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Potential Association (potential + association)
Selected AbstractsAscorbic Acid Induces Collagenase-1 in Human Periodontal Ligament Cells but Not in MC3T3-E1 Osteoblast-Like Cells: Potential Association Between Collagenase Expression and Changes in Alkaline Phosphatase Phenotype,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2003Momotoshi Shiga Abstract Ascorbic acid (AA) enhances osteoblastic differentiation by increasing collagen accumulation, which in turn, results in increased alkaline phosphatase (AP) expression in some osteogenic cells. However, in other cells, including human periodontal ligament (PDL) cells, additional osteoinductive agents are required for this response. To understand the potential basis for the maintenance of the AP phenotype of PDL cells exposed to AA, we examined the modulation of the tissue-degrading matrix metalloproteinases (MMPs) and their inhibitors by AA in short-term cell cultures. Early passage PDL cells in serum-free medium were exposed to AA for 5 days. The samples were analyzed for MMPs and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), AP, collagen I(,1), and osteocalcin. We found that AA dose-dependently increased the expression of collagenase-1, and minimally TIMP-1, but not stromelysin-1 or TIMP-2. Additionally, AA caused substantial increases in levels of type I collagen. AA was unable to increase AP activity or osteocalcin messenger RNA in PDL cells. However, the cells retained the ability to show a significantly greater AP expression in high- versus low-density cultures, and increased osteocalcin as well as AP levels when cultured in the presence of dexamethasone. Moreover, in cells exposed to dexamethasone, increases in AP and osteocalcin were accompanied by a repression of collagenase-1 expression. In contrast to PDL cells, AA did not induce collagenase but produced a significant increase in AP expression in MC3T3-E1 cells. These findings provide the first evidence that AA, by modulating both collagen and collagenase-1 expression in PDL cells, most likely contributes to a net matrix remodeling response in these cells. Furthermore, the relationship between changes in collagenase expression and alterations in AP activity in PDL and MC3T3-E1 cells suggests a potential role for collagenase in modulating the AP phenotype of cells with osteoblastic potential. [source] Potential association between endogenous leptin and sympatho-vagal activities in young obese Japanese womenAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 1 2003Tamaki Matsumoto Leptin is an adipocyte-derived hormone that decreases food intake and increases energy expenditure through the activation of the sympathetic nervous system (SNS). Notwithstanding recent intensive research, the underlying physiological mechanism of leptin as well as the etiology of obesity in humans remains elusive. The present study attempted to investigate the potential association between endogenous circulating leptin and sympatho-vagal activities in age- and height-matched obese and nonobese healthy young women. Plasma leptin concentrations were measured by radioimmunoassay. The autonomic nervous system activity was assessed during the resting condition by means of a recently devised power spectral analysis of heart rate variability, which serves to identify three separate frequency components, very low (VLO), low (LO), and high (HI). Plasma leptin concentrations were greater in the obese than in the control group (45.7 ± 5.89 vs. 11.2 ± 1.10 ng · ml,1, P < 0.01). As to the contribution of endogenous leptin to SNS activity, both the ratios of the VLO frequency component reflecting thermoregulatory sympathetic function and the global SNS index [(VLO + LO)/HI] to plasma leptin concentration were markedly reduced in the obese compared to the control group (VLO per leptin: 5.9 ± 1.39 vs. 37.8 ± 8.1 ms2 · ml · ng,1, P < 0.01; SNS index per leptin: 0.04 ± 0.008 vs. 0.33 ± 0.01 ml,,·,ng,1, P < 0.01). Additionally, a nonlinear regression analysis revealed that these ratios exponentially decreased as a function of body fat content (VLO per leptin r2 = 0.57, P < 0.01; SNS index per leptin r2 = 0.53, P < 0.01). Our data suggest that reduced sympathetic responsiveness to endogenous leptin production, implying peripheral leptin resistance, might be a pathophysiological feature of obesity in otherwise healthy young women. The findings regarding the association of leptin, body fat content, and SNS activity further indicate that the 30% of total body fat, which has been used as a criterion of obesity, might be a critical point at which leptin resistance is induced. Am. J. Hum. Biol. 15:8,15, 2003. © 2002 Wiley-Liss, Inc. [source] Mass spectrometry study of hemoglobin-oxaliplatin complexes in colorectal cancer patients and potential association with chemotherapeutic responsesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2006Rupasri Mandal Oxaliplatin is the most active platinum (Pt)-containing anticancer drug for the treatment of advanced colorectal cancer. We report here the study of potential association of the levels of oxaliplatin-protein complexes in 19 cancer patients with treatment efficacy using size-exclusion high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC/ICPMS) and nanoelectrospray ionization mass spectrometry (nanoESI-MS) techniques. Blood samples from 19 colorectal cancer patients were collected at 1 and 48,h after the first infusion of oxaliplatin. HPLC/ICPMS quantification of the oxaliplatin-protein complexes showed that the levels of Pt-protein complexes in plasma samples at 48,h were reduced by approximately 50% compared to those at 1,h, whereas those in hemolysates did not change significantly. The concentrations of hemoglobin (Hb)-oxaliplatin complexes determined by HPLC/ICPMS ranged from 3.1 to 8.7,µM. NanoESI-MS analysis of the patient hemolysates showed three distinct mass spectral profiles of the Hb-oxaliplatin complexes: (1) 1:1, (2) 1:1 with 1:2, and (3) multiple complexes of 1:1, 1:2, 1:3, and 1:4, corresponding to the Hb-oxaliplatin complex concentrations determined by HPLC/ICPMS. Potential association of variables including Hb-oxaliplatin complex concentrations with time to progress as the treatment efficacy indicator was analyzed using the Cox model. Multivariate analysis of the potential predictors showed that the statistically significant variables were Hb-oxaliplatin complex concentration (p,=,0.02), performance status (p,=,0.02), baseline neutrophil count (p,=,0.05), and the site of the primary cancer (colon vs. rectal, p,=,0.01). The hazard ratio for the concentration of the Hb-oxaliplatin complexes was 2.4, suggesting that the risk of cancer progression significantly increased with increasing of Hb-oxaliplatin complexes in patients. These results demonstrate that the level of the Hb-oxaliplatin complexes in erythrocytes is a potential biomarker for indicating inter-patient variations in oxaliplatin treatment efficacy. Copyright © 2006 John Wiley & Sons, Ltd. [source] Potential association between infertility