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Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 325 records · Page 18Linked to original sources
PubMed1982

T cell subsets in autoimmune and HBV-induced chronic liver disease, HBs antigen carriers with normal histology and primary biliary cirrhosis: a review of the abnormalities and the effects of treatment.

Review of the limited data currently available on the ratios of helper (OKT4+) to suppressor (OKT8+) T cells in autoimmune liver disease (primary biliary cirrhosis and chronic active lupoid hepatitis) and virally induced liver disease indicates that this OKT4+:OKT8+ ratio is elevated in autoimmune liver disease manifesting hyperglobulinemia. This ratio was decreased in patients with chronic hepatitis B virus infection during the HBe antigen-positive phase of viral replication but reverts to normal in the majority of patients in whom HBV replication has ceased (HBe antibody-positive) and these individuals exhibit normal liver histology. Patients with HBV infection who continue to show elevated ratios after the appearance of HBe antibody also continue to exhibit signs of active hepatitis. The implications of these findings for further research in the management of these disorders is discussed.

Antibodies, Monoclonal↗
PubMed1982

Complement activation in chronic liver disease.

Patients with HBsAg positive chronic active liver disease (CALD) and primary biliary cirrhosis (PBC) exhibit increased C3d concentrations and changes in the serum concentrations of the complement components consistent with activation of the classical and alternative pathways. In these patients the concentrations of the regulatory proteins, C3b inactivator (C3bINA) and beta IH globulin, are normal. Patients with HBsAg negative CALD and alcohol induced liver disease (ALD) exhibit no evidence of an increased level of complement system activation. In these patients diminished serum concentrations of complement components appear to be related to diminished hepatic synthetic function. C4 synthesis may be specifically reduced in autoimmune chronic active liver disease.

Complement Activation↗
PubMed1981

Ultrastructural features in chronic non-A, non-B (NANB) hepatitis: A controlled blind study.

Liver biopsies from 12 patients with chronic Non-A, Non-B (NANB) hepatitis, 7 with hepatitis B surface antigen (HBsAg) positive chronic liver disease, 1 HBsAg positive normal carrier, and 4 patients with non-viral liver disease, were examined by electron microscopy for cytoplasmic and nuclear changes. Aggregates of particles measuring 20-35 nm in diameter were noted in the nuclei of 8 of 12 patients with NANB chronic hepatitis, but not in the other groups. The tubular changes seen in the endoplasmic reticulum (ER) of chimpanzees with NANB hepatitis were not noted in biopsies from any of our patients.

Cell Nucleus↗
PubMed1981

T cell subsets in patients with acute and chronic HBV infection, primary biliary cirrhosis and alcohol induced liver disease.

The proportions of inducer and cytotoxic/suppressor T cells and their concentration in peripheral blood have been determined in patients with acute and chronic type B hepatitis, hepatitis B virus (HBV) carriers with normal hepatic histology, patients with alcohol-induced liver disease (ALD), primary biliary cirrhosis (PBC) and chronic extrahepatic cholestasis. During acute type B hepatitis the inducer/suppressor ratio was decreased due to an increase in suppressor cell concentrations. When this ratio returned to normal the HBs antigen was cleared and HBs antibody was detectable. Similar abnormalities were found in patients with HBs + ve chronic hepatitis. In HBs antigen-positive patients with normal histology, normal T cell subsets were found. In some patients with primary biliary cirrhosis the ratio of inducer to suppressor cells was low due to a reduction in the concentration of inducer cells and in others high due to a reduction in suppressor cells. Administration of cyclosporin A to the latter group produced an increase in the concentration of suppressor cells and there was an improvement in liver biochemistry. In alcohol-induced hepatitis and cirrhosis the ratio of inducer/suppressor cells was normal. Whether these imbalances of the regulatory cells of the immune system in patients with chronic HBV-induced hepatitis and PBC are of primary or secondary importance is uncertain. The relationship of the depressed ratio to persistence of the hepatitis B virus is worthy of further study.

