Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer type II astrocytosis is the pathological hallmark of hepatic encephalopathy. These astrocytes undergo a characteristic morphological change and, in addition, lose immunoreactivity for glial fibrillary acidic protein (GFAP). However, a previous study in the portacaval shunted rat, a model of hepatic encephalopathy, revealed increased rather than decreased GFAP immunoreactivity in Bergmann glia, a specialized group of cerebellar astrocytes. In the present study, sections of cerebellar vermis from 15 cirrhotic patients with hepatic encephalopathy and varying degrees of Alzheimer type II astrocytosis were stained using antisera to GFAP. The Bergmann glial cells did not show altered GFAP immunoreactivity compared to controls. In addition, the degree of GFAP immunoreactivity was not correlated with the degree of Alzheimer type II change nor related to the aetiology of the liver disease. These results suggest a differential response of Bergmann glia in human hepatic encephalopathy.
Mol Chem Neuropathol 1997 Aug
PMID:Distinctive pattern of Bergmann glial pathology in human hepatic encephalopathy. 933 69

Plasma collagen-binding vitronectin was assayed in 62 patients with chronic liver disease and 14 healthy control subjects. It was measured by an enzyme immunoassay using type I collagen and monoclonal antibody to vitronectin before and after treatment with heparin or dextran sulfate in vitro. The pretreatment level of plasma collagen-binding vitronectin (mean +/- S.E.M.) was 5.5 +/- 0.5 micrograms/ml in the controls, 8.2 +/- 0.3 micrograms/ml in chronic persistent hepatitis, 8.3 +/- 0.7 micrograms/ml in chronic active hepatitis, 7.9 +/- 0.7 micrograms/ml in liver cirrhosis, and 8.2 +/- 0.5 micrograms/ml in hepatocellular carcinoma with cirrhosis. After treatment with heparin, the percent collagen-binding vitronectin to total vitronectin was 20.6 +/- 2.0% in the controls, 24.7 +/- 4.1% in chronic persistent hepatitis, 28.6 +/- 2.5% in chronic active hepatitis, 42.6 +/- 4.5% in liver cirrhosis, and 31.8 +/- 2.3% in hepatocellular carcinoma. All percents were significantly increased compared to the pretreatment percent. The same pattern was also found after dextran sulfate treatment. Compared to that in the pretreatment state, the collagen-binding vitronectin after these treatments was more closely correlated with the serum levels of 7S collagen and hyaluronic acid. These results suggest that the collagen-binding activity of vitronectin may play an important role in the progression of liver disease and/or fibrosis through its activation with some glycosaminoglycans.
Res Commun Mol Pathol Pharmacol 1997 Sep
PMID:Plasma collagen-binding vitronectin activated by heparin and dextran sulfate in chronic liver disease. 938 91

Hyaluronate in tissue and lymph is known to be heterogenous and to show a wide range of molecular weights (10(4) to 10(7) Da). Serum hyaluronate concentrations are increased under various pathophysiological conditions such as liver disease, post-gastrectomy, and after the ingestion of food. To clarify whether the chromatographic patterns of hyaluronate in serum from patients with chronic liver disease are different under these conditions, we subjected sera to chromatography using a Sephacryl S 400 HR column. The chromatograms revealed that the hyaluronate in serum was eluted as a single peak at the position corresponding to the molecular weight of blue dextran, the molecular weight being more than 2 x 10(6) Da. The patterns of the chromatogram were similar among the patients with liver disease and the healthy subject although the heights of the peaks were different. Ingestion of food and a history of gastrectomy for gastric cancer did not influence the elution patterns of serum hyaluronate. These results indicate that hyaluronate in serum has molecular weight of more than 2 x 10(6) Da, and that its elution patterns are not influenced by pathophysiological factors, such as the severity of liver disease, or history of gastrectomy or by food intake in patients with chronic liver disease.
Res Commun Mol Pathol Pharmacol 1998 Feb
PMID:Molecular weight of hyaluronate in the serum of patients with chronic liver disease. 958 94

