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P Mackay

Publications and source records attributed to P Mackay.

13 recordsLinked to original sources

Islet cell and other organ-specific autoantibodies in healthy first-degree relatives to insulin-dependent.

The presence of organ-specific autoantibodies including islet cell surface, cytoplasmic and cytotoxic as well as thyroid-gastric antibodies were determined in healthy, non-diabetic, first-degree relatives to 30 insulin-dependent diabetic (IDDM) children. Thirty healthy families without family-history of diabetes mellitus served as controls. The prevalence of organ-specific autoantibodies among the healthy members in the diabetic families was increased compared to the control families (p less than 0.005). Islet cell cytoplasmic antibodies were only detected in diabetes families, since 23% (7/30) of the probands and 7% (2/31) of the siblings were positive and all others negative. Organ-specific autoantibodies were associated with HLA DR3 only in the diabetes families (p less than 0.025) while autoantibody positive members in the control families were associated with HLA B7 (p less than 0.01). This study suggests that childhood IDDM occurs in families with an increased prevalence of organ-specific autoantibodies.

Adolescent

Incidence of infection with hepatitis B virus in 56 patients with haemophilia A 1971-1979.

During each of the four-year periods 1971-1975 and 1975-1979, the annual incidence of hepatitis B infection has been assessed in 56 patients with haemophilia A by measuring plasma HBsAg, anti-HBs and anti-HBc levels. Infection rates of 7% and 9.5% per annum respectively were observed for each four-year period despite the screening of individual blood donations for HBsAg by techniques up to the sensitivity of reversed passive haemagglutination. The highest incidence of seroconversion was amongst severe haemophiliacs many of whom had received treatment predominantly with cryoprecipitate. Of the 16 patients in whom serological evidence of hepatitis B infection was obtained only one had an accompanying clinical episode of hepatitis. We conclude that haemophiliacs are still at high risk of infection by hepatitis B virus despite the screening of individual blood donors for HBsAg.

Adolescent

Inhibition of insulin release after passive transfer of immunoglobulin from insulin-dependent diabetic children to mice.

We used the mouse passive transfer model to test whether islet cell antibodies affect beta-cell function. The immunoglobulin (Ig) fraction of plasma from 5 islet cell surface antibody-positive, newly diagnosed insulin-dependent diabetic children or of a pool of plasma from 12 normal subjects was injected daily (7-16 mg IgG/day) for 14 days into normal immunosuppressed BALB/c mice. Insulin secretory responses in the Ig-injected mice were then examined by perfusing the rodent pancreata in vitro. Insulin release induced by 20 mmol/liter D-glucose during 30 min of stimulation decreased from 900 ng insulin (median; range, 814-1138) from pancreata of mice injected with control Ig to 511 ng (range, 130-786) from pancreata of mice injected with diabetic Ig (P less than 0.003). Both the initial peak and the sustained second phase of glucose-stimulated insulin release were depressed in 4 of the 5 pancreata from mice injected with diabetic Ig. These results indicate that circulating antibodies in diabetic children may alter beta-cell function and possibly contribute to the pathogenesis of insulin-dependent diabetes.

Adolescent

Tryptic cleavage of antibody binding sites from hepatitis B surface antigen particles.

The sedimentation of radiolabelled 22 nm hepatitis B surface antigen particles was unaffected by treatment with either trypsin or SDS alone, but combined treatment disrupted the particulate nature of the radiolabelled material. Considerable antibody binding activity by the group-specific determinant (a) was preserved after combined SDS and trypsin treatment but was released from the bulk of the radiolabelled protein; gel filtration indicated an approximate mol. wt. of 5000 to 15000 for the released antibody binding material. This material was precipitated by concanavalin A, suggesting the presence of carbohydrate. Its serological activity was remarkably resistant to boiling and to proteolytic digestion, but was partially sensitive to treatment with 0-01 M-periodate or with mixed carbohydrases and neuraminidase, and was greatly reduced by treatment with reducing agent. These data suggest that the stability of the a determinant is due to the structure of the antibody binding site itself, rather than to involvement in the quaternary structure of the particle, and that intact disulphide bonds and carbohydrate, closely related to the antibody binding site, are necessary for the full expression of serological acitivity.

Binding Sites, Antibody

Examination of the polypeptides of hepatitis B surface antigen.

When the polypeptides of hepatitis B surface antigen were examined by SDS-polyacrylamide gel electrophoresis under a variety of conditions, anomalous results were found to be due to (i) variable and at times incomplete dissociation of polypeptides after boiling with 1% SDS and reducing agent, (ii) reaggregation of solubilized material under certain electrophoretic conditions and during laboratory manipulations, and (iii) the variable presence of additional components in hepatitis B surface antigen prepared from certain individual donors. When these factors were taken into account, two major components were consistently identified by discontinuous buffer polyacrylamide gel electrophoresis, of apparent mol. wt. 60000 to 70000 and 12000 to 14000. However, in view of the demonstrated limitations of this technique in examining HBsAg polypeptides, alternative methods are necessary to confirm the true mol. wt. of the unique virus-specified amino acid sequence present.

Electrophoresis, Polyacrylamide Gel