Acute Disease↗
PubMed1981

Increased serum IgA levels in rats after portacaval shunt but not after portacaval transposition.

Groups of rats were submitted to end-to-side portacaval shunt, portacaval transposition or a control sham operation. There was an 18-fold increase of the IgA level in the serum of portacavally shunted rats (n = 7) at 3-6 weeks after surgery. Gel filtration revealed that this increase was predominantly due to dimeric and polymeric IgA. The serum IgM of these shunted rats, but not the IgG, was also significantly increased (twofold) above their control values. In rats subjected to portacaval transposition (n = 6), there was no significant increase of serum IgA, IgM or IgG when compared with their control values. These data confirm the active transfer, by the healthy rat liver, of IgA and, to a lesser extent, of IgM from the blood into bile. Impairment of this function, leading to the accumulation of polymeric IgA and IgM in the serum, in portacavally shunted but not portacavally transposed animals, may be related to impairment of hepatic flood flow and hepatic atrophy, shown earlier to occur in portacavally shunted but not transposed rats. Such reduction in liver cell mass could also explain the fall in transferrin levels in shunted rats.

Animals↗
PubMed1981

Short incubation non-A, non-B hepatitis transmitted by factor VIII concentrates in patients with congenital coagulation disorders.

Ten cases are reported of short incubation (one to four weeks) non-A, non-B hepatitis occurring after infusion of various preparations of factor VIII concentrates into patients with coagulation disorders. Five patients were symptomatic and, in all, serum transaminase levels were increased for at least six months. These cases of chronic hepatitis exhibited none of the features of autoimmune chronic hepatitis: autoantibodies were negative and serum immunoglobulins were normal. Hepatic histology confirmed acute hepatitis in two cases biopsied early in the illness, and chronic active hepatitis (three) of chronic persistent hepatitis (two) in five cases studied later. Lobular inflammation was a prominent feature in all cases. Other features not commonly associated with type A or B hepatitis included fatty change and damaged bile ducts.

Adolescent↗
PubMed1981

Is mitochondrial antibody diagnostic of primary biliary cirrhosis?

In a series of 218 patients diagnosed as having primary biliary cirrhosis only nine exhibited a negative serum mitochondrial antibody. On examining additional specimens from these patients, seven were found to be positive, giving a final incidence of greater than 99%. The two patients whose sera remained negative for the mitochondrial antibody had liver histology compatible with the diagnosis of primary biliary cirrhosis, but a firm diagnosis could not be reached. Three additional mitochondrial antibody positive subjects who were asymptomatic and exhibited normal serum alkaline phosphatase were shown on liver biopsy to have stage I primary biliary cirrhosis. The presence of a positive serum mitochondrial antibody in a patient with or without abnormalities in liver function tests strongly suggests the diagnosis of primary biliary cirrhosis.

Adult↗
PubMed1981

Clinical and histological features of a group of patients with sporadic non-A, non-B hepatitis.

Twelve serologically proven cases of non-A, non-B (NANB) hepatitis have been described. The clinical course was mild in 11 patients. One patient, however, presented in portal systemic encephalopathy and required steroid treatment. Nine of the 12 patients continued to exhibit raised transaminase (AST) activities six or more months after the onset of the acute hepatitis. In these immunoglobulin concentrations were normal and autoantibodies were not present in significant titre. Four patients had evidence of previous hepatitis B infection, suggesting that the route of transmission of NANB might be similar to that of hepatitis B virus. A further four patients gave a history which suggests a possible parenteral mode of transmission. Liver biopsies were carried out both in the acute (8 cases) and chronic (6 cases) phases of the disease. Histological findings in liver biopsies covered the whole spectrum of acute and chronic hepatitis and 1 patient had cirrhosis. One notable feature in these biopsies was the presence of fatty changes.

Acute Disease↗
PubMed1981

Genetic factors in determining susceptibility to alcohol dependence and development of alcohol-induced liver disease.

