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Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 235 records · Page 13Linked to original sources
PubMed1987

Hepatocellular carcinoma and the hepatitis B virus: a study of British patients.

We have examined the relationship between hepatitis B virus infection and hepatocellular carcinoma in a series of 50 British patients with histologically-proven hepatocellular carcinoma. Serum HBsAg was detected in 10 patients (20 per cent), and of the remainder, 21 per cent of those tested had serological evidence of past hepatitis B virus exposure. None of nine tumour specimens from serum HBsAg negative patients had detectable HBV-DNA integration into the tumour cell genome. The presence or absence of serum HBsAg was of no prognostic significance in British patients with hepatocellular carcinoma. Liver cell dysplasia, a possible pre-malignant lesion, was noted in 53 per cent of patients who had had liver biopsies before the diagnosis of hepatocellular carcinoma, and in 79 per cent of biopsies taken at the time of diagnosis of hepatocellular carcinoma. The presence of liver cell dysplasia was not more common in serum HBsAg positive patients.

Adolescent↗
PubMed1987

Inhibition of hepatitis delta virus (HDV) replication by lymphoblastoid human alpha interferon.

Lymphoblastoid interferon inhibited hepatitis delta virus (HDV) replication in four out of five HDV carriers with chronic active liver disease. Serum HDV-RNA was undetectable in three patients, but in one of these evidence of continuing intrahepatic HDV replication was present on biopsy one year after treatment. In the four cases which showed total or partial inhibition of HDV replication, there was a transient increase in transaminases during treatment, and in three this was followed by improvement. These effects lasted for longer than one year. The lysis of hepatocytes occurring on exposure to interferon may be related to the induction of 2-5A oligosynthetase which, in the presence of the dsRNA of HDV, activates endonucleases which destroy the rRNA of the infected cells.

Adult↗
PubMed1986

Diagnostic and prognostic significance of the IgM antibody to the hepatitis delta virus.

The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each of 70 patients with inflammatory liver disease and at a low titer in one of six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. The IgM antibody persisted in high titer over many years in patients with unremitting or progressive liver disease, but declined or disappeared before the homologous IgG antibody in the patients whose disease improved or resolved. Testing for IgM antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.

Antibodies, Viral↗
PubMed1986

Hepatitis A virus replication in tamarins and host immune response in relation to pathogenesis of liver cell damage.

Hepatitis A virus (HAV) shedding in the faeces, appearance of HAV-Ag (antigen) in the liver, and development of humoral immunity to HAV have been studied in experimentally infected tamarins. The appearance of liver damage measured by transaminase elevation and histology, in relation to the above variables, suggests that the virus is not cytopathic and the immune system contributes to the production of liver cell damage. Preliminary data suggest that HAV replication may occur in the mucosa of the small intestine and in the liver.

Animals↗
PubMed1986

Homology between HBV-DNA and a sequence regulating the interferon-induced antiviral system: possible mechanism of persistent infection.

Treatment of hepatitis B virus (HBV)-infected hepatocytes with lymphoblastoid alpha-interferon (IFN) leads to an increased expression of the core antigen (HBcAg) and reduced expression of surface antigen (HBsAg). We have identified the presence of a nucleotide sequence at the start of the HBc gene in the hepatitis B virus genome similar to a consensus sequence known to occur upstream from genes induced by IFN in mammalian cells. It is possible that interferon influences the expression of the viral genes because of the presence of this homologous sequence. This sequence in the viral genome may determine the site of integration of the virus and could influence the ability of the cell containing the integrated viral sequence to respond to interferon. This "neutralisation" of the interferon system by viral integration might not only facilitate persistent infection but might also adversely affect response to alpha-interferon therapy.

Biopsy↗
PubMed1986

Identification of a dominant immunogenic epitope of the nucleocapsid (HBc) of the hepatitis B virus.

Four monoclonal antibodies to hepatitis B core antigen are described. The antibodies bind to the same or a very closely related epitope. Antibodies to this dominant epitope are present in the sera of patients with either acute or chronic hepatitis B virus (HBV) infection. A high percentage of inhibition of the binding of these antibodies to the core antigen by these four monoclonal antibodies suggests that the core antigen has a restricted antigenicity in man. Radiolabeled or peroxidase labeled forms of these monoclonal antibodies can be used to assay IgM and total anticore in serum.

Animals↗
PubMed1986

Perinatal transmission of hepatitis B virus in Kenya: its relation to the presence of serum HBV-DNA and anti-HBe in the mother.

