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)

Leukotrienes (LTs) are cell-membrane derived lipid inflammatory mediators, synthesized and eliminated by the liver. LTs have effects on liver cells in some pathological conditions. In this study, we measured plasma endogenous and liberated leukotriene (LT) concentration in peripheral blood leukocytes stimulated in vitro by the calcium ionophore (CaA23187) and platelet-activating factor (PAF). Production of LTs was measured in type A (n=37) and type B (n=10) acute hepatitis patients and control subjects (n=10). LTs levels were measured by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). The concentration of LTB4 measured in plasma and stimulated peripheral blood leukocyte supernatants of children with hepatitis A infection was found to be statistically elevated and in positive correlation with serum alanine aminotransferase (ALT) levels. In plasma samples of hepatitis B patients, LTC4 and LTE4 were measured in significantly elevated concentrations. These results suggest that LTB4 may be a critical mediator of hepatitis A virus-induced hepatocellular injury.
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PMID:Blood levels of leukotrienes (LTC4, D4, E4, B4) and synthesis of leukotriene B4 by peripheral leukocytes in children with acute A and B hepatitis. 1077 Jan 13

We have used the Hepatitis B Virus DNA genome as a probe to identify genes clonally mutated in vivo, in human liver cancers. In a tumor, HBV-DNA was found to be integrated into the gene encoding Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA), which pumps calcium, an important intracellular messenger for cell viability and growth, from the cytosol to the endoplasmic reticulum. The HBV X gene promoter cis-activates chimeric HBV X/SERCA1 transcripts, with splicing of SERCA1 exon 11, encoding C-terminally truncated SERCA1 proteins. Two chimeric HBV X/SERCA1 proteins accumulate in the tumor and form dimers. In vitro analyses have demonstrated that these proteins localize to the ER, determine its calcium depletion and induce cell death. We have also shown that these biological effects are related to expression of the SERCA, rather than of the viral moiety. This report involves for the first time the expression of mutated SERCA proteins in vivo in a tumor cell proliferation and in vitro in the control of cell viability. Oncogene (2000).
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PMID:Hepatitis B virus-related insertional mutagenesis implicates SERCA1 gene in the control of apoptosis. 1087 38

The human asialoglycoprotein receptor (ASGPR), also called hepatic lectin, is an integral membrane protein and is responsible for the clearance of desialylated, galactose-terminal glycoproteins from the circulation by receptor-mediated endocytosis. It can be subdivided into four functional domains: the cytosolic domain, the transmembrane domain, the stalk and the carbohydrate recognition domain (CRD). The galactose-binding domains belong to the superfamily of C-type (calcium-dependent) lectins, in particular to the long-form subfamily with three conserved intramolecular disulphide bonds. It is able to bind terminal non-reducing galactose residues and N-acetyl-galactosamine residues of desialated tri or tetra-antennary N-linked glycans. The ASGPR is a potential liver-specific receptor for hepatitis B virus and Marburg virus and has been used to target exogenous molecules specifically to hepatocytes for diagnostic and therapeutic purposes.Here, we present the X-ray crystal structure of the carbohydrate recognition domain of the major subunit H1 at 2.3 A resolution. While the overall fold of this and other known C-type lectin structures are well conserved, the positions of the bound calcium ions are not, indicating that the fold is stabilised by alternative mechanisms in different branches of the C-type lectin family. It is the first CRD structure where three calcium ions form an intergral part of the structure. In addition, the structure provides direct confirmation for the conversion of the ligand-binding site of the mannose-binding protein to an asialoglycoprotein receptor-like specificity suggested by Drickamer and colleagues. In agreement with the prediction that the coiled-coil domain of the ASGPR is separated from the CRD and its N-terminal disulphide bridge by several residues, these residues are indeed not alpha-helical, while in tetranectin they form an alpha-helical coiled-coil.
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PMID:Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor. 1089 Dec 74

