of aspartate aminotransferase greater than or equal to 150 IU/liter was 21.5 (95% confidence interval, 5.2-99.0). Virus was found in throat cultures from 39% of viremic patients, compared with 14% of nonviremic patients (P less than .002); however, the level of virus was usually less than or equal to TCID50/ml. Fewer than 3% of patients were viruric during acute illness, and virus was isolated from three of three samples of cerebrospinal fluid. On admission, 53% of patients had IgG antibodies, and 67% had IgM antibodies. Recovery was not associated with the presence of either IgG or IgM. Virus was isolated from greater than 100 serum specimens that also contained high titers of IgG. Clinical Lassa fever was shown to be a disseminated systemic, primary viral infection, with an outcome highly associated with viremia but not with development of antibody.
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PMID:Clinical virology of Lassa fever in hospitalized patients. 380 73

In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and Lassa virus-convalescent plasma for the treatment of Lassa fever. A serum aspartate aminotransferase level greater than or equal to 150 IU per liter at the time of hospital admission was associated with a case-fatality rate of 55 percent (33 of 60). Patients with the same risk factor who were treated for 10 days with intravenous ribavirin, begun within the first 6 days after the onset of fever, had a case-fatality rate of 5 percent (1 of 20) (P = 0.0002 by Fisher's exact test). Patients whose treatment began seven or more days after the onset of fever had a case-fatality rate of 26 percent (11 of 43) (P = 0.01). Viremia with levels greater than or equal to 10(3.6) TCID50 per milliliter on admission was associated with a case-fatality rate of 76 percent (35 of 46). Patients with this risk factor who were treated with intravenous ribavirin within the first six days after onset of fever had a case-fatality rate of 9 percent (1 of 11) (P = 0.006), whereas those treated after seven days or more of illness had a fatality rate of 47 percent (9 of 19) (P = 0.035). Oral ribavirin was also effective in patients at high risk of death. Lassa-convalescent plasma did not significantly reduce mortality in any of the high-risk groups. We conclude that ribavirin is effective in the treatment of Lassa fever and that it should be used at any point in the illness, as well as for postexposure prophylaxis.
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PMID:Lassa fever. Effective therapy with ribavirin. 394 Mar 12

Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are the accepted sequelae of chronic hepatitis C virus (HCV) infection. However, the real natural history of HCV infection is not still well understood. To approach this problem, we investigated 91 individuals positive for antibodies against HCV (anti-HCV), who have received annual liver function examination in a local town known to have had high carrier rates of hepatitis B virus (HBV) and HCV. Among the 91 anti-HCV-positive individuals, 63 had undertaken the annual examination more than five times in the past 14 years. We analyzed retrospectively the past liver function test results of these 63 subjects and evaluated their present virological status by determining HCV genotypes and estimating quantity of HCV RNA in the sera. Among the 63 subjects, 50 (79.4%) had HCV RNA in the serum and 40 (80%) of the 50 subjects with HCV RNA had abnormal alanine aminotransferase or aspartate aminotransferase level more than once in their records. However, the other 10 (20%) had no abnormal levels during the period examined. Six of 50 (12%) had ultrasonographic findings suggestive of cirrhosis. Thus, HCV-infected individuals in this area did not seem to have progressive liver diseases. Considering the advanced ages of the individuals examined (mean 64 years old), we may have observed a stage in the natural history of HCV infection in which viremia persists in most individuals and the tendency to progress to serious chronic liver disease is mild.
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PMID:A retrospective study of hepatitis C virus carriers in a local endemic town in Japan. A possible presence of asymptomatic carrier. 785 Dec 13

6-Dimethylamino-9-(beta-D-arabinofuranosyl)-9H-purine (ara-DMAP) effectively prevented the development of rash and appreciably reduced viremia in simian varicella virus-infected monkeys. Doses of 100 and 50 mg/kg/day, administered orally, were highly effective. The lowest dose of 20 mg/kg/day was much less effective in preventing moderate viremia. However, the 20 mg/kg/day did prevent the development of rash in two of three monkeys. All three doses of ara-DMAP reduced liver infection as reflected by lower aspartate aminotransferase values in the sera of the African green monkeys. Orally administered ara-DMAP was rapidly absorbed. However, significant variation among individual monkeys in the AUC values, peak plasma levels, and plasma half-lives were observed.
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PMID:6-Dimethylamino-9-(beta-D-arabinofuranosyl)-9H-purine: pharmacokinetics and antiviral activity in simian varicella virus-infected monkeys. 845 45

