Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although case reports of herpes simplex virus (HSV) causing acute hepatitis in otherwise healthy adults have appeared recently in the literature, a prospective study of the incidence of HSV-hepatitis in the general population hitherto has not been reported. In the present study, serum samples from 124 young adults attending a sexually transmitted disease clinic with either genital herpes infections (n = 86) or non-herpes sexually transmitted diseases (n = 38) (controls) were analyzed for liver enzyme abnormalities (including aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). Twelve of eighty-six (14%) herpes-infected patients had mildly abnormal liver enzyme tests (less than or equal to twice the upper limit of normal) as opposed to only 1 of 38 controls (2.6%), (P less than .05). All individuals in the herpes-hepatitis group were anicteric, and only two complained of constitutional symptoms (malaise and fatigue). Liver enzyme tests were repeated in nine herpes-hepatitis patients 1 week after their genital lesions had resolved, and in six of nine patients the results had returned to within normal limits. Four patients subsequently returned at the onset of a recurrence of their genital herpes. In all four, serum ALT levels were elevated from the previous occasion, and in three of the four levels just exceeded the upper limit of normal. One patient was followed through three recurrences of his genital herpes. In that individual, the extent of liver enzyme abnormalities appeared to correlate with the presence or absence of his genital lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genital herpes and hepatitis in healthy young adults. 301 68

We encountered a case which proved to be a mixed infection of herpes simplex virus (HSV) type 1 and type 2 in retrospective terms by in situ hybridization (ISH) and polymerase chain reaction (PCR). The case was a male. The gestational age was 39 weeks and 2 days. The birth body weight was 3024 g. A fever developed from the age of 6 days and he was admitted to the neonatal intensive care unit at the age of eight days. AST was 1042 IU/L, and ALT 206 IU/L. In spite of treatment, the patient died at the age of 12 days. Using paraffin embedded tissues, we performed the ISH and PCR on the cerebrum, lungs, liver, spleen, bone marrow, adrenal gland, and kidneys. With the ISH, the lungs, liver, spleen and adrenal gland were both HSV type 1 and type 2. With the PCR, only the liver was positive for type 1, and the lungs, liver, spleen, and adrenal gland were positive for type 2. In the ISH, a probe showing a cross reaction between type 1 and type 2 was used for type 1 probe this time. But a type 2 probe and PCR did not show a cross reaction. We concluded that this case confirmed the presence of mixed infection (HSV type 1 and type 2) in neonatal HSV infection.
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PMID:[A case of neonatal herpes infection which proved to be a mixed infection of herpes simplex virus type 1 and type 2]. 874 14

Herpes simplex-induced fulminant hepatitis is an infrequently reported cause of hepatitis in adults. Pregnant females and patients with impaired cellular immunity may be at increased risk, although healthy adults have been affected. The diagnosis may be underrecognized due to nonspecific presenting symptoms and lack of typical cutaneous herpes lesions. We present three cases of fatal herpes simplex fulminant hepatitis. Our review of case reports of herpes simplex hepatitis in adults demonstrates improved survival with intravenous acyclovir therapy. We believe that empiric use of acyclovir should be considered while the diagnostic evaluation of non-acetaminophen-induced fulminant hepatitis is underway. Recognition of characteristic liver function abnormalities seen with fulminant herpes simplex hepatitis include marked elevation of transaminases with AST > ALT and a mild hyperbilirubinemia (anicteric hepatitis), and they should prompt acyclovir therapy. This is especially true when there are no obvious risk factors for other forms of hepatitis.
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PMID:Herpes simplex-induced fulminant hepatitis in adults: a call for empiric therapy. 1125 65

Phage display techniques rely on nearly random oligonucleotide sequences inserted into the protein III filament binding protein of an Escherichia coli filamentous phage M13 to generate a library of phage that express more than 10(7) different peptides. Phage that expresses a sequence having high affinity for a specific molecule, cell, or tissue can then be isolated through selective binding and recovery. Selected phage cannot only be used as gene transfer vectors in themselves, but the small peptide epitopes can be sequenced and potentially recombined into the attachment proteins of viral vectors, or used by themselves to target other therapeutic agents and diagnostic imaging radiolabels. Most phage display selections are carried out against purified and/or fixed protein targets, raising concerns as to the relevance of the selected epitopes. We have selected phage from the CMTI library against viable U87-MG human malignant glioma cells using a derivation of biopanning. The library, which initially contained phage expressing 2x10(7) different epitope sequences, collapsed after four rounds of selection such that 42% of recovered clones expressed a consensus sequence. Selective binding to viable adherent U87-MG cells was subsequently demonstrated under physiologic conditions at 167% (+/-27%) unselected phage using a novel, viable enzyme-linked immunosorbent assay technique. In comparison, there was no difference in binding to control 9L rat gliosarcoma, PANC-1 human pancreatic adenocarcinoma, T98-MG human malignant glioma, or AST-4 human malignant glioma cells of selected compared to unselected phage. Using polymerase chain reaction, the epitope was recovered with flanking unique restriction sites for recombination into a herpes simplex virus type-1 vector. This study demonstrates and discusses optimized methodologies for using phage display to target viable cells.
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PMID:Isolation, characterization, and recovery of small peptide phage display epitopes selected against viable malignant glioma cells. 1149 72

