ABSTRACT
OBJECTIVE: This study was performed to examine the influence of tumour necrosis factor-alpha (TNFalpha) promoter polymorphisms on disease susceptibility and clinical features of Behçet's disease (BD) and the association between TNFalpha polymorphisms and human leucocyte antigen (HLA)-B51. METHODS: We examined 115 patients with BD and 114 healthy subjects. Six single nucleotide polymorphisms (SNPs) of the TNFalpha promoter at positions -1031, -863, -857, -308, -238, and -646 were analysed using automated sequencing. We compared the frequencies of alleles and genotypes in patients with BD and controls using the chi(2)-test or Fisher's exact test. Haplotype frequency was also assessed using the chi(2)-test. RESULTS: We found no significant differences in the frequencies of polymorphic genotypes and alleles of the TNFalpha promoter region between BD patients and controls. The resulting haplotype frequencies of the BD patients were also not significantly different from those of controls. None of the TNFalpha promoter polymorphisms analysed here were associated with clinical features. Patients with the novel -646A allele of the TNFalpha promoter region were significantly associated with the expression of the HLA-B51 allele (p(corr) = 0.006), although this novel polymorphic allele was not associated with BD susceptibility. CONCLUSION: The novel -646A TNFalpha allele was associated with the expression of HLA-B51 in Korean BD, although we found no genetic role of TNFalpha promoter polymorphisms in the susceptibility to BD. Further studies to examine the contributions of this gene polymorphism and HLA-B51 to the susceptibility to BD in large populations are required.
Subject(s)
Behcet Syndrome/genetics , HLA-B Antigens/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , Tumor Necrosis Factor-alpha/genetics , Adult , Alleles , Female , HLA-B51 Antigen , Humans , Korea , Male , Middle AgedABSTRACT
OBJECTIVE: To investigate the potential susceptibility to the solute carrier family 11 member 1 (SLC11A1) gene polymorphisms of Korean patients with Behçet's disease (BD). METHODS: Ninety-nine patients with BD and 98 controls were recruited. Analyses of three polymorphisms of the SLC11A1 gene [the 5'-promoter (GT)n, D543N and A318V] were performed, either by denaturing high-performance liquid chromatography for D543N and A318V or by using automatic DNA sequencing for the (GT)n. The genotypes and alleles between patients with BD and the controls were compared using the chi2 test and Yate's correction test. RESULTS: No significant differences were found in the distribution of genotypes and alleles of the (GT)n polymorphism between BD patients and the controls. However, subjects with the allele 3 or the genotype allele 3/allele 3 of this polymorphism had a significantly lower risk of developing BD than those without this allele or genotype [allele: p = 0.029, pc = 0.039, odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.37-0.95; genotype: p = 0.036, pc = 0.048, OR = 0.54, 95% CI 0.31-0.96]. In addition, the distributions of genotypes and alleles of D543N were similar between BD patients and controls (p>0.05). In the case of A318V, all of the BD patients and controls had a wild-type genotype. CONCLUSION: The allele 3 and the genotype allele 3/allele 3 of the 5'-promoter (GT)n in the SLC11A1 gene may have a protective effect for the development of BD in the Korean population. Further studies in other populations are required to confirm our results.
Subject(s)
Asian People/genetics , Behcet Syndrome/genetics , Cation Transport Proteins/genetics , Polymorphism, Genetic , Adult , Behcet Syndrome/ethnology , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease/genetics , Genotype , Humans , Korea/ethnology , Male , Middle AgedABSTRACT
We investigated the cytoprotective mechanisms of flunarizine in cisplatin-induced death of auditory cells. Concomitant with an increase in viability, treatment with flunarizine resulted in a marked dissociation of Nrf2/Keap1 and subsequent intranuclear translocation of Nrf2, which was mediated by PI3K-Akt signaling. Overexpression of Nrf2 protected cells from cisplatin along with transcriptional activation of ARE to generate heme oxygenase-1 (HO-1). Pretreatment with flunarizine predominantly increased the transcriptional activity of HO-1 among Nrf2-driven transcripts, including HO-1, NQO1, GCLC, GCLM, GST micro-1, and GSTA4. Furthermore, both pharmacological inhibition and siRNA transfection of HO-1 completely abolished the flunarizine-mediated protection of HEI-OC1 cells and the primary rat (P2) organ of Corti explants from cisplatin. These results suggest that Nrf2-driven transcriptional activation of ARE through PI3K-Akt signaling augments the generation of HO-1, which may be a critically important determinant in cellular response toward cisplatin and the cytoprotective effect of flunarizine against cisplatin.