and spinal neural tube defects in offspring,,§BIRTH DEFECTS RESEARCH, Issue 10 2006Yvonne W. Wu Abstract BACKGROUND: We examined the possible association between infertility and spinal neural tube defects (NTDs). METHODS: This is a nested case-control study within the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. Among a birth cohort of 110,624 singleton infants ,36 weeks gestation, 1994,1997, we electronically identified cases of spinal NTDs and confirmed the diagnosis by chart review. Controls (n = 1,608) were randomly selected from the birth population. History of infertility was defined as: (1) physician diagnosis of infertility; (2) prescription for an infertility medication noted in the KPMCP pharmacy; and/or (3) evaluation at 1 of 15 infertility clinics in Northern California. RESULTS: Eighteen infants diagnosed with spinal NTDs (prevalence 1.6/10,000) included 13 with spina bifida cystica and 5 with spina bifida occulta. Case mothers were more likely to have a history of infertility (4/18 vs. 96/1,608, OR 4.3, 95% CI 1.01,14.0), and to have been prescribed clomiphene citrate within the window spanning 60 days before to 15 days after conception (3/18 vs. 32/1,608, OR 11.7, 95% CI 2.0,44.8). CONCLUSION: This exploratory study suggests that infertility may be associated with an increased risk of spinal NTDs among liveborn, term infants. Birth Defects Research (Part A), 2006. © 2006 Wiley-Liss, Inc. [source] Genetic association of vasoactive intestinal peptide receptor with rheumatoid arthritis: Altered expression and signal in immune cellsARTHRITIS & RHEUMATISM, Issue 4 2008Mario Delgado Objective Vasoactive intestinal peptide (VIP) has been shown to be one of the endogenous factors involved in the maintenance of immune tolerance. Administration of VIP ameliorates clinical signs in various experimental autoimmune disorders. This study was undertaken to investigate whether the exacerbated inflammatory autoimmune response in rheumatoid arthritis (RA) might result directly from altered expression and/or signaling of VIP receptors in immune cells. Methods The effect of specific agonists of different VIP receptors on collagen-induced arthritis in mice was investigated by clinical and histologic assessment and measurement of cytokine and chemokine production. Expression of VIP receptor type 1 (VPAC1) in synovial cells and monocytes from RA patients was determined by flow cytometry. Potential associations of VPAC1 genetic polymorphisms with RA susceptibility were investigated. Results A VPAC1 agonist was very efficient in the treatment of experimental arthritis, and deficient expression of VPAC1 in immune cells of RA patients was associated with the predominant proinflammatory Th1 milieu found in this disease. Immune cells derived from RA patients were less responsive to VIP signaling than were cells from healthy individuals and showed reduced VIP-mediated immunosuppressive activity, rendering leukocytes and synovial cells more proinflammatory in RA. A significant association between multiple-marker haplotypes of VPAC1 and susceptibility to RA was found, suggesting that the reduced VPAC1 expression in RA-derived immune cells is associated with the described VPAC1 genetic polymorphism. Conclusion These findings are highly relevant to the understanding of RA pathogenesis. They suggest that VIP signaling through VPAC1 is critical to maintaining immune tolerance in RA. In addition, the results indicate that VPAC1 may be a novel therapeutic target in RA. [source] Prevalence and cost of nonadherence with antiepileptic drugs in an adult managed care populationEPILEPSIA, Issue 3 2008Keith L. Davis Summary Purpose: This study assessed the extent of refill nonadherence with antiepileptic drugs (AEDs) and the potential association between AED nonadherence and health care costs in an adult-managed care population. Methods: Retrospective claims from the PharMetrics database were analyzed. Inclusion criteria were: age ,21, epilepsy diagnosis between January 01, 2000 and March 12, 2005, ,2 AED prescriptions, and continuous health plan enrollment for ,6 months prior to and ,12 months following AED initiation. Adherence was evaluated using the medication possession ratio (MPR). Patients with an MPR <0.8 were classified as nonadherent. Multivariate regression was used to assess the effect of AED nonadherence on annualized cost outcomes. Regression covariates included patient demographics, Charlson Comorbidity Index (CCI), and follow-up duration. Results: Among patients meeting all inclusion criteria (N = 10,892), 58% were female, mean age was 44 years, mean CCI was 0.94, and mean follow-up was 27 months. Mean MPR was 0.78 and 39% of patients were nonadherent. AED nonadherence was associated with an increased likelihood of hospitalization (odds ratio [OR]= 1.110, p = 0.013) and emergency room (ER) admission (OR = 1.479, p < 0.0001), as well as increased inpatient and ER costs of $1,799 and $260 (both p = 0.001), respectively, per patient per year. Outpatient and other ancillary costs were not significantly affected by nonadherence. A large net positive effect of nonadherence on total annual health care costs remained (+$1,466, p = 0.034) despite an offset from reduced prescription drug intake. Discussion: Adherence with AEDs among adult epilepsy patients is suboptimal and nonadherence appears to be associated with increased health care costs. Efforts to promote AED adherence may lead to cost savings for managed care systems. [source] A common cortactin gene variation confers differential susceptibility to severe asthmaGENETIC EPIDEMIOLOGY, Issue 8 2008Shwu-Fan Ma Abstract Genomic regions with replicated linkage to asthma-related phenotypes likely harbor multiple susceptibility loci with relatively minor effects on disease susceptibility. The 11q13 chromosomal region has repeatedly been linked to asthma with five genes residing in this region with reported replicated associations. Cortactin, an actin-binding protein encoded by the CTTN gene in 11q13, constitutes a key regulator of cytoskeletal dynamics and contractile cell machinery, events facilitated by interaction with myosin light chain kinase; encoded by MYLK, a gene we recently reported as associated with severe asthma in African Americans. To evaluate potential association of CTTN gene variation with asthma susceptibility, CTTN exons and flanking regions were re-sequenced in 48 non-asthmatic multiethnic samples, leading to selection of nine tagging polymorphisms for case-control association studies in individuals of European and African descent. After ancestry adjustments, an intronic variant (rs3802780) was significantly associated with severe asthma (odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.20,2.43; p=0.003) in a joint analysis. Further analyses evidenced independent and additive effects of CTTN and MYLK risk variants for severe asthma susceptibility in African Americans (accumulated OR: 2.93, 95% CI: 1.40,6.13, p=0.004). These data suggest that CTTN gene variation may contribute to severe asthma and that the combined effects of CTTN and MYLK risk polymorphisms may further increase susceptibility to severe asthma in African Americans harboring both genetic variants. