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Biomedical subjects

I R Mackay

Publications and source records attributed to I R Mackay.

At least 451 records · Page 25Linked to original sources
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Antibody to liver membrane antigens in chronic active hepatitis. IV. Exclusion of specific reactivity to polypeptides and glycolipids by immunoblotting.

The reactivity of sera was examined in patients with autoimmune chronic active hepatitis and other liver diseases by immunoblotting. Polypeptides and glycolipids of liver plasma membrane, liver-specific lipoprotein and kidney membrane were separated and probed with sera from patients and from a rabbit immunized with mouse liver plasma membrane. Chronic active hepatitis sera reacted with a number of polypeptides in the liver plasma membrane preparations; similar but weaker reactivity was observed with sera from patients with other diseases and in some healthy subjects. Chronic active hepatitis sera did not react with glycolipids from liver plasma membrane. The immune rabbit serum reacted with two polypeptides of 180 kd present in liver plasma membrane but absent from kidney membrane, with two polypeptides of 50 kd which were nonliver-specific but species-specific, and with three major glycolipid components of liver plasma membrane: this reactivity thus differed markedly from that of the chronic active hepatitis sera. In studies using dot-blotting, it was found that solubilization of liver plasma membrane in detergents resulted in a marked reduction of the reactivity to liver plasma membrane of chronic active hepatitis sera, but little change in the reactivity of the chronic active hepatitis and other sera with liver-specific lipoprotein by immunoblotting indicated that liver-specific lipoprotein consisted of constituents of liver plasma membrane together with intracellular proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The ethnic distribution of antibodies to glutamic acid decarboxylase: presence and levels of insulin-dependent diabetes mellitus in Europid and Asian subjects.

Our objective was to ascertain the frequency of antibodies to glutamic acid decarboxylase (GAD) in Europids and four Asian ethnic groups with insulin-dependent diabetes mellitus (IDDM) to gain insight into why the prevalence and incidence of IDDM varies so widely among ethnic and/or geographically diverse population groups. The subjects in this study were Europid (n = 49), Japanese (n = 16), Thai (n = 7), Korean (n = 21), and Chinese (n = 13) persons with IDDM with a duration ranging from 5 to 14 years. There were similar numbers of healthy controls matched for each ethnic group. A validated radioimmunoprecipitation assay used GAD from pig brain radiolabeled with 125I using chloramine T. Islet cell cytoplasmic antibodies measured by indirect immunofluorescence were expressed as Juvenile Diabetes Foundation units. The prevalence of antibodies to GAD, compared with Europids (63%), was much lower in all Asian populations with IDDM: Japanese (31%), Thai (29%), Korean (5%), and Chinese (27%). The mean level of antibodies to GAD, however, among diabetics from each population who gave a positive reaction, was similar. For all groups, the prevalence of antibodies to GAD was much higher than that of islet cell cytoplasmic antibodies. Almost all IDDM subjects positive for islet cell antibodies had antibodies to GAD, but the converse did not hold. A radioimmunoprecipitation assay for antibodies to GAD applied to serum from subjects with IDDM in various ethnic groups showed that Europids with IDDM had a much higher prevalence of such antibodies than did Asians. This held for all ethnic groups, and particularly Koreans. Thus, among different populations, there may be etiologic heterogeneity of IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗
PubMedDate not supplied

Lymphopenic effects on mice of a component of ammonia caramel, 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI).

A derivative of ammonia caramel colour (AC) is known to induce a selective lymphopenia in rats. Accordingly, the haematological effects were studied in mice of oral administration in drinking water of 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI), the component of AC responsible for lymphopenia. Initially five groups of BALB/c mice (five mice per group) were given doses of THI ranging from 0 to 200 parts/10(6) and bled weekly. Doses of THI from 5 to 100 parts/10(6) had no effect on circulating leucocytes over 6 weeks, but lymphopenia occurred with 200 parts/10(6). An increase in the concentration of THI to 400 parts/10(6) in the group on the lowest dose resulted in lymphopenia. An increase in dosage in two groups of mice, to 1000 and 2000 parts/10(6), resulted in marked lymphopenia. The number of neutrophils, eosinophils and monocytes remained unchanged throughout the experiment. Measurement of the proportions of CD4(L3T4)+ and CD8(Ly2)+ lymphocytes in lymph nodes from mice on high doses of THI did not show a selective depression of either subset, although both were increased relative to non-T cells. THI causes a selective lymphopenia in mice, as in rats, but at relatively higher doses, and merits investigation in mice as an experimental treatment for states of lymphocyte excess or overactivity.

Animals↗
PubMedDate not supplied

Auto-immune (lupoid) hepatitis: an entity in the spectrum of chronic active liver disease.

The concept of auto-immune hepatitis as a disease entity evolved from the descriptions of 'chronic active hepatitis' (CAH) in the 1950s. Several types of CAH are distinguished by disease-specific features. The distinctive (but not exclusive) markers for auto-immune CAH include: a negative test for HBsAg; female; Northern European ethnic background; multisystem disease expression; histological CAH with large areas of periportal piecemeal necrosis and plasmacytosis; pronounced hypergammaglobulinaemia; serum auto-antibodies the HLA B8-DR3 phenotype; responsiveness to corticosteroid therapy; and rarity of supervening hepatocellular carcinoma. Much weight is attached to the serological marker auto-antibodies to nuclear or smooth muscle (actin) antigens (ANA, SMA). However, these auto-antibodies do not have an absolute association with auto-immune CAH: the serological reactions are not yet standardized; titres decrease with remission of disease; and other auto-antibodies mark variant forms of auto-immune hepatitis. A more confident acceptance of auto-immune hepatitis as an entity requires detection of a liver-specific antigen, a valid experimental disease model in animals, and a better understanding of immune-mediated damage to liver cells.

Autoantibodies↗
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Hepatic and biliary autoantigens.

Chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC) are two enigmatic liver diseases in which autoimmunity is implicated. Provisional criteria to separate the autoimmune type of CAH (A-CAH) from others are specified. Western immunoblotting using disease sera and antibody screening of a rat liver gene expression library were used to identify hepatic and biliary autoantigens relevant to the pathogenesis of A-CAH or PBC. With all reported putative liver-specific autoantigen preparations, serum reactivity in A-CAH and CAH due to infection with hepatitis B virus tends to be similar. In A-CAH, immunoblotting showed multiple reactivities with all liver preparations used, including hepatocyte membrane. In PBC, immunoblotting showed two disease-specific polypeptide antigens of MW 70 and 45 kD. A cDNA clone derived from a rat liver gene expression library was shown to encode the antigenic site of the 70 kD polypeptide. Recently published work in two other laboratories has established that the 70 kD autoantigen is the E2 component of the pyruvate dehydrogenase enzyme (PDH), and a proposed antibody-binding site (autoepitope) is a conserved decapeptide, corresponding to residues 83-92 of the deduced amino acid sequence of M2, which is the binding site of lipoic acid to the E2 component of PDH.

Autoantigens↗