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Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 289 records · Page 16Linked to original sources
PubMed1984

Aetiology of acute sporadic hepatitis in adults in Kenya.

Markers for acute hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis non-A, non-B (HNANB) infections were examined in the sera of 94 patients presenting with acute hepatitis in Kenya. Hepatitis B virus was responsible for 70% of cases, HNANB for 18%, and HAV for only 12%. The use of an IgM anti-HBc assay increased the rate of diagnosis of acute HBV infection, thereby reducing the proportion of cases designated as NANB.

Acute Disease↗
PubMed1984

The immunopathology of autoimmune and hepatitis B virus-induced chronic hepatitis.

In patients with autoimmune chronic liver disease, a defect in the regulatory system of the immune response allows proliferation of clones of cells reacting with hepatocyte antigens. Identification of these target antigens, their isolation, and purification will allow further study of the nature of the immune diathesis and permit development of specific therapy designed to eliminate the malregulated clones of immunocytes. The mechanisms resulting in hepatocyte damage during chronic HBV infection are more complex. Both lobular focal and periportal piecemeal necrosis of hepatocytes is seen. Current evidence is consistent with the view that focal necrosis represents T-cell lysis of hepatocytes containing replicating virus, whereas piecemeal necrosis is a reflection of an autoimmune response to native liver membrane antigens, initiated by viral replication. The latter response would be expected to be greatest during viral replication, but because of the increase in suppressor T-cell concentrations that occurs at this time, the liver membrane antibody response is largely suppressed. When viral replication ceases, in patients with normal suppressor cells, the liver membrane antibody response is suppressed. In some patients, suppressor cells are relatively reduced and the liver membrane antibody response continues after cessation of viral replication. At this stage, the composition of the inflammatory infiltrate in the liver is similar to that seen in autoimmune (lupoid) chronic active hepatitis. The destruction of hepatocytes containing integrated HBV-DNA is probably dependent on an immune response to HBs antigen. Failure of this elimination process, for immunogenetic or environmental reasons, results in persistence of clones of cells from which malignantly derived cells may ultimately arise. Adequate therapy of this condition must not only stop the replication of the virus, thereby reducing hepatic inflammatory activity, but eliminate clones of cells containing integrated HBV-DNA so that the danger of malignant transformation of hepatocytes is removed.

Antigens, Viral↗
PubMed1984

Neurotoxicity associated with adenine arabinoside monophosphate in the treatment of chronic hepatitis B virus infection.

Thirty-one patients with chronic HBV infection were randomized to receive a short or long course of ARA-AMP. Fifteen completed a 4 week course of treatment and 16 completed longer courses varying from 7 to 12 weeks. Eighteen patients did not experience any neurological side effects. Six patients had myalgia. This was not associated with any neurological deficit. Seven patients developed a sensory neuropathy with distressing pain and dysesthesiae in the feet and abnormalities in nerve conduction. The development of neurotoxicity was related to a long duration of treatment and a correspondingly higher total dose but there was no association with the severity of liver disease.

Adolescent↗
PubMed1984

Hepatitis B virus and host cell membrane antigens on a primary hepatocellular carcinoma cell line.

We have defined some membrane antigens of the cultured hepatocellular carcinoma cell line PLC/PRF/5, which contains the integrated genome of hepatitis B virus. Using fluoresceinated antibodies, we identified HLA Class 1 glycoprotein and HB surface antigen on the membrane. Only in a minority of cells was physical association of these antigens demonstrated by co-capping. The presence of a "division" antigen was indicated by reactivity of the cells with the murine monoclonal antibody OKT9.

Animals↗
PubMed1984

Thrice weekly lymphoblastoid interferon is effective in inhibiting hepatitis B virus replication.

