Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the insulin receptor substrate-1 (IRS-1) is the major substrate of the insulin receptor tyrosine kinase and has been shown to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a potential candidate for development of non-insulin-dependent diabetes mellitus (NIDDM). In this study, we have identified IRS-1 gene polymorphisms, evaluated their frequencies in Japanese subjects, and analysed the contribution of these polymorphisms to the development of NIDDM. The entire coding region of the IRS-1 gene of 94 subjects (47 NIDDM and 47 control subjects) was screened by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) analysis. Seven SSCP polymorphisms were identified. These corresponded to two previously identified polymorphisms [Gly971 --> Arg (GGG --> AGG) and Ala804 (GCA --> GCG)] as well as five novel polymorphisms [Pro190 --> Arg (CCC --> CGC), Met209 --> Thr (ATG --> ACG), Ser809 --> Phe (TCT --> TTT), Leu142 (CTT --> CTC), and Gly625 (GGC --> GGT)]. Although the prevalence of each of these polymorphisms was not statistically different between NIDDM and control subjects, the prevalence of the four IRS-1 polymorphisms with an amino acid substitution together was significantly higher in NIDDM than in control subjects (23.4 vs 8.5%, p < 0.05), and two substitutions (Met 209 --> Thr and Ser809 --> Phe) were found only in NIDDM patients. Equilibrium glucose infusion rates during a euglycaemic clamp in NIDDM and control subjects with the IRS-1 polymorphisms decreased by 29.5 and 22.0%, respectively on the average when compared to those in comparable groups without polymorphisms, although they were not statistically significant. Thus, IRS-1 polymorphisms may contribute in part to the insulin resistance and development of NIDDM in Japanese subjects; however, they do not account for the major part of the decrease in insulin-stimulated glucose uptake which is observed in subjects with clinically apparent NIDDM.
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PMID:Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese patients with NIDDM: identification of five novel polymorphisms. 873 21

We have found a 33 bp minisatellite repeat in the 5'-flanking region of the mutated in colon cancer (MCC) gene at chromosome 5q21. Southern blot experiments demonstrated the locus specificity of the repeat. The number of repeat units varied between 5 and 11 with a heterozygosity of 0.56. The sequence 5'-AGG AGT GTG AAT GGG GCA TAG TGA ATG AGG GGA-3' of the repeat units does not match the consensus sequence of chi-related minisatellites. The minisatellite is not expressed as part of a gene transcription unit. However, it can be used as a tool for the detection of allelic changes at chromosome 5q21 on standard agarose gels.
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PMID:A 33 bp minisatellite repeat upstream of the 'mutated in colon cancer' gene at chromosome 5q21. 969 82

The study reports the molecular characterization of a new DQB1 variant initially detected by unusual sequence-specific oligonucleotide (SSO) hybridization patterns in one Caucasoid individual. This new allele is identical to DQB1*0501 except for two silent nucleotide substitutions at codons 49 (GCA-->GCG) and 77 (AGG-->AGA). Compared with DQB1*0502 it differs in three nucleotides at codon 57 changing AGC (encoding Ser) to GTT (encoding Val). Considering the paternal genotype, it appears this new allele might have been generated by an interallelic sequence exchange between the two paternal DQB1 alleles.
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PMID:Identification of a new DQB1 allele that appears to have been generated by an interallelic sequence exchange. 1116 48

By using UV thermal denaturation and isothermal titration calorimetry (ITC), we examine the binding behaviors of a hydrogen bond-forming ligand, 2-acetylamino-7-methyl-1,8-naphthyridine (AcMND), with a guanine base opposite an abasic site (AP site) in a DNA duplex (5'-TCC AGX GCA AC-3'/3'-AGG TCG CGT TG-5', X = AP site, G = target). In the presence of AcMND, the melting temperature (Tm) of the AP site-containing DNA duplex increases by 8.6 degrees C while hardly any change in Tm is observed for a corresponding normal duplex that has no AP sites. The examination by ITC reveals that, in solutions buffered to pH 7.0 (at 10 degrees C, I = 0.11 M), AcMND is able to recognize guanine base with a 1:1 binding constant of 3.4x10(5) M(-1). The ligand-nucleotide interaction is clearly enthalpy driven, with deltaH(o) of -12.5 kcal/mol. We discuss these binding functions of AcMND at the AP site with a view towards development of ligand-based assay for SNPs (single-nucleotide polymorphisms) typing.
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PMID:Strong binding of naphthyridine derivatives to a guanine base in DNA duplexes containing an AP site. 1715 Jul 12

We here report on the thermodynamics of the hydrogen bond-mediated binding of 2-amino-7-methyl-1,8-naphthyridine (AMND) to a cytosine base opposite an abasic site (AP site) in a 21-meric DNA duplex (5'-GCA GCT CCC GXG GTC TCC TCG-3'/3'-CGT CGA GGG CCC CAG AGG AGC-5', X= AP site, C = target). The examination by fluorescence titration experiments shows a 1:1 binding constant of 2.7x10(6) M(-1) at 20 degrees C in solutions containing 110 mM Na(+) (pH 7.0). From the analysis of salt dependence of binding constants, polyelectrolyte (DeltaG(pe)) and non-polyelectrolyte (DeltaG(t)) contributions are calculated as -1.7 kcal/mol and -6.9 kcal/mol, respectively, at 110 mM Na(+) concentration. The binding enthalpy determined by isothermal titration calorimetry (ITC) is -18.5 kcal/mol in 110 mM Na(+) at 20 degrees C. We discuss these results with a view towards further development of our ligand-based fluorescence assay for SNPs (single nucleotide polymorphisms) typing.
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PMID:Thermodynamic characterization of the binding of naphthyridines to the AP site-containing DNA duplexes. 1715 Aug 96

