This study was designed to clone the SNF2/SW12 helicase-related genes from the fission yeast Schizosaccha-romyces pombe and thereafter to elucidate the common functions of the proteins in this family. The $hrp^{2+}$gene was cloned by polymerase chain reaction amplification using degenerative primers from conserved SNF2 motifs within the ERCC6 gene, which encodes a protein involved in DNA excision repair. Like other SNF2/SW12 family proteins, the deduced amino acid sequence of Hrp2 contains DNA-dependent ATPase/7 helicase domains as well as the chromodomain and the DNA binding domain. This configuration is similar to that of mCHD1 (mouse chromo-ATPase/helicase-DNA-dinding protein 1), suggesting that Hrp2 is a S. pombe homolog of mCHD1, which is thought to function in altering the chromatin structure to control the gene expression. To characterize the function of Hrp2, 4 Uracil-Hrp2 fusion protein, it was purified near homogeneity by affinity chromatography on $Ni^{2+}$-NTA agarose, DEAE-Sepharose ion exchange arid Sephacryl S-200 gel filtration chromatographies. The purified fusion protein exhibited DNA-dependent ATPase activity, which was stimulated by both double-stranded and single-stranded DNA. To determine the steady-state level of $hrp^{2+}$ transcripts during growth, cells were cultured in medium and collected at every 2hr to prepare total RNAs. The northern blot analysis showed that the level of $hrp^{2+}$ transcripts reached its maximum before the cells entered the exponential growth phase and then decreased gradually, This result implies that Hrp2 may be required at early stages of cell growth.h.
Purpose: It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. Materials and Methods: From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of $30.6{\sim}59.4 Gy$ (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. Results: When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorph isms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorph isms also affected the decrease of the WBC and platelet count during radiation therapy. Conclusion: Although the present sample size was too small for fully evaluating this hypothesis, this study suggests that Arg399Gln polymorph isms of the XRCC1 genes may be used as one of the predictors for acute complications of chemoradiation therapy in colorectal cancer patients.
Background: The reciptents of aortic valve replacement or a Bentall operation usually display various degrees of mitral regurgitation. When deciding whether or not to correct the mitral regurgitation, one must consider its severity, underlying causes and operative risk. Recently, the operation method for correcting the concomitant mitral regurgitation has been done through aortic root to reduce the operation time and the cardiac trauma. We report our experiences that transaortic mitral valve commissuroplasty done with aortic valve replacement or a Bentall operation has been a simple, less invasive, effective method in the operative management of mitral valve regurgitation without significant organic changes. Material and Method: Between June 2002 and June 2005, twenty patients under-went mitral valve commissuroplasty via the aortic root with aortic valve replacement (n=14) or a Bentall operation (n=7). The mitral valve regurgitation of the patients didn't exceed a moderate (grade 2) degree and there was no significant organic disease. The preoperative diagnosis of MR was established by TTE and intraoperative TEE, and the patients were followed postoperatively by TTE. The operative technique was a simple anterolateral commissuroplasty of the mitral valve with a single mattress suture via the transaortic annular approach after excision of the aortic valve leaflets. Result: The mean patient age was 56.2 years and 65% (n=13) were male. The preoperative MR was mild (grade 1) in 9 (45%), mild to moderate in 8 (40%), and moderate (grade 2) in 3 (15%) patients. There were no operative mortalities. The MR improved in all patients (p=0.002) and the left ventricular ejection fraction (LV EF) improved in 14 (70%) patients (p=0.005). The mean cross-clamp time for the patients who under- went aortic valve replacement with transaortic mitral repair was $62.1{\pm}13.9 min$ and this was $137.5{\pm}7.2 min$ for the patients who underwent a Bentall operation with transaortic mitral repair. Conclusion: For selected patients without significant mitral organic disease, transaortic mitral valve commissuroplasty combined with aortic valve replacement or a Bentall operation may be a feasible, effective method without adding significant aortic cross clamping time and more cardiotomy.
