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Biomedical subjects

W L Stone

Publications and source records attributed to W L Stone.

At least 55 records · Page 3Linked to original sources

A quantitative microscopic analysis of the myocardial interstitial tissue space and myocardial fiber diameter in rats with vitamin E and selenium deficiency.

Vitamin E (E) and selenium (Se) are important antioxidant nutrients, preventing membrane damage by lipid hydroperoxides. In a previous study on E + Se deficient rats it was shown that plasma levels of lipoproteins increase dramatically. In continuation of this study a quantitative microscopic study was undertaken to determine the behavior of myocardial interstitial tissue space (ITS) in E + Se deficient rats as compared to control rats. Four rats fed on normal laboratory chow and 8 rats fed on basal diet supplemented with adequate E + Se served as control. Eight rats were fed on E + Se deficient diet. The animals were sacrificed after 13 to 20 weeks. Qualitative microscopic study showed patchy areas of hemorrhage, edema, infiltration of macrophages and myocardial damage consisting of pyknosis and coagulation necrosis in the deficient rats. Quantitative microscopic study of the apparently normal areas of myocardium of deficient rats showed a shrinkage of ITS (21.0 +/- 1.29% vs 16.51 +/- 4.62%, alpha = 0.01), whereas the ITS of normal laboratory chow and E + Se supplemented groups were similar. The myocardial fiber diameter was unchanged. Using Starling's hypothesis regarding fluid movement across capillary walls, several mechanisms could be advanced to explain this apparently paradoxical phenomenon. We contend that the interstitial fluid of normal areas of the myocardium is either absorbed by the adjacent damaged areas, or before extravasation of the intravascular proteins and swelling of ITS, the interstitial fluid is first absorbed by the intravascular compartment, due to capillary membrane damage.

Animals↗

Effects of dietary selenium and vitamin E on plasma lipoprotein cholesterol levels in male rats.

Male Fischer-344 rats fed a diet deficient in both vitamin E and selenium (Se) for 20 weeks had higher levels of low-density lipoprotein cholesterol than age-matched rats fed an identical diet but supplemented with these micronutrients. The rats supplemented with both vitamin E and Se were switched to a diet deficient in both these micronutrients at week 20. These rats eventually developed elevated levels of low-density lipoprotein cholesterol compared to age-matched rats either continuously maintained on the diet supplemented with vitamin E and Se or rats switched (at week 20) from the vitamin E-and Se-deficient diet to a diet supplemented with both these micronutrients. In a second experiment, we found that Se deficiency alone was sufficient to significantly elevate low-density lipoprotein cholesterol. The basal diet used in these experiments had a very low cholesterol content and the observed alterations in lipoprotein cholesterol levels are likely to reflect alterations in the metabolism of endogenously synthesized cholesterol.

Animals↗

Comprehension of nonverbal communication: a reexamination of the social competencies of learning-disabled children.

This study was designed to determine whether learning-disabled (LD) children differed from nondisabled (NLD) children in their ability to comprehend nonverbal communication when potential attentional differences between the groups were controlled. In addition, the relationship between nonverbal comprehension and social competence was assessed. Thirty LD and 30 NLD boys between 9 and 12 years of age were administered a short form of the Profile of Nonverbal Sensitivity (PONS) to assess nonverbal comprehension; social competence measures included teachers' ratings of aggressive and withdrawn behaviors using the Behavior Problem Checklist, and "blind" judges' ratings of performance on a role-play of friendship-making skills. Under attention-incentive conditions, no performance differences between LD and NLD children were found on the PONS; however, LD children were judged to be more withdrawn and less socially skilled. While PONS scores were not related to other social competence measures, they were associated with academic achievement and IQ. Results emphasize the importance of considering the presence of attentional problems in LD children that may interfere with an accurate assessment of their skills.

Achievement↗

Facilitating the vocational-interpersonal skills of mentally retarded individuals.

