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)

The aim of the present study was to detect acute Hepatitis E virus (HEV) infection in patients with abnormal alanine transaminase (ALT) in which other viral hepatitis infections had been excluded in southern Spain, an area adjacent to regions where this disease is endemic. Of 336 sera tested 30 (8.92%) were positive for IgM antibodies against HEV (anti-HEV IgM) and 7 (2.08%) were negative in a repeated assay. Immunoblot analysis (IBA) was applied to the 37 positive sera in the first assay; its results were positivity for 26 (7.73%), ambiguous for 5 and negative for 6 sera. Amplification of ORF1 and ORF2 of HEV by means of nested RT-PCR was carried out with the 37 sera that were either positive or ambiguous by ELISA; a positive result was obtained only with one serum for the ORF2 protein. IgM antibodies against the HEV ORF2 protein could be a useful marker in the diagnosis of acute infection and a substitute for the determination of viral RNA in serum; this is of both diagnostic and epidemiological importance as it would allow the patients transmitting the infection to be recognized by means of a simple determination of antibodies. The sequence of the ORF2 fragment of HEV occurring in samples taken from both humans and animals amplified in this study has considerable homology with the sequences of HEV strains/isolates of European origin. These results demonstrate that an autochthonous HEV circulates in Spain.
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PMID:Detection of hepatitis E virus in patients sera in southern Spain. 1559 16

Hepatitis E in industrialized countries has not been well studied. To define the possible risk factors for transmission of hepatitis E virus (HEV) and for the severe form of hepatitis E in Japan, we investigated the clinical and virological characteristics of hepatitis E in 32 patients who contracted the mild (n=23) or severe form (n=9) of domestically acquired hepatitis E between 1996 and 2004 in Hokkaido, where hepatitis E is most prevalent in Japan. Nine patients with the severe form of hepatitis E included two patients with fulminant hepatitis E and seven patients who were diagnosed with severe acute hepatitis in which hepatic encephalopathy did not appear during the course of the illness despite low plasma prothrombin activity (<or=40%) and/or increased total bilirubin level (>or=20 mg/dl). At least 25 patients (78%) had consumed uncooked or undercooked pig liver and/or intestine 1-2 months before the onset of hepatitis E. When compared with the seven patients with HEV genotype 3, the 25 patients with HEV genotype 4 had a higher peak alanine aminotransferase (ALT) level (P=0.0338) and a lower level of lowest prothrombin activity (P=0.0340). The severe form of hepatitis E was associated with the presence of an underlying disease (56% [5/9] vs. 17% [4/23], P=0.0454). The study suggests that zoonotic food-borne transmission of HEV plays an important role in the occurrence of hepatitis E in Hokkaido, Japan, and that the HEV genotype and the presence of an underlying disease influence the severity of hepatitis E.
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PMID:Possible risk factors for the transmission of hepatitis E virus and for the severe form of hepatitis E acquired locally in Hokkaido, Japan. 1590 1

Subclinical hepatitis E virus (HEV) infection among healthy individuals was studied serologically and molecularly. Serum samples collected at screening between March and April 2004 (or just before retirement) from 266 medical staff members (35 males, 231 females) who had been working for 8.8 +/- 8.5 (mean +/- standard deviation, range, 0.3-35.1) years in a city hospital in Japan and serum samples that had been collected from these staff members at the start of employment were tested for IgA, IgM, and IgG antibodies to HEV (anti-HEV) by in-house enzyme-linked immunosorbent assays. Overall, six subjects (2.3%) tested positive for anti-HEV IgG at the screening; among them, four subjects (1.5%) had already been positive for anti-HEV IgG at the start of employment and two subjects (0.8%) seroconverted after initiation of employment. Periodic serum samples that had been collected from the two seroconverted subjects were tested for HEV antibodies and HEV RNA. The two subjects became positive for anti-HEV IgG in 1978 or 2003, respectively, with no discernible elevation in alanine aminotransferase (ALT) level, and continued to be seropositive up through the screening date. Although anti-HEV IgM was not detectable in the two subjects, one was infected transiently with Japan-indigenous HEV strain of genotype 3 and the other was positive transiently for anti-HEV IgA. The present study indicates that even an individual with subclinical HEV infection had evidence of transient viremia in the absence of ALT elevation and that anti-HEV IgA detection may be useful for serological diagnosis of recent subclinical HEV infection.
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PMID:Serological and molecular studies on subclinical hepatitis E virus infection using periodic serum samples obtained from healthy individuals. 1597 33

