Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three glycoproteins of intact hepatitis B surface antigen (HBsAg) with mol. wt. of 32 000, 30 000 and 28 000 respectively were identified by reaction with 125I-concanavalin A (Con A) after separation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The antigen was effectively disrupted with Triton X-100 to produce a structure with a sedimentation coefficient of 3.9S. Affinity chromatography of disrupted HBsAg using concanavalin A-Sepharose 4B (Con A-Sepharose) resulted in two fractions. The first contained material which did not bind to the lectin and consisted of a single polypeptide of mol. wt. 64 000. Further studies revealed this component to be serologically identical to serum albumin and to lack any affinity for antibody to HBsAg. A comparison of the tryptic peptide map of this polypeptide with that of purified serum albumin demonstrated identical amino-acid sequences. The second fraction contained material which bound to Con A and contained two polypeptides with mol. wt. of 28000 and 23000 respectively. HBsAg reactivity was associated with this fraction. This procedure allows the prepartion of HBsAg sub-units in milligram quantities for further immunological studies.
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PMID:Analysis of hepatitis B surface antigen components solubilized with Triton X-100. 9 17

Altered glycosylation of alpha-fetoprotein (AFP) has been proposed as a marker of hepatocellular carcinoma (HCC) in humans. The lectin-binding properties of woodchuck AFP were investigated to determine if woodchuck hepatitis virus (WHV)-induced HCCs are also accompanied by changes in AFP glycosylation. Ninety-eight to 100% of the AFP from normal, WHV-free woodchucks with physiologic AFP elevations and from WHV-carrier woodchucks with HCC bound to concanavalin A, indicating that virtually all of the AFP was glycosylated. Three percent or less of the serum AFP of normal woodchucks bound to Lens culinaris agglutinin (LCA). In contrast, the AFP from woodchucks with HCC had an increased LCA-binding fraction (range, 8-77%). The increased LCA-binding AFP in WHV-induced HCC is analogous to that which frequently accompanies hepatitis B virus (HBV)-induced HCC in humans. This study corroborates the relationship of altered glycoconjugate synthesis to virus-induced malignant transformation, confirms the importance of AFP glycoforms as markers of HCC, and demonstrates that the WHV-infected woodchuck should be useful in investigating changes in AFP glycosylation during hepadnavirus hepatocarcinogenesis and HCC growth.
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PMID:Altered glycosylation of alpha-fetoprotein in hepadnavirus-induced hepatocellular carcinoma of the woodchuck. 137 41

Serum alpha-fetoprotein levels were determined in patients (268) with liver disease. Markedly elevated concentrations (greater than 100 micrograms/l) were found in twelve patients with malignant tumours and two with cirrhosis. Molecular variants of alpha-fetoprotein were distinguished by lectin affinity chromatography of these sera. Reversible binding to concanavalin A (86 +/- 5%) and to lentil agglutinin (61 +/- 19%) conformed to expected values for primary hepatocellular carcinoma except in one patient with a metastatic carcinoma whose alpha-fetoprotein binding to concanavalin A was similar to non-liver alpha-fetoprotein (44 +/- 13%), and the two patients with cirrhosis in whom binding to lentil agglutinin was typical for benign liver disorders (less than 20%). Since low levels of serum alpha-fetoprotein and non-characteristic alpha-fetoprotein binding patterns assisted in the regrouping of eleven out of 24 patients initially thought to have primary hepatocellular carcinoma, it was concluded that alpha-fetoprotein determination and lectin affinity chromatography are helpful in distinguishing primary hepatocellular carcinoma from metastatic and benign liver diseases. Slight increases in the alpha-fetoprotein level in the presence of serum hepatitis B surface antigen indicated seven patients at risk for primary hepatocellular carcinoma who should be monitored frequently.
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PMID:Serum alpha-fetoprotein levels and microheterogeneity in patients with different liver diseases. 170 55

Tetanus toxoid (TT) and hepatitis B surface antigen (HBsAg) can suppress lectin-induced responses. The suppression induced by TT is dose-dependent and can also down-regulate the induction of a blastogenic response by anti-CD3 and anti-CD4 monoclonals. In addition, TT can dampen the blastogenic response induced by phytohaemagglutinin (PHA) and anti-CD3. The cellular mechanism involved in the turning off of the blastogenic response was investigated by transferring cells treated for 5 days with TT to freshly obtained syngeneic cells and stimulation with PHA. The response of cultures that had received TT-treated cells was significantly lower than of those that had received cells treated with medium only. The removal of CD4+ cells at the induction phase of the suppression reversed the suppression, whereas the elimination of most CD8+ cells had no effect. We propose that CD4+ cells together with monocytes can dampen the specific and non-specific blastogenic responses.
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PMID:The role of CD4+ lymphocytes in the activation of non-specific suppressor cells by antigen. 252 95