Purpose : To analyze the clinical result of the arthroscopic decompression of meniscal cyst and meniscus resection or repair of meniscus tear. Materials and Methods : From April 1994 and October 2001, 19 patients with diagnosis of meniscal cyst associated with tears of the meniscus were treated by arthroscopic meniscal resection or repair with decompression of the cyst. The mean age was 39.8 years(range, 22-58years). The follow-up period ranged from 3 months to 36 months with an average of 18 months. Seven of 19 patients had tenderness over the joint line with palpable mass. Treatment consists of arthroscopic resection or repair of meniscal tear with decompression of the cyst through transmeniscal approach. Open excision of cyst was performed in one case. Clinical evaluation was performed using Lysholm knee score and Tegner activity. All cases were executed proper treatment using arthroscopy. Results : Twelve cysts involved the lateral meniscus$(64\%)$ and seven cysts were on medial cyst$(36\%)$. Most of lateral meniscal cysts were located in anterior one-third and medial meniscal cyst were on posterior one-third. Meniscal tear were observed in seventeen cases$(89.5\%)$ and most tears were horizontal$(79\%)$. Preoperative symptom disappeared and no cyst recurrences were observed at last follow-up(mean follow-up: 18 months). Conclusion : Meniscal cysts involved lateral side in $64\%$ and most of them were associated with meniscus tear$(89.5\%)$ which consists of mainly horizontal component$(79\%)$.
SOS Chromotest and Ames test were carried out to evaluate the mutagenicity of three chloropropanols. In the SOS Chromotest, 3-monochloro-l,2-propanediol (3-MCPD) and 2,3-dichloro-1-propanol (2,3-DCP) except for 1,3-dichloro-2-propanol (1,3-DCP) induced SOS response in Escherichia coli PQ37 with dose-response relationship and 2,3-DCP was far more genotoxic than 3-MCPD. The genotoxic activities of both compounds, however, were very lower in E. coli PQ35 (PQ37 $uvrA^+)$ as compared to them in E. coli PQ37, whereas much higher in E. coli PQ243 (PQ37 tagA alkA). These results indicate that there are at least two types of DNA lesions caused by these compounds; one is a excision-repairable and the other is 3-methyladenine or any similar lesion which is excision-unrepairable and can induce adaptive response. In Salmonella typhimurium TA100, all the compounds showed strong mutagenicities, establishing the following genotoxic order: 2,3-DCP>3-MCPD>1,3-DCP. But the mutagenic activities were very low in S. typhimurium TA98 and TA97a. These results suggest that the mutation by chloropropanols can be induced by the DNA lesions causing base-pair substitutions. From the result that the mutagenicities of 3-MCPD and 2,3-DCP in S. typhimurium TA1535 were very low as compared to those in S. typhimurium TA100, it was appeared that the mutations by both compounds necessitate error-prone SOS repair.
Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). Results: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.
ERCC2 is an essential component of the nucleotide excision repair pathway which is involved in the effective maintenance of genome integrity. Association studies on ERCC2 polymorphisms and glioma risk have yielded inconclusive results. This meta-analysis was performed to gain a better insight into the relationship between ERCC2 polymorphisms and glioma risk. A systematic literature search updated to December 2, 2013 was performed in the Pubmed and EMBASE databases. Crude pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to estimate the association between ERCC2 polymorphisms and glioma risk under a suitable effect model according to heterogeneity. All analyses were performed using Review Manager 5 (version 5.2) and STATA (version 12.0). The combined results demonstrated rs13181 to be significantly associated with glioma risk (G allele versus T allele: OR=1.15, 95% CI=1.05-1.26, P=0.002; dominant model: OR=1.22, 95% CI=1.07-1.39, P=0.002; recessive model: OR=1.18, 95% CI=0.98-1.41, P=0.070). We also found that rs13181 acts in an allele dose-dependent manner (GG versus TT: OR=1.30, 95% CI=1.07-1.57, P=0.009; TG versus TT: OR=1.20, 95%=CI 1.05-1.37, P=0.009; trend test, P=0.004). However, no evidence was found in analyses for the association between other 3 ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) and susceptibility to glioma development. Our meta-analysis suggests that rs13181 is significantly associated with glioma risk in an allele dose-dependent manner, whereas, 3 other ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) may have no influence.
