Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 217 records · Page 12Linked to original sources

PubMed1987

Interferons as mediators of psychiatric morbidity. An investigation in a trial of recombinant alpha-interferon in hepatitis-B carriers.

A significant increase in psychiatric morbidity, assessed by standard measures, was demonstrated in a group of patients receiving recombinant alpha-interferon for chronic hepatitis-B virus infection. In some cases the psychiatric symptoms were severe enough to need urgent psychiatric attention. The changes seemed most severe in patients with coexistent human immunodeficiency virus infection. The mental state changes are clinically reminiscent of those in the "post-viral" psychiatric syndromes.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Relationships between interhemispheric cortical connections and visual areas in hooded rats.

The correlation between visual topography within striate and lateral extrastriate visual cortex and the pattern of callosal connections to those areas has been studied in gray rats. The procedure was to put multiple injections of horseradish peroxidase (HRP) into the occipital cortex of the right hemisphere. The cortical areas 17 and 18a in the left hemisphere were electrophysiologically mapped upon stimulation of the right eye. Reference lesions were placed at selected recording sites. Horizontal sections of the left cortex were reacted for the demonstration of HRP. This permitted the comparison of the visual and callosal maps in the same animal. Like in other mammals, the callosal projections coincide with the cortical representations of the vertical midline and the more central regions of the visual field. The heavy line of labelled neurons and terminations embedded within the primary callosal band at the 17/18a border coincides with the representation of the vertical meridian. It provides the boundary between V1 and the maps located lateral to it. In area 18a, the anterolateral is contained in its anterior half, whereas areas lateromedial and laterointermediate are contained in its posterior half. The acallosal 'island', caudal to the acallosal 'body', contains the map known as posterolateral. There are two laterolateral (LL) maps which coincide with the acallosal 'islands' lateral to the acallosal 'body'; laterolateral anterior is more rostral than LL and these are retinotopically organized as mirror images of each other. Lateral to LL, there is a suggestion of an additional map, which could correspond to a pararhinal area. These results may be useful to understand aspects of a basic mammalian plan in the organization of visual cortex.

Animals↗

PubMed1987

Characterisation of the polymerised and monomeric human serum albumin binding sites on hepatitis B surface antigen.

Receptors for polymerised human albumin are present on the pre-S sequence of the envelope protein of HBV and on the hepatocyte membrane and are thought to be involved in uptake of the virus by hepatocytes. Using a solid phase radioimmunoassay we demonstrate binding of HBsAg to polymerised human serum albumin (pHSA) in both HBe antigen-positive and -negative patients, and this binding is linearly related to the HBsAg titre in both groups. There are probably several modes of interaction between HBsAg and pHSA. Here we show that pHSA binds to the 22,000-dalton polypeptide of HBsAg, which does not contain the pre-S sequence. This pHSA-HBsAg interaction is inhibited by physiological concentrations of human serum albumin, suggesting that the albumin known to be present in the envelop of HBsAg plays a role in this binding. The inhibition of pHSA/HBsAg interaction by native albumin suggests that this interaction is probably not an important mechanism of virus uptake during infection of hepatocytes.

Animals↗

PubMed1987

Qualitative analysis of the humoral immune response to the "a" determinant of HBs antigen after inoculation with plasma-derived or recombinant vaccine.

Competitive inhibition assays using monoclonal antibodies reacting with defined sequence of the "a" determinant of hepatitis B surface antigen (HBsAg) indicate that the humoral response to plasma-derived and recombinant HBsAg vaccine is similar in quantitative and qualitative terms. Both vaccines evoke an antibody response to the RFHBs 1 epitope, which is known in animal experiments to be protective.

Adolescent↗

PubMed1987

Cloning and characterisation of a delta virus cDNA sequence derived from a human source.

We report the extraction of delta virus RNA from the serum of a delta-virus-infected patient and the subsequent cloning and analysis of a 380-nucleotide-long cDNA (D380). The nucleotide sequence of D380 shows overall differences of approximately 20% when compared with previously published sequences and does not include the viroid consensus sequence previously reported (Wang et al: Nature 323:508-514, 1986). A potentially coding open reading frame extending over the whole length of the D380 has been identified. Our results demonstrate the existence of genetic heterogeneity amongst different delta virus isolates.

Base Sequence↗

PubMed1987

A review of the efficacy of adenine arabinoside and lymphoblastoid interferon in the Royal Free Hospital studies of hepatitis B virus carrier treatment: identification of factors influencing response rates.