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source] Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11IMMUNOLOGY, Issue 1 2007Carlos J. Montoya Summary Identification of human CD1d-restricted T-cell receptor (TCR)-invariant natural killer T (iNKT) cells has been dependent on utilizing combinations of monoclonal antibodies or CD1d tetramers, which do not allow for the most specific analysis of this T-cell subpopulation. A novel monoclonal antibody (clone 6B11), specific for the invariant CDR3 loop of human canonical V,24J,18 TCR , chain, was developed and used to specifically characterize iNKT cells. In healthy individuals studied for up to 1 year, a wide but stable frequency of circulating iNKT cells (range: 0·01,0·92%) was observed, with no differences in frequency by gender. Four stable iNKT cell subsets were characterized in peripheral blood based on the expression of CD4 and CD8, with CD8+ iNKT cells being a phenotypic and functionally different subset from CD4+ and double negative iNKT cells; in particular, LAG-3 was preferentially expressed on CD8+ iNKT cells. In addition, a strong negative linear correlation between the frequency of total iNKT cells and percentage of the CD4+ subset was observed. In terms of their potential association with disease, patients at risk for type 1 diabetes had significantly expanded frequencies of double negative iNKT cells when compared to matched controls and first-degree relatives. Moreover, peripheral blood CD4+ iNKT cells were the highest producers of interleukin-4, while the production of interferon-, and tumour necrosis factor-, was similar amongst all iNKT cell subsets. These differences in iNKT cell subsets suggest that in humans the relative ratio of iNKT cell subsets may influence susceptibility vs. resistance to immune-mediated diseases. [source] Distribution of peroxisome proliferator,activated receptor,gamma polymorphisms in Chinese and Dutch patients with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2010Umid Kumar Shrestha Abstract Background: As peroxisome proliferator,activated receptor,gamma (PPAR-,) is frequently expressed in colon, its genetic polymorphism may play a role in the etiology of inflammatory bowel disease (IBD). The aims of the present study were to determine the distribution of PPAR-, polymorphisms Pro12Ala and C161T and to explore the association between the PPAR-, genotypes and phenotypes of IBD patients. Methods: A total of 244 IBD patients [212 ulcerative colitis (UC) and 32 Crohn's disease (CD)] and 220 controls in the Chinese population and 603 IBD patients (302 UC and 301 CD) and 180 controls in the white Dutch population were enrolled in the study. The phenotypes of Chinese IBD patients were grouped according to disease location. The PPAR-, polymorphisms Pro12Ala and C161T were genotyped by PCR-based methods. Results: In the Chinese population, T carriers of the PPAR-, C161T polymorphism were more common in UC patients than in the controls [37.7% vs. 25.5%, odds ratio 1.77, 95% confidence interval 1.18,2.68, P = 0.007], whereas Ala carriers of the Pro12Ala polymorphism showed no significant association in UC patients, but there was a significant association of Ala carriers with more extensive disease among the UC patients (P = 0.002); Pro12Ala and C161T genotypes did not show any associations with CD patients. No associations were found for the PPAR-, C161T SNP studied in the Dutch IBD population. Conclusions: Our study showed the potential association between the PPAR-, C161T polymorphism and UC patients in the central Chinese population. This finding was not replicated in the Dutch population. Further studies are necessary to explore the functional implication of the PPAR-, C161T polymorphism in Chinese UC patients. (Inflamm Bowel Dis 2009;) [source] Role of the NFKB1 ,94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genesINFLAMMATORY BOWEL DISEASES, Issue 7 2006Jürgen Glas MD Abstract Background: Recently, an association of the NFKB1 polymorphism ,94ins/delATTG with ulcerative colitis (UC) has been reported. This 4-bp insertion/deletion polymorphism is localized in the promoter region of the NFKB1 gene and appears to be functionally relevant. The aim of the present study was to confirm the association of the ,94ins/delATTG (W/D) NFKB1 promoter polymorphism with UC in a population of German origin and to test for a potential association with Crohn's disease (CD). Furthermore, potential interactions of the ,94ins/delATTG polymorphism with the IKBL and the IL-1RN genes should be determined. Materials and Methods: The study population comprised 630 patients with CD, 365 patients with UC, and 974 healthy controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. For statistical evaluation, the chi-square test and the Fisher exact test were used. Results: No significant association of the W/D NFKB1 polymorphism with CD or UC was detected. In addition, no significant interactions between the ,94ins/delATTG NFKB1 polymorphism and polymorphisms within the IKBL and the IL-1RN genes, respectively, were found in CD or UC. Also, no significant interactions of the NFKB1 polymorphism with mutations of the CARD15/NOD2 gene and with clinical phenotypes were detected in CD. Moreover, no associations of the NFKB1 polymorphism were found in UC depending on disease localization. Conclusions: The present study could not confirm the reported association of the ,94ins/delATTG NFKB1 polymorphism with UC and also found no evidence for a role of this polymorphism in CD. The results do not give evidence for a role of this NFKB1 polymorphism in the pathogenesis of UC and CD. [source] Detection of bone marrow-disseminated breast cancer cells using an RT-PCR assay of MUC5B mRNAINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Nora Berois Abstract The evaluation of disseminated epithelial tumor cells in breast cancer patients has generated considerable interest due to its potential association with disease recurrence. Our work was performed to analyze the usefulness of 5 mucin genes expression (MUC2, MUC3, MUC5B, MUC6 and MUC7), using RT-PCR assays, to detect disseminated cancer cells in patients with operable breast cancer. The highest frequencies of positive RT-PCR tests in breast tumor extracts were observed for MUC5B (7/15) and MUC7 (5/12). The best specificity, negative results on all peripheral blood mononuclear (PBMN) cell samples from healthy donors, were shown for MUC2, MUC5B and MUC6 RT-PCR assays. Thus, we selected MUC5B as a target gene for further evaluation. Using a nested RT-PCR, MUC5B mRNA transcripts were detected in 16/31 primary breast tumors (but not in 36 samples of normal PBMN cells) and in the human MCF-7 breast cancer cell line but not in BT20, MDA, T47D and ZR-75 breast cancer cell lines, indicating that MUC5B mRNA is expressed in a population of breast cancer cells. Using this method, 9/46 patients (19.5%) who underwent curative surgery showed positive MUC5B mRNA in bone