A program was designed to teach interpersonal skills to mentally retarded individuals in order to facilitate their vocational adjustment and prevent job termination. Thirty-five retarded young adults were randomly assigned to a skills-training, coaching, or no-treatment control group. The skills-training and coaching groups met for 12 sessions and 6 follow-up meetings. The skills-training group learned appropriate ways of responding to difficult work-related interpersonal situations. Modeling, coaching, and behavioral rehearsal were the treatment procedures. The coaching group discussed the same interpersonal situations; however, modeling and behavioral rehearsal were not employed. Results indicated that the skills-training group improved their interpersonal skills, social competence, vocational problem behavior, and length of employment. Some positive changes were noted for the coaching group. The results provide support for training interpersonal skills prior to community vocational placement.

Adolescent↗

Assessing the problematic interpersonal skills of mentally retarded individuals in a vocational setting.

The present paper reports on two studies which were designed to assess specific interpersonal situations and behaviors which interfere with a mentally retarded individual's adjustment to a vocational setting. In the first study, lists of problematic interpersonal situations and problematic behaviors were generated based on (a) interviews with prevocational teachers, school personnel, and work supervisors in a sheltered workshop setting, and (b) behavioral observations of workers in prevocational classes and a workshop setting. The list of problematic behaviors was further evaluated by work supervisors to determine the frequency and seriousness of each behavior. This information provided a basis for establishing training priorities in an interpersonal skills training program for mentally retarded individuals. In a second study, problem behavior ratings were obtained from prevocational teachers and residential supervisors for 40 mentally retarded individuals. Teachers additionally rated each individual using several standardized assessment scales (Behavior Problem Checklist, AAMD Adaptive Behavior Scale, Vocational Competency Scale). After placement in a sheltered workshop setting, problem behavior ratings were obtained from work supervisors for each individual, and the length of successful employment was assessed. Intercorrelations among measures and across raters provided initial support for the validity and reliability of the problem behavior list. Implications for future researching and training on interpersonal-vocational skills are discussed.

Aggression↗

Increased glutathione-S-transferase activity in antioxidant-deficient rats.

Rats fed a diet deficient in vitamin E and selenium show an increased activity of glutathione-S-transferase (EC 2.5.1.18) in all tissues tested, with the possible exception of the retina. Glutathione-S-transferases are detoxifying enzymes that are induced by a variety of electrophilic drugs or toxins. Therefore, the induction of glutathione-S-transferase in vitamine E- and selenium-deficient rats indicates that substrates for the enzyme probably increase in vivo with dietary antioxidant deficiency. These substrates are likely to be lipid peroxides and/or other lipid peroxidation products.

Animals↗

Effects of vitamin E and selenium deficiency on the fatty acid composition of rat retinal tissues.

The fatty acid composition of retinal tissues was measured in rats maintained for 26--32 weeks on each of the following diets: a purified basal diet deficient in alpha-tocopherol and selenium, an identical control diet supplemented with alpha-tocopherol and selenium, and a commerical laboratory rat chow. Dietary deficiencies of antioxidant nutrients were found to cause a large decrease in total polyunsaturated fatty acids in the retinal pigment epithelium, a small decrease in the retinal rod outer segments, but no change in the whole retina or liver when compared to tissues from animals fed the vitamin E- and selenium-supplemented control diet. The polyunsaturated fatty acid content which we have observed for the retinal pigment epithelium from rats fed commerical lab chow is similar to that which we observed for bovine retinal pigment epithelium. Our results indicate that changes in fatty acid composition are not generalized to all tissues in severely antioxidant-deficient animals, but that changes do occur in some tissues, such as the retinal pigment epithelium, which appears to be particularly sensitive to in vivo lipid peroxidation.

Animals↗

Can regular solution theory be applied to lipid bilayer membranes?

Direct measurement of the partition coefficient of n-hexane into phosphatidylcholine and phosphatidylcholine-cholesterol bilayers showed that (a) isotropic liquids are not good models for lipid bilayers and (b), Regular Solution Theory cannot, in general, be applied to lipid bilayer membranes at temperatures above their phase transition. Theoretical and experimental evidence given.

Cholesterol↗

Binding of iodomercurates to sulfhydryl-blocked beta-lactoglobulin-A, -B, and -C.