Thioglycollate (TG)-elicited murine, peritoneal macrophages express two receptors for activated forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M*)--namely, the low density lipoprotein receptor-related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). We now report that resident peritoneal macrophages express only 400+/-50 alpha2MSR receptors/cell compared to 5000+/-500 receptor/TG-elicited macrophage. By contrast, LRP expression is only 2-2.5-fold greater on elicited cells. The low level of alpha2MSR expression by resident cells is insufficient to trigger signal transduction in contrast to TG-elicited cells which when exposed to alpha2M* demonstrate a rapid rise in inositol 1,4,5-trisphosphate and a concomitant increase in cytosolic free Ca2+. We then studied a variety of preparations injected subcutaneously for their ability to upregulate alpha2MSR. Macroaggregated bovine serum albumin (macroBSA) injection upregulated alpha2MSR and triggered signaling responses by splenic macrophages. Nonaggregated BSA injection alone or in the presence of alum, by contrast, did not alter alpha2MSR expression. Recombivax (hepatitis B antigen adsorbed to alum) injection also upregulated alpha2MSR on splenic macrophages while the alum carrier had no effect. We conclude that macrophage alpha2M* receptors are inducible and their expression may be regulated, in part, by potential antigens.
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PMID:Inducible expression of the alpha2-macroglobulin signaling receptor in response to antigenic stimulation: a study of second messenger generation. 1152 51

Pulmonary hypertension (PH) appears to be more frequent and more rapidly progressive in HIV+ patients than in the general population. We describe 2 cases of PH in HIV+ patients disclosed by right-side heart failure. The patients were ex-intravenous drug users. On had AIDS and the other was asymptomatic. Both patients had cured hepatitis B and chronic hepatitis C and both died 10 and 11 months after PH diagnosis. Pulmonary hypertension is a likely diagnosis in HIV+ patients with unexplained dyspnea. For primary PH patients, HIV+ serology should be performed. There is probably an indirect mechanism linking PH and HIV. The role of associated chronic hepatitis C is unknown. Treatment of PH is symptomatic using diuretics, calcium-channel inhibitors, and anticoagulation, but with no real efficacy in terms of prognosis. Antiretroviral therapy is recommended. In the future treatment with epoprostenol may perhaps provide improvement in the prognosis of PH in HIV+ patients.
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PMID:[Pulmonary hypertension in HIV-infected patients]. 1154 53

Calcitriol has shown a benefit in various small uncontrolled studies of ex vivo immune function. We hypothesized that paricalcitol, a new vitamin D derivative, will have a positive effect on the immune system with minimal adverse effects on calcium homeostasis. Thirty-one hemodialysis patients not administered vitamin D because of low intact parathyroid hormone (PTH) levels were randomized to placebo or 4 microg of paricalcitol intravenously with the hemodialysis session three times weekly for 12 weeks. Effects on in vivo and ex vivo assessments of immune function were evaluated. All patients achieved the target dose of paricalcitol. Twenty patients were anergic at the start of the study; 4 of 11 patients in the paricalcitol group and 0 of 9 patients in the placebo group converted to reactive (P = 0.09). The in vivo response to standard hepatitis B booster vaccine and in vitro proliferation and release of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, and interferon-gamma from stimulated lymphocytes were not different between the groups. In contrast to clinical immune effects, paricalcitol increased serum calcium levels and decreased PTH and bone alkaline phosphatase levels (all P < 0.05). However, hypercalcemia was infrequent. In vitro experiments showed that paricalcitol led to greater dose-dependent thymidine uptake than calcitriol in lymphocytes isolated from either dialysis patients or control subjects. Paricalcitol has a tendency toward improving delayed hypersensitivity reactions, but did not have other proimmune effects. However, as expected, paricalcitol had significant effects on calcium homeostasis compared with placebo. Thus, patients with low PTH levels are unlikely to experience the proimmune effects of vitamin D therapy without more profound and potentially adverse oversuppression of PTH.
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PMID:A placebo-controlled trial to evaluate immunomodulatory effects of paricalcitol. 1157 83

