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G F Combs

Publications and source records attributed to G F Combs.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cellular glutathione peroxidase is the mediator of body selenium to protect against paraquat lethality in transgenic mice.

The antioxidative role of Se-dependent cellular glutathione peroxidase (EC 1.11.1.9, GPX1) in vivo has not been established. Our objective was to determine the effects of GPX1 knockout or overexpression on the susceptibility of mice to paraquat toxicity and the contributions of GPX1, compared with other selenoproteins and vitamin E, to body defenses against such acute oxidative stress. Four experiments were conducted using 111 GPX1 knockout or overexpressing mice and the respective controls. Mice were fed diets supplemented with Se (as sodium selenite) at 0-0.4 mg/kg and/or all-rac-alpha-tocopheryl acetate at 0-75 mg/kg before intraperitoneal injections of 12.5, 50 or 125 mg paraquat/kg body weight. All mice that received 50 or 125 mg paraquat/kg died spontaneously, and the survival time of mice was (independent of dietary levels of Se per se or alpha-tocopheryl acetate) solely a function of tissue GPX1 activity (P < 0.001). Severe acute pulmonary interstitial necrosis was found only in the GPX1 overexpressing mice and the controls that had extended survival time. Thiobarbituric acid reacting substances in postmortem liver inversely correlated with the tissue GPX1 activity and dietary levels of Se and/or alpha-tocopheryl acetate. In contrast, all mice that received 12.5 mg paraquat/kg survived and were killed 2 wk after the injection for tissue collection. Compared with the saline injection, this low dose of paraquat resulted in greater (P < 0.001) liver and lung F2-isoprostanes in both the GPX1 knockout mice and the controls. However, there was no difference in plasma alanine transaminase (EC 2.6.1.2) activity or overt injuries in liver, lung and kidney in either group. Our data indicate that GPX1 is the major, if not the only, metabolic form of body Se that protects mice against the lethal oxidative stress caused by high levels of paraquat; it seems less important, however, in protecting mice against the moderate oxidative stress by the low level of paraquat.

Animals↗
PubMed1998

Emerging relationships of vitamins and cancer risks.

Evidence is emerging that at least some vitamins may play a role in reducing cancer risks. Over the past year, the best evidence for such effects has been presented for vitamins A, D and E; less consistent evidence has been presented for vitamin C. Although there are still many inconsistencies in our understanding of the anti-cancer roles and mechanisms of these vitamins, it is possible that they may account for at least some of the apparently cancer-protective effects associated with certain dietary patterns.

Animals↗
PubMed1997

Reduction of cancer mortality and incidence by selenium supplementation.

PATIENTS AND METHOD: In order to test the hypothesis that a dietary supplement of selenium (Se) may reduce cancer risk, 1312 patients with histories of basa/squamous cell carcinomas of the skin were assigned in random, double-blind fashion to daily oral supplements of either Se-enriched yeast (200 micrograms Se/day), or a low-Se yeast placebo. Patients were recruited in 1983 to 1990 and were followed with regular dermatologic examinations through, 1993 for a total of 8269 person-years of observation. Skin cancer diagnoses were confirmed histologically and plasma Se concentration was determined at 6 to 12 months intervals. All deaths and patient-reported illnesses were confirmed and documented by consultation with the patient medical care providers. RESULTS: Results showed that Se-supplementation did not significantly affect the incidences of recurrent basal/squamous cell carcinomas of the skin. However, Se-treatment was associated with reductions in total cancer mortality and in the incidences of lung, colorectal, prostate and total cancers. These effects were consistent over time and between study clinics. CONCLUSION: The results strongly suggest benefits of Se-supplementation for this cohort of patients and support the hypothesis that supplemental Se can reduce risks to at least some types of cancer.

Aged↗
PubMed1997

Effects of dietary selenium and vitamin E concentrations on phospholipid hydroperoxide glutathione peroxidase expression in reproductive tissues of pubertal maturing male rats.

