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Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 361 records · Page 20Linked to original sources

Comparative clinical study of protein SAP (amyloid P component) and C-reactive protein in serum.

The serum concentration of protein SAP (amyloid P component) has been measured for the first time in a substantial series of normal individuals and patients with various diseases, and the results contrasted with the levels of the related protein C-reactive protein (CRP). The mean +/- s.d. concentration of protein SAP was 43 +/- 14 microgram/ml in seventy-six normal men, 33 +/- 10 microgram/ml in eighty-six normal women and 4 +/- 2 microgram/ml in thirty-six normal cord sera. Unlike CRP, whick is a major acute phase reactant, protein SAP was only slightly elevated in inflammatory and neoplastic diseases in which CRP was greatly increased. The level of protein SAP was significantly depressed in patients with hepatic disease, suggesting that its measurement might be of value in their management.

Amyloid↗

Is primary biliary cirrhosis an immune complex disease?

Large immune complexes are present in the circulation of patients with primary biliary cirrhosis and result in the activation of complement by the classical pathway. Such large complexes are capable of producing tissue damage. The granulomatous lesions surrounding the small bile-ducts within the liver of patients with primary biliary cirrhosis and the vasculitis, rheumatoid arthritis, and associated lesions are all compatible with immune complex injury. It is postulated that such large complexes could be formed in the vicinity of the bile-ducts by an antigen absorbed from the bile or biliary epithelium. Complexes reaching the systemic circulation might be responsible for the associated extra-hepatic diseases.

Antibody Formation↗

Lymphocyte populations in liver biopsy specimens from patients with chronic liver disease.

The characterisation of lymphocytes from liver biopsies indicates that 'activated' T lymphocytes are present in the liver in alcohol induced hepatitis, chronic active hepatitis (HBS+ve and -ve), and in primary biliary cirrhosis but not in inactive cirrhosis, chronic persistent hepatitis, extrahepatic and drug induced cholestasis. A greater percentage of lymphocytes bear Fc-receptors in chronic active hepatitis than in alcohol induced hepatitis or cholestatic liver disease. The concentration of 'activated' T cells in the peripheral blood in all groups studied was within the normal range, suggesting that the 'activated' T cells found in the liver were reacting to either native or foreign antigens within the liver. The data on Fc-receptor bearing cells are consistent with the involvement of antibody assisted K cell mediated cytotoxicity in chronic active hepatitis.

Binding Sites, Antibody↗

Serum alpha-fetoprotein levels in patients with acute and chronic liver disease. Relation to hepatocellular regeneration and development of primary liver cell carcinoma.

Using a radioimmunoassay technique serum alpha-fetoprotein could be detected in healthy adults in concentrations of less than 20 microgram/l. Of patients with acute, viral hepatitis 43% exhibited a transient rise of serum alpha-fetoprotein, the peak occurring eight to nine days after the maximum recorded serum aspartate transaminase activity. Patients with hepatic damage due to paracetamol poisoning were also shown to have transiently raised levels, the peak occurring earlier than in subjects with viral hepatitis. Six subjects with fatal fulminant hepatitis were studied; the three with the more protracted illness were noted to have increased levels before death. Twenty of 163 cases of chronic liver disease also had raised serum alpha-fetoprotein concentrations. In four, primary liver cell cancer developed; in two of these the serum alpha-fetoprotein levels rose progressively, and in two it remained raised but at low levels.

Acetaminophen↗

Transfer factor in the attempted treatment of patients with HBsAg-positive chronic liver disease.

Six patients with hepatitis B surface antigen-positive (HBsAg-pos) chronic liver disease have been treated with transfer factor (TF) prepared from leucocytes of normal blood donors with no history of hepatitis, and with TF from subjects recently recovered from type B hepatitis. In three patients there were transient elevations of aspartate transaminase (AsT) after 'specific' TF, representing damage or destruction of hepatocytes, and in two of these patients there was coincidental complement consumption, suggesting that TF had stimulated production of antibody. In one other patient there was an increase in E-rosetting lymphocyte (ERL) concentration representing a change in T-lymphocyte reactivity. One of the two patients who had no measured response to TF had a primary liver cell carcinoma and was receiving prednisolone therapy. TF prepared from subjects who have recently recovered from type B hepatitis may have temporarily altered the immunological status of patients with HBsAg-pos chronic liver disease, but it did not have a beneficial therapeutic effect.

Adult↗

Immune response to phi X 174 in man. 5. Primary and secondary antibody production in primary biliary cirrhosis.

In primary biliary cirrhosis, the primary immune response to the bacteriophage phi X 174 is normal but the secondary response is significantly reduced. The reduction is primarily of IgG antibody, while IgM is proportionately less affected. These changes may be the result of a reduction in helper T lymphocyte function and may contribute to the increase in the ratio of serum concentration of IgM to IgG.

Adult↗

The immune response in cirrhotic rats. The induction of tolerance to orally administered protein antigens.