marrow aspirates obtained prior to surgery, including 5/24 patients (20.8%) with stage I or II breast cancer, without histopathologic lymph node involvement. These results indicate that MUC5B mRNA could be a specific marker applicable to the molecular diagnosis of breast cancer cell dissemination. A comparative evaluation between MUC5B mRNA, cytokeratin 19 (CK19) mRNA and carcinoembryonic antigen (CEA) mRNA in all bone marrow aspirates suggests a putative complementation for molecular detection of disseminated carcinoma cells. Considering that breast cancer is characterized by a great phenotypic heterogeneity, the use of multimarker approach could contribute to tumor cell detection in bone marrow and blood. © 2002 Wiley-Liss, Inc. [source] The interleukin-25 gene located in the inflammatory bowel disease (IBD) 4 region: no association with inflammatory bowel diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2003C. Büning Summary Genetic predisposition has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). Linkage studies have identified a Crohn's disease susceptibility locus on chromosome 14 (14q11,12; IBD4). Interleukin-25 (IL-25) is a newly identified proinflammatory cytokine that has been shown to promote Th2 responses by inducing cytokines such as IL-4, IL-5 and IL-13. The IL-25 gene is located within this susceptibility region at 14q11.2. As IBDs are characterized by an imbalance of the Th1/Th2 cytokine response, we hypothesized that genetic alterations within the IL-25 gene might contribute to IBD. First, direct sequencing of the coding regions of the IL-25 gene in 40 patients with Crohn's disease or ulcerative colitis revealed only a newly reported polymorphism (c424C/A) in exon 2. Next, the frequency of this polymorphism was further investigated in 151 patients with Crohn's disease, 111 patients with ulcerative colitis, and 119 healthy controls to determine its clinical relevance. The genotypes of the c424C/A polymorphism did not reveal any significant differences between patients with Crohn's disease or ulcerative colitis and controls. Genoytype,phenotype relations in patients with Crohn's disease showed a comparable distribution of the c424C/A polymorphism in all subgroups of the Vienna classification. In summary, our data indicate that genetic alterations in the coding regions of the IL-25 gene are unlikely to play a role in IBDs, but the c424C/A polymorphism in the IL-25 gene should be investigated for a potential association with other chronic inflammatory and inherited disorders such as autoimmune diseases. [source] Diverse Effect of Inflammatory Markers on Insulin Resistance and Insulin-Resistance Syndrome in the ElderlyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2004Angela M. Abbatecola MD Objectives: To evaluate the potential association between different inflammatory markers and insulin resistance (IR), as well as insulin-resistance syndrome (IRS) in a large, population-based study of older, nondiabetic persons. Design: Cross-sectional study. Setting: Outpatient clinic in Greve in Chianti and Bagno a Ripoli (Italy). Participants: One thousand one hundred forty-six nondiabetic subjects ranging in age from 22 to 104. Measurements: Anthropometric measurements; plasma fasting levels of glucose, insulin, and cholesterol (total, high-density lipoprotein, low-density lipoprotein); homeostasis model assessment to estimate degree of insulin resistance; tumor necrosis factor , (TNF-,), interleukin 6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin receptor antagonist (IL-1ra), and C-reactive protein (CRP) plasma concentrations; diastolic, systolic, and mean arterial blood pressure; and echo-color-Doppler duplex scanning examination of carotid arteries. Results: Insulin resistance correlated with age (r=0.102; P<.001) and plasma levels of TNF-, (r=0.082; P=.007), IL-1ra (r=0.147; P<.001), IL-6 (r=0.133; P<.001), sIL-6R (r=,0.156; P<.001), and CRP (r=0.83; P<.001). Subjects in the upper tertile of IR degree were older and had higher serum levels of TNF-,, IL-1ra, and IL-6 and lower levels of sIL-6R than subjects in the lowest tertile. Independent of age, sex, body mass index, waist-to-hip ratio, triglycerides, drug intake, diastolic blood pressure, smoking habit, and carotid atherosclerotic plaques, higher IL-6 (t=2.987; P=.003) serum concentrations were associated with higher IR, whereas sIL-6R levels (t=,5.651; P<.001) were associated with lower IR. Furthermore, IL-1ra concentrations (t=2.448; P=.015) were associated with IRS, and higher sIL-6R plasma levels continued to correlate negatively with IRS. Conclusion: Different inflammatory markers are associated with a diverse effect on IR and IRS in elderly nondiabetic subjects. [source] Myocardial Connections Between Left Atrial Myocardium and Coronary Sinus Musculature in ManJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2001ATSUNOBU KASAI M.D. Connections Between LA Myocardium and CS Musculature.Introduction: Anatomic studies have shown that muscle morphologically identical to that of the atrial myocardium consistently surrounds the coronary sinus (CS). The CS musculature is connected to the left atrial (LA) myocardium in a variable fashion, with fewer connections in its distal portion. The aim of this study was to document the presence of connections between the LA myocardium and the CS musculature, using pacing maneuvers in man, and to study their potential association with natural atrial arrhythmia occurrence. Methods and Results: Thirty patients (19 men; mean age 50.5 years) underwent electrophysiologic study, during which a decapolar catheter with 2-mm interelectrode spacing every 10 mm was inserted into the CS, with the proximal electrode pair positioned at the ostium. Associated atrial arrhythmias were paroxysmal atrial fibrillation in 5, typical atrial flutter in 13, LA flutter in 1, and other in 11. Baseline S1 and a single extrastimulus were delivered during distal and proximal CS pacing, while recordings were obtained from the four remaining bipoles. During distal CS pacing, double potentials with increasing interpotential interval from proximal to distal CS as a function of extrastimulus prematurity were detected in nine patients, suggesting block in a discrete local pathway distally connecting the CS to the LA and leading to reversion of low LA activation. Local delay in this pathway without complete CS-LA block resulting in LA activation fusion was observed in eight patients. A single nonfractionated potential at the distal CS, even at the shortest attainable S1-S2 coupling interval, which was interpreted as no block within distal CS-LA connection(s), was observed in the other 13 patients. History of atrial fibrillation or atypical atrial flutter was found in 8 of 9 patients with block at the distal CS-LA connection but in only 3 of 13 patients with no CS-LA connection block (P = 0.004). Conclusion: The ability to dissociate the LA from the distal CS suggests the presence of discrete connections between these structures in man. This observation appears to be associated with the clinical occurrence