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C Casey

Publications and source records attributed to C Casey.

At least 37 records · Page 2Linked to original sources
PubMed1988

Insulin autoantibody polymorphisms with greater discrimination for diabetes in humans.

Insulin autoantibodies, like islet cell antibodies, are found not only in the sera of newly diagnosed Type 1 (insulin-dependent) diabetic patients and their relatives, but also in patients with other autoimmunities who do not develop diabetes. Insulin autoantibodies are oligo/monoclonal and frequently binding-site restricted. As determinant selection is genetically determined, we questioned whether certain polymorphisms of insulin autoantibodies, identified by their binding site on the insulin molecule, could better discriminate for Type 1 diabetes, which is also HLA determined. First, we raised monoclonal antibodies to human insulin by classic fusion methods in order to determine the range of antibody polymorphism, and identified five distinct types by their binding profiles to a panel of insulin variants, using an enzyme-linked immunosorbent assay. Two of these polymorphisms, type A and type B, were subsequently found in insulin autoantibody positive human sera using the same panel of insulin variants, and successfully distinguished diabetes-related from diabetes-unrelated individuals. Thus, the type B polymorphism was responsible for binding in 60% of 41 insulin autoantibody positive individuals with polyautoimmune disease but no personal or family history of diabetes (diabetes unrelated), but in only 2% of a group which comprised 17 newly-diagnosed insulin autoantibody positive Type 1 diabetic patients, 19 insulin autoantibody positive discordant twins of Type 1 diabetes and six insulin autoantibody positive healthy siblings of Type 1 diabetic patients (diabetes related) (p less than 0.01). Isolation of the type A polymorphism alone reduced the proportion of false negatives in the insulin autoantibody test for diabetes relatedness from 49% to 20% without diminishing its specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Studies in human lactation: milk volumes in lactating women during the onset of lactation and full lactation.

After validation of test-weighing procedures milk volumes produced by 13 multiparous Caucasian women were followed longitudinally through the first year of lactation. All practiced exclusive breast-feeding for at least 5 mo. Milk transfer to the infant was low on days 1 and 2 and increased rapidly to 498 +/- 129 g/d (means +/- SD) on day 5 and then more slowly to 753 +/- 89 g/d during months 3-5. There was a characteristic milk volume for each mother-infant pair that was significantly related neither to milk yield on days 4-6 nor to birth weight. It was, however, strongly related to infant weight at 1 mo, suggesting that infant and/or maternal factors coming into play during the first month of life are strong determinants of subsequent milk transfer to the infant.

Adult↗
PubMed1988

Insulin autoantibodies and insulin assay.

Insulin antibodies are known to interfere with the radioimmunoassay of insulin. We tested intravenous glucose tolerance on 25 insulin autoantibody-positive (IAA+) patients and 25 IAA- controls, who were matched for sex, age, and body mass index, to establish if IAA could also interfere with insulin assay. Insulin content was measured in untreated serum, serum precipitated with polyethylene glycol (PEG, free insulin), and serum extracted with acid and precipitated with PEG (total insulin). The mean untreated first-phase insulin response (I1 + 3) for IAA+ patients was 172 +/- 67.3 mU/L, significantly higher than the mean control value of 108 +/- 47.5 (P less than .001). After PEG precipitation, mean I1 + 3 in the patient group fell significantly to 105 +/- 48.4 mU/L (P less than .001), but the control value was unchanged (104 +/- 45.5). The mean percentage fall after PEG precipitation was 36.9% (patients) and 2.9% (controls) (t = 8.3, P less than .001). There was a strong correlation between the IAA titer and the interference in the insulin assay (r = .81). After total insulin extraction of IAA samples, there was a significant fall in mean I1 + 3 to 134 +/- 55.4 mU/L (P less than .001), but the control value was unchanged. IAA can significantly falsify insulin measurement, and care must be taken in the interpretation of insulin-release tests when IAA is present.

Adolescent↗
PubMed1988

On the relationship between islet cell antibodies and insulin autoantibodies in patients at risk from insulin dependent diabetes.

The frequencies of islet cell antibodies (ICA) and insulin autoantibodies (IAA) were studied in three clinically well defined groups, using an aprotinin sensitised indirect immunofluorescence assay for ICA and a direct binding solid ELISA for IAA, and the association of these two serological markers for insulin dependent diabetes analysed. Frequency of ICA was 10.7% in siblings of diabetics, 15.5% in discordant identical twins and 65.9% in newly diagnosed diabetic patients. Frequency of IAA was 7.1% in siblings, 46.7% in discordant twins and 38.6% in newly diagnosed diabetic patients. No correlation was demonstrated between the two autoantibodies in the siblings. In the newly diagnosed diabetic patients there were sera positive or negative for both, but 22 (50%) of the sera showed dissociation between the two antibodies. The studies of twins showed that IAA and ICA fluctuated independently with time, and demonstrate the inappropriateness of seeking such an association in cross-sectional surveys. An association could not be demonstrated in this group even if data from multiple samples taken at different points in time were pooled, scoring an individual as positive if at any time their sera had been positive for the corresponding antibody. Thus our data showed no correlation between ICA and IAA in any of the groups studied.

