Blood Typing Profile of a School-Aged Population of a North Togo Township

The aim of this study was the determination of hemoglobin (Hb) variants and ABO blood groups in a school population aged 6 to 9 years in the township of Agbandé-Yaka in North Togo. A cross-sectional study was carried out on 570 children of four primary schools at Agbande-Yaka, between March and July 2010. Hemoglobin characterization was done by alkaline buffer electrophoresis and the blood types ABO-Rhesus (Rh) D by immuno-hematological methods. A Hb variant was detected in 37.0% of the schoolchildren. Among them, the AS trait accounted for 11.9% and the AC trait for 20.2%. Homozygous Hb S (HBB: c.20A>T) was not found but Hb C (HBB: c.19G>A) appeared at a frequency of 3.3%, while compound heterozygotes carrying Hb SC were seen at a frequency of 1.6%. The O, B and A blood groups accounted for 49.0, 26.8 and 21.9%, respectively. The Hb anomalies reached a high prevalence in this school population. These results are remarkable by the absence of homozygous Hb S individuals compared to homozygous Hb C individuals, which were as numerous as expected. The frequencies of the ABO blood groups are similar to what has been found in other West African populations.     

High-resolution deletion mapping of 15q13.2-q21.1 in transitional cell carcinoma of the bladder

Deletions found in several types of human tumor, including carcinomas of the colorectum, breast, and lung, suggest the presence of a potential tumor suppressor gene(s) on chromosome 15. Common regions of deletion in these tumors are at 15q15 and 15q21. Here, we have analyzed loss of heterozygosity (LOH) on chromosome 15 to ascertain its potential involvement in the development and progression of transitional cell carcinoma (TCC) of the bladder. A panel of 26 polymorphic markers, spanning 15q12-15q22, were used to map regions of LOH in 51 TCCs. LOH was found for at least one marker in the region 15q14-15q15.3 in 20 of 51 (39%) tumors. Deletion mapping defined two minimum regions of deletion: a distal region between the markers D15S514 and D15S537 at 15q15.1-15q15.3 (estimated as 3 Mb) and a more proximal region between the markers D15S971 and D15S1042 at 15q14 (estimated as 1.1 Mb). Analysis of a panel of 33 bladder tumor cell lines revealed regions of contiguous homozygosity for markers in 15q15, indicating likely LOH. Fluorescence in situ hybridization analysis demonstrated that mitotic recombination is the predicted mechanism of LOH in two of these. These regions of LOH on 15q may contain tumor suppressor genes the loss or inactivation of which is associated with TCC development. The DNA repair gene RAD51 at 15q15.1 represents a candidate 15q tumor suppressor gene. Expression analysis of rad51 protein in tumor cell lines revealed variable levels of expression but no significant loss of expression in cell lines with likely 15q LOH.     

NF kappa B activation in mouse pituitary: comparison of response to interleukin-1 beta and lipopolysaccharide

The mouse anterior pituitary contains both types of interleukin (IL)-1 receptors, IL-1 receptor type I (IL-1RI) and IL-1 receptor type II (IL-1RII). These receptors are expressed mainly on somatotroph cells. In the present study, the ability of the mouse pituitary to respond in vivo to IL-1 or to lipopolysaccharide (LPS) was demonstrated by measuring, with an electrophoretic mobility shift assay, the presence of an active NF kappa B complex in cell nuclei from pituitaries of mice injected intraperitoneally with recombinant rat-IL-1 beta or LPS. Using immunohistochemistry with an antibody directed against the p65 NF kappa B subunit, a rapid and transient NF kappa B response to LPS was observed. This response was present predominantly in the nuclei of glial fibrillary acidic protein (GFAP)-positive cells and F4/80-labelled cells of the posterior and the anterior pituitary 15 min after stimulation and became faint after 2 h. In comparison, the early and strong NF kappa B response to IL-1 beta treatment was localized into somatotroph cells, GFAP positive cells and F4/80-labelled cells of the posterior and anterior pituitary. Activation of NF kappa B in response to IL-1 beta was no longer apparent in IL-1RI knockout mice, confirming that this receptor is essential for the transduction of IL-1 signal in the pituitary, but remained after LPS treatment. In addition, we investigated the effect of IL-1 on target genes by measuring the mRNA and proteins synthesis of growth hormone (GH), IL-6 and IL-1ra in the pituitary and the plasma. IL-1 beta was shown to induce a rapid and strong synthesis of IL-6 and IL-1ra in the pituitary but failed to regulate GH contents or release. These data suggest that the pituitary is able to respond to a systemic infection via cytokine-mediated responses transduced by IL-1.     

