Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four markers for hepatic fibrosis--N-terminal peptide of Type III procollagen (PIIIP), Laminin P1 (laminin), Type IV collagen (Type IV-C), and 7S domain (7S)--were measured in the sera of 90 patients with various chronic liver diseases diagnosed by liver biopsy--fatty liver (FL), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), and liver cirrhosis (LC)--and in the sera of 20 healthy controls. The values of markers were compared with the grade of histologic findings of the liver. Four markers were significantly raised in the CAH group and the LC group, and they were considered to be indicators of hepatic fibrosis. PIIIP reflected necrosis and inflammation as well as fibrosis of the liver. Laminin, Type IV-C, and 7S reflected severe fibrosis. 7S was considered to be useful marker for liver cirrhosis.
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PMID:[Clinical significance of measurement of PIIIP, laminin P1, type IV-C and 7S in patients with chronic liver diseases--with special reference to histological findings]. 140 88

PL/J mice developed chronic relapsing experimental allergic encephalomyelitis (EAE) after receiving syngeneic guinea pig basic protein (GPBP)-immune lymph node cells or spleen cells which were cultured in the presence of GPBP or the encephalitogenic N-terminal peptide of GPBP. The presence of L3T4+ cells and in vitro proliferation in response to GPBP are required for the successful transfer. Pathologically, passively transferred EAE in the virus-free PL/J strain was characterized by an infiltration in the central nervous system by small lymphocytes, followed by the appearance of macrophages, and subsequently by primary demyelination. These findings were similar to those previously observed in chronic relapsing EAE in SJL/J mice. However, in some experiments pathologic examination of the spinal cord showed large demyelinating lesions which were necrotic and infiltrated with eosinophilic polymorphonuclear leukocytes. Sera from mice with this pathology contained antibodies to murine hepatitis virus and extensive search identified a few areas of coronavirus replication. The pathology of autoimmune mediated demyelination may be altered in the presence of coronavirus infection but the clinical pattern of EAE expression did not differ between virus-free and coronavirus-infected mice.
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PMID:Adoptively transferred acute and chronic relapsing autoimmune encephalomyelitis in the PL/J mouse and observations on altered pathology by intercurrent virus infection. 282 23

The murine coronavirus mouse hepatitis virus gene 1 is expressed as a polyprotein, which is cleaved into multiple proteins posttranslationally. One of the proteins is p28, which represents the amino-terminal portion of the polyprotein and is presumably generated by the activity of an autoproteinase domain of the polyprotein (S. C. Baker, C. K. Shieh, L. H. Soe, M.-F. Chang, D. M. Vannier, and M. M. C. Lai, J. Virol. 63:3693-3699, 1989). In this study, the boundaries and the critical amino acid residues of this putative proteinase domain were characterized by deletion analysis and site-directed mutagenesis. Proteinase activity was monitored by examining the generation of p28 during in vitro translation in rabbit reticulocyte lysates. Deletion analysis defined the proteinase domain to be within the sequences encoded from the 3.6- to 4.4-kb region from the 5' end of the genome. A 0.7-kb region between the substrate (p28) and proteinase domain could be deleted without affecting the proteolytic cleavage. However, a larger deletion (1.6 kb) resulted in the loss of proteinase activity, suggesting the importance of spacing sequences between proteinase and substrate. Computer-assisted analysis of the amino acid sequence of the proteinase domain identified potential catalytic cysteine and histidine residues in a stretch of sequence distantly related to papain-like cysteine proteinases. The role of these putative catalytic residues in the proteinase activity was studied by site-specific mutagenesis. Mutations of Cys-1137 or His-1288 led to a complete loss of proteinase activity, implicating these residues as essential for the catalytic activity. In contrast, most mutations of His-1317 or Cys-1172 had no or only minor effects on proteinase activity. This study establishes that mouse hepatitis virus gene 1 encodes a proteinase domain, in the region from 3.6 to 4.4 kb from the 5' end of the genome, which resembles members of the papain family of cysteine proteinases and that this proteinase domain is responsible for the cleavage of the N-terminal peptide.
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PMID:Identification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus. 839 68

Autoantibodies to the ribosomal phospho (-P) proteins P0, P1, and P2, collectively referred to as Rib-P, are specifically found in 10-40% of patients with systemic lupus erythematosus (SLE). These antibodies are believed to be correlated with lupus nephritis, hepatitis, and central nervous system involvement. The major immunoreactive epitope of these ribosomal antigens has been localized to the carboxy terminus, which is a highly conserved domain of all three proteins and contains two phosphorylated serine residues. The phosphorylated amino acids of the P proteins are known not to be critical epitope determinants. Furthermore, epitope-mapping studies have shown that the major epitope is located within the last 11 C-terminal amino acids. Using peptide arrays we identified more precisely this shared epitope as the six C-terminal amino acids GFGLFD and elucidated the molecular recognition events of anti-Rib-P antibodies at the amino acid level. We identified Phe(111) and Phe(114) of Rib-P2 as the key residues for the interaction, with further contributions of Gly-112 and Asp-115. This amino acid stretch is also present in proteins of several pathogenic micro-organisms such as Trypanosoma cruzi, Brugia malayi, Pseudomonas aeruginosa, Candida albicans, several Leishmania species, and Bartonella henselae. Using newly developed ELISA systems with a C-terminal peptide (C22) and the recombinant proteins (P0, P1, and P2) as antigens we found a high specificity of anti-Rib-P antibodies for SLE and demonstrated positive correlations with anti-U1-C, anti-Sm-B/B' and anti-D and anti-dsDNA antibodies. The sensitivity and specificity in the peptide (C22) based assay varied between 12.8%/100% and 23.4%/96.7% for SLE, depending on the assigned cutoff. In contrast to other studies, we found no significant correlation of anti-Rib-P reactivity with central nervous system manifestations or renal involvement in SLE patients. We conclude that the epitope motif GFGLFD in the C-termini of the ribosomal P proteins is the key determinant of anti-Rib-P antibodies, and that the C22 peptide and the recombinant proteins can be used equally well for the detection of anti-Rib-P antibodies. The role of the major Rib-P epitope in the development of anti-ribosomal P antibodies and in the pathogenesis of SLE remains a subject of further investigation.
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PMID:Characterization of the human autoimmune response to the major C-terminal epitope of the ribosomal P proteins. 1268 28