Biomedical subjects

S E Gabriel

Publications and source records attributed to S E Gabriel.

111 records · Page 7Linked to original sources

PubMed1987

Calcium transport affinity, ion competition and cholera toxin effects on cytosolic Ca concentration.

The physiological relevance of an apparent ionophore activity of cholera toxin towards Ca2+ has been examined in several different systems designed to measure affinity, specificity, rates of ion transfer, and effects on intracellular ion concentrations. Half-maximal transfer rates across porcine jejunal brush-border vesicles were obtained at a concentration of 0.20 microM Ca2+. When examined in the presence of competing ions the transfer process was blocked by very low concentrations of La3+ or Cd2+, Sr2+, Ba2+ and Mg2+ were relatively inefficient competitors for Ca2+ transport mediated by cholera toxin. The relative affinities observed would be compatible with a selectivity for Ca2+ transfer at physiological ion concentrations, as well as an inhibition of this ionophore activity by recognized antagonists of cholera toxin such as lanthanum ions. Entry rates of Ca2+ into brush-border vesicles exposed to cholera toxin were large enough to accelerate the collapse of a Ca2+ gradient generated by endogenous Ca, Mg-ATPase activity. The treatment of isolated jejunal enterocytes with cholera toxin caused a significant elevation in cytosolic Ca2+ concentrations as measured by Quin-2 fluorescence. This effect was specifically prevented by prior exposure of the cholera toxin to excess ganglioside GM1. We conclude that cholera toxin has many of the properties required for promoting transmembranes Ca2+ movement in membrane vesicles and appears to be an effective Ca2+ ionophore in isolated mammalian cells.

Animals↗

PubMed1986

Vasculitis in hairy cell leukemia: review of literature and consideration of possible pathogenic mechanisms.

Systemic vasculitis is an unusual but recently recognized complication of hairy cell leukemia. We studied this relationship further in an attempt to better understand pathogenetic mechanisms of vasculitis. We examined the records of 129 cases of hairy cell leukemia seen at the Mayo Clinic between 1976 and 1983, and identified 2 cases with evidence of systemic vasculitis. The first of these cases is discussed in detail. Immunologic studies were performed but we were unable to demonstrate the presence of shared antigen on hairy cells and endothelial cells. The literature is reviewed and reports of this association are summarized. Possible mechanisms of vascular injury are discussed.

Adult↗

PubMedDate not supplied

Health-related quality of life in economic evaluations for osteoporosis: whose values should we use?

OBJECTIVE: To determine whether the source of preference scores has an impact on the cost-effectiveness of osteoporosis interventions. METHODS: Three groups of subjects aged > or =50 years--199 women without fractures and 183 women with osteoporotic fractures-were studied at two major medical centers. Medical history and comorbidity data were obtained from review of medical records. Health status was measured using the Medical Outcomes Study SF-36. Two preference-classification systems (i.e., quality of well-being scores estimated from SF-36 subscales and the Health Utilities Index) were also used. Preferences for current health and for hypothetical health states were assessed using a time tradeoff and implemented with a computer-based utility instrument (U-Titer). Wilcoxon's rank-sum and signed-rank tests were used to compare preferences for current health among women with osteoporotic fractures with 1) directly assessed preferences for osteoporosis health states delineated by outcome descriptions and 2) preference scores obtained from the preference-classification systems. The potential impact of the source of the preference scores was estimated using a Markov state-transition model. RESULTS: The preference scores for hypothetical osteoporosis health states of the non-fracture subjects were approximately 50% lower than those of the women who had actually experienced the health state. Differences of this magnitude would change the estimated cost-effectiveness of a 15-year intervention (which for approximately $280 per year prevents hip fracture about as well as hormone-replacement therapy) from $25,000 per QALY gained when non-fracture subjects' preferences were used to $94,000 per QALY gained when fracture subjects' preferences were used. Preferences estimated using the Health Utilities Index and those directly measured in fracture subjects using the time tradeoff did not differ significantly. CONCLUSIONS: The Health Utilities Index preference-classification system may provide an efficient and inexpensive alternative to direct utility assessment in this patient group. However, there are important differences in the valuation of health states by women who have experienced osteoporotic fractures compared with women who have not. Cost-utility analyses based solely on fracture patients' preferences for osteoporotic health states may undervalue prevention.

Aged↗