Subject(s)
Cisplatin/toxicity , Flunarizine/pharmacology , Heme Oxygenase-1/genetics , NF-E2-Related Factor 2/metabolism , Organ of Corti/drug effects , Organ of Corti/metabolism , Active Transport, Cell Nucleus/drug effects , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Base Sequence , Cell Line , DNA, Complementary/genetics , Heme Oxygenase-1/antagonists & inhibitors , In Vitro Techniques , Mice , NF-E2-Related Factor 2/genetics , Organ of Corti/cytology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/genetics , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Transcriptional Activation/drug effectsABSTRACT
OBJECTIVE: There is strong evidence that Th1-type cytokines play an important role in the pathogenesis of Behçet's disease (BD). Interleukin (IL)-18 is a proinflammatory cytokine that mediates Th1-polarized immune responses, and elevated levels of IL-18 have been observed in the sera and bronchoalveolar lavage fluid of patients with active BD. Therefore, the aim of this study was to investigate the potential associations of two single nucleotide polymorphisms (SNPs) at positions -137 (G/C) and -607 (C/A) in the promoter region of the IL-18 gene with a susceptibility to BD in the Korean population. METHODS: Ninety-eight patients with BD and 105 healthy controls were studied. All of the subjects were genotyped using sequence specific PCR. The genotypes and alleles between patients with BD and controls were compared using the chi2 test, together with Yate's correction where appropriate. Haplotype analysis was assessed using the EH program. RESULTS: The genotype and allele distributions of the two SNPs did not differ significantly between patients with BD and controls. The haplotype frequencies of the IL-18 promoter polymorphisms were also similar between patients with BD and controls. However, the frequency of the GG genotype at position -137 was significantly higher in BD patients with ocular lesions than in those without ocular lesions (p = 0.026, pc = 0.048, OR = 4.1). CONCLUSION: Although the IL-18 gene polymorphisms were not associated with a susceptibility to BD in the Korean population, the patients carrying the GG genotype at position -137 had a higher risk of developing the ocular lesions. Further studies in other populations are required to confirm these results.
Subject(s)
Behcet Syndrome/genetics , Genetic Predisposition to Disease , Interleukin-18/genetics , Polymorphism, Single Nucleotide , Adult , Behcet Syndrome/pathology , Female , Gene Frequency , HLA-B Antigens/genetics , HLA-B51 Antigen , Haplotypes , Humans , Interleukin-18/metabolism , Korea , Male , Polymerase Chain ReactionSubject(s)
Behcet Syndrome/genetics , Interleukin-6/genetics , Polymorphism, Genetic , Adult , Asian People/genetics , Female , Genetic Predisposition to Disease , Humans , Korea , Male , Middle AgedABSTRACT
BACKGROUND: Although video-assisted thoracoscopic surgery for palmar hyperhidrosis is now widely accepted as the approach of choice, the optimal technique has remained a subject of controversy. We have used 2-mm dual port video-assisted thoracoscopic sympathicotomy for primary palmar hyperhidrosis. This study evaluates the short-term results of the technique. METHODS: A retrospective review was carried out of 45 patients, 20 men and 25 women, with a mean age of 24.2 years. In the period from April 1998 to August 1999, 90 consecutive video-assisted sympathicotomy for primary palmar hyperhidrosis either in isolation (n = 56) or in combination with axillary and plantar hyperhidrosis (n = 34) was performed. The mean follow-up period was 11.3 months. Attention was focused on patient's satisfaction, complications, and morbidity. RESULTS: Dry limbs were immediately achieved in all patients after surgery. There was no operative mortality and one case of transient Horner's syndrome developed. Eight of 20 with plantar hyperhidrosis showed simultaneous improvement. The overall mean satisfaction rate was 92% +/- 2% with a median 93% improvement using a visual linear analogue scale from 0% (poor) to 100% (excellent). Only 2 patients were dissatisfied with the operative results owing to compensatory hyperhidrosis, which occurred in 25 patients and improved in 20 patients within the follow-up period. CONCLUSIONS: The video-assisted thoracoscopic sympathicotomy with 2-mm endoscope is a speedy and safe way of controlling hyperhidrosis with excellent cosmetic results while minimizing complications.
Subject(s)
Electrocoagulation/methods , Ganglia, Sympathetic , Ganglionectomy/methods , Hyperhidrosis/surgery , Thoracic Surgery, Video-Assisted/methods , Adolescent , Adult , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
This study detects and defines the patterns of p53 gene mutations in breast cancers. We analyse p53 gene mutations through comparing the results of single-strand-conformation-polymorphism (SSCP) and immunohistochemistry (IHC), and we try to define the differences between the results of SSCP and IHC. Twenty-seven fresh primary breast cancer tissues and eight normal breast tissues were studied. The IHC was done with the usual streptavidin-biotin peroxidase complement method by using monoclonal antibody DO-7. The results of staining was scored. The SSCP method was done by using Cold SSCP Electrophoresis System. Overexpressions of p53 protein were seven (25.9%) among 27 cancer cases on IHC. Four (57.1%) of seven cases were positive in SSCP. In SSCP, the mutations were detected in 10 (37%) among 27 cancer cases. The mutations were two in exon 5, one in exon 8, and seven cases in exon 7. All of 10 mutations were proved by sequencing analysis. Of them, only four (40%) were positive in IHC. We consider the IHC as a screening method for p53 gene mutations.