In Kenya hepatitis B virus (HBV) infection and its sequelae are common. We followed up 49 hepatitis B surface antigen (HBsAg)- positive mothers and their newborn infants for 9 months to determine the importance of perinatal transmission in the African and to relate this to the HBe and HBV-DNA status of the mother. Our study shows that perinatal transmission is relatively unimportant in Kenya and that this may be a consequence of the low levels of circulating HBV-DNA in the maternal plasma. These results imply that vaccination without hyperimmune globulin may be adequate to control HBV infection in Kenya.

DNA, Viral↗
PubMed1986

Human lymphoblastoid interferon. In vitro and in vivo studies in hepatocellular carcinoma.

We have examined the growth inhibitory effects of human lymphoblastoid interferon (IFN) on the human hepatocellular carcinoma (HCC) cell line PLC/PRF/5. In vitro, PLC/PRF/5 cells were sensitive to the antiproliferative effects of IFN, growth inhibition being noted at concentrations as low as 1.25 i.u. ml-1. Athymic mice with xenografted tumours derived from the PLC/PRF/5 cell line were treated daily with IFN or a saline control. An IFN dose of 2 X 10(5) i.u./day was found capable of significantly slowing tumour growth rate and prolonging mouse survival. Further studies to examine the mechanisms involved in growth inhibition in vivo demonstrated that IFN was capable of inducing the activity of the enzyme 2,5-oligoadenylic acid (2,5 A) synthetase, a potent inhibitor of protein synthesis, in tumour xenografts but not in mouse tissue, and that IFN significantly enhanced the membrane display of HLA class I glycoproteins on tumour cells, though histology did not reveal any increase in tumour infiltration by host lymphocytes. We conclude that IFN exerts potent growth inhibitory effects on the HCC cell line PLC/PRF/5 both in vitro and in vivo and its mode of action in this animal model system appears to be predominantly mediated by a direct antiproliferative effect on tumour cells.

2',5'-Oligoadenylate Synthetase↗
PubMed1986

A pilot study of BW A515U (6-deoxyacyclovir) in chronic hepatitis B virus infection.

BW A515U (6-Deoxyacyclovir) is a pro-drug of acyclovir and almost 100% is absorbed orally. 250 mg orally 6-hourly for 10 days was given to 4 hepatitis B surface antigen/e antigen-positive carriers. No consistent effect on productive viral replication, as determined by serum DNA polymerase and DNA levels was observed. The changes that occurred in these markers and transaminases in 1 patient were attributed to a spontaneous depression of productive viral replication.

Acyclovir↗
PubMed1986

Lymphoblastoid and recombinant alpha-A interferon therapy of chronic hepatitis B virus infection. The Royal Free Hospital experience.

Lymphoblastoid interferon (Wellferon), a combination of at least 8 alpha-interferons, has been shown to be effective therapy in male chronic carriers of HBV infection, resulting in the loss of HBeAg and HBV-DNA in 50% of those treated. However, 0/8 women (5 Chinese) treated in this trial responded to treatment. Patients with higher ASTs, CAH on biopsy and a history of acute hepatitis are more likely to respond to treatment. Recombinant alpha-A interferon has not been as successful in our particular group of patients. However, this may be explained by the observation that most of these patients are asymptomatic, homosexuals and have lower transaminases, less histological inflammation and a higher percentage of HTLV-III antibody positivity than the Wellferon group. In the HTLV-III-negative group of HBV carriers, the response to recombinant alpha-A interferon is similar to that achieved with lymphoblastoid interferon.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Identification of factors influencing response rate to antiviral therapy of chronic hepatitis B virus infection. A review of the efficacy of adenine arabinoside and lymphoblastoid interferon in the Royal Free Hospital studies.

We have reviewed the results of treating over 100 HBV carriers with adenine arabinoside, adenine arabinoside monophosphate and lymphoblastoid interferon. In the homosexual group of carriers, adenine arabinoside and its monophosphate have no value. However, in this group, lymphoblastoid interferon will produce a response in over 50% of cases. The lack of effectiveness of adenine arabinoside monophosphate in this group may stem from its immunosuppressant properties. In heterosexual carriers both adenine arabinoside monophosphate and lymphoblastoid interferon are effective in approximately 50-60% of cases. However, the response rate is different in the various racial groups. Northern European and Mediterranean people appear to respond whereas those from the Far East do not. This may reflect the fact that there are at least 2 mechanisms by which the chronic carrier state may arise. In 5-10% of adults, a relative deficiency of alpha-interferon production exists and this defect is found in the majority of HBV carriers in Western Europe. In these, interferon acts as a replacement therapy and excellent results may be obtained if the patient is treated early in the course of the disease. It would appear that as the duration of the infection increases, the virus may integrate into interferon-reactive consensus sites and prevent the cell from responding to interferon. In patients infected at birth, transplacental anti-HBc appears to modulate the immune response and along with immaturity of the immune system at this age, results in failure to lyse infected cells. These patients do not benefit from interferon treatment: some form of immune manipulation is required.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1986

Influence of sexual preference and chronic hepatitis B virus infection on T lymphocyte subsets, natural killer activity, and suppressor cell activity.