Phospholipid hydroperoxide glutathione peroxidase (PHGPX) is the second intracellular selenium (Se)-dependent glutathione peroxidase (GSH-Px) identified in mammals. Our objectives were to determine the effect of dietary vitamin E and Se levels on PHGPX activity expression in testis, epididymis, and seminal vesicles of pubertal maturing rats, and the relationship of PHGPX expression with testicular development and sperm quality. Forty Sprague-Dawley male weanling rats (21-d old), were initially fed for 3 wk a torula yeast basal diet (containing 0.05 mg Se/kg) supplemented with marginal levels of Se (0.1 mg/kg as Na2SeO3) and vitamin E (25 IU/kg as all-rac-alpha-tocopheryl acetate). Then, rats were fed the basal diets supplemented with 0 or 0.2 mg Se/kg and 0 or 100 IU vitamin E/kg diet during the 3-wk period of pubertal maturing. Compared with the Se-supplemented rats, those fed the Se-deficient diets retained 31, 88, 67, and 50% of Se-dependent GSH-Px activities in liver, testis, epididymis, and seminal vesicles, respectively. Testes and seminal vesicles had substantially higher (5- to 20-fold) PHGPX activity than liver. Dietary Se deficiency did not affect PHGPX activities in the reproductive tissues, but reduced PHGPX activity in liver by 28% (P < 0.0001). Dietary vitamin E supplementation did not affect PHGPX activity in liver, whereas it raised PHGPX activity in seminal vesicles by 43% (P < 0.005). Neither dietary vitamin E nor Se levels affected body weight gains, reproductive organ weights, or sperm counts and morphology. In conclusion, expression of PHGPX activity in testis and seminal vesicles was high and regulated by dietary Se and vitamin E differently from that in liver.

Animals↗
PubMed1997

Studies on the effects of selenium on rumen microbial fermentation in vitro.

The effects of selenium (Se) on ruminant microbial fermentation were investigated in vitro using rumen microflora collected from a rumen-fistulated dairy cow. First, the effects of L-selenomethionine (SeMet; at 0.2 or 2 ppm Se) in the presence or absence of wheat bran (WB, 500 mg per incubation flask) were evaluated. Second, the effects of several forms of Se (elemental Se: 50 ppm Se; sodium selenite: 2 ppm Se; SeMet: 2 ppm Se) were compared. Results showed that the amounts of short-chain fatty acids (SCFAs) tended to be increased by SeMet treatment, whereas SeMet in the presence of WB transiently suppressed fermentation. The addition of SeMet tended to increase the production of acetate while reducing the production of butyrate with the without WB supplementation. Among the different Se compounds tested, the amounts of SCFAs were greater with SeMet treatment, which yielded a higher proportion of acetate compared to other treatments. Selenite did not influence the total SCFAs concentrations; however, it increased the relative proportion of butyrate at the expense of acetate. Elemental Se did not significantly affect fermentation. Higher bacterial Se concentrations were observed for selenite than for SeMet. It was concluded that Se supplementation can influence rumen microbial fermentation and that Se compounds differ in this regard.

Acetic Acid↗
PubMed1997

Effects of selenium on colonic fermentation in the rat.

Studies were conducted to determine the effects of dietary selenium (Se) on the hindgut microbial activity in rats. Selenium was fed as L-selenomethionine (SeMet) at either 0 or 2 ppm Se in the presence or absence of wheat bran (WB, 10%), a known substrate for the enteric microflora. Wheat bran feeding caused the greatest fermentation, measured by the production of short-chain fatty acids (SCFAs) along the entire intestinal tract and feces; however, its effects were suppressed by SeMet in the proximal large bowel, cecum, and colon. Selenium significantly enhanced fermentation in the colon and rectum, but not in the cecum or feces. Selenium was found in association with the bacterial cell fractions of gut contents and feces: 40-46% of the total Se was associated with colonic microbes and 58% in fecal microbes. Increased acetate and reduced butyrate production were driven by the addition of Se regardless of whether WB was fed.