Six patients with chronic hepatitis B virus (HBV)-induced liver disease were treated with human lymphoblastoid interferon. Daily, alternate day or thrice weekly regimens were employed in two, one and three patients respectively. Thrice weekly intra-muscular injections of 7.5 to 10 megaunits of interferon/m2 appeared to be as effective as daily injections in producing inhibition of HBV replication, were associated with fewer side effects and could be continued for up to 3 months. The effectiveness of this regimen in producing long-term inhibition of viral replication must now be determined.

Adult↗
PubMed1984

Contribution of low level HBV replication to continuing inflammatory activity in patients with anti-HBe positive chronic hepatitis B virus infection.

The relationship between the histological diagnosis and serological and tissue markers of HBV replication in 41 Greek and 29 British patients with chronic HBV infection were studied. All the nine Greek and 13 British patients who were HBeAg positive had HBV-DNA in serum and HBcAg expression in the hepatocytes. The majority (73%) of these patients had active liver disease. Forty seven per cent of the Greek and 19% of the British patients who were anti-HBe positive continued to display HBcAg in the liver with or without HBV-DNA detected in serum. All but three of these patients had persistently active liver disease. Continuing inflammatory activity in the liver, however, was also found in 31% of anti-HBe positive patients who had no evidence of HBV replication. In these patients, other factors such as delta agent, NANB viruses, alcohol abuse or an autoimmune reaction initiated by HBV may be contributory.

Chronic Disease↗
PubMed1984

Clinical, biochemical, serological, histological and ultrastructural features of liver disease in drug abusers.

Heroin abusers are frequently found to have abnormal liver function tests and hepatic histology. Hepatitis viruses A, B, and NANB, other drugs or drug contaminants and excessive alcohol consumption are factors thought to contribute. One hundred and sixteen heroin abusers attending a London treatment centre were studied. Sixty two (53%) had a raised aspartate transaminase. This was not explained by current infection with hepatitis A and B, cytomegalo or Epstein-Barr viruses, excessive alcohol consumption (greater than 80 g/day) or concomitant drug taking. Abnormal liver function tests were as frequent in those with markers of current or past HBV infection as those without and there was evidence that both HBV infection and the cause of the abnormal liver function tests were acquired in the first few years of intravenous drug abuse. Liver biopsies from eight patients showed chronic hepatitis with a mild lobular and portal inflammatory infiltrate, fatty change and prominent sinusoidal cells. Electron microscopy showed cytoplasmic trilaminar tubular structures and dense fused membranes in dilated endoplasmic reticulum. These clinical, biochemical, serological, and histological features would suggest a major role for NANB virus infection in the aetiology of hepatitis in heroin abusers.

Adult↗
PubMed1984

Analysis of the molecular state of HBV-DNA in the liver and serum of patients with chronic hepatitis or primary liver cell carcinoma and the effect of therapy with adenine arabinoside.

The pattern of replicative intermediates seen in the liver of HBe antigen and antibody positive patients was determined. During the phase of HBe antigenaemia the 3.2 Kb species of HBV-DNA (complete HBV genome) is present in the liver but not in the serum. When HBe antigen to antibody seroconversion occurs, either spontaneously or during antiviral therapy, the 3.2 Kb and lower molecular weight intermediates disappear from the liver and the 3.2 Kb band appears transiently in the serum. Integrated HBV-DNA was found in one of 15 patients during the period of HBe antigenaemia and in three of seven patients in the HBe antibody positive phase of the chronic infection before detection of primary liver cell carcinoma. Integrated sequences were found in tumour tissue of two patients with primary liver cell carcinoma who were anti-HBc positive but were absent from the tissues of two patients developing primary liver cell carcinoma at a late stage of autoimmune liver disease. These studies suggest that integration of the HBV genome occurs rarely or in only a small proportion of hepatocytes during the early (HBe antigen positive) phase of infection in Caucasians. They also show that not all primary liver cell carcinomas necessarily contain HBV-DNA.

Adult↗
PubMed1984

In vitro and in vivo cytotoxic activity of native and ricin conjugated monoclonal antibodies to HBs antigen for Alexander primary liver cell carcinoma cells and tumours.