of atrial arrhythmias. [source] Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controlsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2008Georgios K. Nikolopoulos Abstract Aim: We conducted a systematic review and a meta-analysis, in order to investigate the potential association of cytokine gene polymorphisms with either aggressive or chronic periodontal disease. Material and Methods: A comprehensive literature search was performed. We retrieved a total of 53 studies summarizing information about 4178 cases and 4590 controls. Six polymorphisms were included in our meta-analysis which are the following: IL-1A G[4845]T, IL-1A C[,889]T, IL-1B C[3953/4]T, IL-1B T[,511]C, IL-6 G[,174]C and TNFA G[,308]A. Random effect methods were used for the analysis. We calculated the specific odds ratios along with their 95% confidence intervals to compare the distribution of alleles and genotypes between cases and controls. Results and Conclusions: Using random effect methods we found statistically significant association of IL-1A C[,889]T and IL-1B C[3953/4]T polymorphisms with chronic periodontal disease without any evidence of publication bias or significant statistical heterogeneity. A weak positive association was also found concerning IL-1B T[,511]C and chronic periodontal disease. No association was found for all the cytokines examined as far as the aggressive form of the disease is concerned. Future studies may contribute to the investigation of the potential multigenetic predisposition of the disease and reinforce our findings. [source] Periodontal conditions in male adolescents using smokeless tobacco (moist snuff)JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 12 2006Ulrika Montén Abstract Aim: The aim of this study was to evaluate the potential association of the use of smokeless tobacco (moist snuff) on the periodontal conditions of adolescents. Material and methods: A subject sample of one hundred and three 19-year-old male individuals (33 snuff users, 70 controls) living in Göteborg, Sweden, were clinically examined with regard to oral hygiene, gingivitis, probing pocket depth (PPD), clinical attachment loss (CAL) and gingival recession. Bitewing radiographs were obtained for assessments of alveolar bone level. Information about tobacco and oral hygiene habits was obtained by a structured questionnaire. Student 's t -test, ,2 -test and logistic regression analysis were used for statistical analysis. Results: The mean plaque and gingivitis scores in snuff-users were 59% (SD 21.0) and 47% (18.6), respectively, and in controls 64% (22.4) and 50% (18.3), respectively. The average PPD and CAL in snuff-users amounted to 2.3 mm (0.3) and 0.2 mm (0.1), respectively, and in controls 2.4 mm (0.3) and 0.1 mm (0.1) (p>0.05), respectively. The mean bone level was 1.3 mm (0.2) in both groups. The prevalence of subjects showing recession was 42% among snuff-users and 17% among controls (p=0.006). In snuff users, an average of 4% (0.9) of the teeth showed recession, compared with 1% (0.3) in controls (p<0.001). Limiting the analysis to the maxillary anterior tooth region, 33% of the snuff-users and 10% of the controls presented recessions (p=0.002). The use of snuff entailed an OR=5.1 to have gingival recessions. Conclusion: In the present population sample of adolescents, the use of smokeless tobacco (moist snuff) was not associated with the presence of periodontal disease except for a significantly high prevalence of gingival recessions. [source] The early development of self-injurious behaviour: evaluating the role of social reinforcementJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 8 2005C. Oliver Abstract Background The potential role of social reinforcement in the development of self-injury has not yet been subjected to empirical analysis. In this 2-year prospective study, the pattern of social interactions related to the early presentation of self-injury were examined to identify a potential association with an increase in self-injury. Methods The self-injurious behaviour and social contact with adults of 16 children with intellectual disability (ID) with self-injury of recent onset were observed at 3-month intervals over 2 years. Results Increase in self-injury over a 2-year period was positively correlated with a distribution of social contact relative to episodes of self-injury that is consistent with a mutual social reinforcement paradigm. When this paradigm was operative, self-injury was evoked under stable antecedent conditions over time but tended to evoke increasing levels of social interaction. Conclusions These results support the hypothesis that increases in the frequency of early self-injury in children with ID may be determined by social reinforcement with implications for early intervention and proactive identification of children at risk for increases in self-injury. [source] The association between metabolic syndrome, microalbuminuria and impaired renal function in the general population: impact on cardiovascular disease and mortalityJOURNAL OF INTERNAL MEDICINE, Issue 4 2007K. P. Klausen Abstract. Objective:, Microalbuminuria and metabolic syndrome are both associated with cardiovascular disease (CVD). The aim of this study was to determine the potential association between numbers of components in the metabolic syndrome, different levels of microalbuminuria and renal function. We also aimed to determine the risk of death and CVD at different levels of microalbuminuria and renal function and numbers of components in the metabolic syndrome. Design:, Population-based observational follow-up study Setting:, Epidemiological research unit (Copenhagen City Heart Study). Subjects:, A total of 2696 men and women, 30,70 years of age. Baseline measures:, Urinary albumin excretion (UAE), creatinine clearance and metabolic risk factors were measured in 1992,1994. Main outcome measurements:, The participants were followed prospectively by registers until 1999,2000 with respect to CVD, and until 2004 with respect to death. Results:, We found a strong association between microalbuminuria and the metabolic syndrome: 2% with none and 18% with five metabolic risk factors had microalbuminuria (P < 0.001). No association between impaired renal function defined as creatinine clearance <60 mL min,1 and the metabolic syndrome was found. Microalbuminuria was associated with increased risk of death and CVD to a similar extend as the metabolic syndrome, irrespective of concomitant presence of metabolic syndrome (RR,2; P < 0.001). Impaired renal function was not associated with increased risk of death and CVD in subjects with the metabolic syndrome. Conclusions:, Microalbuminuria (UAE >5 ,g min,1) confers increased risk of death and CVD to a similar extent as the metabolic syndrome. [source] Immunohistochemical study of syndecan-1 down-regulation and the expression of p53 protein or Ki-67 antigen in oral leukoplakia with or without epithelial dysplasiaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2003Hideo Kurokawa Abstract Background:, Leukoplakia is an oral pre-cancerous lesion that