A hepatitis E virus (HEV) ORF2 peptide expressed in an unfused pattern in E. coli, NE2, can self-assembly into homodimers and oligomers, and the immuno-reactivity of the dimers or oligomers to HEV infected serum is much stronger than monomer, which suggested that some important conformational epitopes be better exposed in dimer or oligomer form. Three Rhesus monkeys were vaccinated with three doses (10 microg/dose) purified NE2 in Freud's adjuvant under a schedule of Od, 10d, and 30d. Specific antibodies can be detected on second week, and on sixth week while virus challenge were performed with 106 PCR titer of virus positive stool suspention, the antibody titer of one monkey was 1: 100 000, the other two were both 1: 20 000. Three monkeys in control group presented typical acute hepatitis E manifestation: increased seral amino transferase (ALT), antibody conversion, and continuous virus excretion in stool. In contrast, the ALT of monkeys in vaccinated group continued to be normal, stool virus had not been detected in one monkey, and presented only a short duration in another two. One NE2-vaccinated monkey serum with antibody titer 1: 20 000 was first incubated with HEV (10(3) PCR titer) for neutralization, then the mixture were used to challenge two monkeys, the results showed that two monkeys in control group continued to excrete virus for more than three weeks, sera antibody conversion, and one monkey presented obvious ALT increase. Both two monkeys challenged with antibody neutralized virus had not detected virus in stool, the antibodies decreased slowly, and ALT continued to be normal. These results suggested that the prokaryotic expression recombinant protein NE2 have good immunogenicity and immunoprotectivity, and should be a good candidate for an effective hepatitis E vaccine.
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PMID:[The immuno-protect study of a hepatitis E virus ORF2 peptide expressed in E. coli]. 1627 69

In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.
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PMID:Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan. 1697 Nov 72

Hepatitis E virus (HEV) infection is known to cause epidemic outbreaks as well as sporadic disease in many parts of the world. Clinical presentation of hepatitis E varies from acute icteric viral hepatitis to severe disease with fulminant hepatic failure, and anicteric infection (no jaundice but with ALT elevation). According to available data HEV infection does not lead to chronic liver failure. We are reporting a case of 37 years old army soldier who was admitted as a case of HEV induced acute viral Hepatitis. Later he was found to have chronic liver disease (CLD) with persistence of HEV antibodies and absence of any other detectable cause of CLD.
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PMID:A case of chronic liver disease. Hev induced or cryptogenic? 1697 23

Infection with hepatitis E virus (HEV) may be diagnosed by the presence of HEV RNA or anti-HEV antibodies. An enzyme immunoassay (EIA) was developed for the detection of antigen. Twenty-four monoclonal antibodies (mAbs) were produced. An indirect sandwich EIA was developed to detect HEV antigen using a combination of three mAbs as coating antibodies. Approximately 44.6% (33/74), 28.6% (50/175), and none (0/27) of sera positive for anti-HEV IgM alone, both anti-HEV IgM and IgG, and anti-HEV IgG alone also were positive for HEV antigen using this EIA. Forty-two HEV antibody-positive sera were tested for HEV RNA and antigen in parallel and the concordance was 81.0% (34/42). All PCR products were found to belong to HEV genotype 4. In order to evaluate the temporal relationship between HEV antigen positivity and HEV RNA, anti-HEV IgG and IgM, and ALT concentrations, macaques were infected with HEV genotypes 1 and 4 and serial samples were collected. The results showed that the antigen EIA can detect the capsid proteins of both genotypes. HEV antigen was detectable prior to ALT elevation and the appearance of anti-HEV antibodies in the infected monkeys and lasted for several weeks in all cases. HEV antigen became detectable in the serum at almost the same time as HEV RNA in feces but persisted for 4 weeks less than HEV RNA. This assay should be valuable for the diagnosis of acute hepatitis E, particularly in the window period prior to seroconversion to anti-HEV.
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PMID:Detection of HEV antigen as a novel marker for the diagnosis of hepatitis E. 1699 97

