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Kinds of C Terms modified by C Selected AbstractsPeroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic menJOURNAL OF INTERNAL MEDICINE, Issue 6 2003J. Skogsberg Abstract. Objectives., Peroxisome proliferator activated receptor delta (PPARD) is a transcription factor implicated in the regulation of genes involved in cholesterol metabolism. We recently discovered a common polymorphism in the 5,-untranslated region (5,-UTR) of the human PPARD, +294T/C, that is associated with an increased plasma low-density lipoprotein cholesterol (LDL-C) concentration in healthy subjects. Whether the +294C allele is associated with LDL-C elevation independently of the background lipoprotein phenotype and whether it confers increased risk of coronary heart disease (CHD) is unknown. Against this background, we investigated the relationships between the PPARD polymorphism and plasma lipoprotein concentrations and the risk for contracting CHD in the West of Scotland Coronary Prevention Study (WOSCOPS). Design., A nested case,control study of participants in a randomized double-blind placebo-controlled trial of pravastatin in mildly-to-moderately hypercholesterolaemic men. Subjects., A total of 580 cases of incident CHD and 1160 individuals who remained free of CHD (controls). Main outcome measures., Plasma lipoprotein con-centrations and risk of CHD according to PPARD genotype. Results., Individuals carrying the rare PPARD +294C allele had a significantly lower high-density lipoprotein cholesterol (HDL-C) concentration than subjects homozygous for the common T-allele. Homozygous carriers of the C-allele also showed a tendency towards higher risk of CHD compared with homozygous carriers of the T-allele. In addition, a gene,gene interaction involving the PPARD polymorphism and the PPAR alpha L162V polymorphism may influence the plasma LDL-C concentration. Conclusions., PPARD plays a role in cholesterol metabolism in man. [source] Interleukin-10 is associated with resistance to febrile seizures: Genetic association and experimental animal studiesEPILEPSIA, Issue 4 2009Yoshito Ishizaki Summary Purpose:, Febrile seizures (FS) are the most common form of childhood convulsions. Many reports have shown that a proinflammatory cytokine, interleukin-1 (IL-1) ,, may have a facilitatory effect on the development of FS. We have previously shown that the IL1B -511C/T single nucleotide polymorphism (SNP) is associated with simple FS of sporadic occurrence. The balance between pro- and antiinflammatory cytokines influences the regulation of infections and could, therefore, play a role in the pathogenesis of FS. Here, to determine whether pro- and antiinflammatory cytokine genes are responsible for the susceptibility to FS, we have performed an association study on functional SNPs of cytokine genes in FS patients and controls. Methods:, The promoter SNPs of four inflammatory cytokine genes (IL6 -572C/G, IL8 -251A/T, IL10 -592A/C and TNFA -1037C/T) were examined in 249 patients with FS (186 simple and 63 complex FS) and 225 controls. Because the IL10 -592 SNP showed a positive association with FS, two additional SNPs (IL10 -1082A/G and -819T/C) were subjected to haplotype analysis. Furthermore, we examined the in vivo role of IL-10 in hyperthermia-induced seizures using immature animal models. Results:, The frequencies of the IL10 -592C allele and -1082A/-819C/-592C haplotype were significantly decreased in FS as compared with in controls (p = 0.014 and 0.013, respectively). The seizure threshold temperature in the IL-10,administered rats was significantly higher than that in the saline-treated control ones (p = 0.027). Conclusions:, The present study suggests that IL-10 is genetically associated with FS and, contrary to IL-1,, confers resistance to FS. [source] Combinatorial Search for Quaternary Methanol Tolerant Oxygen Electro-Reduction CatalystFUEL CELLS, Issue 1 2010M. K. Jeon Abstract A combinatorial library containing 645 different compositions was synthesised and characterised for methanol tolerant oxygen electro-reduction reaction (ORR) catalytic performance. The library was composed of compositions involving between 1 and 4 metals among Pt, Ru, Fe, Mo and Se. In an optical screening test, Pt(50)Ru(10)Fe(20)Se(10) composition exhibited the highest ORR activity in the presence of methanol. This composition was further investigated by synthesis and characterisation of a powder version catalyst [Pt(50)Ru(10)Fe(20)Se(10)/C]. At 0.85,V [vs. reversible hydrogen electrode (RHE)] in the absence of methanol, the Pt/C catalyst exhibited higher ORR current (0.0990,mA) than the Pt(50)Ru(10)Fe(20)Se(10)/C catalyst (0.0902,mA). But much higher specific activity (12.7 ,A cmpt,2) was observed in the Pt(50)Ru(10)Fe(20)Se(10)/C catalyst than for the Pt/C catalyst 6.51 ,A cmpt,2). In the presence of methanol, the ORR current decreased by 0.0343 and 0.247,mA for the Pt(50)Ru(10)Fe(20)Se(10)/C and Pt/C catalysts, respectively, which proved the excellent methanol tolerance of the Pt(50)Ru(10)Fe(20)Se(10)/C catalyst. [source] Direct detection of the protein quaternary structure and denatured entity by small-angle scattering: guanidine hydrochloride denaturation of chaperonin protein GroELJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 1 2002Yasutaka Seki A change in the higher-order structure of an oligomeric protein is directly detectable by small-angle scattering. A small-angle X-ray scattering (SAXS) study of the denaturation process of the chaperonin protein GroEL by guanidine hydrochloride (GdnHCl) showed that the disappearance of the quaternary structure can be monitored by using a Kratky plot of the scattered intensities, demonstrating the advantage of the SAXS method over other indirect methods, such as light scattering, circular dichroism (CD), fluorescence and sedimentation. The collapse of the quaternary structure was