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)

Avirulent salmonellae expressing foreign genes are attractive for use as oral vaccine carriers. To facilitate the stable expression of heterologous genes without conferring antibiotic resistance, a deletion of the asdA1 gene was introduced into Salmonella typhimurium and S. typhi delta cya delta crp mutant vaccine strains. An asd-complementing plasmid expressing hybrid hepatitis B virus nucleocapsid-pre-S (HBcAg-pre-S) particles was constructed. These hybrid HBcAg-pre-S particle genes were stably expressed in S. typhimurium and S. typhi delta cya delta crp mutant vaccine strains in this balanced, lethal host-vector combination. A single oral immunization of BALB/c mice with a recombinant S. typhimurium delta cya delta crp mutant synthesizing hybrid HBcAg-pre-S elicited potentially virus-neutralizing anti-pre-S serum immunoglobulin G antibodies. In addition, serum immunoglobulin G recognizing S. typhimurium lipopolysaccharide was induced. Distribution in tissue after oral immunization was analyzed in one plasmid-strain combination. The recombinant S. typhimurium colonized the gut-associated lymphoid tissue and the spleen and persisted for over 4 weeks, retaining the HBcAg-pre-S expression plasmid. An isogenic virulence plasmid-cured S. typhimurium delta cya delta crp strain expressing the same HBcAg-pre-S gene had reduced immunogenicity for the carried antigen after oral immunization.
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PMID:Hybrid hepatitis B virus core-pre-S proteins synthesized in avirulent Salmonella typhimurium and Salmonella typhi for oral vaccination. 816 28

In patients with chronic diarrhoea investigations exceptionally reveal a common variable hypogammaglobulinaemia. A 42-year old man presenting with chronic bronchitis and asymptomatic post-hepatitis B cirrhosis was hospitalized for evaluation of a chronic diarrhoea accompanied by altered general condition. Investigations detected global hypogammaglobulinaemia, diffuse lymphoid hyperplasia of the small bowel, and lambliasis. Treatment with gammaglobulins and antibiotics resulted in disappearance of symptoms. This was a rare disease due to a primary disorder where global hypogammaglobulinaemia was associated with a normal number of circulating B-cells. Prognosis was cautious in view of the risk of malignant proliferation.
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PMID:[Common variable hypogammaglobulinemia. A rare cause of chronic diarrhea. A case]. 827 24

We previously developed a transgenic (Tg) murine lineage (B10.S-Tg31e), which secretes the hepatitis B e Ag (HBeAg) into the serum at a concentration of 10 ng/ml. This serum concentration was sufficient to render B10.S-Tg31e mice functionally tolerant at the T cell but not B cell level. To determine the tolerogenic potential of an intracellular form of this Ag, namely the hepatitis B core Ag (HBcAg), expressed outside the thymus, the B10.S-Tg10c lineage was developed. In B10.S-Tg10c mice the HBcAg is expressed as an intracellular "self"-Ag predominantly in the liver, and cannot be detected in the serum, the thymus or in nonthymic lymphoid tissue. Despite the liver-specific and intracellular location of this transgenic self-protein, B10-STg10c mice demonstrate a significant degree of HBcAg-specific T cell tolerance at the level of T cell proliferation. Similarly, in vivo anti-HBc antibody production after HBcAg immunization is significantly reduced as compared with non-Tg littermate controls. No spontaneous anti-HBc antibody is produced in B10.S-Tg10c mice, however, adoptive transfer of HBcAg-specific T cells from non-Tg B10.S mice elicits anti-HBc specific "autoantibody" production. Interestingly, antibodies with specificity for the HBeAg as well as the HBcAg are produced. Antibody production in B10.S-Tg10c mice adoptively transferred with T cells indicates that sufficient native HBcAg can gain access to the extracellular compartment to engage HBcAg-specific B cells that are clearly not tolerant in this model. No liver injury was observed as a consequence of HBcAg expression, even in B10.S-Tg10c mice adoptively transferred with HBcAg-specific T cells. Unless HBcAg is unique in this regard, these results suggest that organ-specific, intracellular self-Ag may be released during normal cell turnover in sufficient concentrations to elicit systemic T cell tolerance. B10.S-Tg10c mice also serve as an immunologic model system for chronic infection with the HBeAg-negative mutant of the hepatitis B virus.
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PMID:Extrathymic expression of the intracellular hepatitis B core antigen results in T cell tolerance in transgenic mice. 828 30