There is considerable evidence in favour of genetic factors influencing excessive drinking behaviour and development of alcohol dependence (alcoholism), although readily identified markers of these genes have not been established. In addition, environmental factors undoubtedly play an important role. Although the probability of developing a significant liver disease (alcohol-induced hepatitis with or without cirrhosis) is related to the amount of alcohol ingested, there is a great variation in susceptibility which presumably stems from either genetic or additional environmental influences. The probable linkage of development of severe alcohol-induced liver disease with alleles of the HLA-B locus would suggest the influence of a gene(s) on chromosome 6. Such a gene may determine the rate or type of metabolism of alcohol or, since the immune response genes are present on chromosome 6, may indicate genetically controlled variation in the level of the immune and inflammatory response to alcohol-induced changes in liver membrane antigenicity. Further studies are needed to confirm these associations and to determine the type of factor involved.

Alcohol Oxidoreductases↗
PubMed1981

Adenine arabinoside therapy in HBsAg-positive chronic liver disease: a controlled study.

A controlled trial has been undertaken to evaluate adenine arabinoside in the treatment of hepatitis B surface antigen-positive chronic liver disease. Thirteen patients (7 hepatitis B virus DNA polymerase and hepatitis B e antigen-positive, 6 DNA polymerase negative and hepatitis B e antibody-positive) were treated with adenine arabinoside. Eleven comparable patients served as controls, and follow-up was for 6 mo. In the 7 hepatitis B e antigen-positive patients, adenine arabinoside produced a fall in DNA polymerase activity during treatment. When this effect was sustained, it was followed by a loss of e antigen (3 patients). Hepatitis B surface antigen concentrations and aspartate transaminase levels fell significantly at 6 mo (p less than 0.05) in the treated group compared with controls. In the hepatitis B e antibody-positive patients, adenine arabinoside treatment produced no significant change in hepatitis B surface antigen concentrations or aspartate transaminase levels at 6 mo as compared with controls. Adenine arabinoside would appear to reduce either transiently or permanently, hepatitis B virus replication, and it may therefore be useful in reducing the infectivity of some carriers of this virus. In the dose used, adenine arabinoside was ineffective in clearing hepatitis B surface antigen from the serum and eradicating hepatitis B virus from the liver, but combination with other antiviral or immunostimulant agents may enhance its therapeutic effectiveness.

Adult↗
PubMed1980

Effects of cyclosporin A on suppressor and inducer T lymphocytes in primary biliary cirrhosis.

There is a significant decrease in the ratio of inducer (helper) to suppressor T lymphocytes in the peripheral blood of patients with primary biliary cirrhosis (PBC). These changes are not seen in other forms of cholestatic liver disease, but are similar to those described in chronic graft-versus-host disease. Cyclosporin A treatment increased the proportion of suppressor A lymphocytes and improved liver function in 6 patients with PBC. This indicates that cyclosporin A is an immunoregulatory drug. Unfortunately nephrotoxicity precluded long-term use.

Cyclosporins↗
PubMed1980

Primary biliary cirrhosis is a dry gland syndrome with features of chronic graft-versus-host disease.

Primary biliary cirrhosis (PBC) is part of a disease complex characterised by dry eyes, dry mouth, and both biliary and pancreatic hyposecretion: it is a "dry gland" syndrome resulting from damage to ductular epithelium. Additional extraglandular features include scleroderma-like skin lesions, pigmentation, Raynaud phenomenon and severe abnormalities of both humoral and cellular immunity. Identical ductular and extraductal features, including abnormalities of the immune system, are seen in chronic graft-versus-host disease after bone-marrow transplantation. It is suggested that in PBC the ductular lesions and severe disturbance of the immune system including macroglobulinaemia and immune complex formation occur as a result of an immune response to the histocompatibility (HC) complex antigens which are present in high density on ductular epithelial cells of the biliary tree. This response could be caused by altered antigenicity of epithelial cell HC antigens or by failure of the HLA-dependent T cell self-recognition system.

Antigen-Antibody Complex↗