Suicide gene expression in specific tissue of transgenic animals has been used for cell-specific ablation. To examine the influence of hepatocyte removal, we produced the herpes simplex virus thymidine kinase (HSVtk) transgenic rat, whose gene was regulated by an albumin enhancer promoter. The liver presence of HSVtk was demonstrated in one line of the transgenic rats. We injected ganciclovir (GCV, 50mg/kg) into the rat on alternate days. After 28 days of GCV administration, liver tissues, and blood of the rats were collected. The histological investigation revealed infiltration of T cells, macrophages, granulocytes/neutrophils, and hepatocyte cell death. The biochemistry analysis demonstrated elevated levels of AST, ALT, and total bilirubin in transgenic rat. In conclusion, the transgenic rat with expressed albumin-specific HSVtk developed experimental hepatitis with administration of GCV, and will be a useful model to facilitate the evaluation of drug effects for clinical control of liver disease.
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PMID:Inducible liver injury in the transgenic rat by expressing liver-specific suicide gene. 1462 69

Gene transfer into hepatocytes is highly desirable for the long-term goal of replacing deficient proteins and correcting metabolic disorders. Vectors based on herpes simplex virus type-1 (HSV-1) have been demonstrated to mediate efficient gene transfer into hepatocytes both in vitro and in vivo. Large transgene capacity and extrachromosomal persistence make HSV-1/EBV hybrid amplicon vectors an attractive candidate for hepatic gene replacement therapy. To assess liver-directed gene transfer, we constructed (i) a conventional HSV-1 amplicon vector encoding a secreted reporter protein (secreted alkaline phosphatase, SEAP) under the control of the HSV-1 immediate-early 4/5 promoter; (ii) a HSV-1 amplicon encoding SEAP under the control of the artificial CAG promoter (the chicken beta-actin promoter and cytomegalovirus (CMV) immediate-early enhancer); and (iii) a HSV-1/EBV hybrid amplicon, also encoding SEAP under the control of the CAG promoter. While all three vector constructs yielded high SEAP concentrations in vitro and in vivo, use of HSV-1/EBV hybrid amplicon vectors significantly prolonged the duration of gene expression. Using conventional amplicon vectors in cultured hepatocytes, SEAP was detected for two weeks, whereas SEAP was detected for at least six weeks when HSV-1/EBV amplicons were used. Intraparenchymal injection into the liver of SICD mice yielded high (up to 77 ng of SEAP per milliliter serum) and sustained (greater than three weeks) expression of SEAP. Serum transaminases (ALT/AST) were measured at different time points to monitor for hepatocellular damage. While initially elevated four times above baseline, the transaminase levels returned to normal after three to seven days. These results demonstrate the usefulness of HSV-1-based amplicons and SEAP for the evaluation of gene replacement strategies in the liver.
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PMID:Gene transfer into hepatocytes mediated by herpes simplex virus-Epstein-Barr virus hybrid amplicons. 1558

Non-alphabetical hepatitis (Epstein Barr virus -EBV-, cytomegalovirus -CMV-, Herpes simplex virus -HSV-, varicella zoster virus -VZV-etc.) may be a mode of revelation of several underlying chronic liver diseases including autoimmune hepatitis (HAI). We report a peculiar case of acute EBV hepatitis, revealing type I autoimmune hepatitis confirmed by liver biopsy through puncture in a female patient on breast cancer treatment. The study involved a 29-year-old female patient on breast cancer treatment scheduled to receive radiotherapy and chemotherapy, hospitalized for acute severe hepatitis (fever with jaundice, hypertransaminasemia (normal AST level 47 and normal ALT level 23 and prothrombin activity 25%). The test for viral hepatitis A, B, C, and E was negative and subhepatic veins were free on doppler. Non-alphabetical hepatitis was suspected based on fever with jaundice. Patient's assessment showed recent EBV infection diagnosed on the basis of the presence of anti-VAC IgM/G and anti-EBNA Ab IgG. The patient received acyclovir for 10 days. Progression was marked by ascites. The diagnosis of autoimmune hepatitis was retained based on laboratory tests (gamma peak on serum protein electrophoresis and positive anti-nuclear antibodies) and histological examination. Clinical-biological remission was obtained with corticosteroid therapy. EBV infections should be investigated in immunocompromised patients with fever in the clinical course of acute hepatitis. Practitioners should also suspect it in patients with persistent cytolysis following an infectious episode in order to prevent the occurrence of autoimmune hepatitis, in particular in female patients, in a context of self-immunity and negative serological tests for alphabetical viral hepatitis.
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PMID:[Autoimmune hepatitis following acute severe Epstein-Barr virus hepatitis]. 3324 40