Hepatitis E virus (HEV) RNA has been detected in the stool and serum of patients with HEV infection and experimentally infected nonhuman primates. However, dynamics of HEV levels in the stool and serum during clinical and subclinical infections have not been determined. A real-time reverse transcription polymerase chain reaction assay, using SYBR Green I in a LightCycler, was developed and optimized to allow quantification of HEV RNA in the stool and serum of both genotype 1 and 2 isolates. The specificity of the assay was confirmed by testing known HEV-RNA-positive and -negative stool and serum specimens and the sensitivity was evaluated using a synthetic HEV RNA standard. Profiles of viraemia and faecal shedding in two chimpanzees inoculated with an isolate of HEV genotype 1 showed the appearance of virus in the stools on day 4 postinoculation (5.65-6.85 log copies/mg) and in the serum on day 7 postinoculation (6.0-6.93 log copies/mL). Peak HEV RNA levels in the stool and serum coincided with peak alanine aminotransferase (ALT) levels observed on day 22 postinoculation in the two chimpanzees. At the time of detection of IgG anti-HEV in serum, viral RNA was no longer detectable in the stool or serum and ALT values had returned to normal levels in both chimpanzees, suggesting the efficacy of the immune response in terminating viral replication. Quantitative evaluation of HEV RNA in humans may allow determining the role of virus levels in the pathogenesis and transmission of HEV.
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PMID:Quantitative detection of hepatitis E virus RNA and dynamics of viral replication in experimental infection. 1710 83

Ongoing subclinical infection of hepatitis E virus (HEV) has not been fully studied. In the present study, serum samples were collected from 6700 voluntary blood donors with an elevated alanine aminotransferase (ALT) level of 61-476 IU/l at a Japanese Red Cross Blood Center, and were tested for the presence of IgG, IgM and IgA classes of antibodies to HEV (anti-HEV) by in-house ELISA and HEV RNA by nested RT-PCR. Overall, 479 blood donors (7.1%) were positive for anti-HEV IgG, including 8 donors with anti-HEV IgM and 7 donors with anti-HEV IgA. Among the nine donors with anti-HEV IgM and/or anti-HEV IgA, six had detectable HEV RNA. The presence of HEV RNA was further tested in 10-sample minipools of sera from the remaining 6691 donors, and three donors including one without anti-HEV IgG were found to be positive for HEV RNA. When stratified by ALT level, the prevalence of HEV RNA was significantly higher among the 109 donors with ALT > or = 201 IU/l than among the 6591 donors with ALT of 61-200 IU/l (2.8% vs. 0.1%, P < 0.0001). The HEV isolates obtained from the nine viremic donors segregated into genotype 3, shared a wide range of identities of 85.6-98.5% and were 87.3-93.9% similar to the Japan-indigenous HEV strain (JRA1), in the 412-nucleotide sequence of open reading frame 2. This study suggests that approximately 3% of Japanese individuals with ALT > or = 201 IU/l have ongoing subclinical infection with various HEV strains.
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PMID:Ongoing subclinical infection of hepatitis E virus among blood donors with an elevated alanine aminotransferase level in Japan. 1745 24

Hepatitis E is rare in Japan but is occurring more frequently than previously thought. To investigate whether de novo subclinical infection of hepatitis E virus (HEV) has recently increased in Japan, HEV RNA was assayed in serum samples obtained from 4019 Japanese voluntary blood donors with alanine aminotransferase (ALT) of > or =61 IU/l, who are likely to have ongoing HEV infection, during 1991-2006. The overall rates of IgG-class antibody to HEV (anti-HEV IgG), anti-HEV IgM/IgA and HEV RNA among 3185 donors in 2004-2006 were comparable with those among 594 donors in 1998 (5.3 vs. 5.2%, 0.2 vs. 0.5%, and 0.2 vs. 0.3%, respectively). Among blood donors with ALT > or = 201 IU/l in three groups according to the year of blood collection (1991-1995 [n = 156], 1996-1999 [n = 116] and 2004-2006 [n = 61]), there were no appreciable differences in the prevalence of anti-HEV IgG (5.8, 4.3, and 6.6%, respectively), anti-HEV IgM/IgA (1.9, 3.4, and 3.3%, respectively) and HEV RNA (1.3, 3.4, and 3.3%, respectively). The eleven HEV isolates obtained in the present study differed from each other by 1.7-22.8% in the ORF2 sequence and segregated into genotype 3 or 4. The occurrence rate of subclinical infection with divergent HEV strains has essentially remained unchanged during 1991-2006 in Japan.
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PMID:Unchanged high prevalence of antibodies to hepatitis E virus (HEV) and HEV RNA among blood donors with an elevated alanine aminotransferase level in Japan during 1991-2006. 1753 50


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