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Biomedical subjects

I H Frazer

Publications and source records attributed to I H Frazer.

At least 109 records · Page 6Linked to original sources
PubMed1985

Antibody to G-actin in different categories of alcoholic liver disease: quantification by an ELISA and significance for alcoholic cirrhosis.

Autoantibodies to smooth muscle (ASMA), and to actin which is a major determinant of such reactivity, were measured in the serum of 94 patients with three defined categories of alcoholic liver disease, fatty liver, alcoholic hepatitis, and alcoholic cirrhosis, and in controls matched individually by age and sex with the patients. Autoantibody to monomeric G-actin was detected by an ELISA and autoantibody to polymeric F-actin by immunofluorescence staining of fibroblast stress fibers in cultured cells. Values for the ELISA were expressed as a percentage of the value for a strongly reactive standard serum. The mean value for antibody to G-actin in 40 patients with alcoholic cirrhosis (70 +/- 33%) was significantly greater than that for the matched controls (28 +/- 18%), but the mean value for the 30 patients with alcoholic hepatitis (46 +/- 16%) and the 24 with fatty liver (42 +/- 24%) did not differ significantly from the controls. High levels of reactivity with G-actin correlated significantly with HLA B7. ASMA was demonstrable to low titer in 11 of the 94 sera, and positive ASMA reactions by immunofluorescence correlated with high binding values to G-actin in the ELISA. Antibody to F-actin was found in only one serum and no controls. Thus in different liver diseases the reactivity of antibodies to monomeric G-actin and polymeric F-actin may differ, presumably because of specificity for different determinants of the actin molecule. Reactivity to G-actin may distinguish a group of alcoholic subjects in whom a predisposition to autoimmune reactivity is one of the determinants of progression of liver damage to cirrhosis.

Actins↗
PubMed1985

Assessment of delayed-type hypersensitivity in man: a comparison of the "Multitest" and conventional intradermal injection of six antigens.

Recall of delayed type hypersensitivity (DTH) as a test for cell-mediated immune competence was assessed in 254 subjects using the Multitest device which delivers seven skin-test antigens intradermally; 77 subjects were tested concurrently by Multitest and a conventional panel of six antigens. Similar results were obtained with Multitest and the conventional panel (R = 0.65). Reproducibility of Multitest between three observers, who independently assessed the aggregate size of reactions (the reaction score) in 45 subjects, was high (R = 0.89). Twenty-four subjects were tested twice 3 months apart; the correlation for the reaction score was high (R = 0.88), demonstrating the suitability of Multitest for serial studies of immune function. Anergy was infrequent (1%) among 110 healthy male controls but was more frequent (8%) among a group of 101 healthy male homosexuals (P less than 0.05). The response rate to particular test antigens differed for the three Australian groups tested and a previously studied French group. Hence there is a need to establish normal profiles of DTH responsiveness for different geographic areas, as well as among subjects of known age and sex, when assessing cell-mediated immunity by the level of DTH responsiveness to multiple skin test antigens.

Adolescent↗
PubMed1985

The cellular infiltrate in the liver in auto-immune chronic active hepatitis: analysis with monoclonal antibodies.

The mononuclear cell infiltrate in the liver was analyzed, using a panel of monoclonal antibodies (MAbs) of known specificity, in 10 patients with auto-immune chronic active hepatitis and, for contrast, in 14 with other types of chronic parenchymal liver diseases. In all cases, the mononuclear cell (MNC) infiltrate in the liver consisted mostly of T lymphocytes. Helper (Th) cells were more frequent than suppressor/cytotoxic T cells (Tsc) in the portal tracts and cirrhotic scar tissue, while Tsc were more common in the hepatic parenchyma. The number of Tsc cells in the parenchyma was greatest in patients with histologically active CAH and least in patients with quiescent cirrhosis. "Plasmacytoid" cells with the morphology of plasma cells, a hallmark of the MNC infiltrate in auto-immune CAH, were more frequent in histologically active CAH than in quiescent cirrhosis. These plasmacytoid cells were T200 + ve, and hence of bone marrow origin, but the majority expressed neither membrane nor cytoplasmic immunoglobulin nor any lineage-specific marker antigens, and hence did not fulfil criteria for B lymphocytes; however, these cells were positive for OKT10 and HLA DR. No difference was evident between the MNC infiltrate in the liver in auto-immune CAH and that in the other acute or chronic liver diseases studied, including HBV-associated CAH; hence immunohistological studies do not point to any pathological processes uniquely responsible for the pattern of hepatocyte damage seen in auto-immune CAH.