To determine whether abnormalities of cell-mediated immunity are associated with chronic hepatitis B virus infection or with homosexuality, we studied 15 homo- and 11 heterosexual men with chronic hepatitis B virus infection, as well as 11 homo- and 16 heterosexual apparently healthy men. T lymphocyte subsets, natural killer activity, and suppressor cell activity were determined. Homosexual men had significantly lower peripheral blood T4/T8 ratios resulting from a significant increase in T8-positive (suppressor/cytotoxic) cells, and they also had lower natural killer activity. These effects of homosexuality were independent of chronic hepatitis B virus infection, which caused no significant changes independent of homosexuality, and they were not caused by infection with human immunodeficiency virus (formerly HTLV-III/LAV). Suppressor cell function was unaltered in this study. We conclude that studies of cellular immunity in hepatitis B virus infection must take male sexual preference into account.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Chronic hepatitis B virus infection. Viral replication and patterns of inflammatory activity: serological, clinical and histological correlations.

We have studied serum and tissue markers of viral replication in 39 patients with chronic hepatitis B virus (HBV) infection and correlated these with periportal and lobular activity in liver biopsies. HBV DNA positivity correlated with the presence of hepatitis B e antigen (HBeAg, P less than 0.001) and aspartate transaminase (AST) levels (P less than 0.005). The lobular but not the periportal inflammatory activity was significantly associated with the presence of HBV DNA (P less than 0.02) and HBeAg (P less than 0.001) and with higher AST levels. The periportal activity correlated with the periportal and lobular display of beta 2-microglobulin on hepatocytes (P less than 0.001 and P less than 0.002, respectively). In patients with chronic HBV infection therefore, the lobular rather than the periportal component of activity was related to viral replication. The association of display of beta 2-microglobulin on hepatocytes with the inflammatory process, in patients with active viral replication, is consistent with the hypothesis that increased display of HLA type I enhances recognition of hepatocytes bearing viral proteins and allows lysis of immune cells.

Adult↗
PubMed1986

Virus-neutralizing antibodies to hepatitis B virus: the nature of an immunogenic epitope on the S gene peptide.

Using a murine monoclonal antibody (RF-HBs-1) which has been shown to be capable of neutralizing both ad and ay subtypes of hepatitis B virus (HBV), we have devised a competitive inhibition assay to measure the presence of virus-neutralizing antibodies in the sera of patients who have recovered from acute type B hepatitis. The majority of patients have this antibody in their serum. We also show that this antibody inhibits the binding of polymerized human serum albumin (pHSA) to the pHSA receptor site of the HBV particle, which has been proposed as an important site for the entry of HBV into liver cells. We have demonstrated that the epitope recognized by this antibody is dependent on the linkage of 24,000 and 28,000 mol. wt. polypeptides via a disulphide bond. This conformational determinant in the coat of the virus which is part of or near to the pHSA binding site is important in evoking a virus-neutralizing response.

Antibodies, Monoclonal↗
PubMed1986

Cloning and analysis of integrated hepatitis B virus DNA of the adr subtype derived from a human primary liver cell carcinoma.

A 10 kb genomic DNA fragment derived from a human primary liver cell carcinoma (PLC) and containing integrated hepatitis B virus (HBV) DNA was cloned and analysed. Physical mapping showed the viral DNA to comprise a linear sequence of at least 2.8 kb (87%) of the HBV genome and to be of the adr subtype. Integration appeared to have occurred in the region of the viral genome spanning the cohesive ends. The cellular flanking DNA sequences to one side of the integrated viral DNA contained repeats of the Alu family. The finding of no apparent rearrangements of the integrated HBV DNA sequences in this clone is in contrast to the situation in the huSP and PLC/PRF/5 PLC cell lines in which the integrated viral DNA sequences are greatly rearranged and suggests that such rearrangements may be atypical of solid PLCs.

Base Sequence↗