Neurotensin, vaso-active intestinal polypeptide and gastrin levels in plasma and portal venous blood in experimental mesenteric ischaemia

The effect of mesenteric ischaemia on the levels of neurotensin, vaso-active intestinal polypeptide and gastrin in portal venous blood and in the peripheral circulation was studied in two groups of 7 and 6 baboons (Papio ursinus). In peripheral blood a decreasing trend in levels of neurotensin was observed, while vaso-active intestinal polypeptide and gastrin levels were unchanged. There was a similar trend in neurotensin levels in portal venous blood, together with an increasing trend in levels of vaso-active intestinal polypeptide. Gastrin levels were unchanged. Further investigation of these apparent trends in a larger number of animals is warranted

Dynamic Scaling and Two-Dimensional High-Tc Superconductors

There has been ongoing debate over the critical behavior of two-dimensional superconductors; in particular for high Tc superconductors. The conventional view is that a Kosterlitz-Thouless-Berezinskii transition occurs as long as finite size effects do not obscure the transition. However, there have been recent suggestions that a different transition actually occurs which incorporates aspects of both the dynamic scaling theory of Fisher, Fisher, and Huse and the Kosterlitz-Thouless-Berezinskii transition. Of general interest is that this modified transition apparently has a universal dynamic critical exponent. Some have countered that this apparent universal behavior is rooted in a newly proposed finite-size scaling theory; one that also incorporates scaling and conventional two-dimensional theory. To investigate these issues we study DC voltage versus current data of a 12 angstrom thick YBCO film. We find that the newly proposed scaling theories have intrinsic flexibility that is relevant to the analysis of the experiments. In particular, the data scale according to the modified transition for arbitrarily defined critical temperatures between 0 K and 19.5 K, and the temperature range of a successful scaling collapse is related directly to the sensitivity of the measurement. This implies that the apparent universal exponent is due to the intrinsic flexibility rather than some real physical property. To address this intrinsic flexibility, we propose a criterion which would give conclusive evidence for phase transitions in two-dimensional superconductors. We conclude by reviewing results to see if our criterion is satisfied.Comment: 14 page

Association of Forced Vital Capacity with the Developmental Gene NCOR2

Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (p<0.002; 0.05/25), with a nominal p-value considered as suggestive evidence. For SNPs with evidence of replication, effects on the expression levels of nearby genes in lung tissue were tested in 1,111 lung samples (Lung eQTL consortium), with further functional investigation performed using public epigenomic profiling data (ENCODE). Results NCOR2-rs12708369 showed strong replication in children (p = 0.0002), with replication unavailable in adults due to low imputation quality. This intronic variant is in a strong transcriptional enhancer element in lung fibroblasts, but its eQTL effects could not be tested due to low imputation quality in the eQTL dataset. SERPINE2-rs6754561 replicated at nominal level in both adults (p = 0.036) and children (p = 0.045), while WNT16-rs2707469 replicated at nominal level only in adults (p = 0.026). The eQTL analyses showed association of WNT16-rs2707469 with expression levels of the nearby gene CPED1.We found no statistically significant eQTL effects for SERPINE2-rs6754561. Conclusions We have identified a new gene, NCOR2, in the retinoic acid signalling pathway pointing to a role of Vitamin A metabolism in the regulation of FVC. Our findings also support SERPINE2, a COPD gene with weak previous evidence of association with FVC, and suggest WNT16 as a further promising candidate

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Circulating acute phase reactive proteins as indicators of infection in poorly controlled diabetes mellitus

Serum levels of six acute phase proteins (APP) - C-reactive protein (CRP), serum amyloid A (SAA), α1-antitrypsin, haptoglobin and complement fractions C3 and C4 - were serially studied in 24 patients with poorly controlled diabetes mellitus, ten of whom had unequivocal evidence of an underlying infection. In diabetic patients without infection, no change in APP levels was noted suggesting that hyperglycaemia per se does not quantitatively influence the acute phase response. No correlation between the presence of infection, and fever, leukocytosis, a raised erythrocyte sedimentation rate, or serum levels of α1-antitrypsin, haptoglobin or complement was apparent in these patients. However, serum CRP and SAA were initially increased 10-100 times above normal in diabetic patients with an underlying infection (P &lt; 0.01); during the following week circulating levels of CRP and SAA decreased steadily in response to the infection being brought under control. We conclude that serial measurement of CRP and/or SAA is a sensitive, albeit non-specific, parameter to detect and monitor the activity of infection in patients with diabetes.Articl

Cerebrospinal fluid C-reactive protein in infective meningitis in childhood

The value of cerebrospinal fluid C-reactive protein (CSF CRP) determination as a diagnostic aid in infective meningitis has been investigated in four groups of children. In a "no meningitis" group of 10 children, a median CSF CRP value of 0.08 μg/ml was obtained (range 0 to 0.31 μg/ml); in a viral meningitis group of 21 children a median value of 0.01 μg/ml (range 0 to 3.06 μg/ml); in a bacterial meningitis group of 27 children a median value of 9.6 μg/ml (range 0 to 31.5 μg/ml); and in a tuberculous meningitis group of 18 children a median value of 0.29 μg/ml (range 0 to 4.9 μg/ml). CSF CRP values in the bacterial meningitis group differed significantly from those of each of the other groups (P < 0.01), but considerable overlap between the groups detracted from the diagnostic value of the test. In six patients with bacterial meningitis with ambiguous conventional CSF chemistry results, normal CSF CRP values were found. Simultaneous serum CRP was determined in nine patients with tuberculous meningitis and 11 with bacterial meningitis, and the CRP response in both the serum and CSF appears subdued in tuberculous meningitis in comparison with bacterial meningitis. CSF CRP and total protein values were determined intermittently during a 24-hour period in ventricular CSF from two children with tuberculous meningitis who underwent temporary direct ventricular drainage. A considerable and apparently parallel diurnal variation in both values was seen. CSF CRP values have limited application in the etiologic diagnosis of meningitis. © 1985.Articl