Biomedical subjects

E P Sullivan

Publications and source records attributed to E P Sullivan.

4 recordsLinked to original sources

PubMed2001

Comparison of the prevalence of glutamic acid decarboxylase (GAD65) and gliadin antibodies (AGA) in a randomly selected adult estonian population.

We aimed to test the hypothesis that gluten might be associated with the development of islet cell autoimmunity. A random sample of 200 persons (87 males, mean age 42.4 years) from Estonia including one patient with type I diabetes mellitus was studied. IgG-type glutamic acid decarboxylase (GAD65) antibodies were determined using radioligand-binding assay and IgG/IgA-type gliadin antibodies (AGA) by enzyme-linked immunosorbent assay. Generic HLA-DRB1* alleles were analyzed using a polymerase chain reaction. Although our results revealed the highest GAD65Ab index and a high IgA-type AGA in a person with diabetes, no correlation between GAD65Ab and AGA values was revealed among the other 199 persons (p > 0.05). There were also no differences between test values among persons with and without different HLA-DRB1* alleles (p > 0.05). In the GAD65Ab assay, one person (0.5 %; 95 % CI: 0 - 1.5) out of 199 exceeded the 99(th) centile of the GAD65Ab index. In summary, the present study does not confirm the possibility that there is a relationship between the immune reactivity against GAD65 and gliadin, at least in persons without type I DM.

Adolescent↗

PubMed1999

Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index.

AIMS/HYPOTHESIS: Our aims were to investigate the concentrations and prevalence of autoantibodies against the Mr 65.000 isoform of glutamate decarboxylase (GAD65) and the tyrosine phosphatase-like protein (IA-2) in adults and to test the hypothesis that GAD65 and IA-2 autoantibodies in a regional population are related to abnormal oral glucose tolerance. METHODS: We analysed serum from 2157 Swedish subjects aged either 30, 40, 50 or 60 years old who, in 1988-1992, participated in the Västerbotten County Health Project and were subjected to the World Health Organisation (WHO) standard oral glucose tolerance test at entry into the study. RESULTS: We found 23 of 2157 (1.1%) and 17 of 2152 (0.8%) subjects exceeded the 99th centile of GAD65 autoantibody index and IA-2 autoantibody index, respectively. In 18 subjects with diabetic oral glucose tolerance test, GAD65 autoantibody concentrations were higher than in those with normal oral glucose tolerance test (p = 0.02). Subjects with IGT (n = 185) [corrected] and diabetes (n = 18), i.e. abnormal OGTT (n = 203) [corrected], had higher GAD65Ab [corrected] index compared with those with normal OGTT (p = 0.026) [corrected]. A stepwise multiple logistic regression test showed that the odds ratios for subjects in the highest BMI group to exceed the 95th or 99th GAD65 autoantibody centile were 3.6 (CI 1.4-8.9) and 17.6 (CI 2.6-121.6), respectively. CONCLUSION/INTERPRETATION: GAD65 and IA-2 autoantibodies, are associated with impaired or diabetic glucose tolerance in an adult regional population. This observation together with the association between GAD65 autoantibody concentrations and body mass index indicate a possible relation between islet autoimmunity and beta-cell function abnormalities with obesity and insulin resistance.

Adult↗

PubMed1993

Electron transfer in sulfite oxidase: effects of pH and anions on transient kinetics.

Intramolecular electron transfer (ET) rates in sulfite oxidase (SO) were measured using flavin semiquinone reductants [5-deazariboflavin (dRFH.) and lumiflavin (LFH.)] generated by laser flash photolysis. Rapid bimolecular reduction of the heme by the dRF semiquinone occurred (k = 4 x 10(8) M-1 s-1 at pH 6; 1 x 10(8) M-1 s-1 at pH 9), followed by heme Fe(II) reoxidation due to intramolecular electron transfer to Mo(VI). Flash-induced difference spectra indicated that only spectral processes due to reduction and oxidation of the b-type heme prosthetic group were observed, with no detectable spectral contribution from the Mo cofactor. The extent of reoxidation decreased greatly from pH 6 to 9 (50% to 3%), as expected from the shifts in the redox potentials of the heme and Mo cofactor with pH, consistent with an electron transfer equilibrium between the two redox centers. The observed rate constant for the Fe(II) to Mo(VI) electron transfer decreased from 1650 s-1 at pH 6 to 60 s-1 at pH 9 and showed a maximum of 2400 s-1 at pH 7. Increases in salt concentration greatly decreased intramolecular ET rate constants (direct reduction by flavin semiquinone was unchanged), due to the binding of anions. Titration with the sodium salts of Cl-, SO4(2-), and H2PO4-/HPO4(2-) resulted in decreases in rate constants of intramolecular ET from 1500 s-1 to < 100 s-1 at pH 6 and 7. Similar dissociation constants were measured for the binding of these anions by flash photolysis and by steady-state enzyme kinetics using the inhibition of the sulfite/cytochrome c assay reaction for sulfite oxidase. A mechanism is proposed in which anion binding to the enzyme inhibits the rate of intramolecular electron transfer.

Animals↗

PubMed1989

Modeling low-pH hemoproteins.

A tetracoordinate ferrous heme (iron-porphyrin) has been proposed as an intermediate at low pH (less than 3.0) for respiratory hemoproteins, peroxidases, and model heme complexes. This intermediate is believed to arise via protonation of the N(epsilon) atom of the proximal histidine and consequent cleavage of the Fe-N(epsilon) bond. To establish a spectral signature for the proposed low-pH tetracoordinate species, we have obtained Soret excitation resonance Raman spectra on samples of crystallographically defined, tetracoordinate iron(II)-octaethylporphyrin (Fe.OEP; S = 1). The high-frequency (greater than or equal to 900 cm-1) resonance Raman spectral features of Fe.OEP are clearly distinct from those of high-spin pentacoordinate or low-spin hexacoordinate ferrous hemes. Rather, they are at frequencies more typically observed for low-spin hexacoordinate ferric porphyrins. Comparative spectral analysis of tetracoordinate Fe.OEP and other proposed tetracoordinate ferrous hemes (e.g. iron(II)-protoporphyrin IX) demonstrates little or no macrocycle effect on the resonance Raman frequencies above 900 cm-1. This work thus serves to provide a testable spectral signature by which the existence of the proposed tetracoordinate biological intermediate may be verified and by which its functional significance may be tested.

Cytochromes b5↗