detected at a GdnHCl concentration of 0.8,M for a solution containing ADP (adenosine diphosphate)/Mg2+(2,mM)/K+. From pairwise plots of the change in forward scattering intensity J(0)/C (weight-average molecular weight) and the z -average (root mean square) radius of gyration against the GdnHCl concentration, the stability and nature of the denatured protein can be determined. The SAXS results suggest that the GroEL tetradecamer directly dissociates to the unfolded coil without going through a globular monomer state. The denatured ensemble is not a single unfolded monomer coil particle, but some mixture of entangled aggregates and a monomer of the coil molecules. Small-angle scattering is a powerful method for the detection and study of changes in quaternary and higher-order structures of oligomeric proteins. [source] Ethanol-tolerant Pt-alloy cathodes for direct ethanol fuel cell (DEFC) applicationsASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 1 2009F. J. Rodríguez Varela Abstract The electroactivity of Pt1Co1(a/o)/C and Pt3Cr1(a/o)/C for the oxygen reduction reaction (ORR) in ethanol-containing medium was studied. It was found that these cathodes present a high tolerance to this alcohol. The onset potential of the ORR decreased at 14 and 12 mV in the presence of 0.5 M ethanol on Pt1Co1/C and Pt3Cr1/C, respectively. The tolerance of the Pt alloys is one order of magnitude higher than that shown by Pt-alone catalysts in previous works. Exceptionally, the Pt1Co1/C alloy maintained a very important electrocatalytic activity, i.e. a very small variation in current density at 400 mV in electrochemical cell measurements and improved performances in a direct ethanol fuel cell (DEFC). The current densities obtained from the DEFC equipped with a 10% Pt1Co1/C cathode were similar to those obtained when 20% Pt3Cr1/C was used. However, a higher performance in terms of Pt content was shown by PtCo/C. These electrochemical characteristics indicate the advantage of using PtCo alloys as cathodes in DEFCs. Copyright © 2008 Curtin University of Technology and John Wiley & Sons, Ltd. [source] The modifying effect of C-reactive protein gene polymorphisms on the association between central obesity and endometrial cancer riskCANCER, Issue 11 2008Wanqing Wen MD Abstract BACKGROUND. Obesity is a major risk factor for endometrial cancer. Obesity, particularly central obesity, is considered as a systemic inflammatory condition and is related strongly to insulin resistance. C-reactive protein (CRP) is the most recognized biologic marker of chronic systematic inflammation, and it is conceivable that the CRP gene may work together with obesity in the development of endometrial cancer. METHODS. On the basis of a population-based case,control study in a Chinese population, the authors obtained obesity measurements and data on 6 CRP single-nucleotide polymorphisms (SNPs) from 1046 patients with newly diagnosed endometrial cancer (cases) and from 1035 age frequency-matched controls. The association of the CRP SNPs with endometrial cancer risk and their modification on the association between obesity and endometrial cancer risk were evaluated. RESULTS. Although CRP SNPs alone were not associated with endometrial cancer, the associations of endometrial cancer with central obesity, measured as the waist-to-hip ratio (WHR) and the waist circumference, seemed to be stronger in women who were homozygous for the major allele of reference SNP (rs)1130864 (cytidine [C]/C) than in women who had the C/thymidine (T) and T/T genotypes (interaction test: P = .013 for WHR; P = .083 for waist circumference). When the women were stratified further by menopausal status, the observed interactions persisted mainly in premenopausal women (interaction test: P < .001 for WHR; P = .002 for waist circumference). CONCLUSIONS. The current results suggested that, in the Chinese population that was studied, obesity-related insulin resistance and proinflammatory effects may play an important role in endometrial cancer risk, and these effects were modified significantly by the CRP SNP rs1130864. Cancer 2008. © 2008 American Cancer Society. [source] Growth and characterisation of potassium cobalt nickel sulfate hexahydrate for UV light filtersCRYSTAL RESEARCH AND TECHNOLOGY, Issue 10 2006Xinxin Zhuang Abstract A new single crystal for ultraviolet light filter, KCNSH (Potassium Cobalt Nickel Sulfate Hexahydrate) was designed and its crystal structure was studied using X-ray diffraction in this paper. The empirical of the title compound is K2Co0.1Ni0.9(SO4)2.6H2O with formula weight 437.15. KCNSH crystal belongs to the monoclinic space group P2(1)/c, a=6.1390(3)Å, b=12.1839(6)Å, c=9.0095(4)Å, ,=,=90°, ,=105.060(2)°, V=650.74(5)Å3, Z=2, Dc=2.231g/cm3. Using the cooling solution method, we have grown a deep green KCNSH crystal with dimension of 12×12×40mm3. The transmission spectrum of KCNSH in the range from UV to near IR wavelengths, its thermal properties, and the relationship between the structure and optical transmission properties are also studied and further discussed in this paper. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Quality control of protein standards for molecular mass determinations by small-angle X-ray scatteringJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 2 2010Shuji Akiyama Small-angle X-ray scattering (SAXS) is a powerful technique with which to evaluate the size and shape of biological macromolecules in solution. Forward scattering intensity normalized relative to the particle concentration, I(0)/c, is useful as a good measure of molecular mass. A general method for deducing the molecular mass from SAXS data is to determine the ratio of I(0)/c of a target protein to that of a standard protein with known molecular mass. The accuracy of this interprotein calibration is affected considerably by the monodispersity of the prepared standard, as well as by the precision in estimating its concentration. In the present study, chromatographic fractionation followed by hydrodynamic characterization is proposed as an effective procedure by which to prepare a series of monodispersed protein standards. The estimation of molecular mass within an average deviation of 8% is demonstrated using monodispersed bovine serum albumin as a standard. The present results demonstrate the importance of protein standard quality control in order to take full advantage of interprotein calibration. [source] Oxidative stress activates a positive feedback between the ,- and ,-secretase cleavages of the ,-amyloid precursor proteinJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Elena Tamagno Abstract Sequential cleavages of the ,-amyloid precursor protein cleaving enzyme 1 (BACE1) by ,-secretase and ,-secretase generate the amyloid ,-peptides, believed to be responsible of synaptic dysfunction and neuronal cell death in Alzheimer's disease (AD). Levels of BACE1 are increased in vulnerable regions of the AD brain, but the underlying mechanism is unknown. Here we show that oxidative stress (OS) stimulates BACE1 expression by a mechanism requiring ,-secretase activity involving the c- jun N-terminal kinase (JNK)/c- jun pathway. BACE1 levels are increased in response to OS in normal cells, but not in cells lacking presenilins or amyloid precursor protein. Moreover, BACE1 is induced in association with OS in the brains of mice subjected to cerebral ischaemia/reperfusion. The OS-induced BACE1 expression correlates with an activation of JNK and c- jun, but is absent in cultured cells or mice lacking JNK. Our findings suggest a mechanism by which OS induces BACE1 transcription, thereby promoting production of pathological levels of amyloid , in AD. [source] Semaphorin 3A and neurotrophins: a balance between apoptosis and survival signaling in embryonic DRG neuronsJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Ayal Ben-Zvi Abstract Large numbers of neurons are eliminated by apoptosis during nervous system development. For instance, in the mouse dorsal root ganglion (DRG), the highest incidence of cell death occurs between embryonic days 12 and 14 (E12,E14). While the cause of cell death and its biological significance in the nervous system is not entirely understood, it is generally believed that limiting quantities of neurotrophins are responsible for neuronal death. Between E12 and E14, developing DRG neurons pass through tissues expressing high levels of axonal guidance molecules such as Semaphorin 3A (Sema3A) while navigating to their targets. Here, we demonstrate that Sema3A acts as a death-inducing molecule in neurotrophin-3 (NT-3)-, brain-derived neurotrophic factor (BDNF)- and nerve growth factor (NGF)-dependent E12 and E13 cultured DRG neurons. We show that Sema3A most probably induces cell death through activation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway, and that this cell death is blocked by a moderate increase in NGF concentration. Interestingly, increasing concentrations of other neurotrophic factors, such as NT-3 or BDNF, do not elicit similar effects. Our data suggest that the number of DRG neurons is determined by a fine balance between neurotrophins and Semaphorin 3A, and not only by neurotrophin levels. [source] Preparation, Structural Characterization and Luminescent Property of Binuclear Silver (I) Complex Formed by Benzotriazole and 1-Hydroxymethyl BenzotriazoleCHINESE JOURNAL OF CHEMISTRY, Issue 9 2002Qing-Xiang Liu Abstract Dinuclear silver (I) six-membered ring complex [Ag2 (bta)2 -(hmbta)2] (ClO4)2 (3) has been synthesized by the reaction of benzotriazole (bta) (1) and 1-hydroxymethyl benzotriazole (hmbta) (2) with Ag (CH3CN)4ClO4. The structures of compound 2 and Complex 3 have been studied by single crystal X-ray diffraction analysis. The change of luminescent intensity of 1, 2 and 3 was reported. Compound 2 crystallizes in the monoclinic system with space group P2 (1)/c, a = 0.7655 (10) nm, b = 1.0126 (14) nm, c =0.9502 (13) nm, , = 95.07 (2)°, V = 0.7337 (17) nm3 and Z = 4. Complex 3 crystallizes in the triclinic system with space group P1, a = 0.73611 (18) nm, b = 0.9152 (2) nm, c = 1.2277 (3) nm, , = 87.170 (5)°, V = 0.8221 (3) nm3 and Z = 1. The main structural feature of complex 3 is a symmetric dinuclear six-membered ring formed by two silver (I) atoms and four N-atoms from two benzotriazoles. The second structural feature of complex 3 is the ,-, stacking interaction between two adjacent molecular planes, which forms the two-dimentional layer structure. Besides, compared with 2, the luminescent intensity of complex 3 shows a remarkable enhancement. [source] Phosphorylation-dependent dimerization and subcellular localization of islet-brain 1/c-Jun N-terminal kinase-interacting protein 1JOURNAL OF NEUROSCIENCE RESEARCH, Issue 16 2007T. Borsello Abstract Islet-brain 1 [IB1; also termed c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP-1] is involved in the apoptotic signaling cascade of JNK and functions as a scaffold protein. It organizes several MAP kinases and the microtubule-transport motor protein kinesin and relates to other signal-transducing molecules such as the amyloid precursor protein. Here we have identified IB1/JIP-1 using different antibodies that reacted with either a monomeric or a dimeric form of IB1/JIP-1. By immunoelectron microscopy, differences in the subcellular localization were observed. The monomeric form was found in the cytoplasmic compartment and is associated with the cytoskeleton and with membranes, whereas the dimeric form was found in addition in nuclei. After treatment of mouse brain homogenates with alkaline phosphatase, the dimeric form disappeared and the monomeric form decreased its molecular weight, suggesting that an IB1/JIP-1 dimerization is phosphorylation dependent and that IB1 exists in several phospho- forms. N-methyl-D-aspartate