Translational research : the journal of laboratory and clinical medicine
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The macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine central to the response to endotoxemia, is a putative biomarker in acute lung injury (ALI). To explore MIF as a molecular target and candidate gene in ALI, the MIF gene and protein expression were examined in murine and canine models of ALI (high tidal volume mechanical ventilation, endotoxin exposure) and in patients with either sepsis or sepsis-induced ALI. ⋯ Genotyping in 506 DNA samples (sepsis patients, sepsis-associated ALI patients, and healthy controls) revealed haplotypes located in the 3' end of the MIF gene, but not individual SNPs, associated with sepsis and ALI in both populations. These data, generated via functional genomic and genetic approaches, suggest that MIF is a relevant molecular target in ALI.
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Endothelial cells are an attractive vehicle for gene therapy because they may be used in an autologous fashion and may allow for direct exposure of the gene product into the intravascular space. To explore this future potential, a reproducible system was developed for the culture of murine blood outgrowth endothelial cells. These cells demonstrated acetylated low-density lipoprotein (LDL) incorporation, matrigel tube formation, and specific endothelial staining characteristics, namely P1H12, VeCAD, vascular cell adhesion molecule (VCAM), vWF, platelet endothelial cell adhesion molecule (PECAM-1), and vascular endothelial growth factor receptor-2 (VEGFR2). ⋯ Moreover, these cells were amendable to gene transfer with red fluorescent and green fluorescent expression vectors as well as human Factor VIII (hFVIII) while maintaining endothelial characteristics. Both source- and gene-introduced cells also manifested excellent proliferative potential. Furthermore, murine blood outgrowth endothelial cells (BOECs) demonstrated persistent in vivo seeding in the liver, lung, spleen, and bone morrow of recipient mice.
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Chronic excessive alcohol consumption is the strongest risk factor for upper aerodigestive tract (UADT) cancer. Multiple mechanisms are involved in alcohol-associated cancer development of the UADT, including acetaldehyde (AA) effects. AA is toxic, mutagenic, and carcinogenic. ⋯ In Caucasians, alcohol dehydrogenase 1*1 (ADH1C*1) allele encodes for an alcohol dehydrogenase (ADH) isoenzyme, which produces 2.5 times more AA than the corresponding allele ADH1C*2. The authors found that the ADH1C*1 allele frequency and rate of homozygosity was significantly associated with an increased risk for alcohol-related cancer. AA seems to be an important factor in alcohol-associated carcinogenesis of the UADT.
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The hypothesis was tested that plasma levels of adiponectin would be associated with coronary artery disease (CAD) across African-American and Caucasian ethnicity and gender. Adiponectin levels, cardiovascular risk factors, and extent of CAD were measured in 453 subjects (173 African-American and 280 Caucasian men and women). The distribution of adiponectin levels differed significantly between African-Americans and Caucasians (P<0.0001). ⋯ Among lipid parameters, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were negatively correlated with adiponectin, whereas the high-density lipoprotein cholesterol level correlated positively for both African-Americans and Caucasians. In a multiple regression model, controlling for gender, ethnicity, and other CAD risk factors, adiponectin levels were negatively associated with CAD (P<0.05). The results indicate that, across gender and ethnicity, low adiponectin levels may be an independent risk factor for CAD.
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Hemoglobin A1c (HbA1c) has been widely used as a measure of glycemic control in patients with diabetes mellitus. However, the role of HbA1c in the prediabetic stage has received little attention, although the effectiveness of early intensive intervention for the prediabetic patients defined by plasma glucose is well documented. In this study, routine clinical data in a Japanese university hospital were used to address whether the level of HbA1c predicted drug treatment for diabetes mellitus. ⋯ The rate (95% confidence interval; CI) of beginning anti-diabetic drug therapy was 1.5 (0.9-2.5)/1000 patient-years in patients with a normal level of HbA1c (<5.6%), which is similar to 2.1 (1.8-2.5)/1000 patient-years in patients with no HbA1c data, but lower than the value of 23.0 (18.6-28.6) and 161.8 (144.8-180.7)/1000 patient-years in those with borderline and high levels of HbA1c, respectively (P < 0.001). In a small group of 513 middle-aged patients, the rates of initial drug treatment for type 2 diabetes mellitus were 39.4 (28.1-55.1)/1000 patient-years and 270.4 (209.4-349.0)/1000 patient-years in those with borderline and high levels of HbA1c, respectively. A borderline (5.6-6.4%) or high (>or=6.5%) level of HbA1c was found to strongly predict future drug treatment for diabetes mellitus.