PubMed Health⌕ Search

Biomedical subjects

W J Riley

Publications and source records attributed to W J Riley.

At least 73 records · Page 4Linked to original sources
PubMed1987

Competitive insulin autoantibody assay. Prospective evaluation of subjects at high risk for development of type I diabetes mellitus.

A quantitative fluid-phase radioassay for autoantibodies reacting with insulin (competitive insulin autoantibody assay, CIAA) was developed. The assay's features include 1) use of a physiologic amount of 125I-labeled insulin, 2) parallel incubations with supraphysiologic cold insulin (competitive), and 3) an incubation time of 7 days and a single-step multiple-wash polyethylene glycol separation. Mean +/- SE CIAA levels in 50 controls were 8 +/- 1.4 nU/ml (range -16-33.3). In 36 cytoplasmic islet cell antibody (ICA)-positive nondiabetic first-degree relatives of type I (insulin-dependent) patients less than 30 yr of age, CIAA levels exceeded the normal range in 20 (55.6%) of 36 (mean 86.8 +/- 17.1 nU/ml). In 26 ICA-positive relatives greater than 30 yr of age, only 5 (19.2%) of 26 exceeded the normal range (mean 26.1 +/- 9.4 nU/ml); P less than .001 compared with younger ICA-positive relatives). Six ICA-negative HLA-identical siblings of type I diabetic patients had normal CIAA levels (mean 3.6 +/- 5.8 nU/ml), and only 2 of 13 ICA-negative identical twins discordant for diabetes (mean 15.4 +/- 6.6 nU/ml) exceeded the normal range. Nine (50%) of 18 ICA-positive schoolchildren exceeded the normal range (mean 105.3 +/- 36.7 nU/ml). Genetically susceptible subjects negative for CIAA (with only 3 exceptions) remained negative for CIAA on multiple determinations (3 conversions observed), and CIAA levels of positive subjects were relatively stable. Linear regression of the first CIAA level versus last (interval between sampling 1 mo to 10 yr) in genetically susceptible individuals showed a highly significant correlation (r = .95, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1987

Application of an immunoradiometric assay for thyrotrophin in evaluation of thyroidal and nonthyroidal disease states.

We evaluated an immunoradiometric assay for serum TSH (IRMA-TSH) and compared it with established indices of thyroid function in 208 patients with either frank thyroid disease, conditions of abnormal thyroxine protein binding, or conditions which are known to produce discordant thyroid results, viz. pregnancy or estrogen treatment and nonthyroidal illness (NTI). As expected, a wide scatter of TSH results was found in treated thyroid disease: 53 patients (53%) from both groups (initially hypo- or hyperthyroid) had TSH values less than 0.5 mU/l, but only one was considered to be clinically mildly toxic. All the pregnant, estrogen-treated and abnormal thyroxine protein-binding patients had TSH results within the reference range 0.5-6.0 mU/l, except one familial dysalbuminemic hyperthyroxinemia (FDH) patient (T4 level, 178 nmol/l) lost to follow-up with a TSH level of 8.5 mU/l, and one euthyroid, low-TBG patient being treated inappropriately with thyroxine, with a TSH level less than 0.5 mU/l. All the untreated thyrotoxic patients and 15 (26.3%) of the NTI patients had TSH results of 0.5 mU/l or lower. Because of this high incidence of low TSH levels in euthyroid NTI, we cannot recommend this IRMA-TSH as the initial test of thyroid function.

Estrogens↗
PubMed1987

Is insulin-dependent diabetes mellitus a preventable disease?

Despite improvements in the ongoing care of individuals with insulin-dependent diabetes, the disease continues to produce significant morbidity and mortality, especially early in life, in individuals developing insulin-dependent diabetes in childhood or adolescence. In order to have a major impact on disease outcome, the best therapeutic approach is disease prevention. Because insulin-dependent diabetes results from autoimmune pancreatic beta cell destruction, the disease may be amenable to immunological intervention with immunotherapy. This is particularly exciting as we develop tools, such as islet cell autoantibody determinations, that allow diagnosis of individuals prior to clinical presentation. It is during this time-period when immune manipulation may be most efficacious in preventing further beta cell destruction, and otherwise eventual insulin dependence. As such trials are highly experimental, they must be conducted only in research centers staffed by physicians and scientists with expertise in diabetes, autoimmunity, and immunology.

