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871.
Cañueto J Labrador J Román C Santos-Briz A Contreras T Gutiérrez NC García-Sanz R 《European journal of haematology》2012,88(5):450-454
Scleromyxedema (SM) is a rare primary cutaneous inflammatory mucinosis characterised by papular mucinosis, monoclonal gammopathy and extracutaneous involvement. Most therapeutic options have failed in SM but high-dose therapy followed by autologous peripheral blood stem cell transplantation (APBSCT) appears to be highly effective, although SM normally relapses. We report the case of a 29-yr-old patient with severe SM who achieved stringent complete response with Bortezomib plus Dexamethasone after an early relapse subsequent to a high-dose melphalan regimen followed APBSCT. It is of particular note that dermatological lesions responded to both therapies before M-component modifications, suggesting that SM is independent of M-component characteristics. However, treatment should be directed towards the underlying plasma cell malignancy with typical anti-myeloma agents. 相似文献
872.
No drug therapy is completely risk free, and the costs associated with non-response and adverse effects can exceed the cost of the therapy. The ultimate goal of pharmacogenetic research is to find robust genetic predictors of drug response that enable the development of prospective genetic tests to reliably identify patients at risk of non-response or of developing an adverse effect prior to the drug being prescribed. Currently, thiopurine S-methyltransferase (TPMT) deficiency is the only pharmacogenetic factor that is prospectively assessed before azathioprine or 6-mercaptopurine immunomodulation is commenced in patients with Crohn's disease (CD). As yet no other inherited determinant of drug response has made the transition from bench to bedside for the management of this disease. In this review we summarize what is known about TPMT deficiency and explore whether there is evidence to support a role of other genetic polymorphisms in predicting the response of CD patients to thiopurine drugs, methotrexate, and anti-tumor necrosis factor α (TNFα) therapy. 相似文献
873.
Zhong S Yang JH Liu K Jiao BH Chang Z 《Journal of gastroenterology and hepatology》2012,27(2):231-237
Background and Aim: Previous studies investigating the association between the glutathione S‐transferase Tl (GSTT1) null genotype and colorectal cancer (CRC) risk in the Asian population have reported controversial results. Thus, a meta‐analysis was performed to clarify the effect of the GSTT1 null genotype on CRC risk in the Asian population. Methods: A comprehensive study was conducted, and 12 case‐control studies were finally included, involving a total of 4517 CRC cases and 6607 controls. Subgroup analyses were performed by the sample size. Results: A meta‐analysis of all 12 studies showed that the GSTT1 null genotype was significantly associated with an increased CRC risk in the Asian population (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.02–1.19, the P‐value of the OR [POR] = 0.02, the value of the heterogeneity analysis [I2] = 42%). A more obvious association was observed after the heterogeneity was eliminated by excluding one study (OR = 1.15, 95% CI: 1.06–1.25, POR = 0.001, I2 = 0%). This association was further identified by both subgroup analyses and a sensitivity analysis. Conclusions: This meta‐analysis suggests that the GSTT1 null genotype contributes to an increased colorectal cancer risk in the Asian population. 相似文献
874.
下呼吸道感染患者铜绿假单胞菌分离株氨基糖苷类耐药相关基因分析 总被引:1,自引:0,他引:1
目的探讨分离自下呼吸道感染患者的氨基糖苷类耐药铜绿假单胞菌的耐药机制。方法从下呼吸道感染患者痰液中分离出52株对氨基糖苷类耐药的铜绿假单胞菌,PCR法检测6种氨基糖苷类修饰酶(AMEs)基因,并检测其中泛耐药菌的6种16S rRNA甲基化酶基因(以下简称甲基化酶基因)。对阳性产物测序加以证实。结果 52株铜绿假单胞菌中检出4种AMEs基因[aac(3)-Ⅱ、aac(6’)-Ⅰb、aac(6’)-Ⅱ和ant(2″)-Ⅰ],AMEs基因总检出率为92.3%。泛耐药菌中检出1种甲基化酶基因(rmtB)。16株高水平泛耐药菌中rmtB基因的检出率为81.3%。结论分离自下呼吸道感染患者的氨基糖苷类耐药铜绿假单胞菌中AMEs基因携带率高,其对氨基糖苷类耐药与aac(3)-Ⅱ、aac(6’)-Ⅰb、aac(6’)-Ⅱ和ant(2″)-Ⅰ有关;对氨基糖苷类高水平泛耐药主要与甲基化酶基因rmtB有关。 相似文献
875.
