Mouse NK cell-mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing

Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49(+) subsets in BMC rejection by using β2-microglobulin deficient (β2m(-/-)) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind "self-MHC" were found to be the dominant subset responsible for β2m(-/-) BMC rejection. This provides in vivo evidence for host MHC class I-dependent functional education. Interestingly, all H2(d) strain mice regardless of background were able to resist significantly greater amounts of β2m(-/-), but not wild-type BMC than H2(b) mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability.     

Metabolic syndrome in Spain: prevalence and coronary risk associated with harmonized definition and WHO proposal. DARIOS study

Introduction and objectives

To update the prevalence of metabolic syndrome and associated coronary risk in Spain, using the harmonized definition and the new World Health Organization proposal (metabolic premorbid syndrome), which excludes diabetes mellitus and cardiovascular disease.

Methods

Individual data pooled analysis study of 24 670 individuals from 10 autonomous communities aged 35 to 74 years. Coronary risk was estimated using the REGICOR function.

Results

Prevalence of metabolic syndrome was 31% (women 29% [95% confidence interval, 25%-33%], men 32% [95% confidence interval, 29%-35%]). High blood glucose (P=.019) and triglycerides (P<.001) were more frequent in men with metabolic syndrome, but abdominal obesity (P<.001) and low high-density lipoprotein cholesterol (P=.001) predominated in women. Individuals with metabolic syndrome showed moderate coronary risk (8% men, 5% women), although values were higher (P<.001) than in the population without the syndrome (4% men, 2% women). Women and men with metabolic syndrome had 2.5 and 2 times higher levels of coronary risk, respectively (P<.001). Prevalence of metabolic premorbid syndrome was 24% and the increase in coronary risk was also proportionately larger in women than in men (2 vs 1.5, respectively; P<.001).

Conclusions

Prevalence of metabolic syndrome is 31%; metabolic premorbid syndrome lowers this prevalence to 24% and delimits the population for primary prevention. The increase in coronary risk is proportionally larger in women, in both metabolic syndrome and metabolic premorbid syndrome.Full English text available from:www.revespcardiol.org     

Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case-control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.     

Quality of Life in Functional Dyspepsia

Our purpose was to assess the quality of life of functional dyspepsia patients using the SF-36 generic scale and the Gastrointestinal Symptoms Rating Scale (GSRS). In all, 328 dyspeptic patients were included in a multicenter, prospective, observational study. Both scales were filled out at baseline and one and three months after a prokinetic agent was given as a single-drug therapy. A total of 250 patients completed the study. An improvement in all SF-36 dimensions was observed, although the final scores were lower than the population reference values. Physical role (27% change), emotional role (20%), and physical pain (16%) dimensions showed the greater change. The GSRS total and domain scores also showed significant decreases. The best predictors of quality of life improvement were certain basal symptoms, drug compliance, and the absence of idiopathic dyspepsia. In conclusion, both the generic and the specific scales provide useful and sensitive measures of quality of life in functional dyspepsia patients on single-drug treatment.