The aim of this study was to assess whether the functional regeneration of a lyophilized autografted cartilage could be improved by implanting a vascularized muscle flap into the medullary canal of autografted proximal humerus. A hemijoint reconstruction using a lyophilized osteochondral autograft in proximal humerus was done in 4 rabbits for control, and combined with an vascularized intramedullary muscle flap in another 4 rabbits for the experimental group. Graft healing and the repair process of osteochondral graft were followed by serial radiographs and histologic changes for 9 weeks after experiments. Each two rabbits in control and in experimental group on 5th and 9th week after implantation of hemijoint were sacrified. The results were as follows: 1. All of control and experimental froups on 5th week united solidly on osteotomized site radiologically, but their articular cartilages were destroyed more seriously in the control than that in experimental group with muscle flap on 5th and 9th week after experiment... 2. Histochemically, the cartilage surface are completely destroyed and revealed with severe osteoarthritic changes on all cartilage layers in control, but cartilaginous erosions are mild to moderate and their arthritic changes are also mild with somewhat regeneration of chondrocytes on deep layers more prominetly on 9th week of the experimental group. 3. The amount of collagen and protenized matrix which was determined by Masson-Trichrome stain was markedly decreased that means the weakness of bony strength and low osteogenic potential in lyophilized cartilage. These results suggest that an intramedullary vascularized muscle flap can improve the functional results of lyophilized osteochondral autograft by providing both increased vascularity and populations of mesenchymal cells to initiate new bone formation on osteotomized site as well as the regeneration of deep layers in articular cartilage. In clinical relevances, this lyophilized hemijoint autograft combined with an intramedullary vascularized muscle pedicle graft might be used very effectively for the treatment of malignant long bone tumors to preserve the joint functions, all or partly, and so to replace it with the artificial joint after tumor excision and hemijoint autograft.
Background: Among the various techniques for the adequate exposure of the mitral valve, the extended transseptal approach is the essential prerequisite for accurate repair or replacement of the mitral apparatus. But the efficacy and safty of the extended transseptal approach has not determined in Korea yet. Materials and methods: Retrospective data of 80 consecutive patients, operated from September 1992 to July 1997 were reviewed. Seventy- eight patients underwent mitral valve replacement and 2 patients underwent excision of left atrial myxoma. Thirty-eight of 78 patients had other concomitant procedures such as aortic valve replacement(n=22), tricuspid annulopasty(n=14), coronary artery bypass graft(n=1) and closure of ventricular septal defect(n=1). Mean follow up was 23.3±15.0 months and total follow up was 1792 patient-months. Results: The hospital mortality rate was 3.8%(3 patients). Two deaths were due to low cardiac output and one due to postoperative bleeding of coagulopathy. Among the 46 patients who had atrial fibrillation preoperatively, 45 had atrial fibrillation postoperatively and 1 converted to sinus rhythm. All 34 patients who were in normal sinus rhythm preoperatively remained in sinus rhythm after the operation. Mean aortic cross clamping time was 62 minutes for isolated mitral procedure and 90 minutes for concomitant procedures. There were no specific complications related to this approach. Conclusions: We suggest that the extended transseptal approach is an easy and good method for mitral valve surgery, especially in patients with small sized left atrium.
Purpose : To evaluate the efficacy of arthroscopic management of the triangular fibrocartilage complex(TFCC). Materials and Methods : Thirteen patients(14 wrists) with acute or chronic traumatic triangular fibrocartilage complex lesions were included in the study. The mean patients' age was 28.3 years, with a range of 21 to 45 years. All patients were diagnosed by physical examination, arthrographic or magnetic resonance imaging studies. Eight of the 14 wrists had central TFCC tear while 6 wrists had peripheral tear. Under arthroscopic control, injuries to the central portions were treated by debridement and excision of unstable tissue fragment while peripheral tears were repaired. The follow-up period averaged 28 months. The results were analyzed clinically using the Mayo modification of the Green and O' Brien wrist scoring system. Results : Nine of the 14 wrists were rated excellent,3 good and 2 fair Overall, 12 of the 14 patients rated as satisfactory and returned to sports or work activities. Conclusion : Arthroscopic treatment of TFCC resulted in a high degree of patient satisfaction and an increase in the ability to perform at workshop.
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