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. This 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 interferons are effective in approximately 50% to 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 two mechanisms by which the chronic carrier state may arise. In 5% to 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)

Arabinonucleotides↗

PubMed1987

Use of biotinylated probes in serum hepatitis B virus DNA detection.

A dot-blot hybridisation assay for serum HBV DNA is described using a non-radioactive (biotinylated) DNA probe. The assay is both sensitive (1 pg of HBV DNA) and reproducible, and shows several advantages over similar assays which use 32P-labelled probes for the routine detection of infectious virus particles both in blood and in other biological fluids.

Biotin↗

PubMed1987

Cytotoxic T-cell responses to the nucleocapsid proteins of HBV in chronic hepatitis. Evidence that antibody modulation may cause protracted infection.

The nucleocapsid antigens (HBc and HBe) are present on the membranes of HBV-infected hepatocytes from HBV carriers. In autologous cytotoxicity experiments we demonstrate that cytotoxic T cells sensitised to the nucleocapsid proteins of hepatitis B are present in HBe antigen-positive HBV carriers with chronic hepatitis and can be blocked by monoclonal anti-HBc and anti-HBe. Passive immunisation of chimpanzees with monoclonal anti-HBc and anti-HBe offers no protection against HBV infection but in both cases leads to an unusually prolonged hepatitis probably by modulation of HBc and HBe antigen display on the hepatocytes. High-titre anti-HBc in the circulation of HBe antigen-positive patients probably modulates the former protein making HBe the important target antigen for cytotoxic T cells mediating liver damage in chronic carriers. These data also support the hypothesis that passive transfer of IgG anti-HBc across the placenta may be one major factor promoting development of persistent infection in neonates infected from carrier mothers.

Animals↗

PubMed1987

In vitro and in vivo tumour localisation with a monoclonal antibody directed against a membrane antigen on the human hepatocellular carcinoma cell line PLC/PRF/5.

A monoclonal antibody, designated K-PLC1, has been produced to a tumour-associated antigen on the cell membrane of the PLC/PRF/5 cell line. Using an indirect immunofluorescence technique this antibody produced membrane staining of three hepatocellular carcinoma (HCC) cell lines and it has positively stained 10 of 11 human HCC biopsy specimens. In vitro, 125I-labelled K-PLC1 binds specifically to PLC/PRF/5 cells, as shown by competitive inhibition experiments. Tumours derived from the PLC/PRF/5 cell line were grown in nude mice and groups of tumour-bearing animals were injected with either [125I]K-PLC1 or [125I]mouse IgG, and then killed at 1, 4 or 7 days post injection. Bound radioactivity was counted in a variety of solid organs. Tumour:liver ratios for K-PLC1 were greater than those for mouse IgG at each time point, the differences being greatest on day 4 (ratio K-PLC1 4.4 +/- 0.93, ratio mouse IgG 1.53 +/- 0.60, mean +/- SD, P less than 0.05). The amount of [125I]K-PLC1 bound was greater in the tumour than in any other solid organ, the differences again being maximal on day four. Blood pool radioactivity however remained high throughout the study period. We conclude that anti-HCC monoclonal antibodies may be of value as immunodiagnostic and immunotherapeutic agents in human HCC.

Animals↗

PubMed1987

Lymphoblastoid interferon therapy of chronic HBV infection. A comparison of 12 vs. 24 weeks of thrice weekly treatment.

This study set out to examine the relative effectiveness and tolerability of 12- versus 24-week courses of thrice weekly intramuscular lymphoblastoid interferon in the treatment of hepatitis B 'e' antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, and to identify pretreatment factors predicting the outcome of therapy. Twenty patients were randomised to each treatment group. Treatment was associated with clearance of HBeAg and HBV-DNA in 59% of the 32 male patients, whereas none of the eight women responded (48% overall response rate). This response rate in males is at least three times the recorded spontaneous seroconversion rates in this population. Most of the women (5/8) were of Oriental origin and had minimal disease, factors that may have influenced response. The longer course was poorly tolerated and was therefore no more effective: eight of 20 patients withdrew because of side-effects. Variables associated with response included high AST (aspartate transaminase), short duration of disease and previous history of acute hepatitis. A response to antiviral therapy was accompanied by clinical and biochemical evidence of improvement in liver disease.