alpha 1-Antitrypsin (alpha 1AT) provides the major protection in the lung against neutrophil elastase-mediated proteolysis. Inheritance of alpha 1AT deficiency alleles is associated with an increased risk of emphysema and liver disease. alpha 1AT null alleles cause the total absence of serum alpha 1AT and represent the ultimate in a continuum of alleles associated with alpha 1AT deficiency. The molecular mechanisms responsible for absence of serum alpha 1AT include splicing abnormalities, deletion of alpha 1AT coding exons, and premature stop codons. We identified an Italian individual with asthma, emphysema, and a very low level of serum alpha 1AT. DNA sequencing demonstrated the Mprocida deficiency allele and a novel null allele, QOtrastevere (c654 G-->A, W194Z), a nonsense mutation near the intron 2 (IVS2) splice acceptor site. To determine the molecular basis of QOtrastevere and specifically to evaluate whether this nonsense mutation interfered with mRNA processing by altered splicing, we used a Chinese hamster ovary cell line permanently transfected with QOtrastevere or normal M alpha 1AT with and without IVS2. Northern blot analysis demonstrated that the normal M construct, with or without IVS2, expressed alpha 1AT mRNA of a similar size. The nonsense mutation was associated with moderately reduced alpha 1AT mRNA regardless of the presence or absence of IVS2. Reduction in alpha 1AT mRNA regardless of the opportunity for splicing supports a translational-translocation model as the cause of reduced alpha 1AT mRNA rather than the nuclear scanning model. Pulse-chase studies followed by immunoprecipitation demonstrated an endoplasmic reticulum-retained 31 kDa QOtrastevere alpha 1AT, which was rapidly degraded. Although mRNA content was moderately reduced, retention and rapid intracellular degradation of the truncated form are the major mechanisms for the absence of secreted alpha 1AT.
Mol Genet Metab 1998 Apr
PMID:Alpha 1-antitrypsin nonsense mutation associated with a retained truncated protein and reduced mRNA. 963 95

Preparation of a pure autoantigen by way of recombinant DNA technology has an important value in an accurate diagnosis or prognosis of an autoimmune disease. BCOADC-E2 subunit, a mitochondrial protein, has been known to be the autoantigen of primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, as well as idiopathic dilated cardiomypathy (IDCM), a chronic autoimmune heart disease. Recombinant form of this molecule had been expressed in E. coli but with low yield and severe degradation. Furthermore, sera from IDCM patients failed to recognized BCOADC-E2 molecule produced in prokaryotic expression system. In this study, a recombinant bovine BCOADC-E2 fusion protein has been expressed in insect cells using baculovirus expression system and analyzed anti-BCOADC-E2 reactivity in sera from patients with PBC or with IDCM. Optimal production of the recombinant fusion protein has been achieved at 20 multiplicity of infection (MOI), and the protein was affinity-purified using metal-binding resins. The affinity-purified BCOADC-E2 protein was successfully recognized by sera from PBC patients, but not by sera from IDCM patients suggesting that the different auto-immune response against BCOADC-E2 is needed to be elucidated in terms of epitope recognition.
Exp Mol Med 1998 Jun 30
PMID:Expression of a recombinant branched chain alpha-oxo acid dehydrogenase complex E2 (BCOADC-E2) in insect cells and its immunoreactivity to autoimmune sera. 987 25

Autoantibodies against soluble liver enzymes have been reported among alcoholics, but the targets of self-reactivity toward membrane proteins of the liver have not been characterized. Previously, among alcoholics, we found antibodies against ethanol-derived radical protein adducts that are dependent on cytochrome P-4502E1 (CYP2E1) for their formation. To further investigate autoantibodies against cytochrome P-450s during alcohol abuse, sera of rats chronically treated with ethanol in the total enteral nutrition model and sera from alcoholics with or without alcohol liver disease and from control subjects were analyzed by enzyme-linked immunosorbent assay and Western blotting for the presence of IgG against rat and human CYP2E1, rat CYP3A1, and human CYP3A4. A time-dependent appearance of IgG against rat CYP3A1 and CYP2E1 was evident during chronic ethanol feeding of rats. Anti-CYP2E1 reactivity showed positive correlation with the levels of hepatic CYP2E1 and was inhibited by the CYP2E1 transcriptional inhibitor chlormethiazole. Screening of the human sera by enzyme-linked immunosorbent assay revealed reactivity against CYP3A4 and CYP2E1 in about 20 to 30% and 10 to 20% of the alcoholic sera, respectively. No difference were noted between sera from alcoholics with or without hepatitis C virus infection, and only very little reactivity was seen in sera from control subjects. Western blotting analysis revealed anti-human CYP2E1 reactivity in 8 of 85 alcoholic sera and 3 of 58 control sera, whereas anti-CYP3A4 reactivity was detected in 18 of 85 alcoholic sera and 4 of 58 control sera, which were different from the sera reactive with CYP2E1. Immunoblot reactivity of CYP3A4-positive alcoholic sera was found against glutathione-S-transferase fusion proteins containing truncated forms of CYP3A4, and such sera were also able to immunoprecipitate in vitro translated CYP3A4. Seven of eight sera showed reactivity toward domains C-terminal of position Ser281, and 1 of 8 sera recognized autoepitopes within the region Thr207-Ser281. These findings indicate that alcoholics develop autoantibodies against CYP2E1 and CYP3A4 that the CYP3A4 C-terminal domain is a target for the autoantibody reactions among a subset of alcoholics. The novel finding of CYP3A4 autoantibodies and their significant expression among alcoholics warrants further investigation. Attention should be given to immune toxicity associated with CYP3A4 autoantibodies and cases of alcohol abuse that are accompanied by exposure to drugs and substances that are CYP3A substrates.
Mol Pharmacol 1999 Feb
PMID:Autoantibodies against cytochromes P-4502E1 and P-4503A in alcoholics. 992 12