receptor activation induced a dephosphorylation of IB1/JIP-1 in primary cultures of cortical neurons and reduced homodimerization. In conclusion, these data suggest that IB1/JIP-1 monomers and dimers may differ in compartmental localization and thus function as a scaffold protein of the JNK signaling cascade in the cytoplasm or as a transcription factor in nuclei. © 2007 Wiley-Liss, Inc. [source] Association of the OGG1 Ser326Cys polymorphism with tooth lossJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2006Yoshinori Hasui Abstract Although tooth loss is a serious health problem for elderly people, little is known about the genetic basis for susceptibility to it. In the present study we aimed to find a single nucleotide polymorphism (SNP) associated with tooth loss. DNA samples from 119 outpatients (mean age=78.8 years) were genotyped on seven polymorphisms (tumor necrosis factor-, ,1031T/C, interleukin-1, ,511C/T, interleukin-6 ,634C/G, macrophage migration inhibitory factor ,173G/C, interleukin-1 receptor antagonist variable number of tandem repeat in intron 2, matrix metalloproteinase-1 ,16071G/2G, and oxoguanine glycosylase 1 (OGG1) Ser326Cys (1245C/G)), and the results were statistically evaluated. Of the seven polymorphisms tested, only OGG1 Ser326Cys was revealed to associate with tooth loss at a statistically significant level (P=0.0086). In addition, a multivariate logistic regression analysis in which age, gender, body mass index (BMI), and ischemic heart disease were included as independent variables indicated that Ser326Cys could be an independent factor affecting tooth loss (OR, 3.191; 95%CI, 1.174,8.672). The data suggest that the OGG1 Ser326Cys polymorphism may be associated with tooth loss. J. Clin. Lab. Anal. 20:47,51, 2006. © 2006 Wiley-Liss, Inc. [source] Testing Genetic Susceptibility Loci for Alcoholic Heart Muscle DiseaseALCOHOLISM, Issue 10 2001Olli A. Kajander Background: Although many heavy alcohol users have subclinical alcoholic heart muscle disease, only a very few develop severe dilated cardiomyopathy. Therefore, and because cardiac abnormalities correlate only weakly with the duration or quantity of drinking, individual susceptibility differences may exist. In this work we examined whether common gene variants previously associated with cardiac hypertrophy or altered alcohol metabolism could modify the effects of alcohol on the heart. Methods: We studied 700 middle-aged male victims of sudden death who underwent a medicolegal autopsy. In addition to routine postmortem examination, the weights and the cavity and wall dimensions of the left and right ventricle were measured. Coronary artery stenoses were determined from a silicone rubber cast of the arteries. Alcohol consumption and cardiovascular risk factors were assessed by a structured interview of the spouse. The following gene polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism and solid-phase minisequencing techniques: angiotensin converting enzyme I/D, angiotensin II type 1 receptor 1166A/C, aldosterone synthase ,344C/T, alcohol dehydrogenases 2 and 3, acetaldehyde dehydrogenase 2, and cytochrome P-450 2E1 Dra I, Pst I, Rsa I, and Msp I. Results: The most consistent effects of alcohol (p < 0.05) were a higher total heart weight and a larger right ventricle size with increasing daily drinking. However, these and other effects of alcohol were statistically fully independent of the studied genotypes. Conclusions: The gene polymorphisms selected for and analyzed in our study are unlikely to modify the effects of alcohol on the heart. Other unknown factors determine the individual susceptibility to alcoholic heart muscle disease. [source] Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese populationINFLAMMATORY BOWEL DISEASES, Issue 12 2005T Takagawa MD Abstract Background: Interleukin-18 (IL-18) is a pleiotropic cytokine that induces the production of interferon (IFN)-, and also to regulate Th2 cytokines. Recently, association studies between IL-18 gene promoter polymorphisms and several Th1- or Th2-mediated inflammatory diseases were reported. In inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), recent evidence suggests that IL-18 is involved in the pathogenesis. Methods: Using DNA direct sequencing, we investigated IL-18 gene promoter polymorphisms at ,607C/A and ,137G/C. Allele, genotype, and haplotype frequencies were determined in 210 Japanese patients with UC, 205 patients with CD, and 212 controls. Results: In UC, the ,137C allele frequency was significantly higher in the proctitis-type patients than in controls (Pc = 0.0068). The ,137 genotype frequency was also significantly different in the proctitis-type patients than in controls (Pc = 0.032). No other allele and genotype frequencies were significantly associated with UC after Bonferroni correction. Furthermore, the frequency of haplotype 2 (,607A, ,137C), which had a lower promoter activity and IFN-, mRNA level than the other haplotypes as previously reported, was significantly higher in the proctitis-type patients than in controls (Pc = 0.01). In CD, we could not find any significant differences. Conclusions: IL-18 gene promoter polymorphisms may not be associated with disease susceptibility but related to the extent of disease in UC. [source] The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma.CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2006The SAPALDIA Cohort Study Summary Background IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. Objective To examine the relationship of a genetic, haplotype-tagging promotor variant ,137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. Methods Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. Results The G-allele of the IL-18 promotor variant (,137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 ,137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64,8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66,1.94). The