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Biomedical subjects

J C Evans

Publications and source records attributed to J C Evans.

At least 91 records · Page 5Linked to original sources

Risk of coronary heart disease in subjects with chest discomfort: the Framingham Heart Study.

PURPOSE: To examine the risk of coronary heart disease (CHD) events in subjects of the Framingham Study reporting new chest discomfort. SUBJECTS AND METHODS: Original cohort subjects with chest discomfort were classified by their history into three groups: definite angina, possible angina, or nonanginal chest discomfort. Subjects were followed for 2 years for CHD events, including coronary insufficiency, myocardial infarction, or CHD death. RESULTS: Compared to that in subjects without chest discomfort, the relative odds of a CHD event was 3.7 (95% confidence interval [CI] 2.11, 6.60) in men with definite angina and 3.0 (95% CI 1.33, 6.69) in men with possible angina. Comparable increased CHD risk was also observed in women with definite or possible angina, with relative odds of 5.4 (95% CI 3.08, 9.30) and 2.9 (95% CI 1.13, 7.17), respectively. The increase in CHD risk associated with definite or possible angina persisted after adjustment for cardiac risk factor profile. There was no increase in risk associated with nonanginal chest discomfort. CONCLUSION: CHD risk is increased in subjects with new chest discomfort that on the basis of history is consistent with definite or possible angina, whereas CHD risk is not increased in subjects with nonanginal chest discomfort. The presence of chest discomfort and its characteristics facilitate the classification of subjects into meaningful categories that offer prognostic information beyond that provided by traditional CHD risk factors.

Adult↗

The photochemical binding of bithionol to soluble proteins and peptides.

The photochemical reactions of the bacteriocide bithionol (a known photoallergen in man) with soluble proteins and peptides, were investigated. Solutions of human serum albumin (HSA), human gamma-globulin, bovine insulin and poly-L-lysine were irradiated with ultraviolet light of wavelength 313 nm in the presence of [35S]-bithionol and the extent of photochemical (covalent) binding determined. HSA bound at least four molecules of bithionol per molecule of HSA. Bithionol was also found to bind to gamma-globulin to a similar extent; lower levels of binding were achieved with bovine insulin and poly-L-lysine. A bithionol-HSA photoadduct was treated with cyanogen bromide to determine the selectivity of binding. Fractionation after cyanogen bromide treatment showed that bithionol was bound to both major fragments of HSA, with a preference for the N-terminal region of the protein.

Bithionol↗

ESR analysis of irradiated frogs' legs and fishes.

Electron spin resonance (ESR) spectral analysis of different parts (bones, scales, jaw, etc.) from ionized (irradiated) frozen frogs' legs and fishes (brown trout and sardine) were recorded. There is always present, after treatment, a signal due to the irradiation. ESR and ENDOR experiments lead us to assign it to h1 centers from hydroxyapatite, as in the case of other irradiated meat bones. The use of ESR to prove whether one of these foods has been irradiated or not is discussed.

Animals↗

Electron spin resonance detection of oxygen-centred radicals in murine macrophages stimulated with bacterial endotoxin.

The production of oxygen radicals by Bacille-Calmette-Guerin primed mouse macrophages stimulated with bacterial endotoxin has been investigated. Superoxide radicals were spin-trapped in this system with dimethylpyrroline-N-oxide after a lag period of 20-40 minutes. The electron spin resonance signals due to the superoxide radical adduct could be inhibited by superoxide dismutase but not by catalase.

Animals↗

Radicals involved in photoallergen/protein interactions.

Aqueous solutions (pH = 8) of both 3,3'-dimethyl and 4,4'-dimethyl substituted analogues of the photoallergen fentichlor (bis(2-hydroxy-5-chlorophenyl)sulphide) produced stable semiquinone radicals when irradiated with u.v. light (greater than 310 nm). These radicals have been characterised using electron spin resonance techniques: the results confirm the assignment of hyperfine coupling constants for the parent fentichlor radical. The binding of fentichlor to HSA was found to be partly oxygen dependent demonstrating a role for semiquinone type radicals in the binding mechanism. The stoichiometry and specificity of the binding of the dimethyl analogues to soluble proteins were found to be similar to that of fentichlor itself.