sometimes develops into squamous cell carcinoma. Therefore, leukoplakia with epithelial dysplasia is useful for studying carcinogenesis at the cellular level. The purpose of this study was to evaluate a potential association between the loss of syndecan-1 expression and the expression of p53 protein and Ki-67 antigen, and to identify reliable markers for predicting malignant changes in oral leukoplakia with epithelial dysplasia. Methods:, Changes in the expression of syndecan-1, p53, and Ki-67 were examined immunohistochemically in 43 cases of oral leukoplakia with or without epithelial dysplasia. The subjects were categorized as: none, 13 cases; mild dysplasia, 5 cases; moderate dysplasia, 17 cases; and severe dysplasia, 8 cases. The expression of these molecules in normal oral epithelia (22 cases) was also investigated. Results:, Strong syndecan-1 expression was observed on the surface of keratinocytes in normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. In normal epithelium, p53 and Ki-67 appeared mainly in the basal cell layer, while they were more widely distributed in leukoplakia. Specifically, significant changes were observed in the labeling index of p53 and Ki-67 in leukoplakia as epithelial dysplasia progressed from mild to moderate or severe. Conclusion:, Our results reveal that overexpression of p53 protein and Ki-67 antigen, and down-regulation of syndecan-1 expression in the lower part of the epithelium, are associated with dysplastic changes. Therefore, the down-regulation of syndecan-1 expression may be the most important reliable marker for dysplastic changes. [source] The association between MIF-173 G>C polymorphism and prostate cancer in southern ChineseJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2009G.X. Ding MD Abstract Background and Objectives Accumulating epidemiological and molecular evidence suggests that inflammation is an important component in the etiology of PCa. Macrophage migration inhibitory factor (MIF) plays an important role in the pro- and anti-inflammatory response to infection. This study is aimed at investigating the potential association between MIF-173 G>C polymorphism, Gleason score, clinical stage, and prostate-specific antigen (PSA) value with respect to PCa incidence among the Han nationality in Southern China. Methods Genotyping was performed by using tetraprimer polymerase chain reaction (PCR) on 259 PCa patients and 301 cancer-free controls. Results We found that the MIF-173*C variant allele was significantly associated with an increased risk of PCa [adjusted odd ratio (OR),=,2.99, 95% confident interval (CI): 1.94,4.60] and higher Gleason scores from the PCa subjects (adjusted OR,=,10.72, 95% CI: 5.35,21.49). In addition, we noted that the MIF ,173*C variant allele was related to higher clinical stages and PSA values in PCa patients (adjusted OR,=,15.68, 95% CI: 7.40,33.23; adjusted OR,=,4.37, 95% CI: 2.41,7.92, respectively). Conclusion Our data suggest that MIF-173 polymorphisms may be associated with a higher incidence of prostate cancer compared to controls, and appears to be associated with higher Gleason scores, higher clinical stages, and PSA values in those with prostate cancer. J. Surg. Oncol. 2009;100:106,110. © 2009 Wiley-Liss, Inc. [source] REM sleep behavior disorder is not linked to postural instability and gait dysfunction in Parkinson,MOVEMENT DISORDERS, Issue 11 2010David H. Benninger MD Abstract To evaluate a potential association of REM-sleep behavior disorder (RBD) with gait and postural impairment in Parkinson's disease (PD). Gait difficulties and postural impairment are frequent in PD and are a major cause of disability. Animal studies indicate a key role of the pedunculopontine nucleus (PPN) in gait, postural control, and REM sleep, and also in the pathophysiology of RBD. In humans, such an association has not been investigated. Twenty-six patients with mild-to-moderate PD (13 with polysomnography confirmed and 13 with excluded RBD), and 20 age-matched healthy controls were prospectively investigated. Gait assessment on a treadmill, and static and dynamic posturography were performed. PD patients with RBD do not differ from those without RBD in gait and postural control. Greater severity of PD or prevalence of gait and postural disturbances in the presence of RBD were not found. RBD was not associated with any particular motor phenotype. We found no association of RBD with gait disturbances and postural impairment. Human gait and postural control and RBD appear to depend upon different neuronal circuits. © 2010 Movement Disorder Society [source] A dose-response relationship between maternal smoking during late pregnancy and adult intelligence in male offspringPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 1 2005Erik Lykke Mortensen Summary An association between maternal smoking during pregnancy and cognitive and behavioural development has been observed in several studies, but potential effects of maternal smoking on offspring adult intelligence have not been investigated. The objective of the present study was to investigate a potential association between maternal smoking during pregnancy and offspring intelligence in young adulthood. Adult intelligence was assessed at the mean age of 18.7 years by a military draft board intelligence test (Břrge Priens Prřve) for 3044 singleton males from the Copenhagen Perinatal Cohort with information regarding maternal smoking during the third trimester coded into five categories (about 50% of the mothers were smokers). The following potential confounders were included as covariates in multivariable analyses: parental social status and education, single mother status, mother's height and age, number of pregnancies, and gestational age. In separate analyses, birthweight and length were also included as covariates. Maternal cigarette smoking during the third trimester, adjusted for the seven covariates, showed a negative association with offspring adult intelligence (P = 0.0001). The mean difference between the no-smoking and the heaviest smoking category amounted to 0.41 standard deviation, corresponding to an IQ difference of 6.2 points [95% confidence interval 0.14, 0.68]. The association remained significant when further adjusted for birthweight and length (P = 0.007). Both unadjusted and adjusted means suggested a dose-response relationship between maternal smoking during pregnancy and offspring adult intelligence. When subjects with missing data were excluded, essentially the same results were obtained in the reduced sample (n = 1829). These results suggest that smoking during pregnancy may have long-term negative consequences on offspring adult intelligence. [source] Potential association between endogenous leptin and sympatho-vagal activities in young obese Japanese womenAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 1 2003Tamaki Matsumoto Leptin is an adipocyte-derived hormone that decreases food intake and increases energy expenditure through the activation of the sympathetic nervous system (SNS). Notwithstanding recent intensive research, the