Animals↗
PubMed1997

Overexpression of cellular glutathione peroxidase does not affect expression of plasma glutathione peroxidase or phospholipid hydroperoxide glutathione peroxidase in mice offered diets adequate or deficient in selenium.

Selenium-dependent cellular glutathione peroxidase (GPX1) overexpressing [GPX1(+)] mice were derived by microinjecting a 5.3-kb cloned entire mouse GPX1 genomic DNA into fertilized eggs. The objective of this study was to determine the effect of GPX1 overexpression and dietary selenium on the expression of selenoperoxidases and the status of lipid peroxidation of these transgenic animals. An experiment with a 2 x 2 factorial arrangement of treatments with 15 GPX1(+) and 15 control mice (2 mo old) was conducted for 8 wk. Ten mice of each group (half males and females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) and five mice (three males and two females) were fed the basal diet supplemented with 0.51 mg Se/kg as Na2SeO3. The GPX1(+) mice had greater GPX1 activities (one- to sixfold, P < 0.0001) than the control mice at both levels of dietary selenium in all tissues except for liver, in which such difference (100%, P < 0.05) was observed only in Se-deficient mice. The GPX1 mRNA level in kidney and in lung of the Se-deficient GPX1(+) mice was 81% and 7.5-fold greater (P < 0.003) than the respective control level. Overexpression of GPX1 did not alter phospholipid hydroperoxide glutathione peroxidase (GPX4) activities and mRNA levels or glutathione S-transferase (GST) activities in most of the tissues, plasma glutathione peroxidase (GPX3) activity or plasma Se concentrations. No differences in lipid peroxidation in kidney, lung or intestine were observed between the Se-deficient GPX1(+) and control mice. In conclusion, the overexpression of the GPX1 gene in these mice was tissue specific and did not affect the expression of GPX3, GPX4 or GST and plasma Se levels; dietary Se appeared to affect the GPX1 overexpression at its mRNA level.

Animals↗
PubMed1997

Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues.

Selenium-dependent cellular glutathione peroxidase (GPX1) knockout [GPX1(-)] mice were derived from 129/SVJ x C57BL/6 hybrid mice by microinjecting C57BL/6 blastocysts with recombinant embryonic stem cells carrying a target mutation in the GPX1 gene. Experiment 1 was conducted to determine the effects of the GPX1 knockout on the susceptibility of mice to dietary vitamin E and Se deficiency and on the expression of the Se-dependent plasma glutathione peroxidase (GPX3) and phospholipid hydroperoxide glutathione peroxidase (GPX4), and the Se-independent glutathione S-transferase (GST). Eleven GPX1(-) and 11 control mice (5 wk old, six males and five females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) or the basal diet supplemented with 0.5 mg Se/kg (as Na2SeO3) for 13 wk. Experiment 2 was conducted to determine the effect of the GPX1 knockout on the total Se concentration in the liver of Se-adequate mice. Six GPX1(-) and four control mice (5 wk old, half males and females) were fed the basal diet supplemented with 0.2 mg Se/kg and 15 mg of all-rac-alpha-tocopheryl acetate/kg for 5 wk. There was no difference in body weight gain or apparent susceptibility to dietary vitamin E and Se deficiency between the GPX1(-) and control mice. Knockout of GPX1 resulted in almost complete abolishment of GPX1 activity in various tissues, but had no effect on the GPX3 or GPX4 mRNA level and activity or the GST activity in several tissues at either level of dietary Se. The liver total Se concentration in the Se-adequate GPX1(-) mice was only 42% of that in the controls (P < 0. 0001). These results indicate that GPX1 is expressed independently of GPX3 or GPX4 and represents approximately 60% of the total hepatic Se in Se-adequate mice.