Anti-Infective Agents, Local↗

Effects of E. coli 0111.B4 lipopolysaccharide on spin-labelled murine macrophage and hepatocyte membranes.

Macrophages and hepatocytes from normal and BCG-primed mice have been spin-labelled in their membranes with 5- and 16-doxyl stearic acid. Incubation of spin-labelled cells from BCG-primed animals with lipopolysaccharide from E. coli 0111.B4 produced a detectable and transient disturbance in the cell membranes as reflected by an increase in the order parameter measured from the electron spin resonance spectra of 5-doxyl-stearate. This membrane disturbance was maximal at 3-4 hours of incubation and was only detected with cells from mice primed with BCG. Spectra obtained from the 16-doxyl-stearate-labelled cells showed no change in order parameter on incubation with lipopolysaccharide.

Animals↗

Nitroimidazole and oxygen derived radicals detected by electron spin resonance in hydrogenosomal and cytosolic fractions from Trichomonas vaginalis.

Hydrogenosome-enriched fractions from Trichomonas vaginalis reduce a number of nitroimidazole derivatives to their respective electron spin resonance-detectable nitro-anion radicals. In the presence of of oxygen and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) a superoxide spin trapped adduct of DMPO was formed; the rate-determining step was the prior formation of the nitro-anion radical. Oxygen-derived radicals were detected with cytosolic fractions from a metronidazole-resistant isolate (CDC-85) when incubated with NADH or NADPH as respiratory substrate. The requirement for superoxide dismutase and catalase to completely abolish formation of these signals suggests contributions from both superoxide and peroxide. No oxygen-derived radicals were observed with cytosolic fractions from a metronidazole-susceptible strain (C1-NIH).

Animals↗

Reduction of niridazole by metronidazole resistant and susceptible strains of Trichomonas vaginalis.

The inhibitory effect of niridazole on hydrogen production by metronidazole-resistant (CDC-85) and susceptible (C1-NIH) Trichomonas vaginalis strains was investigated. The results show that niridazole is more effective than metronidazole in inhibiting hydrogen production by the resistant isolate. In CDC-85 aerobic inhibition requires a 4-fold increase in metronidazole concentration compared with that required anaerobically, but the corresponding factor for niridazole is only 1.5-fold. Reduction of the drug by a hydrogenosome-enriched preparation gave rise to a multiline electron spin resonance detectable signal, which is due to a nitrogen-centred radical.

Animals↗

The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillation.

A comparison was made of the distribution of dust in the rat lung following its administration by inhalation and by a single intratracheal instillation. Due to the wide variety of instillation techniques, an "average" method was adopted based on the results from a survey of 15 laboratories in Europe and the USA. Novel techniques were developed to quantify the distribution of dust within the lung both microscopically and macroscopically. The distribution of dust obtained by instillation was shown to be much less homogeneous that that obtained by inhalation and penetration to the periphery was minimal. The effects of (a) changing the volume of suspension, (b) changing the concentration of the suspension, and (c) introducing air into the syringe were investigated. Although the use of air in the syringe was beneficial, none of the other modifications effected any improvement in the distribution. The difference in distribution following inhalation and instillation leads to the conclusion that the latter may be of use in establishing the nature and comparative response of the lung to different dusts, but not for establishing an absolute dose-response relationship. It is recommended that no more than 1 mg of fibrous or 5 mg of nonfibrous dust be given in a single instillation to adult rats.

Animals↗

Activation of spin-labeled chicken pepsinogen.

