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Biomedical subjects

S Wallick

Publications and source records attributed to S Wallick.

5 recordsLinked to original sources

Differential effect of National Cholesterol Education Program (NCEP) Step II diet on HDL cholesterol, its subfractions, and apoprotein A-I levels in hypercholesterolemic women and men after 1 year: the beFIT Study.

We previously reported that high density lipoprotein cholesterol (HDL-C) decreases more in hypercholesterolemic (HC) women than in HC men ingesting an National Cholesterol Education Program (NCEP) Step II diet for 6 months. We examined these subjects to determine whether the differential HDL-C reduction persists after 12 months and whether it is associated with decreased HDL(2)-C and apoprotein A-I. Subjects were screened from an industrial workforce and were defined as HC if 2 low density lipoprotein cholesterol measurements were >/=75th percentile or defined as combined hyperlipidemic (CHL) if triglycerides were also >/=75th percentile. The subjects were then taught the NCEP Step II diet in 8 weekly classes and counseled quarterly. Seventy-three HC and 92 CHL women (mean ages 43 and 44 years, respectively) and 112 HC and 106 CHL men (ages 45 and 41 years, respectively) were studied. All groups reported similar total fat (24% to 26% kcal) and saturated fat (7.1% to 7.9% kcal) intakes at 1 year. HDL-C decreased 7.6% in HC women (P<0.01), exceeding the nonsignificant 1.3% decrease in HC men (P=0.000). HDL(2)-C decreased 16.7% in HC women (P<0.01) compared with the nonsignificant 0.5% increase in HC men (P=0.000). In CHL women and men, HDL-C decreased 3.5% and 3.9% (both P<0.01); HDL(2)-C decreased more in women (7.1%, P<0.01) than in men (4.3%, a nonsignificant difference). Apoprotein A-I decreased significantly (5.3%, P<0.01) in HC women only. Plasma triglycerides were unchanged. Low density lipoprotein cholesterol and weight changes were not different among the 4 groups. HDL-C, HDL(2)-C, and apoprotein A-I levels decreased more in HC women than in HC men after following the NCEP Step II diet for 1 year, continuing a trend observed with HDL-C at 6 months. The total HDL-C and HDL(2)-C reductions narrow the baseline differences between men and women by 50%. Whether this reduction impacts women's protection from cardiovascular disease deserves future study. Nonetheless, the results point to sex-based differences in intrahepatic glucose and fatty acid metabolism linked to alterations in HDL formation and removal.

Adult↗

Iron and zinc status of women and men who followed cholesterol-lowering diets.

OBJECTIVE: To determine if men and women taught the National Cholesterol Education Program step 2 diet experienced diminished iron or zinc status after 2 years of consuming the diet. DESIGN: Subjects attended 8 weeks of diet classes and followup counseling. Four-day food records, zinc protoporphyrin/ heme (ZPP/H, a measure of iron stores), hematocrit, and plasma zinc values were collected at baseline, 1 year, and 2 years. SUBJECTS: Participants in a study of the efficacy of the step 2 diet (213 men and 151 women) who had low-density lipoprotein cholesterol levels above the 75th percentile, and who were not taking lipid-altering medication. STATISTICAL ANALYSES: Paired t tests to compare preintervention and postintervention test results. Two-sample t tests to compare gender, menopause status, and hormone-use groups. Analysis of variance was performed to compare plasma zinc levels among diet-adherence subgroups. Individual evaluation of outlying values and backward stepwise regression to determine the independent effects of variables were also completed. RESULTS: Mean dietary intake approached or exceeded step 2 guidelines. Density of iron intake increased. Density of zinc intake was unchanged, but mean intake was low. Mean ZPP/H and hematocrit did not change for premenopausal or postmenopausal women with or without supplemental hormones; men's values changed only slightly. Abnormal ZPP/H and hematocrit occurred sporadically. Mean plasma zinc levels did not differ from baseline for women, increased slightly for men, and did not differ by level of dietary adherence. No plasma zinc concentrations were below normal. APPLICATION: In this large-scale, 2-year prospective study of women and men, no adverse effects on intake or plasma indicators of iron and zinc were detected as a result of subjects being taught the NCEP step 2 diet.

Adult↗

TGF-beta: a possible autocrine immune regulator.

TGF-beta is a potent regulator of immune functions both in vitro and in vivo. The majority of studies have examined changes in immune functions after the addition of TGF-beta that had been previously activated by acid treatment. Peripheral blood mononuclear cells (PBMC) and tumour cells can each produce latent TGF-beta. The role of endogenously produced latent TGF-beta as an autocrine or paracrine regulator of immune functions has not been extensively studied. Monoclonal antibody (mAb) 4A11 was used to detect and neutralize the activity of endogenous TGF-beta 1 produced during lymphocyte activation. We demonstrate that PBMC, after stimulation with interleukin 2 or phytohaemagglutinin-P/12-O-tetradecanoylphorbol 13-acetate, secrete significant quantities of latent TGF-beta 1. Addition of neutralizing mAbs specific for TGF-beta 1 enhances the proliferative response of the PBMC. CHO cell lines engineered to produce latent TGF-beta 1 were poor stimulators of cytotoxic T lymphocyte generation in vitro and significantly suppress natural killer cell activity in nu/nu mice. We conclude that mechanisms exist in vitro and in vivo to convert latent TGF-beta into an active form which can then regulate immune functions in an autocrine/paracrine manner. The possible role of latent TGF-beta produced by tumour cells in immune surveillance is discussed.

Animals↗

Genetically engineered antibody molecules and their application.

Immunoglobulin genes can be efficiently expressed following transfection into myeloma cells. Using protoplast fusion, transfection frequencies greater than 10(-3) can be achieved. Compatible plasmids containing two different selectible markers are used to simultaneously deliver heavy and light chain genes to the same cell. To produce molecules with differing specificities the rearranged and expressed variable regions can be cloned from the appropriate hybridoma. In some cases, variable regions from cDNAs can be inserted into the expression vectors. It is possible to manipulate the immunoglobulin genes and produce novel antibody molecules. Antibodies have been produced in which the variable regions from mouse antibodies have been joined to human constant regions. In addition, antibodies with altered constant regions have been produced. These genetically engineered antibodies provide a unique set of reagents to study structure-function relationships within the molecule. They also can potentially be used in the diagnosis and therapy of human disease.

Animals↗

Resistance to Streptococcus pneumoniae is induced by a phosphocholine-protein conjugate.

Previous studies demonstrated that naturally occurring antibodies to the pneumococcal cell wall hapten phosphocholine (PC) are important for the survival of mice against infection with Streptococcus pneumoniae, and that passively administered hybridoma antibody to PC results in added resistance. To determine if a PC-protein conjugate could elicit protective levels of anti-PC antibody, mice were immunized with PC-keyhole limpet hemocyanin (KLH) and tested for their ability to resist challenge with virulent S. pneumoniae. PC-KLH-immunized mice were observed to be resistant to 10- to 1000-fold more organisms than unimmunized control animals. The levels of protection were comparable to those induced with capsular polysaccharide antigens, but had the advantage of not being type-specific; immunization with PC-KLH protected mice against both type 1 and type 3 organisms. The induced immunity appeared to be antibody-mediated; it could be passively transferred with immune serum, and absorption of the immune serum with PC-Sepharose removed its protective capacity. Anti-PC antibodies in the serum of immunized mice were primarily IgM and IgG3 and possessed predominantly the T15 idiotype. Antibodies with these particular isotypes and this idiotype also arise after immunization with heat-killed rough pneumococci and recently were shown to be important in the resistance of mice to pneumococcal infection.

Animals↗