Peripheral monocytes from diabetic patients with coronary artery disease display increased bFGF and VEGF mRNA expression

BACKGROUND: Macrophages can produce vascular endothelial growth factor (VEGF) in response to hypoxia, transforming growth factor β1 (TGF-β1), angiotensin II, basic fibroblast growth factor (bFGF), and interleukin-1. These factors have been found in the serum of coronary artery disease (CAD) patients as well as in atherosclerotic lesions. The aim of the present study was to test the hypothesis that the expression of VEGF, TGF-β1 and bFGF in peripheral monocytes and lymphocytes is related to CAD. METHODS: Human Mononuclear cells and lymphocytes from peripheral blood were isolated from 53 donors undergoing angiography. Seventeen were found to be healthy and 36 were diagnosed with CAD. The respective mRNAs were extracted and quantified. RESULTS: The statistical analysis revealed a significant increase of the basal level expression for macrophage VEGF and bFGF in the CAD SA (stable angina) patient group compared to the noCAD (control) (p = 0.041 and p = 0.022 respectively) and CAD UA (unstable angina) (p = 0.024 and p = 0.005 respectively) groups, which was highly dependent on the diabetic status of the population. Furthermore, we demonstrated with an in vitro cell culture model that the levels of VEGF and bFGF in monocytes of healthy donors are not affected by short term exposure to increased glucose levels (usually observed in the diabetic patients) and/or statin. CONCLUSION: Our findings display a statistically significant association of the increased VEGF and bFGF levels in peripheral monocytes, with stable angina and diabetes in coronary artery disease. The results give new insight to CAD and the impaired collateral vessel formation in diabetics

Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties

<p>Abstract</p> <p>Background</p> <p>The V3 loop of the glycoprotein gp120 of HIV-1 plays an important role in viral entry into cells by utilizing as coreceptor CCR5 or CXCR4, and is implicated in the phenotypic tropisms of HIV viruses. It has been hypothesized that the interaction between the V3 loop and CCR5 or CXCR4 is mediated by electrostatics. We have performed hierarchical clustering analysis of the spatial distributions of electrostatic potentials and charges of V3 loop structures containing consensus sequences of HIV-1 subtypes.</p> <p>Results</p> <p>Although the majority of consensus sequences have a net charge of +3, the spatial distribution of their electrostatic potentials and charges may be a discriminating factor for binding and infectivity. This is demonstrated by the formation of several small subclusters, within major clusters, which indicates common origin but distinct spatial details of electrostatic properties. Some of this information may be present, in a coarse manner, in clustering of sequences, but the spatial details are largely lost. We show the effect of ionic strength on clustering of electrostatic potentials, information that is not present in clustering of charges or sequences. We also make correlations between clustering of electrostatic potentials and net charge, coreceptor selectivity, global prevalence, and geographic distribution. Finally, we interpret coreceptor selectivity based on the N⁶X⁷T⁸|S⁸X⁹sequence glycosylation motif, the specific positive charge location according to the 11/24/25 rule, and the overall charge and electrostatic potential distribution.</p> <p>Conclusions</p> <p>We propose that in addition to the sequence and the net charge of the V3 loop of each subtype, the spatial distributions of electrostatic potentials and charges may also be important factors for receptor recognition and binding and subsequent viral entry into cells. This implies that the overall electrostatic potential is responsible for long-range recognition of the V3 loop with coreceptors CCR5/CXCR4, whereas the charge distribution contributes to the specific short-range interactions responsible for the formation of the bound complex. We also propose a scheme for coreceptor selectivity based on the sequence glycosylation motif, the 11/24/25 rule, and net charge.</p

Miliary tuberculosis with no pulmonary involvement in myelodysplastic syndromes: a curable, yet rarely diagnosed, disease: case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Although tuberculosis is not uncommon among patients with myelodysplastic syndrome (MDS), only a few reports of such patients suffering from miliary tuberculosis (MT) exist. MT often presents as a fever of unknown origin and it is a curable disease, yet fatal if left untreated.</p> <p>Case presentation</p> <p>We report a case of MT with no clinical or laboratory indications of pulmonary involvement in a patient with MDS, and review the relevant literature. <it>Mycobacterium tuberculosis </it>was isolated from the liquid culture of a bone marrow aspirate.</p> <p>Conclusion</p> <p>Even if the initial diagnostic investigation for a fever of obscure etiology is negative, MT should not be excluded from the differential diagnosis list. Since it is a curable disease, persistent and vigorous diagnostic efforts are warranted. In suspected cases, mycobacterial blood cultures should be collected as soon as possible after hospital admission and early bone marrow aspirate with mycobacterial cultures is advocated.</p

Report of 2 indigenous cases of leprosy from a European country: use of polymerase chain reaction-restriction fragment length polymorphism analysis of hsp65 gene for identification of Mycobacterium leprae directly from a clinical sample

In this article, we report on 2 indigenous cases of leprosy detected in a European country. We also report on the use of polymerase chain reaction-restriction fragment length polymorphism analysis of hsp65 gene for rapid identification of Mycobacterium leprae directly froth the clinical sample. (C) 2009 Elsevier Inc. All rights reserved

CCR2-64I and CXCL12 3\u27A alleles confer a favorable prognosis to AIDS patients undergoing HAART therapy

BACKGROUND: The chemokine receptor polymorphisms CCR5Delta32, CXCL12 3\u27A, CCR2-64I and CCR5-59029 G/A have been demonstrated to affect HIV-1 infection and progression. OBJECTIVE: We studied the impact of the above polymorphisms on the effectiveness of a 30-month treatment with highly active antiretroviral therapy (HAART) in 149 HIV-1 patients. STUDY DESIGN: We stratified the patients according to CD4 CDC criteria and applied Kaplan-Meier analysis using the following end-point criteria: (a) the time from HAART initiation to undetectable viral load (VL) counts (VL\u3c50 copies/ml), (b) the duration of undetectable VL status and (c) the time required for CD4+ T-cell counts to pass over the 500 cells/ml threshold. RESULTS: Our results in the second group (CD4 201-500) revealed that patients with the CCR2-64I allele achieved undetectable VL counts at 3.5+/-0.48 months as compared to 10.26+/-1.42 months in the control group (p=0.018). The VL remained undetectable for 28+/-2 months, in contrast to 20+/-2 months in the control group (p=0.048). Patients carrying CXCL12 3\u27A restored the CD4 population faster than the control group (9+/-2 and 14+/-2 months, respectively, p=0.023). The CCR5Delta32 and CCR5-59029 G/A alleles did not appear to affect the parameters studied. CONCLUSIONS: Our results suggest that patients carrying either CCR2-64I or CXCL12 3\u27A have a more favorable prognosis during HAART treatment