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)

The prevalence of hepatitis B surface antigen (HBS Ag) was determined in 210 Nigerian diabetics and in 210 non-diabetic controls matched for age and sex. Nineteen diabetics (9.0%) were found to have HBS Ag in their sera compared to six (2.9%) of the non-diabetic controls. The difference is statistically significant and may be attributable to the common practice of injudicious administration of insulin injections among Nigerian diabetics. There was no correlation between the prevalence of HBS Ag and the degree of control of diabetes. The prevalence of HBS Ag among new diabetics was found to be low. It is unlikely that diabetics have impaired ability to remove the hepatitis B virus once they are infected or that serum hepatitis plays any role in the causation of diabetes.
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PMID:The prevalence of hepatitis B surface antigen in Nigerian diabetics. 699 9

Serum samples from 2,465 diabetics were examined by radioimmunoassay for HBsAg, anti-HBs and anti-HBc at the Centro Antidiabetico of the Ospedale Maggiore di Lodi; during the same period, the same tests were carried out on serum samples from 2,176 control subjects, who had been admitted to the surgical, casualty and obstetrical departments for reasons that had nothing whatsoever to do with any form of liver disease. The ages of the two groups ranged from 6 to 90 years. The diabetics were divided into three groups; insulin-dependent, non-insulin-dependent and diabetics treated with insulin for diabetic complications. The overall frequency of HBsAg in the various groups of diabetics was 3.5%, while in the controls it was 6.1% (p less than 0.001). In the group of young insulin-dependent diabetics, the frequency was 1.7%, as compared to 6.9% for the controls in the same age group (p less than 0.05). In the group of patients treated with insulin for diabetic complications, the frequency increased to 11.5%, while for the controls in the same age group it was 5.5%. The levels of HBsAg were practically the same in the diabetics and in the controls, whereas the level of anti-HBc was higher in the diabetics: 55.6% compared to 50% (p less than 0.005). This last result indicates that the chances of hepatitis B virus infection were greater for the diabetics than for the controls. Diabetics, and especially those insulin-dependent are, therefore, believed to possess a greater capacity of resistance through their T cell-mediated immune response to the hepatitis B virus.
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PMID:Unexpected lower prevalence of HBsAg in diabetics than in controls. (A study on 2,465 patients). 711 84

Carboxypeptidase E (CPE) is involved in the biosynthesis of most neuropeptides and peptide hormones. Until recently, CPE was the only intracellular carboxypeptidase thought to be involved in neuroendocrine peptide processing. However, the finding that fat/fat mice, which have a mutation within the CPE gene that inactivates the enzyme, are capable of a reduced amount of insulin processing suggests that another carboxypeptidase is present within the secretory pathway. We have detected a CPE-like enzyme, designated CPD, which has many properties in common with those of CPE. Like CPE, CPD is a metallocarboxypeptidase that has a pH optimum of 5.5-6. The Km and Kcat values for a series of short peptide substrates show only minor differences between CPD and CPE. Several active site-directed inhibitors also show generally similar potency toward the two enzymes, although guanidinoethylmercaptosuccinic acid is approximately 10-fold more potent, and hippuryl-Arg is approximately 100-fold more potent as an inhibitor of CPD than of CPE. A major difference between the two enzymes is the molecular masses; CPE is 50,000-56,000, whereas CPD is approximately 180,000. Also, CPD does not elute from a substrate affinity column when the pH is raised to 8, which elutes CPE, although CPD can subsequently be eluted by arginine. Both CPE and CPD are present in purified bovine anterior pituitary secretory vesicles, but the tissue distribution of CPD is more uniform than that of CPE. Antisera to the N- and C-terminal regions of CPE do not recognize CPD. The partial N-terminal amino acid sequence of bovine CPD shows 30-40% homology with an N-terminal region of bovine and rat CPE and 70% homology with a duck protein known as gp180, a hepatitis B virus particle binding protein that shows 47% homology to CPE. Taken together, these results suggest that CPD is a novel secretory pathway enzyme that may be the bovine homologue of gp180.
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PMID:Purification and characterization of carboxypeptidase D, a novel carboxypeptidase E-like enzyme, from bovine pituitary. 755 30