interaction between IL-18 ,137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. Conclusion Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma. [source] NRAMP1 (SLC11A1) gene polymorphisms that correlate with autoimmune versus infectious disease susceptibility in tuberculosis and rheumatoid arthritisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2009Ö. Ates Summary NRAMP1 gene has multiple pleiotropic effects on macrophage activation pathways. These pleiotropic effects may increase resistance to infections such as tuberculosis (TB), but may also lead to susceptibility of autoimmune diseases such as rheumatoid arthritis (RA). It has been hypothesized that allele 3 would be associated with autoimmune diseases, whereas allele 2 would be associated with infectious diseases, and genetic factors that enhanced survival in the epidemics of TB might have led to susceptibility for the development of RA. We analysed four NRAMP1 gene polymorphisms including 5, promoter (GT)n (rs34448891), INT4 (469 + 14G/C) (rs3731865), 3,UTR (1729 + 55del4) (rs17235416) and D543N (codon 543, Asp to Asn) (rs17235409) in 112 patients with TB, 98 patients with RA, 80 healthy controls for TB and 122 healthy controls for RA using ARMS-PCR and PCR-RFLP. We found a significant association between INT4 and RA (P = 0.004, odds ratio: 2.06, 95% CI: 1.24,3.41), but no significant differences between 5, promoter, D543N, 3,UTR polymorphisms and RA. There were no associations between NRAMP1 gene polymorphisms and TB. Similarly, no significant differences were observed between NRAMP1 polymorphisms and rheumatoid factor positivity and erosive disease in RA and localization of TB. INT4 polymorphism may be associated with RA in Turkish patients. [source] CTLA-4 gene promoter and exon 1 polymorphisms in Iranian patients with gastric and colorectal cancersJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2007Abolghasem Hadinia Abstract Background and Aim:, Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by down-regulating T-cell activation. Effects of several polymorphisms in CTLA-4 on CTLA-4 expression and function have been previously documented. The aim of this study was to investigate the putative effect of CTLA-4 polymorphisms on susceptibility to gastric and colorectal cancers in an Iranian population. Methods:, A total of 155 patients (109 with colorectal cancer and 46 with gastric cancer) and 190 age- and sex-matched healthy controls were evaluated. Genotyping of ,1722T/C, ,1661A/G, and +49A/G were performed by PCR restriction fragment length polymorphism methods and of ,318C/T by a PCR amplification refractory mutation system technique. Results:, No statistically significant differences were found in the genotype distribution and allele frequencies among patients and controls. Haplotype analysis demonstrated that the TACG haplotype (,1722T, ,1661A, ,318C, +49G) frequency was significant increased in patients with colorectal cancer (P = 0.009) and gastric cancer (P = 0.006) in comparison to the control group. In contrast, the TACA haplotype frequency was significantly decreased in patients with colorectal cancer (P = 0.02) and not significantly decreased in patients with gastric cancer (P = 0.13) compared to the control group. Conclusion:, A positive association between CTLA-4 TACG haplotype and gastric and colorectal cancers was found in an Iranian population. A protective role for TACA haplotype is postulated. [source] Association of the OGG1 Ser326Cys polymorphism with tooth lossJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2006Yoshinori Hasui Abstract Although tooth loss is a serious health problem for elderly people, little is known about the genetic basis for susceptibility to it. In the present study we aimed to find a single nucleotide polymorphism (SNP) associated with tooth loss. DNA samples from 119 outpatients (mean age=78.8 years) were genotyped on seven polymorphisms (tumor necrosis factor-, ,1031T/C, interleukin-1, ,511C/T, interleukin-6 ,634C/G, macrophage migration inhibitory factor ,173G/C, interleukin-1 receptor antagonist variable number of tandem repeat in intron 2, matrix metalloproteinase-1 ,16071G/2G, and oxoguanine glycosylase 1 (OGG1) Ser326Cys (1245C/G)), and the results were statistically evaluated. Of the seven polymorphisms tested, only OGG1 Ser326Cys was revealed to associate with tooth loss at a statistically significant level (P=0.0086). In addition, a multivariate logistic regression analysis in which age, gender, body mass index (BMI), and ischemic heart disease were included as independent variables indicated that Ser326Cys could be an independent factor affecting tooth loss (OR, 3.191; 95%CI, 1.174,8.672). The data suggest that the OGG1 Ser326Cys polymorphism may be associated with tooth loss. J. Clin. Lab. Anal. 20:47,51, 2006. © 2006 Wiley-Liss, Inc. [source] Identification of a new genotype H wild-type mumps virus strain and its molecular relatedness to other virulent and attenuated strainsJOURNAL OF MEDICAL VIROLOGY, Issue 2 2003Georgios Amexis Abstract A single clinical isolate of mumps virus designated 88-1961 was obtained from a patient hospitalized with a clinical history of upper respiratory tract infection, parotitis, severe headache, fever and lymphadenopathy. We have sequenced the full-length genome of 88-1961 and compared it against all available full-length sequences of mumps virus. Based upon its nucleotide sequence of the SH gene 88-1961 was identified as a genotype H mumps strain. The overall extent of nucleotide and amino acid differences between each individual gene and protein of 88-1961 and the full-length mumps samples showed that the missense to silent ratios were unevenly distributed. Upon evaluation of the consensus sequence of 88-1961, four positions were found to be clearly heterogeneous at the nucleotide level (NP 315C/T, NP 318C/T, F 271A/C, and HN 855C/T). Sequence analysis revealed that the amino acid sequences for the NP, M, and the L protein were the most conserved, whereas the SH protein exhibited the highest variability among the compared mumps genotypes A, B, and G. No identifying molecular patterns in the non-coding (intergenic) or coding regions of 88-1961 were found when we compared it against relatively virulent (Urabe AM9 B, Glouc1/UK96, 87-1004 and 87-1005) and non-virulent mumps strains (Jeryl Lynn and all Urabe Am9 A substrains). J. Med. Virol. 