Animals↗
PubMed1997

Reduction of cancer risk with an oral supplement of selenium.

The hypothesis that a dietary supplement of selenium (Se) may reduce cancer risk was tested experimentally in humans. Patients with histories of basal/squamous cell carcinomas of the skin were assigned randomly in double-blind fashion to daily oral supplements of either Se-enriched yeast (200 micrograms Se/day), or a low-Se yeast placebo. A total of 1312 patients recruited in 1983-1990 were followed with regular dermatologic examinations through 1993 for a total of 8269 person-years of observation. Skin cancer diagnoses were confirmed histologically. Plasma Se concentration was determined at 6-12 months intervals. All deaths and patient-reported illnesses were recorded; reported cancers were confirmed and documented by consultation with the patient medical care providers. The results indicate that Se did not significantly affect the primary endpoints: incidences of recurrent basal/squamous cell carcinomas of the skin. However, Se-treatment was associated with reductions in several secondary endpoints: total mortality, mortality from all cancers combined, as well as the incidence of all cancers combined, lung cancer, colorectal cancer and prostate cancer. The consistencies of these associations over time, between study clinics and for the leading cancer sites strongly suggests benefits of Se-supplementation for this cohort of patients, supporting the hypothesis that supplemental Se can reduce cancer risk. Although Se did not shown protective effects against non-melanoma skin cancers, the suggested reductions in risks to other frequent cancers demand further evaluation in well controlled clinical intervention trials.

Basal Cell Carcinoma↗
PubMed1997

Food systems for improved health: linking agricultural production and human nutrition.

OBJECTIVES: Link traditional agricultural production disciplines to the food sciences and the various disciplines concerned with human nutrition and health in order to find sustainable solutions to malnutrition. DESIGN: Develop a new integrated program area within a university by forging explicit linkages within a wide array of disciplines concerned with food systems and human health. SETTING: The College of Agriculture and Life Sciences, the College of Human Ecology, the Division of Nutrition, and the Cornell International Institute for Food, Agriculture, and Development at Cornell University, Ithaca, New York, USA. INTERVENTIONS: Use food-based, system approaches to meet human nutrition goals. Current focus is on the provision of micronutrients (especially iron, vitamin A and iodine) for people globally. RESULTS: A new program area 'Food Systems for Health' has been developed at Cornell University. The program fosters effective interdisciplinary research, teaching and extension activities directed towards sustainable improvements in human nutrition and health. CONCLUSIONS: The old paradigms of agriculture, human nutrition, and public health must be shifted from current linear approaches to integrated and interactive approaches if effective long-term, food-based solutions to micronutrient malnutrition are to be found.

Agriculture↗
PubMed1996

Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.

OBJECTIVE: To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. DESIGN: A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. SETTING: Seven dermatology clinics in the eastern United States. PATIENTS: A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. INTERVENTIONS: Oral administration of 200 microg of selenium per day or placebo. MAIN OUTCOME MEASURES: The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. RESULTS: After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. CONCLUSIONS: Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made

Adult↗
PubMed1996

Bioavailability of selenium accumulated by selenite-reducing bacteria.

The bioavailability of selenium (Se) was determined in bacterial strains that reduce selenite to red elemental Se (SeO). A laboratory strain of Bacillus subtilis and a bacterial rod isolated from soil in the vicinity of the Kesterson Reservoir, San Joaquin Valley, CA, (Microbacterium arborescens) were cultured in the presence of 1 mM sodium selenite (Na2SeO3). After harvest, the washed, lyophilized B. Subtilis and M. arborescens samples contained 2.62 and 4.23% total Se, respectively, which was shown to consist, within error, entirely of SeO. These preparations were fed to chicks as supplements to a low-Se, vitamin E-free diet. Three experiments showed that the Se in both bacteria had bioavailabilities of approx 2% that of selenite. A fourth experiment revealed that gray SeO had a bioavailability of 2% of selenite, but that the bioavailability of red SeO depended on the way it was prepared (by reduction of selenite). When glutathione was the reductant, bioavailability resembled that of gray SeO and bacterial Se; when ascorbate was the reductant, bioavailability was twice that level (3-4%). These findings suggest that aerobic bacteria such as B. subtilis and M. arborescens may be useful for the bioremediation of Se-contaminated sites, i.e., by converting selenite to a form of Se with very low bioavailability.