Acute Disease↗

PubMed1987

Delta hepatitis in Lebanon. Prevalence studies and a report on six siblings with chronic delta-positive active hepatitis.

The prevalence of delta infection in Lebanon is reported for the first time. Delta antigen and antibody were screened for in serum of 43 patients consecutively seen in hospital, 22 with acute hepatitis B (anti-HBc IgM-positive), and 21 with histological evidence of chronic active hepatitis, 6 of whom were brothers in a sibship of eleven. Twenty asymptomatic HBsAg carriers without clinical or biochemical evidence of liver disease were similarly studied. None of the asymptomatic carriers or acute hepatitis B patients had markers of delta infection. In contrast, delta antibody in high titre (greater than 1:5000) was found in 12 (57%) of the patients with chronic active hepatitis, including all six brothers. Five sisters in the sibship were anti-HBs-positive without evidence of liver disease, suggesting a horizontal mode of transmission of the delta virus, as a superinfection on a hepatitis B carrier state. Excluding the sibship, delta infection was present in 6 of 15 (40%) chronic active hepatitis patients. This prevalence is similar to other Middle Eastern countries. Delta infection was associated with severe liver disease.

Acute Disease↗

PubMed1987

Effect of human immunodeficiency virus (HIV) infection on chronic hepatitis B hepatic viral antigen display.

Immunofluorescent and immunoperoxidase monoclonal antibody-based techniques were used to demonstrate hepatitis B e antigen (HBeAg) and hepatitis B c antigen (HBcAg) display in the liver biopsy specimens of 45 chronic hepatitis B virus (HBV) carriers. Anti-human immunodeficiency virus (anti-HIV)-positive HBV carriers had many more HBe- and HBc-positive hepatocyte nuclei than anti-HIV-negative carriers (P less than 0.0003 and less than 0.02, respectively), and HBV-DNA levels were slightly, but not significantly, increased in the positive subjects. The number of HBe- and HBc-positive nuclei were positively correlated with serum HBV-DNA levels (P less than 0.05 comparing high serum HBV-DNA levels of greater than 2880 pg/ml and levels of 1-480 pg/ml), and were negatively correlated with disease activity (P less than 0.05 comparing those with severe chronic active hepatitis (CAH) and those with mild CAH and chronic persistent hepatitis (CPH]. These results indicate that male homosexual HBV carriers, positive for anti-HIV, may be immunosuppressed before there are clinical signs of immunodeficiency, and this allows an increased level of replication of at least one other virus (HBV).

Acquired Immunodeficiency Syndrome↗

PubMed1987

Human lymphoblastoid interferon does not increase survival when added to mitozantrone in the treatment of hepatocellular carcinomas.

Human lymphoblastoid interferon, in an initial dose of 2.5 MU m-2 weekly i.m., was given with mitozantrone 12 mg m-2 i.v. every 3 weeks to 15 patients with hepatocellular carcinoma. The survival curve for these patients was worse than that of 15 patients previously treated with mitozantrone alone; there were more long-term survivors in those not given interferon; more side-effects were seen in the group given interferon. The addition of interferon to mitozantrone in the management of hepatocellular carcinoma is not recommended.

Adolescent↗

PubMed1987

A preliminary study of hepatitis B virus replication during short-term (7-day) social drinking.

The purpose of this study is to determine the effect of short-term social drinking on hepatitis B virus (HBV) replication as measured by serum levels of hepatitis B virus DNA (HBV-DNA). We studied five male carriers of hepatitis B e antigen who were social drinkers. Levels of HBV-DNA, blood alcohol, and aspartate aminotransferase (AST) were measured during abstinence from alcohol, before and during a test dose (29.8 g) of alcohol which followed one week of abstinence, and before and during the same test dose which followed social drinking for one week. We observed no significant changes in HBV-DNA or AST levels. These data suggest that a single one-week period of social drinking in patients with chronic HBV infection does not cause enhanced viral replication. The risks of repeated ingestion of moderate amounts of alcohol by such patients have not been established. Interpretation of our data is limited by the small number of subjects, and further studies are needed. Nevertheless, our results are consistent with published recommendations that social drinking by nonalcoholic HBV carriers should be restricted but need not be totally forbidden.

Adult↗

PubMed1987

Bronchobiliary fistula due to acute cholecystitis in a suprahepatic gall bladder.