Antibodies, Monoclonal↗
PubMed1985

A graphical presentation of counts of T lymphocyte subpopulations and Th-Ts ratios.

A method is described for the graphical display of the absolute number of two major subpopulations of blood T lymphocytes, the helper (Th) and the suppressor/cytotoxic (Ts) cells, and their ratio, the Th/Ts ratio. Such a display permits distinction between patients with a low Th/Ts ratio due to decreased numbers of Th cells, which correlates with in vivo tests for immunodeficiency and is seen in the acquired immune deficiency syndrome (AIDS), and patients with a low Th/Ts ratio due to increased numbers of Ts cells but no immunodeficiency by in vivo tests, as seen in some homosexual men who have had recurrent infections.

Humans↗
PubMed1985

Reactivity of anti-mitochondrial autoantibodies in primary biliary cirrhosis: definition of two novel mitochondrial polypeptide autoantigens.

Sera that contained autoantibodies to mitochondria (AMA) by immunofluorescence were examined by immunoblotting for reactivity with mitochondrial polypeptides from various mammalian species, yeast, and E. coli. Mitochondrial polypeptides were separated by polyacrylamide gel electrophoresis, were immobilized on nitrocellulose, and were exposed to sera. The sera tested included 18 AMA-positive sera from patients with primary biliary cirrhosis (PBC), two AMA-positive sera from patients without PBC, and 53 AMA-negative sera. All AMA-positive sera reacted with either one or the other, or usually both of two human mitochondrial polypeptides of 70 kilodalton (kD) and 45 kD. The 53 AMA-negative sera were not reactive with the 70 kD polypeptide, but six reacted with the 45 kD polypeptide. The reactivity of the 70 kD and the 45 kD polypeptide was destroyed by brief exposure to trypsin. The counterpart of the 70 kD reactive polypeptide in human mitochondria was a 65 to 70 kD polypeptide in rat and mouse mitochondria, and a 55 kD polypeptide in yeast and in E. coli. The apparent 45 kD polypeptide was similar in all mitochondrial preparations tested, but no counterpart could be identified in E. coli. Beef heart mitochondria were used to show that the reactive polypeptides were present in a semipurified preparation of the F1 portion of mitochondrial H+ ATPase; however, sera did not react with the beta subunit of ATPase, proposed as a candidate mitochondrial autoantigen. The present molecular characterization of two particular antigens should lead to the more precise identification of these antigens, and also to a clearer insight into the pathogenesis of PBC.

Antibody Specificity↗
PubMed1985

Absence of autoimmune serological reactions in chronic non A, non B viral hepatitis.

In 18 cases of chronic liver disease due to non-A, non-B hepatitis virus(es) in which the diagnosis was established by transmission, including chimpanzee inoculation in nine, sera were tested for the autoantibodies characteristically associated with autoimmune chronic active hepatitis. The frequency of autoantibodies to nuclear, smooth muscle, cytofilament, mitochondrial and liver membrane antigens was low, being not greater than that recorded for a normal population, and the few positive reactions obtained were at very low titre. These findings suggest that among cases of 'HBsAg negative' chronic hepatitis, those due to NANB infection are distinguishable from those due to autoimmune chronic hepatitis by negative serological tests for autoantibodies.

Actins↗
PubMed1984

Antibody to human T cell leukaemia virus type III in Australian homosexual men with lymphadenopathy.

Sera from Australian homosexual men with idiopathic lymphadenopathy syndrome (ILS), a disease related to the acquired immune deficiency syndrome (AIDS), were tested for antibodies to two serotypes of human T leukaemia virus (HTLV), types I and III; type III is the type recently recognized in the USA as being associated with AIDS. Sera were tested also from other homosexual men and heterosexual controls. Antibody to high titre to HTLV-III was present in the serum of all six subjects with ILS. In contrast, antibody to low titre was present in only one of six healthy homosexual men and in one of five homosexual men with immunodeficiency but no lymphadenopathy. Antibody to HTLV-III was not detected in serum in the one subject with AIDS who was tested, but was detected in his healthy sexual partner. Antibody to HTLV-I, earlier believed to be related to AIDS, was lacking in all subjects. These results suggest, in an Australian setting, that infection with HTLV-III is the cause of ILS and, by inference, may also be the cause of AIDS. We suggest that there are as yet undetermined factors associated with male homosexual practices which cause immunodeficiency which, in turn, increases susceptibility to HTLV-III, the actual causal agent of ILS and, probably, AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Antibodies to liver cell membrane antigens in chronic active hepatitis (CAH). III. Partial characterization of the liver cell membrane antigens and comparison of reactivities in sera from patients with various liver diseases.