70: 284,286, 2003. © 2003 Wiley-Liss, Inc. [source] Pharmacological characterization of ,2 -adrenoceptor-mediated responses in pig nasal mucosaAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2003M. R. Corboz Summary 1 Pig nasal mucosal strips were incubated with ,-adrenoceptor antagonists followed by ,2 -adrenoceptor agonist concentration,response curves. 2 Contractions elicited by the ,2 -adrenoceptor agonists BHT-920 (pD2 = 6.16 ± 0.07), UK 14,304 (pD2 = 6.89 ± 0.13) and PGE-6201204 (pD2 = 7.12 ± 0.21) were blocked by the ,2 -adrenoceptor antagonist yohimbine (0.1 ,m). In contrast, the ,1 -adrenoceptor antagonist prazosin (0.03 ,m) had no effect on the BHT-920-, UK 14,304- and PGE-6201204-induced contractions, but blocked the contractile response to the ,1 -adrenoceptor agonist phenylephrine (pD2 = 5.38 ± 0.04) and the mixed ,1 - and ,2 -adrenoceptor agonist oxymetazoline (pD2 = 6.30 ± 0.22). 3 The ,2 -adrenoceptor antagonist yohimbine (0.01,0.1 ,m, pA2 = 8.04), ,2B/C -adrenoceptor antagonist ARC 239 (10 ,m, pKb = 6.33 ± 0.21), ,2A/C -adrenoceptor antagonist WB 4101 (0.3 ,m, pKb = 8.01 ± 0.24), ,2A -adrenoceptor antagonists BRL44408 (0.1 ,m, pKb = 6.82 ± 0.34) and RX 821002 (0.1 ,m, pKb = 8.31 ± 0.35), ,2C -adrenoceptor antagonists spiroxatrine (1 ,m, pKb = 7.32 ± 0.32), rauwolscine (0.1 ,m, pKb = 8.16 ± 0.14) and HV 723 (0.3 ,m, pKb = 7.68 ± 0.14) inhibited BHT-920-induced contractions in pig nasal mucosa. 4 The present antagonist potencies showed correlations with binding affinity estimates (pKi) obtained for these antagonists at the human recombinant ,2A - and ,2C -adrenoceptors (r = 0.78 and 0.83, respectively) and with binding affinity estimates (pKd) obtained in pig native ,2A - and ,2C -monoreceptor assays (r = 0.85 and 0.78, respectively). No correlation was observed for the ,2B -subtype. 5 In conclusion, contractile responses to phenylephrine, BHT-920, UK 14,304, PGE-6201204 and oxymetazoline indicate that ,1 - and ,2 -adrenoceptors are present and mediate vasoconstriction in pig nasal mucosa. Furthermore, correlation analysis comparing antagonist potency in pig nasal mucosa with affinities for human recombinant ,2 -adrenoceptors and native pig ,2 -adrenoceptors suggest that ,2A - and ,2C -adrenoceptor subtypes constrict pig nasal mucosa vasculature. [source] Antinociceptive Synergism of MD-354 and Clonidine.BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Part II. In the present investigation, a possible role for ,2 -adrenoceptors was examined. Mechanistic studies using yohimbine (a subtype non-selective ,2 -adrenoceptor antagonist), BRL 44408 (a preferential ,2A -adrenoceptor antagonist) and imiloxan (a preferential ,2B/C -adrenoceptor antagonist) on the antinociceptive actions of a MD-354/clonidine combination were conducted. Subcutaneous pre-treatment with all three antagonists inhibited the antinociceptive synergism of MD-354 and clonidine in the mouse tail-flick assay in a dose-dependent manner (AD50 = 0.33, 2.1, and 0.17 mg/kg, respectively). Enhancement of clonidine antinociception by MD-354 did not potentiate clonidine's locomotor suppressant activity in a mouse locomotor assay. When [ethyl- 3H]RS-79948-197 was used as radioligand, MD-354 displayed almost equal affinity to ,2A - and ,2B -adrenoceptors (Ki = 110 and 220 nM) and showed lower affinity at ,2C -adrenoceptors (Ki = 4,700 nM). MD-354 had no subtype-selectivity for the ,2 -adrenoceptor subtypes as an antagonist in functional [35S]GTP,S binding assays. MD-354 was a weak partial agonist at ,2A -adrenoceptors. Overall, in addition to the 5-HT3 receptor component, the present investigation found MD-354 to be a weak partial ,2A -adrenoceptor agonist that enhances clonidine's thermal antinociceptive actions through an ,2 -adrenoceptor-mediated mechanism without augmenting sedation. [source] Hepatitis C virus infection among HIV-1 infected individuals from northern MexicoHEPATOLOGY RESEARCH, Issue 5 2007Ana M. Rivas-Estilla Aims:, The prevalence of hepatitis C virus (HCV) infection, risk factors and HCV genotypes in 140 HIV-1 infected individuals from northern Mexico was determined. Methods:, Hepatitis C infection was confirmed by the detection of anti-HCV antibodies and HCV-RNA in sera, and genotyping was performed by the InnoLiPA-HCV genotype assay. Results:, Seventeen (12.1%) out of 140 HIV-infected individuals were found to be HCV-positive. Coinfected individuals were more likely to be male (87%). The most frequent genotype was 1a (41%), followed by 1b (29.4%), 2a/c (17.6%), 2b (5.9%) and 3 (5.9%). Serum transaminase concentrations (AST and ALT) were higher in coinfected patients. Among the risk factors for coinfection: sexual transmission was the most frequently observed (men who have sex with men (MSM); 64.7% and bisexual behavior; 64.7%) followed by intravenous drug users (IVDU) (53%). There was no association of the HCV genotypes with the age and risk factors for HIV-1 and HCV infection observed in the studied patients. Conclusion:, The results suggest that the prevalence of HIV-1/HCV coinfection in Mexico is lower than in other American countries. [source] Sequence variants of the secreted phosphoprotein 1 gene are associated with total serum immunoglobulin E levels in a Japanese populationCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2006Y. Tanino Summary Background Secreted phosphoprotein 1 (SPP1) is a cytokine with pleiotrophic immunological