Hepatitis B core antigen (HBcAg)-specific T cell lines were established from hepatic lymphomononuclear cells derived from five patients with chronic active hepatitis B. No hepatitis B virus envelope antigen-specific cell lines were established. Proliferation in response to recombinant and native HBcAg, but not to native hepatitis B surface antigen containing the pre-S(2) region, confirmed the specificity of the five T cell lines. All cell lines represented mixed populations of CD4+ and CD8+ T cells. The CD4+ subset provided antigen-specific help to autologous B cells with respect to anti-HBc production and to CD8+ cells with regard to HBcAg-induced proliferation and suppressor activity. The CD8+ subset contained suppressor cells that selectively inhibited the proliferative response of autologous HBcAg-specific CD4+ cells without inhibiting CD4+ cells of unrelated specificity (tetanus toxoid). Moreover, the CD8+ cells were also capable of suppressing HBcAg-stimulated antibody to HBcAg production without showing inhibition of total immunoglobulin production stimulated by pokeweed mitogen. The cytotoxic potential of the T cell lines was established in a lectin-dependent cytotoxicity system; natural killer cytotoxicity was completely absent. Our data suggest that the lesional T cells present at the site of hepatocellular injury in chronic active hepatitis B are primarily HBcAg-specific lymphocytes of the helper and suppressor/cytotoxic phenotypes and that both are functionally competent.
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PMID:Intrahepatic, nucleocapsid antigen-specific T cells in chronic active hepatitis B. 295 46

To explore the mechanisms underlying liver-directed autoimmune reactions in acute Hepatitis B Virus (HBV) infection, we followed five subjects who were identified in the early incubation phase (30-70 days before the first elevation of transaminases). We assessed serially cellular (using a T-lymphocyte migration inhibitory factor assay) and humoral (RIA) immunity to LSP (a macromolecular, liver-derived lipoprotein complex) and hepatic lectin (HL), the liver-specific receptor for desialylated glycoproteins, which appears to be a major target antigen for autoreactions in autoimmune chronic active hepatitis. Anti-LSP and anti-HL autoantibodies were found, at some stage during acute HBV infection, in 4/5 subjects, whereas cellular immunity to the same antigens was detected in only two patients. Sustained production of anti-HL antibodies was noted only in patients showing cellular immunity to this antigen and was apparently secondary to liver damage, whereas anti-LSP antibodies were first detected at the onset of liver injury when there was no evidence of T-cell immunity to the same antigenic complex. One explanation for this apparent dichotomy between cellular and humoral responses to LSP is that a helper T-cell response to the major envelope component of HBV, HBsAg, which precedes by 10-20 days the development of anti-LSP antibodies, promotes a humoral reaction to autoantigens contained in the LSP preparation, coexpressed with HBsAg, on the surface of infected hepatocytes.
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PMID:Serial study of liver-directed autoantibodies and autoreactive T-lymphocytes in acute viral hepatitis B. 307 30

Circulating autoantibodies reacting with affinity-purified, hepatic asialoglycoprotein receptor protein, hepatic lectin (HL), were detected by radioimmunoassay in 15 (83%) of 18 patients with autoimmune chronic active hepatitis (AI-CAH) who had active disease, at titres that showed a positive correlation (P less than 0.05) with severity of periportal inflammation assessed histologically. In contrast, 10 AI-CAH patients whose disease was in remission were all anti-HL seronegative. Anti-HL was also detected in 16 (73%) of 22 patients with hepatitis B virus-related CAH-a similar frequency to that in active AI-CAH but at significantly lower (P less than 0.005) titres. Only 1 of 8 patients with chronic active liver disease due to presumed non-A, non-B (NANB) viral infection and 5 (22%) of 23 with primary biliary cirrhosis were anti-HL seropositive (P less than 0.001 vs active AI-CAH and HBV-CAH) and there was no correlation with severity of periportal inflammation. Anti-HL antibodies were also found in sera from 7 (35%) of 20 patients with acute virus B hepatitis (AVH-B) but were not detected in 10 patients with AVH-A nor in 12 with AVH due to presumed NANB infection. Anti-HL was not found in sera of 12 patients with autoimmune thyroid disease. Hepatic lectin, a highly purifiable, liver-specific cell surface component, by analogy with the acetylcholine and thyrotropin receptors which are, respectively, targets of the pathogenetically-related autoimmune reactions in myasthenia gravis and autoimmune thyroid disease, may be an important target of autoreactions in liver disease.
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PMID:Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders. 379 1