Chicken pepsinogen has been spin-labeled by the attachment of four nitroxides to epsilon-amino groups near the protein's amino terminus. Acidification results in a bond cleavage, generating a nonlabeled, enzymatically active protein. Electron spin resonance spectra of the spin-labeled zymogen, acidified in the presence or absence of pepstatin, are identical and indicate that the nitroxides are quite mobile, compared to the nonacidified zymogen. This mobilization is interpreted as the freeing of the peptide to which the spin-labels are attached, from the protein, subsequent to the acidification that causes a peptide bond cleavage. The rate at which the peptide leaves the protein is 1 order of magnitude slower than the cleavage of the peptide bond, measured by the rate of appearance of milk-clotting activity (first-order rate constants of 0.3 min-1 vs. 6 min-1 at pH 2, 22 degrees C). The inclusion of pepstatin, at molar ratios above 2 during activation, decreases the rate of peptide leaving. These observations, and those previously reported for activation of spin-labeled pig pepsinogen, are incorporated into a model of pepsinogen activation.

Amino Acid Sequence↗

Comparison of the photodynamic action of Rose Bengal and tetrachlorosalicylanilide on isolated porcine erythrocyte membranes.

The light-mediated effects of Rose Bengal and 3,3',4',5-tetrachlorosalicylanilide (T4CS) on porcine erythrocyte membranes have been investigated. Irradiation in the presence of Rose Bengal and oxygen causes extensive destruction of the unsaturated fatty acids of the erythrocyte membrane. This results in a decrease in the membrane flexibility as measured by a nitroxide spin probe. Irradiation in the presence of T4CS and oxygen had no measurable effect on the unsaturated fatty acids or on the membrane flexibility. Irradiation of erythrocyte membranes both in the presence of Rose Bengal and oxygen and of T4CS gave rise to polymerisation of the membrane proteins. This was evident by polyacrylamide gel electrophoresis and by freeze-fracture electron microscopy. Aggregation of membrane proteins could be observed with low levels of Rose Bengal and short irradiation times at which no loss of unsaturated fatty acids could be detected. Irradiation of the n-butanol-extracted apoprotein of porcine erythrocyte membranes both in the presence of Rose Bengal and of T4CS resulted in polymerisation of the protein as measured by gel electrophoresis and electron microscopy. The results obtained from the two photodynamic compounds are compared in terms of their different mechanisms of action on the membrane. The implications of the results in determining the molecular events leading to photohaemolysis are discussed.

Allergens↗

Retention, distribution, and excretion of lead by the rat after intravenous injection.

The distribution and excretion of lead was studied during a period of about a week after a single intravenous injection of 203Pb as chloride accompanied by less than 1 microng of lead carrier. The peak concentration in venous blood was reached after about an hour when it contained 35 to 40% of the administered activity. The subsequent decline in concentration was much more rapid than is observed in man. The main storage organs were the kidneys and bone. Initially, 20% of the dose could be accounted for in the kidney and the biological half-life was about 100 hours. The level in bone built up rapidly at first and then more slowly. After a week, between 25 and 30% of the dose was present in bone.

Age Factors↗

Fractionated dose of 35-MEV fast neutrons and hypoxic tumor cell survival curve.

The determination of the RBE for the MANTA fast neutrons produced by NRL is inprogress, with the model system using tumor cell population kinetic response patterns assayed in vitro after irradiation in vivo. Ascites tumor cells BW-5147 were irradiated with a clinically usable fast neutron beam from the NRL cyclotron, which is produced by accelrating deuterons to 35 MeV and using htem to bombard a thick berylliumtarget. The comparison of dose-effect relationships was made for doses ranging from30 to 1000 rads. The doses required for an isoeffect on BW-5147 hypoxic tumor cell survival and impairment of its reproductive capacity from fast neutron exposure were not different wheither it was given a single dose or the same dose given in three fractions separated by long recovery periods in situ. No intracellular repair of sublethal injury when the dose was given in three fractions, although the hypoxic BWp5147 tumor cells haveno effective reoxygenation or repopulation in this time interval. The RBE for the fast neutron beam is 4 relative to x rays for fractionated doses at the surviving fractionlevel of 0.6-0.7, while the RBE IS 2.5 FOR SINGLE DOSES. However, at a surviving fraction of 0.1, the RBE is 1.9 for single and 2.8 for fractionated doses. Analysis of thedaily cell population rate or mitotic delay between the two types of radiations at a similiar level of survival.

Animals↗