Adolescent↗
PubMed1985

Value of insulin autoantibodies as serum markers for insulin-dependent diabetes mellitus.

Insulin autoantibodies (IAA) were studied in newly diagnosed insulin-dependent diabetics before the start of insulin treatment and in unaffected identical twins of insulin-dependent diabetics. In 15 of the 40 (38%) diabetics and 27 of the 58 (47%) twins IAA levels exceeded those of 100 controls. Frequency of IAA in unaffected twins was not related to duration of diabetes in their affected twin. In 11 unaffected twins, IAA levels differed in two samples taken 1-12 years apart; IAA were detected at least once in all twins and in one on both occasions. IAA in the twins were not related to the presence of islet-cell antibodies or to HLA-DR 3 or 4. As the unaffected twins of longstanding diabetics are unlikely to develop diabetes, these observations suggest that IAA do not always presage diabetes and are probably not a consequence of the disease; they may reflect an inherited autoimmune tendency to diabetes.

Adolescent↗
PubMed1985

A micro enzyme-linked immunosorbent assay for insulin antibodies in serum.

A solid-phase micro enzyme-linked immunosorbent assay for the measurement of insulin antibodies in serum is described and its performance compared with that of an established radiobinding assay. Interassay precision in the ELISA was 10% or less at widely spaced points on the dilution curves for human, porcine and bovine insulins. Specificity was demonstrated by substituting purified human gamma-globulin for the test serum and glucagon for the insulin. The influence on ELISA of endogenous insulin in the test serum was examined by measuring antibody binding before and after extraction of the insulin. The correlation between results from extracted and unextracted sera was 0.96 and the fit ideal: y = 1.00x + 0.38%. The correlation between the results of measuring insulin antibody in 256 diabetic sera by the 2 assays was r = 0.74, P less than 0.001 (human insulin) and r = 0.71, P less than 0.001 (porcine insulin). ELISA is cheap and simple to perform. We believe it may prove to be a practical alternative to radioassay in both the routine detection and investigative research of insulin antibodies.

Animals↗
PubMed1984

The distribution of immunoglobulin-containing cells in human autoimmune thyroiditis.

The peroxidase-antiperoxidase (PAP) staining method was used to identify immunoglobulin-containing cells in the lymphoid infiltrates of thyroids removed from patients with Hashimoto's autoimmune thyroiditis. A composite picture of the distribution of such cells in the thyroid infiltrate was obtained by carefully superimposing cell-distribution maps from serial histological sections, each stained for a different immunoglobulin class. Ig-containing cells were present to varying extents in all areas of the gland, but were most dense in areas of epithelial 'invasion'. IgG was the commonest immunoglobulin, but there were more cells containing IgD and IgE than IgA or IgM. Both lambda and K light chains were identified in cells occupying the follicle centres. Lymphoid follicle structure was strikingly similar to that described previously for gut-associated lymphoid tissue (GALT), and the theory is advanced that autoimmune thyroiditis represents a form of ectopic GALT in which B-cells, which normally home on markers in the gut, are attracted instead to antigenically active sites in the thyroid.

Adult↗
PubMedDate not supplied

Reverse zymography studies of protease inhibitors in the secretions of different lobes of rat prostate.

The purpose of this study was to determine whether protease inhibitors were a constituent of secretions from the different lobes of the rat prostate. A reverse zymography method was used employing gelatin substrate-SDS-polyacrylamide gel electrophoresis to detect inhibitors of trypsin in secretions of the ventral, lateral, and dorsal prostate lobes of the Sprague-Dawley rat. Inhibitors of approximately 34 and 63 kDa were detected in ventral prostate secretion and of about 63 and 73 kDa were found in lateral lobe secretion. However, no inhibitor activities were detected in secretions of the dorsal lobe. The protease inhibitors of ventral prostate secretion were partially purified by preparatory isolectric focusing and SDS-polyacrylamide gel electrophoresis. The 34-kDa (pI 5.6-6.4) inhibitor had a higher activity against trypsin, whereas the 63-kDa (pI 6.4-7.0) inhibitor was more active against chymotrypsin. The rat prostate appears to have a lobe-specific distribution of secretory serine protease inhibitors.

Animals↗