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

A sequence of 3299 nt, contiguous with the previously sequenced quinate permease-encoding (qutD) gene and encompassing the dehydroshikimate dehydratase-encoding (qutC) gene, has been determined. Northern-blot analysis detected (i) a quinate-inducible mRNA of the expected size for the qutC gene, and (ii) a quinate-inducible mRNA of 1.45 kb divergently transcribed away from qutC towards qutD. Computer-aided sequence analysis identified an ORF of 1047 nt corresponding to the qutC gene encoding dehydroshikimate dehydratase. In addition, a genetically uncharacterized 1188-nt gene, designated qutH and containing a putative intron of 61 nt, was identified between qutC and qutD. The inferred protein sequence encoded by qutH contains a putative 'zinc cluster' motif and has a low (16%) but significant similarity with the DNA-directed DNA polymerase of hepatitis B virus. The results are interpreted as being consistent with the view that the qutH gene encodes a DNA-binding protein, possibly involved in the regulation of genes essential for the utilisation of protocatechuic acid.
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PMID:A second gene (qutH) within the Aspergillus nidulans-quinic-acid utilisation gene cluster encodes a protein with a putative zinc-cluster motif. 133 61

It has been postulated that hepatocyte injury resulting from infection with hepatitis D virus may be caused by a direct virus cytotoxicity in contrast to immune-mediated injury associated with hepatitis B virus. We have transfected HeLa and HepG2 continuous cell lines with a recombinant plasmid containing the hepatitis D antigen gene under the inducible control of the human metallothionein promoter. The addition of zinc to the cell culture medium then led to the expression of hepatitis D antigen associated with, in the short term, a significant reduction in the rate of RNA but not DNA synthesis and, in the longer term, cell death. The necrotic cells had pyknotic nuclei and shrunken eosinophilic cytoplasm; these necrotic cells resembled the apoptotic bodies seen in hepatitis D virus-related hepatitis. The level of hepatitis D antigen in individual cells that produced these changes was similar to the level of hepatitis D antigen in hepatocytes from a chimpanzee with acute hepatitis D virus infection. We conclude that the expression of hepatitis D antigen resulted in significant cytotoxic changes in these cells, providing strong support for the view that hepatitis D antigen may be specifically cytotoxic to infected hepatocytes in vivo.
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PMID:Direct evidence for cytotoxicity associated with expression of hepatitis delta virus antigen. 170 11

The depression of immunity to various antigens in chronic uremia is a frequently encountered phenomenon. Zinc deficiency might well be an important factor in its genesis. The aim of this study was to investigate the role of zinc deficiency in this reduced immune response. Two groups of 7 patients on haemodialysis who had failed to respond with seroconversion to an earlier vaccination against hepatitis B were revaccinated. One group received zinc by the addition of zinc chloride to the dialysate. Before initiation of the study zinc in plasma and leucocytes was measured. No difference in plasma and leucocyte zinc was observed between the two groups. Zinc in leucocytes was lower in patients than in a group of healthy volunteers (61.5 pmol/10E6 cells +/- 4.6 versus 73.8 +/- 5.6, p less than 0.005). Plasma zinc showed no difference between patients and healthy volunteers. During zinc supplementation zinc in plasma rose in the patient group receiving zinc (10.4 mmol/L +/- 1.5 to 14.2 +/- 1.9, p less than 0.005). However, no rise in leucocyte zinc was seen. At the end of the trial seroconversion had occurred in 2 patients in each group. It is concluded that zinc supplementation in haemodialysis patients does not lead to the restoration of leucocyte zinc to normal levels. Neither did it lead to an enhanced antibody response in our population after revaccination of haemodialysis patients against hepatitis B.
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PMID:Effects of zinc supplementation on zinc status and immunity in haemodialysis patients. 182 9

The serum zinc concentration seems unlikely to be an important factor influencing immune response to hepatitis B vaccination in hemodialysis patients, on the basis of the following results: the absence of statistically significant differences in serum zinc concentrations between patients with absence of post-vaccine seroconversion or non protective seroconversion and patients with excellent seroconversion (anti-HBs concentrations over 124.6 mUI/ml); the association of protective antibody responses in 50% of non responders after an additional dose of HBV vaccine, without preliminary corrections of zinc balance.
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PMID:[Serum zinc concentration and antibody response to hepatitis B vaccine in hemodialysis patients]. 213 58

The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well-designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven.
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PMID:Current therapy of chronic liver disease. 219 64

Abnormalities of humoral and cell-mediated immunity have been described in Down syndrome but reported findings have been inconsistent. Confounding factors have included age, institutional versus home life, hepatitis B antigenemia, and zinc deficiency. To clarify this problem, we studied 64 children with Down syndrome (DS) compared with an age-matched control group. All children had always lived at home. All the DS children were negative for hepatitis B surface antigen. Serum zinc concentration in the DS group was on average 12 micrograms/dl lower than age-matched control children. They also had significantly lower levels of immunoglobulin M, total lymphocyte count, T and B lymphocytes, and T helper and suppressor cells. In vitro lymphocyte response to phytohemagglutinin and concanavalin A was significantly reduced at all ages in the DS group. Lymphocyte response to pokeweed mitogen increased with age in control children but decreased in the DS children. By 18 yr, the mean response for DS was 60000 cpm lower than controls. The DS group had significantly higher concentrations of immunoglobulins A and G than controls and the difference increased with age. Complement fractions C3 and C4 were also higher in the DS group at all ages. The number of HNK-1 positive cells was higher in the DS group than controls at all ages. When hepatitis and institutionalization are excluded as confounding factors, DS children still differ in both humoral and cell-mediated immunity from an age-matched control group.
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PMID:Age-related changes in humoral and cell-mediated immunity in Down syndrome children living at home. 296 Sep 48