Here we report on a significant enhancement of the binding affinity of naphthyridine-based fluorescence ligands that can selectively bind to cytosine opposite an AP site in a DNA duplex (5'-TCC AGX GCA AC-3'/3'-AGG TCC CGT TG -5', X = AP site, C = target). We have previously reported that 2-amino-7-methyl-1,8-naphthyridine (AMND) binds to cytosine with a dissociation constant of 370 nM (pH 7.0, I = 0.11 M, at 20 degrees C). In this work, AMND is modified simply by introducing two methyl groups to the naphthyridine ring. The present ligand, 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND), shows a stronger binding affinity for cytosine, and a dissociation constant reaches 56 nM. ATMND is effectively applicable to the analysis of cytosine-related mutation of PCR products. These promising abilities of ATMND are presented based on the examination by melting temperature (T(m)) and fluorescence measurements.
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PMID:Strong binding of naphthyridine derivatives to cytosine in an AP site-containing DNA duplex and their application to fluorescence detection of single nucleotide polymorphisms. 1802 12

Alloxazine can bind to adenine selectively over other nucleobases opposite an abasic site in DNA duplexes (5'-TCC AGX GCA AC-3'/3'-AGG TCN CGT TG-5', X=AP site, N=A, T, C, G) with a dissociation constant of 0.82 microM (pH 7.0, I=0.11 M, at 5 degrees C), and it is applicable to SNPs typing of PCR amplification products based on the binding-induced fluorescence response.
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PMID:Alloxazine as a ligand for selective binding to adenine opposite AP sites in DNA duplexes and analysis of single-nucleotide polymorphisms. 1826 65

By using lumichrome (Lch) as a masking ligand, we successfully control the binding selectivity of 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND) when binding to nucleobases in AP site-containing DNA duplexes (5'-TCT GCG TCC AGX GCA ACG CAC AC-3'/3'-AGA CGC AGG TCN CGT TGC GTG TG-5', X = AP site; Spacer C3, N = C or T). In solutions buffered to pH 7.0 (I = 0.11 M, at 5 degrees C), ATMND binds to cytosine and thymine with a comparable binding affinity (K(d) / nM: C: 7.7, T: 15). By contrast, in the presence of Lch, ATMND shows a clear binding selectivity for cytosine over thymine (K(d)/nM: C: 17, T: 204). Such competitive binding events are discussed with a view towards development of ligand-based fluorescence assay for single-nucleotide polymorphisms (SNPs) typing.
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PMID:Competitive binding of small ligands to nucleobases in AP site-containing DNA duplexes. 1877 82

6,7-Dimethyllumazine more selectively binds to adenine (A) base opposite the abasic site in DNA duplexes (5'-TCC AGX[combining low line] GCA AC-3'/3'-AGG TCN CGT TG-5', X = AP site (Spacer C3), N= A, T, C and G) than the other three nucleobases with a dissociation constant K(d) of ca. 1.0 microM; substituted methyl groups enhance the binding affinity to A and the selectivity for A over T, compared to the parent molecule, lumazine.
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PMID:6,7-Dimethyllumazine as a potential ligand for selective recognition of adenine opposite an abasic site in DNA duplexes. 1905 88

The duration of hepatitis C virus (HCV) infection and the response to the standard therapy is strongly related to the HCV genotypes. In addition, the geographical distribution of HCV genotypes is important for the epidemiological studies in terms of distribution and possible risk groups. The aim of this retrospective study was to investigate the distribution of HCV genotypes in Manisa region (located at the Aegean part of Turkey). A total of 100 anti-HCV (microparticle EIA; Abbott Laboratories, USA) and HCV-RNA (real time RT-PCR; Applied Biosystems, USA) positive patients (53 female, 47 male; mean age: 44.4 +/- 10.4 years), who were admitted to Celal Bayar University Medical School Hospital between 2002-2005, were included to the study. Quantitative HCV-RNA levels of the patients were between 10(4)-10(8) copies/ml. Complementary DNAs obtained from HCV-RNAs isolated by Invitek RTP DNA/RNA Virus Mini Kit were used for genotyping with selected primers [primer 11 (5'-AGG TCT CTG AGA CCG TGC ACC ATG AGC AC-3') and primer 13 (5'-CTG TGA GGA ACT ACT GTC TT-3') for the first PCR; primer 12 (5'-ACT GCC TGA TAG GGT GCT TGC GAG TG-3') and primer 14 (5'-CAC GCA GAA AGC GTC TAG-3') for the second PCR]. The RT-PCR products were purified with Invisorb Spin PCRapid Kit and sequenced by BigDye Terminator v3.1 Cycle Sequencing Kit in ABI Prism 310 Genetic Analyzer. Genotype 1 was found in 92% of the patients (92%) and genotypes 2 and 4 were found in 7% of the patients, while HCV genotype could not be identified in one patient (1%). When evaluating the subtypes, genotype 1b was determined in 90 patients (90%), genotype 4a in five patients (5%), genotype 1a in two patients (2%) and genotype 2a in two patients (2%). In conclusion, 1b was found to be the most common HCV genotype in Manisa region in concordance with the previous data obtained in Turkey, followed by genotype 4a, although a rare one. The data of this study is noteworthy especially for the arrangement of treatment and follow-up of HCV infected patients.
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PMID:[Distribution of hepatitis C virus genotypes in Manisa region, Turkey]. 2008 14


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