Abnormal hepatic copper accumulation is recognized as an inherited disorder in man, mouse, rat and dog. The major cause of hepatic copper accumulation in man is a dysfunctional ATP7B gene, causing Wilson disease (WD). Mutations in the ATP7B genes have also been demonstrated in mouse and rat. The ATP7B gene has been excluded in the much rarer human copper overload disease non-Indian childhood cirrhosis, indicating genetic heterogeneity. By investigating the common autosomal recessive copper toxicosis (CT) in Bedlington terriers, we have identified a new locus involved in progressive liver disease. We examined whether the WD gene ATP7B was also causative for CT by investigating the chromosomal co-localization of ATP7B and C04107, using fluorescence in situ hybridization (FISH). C04107 is an anonymous microsatellite marker closely linked to CT. However, BAC clones containing ATP7B and C04107 mapped to the canine chromosome regions CFA22q11 and CFA10q26, respectively, demonstrating that WD cannot be homologous to CT. The copper transport genes CTR1 and CTR2 were also excluded as candidate genes for CT since they both mapped to canine chromosome region CFA11q22. 2-22.5. A transcribed sequence identified from the C04107-containing BAC was found to be homologous to a gene expressed from human chromosome 2p13-p16, a region devoid of any positional candidate genes.
Hum Mol Genet 1999 Mar
PMID:Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16. 994 9

The purpose of this study was to determine the frequency of infection by hepatitis A, B, C, D, E, and G in liver biopsy specimens from symptomatic patients and to correlate viral localization with the expression of interferon tau, interleukin 4, and tumor necrosis factor messenger RNA. Tissue biopsy specimens were taken from 78 patients as follows: 14 patients with transplants, 23 patients with cirrhotic livers, and 41 patients with chronic hepatitis. At least one of the hepatitis viruses was detected in 60 of 78 (77%) specimens; multiple infection was evident in 18 of 78 (23%) specimens. The overall incidence of the different viruses was as follows: 8% hepatitis A, 3% hepatitis B, 52% hepatitis C, 1% hepatitis D, 24% hepatitis E, 18% hepatitis G. Throughout each category, hepatitis C was the most common virus detected. No histologic variable correlated with either the percentage of infected hepatocytes per lobule or nodule or with the specific viral type. The cytokines localized to monocytes or lymphocytes adjacent to infected hepatocytes. These results demonstrate that viral infection is present in most biopsy specimens of patients with chronic hepatitis and liver transplants and that hepatitis C, E, and G account for most of the infections. The results also suggest that direct viral infection in conjunction with expression of different cytokines is important in the pathophysiology of viral-induced liver disease.
Diagn Mol Pathol 1998 Oct
PMID:Histologic distribution of hepatitis A, B, C, D, E, and G with concomitant cytokine response in liver tissue. 999 Apr 85

Acute hepatitis models are widely used for the evaluation of drugs for liver disease or for basic research on hepatitis. However, it is difficult to produce similar liver conditions to human chronic hepatitis with an acute hepatitis model. The interferon-gamma (IFN-gamma) transgenic mouse, which carries the mouse IFN-gamma gene, strongly expresses the IFN-gamma gene in the liver and develops chronic hepatitis from the age of 6-10 weeks. We found that the hepatitis in this mouse reflects human chronic hepatitis at least in the following points, i) infiltration by lymphoid cells into the portal areas and necroinflammation in the lobules, and ii) expression of Fas antigen and Fas ligand mRNAs in the liver. Furthermore, the induction of CPP32-like protease activity in the transgenic mouse liver suggests the involvement of this protease activity in the development of chronic hepatitis.
Int J Mol Med 1999 May
PMID:The mouse interferon-gamma transgene chronic hepatitis model (Review). 1020 84

The Dubin-Johnson syndrome (DJS) is a rare autosomal recessive liver disease characterized by chronic conjugated hyperbilirubinemia. The phenotype of this syndrome is thought to be caused by the impaired expression of the canalicular multispecific organic anion transporter (cMOAT), which transports non-bile salt organic anions into the bile. Recently, a mutation from arginine (Arg) to stop-codon at codon 1066 in the cMOAT gene has been reported in one Caucasian patient with DJS. In this study, we investigated whether this mutation is found in Japanese patients with DJS. Genomic DNAs were extracted from the leukocytes of six Japanese patients and the fragments spanning codon 1066 were amplified by polymerase-chain reaction. The digest of the amplified fragments with a restriction enzyme, Taql, demonstrated that all of six patients did not exhibit an R1066X mutation. No mutation at Arg1066 was also confirmed by direct sequencing of the amplified products. These findings suggested that this R1066X mutation was not a major mutation in Japanese patients with DJS. Further investigation will be required in an attempt to search other mutations in cMOAT gene in Japanese patients with DJS.
Biochem Mol Biol Int 1999 Apr
PMID:Absence of R1066X mutation in six Japanese patients with Dubin-Johnson syndrome. 1031 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>