This study sought to establish whether administration of dehydroepiandrosterone (DHEA) or its sulfate derivative to aged mice could effectively correct the immunosenescent phenotype. Supplemental DHEA sulfate and topical DHEA fully corrected the age-associated dysregulated production of T cell lymphokines by cells from all of the different lymphoid organs tested. Either DHEA or DHEA sulfate supplementation promoted enhanced antibody responses against recombinant hepatitis B surface antigen (rHBsAg) by the aged recipients when incorporated directly into the vaccine. When DHEA was provided either topically or was incorporated directly into vaccine, vigorous primary and secondary antibody responses were detected in the aged mice given a single administration of DHEA, regardless of the mode of administration. It was also established that DHEA treatment could enhance specific antibody responses to rHBsAg in aged animals that had previously not been effectively immunized by conventional vaccination procedures.
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PMID:Reversal of the immunosenescent phenotype by dehydroepiandrosterone: hormone treatment provides an adjuvant effect on the immunization of aged mice with recombinant hepatitis B surface antigen. 845 Feb 48

In this retrospective study, we have investigated the early intragraft inflammatory events of 12 liver allografts leading to chronic rejection. The cytological findings and clinical follow-up were analyzed in detail. Nine patients underwent at least one typical lymphoid activation of acute rejection, and three of them were treated more than once. Diagnosis of rejection was based on biopsy histology, cytology and liver dysfunction. In addition to the acute rejections, cytological analysis demonstrated in 11 of 12 grafts an unidentified lymphoid episode that differed from that of rejection. These lymphoid responses were associated with viral infections; cytomegalovirus (CMV) infection in 10 of 12 patients, hepatitis C virus (HCV) infection in 2 of 12 patients, 1 combined with CMV, and hepatitis B virus (HBV) infection in 1 patient. Graft dysfunction was still seen at the end of the follow-up. Thus, intragraft inflammation caused either by acute rejection or by viral infections may be involved in the induction of chronic rejection.
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PMID:Early intragraft inflammatory events of liver allografts leading to chronic rejection. 857 35

Carcinogenesis is a multistage process involving activation of protooncogenes, e.g., ras, and inactivation of tumor suppressor genes, e.g., p53 and p16INK4.p53 is a prototype tumor suppressor gene that is well suited for analysis of mutational spectrum in human cancers; it is the most common genetic lesion in human cancers, it is a reasonable size for a molecular target, and it may indicate selection of mutations with pathobiological significance. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain and lymphoid malignancies. Mutational hotspots at CpG dinucleotides in codons 175, 245, 248, 273 and 282 may reflect endogenous mutagenic mechanisms, e.g., deamination of 5-methylcytosine to thymidine. Oxy-radicals including nitric oxide may enhance the rate of deamination. G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung, breast, esophagus and liver, and are more likely to be due to bulky carcinogen-DNA adducts. G to T transversion is more common in lung cancers from smokers when compared to never smokers. The high frequency of p53 mutations in the nontranscribed DNA strand is a reflection of strand specific repair, p53 mutation and/or accumulation of p53 protein can be preinvasive events in bronchial or esophageal carcinogenesis, p53 mutations also generally indicate a poor prognosis. In geographic areas where hepatitis B virus (HBV) and aflatoxin B1 are cancer risk factors, most mutations are at the third nucleotide pair of codon 249. In geographic areas where hepatitis B and C virus--but not aflatoxin B1--are risk factors, the p53 mutations are distributed in numerous codons. HBV X protein complexes with the p53 protein and inhibits its sequence specific DNA binding, transactivating and apoptotic capacity. The mutation load of 249ser mutant cells in nontumorous liver is positively correlated with dietary aflatoxin B1 exposure. The induction of skin carcinoma by ultraviolet light is indicated by the occurrence of p53 mutations at dipyrimidine sites including CC to TT double base changes. In summary, these differences in mutational frequency and spectrum among human cancer types suggest the etiological contributions in both exogenous and endogenous factors to human carcinogenesis and have implications for human cancer risk assessment.
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PMID:1995 Deichmann Lecture--p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology and cancer risk assessment. 859 35