We have shown previously that insulin at the physiological concentration suppresses hepatitis B surface antigen (HBsAg) gene expression in cultured human hepatoma Hep3B cells, and this suppression phenomenon is concomitant with the stimulation of cell proliferation. We have now examined whether these two distinct insulin actions on the Hep3B cells are mediated through the same or different signaling pathways. After prolonged treatment with high concentration of tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), the protein kinase C-alpha (PKC-alpha) level in the Hep3B cells was diminished and could not be detected by Western blot analysis. Under this condition, TPA treatment has no effect on the number or affinity of the insulin receptor on Hep3B cells. However, insulin-stimulated cell proliferation was completely abolished in the PKC-alpha depleted cells. In contrast, insulin still suppressed HBsAg gene expression with the same ED50 (approximately 0.5 nM) as the control cell. The induction of proto-oncogene egr-1 (early-growth-regulatory-1) by insulin and TPA under similar conditions were also examined. Both insulin and TPA stimulated egr-1 gene expression up to 10-fold in the control cell, but neither of these two agents showed any effect on egr-1 gene expression in the PKC-alpha down-regulated Hep3B cells. These observations indicate that the PKC-alpha may be involved in the insulin induced egr-1 expression and cell proliferation but not in the insulin suppressed HBsAg gene expression in human hepatoma cells.
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PMID:Differential pathways of insulin action upon the hepatitis B surface antigen gene expression and cell proliferation in human hepatoma cells. 778 17

Gene/biotechnology products can be either physiological peptides for the purpose of substitution of deficiencies or for therapeutic purposes in superphysiological concentrations, or nonphysiological peptides, or newer biotechnology products like monoclonal antibodies. The rules for clinical trials developed so far are also valid for clinical trials with gene/biotechnology products. Nevertheless, a major challenge for the clinical pharmacologist is the species specificity of many reactions induced by gene/biotechnology products in man. In general, animal experiments may be less predictive, so there is a greater demand for human pharmacology studies. Gene/biotechnology products offer more chances for treatment of many diseases, but during the clinical trials the clinician has to always be aware of unexpected side effects. Several newer gene technology products offer superior safety as compared to older biological products like Factor VIII preparations and human growth hormone. More than 19 therapeutics produced by gene/biotechnology have already been approved by health authorities all over the world. Major clinical benefit could be shown with hepatitis B vaccine, insulin, human growth hormone, TPA, erythropoietin, GM-CSF, G-CSF, and monoclonal antibodies for immune suppression. There is also good evidence of efficacy of interferon alpha in chronic hepatitis. So far, our knowledge about cytokines is still limited. In several cancer diseases, interferons show efficacy as well as in several autoimmune diseases. Well designed clinical pharmacology studies will be important to elaborate the therapeutic potential of drugs arising from gene/biotechnology.
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PMID:Clinical trials of gene/biotechnology products. 788 81

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
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PMID:[Interferon-alpha, beta, gamma]. 799 28

The study aimed to evaluate the immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus (IDDM), in view of reports of reduced efficacy in adults with IDDM. Sixty-five young people with IDDM, age 4.5 to 27.5 and diabetes duration 0.3 to 19 years and 174 age- and sex-matched healthy subjects were injected with a recombinant hepatitis B vaccine at 0, 1 and 6 months intramuscularly in the deltoid region. Three (4.6%) IDDM patients and 2 (1.1%) controls were non-responders (HBsAb titre, < 2 IU l-1) and 1 control was a low responder (HBsAb titre = 10 IU l-1). Among the 3 non-responder IDDM subjects, 2 had other autoimmune disease. Median HBsAb titre was similar in responding patients (120 IU l-1 and controls (125 IU l-1). There were no significant correlations between antibody titre and age, diabetes duration, HbA1c or insulin requirement. No association was found between HBsAb titre and any HLA genotype or the presence of microangiopathy. IDDM does not adversely affect the immune response to a recombinant hepatitis B vaccine in children, adolescents, and young adults, who can thus expect to benefit from its use in situations of risk of contracting hepatitis.
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PMID:Successful immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus. 884 96