The reactivity of sera in liver diseases was investigated by an immunoradiometric assay for antibody to liver membrane antigens (LMAg). Serum reactivity was similar using glutaraldehyde treated hepatocytes from man and several animals, but the reactivity with human hepatocellular carcinoma cell lines was weak and irregular. F(ab)2 fragments from reactive sera were used in competitive inhibition experiments to ascertain whether anti-LMAg from different liver diseases reacted with the same or different antigenic determinants of the liver membrane. Sera from different patients with autoimmune CAH reacted predominantly with the same membrane components, as did sera from hepatitis B virus associated CAH (CAH-B); however sera from acute viral hepatitis A did not and, since such sera were reactive to LMAg in the assay, other membrane antigens are presumably involved. Enzymatic treatment of viable hepatocytes was performed to determine the nature of the reactive antigen(s): proteases or periodate resulted in reduced binding of reactive sera, but neuraminidase did not, suggesting that the LMAg recognized by CAH sera comprises species non-specific membrane glycoproteins. We conclude, on the basis of quantitative data from a immunoradiometric assay, that antibody to LMAg is more probably reactive than pathogenic, and that assessment of the antigenicity of specific membrane components is necessary.

Actins↗
PubMed1984

Autoantibodies, sheep cell agglutinins and anti-albumin antibodies in alcoholic liver disease.

The frequency of serum autoantibodies including anti-albumin antibodies was investigated for patients with various categories of alcoholic liver disease (ALD). The 95 patients were grouped into 3 categories: fatty liver (25 cases), alcoholic hepatitis (29 cases), and alcoholic cirrhosis (41 cases), and each group was matched with healthy controls by age, sex, ethnic origin and socio-economic status. For all patients with ALD, there was a 5-fold greater frequency over the controls of positive tests for antinuclear antibody (ANA), but titres were low; the pattern of ANA reactions was speckled in 50% of the cases. For patients with alcoholic cirrhosis, there was an 8-fold increase in frequency over the controls in anti-smooth muscle antibody (ASMA), but titres were low, pointing to a possibility that autoimmunity might be one of several determinants of progression of alcoholic hepatitis to cirrhosis. For none of the groups was there an increase over the controls in the mean titre of sheep red cell agglutinins, nor were there increased haemagglutinin titres of antibody to bovine serum albumin or to human albumin, arguing against a general increase in antibody production in ALD. Greater knowledge of the frequency, significance and pathogenicity of reactive autoantibodies which occur in response to various types of tissue damage is required for interpretation of the increase in ANA and ASMA in alcoholic liver disease.

Adult↗
PubMed1983

Pleuroperitoneal effusion without ascites.

A recurrent unilateral pleural effusion developed without obvious cause in two patients with cirrhosis of the liver. By the demonstration of the rapid passage of a radiolabelled colloid from abdomen to thorax, these effusions were proved to be secondary to clinically undetectable peritoneal effusions. A diaphragmatic tear, which had occurred during a previous splenectomy and which was apparent only at autopsy, was the cause of peritoneopleural communication in one patient. Previous surgery could also have been responsible for the pleural effusion in the other patient.

Child↗
PubMed1983

A rapid micromethod for evaluating T cell subsets in blood using monoclonal antisera.

A simple accurate method is described for enumerating T cell subsets in whole blood. The method, which depends on indirect immunofluorescence using biotin-coupled monoclonal antisera and fluorescein-coupled avidin, and propidium iodide for nuclear counterstaining, was compared with the conventional method based on initial separation of lymphocytes by density flotation and exposure to monoclonal antisera. Accurate identification of mononuclear cells in whole blood by nuclear staining with propidium iodide was established. The whole blood method gave numbers for T cell subpopulations generally comparable with those obtained by the conventional method, but slightly higher numbers of Leu2a+ cells were found by the whole blood method, and shown to be higher because of selective loss of Leu2a+ plastic-adherent cells in the conventional method. The whole blood method is quicker, uses only 0.5 ml blood and is economical in use of monoclonal reagents.