In in vitro and in vivo systems, native or ricin conjugated monoclonal anti-HBs, are capable of inhibiting or slowing the growth of Alexander primary hepatocellular carcinoma cells. Failure of the immune response to this component of the hepatitis B virus may be one permissive factor in the development of some primary liver cell carcinoma in chronic HBV carriers.

Animals↗
PubMed1983

Retinotopic organization of striate and extrastriate visual cortex in the hooded rat.

The visuotopic organization of the primary visual cortex (area 17) and the extrastriate visual regions surrounding it (areas 18a and 18) has been studied in gray rats using standard microelectrode mapping techniques. The results confirm and extend previous observations in the rat. Apart from the representation of the contralateral visual field (VF) in area 17, in which the upper VF is represented caudally and the nasal VF laterally, there are additional representations of the VF in the extrastriate cortex. In lateral extrastriate cortex (area 18a) there are at least 4 such representations, namely lateromedial (LM), anterolateral (AL), laterointermediate (LI) and laterolateral (LL). In LM (second visual area) the upper VF is represented caudally and the nasal VF medially, being thus a mirror image of V1. In AL (third visual area) the upper VF is represented rostrally and the nasal VF, medially, being thus a mirror image of LM. In LI, the upper VF is medial and the nasal VF, lateral, being thus a mirror image of LM, or a reduced copy of V1. In medial extrastriate cortex (area 18) there are two representations of the temporal VF, labeled anteromedial (AM) and posteromedial (PM). In AM, the upper temporal VF is medial and the lower temporal VF, lateral, the extreme temporal field being rostral. The 30 degrees azimuth provides the boundary between AM and PM. Thus, AM is organized as a counter-clockwise rotation by 90 degrees of the V1 representation. In PM, the upper lower VF topography is like in AM, but the extreme temporal VF is caudal, being thus a mirror image of AM.

Animals↗
PubMed1983

Experimental infection of Tamarins with human non-A, non-B hepatitis virus.

Non-A, non-B (NANB) viral hepatitis was successfully transmitted to two colony-born Tamarins following inoculation with antihaemophilic factor VIII concentrate or the "H" inoculum. Both animals showed histological and ultrastructural evidence of viral hepatitis, with raised alanine aminotransferase (ALT) levels from the second week after inoculation through to the end of follow-up, 5 months later.

Alanine Transaminase↗
PubMed1983

Failure to detect nucleic acid homology between some non-A, non-B viruses and hepatitis B virus DNA.

Some studies suggest that there is antigenic and nucleic acid homology of one type of non-A, non-B hepatitis virus with hepatitis B viral (HBV) proteins and DNA. Using molecular hybridization under high and low stringency conditions with high specific activity 32P-HBV DNA as a probe, serum and liver samples from patients and nonhuman primates infected with non-A, non-B hepatitis were examined. Our results provide no evidence of significant homology between the DNA extracted from serum and liver of patients and nonhuman primates infected with one type of non-A, non-B hepatitis and HBV DNA.

Animals↗
PubMed1983

Growth characteristics of alpha-foetoprotein-secreting human hepatocellular carcinoma in athymic (nude) mice.

1. The growth characteristics of a human hepatocellular carcinoma, derived from the PLC/PRF/5 cell-line ('Alexander'), transplanted into sub-lethally irradiated athymic (nu/nu) mice have been examined. The xenograft re-expresses alpha-foetoprotein production although this tumour marker was not detected during cell culture in vitro. 2. There is a positive correlation between serum alpha-foetoprotein concentration and tumour mass (r = 0.978), validating the use of this tumour marker to assess growth. 3. In mice with progressively growing xenografts there is a linear correlation between log serum alpha-foetoprotein concentration and time, compatible with exponential tumour growth. Growth of the human hepatocellular carcinoma xenograft is rapid, with an alpha-foetoprotein doubling time of 6.1 +/- 2.1 days (+/- standard deviation) and a mass doubling time of 3.6 +/- 1.2 days (+/- standard deviation). 4. The tumour cell birth or production rate, determined by a stathmokinetic (metaphase arrest) technique using vincristine, is 15.7 +/- 3.8 (95% confidence limits) cells per 1000 cells per hour. The tumour cell loss factor (49%) is low and may contribute to the rapid growth of this human hepatocellular carcinoma xenograft.