Experimental infection of three indigenous breeds of sheep in Nigeria, namely the West African Dwarf (WAD), Yankasa and Ouda resulted in fatal disease with the Zinga Rift Valley Fever virus. Infected sheep of the three breeds responded by pyrexia within 24 h of infection, that lasted 6 to 7 days, but peaked between day 2 and 4 post-infection. Viraemia coincided with pyrexia and peaked (10(9) PFU/ml) 3 days p.i. in Yankasa and WAD sheep, but with highest titre (10(7.5) PFU/ml) in Ouda sheep. Zinga Rift Valley Fever virus infection of sheep was characterised by hyperactivity, watery and mucoid nasal discharges, projectiles and bloody diarrhoea, external haemorrhage and clinical manifestations of nervous disorders. Viraemia was followed by low level of antibody development in all the infected sheep. Haemotological changes included a sharp fall in the PCV, Hb concentration and total RBC count during the course of the disease. These changes were most severe in the Yankasa, followed by WAD and Ouda breeds. There were thrombocytopaenia, prolongation of prothrombin and clotting times in all the infected sheep. There was also progressive leucopaenia associated with lymphopaenia. The total protein and albumin levels were depressed, but the globulin level rose from day 5 p.i. The changes in the serum biochemical constituents included sharp and progressive increase in the level of alanine aminotransferase and aspartate aminotransferase. The sodium level decreased gradually while that of potassium was initially stable but later increased until the infected animals died. There was a significant increase in the level of blood urea nitrogen from day 3 p.i. that continued until the infected animals died. Gross and microscopic examinations of the carcasses of the infected sheep showed significant lesions in many organs, including disseminated intravascular coagulation.
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PMID:Experimental infection of three Nigerian breeds of sheep with the Zinga strain of the Rift Valley Fever virus. 888 13

Infection with hepatitis C virus (HCV) genotype 1b has been reported to be associated with more severe posttransplantation liver disease than infection with non-1b genotypes. To address this issue, we evaluated the outcome in 124 patients who underwent liver transplantation for chronic HCV infection. The HCV genotype and/or serotype responsible for infection was determined by four different methods. HCV RNA was detected in serum samples by polymerase chain reaction (PCR) amplification, and quantified by branched DNA assay. Disease severity was expressed as a histological score (which included grading of portal inflammation, lobular activity, fibrosis, and cytopathic changes). Median duration of histological follow-up was 25 months (range 1-75 months). Genotype was assignable in 112 (92.5%) patients. Genotypes responsible for infection were as follows: 1a = 32.2%, 1b = 27.3%, 2a = 7.4%, 2b = 8.3%, 3a = 14%, and mixed infection (more than one subtype) = 3.3%. Level of viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and total histological score were not significantly different in patients infected with type 1b compared with patients infected with other genotypes. While duration of histological follow-up was greater in patients infected with type lb versus other types (P = .02), by univariate and multivariate analysis neither HCV genotype (lb versus others), level of viremia nor duration of histological follow-up were associated with disease severity. Moreover, there was no significant difference in the actuarial graft survival in patients infected with type lb compared with that of patients infected with non-lb types (82% and 87% at 3 years, respectively). Reanalysis using HCV genotype 1 showed no association with disease severity, graft survival, and patient survival. We conclude that HCV genotype 1 and subtype 1b are not associated with disease severity or graft survival in liver transplantation recipients.
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PMID:Severity of liver disease in liver transplantation recipients with hepatitis C virus infection: relationship to genotype and level of viremia. 890 72