Animals↗
PubMed1996

Should intakes with beneficial actions, often requiring supplementation, be considered for RDAs?

The conceptual framework upon which the Recommended Dietary Allowance (RDA) was derived is being replaced by a new, less population-based and more individualistic view of nutrition that relates to health more broadly than merely the prevention of overt nutrient deficiency disease. As this has occurred, problems have become apparent concerning the RDA, which constitutes the key linkage between nutrition understanding and dietary guidance, calling for its redefinition. Any reconstruction of the RDA must be based on the paradigm for nutrition that has, in fact, been adopted; this will require, where evidence warrants, the incorporation into the new construct of intakes with beneficial actions without regard for whether this may require supplementation in the context of contemporary diets.

Deficiency Diseases↗
PubMed1994

Celebration of the past: nutrition at USDA.

The knowledge gained in the past 100 years about how nutrients in our foods can affect our health represents a great achievement. This knowledge was essential for the widespread improvements in human health, and the major advances in food production and economic development. USDA and State Experiment Stations were the first scientific organizations in the U.S. to establish a food and nutrition research program and make the results available to people. Human nutrition activities in USDA, initiated by W. O. Atwater in 1894, always have been linked with the nutritive value of foods, human nutritional requirements, the kinds and amounts of foods that Americans consume relative to their needs, and strategies for improving diets and the food supply. Despite recent progress, the science of nutrition is still relatively new, and our knowledge is far from complete. Application of new technologies can be expected to identify the basis for individual differences in nutritional requirements, describe nutrient interactions and define those food constituents needed for healthful diets. Consumers must be given sound research-based information about foods and nutrition, as demand in the market place ultimately determines the foods agriculture and industry produce.

Diet↗
PubMed1994

Effect of dietary vitamin E and selenium deficiency on chicken splenocyte proliferation and cell surface marker expression.

Beginning at hatching, chicks were fed a Basal diet, without vitamin E or selenium (Se) or the same diet supplemented with vitamin E (100 IU/kg) and Se (0.2 ppm). The effect of these treatments on the expression of cell surface markers (CT-1a, CD3, CD4, CD8, sIgs, and Ia) defining specific thymocyte and peripheral blood leukocyte (PBL) subpopulations were examined using flow cytometric analyses. In parallel studies the effect of the dietary deficiencies on splenocyte proliferative responses to ConA or PHA stimulation was examined. The mean expression of CD3 and CT-1a per cell was increased while CD8 and CD4 expression was decreased on thymocytes from chicks fed the Basal diet. The proportion of double negative (CD4-, CD8-) thymocytes and single positive CD8+ thymocytes was significantly decreased while single positive CD4+ and double positive (CD4+, CD8+) thymocytes were significantly increased by the dietary vitamin E and Se deficiencies. The dietary deficiencies resulted in a decreased proportion of peripheral T cells and specifically decreased the number of CD4+ PBL. The proliferative response to both ConA and PHA was impaired by the vitamin E and Se dietary deficiencies. The proliferative response could be fully reconstituted but only after vitamin E and Se supplementation for periods longer than 1 week. Plasma SeGSHpx and alpha-tocopherol levels paralleled the mitogen responsiveness observed. These results support the conclusion that vitamin E and Se deficiencies may affect both the maturation of specific lymphocyte subpopulations and the functional and proliferative capabilities of the peripheral lymphocytes.

Animals↗