Association Between Cardiorespiratory Fitness and the Determinants of Glycemic Control Across the Entire Glucose Tolerance Continuum

OBJECTIVECardiorespiratory fitness (VO_2max) is associated with glycemic control, yet the relationship between VO_2max and the underlying determinants of glycemic control is less clear. Our aim was to determine whether VO_2max is associated with insulin sensitivity, insulin secretion, and the disposition index, a measure of compensatory pancreatic β-cell insulin secretion relative to insulin sensitivity, in subjects representing the entire range of the glucose tolerance continuum.RESULTSA low VO_2max was associated with high HbA_1c (r = −0.33), high fasting glucose (r = −0.34), high 2-h OGTT glucose (r = −0.33), low Si_OGTT (r = 0.73), and high early-phase (r = −0.34) and late-phase (r = −0.36) GSIS_OGTT. Furthermore, a low VO_2max was associated with low early- and late-phase DI_OGTT (both r = 0.41). Interestingly, relationships between VO_2max and either glycemic control or late-phase GSIS_OGTT deteriorated across the glucose tolerance continuum.CONCLUSIONSThe association between poor cardiorespiratory fitness and compromised pancreatic β-cell compensation across the entire glucose tolerance continuum provides additional evidence highlighting the importance of fitness in protection against the onset of a fundamental pathophysiological event that leads to type 2 diabetes.     

Astrocyte‐derived adenosine modulates increased sleep pressure during inflammatory response

Activation of the immune system elicits several behavioral changes collectively called sickness. Among the behavioral changes, systemic infections induce an increase in time spent in nonrapid‐eye‐movement (NREM) sleep and an increase of slow wave activity (or “sleep pressure”). Using an inducible, astrocyte‐specific transgenic dominant negative SNARE (dnSNARE) mouse line we recently demonstrated that gliotransmission plays an important role in sleep homeostasis through an adenosine receptor 1 (A1R)‐sensitive pathway. It has been hypothesized that systemic infection, mimicked by peripheral administration of lipopolysaccharide (LPS), increases sleeping behavior in part through upregulation of central adenosine levels. Moreover, as a source of immunologically relevant factors, astrocytes play a pivotal role in the central nervous system immune and inflammatory responses. However, little is known about the role of astrocytes in the CNS response to a peripheral immune challenge. We hypothesize that LPS impacts sleep homeostasis through the modulation of astrocyte‐derived adenosine accumulation. We therefore used dnSNARE mice to determine whether astrocytes contribute to the increased sleep pressure under immune challenge and whether this is a result of changes in adenosine signaling. We demonstrate that dnSNARE‐mediated gliotransmission is required for the ability of LPS to elevate sleep pressure as measured by the power of slow wave activity during NREM sleep. Moreover, in agreement with a role of astrocyte‐derived adenosine in modulating sleep homeostasis, we find that intracerebroventricular infusion of the A1R antagonist 8‐cyclopentyl‐1,3‐dimethylxanthine (CPT) mimics this dnSNARE phenotype. Taken together, our data demonstrate that astrocytic adenosine acting through A1 receptors contributes to the modulation of sleep pressure by LPS. GLIA 2013