Hepatitis C virus is the leading cause of acute and chronic liver disease in hemodialysis patients. There are at least six major HCV-genotypes, with a well documented geographical distribution in the general population. Moreover, HCV-genotype is one of the major determinants of the therapeutic response to Interferon Alpha in affected patients. Since the therapeutic outcome in HCV-positive hemodialysis patients, especially with regard to the different HCV-genotypes, is of interest, a multicentre epidemiologic study was performed in HCV-antibody positive hemodialysis patients of two geographically remote countries, i.e. in Flanders (Belgium) and in Saudi-Arabia. 184 chronic hemodialysis patients, with a positive second or third generation Elisa assay for HCV, were tested for HCV-viremia and HCV-genotype, using a 5' untranslated region (UR) nested PCR for the detection of HCV-RNA and subsequently type-specific probes to hybridize with HCV-RNA (Inno-Lipa). Additionally, clinical data were collected by means of a standardized questionnaire, thoroughly completed by the nephrologist in charge of each respective patient. Viremia was present in 79% of the patients (146 out of 184). The prevalence of HCV-genotypes differed significantly between Belgian and Saudi-Arabian dialysis-patients. In Belgian dialysis patients HCV-genotype 1b was most prevalent (i.e. 62%), while in Saudi-Arabian patients HCV-genotypes 4, 1b, and la were present in respectively 36,4%, 31,7%, and 25,8% of the HCV-PCR positive patients. Although there were significant differences between Belgian and Saudi-Arabian dialysis patients, no clinical data showed any significant correlation with the HCV-genotype. Transaminases, determined over a six months period, showed normal average values. Doubling of the transaminases, in at least one out of six measurements over a six monthly period, occurred only in 14% (alanine aminotransferase, ALT) and 10% (aspartate aminotransferase, AST) of the patients. In Belgian dialysis patients, HCV-genotype 4 (or HCV-genotype 5) significantly correlated with a more recent start of dialysis treatment. We conclude that there is a significant different geographical prevalence of HCV-genotypes in HCV-affected hemodialysis patients. None of the different HCV-genotypes shows any particular clinical expression. Transaminases are not a sensitive marker for ongoing HCV-replication in hemodialysis patients. In Belgian dialysis patients, a changing pattern of HCV-infection is suggested, with an increasing prevalence of HCV-genotype 4 (or HCV-genotype 5) in more recent years. These data suggest possible implications for the therapeutic strategy in dialysis patients.
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PMID:Prevalence and clinical expression of HCV-genotypes in haemodialysis-patients of two geographically remote countries: Belgium and Saudi-Arabia. 912 93

It is known that patients on chronic haemodialysis are frequently infected with hepatitis C virus (HCV). It has recently been found that GB virus-C (GBV-C) and hepatitis G virus frequently coinfect patients with HCV. This study aimed at elucidating the clinical implications of GBV-C infection among haemodialysis patients who have and do not have HCV infection. GBV-C RNA was detected in sera of randomly selected 98 anti-HCV-positive and 85 -negative patients on dialysis by reverse transcription-polymerase chain reaction using two sets of amplification primers made from the reported sequences of the non-structural protein 3 and 5' untranslated regions. In these patients, liver function tests were carried out at regular intervals. There were six patients who were coinfected with HCV and GBV-C and three who had only GBV-C RNA. All had a history of past blood transfusion. The onset of mild hepatitis was identified in three HCV-negative patients; elevation of alanine aminotransferase (ALT) following blood transfusion was very mild but recognizable, and aspartate aminotransferase (AST) was higher than ALT. In two of six coinfected patients, the onset of liver disease was recognized with a peak ALT of 72 and 90 IU/L, respectively. Two of these six were Amplicore (HCV-RNA) negative and asymptomatic, two had low-grade HCV viraemia and two moderate-grade HCV viraemia. Of the 98 anti-HCV-positive cases, 41 were thought to have had nosocomial infection of HCV or non-A, non-B virus; none of them had GBV-C. GBV-C RNA was negative in nine patients who had chronic non-A-E hepatitis. GBV-C infection was detected in 6.1% of anti-HCV-positive and in 3.5% of -negative dialysis patients. All had blood transfusion in the past, and there was no evidence of patient-to-patient spread of GBV-C in hospital. The liver disease was very mild and self-limited in GBV-C infection alone. The natural history of coinfected patients may be similar to that of those with chronic HCV infection, but the liver disease appears to be milder.
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PMID:GB virus-C infection among chronic haemodialysis patients: clinical implications. 943 45

Hepatitis C virus (HCV) infection usually recurs after orthotopic liver transplantation (OLT), and most patients develop graft damage. This study compared the efficacy of interferon alfa (IFN-alpha) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT recipients with chronic hepatitis C were randomized to receive either IFN-alpha (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks. Virological, biochemical, and histological responses to treatment were assessed. Twenty-eight patients completed the treatment regimen, two ribavirin-treated patients being withdrawn because of severe hemolysis. Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin (93%) and 6 of 14 patients receiving IFN-alpha (43%; P=.01). Lobular inflammation was reduced in 9/14 ribavirin-treated (64%) and 3 of 14 IFN-alpha-treated patients (21%; P=.05), each of whom had a biochemical response. However, the total histological activity index did not improve in either the interferon (P=.43) or the ribavirin (P=.96) group. Posttreatment viremia levels were significantly reduced in IFN-alpha-treated (P=.05) but not in ribavirin-treated (P=.88) patients. Hemolysis occurred in all ribavirin-treated patients, with serum hemoglobin decreasing to < 10 g/dL in 50%. Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment (P=.02 and P=.004, respectively). We concluded that in patients with chronic hepatitis C after OLT, IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation, but not the total histological activity index. These findings provide a rationale for combination therapy in the post-OLT setting, although patients must be carefully monitored for hemolysis.
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PMID:A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation. 958 98


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