Sulfhydryl-blocked beta-lactoglobulins (beta-LG-S-SCH2CH2OH)-A, -B, and -C bind only one iodomercurate species, HgI3-, at only one site, with a dissociation constant of 4.0 X 10(-5) M at 25 degrees, pH 5.0, 0.10 ionic strength. (Binding to native beta-LG-SH-A, -B, and -C is more complex, involving the sulfhydryl and two other sites and several iodomercurates.) The red shift of the HgI3- spectrum on binding would ordinarily suggest a hydrophobic site, but the HgI3- site is distinct from, and independent of, the alkane-binding site of native and blocked beta-LG; HgI3- may bind a group that shifts its trigonal planar structure toward the tetrahedron of HgI4(2-). Binding of HgI3- to blocked beta-LG interferes with the well-known association of beta-LG-A to octamers at pH 4.6 and low temperature. The relation of the HgI3- site to the crystallographic iodomercurate-binding sites of beta-LG-SH is examined. To facilitate these and future studies of iodomercurate binding, the 200-400 nm spectra of HgI2, HgI3-, and HgI4(2-) in aqueous solutions and the thermodynamic formation constants at 25 degrees for the equilibria HgI2 + I- = HgI3- (4.9 X 10(3) M-1) and HgI3- + I- = HgI4(2-) (0.118 X 10(3) M-1) were obtained.

Animals↗

Fluorescent pigment accumulation in retinal pigment epithelium of antioxidant-deficient rats.

A yellow autofluorescent pigment, generally thought to be indicative of membrane autoxidation, was found to accumulate in the retinal pigment epithelium (RPE) of rats maintained for 32 weeks on diets producing physiological antioxidant deficiency. The largest build-up of fluorescent pigment occurred in rats fed a diet high in polyunsaturated fatty acids (PUFAs) and deficient in alpha-tocopherol (vitamin E), selenium, sulfur-containing amino acids, and chromium. These latter four nutrients have all been implicated in maintaining the antioxidant status of tissues, whereas PUFAs are pro-oxidants. Dietary supplementation with methionine and chromium significantly reduced the amount of fluorescent pigment accumulated in the RPE. Supplementation with all four nutrients further reduced the amount of fluorescent pigment to a very low level. Rats maintained on a normal laboratory diet, relatively low in PUFAs and presumably adequate in other nutrients, accumulated relatively small amounts of fluorescent pigment in the RPE. Of all tissues in the retina and choroid, the autofluorescent pigment was found to be almost entirely restricted to the RPE. The autofluorescence produced in the RPE by antioxidant deficiency was more concentrated than that produced in the testes, kidney, intestine, and heart. This suggests that the RPE is particularly sensitive to physiological antioxidant deficiencies. The increased fluorescent pigment build-up in the RPE of antioxidant-deficient rats appears to correlate with a decreased RPE melanin content. Similar changes in pigmentation have been reported to occur in human RPE with age and in dominantly inherited retinitis pigmentosa. Thus, with respect to its effect on RPE pigmentation, antioxidant deficiency appears to mimic aging and possibly some aspects of one type of retinitis pigmentosa.

Amino Acids, Sulfur↗

Interaction of L-alpha-didecanoyl phosphatidylcholine with the AI polypeptide of high density lipoprotein.

Cooperative interaction of L-alpha-didecanoyl phosphatidylcholine with the AI polypeptide from human serum high density lipoprotein results in a complex particle containing 2 molecules of AI and 190 molecules of the lipid. Binding occurs two orders of magnitude above the critical micelle concentration of the lipid and requires the simultaneous presence of low levels of single-chain amphiphiles. The present investigation and previous studies from this laboratory suggest that AI contains "pockets" capable of interacting with a fixed hydrophobic volume and that amphiphilic head groups do not affect the binding capacity.

Apolipoproteins↗

The self-association of the apo-Gln-I and apo-Gln-II polypeptides of human high density serum lipoproteins.

The major polypeptide components of human high density lipoprotein, apo-Gln-I and apo-Gln-II, self-associate at pH 8.3 and ionic strength 0.045. The dimeric (MW = 56,800) association constant for apo-Gln-I is 1.3 X 10(4)liters/mol. apo-Gln-II is tetrameric at all experimentally accessible concentrations. Self-association of apo-Gln-I is accompanied by minor conformational alterations distinct from that induced by saturating levels of bound amphiphilic ligands. These results are discussed with respect to the design of reconstitution experiments between the apoproteins and lipids.

Apoproteins↗