Prospective associations between serum biomarkers of lipid metabolism and overall,breast and prostate cancer risk

Experimental studies provided evidence about mechanisms by which cholesterol, especially high density lipoprotein cholesterol (HDL-C), could influence carcinogenesis, notably through antioxidant and anti-inflammatory properties. However, prospective studies that investigated the associations between specific lipid metabolism biomarkers and cancer risk provided inconsistent results. The objective was to investigate the prospective associations between total cholesterol (T-C), HDL-C, low density lipoprotein cholesterol, apolipoproteins A1 (apoA1) and B, and triglycerides and overall, breast and prostate cancer risk. Analyses were performed on 7,557 subjects of the Supplémentation en Vitamines et Minéraux Antioxydants Study, a nationwide French cohort study. Biomarkers of lipid metabolism were measured at baseline and analyzed regarding the risk of first primary incident cancer (N = 514 cases diagnosed during follow-up, 1994–2007), using Cox proportional hazards models. T-C was inversely associated with overall (HR_{1mmol/L increment} = 0.91, 95 % CI 0.82–1.00; P = 0.04) and breast (HR_{1mmol/L increment} = 0.83, 95 % CI 0.69–0.99; P = 0.04) cancer risk. HDL-C was also inversely associated with overall (HR_{1mmol/L increment} = 0.61, 95 % CI 0.46–0.82; P = 0.0008) and breast (HR_{1mmol/L increment} = 0.48, 95 % CI 0.28–0.83; P = 0.009) cancer risk. Consistently, apoA1 was inversely associated with overall (HR_{1g/L increment} = 0.56, 95 % CI 0.39–0.82; P = 0.003) and breast (HR_{1g/L increment} = 0.36, 95 % CI 0.18–0.73; P = 0.004) cancer risk. This prospective study suggests that pre-diagnostic serum levels of T-C, HDL-C and ApoA1 are associated with decreased overall and breast cancer risk. The confirmation of a role of cholesterol components in cancer development, by further large prospective and experimental studies, may have important implications in terms of public health, since cholesterol is already crucial in cardiovascular prevention.     

The effects of decanted sediments on embryogenesis in oysters (Crassostrea gigas)

Sediments act as sinks for contaminants of natural and anthropogenic origin, constituting a risk to the living organisms. In this study, sediments were collected from three sites on the coast of southwest France. The objective of this research was to determine the effects of sediments on embryonic development of bivalves and to identify precisely when the contaminants affect the embryos and induce them to develop in an abnormal way. The toxicity of decanted sediments and overlying waters were assessed using the oyster embryo bioassay. The physical characteristics and contaminant levels in the sediments were measured, including polycyclic aromatic hydrocarbon (PAH) and metal concentrations. Despite contaminant concentrations for PAH and metals only exceeding the effects range-low levels, all decanted sediments tested induced deleterious effects on the embryonic development of oysters, while no significant abnormalities were observed for overlying waters. The study results suggest that abnormal larvae mainly are caused by direct contact with contaminated sediments.     

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Reliability of a new device to assess the oxygen consumption of human respiratory muscles.

PURPOSE: This study tests the reliability of a new device for assessing the oxygen consumption of the respiratory muscles (VO2 resp.). METHODS: Fourteen healthy male volunteers participated in the study. The device consists of an expandable external ventilatory dead space created with pieces of plastic tubing and a spirometer filled with 100% oxygen. It also incorporates a carbon dioxide absorber. Total VO2 (VO2 tot.) was recorded from the spirometric closed circuit and ventilation (V(E)), from the spirometer tracing. For each subject the test procedure was carried out in duplicate (T1 and T2) after an overnight fast. The dead space was increased at a constant rate of 260 mL every 90 s, and VO2 tot. and V(E) increased progressively. Because log VO2 tot. was linearly related to V(E), we calculated the slope value (log VO2-V(E)) and the Y-intercept (VE = 0) of the semilog regression representing, respectively, VO2 resp. and metabolic VO2 (VO2 met.). RESULTS: When compared with values in the literature, these values did not differ from those recorded in subjects of a similar age group. The VO2 resp. and VO2 met. calculated in T1 and T2 were not different (VO2 resp. = 0.0066 +/- 0.0005 for T1 vs 0.0067 +/- 0.0005 log mL x min(-1)/L x min(-1) for T2 and VO2 met. = 269.3 +/- 28.6 for T1 vs 281.9 +/- 24.1 mL x min(-1) for T2). The coefficients of variation were: 25% at T1 and 23% at T2 for VO2 resp. and 34% at T1 and 29% at T2 for VO2 met. Moreover, significant correlations (r = 0.96, P < 0.001 for VO2 resp., r = 0.95, P < 0.001 for VO2 met.), high coefficients of determination (r2 = 0.92 for VO2 resp., r2 = 0.90 for VO2 met.) and negligible SEE (0.0005 for VO2 resp., 0.2 mL x min(-1) for VO2 met.) were found between the two tests. When we plotted the mean values of VO2 resp. and VO2 met. measured at T1 and T2 against their respective differences, more than 95% of the slight differences ranged between the limits defined by mean value +/- 2 SD, reflecting the small discrepancy between duplicate measurements. CONCLUSION: The results confirm that the test performed with this device is useful and reliable for assessing the VO2 resp. in healthy subjects.     

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Clonal drift demonstrates unexpected dynamics of the T-cell repertoire in T-large granular lymphocyte leukemia

T-cell large granular lymphocyte leukemia (T-LGLL) is characterized by chronic lymphoproliferation of cytotoxic T lymphocytes (CTLs) and is associated with lineage-restricted cytopenias. Introduction of T-cell receptor (TCR) variable β-chain (Vβ) monoclonal antibodies has facilitated identification and enumeration of clonal CTLs by flow cytometry. A highly skewed TCR Vβ repertoire identified by flow cytometry is strongly associated with monoclonal CDR3 regions by quantitative sequencing and positive TCRγ rearrangement assays. Therefore, Vβ expansions can serve as surrogate markers of CTL clonality to assess clonal kinetics in T-LGLL. We analyzed the TCR repertoire in 143 patients, 71 of which were available for serial measurements over 6 to 96 months. Although the majority (38/71, 54%) maintained a consistent monoclonal expansion, many (26/71, 37%) unexpectedly displayed a change in the dominant clone, whereby the original CTL clone contracted and another emerged as demonstrated by Vβ typing. Our results demonstrate that the T-cell repertoire is more dynamic in T-LGLL than recognized previously, illustrating the heterogeneity of disorders under this categorization.