Animals↗
PubMed1983

Acyclovir in hepatitis B antigen-positive chronic liver disease: inhibition of viral replication and transient renal impairment with iv bolus administration.

Six patients with hepatitis B virus (HBV) related chronic liver disease were treated with acyclovir, 5-15 mg/kg 8 hourly, given as an iv bolus or iv infusion over 1 h for up to 7 days. Two patients treated with 10 and 15 mg/kg 8 hourly showed a decrease in HBV-DNA polymerase and HBV-DNA when mean trough acyclovir plasma concentrations of 5.0 +/- 0.6 and 13.2 +/- 3.0 microM were attained. Inhibition of viral replication was not seen in patients treated with lower doses. Transient renal impairment was seen in two patients who received high dosage by the iv bolus mode of administration. This complication may be prevented by a high oral fluid intake or iv infusion of the drug over 1 h. Further study with acyclovir 15 mg/kg 8-hourly given as an iv infusion for longer periods is warranted.

Acyclovir↗
PubMed1983

Defective hepatitis B virus DNA molecules detected in a stable integration pattern in a hepatoma cell line, and in induced tumours and derived cell lines.

Hepatitis B virus (HBV) DNA was found to be integrated into seven sites in the DNA of the PLC/PRF/5 hepatoma cell line as determined by digestion with the restriction endonuclease HindIII which does not cut through the viral genome. The integration pattern was stable in the cell line, in tumours induced in athymic mice by this line and in cell lines derived from such tumours. Syntheses of hepatitis B surface antigen and alphafoetoprotein were maintained in the induced tumours and derived cell lines. A defective HBV DNA molecule (approx. 2.8 kilobase pairs) appears to be integrated in a head-to-tail tandem arrangement and it is proposed that such defective molecules may be involved in the process of neoplastic transformation by HBV.

Animals↗
PubMed1983

Incidence of hepatitis B virus infection in alcoholic liver disease, HBsAg negative chronic active liver disease and primary liver cell cancer in Britain.

A study has been undertaken to determine the incidence of serum markers of hepatitis B virus (HBV) infection in British caucasian patients with biopsy-proven alcoholic liver disease (n = 56), HBsAg negative chronic active liver disease (CALD) (n = 47) and primary liver cell cancer (PLCC) (n = 27), compared to a hospital control population without liver disease (n = 112). No increased incidence of any serum marker of HBV infection was found in alcoholic liver disease or in 'lupoid' CALD (antinuclear factor positive 1:40 and/or smooth muscle antibody positive greater than 1:40). In contrast, the incidence of antibody to HB surface and core antigens was significantly increased (p less than 0.05) in patients with cryptogenic CALD. The incidence of hepatitis B surface antigen and antibodies to HB core and 'e' antigens was significantly increased (p less than 0.005) in PLCC.

Female↗
PubMed1983

Significance of delta agent infection in chronic hepatitis B virus infection: a study in British carriers.

Delta antigen (delta) is a transmissible agent requiring hepatitis B virus (HBV) for its replication. Antibody to delta (anti-delta) was present in nine of 71 (13%) British HBV carriers: six were intravenous drug abusers and two were haemophiliacs. Anti-delta was negative in 30 HBsAg positive homosexuals. Cirrhosis was common in patients with anti-delta and those with anti-delta positive cirrhosis were significantly younger than those with anti-delta negative cirrhosis. In British HBV carriers delta infection is associated with intravenous drug abuse and haemophilia and perhaps a more rapid progression of chronic liver disease.

Adolescent↗