Proviral tagging has been used in animals as a powerful tool for cancer genetics. We show that a similar approach is possible in patients with hepatocellular carcinoma (HCC) infected by Hepatitis B Virus (HBV), a human pararetrovirus which may act by insertional mutagenesis. In this work, the HBV genome is used as a probe to identify cancer-related genes. By using HBV-Alu-PCR, we obtained 21 HBV/cellular DNA junctions from 18 different patients. In six of 21, we found the HBV DNA integrated into a cellular gene: (1) Sarco/Endoplasmic Reticulum Calcium ATPase1 Gene; (2) Thyroid Hormone Receptor Associated Protein 150 alpha Gene; (3) Human Telomerase Reverse Transcriptase Gene; (4) Minichromosome Maintenance Protein (MCM)-Related Gene; (5) FR7, a new gene expressed in human liver and cancer tissues; and (6) Nuclear Matrix Protein p84 Gene. Seven junctions contained unique cellular sequences. In the remaining eight, the HBV DNA was next to repetitive sequences, five of them of LINE1 type. The cellular genes targeted by HBV are key regulators of cell proliferation and viability. Our results show that studies on HBV-related HCCs allow to identify cellular genes involved in cancer. We therefore propose this approach as a valuable tool for functional cancer genomic studies in humans.
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PMID:Identification of human cancer-related genes by naturally occurring Hepatitis B Virus DNA tagging. 1159 32

There may be drugs and a useful vaccine available to combat the hepatitis B virus, but one aspect of this pathogen remains a puzzle: the function of its HBx protein. As Ganem reveals in his Perspective, new findings (Bouchard et al.) show that this versatile viral protein is an activator of calcium-dependent Ras signaling, an observation that may explain many of its biological effects.
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PMID:Virology. The X files--one step closer to closure. 1174 8

Hepatitis B virus (HBV) infects more than 300 million people and is a leading cause of liver cancer and disease. The HBV HBx protein is essential for infection; HBx activation of Src is important for HBV DNA replication. In our study, HBx activated cytosolic calcium-dependent proline-rich tyrosine kinase-2 (Pyk2), a Src kinase activator. HBx activation of HBV DNA replication was blocked by inhibiting Pyk2 or calcium signaling mediated by mitochondrial calcium channels, which suggests that HBx targets mitochondrial calcium regulation. Reagents that increased cytosolic calcium substituted for HBx protein in HBV DNA replication. Thus, alteration of cytosolic calcium was a fundamental requirement for HBV replication and was mediated by HBx protein.
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PMID:Calcium signaling by HBx protein in hepatitis B virus DNA replication. 1219 70

In order to evaluate the nature and frequency of adverse reactions associated with Therapeutic Apheresis (TA), database information from two large mobile apheresis services was analyzed. A total of 17,940 procedures performed on 3,583 patients were studied using an Access Database. Seventy percent (12,558) of the procedures were performed on a Fresenius AS104 blood cell separator and 30% (5,382) were performed on a COBE Spectra. The five most commonly treated diseases were Guillain-Barre Syndrome (25%), thrombotic thrombocytopenic purpura (20%), myasthenia gravis (18%), the hyperviscosity syndrome (12%), and chronic inflammatory demyelinating polyneuropathy (9%). All patients received calcium gluconate supplement during the procedures. Cardiac monitoring was used during 80% of the procedures and blood pressure monitoring was used during all procedures. All procedures were supervised by a physician. Both apheresis services fully comply with the ASFA Guidelines for Therapeutic Apheresis Providers. Adverse reactions occurred in 3.9% of all procedures. The following adverse reactions were documented: reactions related to ACD toxicity (3%), vasovagal reactions (0.5%), vascular access related complications (0.15%), reactions related to FFP (0.12%), hepatitis B from FFP (0.06%), arrhythmias (0.01%), hemolysis due to inappropriate dilution of 25% albumin (0.01%), and one death (from underlying disease) during a TA procedure (0.006%). These data demonstrate that therapeutic apheresis is associated with a low rate of side effects when performed by well-trained and certified nurses under the direction of experienced physicians, even in the diverse setting of large mobile therapeutic apheresis programs.
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PMID:Adverse reactions associated with mobile therapeutic apheresis: analysis of 17,940 procedures. 1174 39


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