Autoantibodies↗
PubMed1986

Preferential transmission of diabetic alleles within the HLA gene complex.

Several studies suggest a higher incidence of insulin-dependent diabetes mellitus (IDDM) among the offspring of men with the disease than among those of female diabetics. Differential transmission by the father of genes that predispose to diabetes may explain this phenomenon. To test this hypothesis, we examined parent-to-offspring transmission of HLA haplotypes and DR (D-related) alleles in 107 nuclear families in which a child had IDDM. We observed that fathers with a DR4 allele were significantly more likely to transmit this allele to their diabetic or nondiabetic children than were mothers with a DR4 allele (72.1 vs. 55.6 percent, P less than 0.001). No differences between parents were observed for HLA-DR3; however, DR3 was transmitted significantly more than 50 percent of the time from either parent (P less than 0.001). These data suggest that differential parental transmission of the HLA-DR4-linked diabetes-predisposing allele may explain the higher risk of diabetes among children of diabetic fathers than among those of diabetic mothers. In addition, the excess transmission of diabetogenic HLA alleles from parent to offspring may explain how these deleterious genes continue to recur at such high frequencies in the general population.

Alleles↗
PubMed1986

HLA haplotype sharing and proband genotype in IDDM.

We previously proposed that the HLA-related genetic susceptibility to insulin dependent diabetes mellitus (IDDM) is best explained by at least two different susceptibility alleles, one preferentially associated with DR3, the other with DR4. This IDDM HLA heterogeneity model predicts that HLA haplotype sharing among affected sibpairs will be increased when the index case is a compound heterozygote (i.e., DR3/DR4). This prediction was tested and confirmed using the GAW IV IDDM data set. A significantly increased sharing of HLA haplotypes was seen when the index sib was DR3/DR4 compared to those of other genotypes (68% versus 37% sharing 2 haplotypes, p less than .01).

Alleles↗
PubMed1986

Inherited susceptibility to autoimmune Addison's disease is linked to human leukocyte antigens-DR3 and/or DR4, except when associated with type I autoimmune polyglandular syndrome.

The inherited susceptibility to autoimmune Addison's disease was found to be strongly associated with human leukocyte antigens (HLA)-DR3 and DR4 alleles. In a study of 45 white patients from the United States with the disease, the relative risks (the number of times that an individual is at risk for Addison's disease if they had a marker, compared to those without such marker) were found to be 6.0, 4.6, and 26.5 for the DR3 allele, the DR4 allele, and for DR3/DR4 heterozygotes, respectively. Frequencies of DR2, DR5, and DR7 in the patients with Addison's disease were significantly decreased in comparison to 265 individuals in the control population. These HLA-DR frequencies in patients with Addison's disease were similar to those for 723 patients with insulin-dependent diabetes (IDD). However, the above HLA-DR associations persisted even when only data from the 37 patients with Addison's disease who did not have IDD were considered. Adrenocortical autoantibodies in 23 patients with IDD who did not have Addison's disease were equally frequent among those with DR4 and DR3 alleles. In contrast, HLA-DR frequencies in 17 patients with type I autoimmune polyglandular syndrome (chronic mucocutaneous moniliasis, hypoparathyroidism, Addison's disease, etc.) were not different from control. We conclude that genetic susceptibility to autoimmune Addison's disease may involve the same HLA-associated genetic determinants as IDD, except when Addison's disease occurs as part of type I autoimmune polyglandular syndrome.

Addison Disease↗
PubMed1986

Lymphocyte subsets and activation in prediabetes.