The study described in this report demonstrates that peripheral lymph nodes draining nonmucosal tissues can effectively serve as induction sites for the establishment of common mucosal immunity if the microenvironmental conditions are altered to mimic those normally present within mucosa-associated lymphoid tissues (e.g., Peyer's patches). Lymph node lymphocytes exposed in situ to the immunomodulatory influences of the hormone 1 alpha, 25-dihydroxy vitamin D 3 were found to produce less gamma interferon and interleukin-2 (IL-2) and far more IL-4, IL-5 and IL-10 than lymphocytes from control animals. When couples with vaccination with hepatitis B surface antigen (HBsAg), the hormone, immunomodulated switch from a peripheral lymph node phenotype to a Peyer's patch-like pattern promoted the induction of both a systemic and a common mucosal immune response. This was determined by the observed increased concentrations of serum anti-HBsAg antibody and by finding that anti-HBsAg secretory antibodies were detectable in urogenital, lachrymal, fecal and oral secretions only in the hormone-treated animals. In addition, specific antibody-secreting cells were detectable in the lamina propria of the lungs and small intestines of the hormone-treated animals subsequent to vaccination, indicating that the homing properties of antigen-specific B cells were being affected by the treatment procedure. The humoral and mucosal immune responses were further augmented if both 1 alpha, 25-dihydroxy vitamin D 3 and dehydroepiandrosterone were used together as hormonal immunomodulators. This novel immunization technique may afford new opportunities to effectively intervene in sexually transmitted diseases and other diseases caused by mucosal pathogens.
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PMID:Induction of common mucosal immunity by hormonally immunomodulated peripheral immunization. 860 65

Hepatitis C viral recurrence after orthotopic liver transplantation is almost universal. Hepatitis C induced graft failure may occur, but the clinical and histologic profiles are not well defined. The aim of this study was to describe the pattern of early graft failure in patients with recurrent hepatitis C after liver transplantation. Thirty patients with hepatitis C underwent liver transplantation from October 1989 through September 1994. Four patients were excluded because of death (2 patients), graft failure unrelated to hepatitis C (1 patient), and lost to follow-up (1 patient). Hepatitis C recurred in 24 of the 26 remaining patients. In 4 patients with hepatitis C virus recurrence and cholestasis, graft failure developed at 5.25, 11.0, 11.0, and 18.5 months. The medical records and liver biopsies were reviewed. In all 4 patients, a histologic pattern characterized by centrilobular ballooning degeneration developed and progressed to involve more than two-thirds of the lobules. Moderate to severe cholestasis and bridging fibrosis were present in all grafts at explant. Two patients had portal inflammation on 3-month biopsies consistent with viral hepatitis. All patients had mild macrovesicular steatosis, but only 1 patient had significant lymphoid aggregates. No patient had evidence of hepatic artery thrombosis. One patient had potential drug-induced cholestasis. One patient had 3 episodes of rejection that were not believed to contribute to graft loss. All 4 patients developed clinical features of hepatic failure and were retransplanted. Two patients had early recurrence of graft failure. We conclude that a pattern of progressive centrilobular ballooning degeneration, bridging fibrosis, and cholestasis occurs in some patients with hepatitis with early graft failure, similar to fibrosing cholestatic hepatitis seen in some transplant patients with recurrent hepatitis B.
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PMID:Clinical and histologic patterns of early graft failure due to recurrnet hepatitis C in four patients after liver transplantation. 860 70