Hepatic cirrhosis reduced the susceptibility of rats to the induction of tolerance by the oral administration of a protein antigen. Rats with portacaval shunt were rendered tolerant as readily as normal rats. The orally induced state of partial tolerance was shown to be dependent on thymus-dependent lymphocytes: B lymphocytes reacted normally to challenge when injected with T lymphocytes from normal rats. Several factors may contribute to the reduced responsiveness of the cirrhotic rats to the tolerance regime. First, the cirrhotic liver was shown to have a reduced capacity to separate immunogen from tolerogen. Second, because of the reduced phagocytic capacity of the liver, increased quantities of lipopolysaccharide, derived from intestinal microorganisms, enter the blood stream. These substances and products of hepatocyte necrosis have adjuvant activity and may therefore contribute to the changed state of responsiveness of rats with cirrhosis.

Administration, Oral↗

Peripheral blood lymphocyte populations in chronic liver disease.

Mature T lymphocyte concentrations are reduced, null cell concentrations are increased, and Fc receptor bearing (B and K) lymphocyte concentrations are normal, in the peripheral blood of patients with chronic hepatocellular or cholestatic liver disease. Some null cells can be stimulated by either thymosin or levamisole to form rosettes with sheep erythrocytes. These changes are present in viral, alcohol associated and 'autoimmune' liver disease and are therefore probably secondary phenomena relating to liver damage.

Adult↗

Double-stranded DNA-binding capacity of serum in acute and chronic liver disease.

Serum antibodies to double-stranded 'native' DNA have been measured in acute and chronic liver diseases using the Farr technique. Elevated levels of DNA binding were found in all groups of patients, with the highest levels in acute viral hepatitis and lowest in primary biliary cirrhosis. All patients with hepatitis B surface antigen-positive chronic active hepatitis had elevated levels, hence persistent elevation of DNA binding after acute type B hepatitis might be an unfavourable prognostic marker indicating progression to chronic active hepatitis, DNA antibody levels will not offer diagnostic help in liver diseases, or help to follow the response of patients with 'lupoid' hepatitis to corticosteroid therapy. Production of DNA antibody may be a response to release of DNA from damaged hepatocytes.

Alcoholism↗

The immune response in cirrhotic rats. Antigen distribution, humoral immunity, cell-mediated immunity and splenic suppressor cell activity.

The immunological disturbances occurring as a result of liver disease have been studied in an animal model of cirrhosis. The mononuclear phagocytic cells of the normal liver phagocytose large amounts of antigen irrespective of whether that antigen is injected directly into the portal or into the systemic circulations. The liver therefore acts as a filter 'in series' and 'in parallel' with the spleen and reduces the immunogenicity of antigens entering the organism by either of these routes. In rats with hepatic cirrhosis, there is a reduction in the capacity of the liver to phagocytose the flagellar antigen of Salmonella adelaide. This results in increased stimulation of splenic lymphoid tissue and in an increased antibody response to this thymus-independent antigen. The increased antigenic stimulus to the spleen may also be responsible for the increased suppressor-cell activity which has been demonstrated in these rats, and may be the mechanism of the diminished cell-mediated immune response both in this animal model of cirrhosis and in the human disease state. These studies suggest that many of the immunological disturbances associated with chronic liver disease may be the result of maldistribution of antigen occurring because of impaired hepatic phagocytic capacity.

Animals↗

Incidence and clinical significance of e antigen and antibody in acute and chronic liver disease.

"e" is a serum antigen associated with type-B hepatitis. It is found only in hepatitis B surface antigen (HBsAg) positive sera, but is antigenically distinct from HBsAg. e antigen was not detected in the serum of any of 99 cases of acute type-B hepatitis who recovered normally. Its antibody, anti-e, was found in 14 (14%). The antibody usually appeared before clearance of HBsAg and before appearance of HBsAb. Serum e was not detected in any of 29 symptom-free carriers of HBsAg, but 21 (73%) showed anti-e. Serum e was found in chronic active hepatitis (44%) and chronic persistent hepatitis (31%). The antibody, however, was detected in only 2 of 79 patients with chronic active hepatitis but in 7 (44%) of chronic persistent hepatitis. Serum e was not found in 5 patients with primary liver-cell carcinoma or 5 with inactive HBsAg-positive cirrhosis. The antibody was, however, found in all 5 of those with inactive cirrhosis and in 4 of the 5 with primary cancer. These results suggest that the presence of e antigen is associated with active and usually continuing liver disease. Anti-e, however, is associated with inactive liver disease and asymptomatic carriage of HBsAg, and its presence must be regarded as a valuable sign in predicting those who will escape progressive chronic liver disease.

Acute Disease↗

Antibodies to Escherichia coli in chronic liver diseases.

Patients with chronic active hepatitis or alcoholic cirrhosis have serum antibodies to many more serotypes of Escherichia coli than do patients with primary biliary cirrhosis or cryptogenic cirrhosis, or normal controls. They also have antibodies against more serotypes than cirrhotic patients with a portacaval shunt. These observations suggest that factors other than shunting of blood away from the liver are responsible for the increased range of antibodies. These factors are discussed. There was no correlation between the number of serotypes to which antibodies were present and the serum immunoglobulin concentration. In three patients, each with chronic active hepatitis, the antibodies were predominantly of the IgM class, while the elevation of globulin in general was mainly due to increased IgG and IgA levels. Antibodies to Escherichia coli, therefore, probably contribute only a small part of the increased globulin levels found in patients with chronic liver disease.

Adolescent↗