Peripheral blood lymphocytes were obtained from 65 individuals: 34 nondiabetic patients with islet cell autoantibodies (ICA) (prediabetic phase), 9 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM), 6 ICA-negative siblings or offsprings of IDDM patients, and 16 ICA-negative controls. The presence of lymphocyte abnormalities and/or activation was examined with dual fluorescence flow cytometry. The percentages of B cells, total T-lymphocyte, and helper T-lymphocyte (Th) and cytotoxic/suppressor T-lymphocyte (Tc/s) subsets and their ratio were not significantly different among the patient groups. No increased expression of interleukin 2 receptor on T-lymphocyte was found in newly diagnosed IDDM or prediabetic individuals. Sixteen of 49 patients had significantly increased number of T-lymphocyte expressing HLA-DR. A significant increase in the number of both Th and Tc/s subsets expressing HLA-DR was found in only 3 of 16 patients. This increase was unrelated to the patients's relative ICA titer or HLA-DR phenotype. On the other hand, the relative density of the DR antigen (RAD-DR) was significantly increased on both Th (886 +/- 120) and Tc/s (1250 +/- 273) in 13 of 38 patients compared with control patients (Th 484 +/- 129 and Tc/s 460 +/- 166). The RAD-DR on Tc/s correlated with the relative ICA titer and was greatest on DR3/4-phenotyped T-lymphocytes. In addition, significantly increased RAD-DR was found in noncontrol patients with impaired insulin release responses at 1 and 3 min to intravenous glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Are insulin autoantibodies markers for insulin-dependent diabetes mellitus?

Recent studies have shown that insulin autoantibodies occur in patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) before exogenous insulin treatment. Our study was designed to test the hypothesis that insulin autoantibodies, like cytoplasmic islet cell antibodies (ICAs), can identify individuals with ongoing autoimmune beta-cell destruction and increased risk of IDDM development. Insulin autoantibodies detected by use of a radioligand-binding assay were found in 1.4% of normal controls, 4% of first-degree relatives of IDDM patients, and in 37% of newly diagnosed IDDM patients. A strong positive correlation between insulin autoantibodies and ICAs was observed. HLA typing of insulin-autoantibody-positive first-degree relatives of IDDM patients, as well as in the general population, revealed a strong association with HLA-DR3 and/or-DR4, suggesting that insulin autoantibodies are restricted to persons genetically susceptible to IDDM. In an ongoing study of beta-cell function in ICA-positive nondiabetic individuals, the additional presence of insulin autoantibodies significantly increased the likelihood of beta-cell dysfunction. After intravenous glucose stimulation, insulinopenia was present in 70% of ICA and insulin-autoantibody-positive individuals in contrast to only 23% of ICA-positive, insulin-autoantibody-negative persons. These data document a significant association between insulin autoantibodies and ICAs and support the contention that insulin autoantibodies, like ICAs, are markers of ongoing beta-cell destruction.

Autoantibodies↗
PubMed1984

Thyroid hormone abnormalities at diagnosis of insulin-dependent diabetes mellitus in children.

Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.

Adolescent↗
PubMed1984

Adrenal dysfunction in asymptomatic patients with adrenocortical autoantibodies.

Autoantibodies to the adrenal cortex (AA) were sought by indirect immunofluorescence using unfixed human adrenal tissue in 1675 patients with insulin-dependent diabetes (IDD), 2032 relatives of patients with IDD, and 2543 normal subjects. The frequencies of AA were significantly greater in patients with IDD (1.8%) and their relatives (1.4%) than in normal subjects (0.6%; P less than 0.013). Women more frequently had AA than men (P less than 0.011). There were no differences in the frequencies of AA between caucasoid and black individuals in all three patient groups. Patients with AA had higher frequencies of thyroid microsomal and gastric parietal cell autoantibodies than age-, sex-, and race-matched normal subjects (P less than 0.01). Adrenal function was studied in 30 asymptomatic patients (13 with AA, including 5 with IDD, and 17 subjects with no AA, including 8 with IDD). The mean plasma levels of ACTH at 0600 and 2000 h were significantly higher in those with AA than in matched subjects with no AA (P less than 0.01). The mean PRA levels (both recumbent and upright) were also significantly higher in those with AA than in subjects without AA (P less than 0.01). However, serum cortisol and aldosterone concentrations or 24-h urinary cortisol and aldosterone excretion were no different between the groups. These patients, therefore, appear to have compensated adrenal hypofunction, with the compensation maintained by increased ACTH and renin secretion. Whether these patients will remain in this compensated state of adrenal dysfunction or whether they will develop overt adrenal insufficiency requires longer follow-up.

Adolescent↗