Evaluation of liver biopsies in hepatitis C is aimed at confirming the clinical and serologic diagnosis, grading of necroinflammatory activity, staging of consecutive fibrosis, ruling out or confirming liver diseases of different etiology, and assessment of therapeutic effects. Usually, the course of chronic hepatitis C virus (HCV) infection is slow, with mild inflammatory changes. Nevertheless, even in mild asymptomatic chronic hepatitis C episodes of higher inflammatory activity associated with extensive piecemeal necrosis and porto-central bridging, necrosis can accelerate the course of the disease. For this reason, the traditional, morphologically based classification of chronic hepatitis and the term "chronic persistent hepatitis" have lost their predictive usefulness, especially in hepatitis C. Chronic hepatitis should be characterized by etiologic designation as well as grade and stage of the disease. Portal lymphoid aggregates, some inflammatory bile duct damage and mild steatosis are the most characteristic features by which hepatitis C can be differentiated from other progressive inflammatory liver diseases. Antibodies directed against HCV antigens allow identification of viral proteins by immunohistochemistry. Immunostaining for hepatitis B antigens, for alpha-1-antitrypsin and copper staining are helpful in detecting hepatitis B and congenital liver diseases (Wilson's disease, alpha-1-antitrypsin deficiency) as possible causes of chronic progressive inflammatory liver disease. Centrilobular Mallory's hyalin, identified by immunostaining for ubiquitin in combination with perivenular fibrosis, is helpful in diagnosing concomitant alcoholic liver disease. In our own biopsy material (n = 100) and autopsy material (n = 58), HIV/HCV-coinfected patients have a significantly higher rate of fibrosis and cirrhosis than HIV patients without HCV infection. Hepatitis C can apparently aggravate the course of HIV infection. Our morphologic findings support the clinical observation that chronic HCV infection seems to be the main cause of liver failure, especially in the risk group of HCV/HIV-coinfected hemophiliacs.
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PMID:Histopathologic findings in chronic hepatitis C. 883 87

The aim of this study was to investigate whether hepatitis C virus (HCV) may perturb the immune system towards autoreactivity. We studied the relationship between the prevalence of anti-HCV and the presence of laboratory and/or clinical autoimmune features in 300 patients: lymphoid malignancies (167) and autoimmune disorders (connective tissue diseases 100; idiopathic thrombocytopenic purpura (ITP) 33). As a control, hepatitis B surface antigen (HBV) and anti-hepatitis B core antigen (anti-HBc) were related to the same parameters. Anti-HCV and anti-HBV were detected in 68/300 (22.6%) and 70/300 (24.6%) patients, respectively. HCV prevalence was 18% in lymphoproliferative disorders (anti-HBc 28.1%) and 26% in connective tissue disease (anti-HBc 16.3%). Among ITP cases, 12/33 (36.4%) were anti-HCV+ and 10/33 (30.3%) anti-HBc+. In 24/30 (80%) anti-HCV+ patients with lymphoproliferative disorders at least one serologic or clinical autoimmune abnormality was detected. To the contrary, only 10/45 (22.2%) anti-HBc+ patients with lymphoproliferative disorders had at least one serologic or clinical abnormality (P < 0.0001). A statistically significant correlation was observed between HCV prevalence and the number of autoimmune alterations in both lymphoproliferative and connective tissue disorders, which was not found for anti-HBc. These data suggest that HCV may skew the immune system toward the production of autoantibodies and also support the possibility that some cases of ITP may be linked to both HCV and HBV infection.
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PMID:High prevalence of autoimmune phenomena in hepatitis C virus antibody positive patients with lymphoproliferative and connective tissue disorders. 885 62


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