underlying physiological mechanism of leptin as well as the etiology of obesity in humans remains elusive. The present study attempted to investigate the potential association between endogenous circulating leptin and sympatho-vagal activities in age- and height-matched obese and nonobese healthy young women. Plasma leptin concentrations were measured by radioimmunoassay. The autonomic nervous system activity was assessed during the resting condition by means of a recently devised power spectral analysis of heart rate variability, which serves to identify three separate frequency components, very low (VLO), low (LO), and high (HI). Plasma leptin concentrations were greater in the obese than in the control group (45.7 ± 5.89 vs. 11.2 ± 1.10 ng · ml,1, P < 0.01). As to the contribution of endogenous leptin to SNS activity, both the ratios of the VLO frequency component reflecting thermoregulatory sympathetic function and the global SNS index [(VLO + LO)/HI] to plasma leptin concentration were markedly reduced in the obese compared to the control group (VLO per leptin: 5.9 ± 1.39 vs. 37.8 ± 8.1 ms2 · ml · ng,1, P < 0.01; SNS index per leptin: 0.04 ± 0.008 vs. 0.33 ± 0.01 ml,,·,ng,1, P < 0.01). Additionally, a nonlinear regression analysis revealed that these ratios exponentially decreased as a function of body fat content (VLO per leptin r2 = 0.57, P < 0.01; SNS index per leptin r2 = 0.53, P < 0.01). Our data suggest that reduced sympathetic responsiveness to endogenous leptin production, implying peripheral leptin resistance, might be a pathophysiological feature of obesity in otherwise healthy young women. The findings regarding the association of leptin, body fat content, and SNS activity further indicate that the 30% of total body fat, which has been used as a criterion of obesity, might be a critical point at which leptin resistance is induced. Am. J. Hum. Biol. 15:8,15, 2003. © 2002 Wiley-Liss, Inc. [source] Occupational categories at risk for Parkinson's diseaseAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 6 2001Kandace L. Kirkey MPH Abstract Background The etiology of Parkinson's disease (PD) is considered to have a strong environmental component, but relatively few studies have investigated the potential association between occupation and the disease. Methods In a population-based case-control study, we collected comprehensive occupational histories from all study participants, 144 case and 464 control subjects. Results Chi-square analysis revealed that working in an agricultural occupation increased estimated PD risk (OR,=,1.74; 95% CI,=,0.85, 3.60). In contrast, a history of ever working in a service occupation was negatively associated with PD risk (OR,=,0.69; 95% CI,=,0.47, 1.00). Risk estimates were close to one for specific service occupations. Adjusted odds ratios for all non-service occupational and industrial categories were similar, and working in a service occupation was the only significant inverse predictor of PD risk. Conclusions Future investigations focusing on lifestyle factors and environmental exposures within the agricultural and service occupational categories are warranted. Am. J. Ind. Med. 39:564,571, 2001. © 2001 Wiley-Liss, Inc. [source] Effect of maternal smoking on prenatal screening for Down syndrome and trisomy 18 in the first trimester of pregnancyPRENATAL DIAGNOSIS, Issue 3 2008Pierre Miron Abstract Objectives To assess the impact of maternal smoking on first-trimester prenatal screening results for Down syndrome and trisomy 18. Methods Data on maternal smoking status, maternal age, gestational dating, levels of free beta-human chorionic gonadotrophin (,-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal blood and fetal nuchal translucency (NT) thickness were analyzed from a cohort of 53 114 women. Statistical analyses were carried out for crude and adjusted comparisons between smoking and nonsmoking groups. Results In women who smoked during the first trimester of pregnancy, PAPP-A and free ,-hCG levels from dried blood were significantly decreased (p < 0.001) and fetal NT thickness was significantly increased (p < 0.001). For an overall risk assessment combining maternal age and biochemical and ultrasound markers, no significant changes for Down syndrome were found with smoking, but significant increases in average risk as well as in positive rates were found for trisomy 18 (p < 0.001). A potential association between maternal smoking and trisomy 18 remains to be clarified. Conclusion Adjustment for smoking is recommended in first-trimester prenatal screening for trisomy 18 and probably not warranted for Down syndrome because of the cancelling effects of decreased free ,-hCG and increased NT. Further research is required to demonstrate a biological association between maternal smoking and trisomy 18. Copyright © 2008 John Wiley & Sons, Ltd. [source] CLOCK gene 3111C/T polymorphism is not associated with seasonal variations in mood and behavior in Korean college studentsPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2007JONG-WOO PAIK md Abstract, The present study tested the potential association between the 3111C/T polymorphism of the CLOCK gene and seasonal variations in mood and behavior. A total of 297 Korean college students were genotyped for the CLOCK polymorphism and the seasonal variation was evaluated using the Seasonal Pattern Assessment Questionnaire (SPAQ). The seasonality scores were not different between CLOCK gene variants (P > 0.05). Comparison between seasonals (syndromal plus subsyndromal seasonal affective disorder according to SPAQ) and non-seasonals found no significant difference in frequencies of genotypes (P > 0.05). These findings suggest that the CLOCK polymorphism does not play a major role in susceptibility to seasonal variations in a Korean population. [source] Mass spectrometry study of hemoglobin-oxaliplatin complexes in colorectal cancer patients and potential association with chemotherapeutic responsesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2006Rupasri Mandal Oxaliplatin is the most active platinum (Pt)-containing anticancer drug for the treatment of advanced colorectal cancer. We report here the study of potential association of the levels of oxaliplatin-protein complexes in 19 cancer patients with treatment efficacy using size-exclusion high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC/ICPMS) and nanoelectrospray ionization mass spectrometry (nanoESI-MS) techniques. Blood samples from 19 colorectal cancer patients were collected at 1 and 48,h after the first infusion of oxaliplatin. HPLC/ICPMS quantification of the oxaliplatin-protein complexes showed that the levels of Pt-protein complexes in plasma samples at 48,h were reduced by approximately 50% compared to those at 1,h, whereas those in hemolysates did not change significantly. The concentrations of hemoglobin (Hb)-oxaliplatin complexes determined by HPLC/ICPMS ranged from 3.1 to 8.7,µM. NanoESI-MS analysis of the patient hemolysates showed three distinct mass spectral profiles of the Hb-oxaliplatin complexes: (1) 1:1, (2) 1:1 with 