activities, including activation of macrophage chemotaxis and T-helper type 1 (Th1) immune responses. SPP1 gene polymorphisms have been shown to be associated with several immune inflammatory diseases including multiple sclerosis (MS), which is characterized by fewer allergic symptoms and lower numbers of allergen sensitizations. Objective The present study examined whether SPP1 gene polymorphisms are associated with total serum IgE levels, atopy and asthma in a Japanese population. Methods This case,control association analysis examined 611 subjects, including 268 subjects with asthma. We genotyped three promoter and two exon polymorphisms at SPP1: ,1687A/G; ,381T/C; ,94 deletion/G; 5891C/T; and 7052T/C. Results Association analyses of SPP1 polymorphisms showed that homozygosities for the 5891T allele (P=0.009) and 7052C allele (P=0.001) were significantly associated with increased levels of total IgE in non-asthmatic subjects. However, these variants were not associated with asthma and atopy. Interestingly, individuals carrying the 5891C allele, which is more prevalent in patients with MS in Japanese populations, displayed significantly lower levels of total serum IgE. Individuals homozygous for the 7052C allele, which is associated with development of systemic lupus erythematosus, displayed significantly higher total serum IgE levels. Conclusion These findings suggest that genetic polymorphisms in SPP1 may play a role in controlling basal levels of total serum IgE, independent of atopy. [source] Study of V1a vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsivenessJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2006Kazi N. Hasan Abstract There is a significant heterogeneity among individuals in terms of platelet aggregation response to arginine vasopressin (AVP). The aim of this study was to evaluate whether four single nucleotide polymorphisms (SNPs) in the promoter region of vasopressin V1a receptor gene (V1aR) could be used as genetic markers for divergent platelet aggregation response to AVP. Seventeen of 33 subjects showed more than 60% of maximum platelet aggregation and were classified as responders. Sixteen were classified as nonresponders because they had less than 30% aggregation. In a preliminary study, V1aR gene sequences were determined in two responders and two nonresponders. We found four SNPs in the promoter region of the V1aR gene: ,6951G/A, ,4112A/T, ,3860T/C, and ,242C/T. In all 33 subjects the genotypes of four SNPs were determined using either polymerase chain reaction (PCR) with allele-specific primers or PCR followed by restriction-fragment length polymorphism (RFLP). There were no differences in the AVP-induced aggregation between the subjects with and without variant alleles of each four SNPs. The genotype frequencies of four SNPs of V1aR were almost identical between AVP responders and nonresponders. These results suggest that the four SNPs in the promoter region of the V1aR gene may not be useful as genetic markers for platelet aggregation heterogeneity. J. Clin. Lab. Anal. 20:87,92, 2006. © 2006 Wiley-Liss, Inc. [source] The two-hydrophobic domain tertiary structure of reticulon proteins is critical for modulation of ,-secretase BACE1JOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2009Hideaki Kume Abstract ,-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is a membrane-bound protease that is essential for the production of ,-amyloid protein (A,). Given the crucial role of A, accumulation in Alzheimer's disease (AD), inhibition of BACE1 activity may represent a feasible therapeutic strategy in the treatment of AD. Recently, we and others identified reticulon 3 (RTN3) and reticulon 4-B/C (RTN4-B/C or Nogo-B/C) as membrane proteins that interact with BACE1 and inhibit its ability to produce A,. In this study, we employed various mutants of RTN3 and RTN4-C and C. elegans RTN to investigate the molecular mechanisms by which RTNs regulate BACE1. We found that RTN3 mutants lacking the N-terminal or C-terminal or loop domain as well as a RTN4-C mutant lacking the C-terminal domain bound to BACE1 comparably to wild-type RTN3 and RTN4-C. Furthermore, overexpression of wild-type RTN3, RTN4-C, and these RTN mutants similarly reduced A,40 and A,42 secretion by cells expressing Swedish mutant APP. C. elegans RTN, which has low homology to human RTNs, also interacted with BACE1 and inhibited A, secretion. In contrast, two RTN3 mutants containing deletions of the first or second potential transmembrane domains and an RTN3 swap mutant of the second transmembrane domain bound BACE1 but failed to inhibit A, secretion. Collectively, these results suggest that the two-transmembrane-domain tertiary structure of RTN proteins is critical for the ability of RTNs to modulate BACE1 activity, whereas N-terminal, C-terminal and loop regions are not essential for this function. © 2009 Wiley-Liss, Inc. [source] The functional ,443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factorMOLECULAR CARCINOGENESIS, Issue 1 2009Julia Schultz Abstract In the present report, the possible role of a recently described functional polymorphism of the osteopontin (OPN) promoter at position ,443 (,443T/C) for OPN expression in melanoma cells was addressed. As shown by real-time PCR analysis, melanoma metastases that were homozygous for the ,443C allele expressed significantly higher levels of OPN mRNA compared with those that were either heterozygous (,443T/C) or homozygous for the ,443T allele. In line with this, immunoblotting showed significantly enhanced baseline and bFGF-induced OPN protein expression in melanoma cell lines which were homozygous for the ,443C allele, compared with cell lines with other allelic variants. Similar results were obtained in in vitro luciferase assays. Chromatin immunoprecipitation (ChIP) demonstrated binding of c-Myb to the ,443 OPN promoter region, and binding could significantly be enhanced