In view of the suggested physiological role of natural killer (NK) cells in immunosurveillance and defence against viral infections, we have investigated the relationship between hepatitis B virus (HBV) infection and NK activity against K-562 cells in patients with post-necrotic cirrhosis. Overall, the NK activity in cirrhotic patients did not differ from age- and sex-matched controls. However, cirrhotic males with evidence of HBV infection with or without HBs antigenemia tend to have lower NK activity than controls. Cirrhotic males without evidence of HBV infection do not differ from controls. Such a trend was not observed in the female cirrhotic patients examined. In addition significantly reduced NK activity was observed in cirrhotic patients with low plasma zinc levels. This relationship is of interest because of the known association between zinc deficiency and various immunodeficiencies.
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PMID:Natural killer cell activity in post-necrotic cirrhotic patients as related to hepatitis-B virus infection and plasma zinc levels. 346 62

HCC occurs in a higher incidence in some subsets of human populations residing in specific geographic areas around the world. These include black populations residing south of the Sahara, particularly in South and East Africa; in populations of Southeast Asia and the Western Pacific; in India, China, and in some other circumscribed areas. These epidemiologic observations strongly suggest that environmental factors are involved in the etiology of HCC. Evidence from human and animal data point toward a multicausal etiology, including dietary or environmental contamination with mycotoxin carcinogens, acting in concert with hepatitis B viral infection and, in some areas, with malnutrition. Dietary factors that appear to influence susceptibility to HCC include fat, protein and amino acids, vitamin A, selenium, and zinc. In addition, alcohol consumption, environmental chemicals that are natural or man made, and genetic predisposition must also be considered. It seems likely that identification of etiologic agents (hepatitis B infection, aflatoxin, malnutrition) and correction or prevention of these are the most promising means for controlling HCC in man.
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PMID:Chemical carcinogenesis: mycotoxins and other chemicals to which humans are exposed. 608 58

The employees of the Japan National Railways Co. working in the Tokyo area, comprising 98% men over the age of 40 yr, were examined for hepatitis B virus seromarkers and routine liver function tests (serum glutamic oxaloacetic transaminase, alkaline phosphatase, and zinc turbidity test) and were followed for 5 yr. The examinees included 202 hepatitis B surface antigen carriers, 502 positive for hepatitis B surface antibody, and 2426 negative for both. We found that the frequency of continuously abnormal liver function test was higher in hepatitis B surface antigen carriers compared with noncarriers. Of the 202 carriers, 4 (1.98%) died from hepatocellular carcinoma with or without cirrhosis, whereas in 2928 noncarriers only 2 (0.07%) died from liver diseases unrelated to hepatitis B virus, the difference being 28.3-fold. Three of the 4 who died from hepatocellular carcinoma initially had normal liver function tests. Mortality in carriers with initially normal liver function tests was 44.5 times higher than that in noncarriers with normal tests. Thus, asymptomatic carriers carry a high risk of dying from chronic liver disease. Routine liver function tests appear of limited value in predicting prognosis.
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PMID:Prognosis of hepatitis B virus surface antigen carriers in relation to routine liver function tests: a prospective study. 707 36

This study was conducted to determine and compare serum trace metal levels in viral hepatitis-associated chronic liver disease. Of 98 patients aged 43 (+/- 13) [mean (+/- SD)] years, 83 (85%) were seropositive for hepatitis B surface antigen (HBsAg) and 15 (15%) were seropositive for anti-hepatitis C virus (HCV). Twenty-five patients had chronic persistent hepatitis, 32 chronic active hepatitis, 21 post-necrotic cirrhosis, and 20 hepatocellular carcinoma. Determination of fasting serum trace metal levels (zinc, copper, calcium, magnesium, and phosphorus) was performed after the patients had been on a 2-day diet containing 10-12 mg zinc/day. Compared to healthy volunteers (n = 30), serum zinc levels were significantly decreased in patients with chronic active hepatitis, cirrhosis, and hepatocellular carcinoma (P < or = 0.0001), and copper levels were significantly elevated only in patients with hepatocellular carcinoma (P < 0.0001). The overall serum levels of calcium, magnesium, and phosphorus were within normal ranges, and levels of calcium and magnesium correlated with serum zinc (P = 0.01-0.03). Serum zinc levels correlated with bilirubin, albumin, and cholesterol (P = 0.0004 < or = 0.0001), but not with daily urinary zinc excretion. Serum copper levels correlated with alkaline phosphatase and gamma-glutamyltransferase (P = 0.008-0.0001). These results suggested that changes in liver cell pathology compounded by functional impairment may alter the metabolism of trace metals, in particular, zinc and copper. The possible relationship of these changes to the pathogenesis of chronic liver disease is discussed.
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PMID:Serum trace metals in chronic viral hepatitis and hepatocellular carcinoma in Thailand. 800 May 10


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