1:2, and (3) multiple complexes of 1:1, 1:2, 1:3, and 1:4, corresponding to the Hb-oxaliplatin complex concentrations determined by HPLC/ICPMS. Potential association of variables including Hb-oxaliplatin complex concentrations with time to progress as the treatment efficacy indicator was analyzed using the Cox model. Multivariate analysis of the potential predictors showed that the statistically significant variables were Hb-oxaliplatin complex concentration (p,=,0.02), performance status (p,=,0.02), baseline neutrophil count (p,=,0.05), and the site of the primary cancer (colon vs. rectal, p,=,0.01). The hazard ratio for the concentration of the Hb-oxaliplatin complexes was 2.4, suggesting that the risk of cancer progression significantly increased with increasing of Hb-oxaliplatin complexes in patients. These results demonstrate that the level of the Hb-oxaliplatin complexes in erythrocytes is a potential biomarker for indicating inter-patient variations in oxaliplatin treatment efficacy. Copyright © 2006 John Wiley & Sons, Ltd. [source] Analysis of the macrophage scavenger receptor 1 gene in Swedish hereditary and sporadic prostate cancerTHE PROSTATE, Issue 2 2004Fredrik Lindmark Abstract BACKGROUND The macrophage scavenger receptor 1 (MSR1) gene on chromosome 8p22 was recently reported as a candidate gene for hereditary prostate cancer (HPC). Here, we further elucidate the role of MSR1 in both Swedish families with HPC and in a cohort of unselected prostate cancer. METHODS DNA samples from 83 Swedish HPC families and 215 unselected population based cases of prostate cancer as well as 425 age-matched controls were genotyped. RESULTS A total of 18 variants were identified, including 2 exonic, 7 intronic changes, and 9 changes in the 5,- or 3,-uncoding region. Of the two exonic changes, one previously reported truncation mutation was identified, a R293X nonsense mutation. This mutation was found in 2 of the 83 (2.4%) HPC families. The R293X mutation was found more frequently in men with PC (4.9%) than in unaffected men (2.7%), consistent with previous published results, however our results were not significant (P,=,0.16). To additionally test for potential association of common sequence variants and increased risk for the disease, five common polymorphisms (PRO3, INDEL1, IVS5-57, P275A, INDEL7) were genotyped in the group of 215 prostate cancer cases and 425 age-matched controls. No association between any of the five common sequence variants and prostate cancer were found. CONCLUSION Our results suggest that mutations in MSR1 gene might play a role in prostate cancer susceptibility, particularly the R293X mutation. This study warrants further investigations of the role of MSR1 in prostate cancer etiology. © 2004 Wiley-Liss, Inc. [source] Epidemics of Tomato torrado virus, Pepino mosaic virus and Tomato chlorosis virus in tomato crops: do mixed infections contribute to torrado disease epidemiology?ANNALS OF APPLIED BIOLOGY, Issue 3 2010P. Gómez Torrado disease was first observed in protected tomato crops in the Murcia province of Spain in spring 2001, causing serious concern to regional tomato producers. The disease-causing agent was initially identified as a picorna-like bipartite plant RNA virus, now known as Tomato torrado virus (ToTV), but several additional torradoviruses inducing similar disease symptoms have been described more recently. We studied the incidence of torradoviruses between 2005 and 2008 in two parts of Murcia (Spain) where tomato crops are grown commercially. We also analysed the potential association among ToTV, Pepino mosaic virus (PepMV) and Tomato chlorosis virus (ToCV) in samples showing torrado symptoms of varying severity. ToTV was the only torradovirus found in the samples (predominantly as single infections), but double and triple infections comprising ToTV, PepMV and/or ToCV were also detected. There was no evidence of a specific association among the viruses as the frequencies of mixed infections did not deviate from those expected to occur by chance. Statistical analysis of the potential association between torrado symptoms and the type of infection (single or multiple) was inconclusive. To determine whether co-infections with ToTV and PepMV have any marked influence on the torrado disease, we analysed torrado symptom severity and virus accumulation in tomato plants experimentally infected with ToTV-CE, PepMV-Sp13 and PepMV-PS5 in single and mixed infections. The severity of the torrado symptoms was not affected by the presence of PepMV. In single infections, the ToTV titre remained very low, reaching its maximum in the early stages of infection and declining rapidly thereafter, whereas the disease symptoms became more severe over the same timescale. In mixed infections, the accumulation of both ToTV and PepMV was altered with respect to single infections, and the magnitude of this alteration appeared to be virus and strain specific. Therefore, ToTV and PepMV mixed infections may modulate the epidemiology of both viruses in a complex way by altering virus fitness. The impact of our studies on efforts to track and prevent the spread of torrado disease is discussed. [source] Macrophage migration inhibitory factor promoter polymorphisms and the clinical expression of sclerodermaARTHRITIS & RHEUMATISM, Issue 11 2006Sou-Pan Wu Objective To investigate the potential association between functional polymorphisms in the gene for the innate mediator, macrophage migration inhibitory factor (MIF), and the clinical expression of systemic sclerosis (SSc). Methods Genomic DNA samples and clinical data were collected from the Scleroderma Family Registry and DNA Repository at the University of Texas Health Science Center at Houston. A total of 740 subjects were studied; 203 of them had diffuse cutaneous SSc (dcSSc), 283 had limited cutaneous SSc (lcSSc), and the remaining 254 healthy subjects served as controls. Association analyses were performed on the whole data set and on patient and sex subsets. Significant relationships were determined between clinical variables and MIF polymorphisms for each disease subtype in the studied groups. Results The frequency of the ,173*C MIF allele, which was previously reported to be associated with high production of MIF, was lower in the lcSSc group (12.6%) than in the dcSSc (19.2%) or control (18.5%) groups (P = 0.010 and P = 0.011, respectively). Haplotype analysis for 2 closely linked polymorphisms in the MIF promoter showed that in white subjects with lcSSc or dcSSc, the lcSSc population had a significantly lower representation of the high-expression MIF haplotype defined by ,173*C and ,794 with 7 CATT repeats (C7) (P = 0.015, odds ratio 1.94 [95% confidence interval 1.14,3.32]). Fibroblasts encoding the C7 MIF haplotype were observed to produce more MIF upon in vitro stimulation than those with a non-C7 haplotype. Conclusion Functional promoter polymorphisms in the MIF gene affect the clinical presentation of SSc. The proinflammatory haplotype defined by C7 is underrepresented in patients with lcSSc. [source] | |||||||||||||||||||||||||||||||