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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpes simplex virus (HSV) hepatitis is rare in adults, usually occurring in immunocompromised individuals and in otherwise healthy women in the third trimester of pregnancy. Three cases of HSV hepatitis occurring in pregnant women were diagnosed at our institution between 1981 and 1990. This diagnosis was not suspected clinically, and in each case was made on the basis of histology, immunoperoxidase studies, and viral cultures of liver tissue. Clinically, the patients had severe anicteric liver failure with markedly elevated serum aspartate aminotransferase and alanine aminotransferase levels; two of the three patients died. None had mucocutaneous lesions at the time of diagnosis. Histologically, two distinct patterns of necrosis and inflammation were seen. Two of the cases had well-demarcated foci of necrosis scattered randomly throughout the lobules with neutrophilic infiltration, giving the impression of abscess formation. Hepatocytes at the periphery of these areas of necrosis had enlarged nuclei with "ground-glass" inclusions; however, no Cowdry type A inclusions were seen. Rare multinucleated cells were present. Immunoperoxidase staining using antibodies to HSV was positive primarily in the hepatocytes with inclusions. The third case had diffuse, almost total hepatic necrosis with no viral inclusions and virtually no inflammatory response. This histologic pattern is similar to that seen in neonates with HSV infection. Immunoperoxidase studies in this case were negative; however, viral cultures were positive. While HSV hepatitis may be suspected or diagnosed on the basis of histology alone, viral cultures are an important adjunct since viral inclusions may be absent. Prompt diagnosis is important since antiviral therapy is now available.
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PMID:Herpes simplex virus hepatitis in pregnancy: a clinicopathologic study of three cases. 174 Mar 3

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

2'-Fluoro-5-iodoarabinosylcytosine (FIAC) has potent antiviral activity in vivo against herpes simplex virus types 1 and 2 and cytomegalovirus. For examination of the clinical efficacy of FIAC, a randomized, double-blind study of FIAC versus adenine arabinoside (ara-A) was conducted in 34 immunosuppressed individuals with varicella-zoster virus infections. The median time to the appearance of the last new lesion was shorter in patients who received FIAC relative to those who received ara-A (two versus five days, respectively; P less than .001) FIAC also reduced pain and accelerated initial crusting within 72 hr in a significantly greater proportion of patients when compared with ara-A (P = .004 and P = .0009, respectively). FIAC caused few toxic reactions (mild nausea and transient elevation in activity of serum aspartate aminotransferase). Thus FIAC is therapeutically superior to ara-A for the treatment of varicella-zoster virus infections in immunosuppressed subjects.
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PMID:2'-Fluoro-5-iodoarabinosylcytosine, a new potent antiviral agent: efficacy in immunosuppressed individuals with herpes zoster. 352 94

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

The compound 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent inhibitor of a number of viruses in vitro such as human immunodeficiency virus types 1 and 2, herpes simplex virus types 1 and 2, hepatitis B virus, cytomegalovirus, and Epstein-Barr virus. PMEA also proved to be effective in vivo against feline immunodeficiency virus in cats and simian immunodeficiency virus in rhesus monkeys. In an open, non-placebo-controlled trial, the safety of weekly doses of PMEA in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was studied for a period of 11 weeks. CD4+ T-cell counts at baseline were between 10 and 450/mm(3). The drug was administered intravenously at a dose of 1000 mg. No serious side-effects were seen. On one occasion one patient showed alanine aminotransferase and aspartate aminotransferase levels 5 times higher than the upper limit of normal and another patient showed on one occasion aspartate aminotransferase levels 5 times higher than the upper limit of normal. In another patient serum amalyse levels increased, on one occasion 1.5 times above the upper limit of normal. An improvement in general well-being was reported by all patients. For patients with a CD4+ T-cell count > 100/mm(3) at baseline, the CD4+ T-cell count increased from a mean of 283/mm(3) at baseline to a mean of 448/mm(3) at the end of the study. Repeat infusions of PMEA at a dose of 1000 mg were safe and well tolerated. Our results suggest that PMEA, administrated according to this treatment schedule, may be effective in treating patients with human immunodeficiency virus infection.
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PMID:Safety of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in patients with human immunodeficiency virus infection: a pilot study. 886 29

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

Connexins are subunits of gap junction channels, which allow direct transfer of ions, secondary messenger molecules, and other metabolites between contacting cells. Gap junctions are believed to be involved in tissue homeostasis, embryonic development, and control of cell proliferation. Several studies have shown that cell damage signals are transmitted through gap junctions when cells are irradiated or when cells bearing the herpes simplex virus-thymidine kinase (HSV-TK) gene are treated with ganciclovir. We established 2 lines of transgenic rats with a dominant-negative mutant of connexin 32 gene under control of the albumin promoter. In the livers of transgenic rats, membrane localization of normal endogenous connexin 32 protein is disturbed, and gap junction capacity measured by scrape dye-transfer assay in vivo is markedly decreased when compared with wild-type rats. The present investigation concerned susceptibility to the liver-toxic substances D-galactosamine and carbon tetrachloride. These toxicants induced massive liver cell death and elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the wild-type rats; however, much fewer liver cells were damaged and serum enzyme elevation was much lower in the transgenic rats. In conclusion, gap junctional intercellular communication (GJIC) plays an important role in toxic effects of chemicals; damage or death signals may pass through gap junctions in the rat liver in vivo.
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PMID:Connexin 32 dominant-negative mutant transgenic rats are resistant to hepatic damage by chemicals. 1523 4

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


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