To determine whether circulating antibodies against the liver-specific membrane lipoprotein complex (LSP), which occur in a number of liver disorders, are directed at the hepatic asialoglycoprotein receptor protein (hepatic lectin)--recently shown to be a constituent of LSP--a radioimmunoassay for anti-hepatic lectin antibodies was developed based on the use of protein A in situ on staphylococcal cells to precipitate 125I-labelled rabbit hepatic lectin/anti-lectin immune complexes. The assay was used to test sera from 30 patients (15 anti-LSP-positive and 15 anti-LSP-negative) with autoimmune chronic active hepatitis (CAH), hepatitis B virus-positive CAH or primary biliary cirrhosis. Anti-lectin antibodies (at titres of 1:200 to 1:1600) were found in all 15 anti-LSP-positive sera and were not detected in the 15 anti-LSP-negative patients. Hepatic lectin is a highly purifiable, liver-specific, hepatocellular surface component and the anti-lectin assay (which proved sensitive, reliable and easy to perform) will permit further exploration of the role of autoimmune mechanisms in the pathogenesis of various liver diseases.
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PMID:A radioimmunoassay for detection of circulating antibodies reacting with the hepatic asialoglycoprotein receptor protein. 398 Oct 1

beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mannose of the trimannosyl core of N-linked oligosaccharides and forms a bisecting GlcNAc structure. Although the biological meaning of the bisecting GlcNAc structure remains unclear, it is known that the attachment of a bisecting GlcNAc inhibits further processing of oligosaccharides by other glycosyltransferases. To investigate whether or not structural changes of oligosaccharides affect secretion and gene expression of hepatitis B virus (HBV), we introduced the GnT-III gene into a human hepatoma cell line, HB611, which secreted HBV-related proteins into the medium. Positive transfectants were cloned by hygromycin resistant selection. Three clones have high activities of GnT-III and secreted lower levels of HBV-related proteins into the medium in comparison with other clones. These clones showed marked suppression of HBV-related mRNAs and an increased binding with E-PHA as judged by lectin blot. Expression of beta actin, alpha fetoprotein, albumin, and prealubmin was not correlated with GnT-III activity in all the seven clones. Treatment of these cells with tunicamycin or swainsonine resulted in enhanced expression of HBV-related mRNA. These results indicate that some glycoproteins whose oligosaccharide structures are changed by over-expression of GnT-III suppress HBV gene expression.
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PMID:Transfection of N-acetylglucosaminyltransferase III gene suppresses expression of hepatitis B virus in a human hepatoma cell line, HB611. 749 30

We have used the hepatitis B surface antigen (HBsAg) as a tool to explore mechanisms by which polarized epithelial cells address specific proteins to their apical domain. It recently has been proposed that N-glycans can serve as apical signals recognized by lectin-like sorting receptors in the trans-Golgi network. We found, however, conclusive evidence that the HBsAg follows an apical pathway not mediated by N-glycan signaling. Neither tunicamycin treatment nor replacement of its single glycosylated residue, Asn-146, altered its predominant (>85%) apical secretion from transfected Madin-Darby canine kidney cells (MDCK). Although HBsAg is known to be secreted as a lipoprotein particle, our results suggest that the exocytic machinery involved in its N-glycan-independent pathway overlaps, at least partially, with that of other apically targeted proteins, including the endogenous gp80, as judged by the effects of brefeldin A. We also tested whether its sorting behavior could be ascribed to association with glycosylphosphatidylinositol (GPI)-anchored proteins, which, together with glycosphingolipids, primarily are targeted to the apical domain of MDCK cells. HBsAg was preferentially secreted from the apices of transfected Fisher rat thyroid cells, which, in contrast to MDCK cells, address GPI-proteins and glycosphingolipids to their basal domain. Moreover, complete inhibition of GPI biogenesis by mannosamine treatment did not impair the HBsAg apical secretion, discarding the possibility that HBsAg could be "hitchhiking" with a newly synthesized GPI-protein. Thus, the HBsAg provides a unique model system to search for yet-unknown apical sorting mechanisms that could depend on proteinaceous targeting signals interacting with cognate trans-Golgi network receptors that are at present unidentified.
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PMID:Apical sorting of hepatitis B surface antigen (HBsAg) is independent of N-glycosylation and glycosylphosphatidylinositol-anchored protein segregation. 905 Aug 65


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