Antibodies, Monoclonal↗
PubMed1983

Antibodies to liver membrane antigens in chronic active hepatitis (CAH). II. Specificity for autoimmune CAH.

An immunoradiometric assay for IgG class autoantibody to liver membrane antigens, based on serum binding to glutaraldehyde treated monkey hepatocytes, was used to examine sera from patients with chronic active hepatitis (CAH) and other acute and chronic liver diseases. All sera from normals and patients showed binding, up to a titre of 1/2,048. For comparison of assays, results were normalized by selecting two reference sera, one with a high degree of binding, and one from a healthy subject with a low degree of binding: at a dilution of 1/2,048, these sera were given binding values of 100% and 0%. The values for the binding of unknown sera at the same dilution were calculated from these two reference values. For 26 patients with autoimmune CAH, the mean (+/- s.d.) percentage binding value (70 +/- 33%) was significantly higher than the mean value for 26 healthy subjects (10 +/- 15%), and high binding values were significantly associated with biochemically active hepatitis. The mean percentage binding value was moderately increased for eight patients with HBsAg associated CAH (42 +/- 12%), 13 patients with alcoholic hepatitis with cirrhosis (37 +/- 25%) and 45 patients with acute viral hepatitis A (40 +/- 27%) or B (52 +/- 37%). At a cut-off binding value of 65%, the assay as a single diagnostic procedure was shown to have a 70% sensitivity and a 95% specificity for the diagnosis of autoimmune CAH. Better understanding of the pathogenetic significance of antibodies to liver membrane antigens in CAH and other liver diseases will depend upon biochemical analysis of the presumably multiple antigenic determinants on the hepatocyte membrane.

Antigens, Surface↗
PubMed1982

T lymphocyte subpopulations defined by two sets of monoclonal antibodies in chronic active hepatitis and systemic lupus erythematosus.

Lymphocyte subpopulations were enumerated in human peripheral blood using murine monoclonal antibodies with specificity for all peripheral blood T lymphocytes (OKT3, alpha-Leu 1) and for the helper subset (OKT4, alpha Leu 3a) and suppressor/cytotoxic subset (OKT8, alpha Leu 2a). Patients with chronic active hepatitis (CAH) (23) or systemic lupus erythematosus (SLE) (10), compared with healthy subjects (20), had a lower mean T lymphocyte count. Patients with CAH had normal numbers of suppressor/cytotoxic (TSC) cells, but fewer helper (TH) cells than healthy subjects (0 . 96 +/- 0 . 11 X 10(9)/1 versus 1 . 45 +/- 0 . 15 X 10(9)/1), and those with SLE also had fewer TH cells (0 . 93 +/- 0 . 11 X 10(9)/1). Patients with CAH receiving azathioprine (n = 8) had significantly fewer TSC cells, and a higher TH/TSC ratio (2 . 69 +/- 0 . 35) than those (n = 15) not on this therapy (1 . 85 +/- 0 . 15). When patients taking azathioprine were excluded, no correlation was found between disease activity and the TH/TSC ratio for either disease.

Adult↗
PubMed1982

Autoantibodies to liver antigens in chronic liver disease. I. A radioimmunoassay for antibody to liver membrane antigens.

A radioimmunoassay using a single cell suspension of glutaraldehyde-treated monkey hepatocytes was developed to measure antibody in human serum to liver membrane antigens. Hepatocytes were exposed to doubling dilutions of test sera in microtitre trays and binding of serum IgG was determined by exposure of the washed cells to 125I-labelled staphylococcal protein A. Specificity of binding was established according to several criteria including use of non-hepatic cells such as monkey kidney cells and various cell lines, IgG depletion of serum, absorption of binding activity by pre-exposure of serum to liver cells, and demonstration that binding was mediated by the F(ab) rather than Fc portions of immunoglobulin molecules. This radioimmunoassay distinguished autoimmune-type chronic active hepatitis (CAH) from other categories of liver disease. It should prove useful for diagnosis and classification of cases of CAH, and could facilitate identification of a liver-specific membrane antigen relevant to pathogenesis of autoimmune hepatitis.

Animals↗