Since the onset of genetic engineering, yeasts belong to the preferred host cells for the production of heterologous proteins. They combine ease of genetic manipulation and cultivation with the ability to process and to modify the produced compounds according to a general eukaryotic scheme. Since yeasts do not contain pathogens, pyrogens or viral inclusions they constitute attractive production systems for proteins considered for therapeutic administration. At the beginning of gene technology the attention of biotechnologists focussed on the use of the best characterized species Saccharomyces cerevisiae. Insulin and hepatitis B vaccines are examples for S. cerevisiae-derived therapeutics. In recent years alternative yeast have become accessible for the techniques of modern molecular genetics and thus for potential applications in biotechnology. In this respect the methylotrophic yeast Hansenula polymorpha offers especially advantageous characteristics as host for the production of pharmaceutical proteins. As a consequence, production systems based on this yeast have been established for serum proteins, vaccines and other therapeutically important compounds. Some H. polymorpha-derived products are under preclinical or clinical trials at present and are expected to reach the market within the near future. In the following article the current status of this system is presented and discussed comparing it with other expression systems.
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PMID:Methylotrophic yeast hansenula polymorpha as production organism for recombinant pharmaceuticals. 887 47

In vitro DNase I footprint analysis of the rat fatty acid synthase (FAS) promoter from -568 to -468 revealed four protein binding sites: A, B, and C boxes and the FAS insulin-responsive element 1 (FIRE1). As demonstrated by gel mobility shift analysis and supershift experiments, FIRE1, located between -516 and -498, is responsible for binding NF-Y. The C box located downstream of FIRE1 was shown by in vitro footprinting to be a Sp1 binding site, and furthermore, competition with Sp1 also abolished FIRE1 binding. Since the half-life of the Sp1.NF-Y.DNA complex is significantly longer than the half-lives of the Sp1.DNA or NF-Y.DNA complexes, the two transcription factors are deemed to bind cooperatively in the FAS promoter at -500. It is unusual that NF-Y binds at this distance from the start site of transcription. NF-Y binding sites are found in the promoters of at least three other FAS genes, viz. goose, chicken, and man. A second NF-Y binding site is located in the FAS promoter at the more usual position of -103 to -87, and it too has a neighboring Sp1 site. CTF/NF-1 competes for proteins binding to the B box. The A box binds Sp1 and contains a 12/13 match of the inverted repeat sequence responsible for binding the nuclear factor EF-C/RFX-1 in the enhancer regions of hepatitis B virus and the major histocompatibility complex class II antigen promoter. The same relative positions of NF-Y and Sp1 binding sites in the promoters of FAS genes of goose, rat, chicken, and man emphasize the involvement of these transcription factors in the diet and hormonal regulation of FAS.
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PMID:Cooperative binding of NF-Y and Sp1 at the DNase I-hypersensitive site, fatty acid synthase insulin-responsive element 1, located at -500 in the rat fatty acid synthase promoter. 926 Nov 84

A 43-year-old Japanese man who was positive for hepatitis B surface (HBs) antigen and HB e antibody, underwent chemotherapy for non-Hodgkin's lymphoma. After the chemotherapy he suffered from acute exacerbation of hepatitis because of reactivation of HBV. Recovery was achieved with interferon-alpha, glucagon-insulin therapy, and plasma exchange. Mutations were detected in codons 97, 100, 129, and 131 of the core region of HBV. The peptide encoded from the core region including such mutations possibly had greater antigenicity to induce cytotoxic T cell activity in the host. Core region mutations may be a crucial cause of the acute exacerbation of hepatitis B seen after chemotherapy.
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PMID:Acute exacerbation of hepatitis due to reactivation of hepatitis B virus with mutations in the core region after chemotherapy for malignant lymphoma. 934 95


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