Genome-wide scan for blood pressure in Australian and Dutch subjects suggests linkage at 5P, 14Q and 17P.

Large-scale studies estimate the heritability of blood pressure at ≈50%. We carried out a genome-wide linkage analysis to search for chromosomal loci that might explain this heritability using longitudinal, multiple measures of systolic and diastolic blood pressure obtained in sibling pairs and dizygotic twin pairs from 2 countries (a total of 286 pairs from Australia and 636 pairs from the Netherlands). These pairs and a large number of their parents were genotyped with microsatellite markers. Multivariate linkage analysis of the combined data of both countries, using a variance components approach, showed suggestive linkage for diastolic blood pressure on chromosomes 5p13.1 (logarithm of odds score: 2.48), 14q12 (logarithm of odds score: 2.40) and 17q24.3 (logarithm of odds score: 2.36). The highest logarithm of odds score of 1.21 for systolic blood pressure was observed on chromosome 13q34. These results replicate earlier findings and add to a slowly emerging picture of multiple loci contributing to quantitative blood pressure variation. © 2007 American Heart Association, Inc

Isolation of anonymous, polymorphic DNA fragments from human chromosome 22q12-qter

A series of 195 random chromosome 22-specific probes, equivalent to approximately 1% of the size of this chromosome, have been isolated from a chromosome 22-specific bacteriophage lambda genomic library. These probes were mapped to four different regions of chromosome 22 on a panel of five somatic cell hybrids. Restriction fragment length polymorphisms were detected by 28 of the probes mapping to 22q12-qter. Evolutionarily conserved sequences in human, mouse, and Chinese hamster DNA were detected by 12% of the isolated probes

Bigger is not always better: Viability selection on body mass varies across life stages in a hibernating mammal

Body mass is often viewed as a proxy of past access to resources and of future survival and reproductive success. Links between body mass and survival or reproduction are, however, likely to differ between age classes and sexes. Remarkably, this is rarely taken into account in selection analyses. Selection on body mass is likely to be the primary target accounting for juvenile survival until reproduction but may weaken after recruitment. Males and females also often differ in how they use resources for reproduction and survival. Using a long-term study on body mass and annual survival in yellow-bellied marmots (Marmota flaviventer), we show that body mass was under stabilizing viability selection in the first years of life, before recruitment, which changed to positive directional selection as age increased and animals matured. We found no evidence that viability selection across age classes on body mass differed between sexes. By investigating the link between running speed and body mass, we show that the capacity to escape predators was not consistent across age classes and followed a quadratic relationship at young ages only. Overall, our results indicate that mature age classes exhibit traditional patterns of positive viability selection on body mass, as expected in a hibernating mammal, but that mass in the first years of life is subjected to stabilizing selection which may come from additional predation pressures that negate the benefits of the largest body masses. Our study highlights the importance to disentangle selection pressures on traits across critical age (or life) classes

Analysis of the Association of PTGER4 Gene Variants with Radiological Joint Damage in Rheumatoid Arthritis

Pathophysiology and treatment of rheumatic disease

Cognitive performance in relation to metabolic disturbances in patients with COPD

BACKGROUND & AIMS: Cognitive impairment (CI) and metabolic abnormalities, including the metabolic syndrome (MetS) and sarcopenia, are more prevalent in COPD patients compared to controls without diagnosed lung disease. Because earlier studies have shown these metabolic abnormalities may affect cognitive performance, this study investigated whether cognitive performance is more impaired in subgroups of COPD patients with MetS or sarcopenia. METHODS: Cognitive performance patterns of 170 COPD patients referred for pulmonary rehabilitation (53.5% male, 63.4 ± 9.4 years, FEV1 54.5 ± 22.7% predicted) were compared between COPD subgroups stratified by presence of MetS and sarcopenia. Cognitive performance was assessed using a detailed neuropsychological test battery, which measured psychomotor speed (Stroop Color-Word Test, Concept Shifting Test, Letter-Digit Substitution Test), planning (Behavioral Assessment of the Dysexecutive Syndrome), working memory (Visual-Verbal Learning Test, Digit Span), verbal memory (Visual-Verbal Learning Test) and cognitive flexibility (Stroop Color-Word Test, Concept Shifting Test). MetS was determined according to the NCEP ATP-III criteria. Sarcopenia was determined based on decreased appendicular lean mass by dual-energy x-ray absorptiometry and impaired physical performance by 6-min walking distance. RESULTS: MetS was observed in 54.7% and sarcopenia in 30.0% of COPD patients. The prevalence of general CI was not different between patients with and without MetS (30.4% and 39.0%, respectively) or those with and without sarcopenia (34.0% and 34.5%, respectively, both p > 0.05). Domain-specific cognitive performance was not different between metabolic subgroups, but those with sarcopenia displayed a lower prevalence of CI on verbal memory than those without (21.7% and 29.7%, respectively, p = 0.011). Only the digit span (working memory) subtest was significantly different between metabolic subgroups, in favor of those without MetS (p = 0.017). CONCLUSION: Cognitive performance was not affected more in COPD patients with sarcopenia or MetS

High-dose imatinib versus high-dose imatinib in combination with intermediate-dose cytarabine in patients with first chronic phase myeloid leukemia:A randomized phase III trial of the Dutch-Belgian HOVON study group

Despite the revolutionary change in the prognosis of chronic myeloid leukemia (CML) patients with the introduction of imatinib, patients with resistant disease still pose a considerable problem. In this multicenter, randomized phase III trial, we investigate whether the combination of high-dose imatinib and intermediate-dose cytarabine compared to high-dose imatinib alone, improves the rate of major molecular response (MMR) in newly diagnosed CML patients. This study was closed prematurely because of declining inclusion due to the introduction of second generation tyrosine kinase inhibitors and only one third of the initially required patients were accrued. One hundred nine patients aged 18-65 years were randomly assigned to either imatinib 800 mg (n = 55) or to imatinib 800 mg in combination with two successive cycles of cytarabine 200 mg/m2 for 7 days (n = 54). After a median follow-up of 41 months, 67 % of patients were still on protocol treatment. The MMR rate at 12 months was 56 % in the imatinib arm and 48 % in the combination arm (p = 0.39). Progression-free survival was 96 % after 1 year and 89 % after 4 years. Four-year overall survival was 97 %. Adverse events grades 3 and 4 were more common in the combination arm. The addition of intermediate-dose of cytarabine to imatinib did not improve the MMR rate at 12 months. However, the underpowering of the study precludes any definitive conclusions. This trial is registered at www.trialregister.nl (NTR674).</p