after bFGF stimulation. Moreover, as shown by electrophoretic mobility shift assays (EMSA), recombinant DNA-binding domain of c-Myb bound in a sequence-specific manner to this region. Finally, the role of c-Myb for OPN gene regulation via binding to the ,443 promoter region could be further substantiated by ectopic overexpression of c-Myb in melanoma cells, using different reporter gene constructs. Taken together, it is demonstrated that the ,443 promoter region exerts influence on OPN gene expression in melanoma cells, and differential binding of c-Myb transcription factor appears to play a major role in this process. These findings might be a feasible explanation for different OPN expression levels in metastatic tumors and may also have prognostic and therapeutic relevance. © 2008 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Association Study of Vascular Endothelial Growth Factor and Polymorphisms of its Gene with Ectopic PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010Julio Elito Jr Citation Elito J Jr, Daher S, Fernandes da Silva MO, Marconi NMH, Pendeloski KPT, Moron AF, Camano L. Association study of vascular endothelial growth factor and polymorphisms of its gene with ectopic pregnancy. Am J Reprod Immunol 2010; 63: 120,125 Problem, In ectopic pregnancy, increased levels of vascular endothelial growth factor are present. The aims of this study were to determine the association between ,634C/G, ,460T/C, and +936C/T vascular endothelial growth factor (VEGF) polymorphisms and ectopic pregnancy, and to determine whether serum levels of VEGF were affected by genetic factors. Method of study, This is a case,control study wherein 74 women with a history of ectopic pregnancy in a tertiary care center were compared to 134 post-menopausal controls with two pregnancies and no ectopic pregnancy for the genotyping of VEGF polymorphisms. For 35 patients with the diagnosis of ectopic pregnancy, serum concentrations of VEGF were obtained before the treatment. Genotyping of VEGF (,634C/G, ,460T/C, and +936C/T) polymorphisms was performed by PCR, followed by endonuclease digestion. ELISA was performed to evaluate the VEGF serum levels. Results, The ,634C/G, ,460T/C, and +936C/T VEGF polymorphisms were not associated with ectopic pregnancy (P = 0.170, P = 0.285, and P = 0.700, respectively). The serum levels of VEGF were not associated with the genotype of ,634C/G, ,460T/C, and +936C/T VEGF polymorphisms (P = 0.702; P = 0.347, and P = 0.256, respectively). Conclusion, There was no association between ectopic pregnancy and ,634C/G, ,460T/C, and +936C/T VEGF polymorphisms. There was no correlation between VEGF genotype and the expression of VEGF in blood samples. [source] ORIGINAL ARTICLE: Contribution of Interferon-, Receptor 1 Gene Polymorphisms to Pre-Eclampsia in ChinaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Li-Juan Chen Citation Chen L-J, Gao H, Zhou H, Zou L, Zou P. Contribution of interferon-, receptor 1 gene polymorphisms to pre-eclampsia in China. Am J Reprod Immunol 2010; 63: 331,338 Problem, As gene polymorphisms of cytokines receptors have been found to significantly influence cell responses to cytokines, the aim of this study was to test the hypothesis that IFN-, receptor 1 (IFNGR1) gene polymorphisms may contribute to the pathogenesis of pre-eclampsia. Method of study, One hundred and sixty-four pre-eclamptic patients (121 patients with mild pre-eclampsia and 43 patients with severe pre-eclampsia) and 171 controls were included. Polymorphisms of the IFNGR1 gene at positions ,611, ,270, +56 and +95 were genotyped with the matrix-assisted laser desorption/ionization time of flight mass spectrometry. Results, This study showed a positive association between ,56C/C genotype (OR = 1.7; 95% CI = 1.1,2.7) and pre-eclampsia. Although the genotype frequencies (except for ,56C/C) of the two polymorphisms were comparable between cases and controls, higher frequency of the ,611A/,56C haplotype (OR = 1.450; 95% CI = 1.070,1.966) was noticed in patients versus controls. All patients and controls were homozygous for the ,270T/T and +95T/T genotypes. Specifically, the frequency of the ,56C allele (OR = 1.838; 95% CI = 1.127,2.995) was higher among patients with severe pre-eclampsia. Conclusion, The IFNGR1 gene polymorphisms may contribute to the pathogenesis of pre-eclampsia in our population. [source] Combined effect of IL-10 and TGF-,1 promoter polymorphisms as a risk factor for aspirin-intolerant asthma and rhinosinusitisALLERGY, Issue 8 2009S.-H. Kim Background:, It has been known that interleukin (IL)-10 promoter polymorphisms at ,1082A/G, ,819T/C and ,592A/C, may influence IL-10 expression and associate with asthma. Interleukin-10 facilitates the regulatory function of transforming growth factor (TGF)-,. The goal of this study was to investigate a gene,gene interaction between IL-10 and TGF-,1 polymorphisms in Korean asthmatics with aspirin hypersensitivity. Methods:, Single-nucleotide polymorphism genotyping of IL-10 and TGF-,1 genes was performed and the functional effect of the IL-10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay. Results:, Among the patients with asthma, polymorphism at ,1082A/G was significantly associated with the phenotype of aspirin-intolerant asthma, AIA (P = 0.007, Pc = 0.021). Moreover, a synergistic effect between the TGF-,1,509C/T and IL-10,1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF-,1,509C/T and AG or GG genotype of IL-10,1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504,11.235). In an in vitro functional assay, the ,1082G reporter plasmid exhibited significantly greater promoter activity when compared with the ,1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc-associated zinc-finger protein preferentially bound the ,1082G allele. Conclusion:, Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-,1. [source] | ||||||||||||||||||||||||||||||||||||||||||||||