We describe a patient presenting with painless jaundice, anorexia and pruritus. The gall bladder was found to be lying above and behind a hypoplastic right lobe of liver. There was no evidence of cholangitis or biliary obstruction. The patient subsequently developed a bronchobiliary fistula with severe wheeze, cough and bile-stained sputum. Emergency percutaneous drainage of the gall bladder led to immediate cessation of bronchospasm and biloptysis, rendering the patient fit for definitive surgery.

Acute Disease↗

PubMed1987

Natural killer cell activity in hepatocellular carcinoma. In vitro and in vivo responses to interferon.

We have measured natural killer (NK) cell activity in patients with hepatocellular carcinoma (HCC) and have examined the effects of in vitro and in vivo administration of alpha-interferon (IFN) on NK cell activity. The NK cell cytotoxicity of HCC patients was significantly lower than that of patients with cirrhosis or healthy controls. Reduced NK cell cytotoxicity in HCC did not correlate significantly with either the serum alpha-foetoprotein concentration or the patient WHO performance grade. NK cell cytotoxicity in all groups could be increased by prior incubation of effector cells with IFN, but this was significant only in HCC patients, in whom 10 IU/ml of IFN increased NK cell cytotoxicity from 37 +/- 10% to 53 +/- 8% (effector to target ratio, 50:1, mean +/- SEM; p less than 0.05). Further increases in IFN concentration failed to increase NK cell activity further. NK cell cytotoxicity was measured immediately before and 24 h after 2.5 x 10(6) IU/m2 of IFN was given subcutaneously to four HCC patients. NK cell cytotoxicity rose from 27 +/- 9% to 61 +/- 5% (effector to target ratio, 50:1, mean +/- SEM; p = 0.05).

Carcinoma, Hepatocellular↗

PubMed1987

The immune response to hepatitis B virus.

Cell-mediated immune response to nucleocapsid determinants, including HBcAg and HBeAg, are important in the clearance of HBV-infected hepatocytes. This process is modulated by interferon and humoral responses to these antigens. Antibodies to the envelope proteins contribute to protective immunity, but the relative importance of pre-S and S determinants in evoking a response and the relative contributions of these antibodies in virus neutralization remains unclear. It is known, however, that antibodies binding to the RFHBs1 epitope on the HBs sequence 124-137 are capable of protecting against further infection and are present in convalescent subjects and in recipients of the plasma-derived and recombinant hepatitis B vaccines. Detailed analysis of the specificity of the anti-HBs response in vaccinees shows it to be qualitatively similar to that seen during recovery from natural infection.

Animals↗

PubMed1987

Immunological properties of recombinant HBsAg produced in yeast.

Although currently available plasma-derived vaccines (PDV) against hepatitis B based on the surface antigen of the virus (HBsAg) are well-tolerated and effective, their supply is limited and time-consuming controls are necessary to assess their safety. It is therefore desirable that an alternative source of HBsAg be found. Recombinant DNA technology has provided the possibility of obtaining HBsAg in large quantities. However, it is important that a recombinant DNA hepatitis B vaccine be not only antigenically similar but also elicits a similar immune response in humans. Using the Ausria kit, the recombinant DNA vaccine of SmithKline Biologicals produced in yeast appears to have a higher antigenic content than a reference plasma-derived HBsAg preparation of similar purity when compared at equivalent protein concentrations. In competition experiments, however, antibodies obtained by immunization with PDV similarly recognized yeast-derived and plasma-derived antigens. Monoclonal antibodies directed to the common a determinant of the whole virus were also used to identify distinct epitopes on the recombinant DNA vaccine. The yeast-derived HBsAg is therefore antigenically similar to plasma-derived HBsAg. The yeast-derived vaccine (YDV) was highly immunogenic in mice, rabbits, goats, monkeys, chimpanzees, and humans. High titres of anti-HBs were reached in humans after three doses administered at 0, 1, and 6 months. The antibodies raised in humans after three doses of YDV were predominantly directed to the common a determinant. Competition studies using monoclonal antibodies raised against the whole virus showed that the antibodies had the same specificity as the antibodies induced by PDV. The affinity for the plasma-derived antigen of antibodies stimulated by YDV and PDV and antibodies present in the sera of convalescent subjects were also similar. Finally, competition experiments showed that the antibodies induced in humans by YDV and antibodies from convalescent subjects were directed to the same binding sites of the plasma-derived antigen. These studies indicate that the yeast-derived vaccine is immunologically similar to the plasma-derived vaccines both in vitro and in vivo and can therefore be expected to have similar protective efficacy.

Animals↗