Wu PY Zhang Z Wang JM Guo WW Xiao N He Q Wang YP Fan YM 《World journal of gastroenterology : WJG》2012,18(1):70-78
AIM: To explore germline hypermethylation of the tumor suppressor genes MLH1, CDH1 and P16INK4a in suspected cases of hereditary gastric cancer (GC).METHODS: A group of 140 Chinese GC patients in whom the primary cancer had developed before the age of 60 or who had a familial history of cancer were screened for germline hypermethylation of the MLH1, CDH1 and P16INK4a tumor suppressor genes. Genomic DNA was extracted from peripheral blood leukocytes and modified by sodium bisulfite. The treated DNA was then subjected to bisulfite DNA sequencing for a specific region of the MLH1 promoter. The methylation status of CDH1 or P16INK4a was assayed using methylation-specific PCR. Clonal bisulfite allelic sequencing in positive samples was performed to obtain a comprehensive analysis of the CpG island methylation status of these promoter regions.RESULTS: Methylation of the MLH1 gene promoter was detected in the peripheral blood DNA of only 1/140 (0.7%) of the GC patient group. However, this methylation pattern was mosaic rather than the allelic pattern which has previously been reported for MLH1 in hereditary non-polyposis colorectal cancer (HNPCC) patients. We found that 10% of the MLH1 alleles in the peripheral blood DNA of this patient were methylated, consistent with 20% of cells having one methylated allele. No germline promoter methylation of the CDH1 or P16INK4a genes was detected.CONCLUSION: Mosaic germline epimutation of the MLH1 gene is present in suspected hereditary GC patients in China but at a very low level. Germline epimutation of the CDH1 or P16INK4a gene is not a frequent event. 相似文献
876.
The involvement of S100A4 in modulating invasiveness of esophageal squamous cell carcinoma (ESCC) cell lines was explored. It was shown that S100A4 expression is positively correlated with the degree of invasiveness in human ESCC cells. The S100A4‐rich EC‐1 cells displayed higher migratory and invasive cell behavior while ET‐1 cells with low S100A4 expression levels displayed lower migratory and invasive cell behavior. S100A4 silencing by small interfering (siRNA) in EC‐1 cells induced E‐cadherin expression, and overexpression of S100A4 in a lowly invasive TE‐1 cells suppressed E‐cadherin expression. It is suggested that S100A4 silencing inhibit invasion via E‐cadherin upregulation, and overexpression of S100A4 promote invasion via E‐cadherin downregulation in ESCC cells. Compared with the vector‐transfected cells, S100A4 silencing in EC‐1 cells showed reduced ability of migration and invasiveness, and overexpression of S100A4 in TE‐1 cells showed increased ability of migration and invasiveness via wound‐healing and Transwell assay, and pseudometastatic model assay. Furthermore, re‐expression of S100A4 could increase the invasive phenotypes in S100A4 siRNA transfected EC‐1 cells, and S100A4 silencing could decrease the invasive phenotypes in S100A4 circular DNA (cDNA) transfected TE‐1 cells. It was found that Slug is downregulated in S100A4 siRNA transfected EC‐1 cells, and Slug is upregulated in S100A4 cDNA transfected TE‐1 cells. It was also discovered S100A4 cDNA induced protein kinase B (AKT) phosphorylation at Serine‐473(phospho‐AKT [p‐AKT]) levels, followed by the Slug upregulation, and S100A4 siRNA decreases the phospho‐AKT levels, followed by the Slug downregulation. The data suggested that S100A4 could regulate migratory and invasive behavior of human ESCC cells through modulating AKT/Slug pathway. 相似文献
877.
Bharadwaj R Swaminathan S Salimnia H Fairfax M Frey A Chandrasekar PH 《Transplant infectious disease》2012,14(2):206-212
Molecular method of 16S rRNA sequencing is reported to be helpful in the accurate identification of organisms with ambiguous phenotypic profiles. We analyzed the use of 16S rRNA sequencing method to identify clinically significant, “difficult‐to‐identify” bacteria recovered from clinical specimens, and evaluated its role in patient management and consequent clinical outcome. Among the 172 “difficult‐to‐identify” bacteria recovered over a 4‐year period, 140 were gram‐positive cocci or gram‐negative bacilli; identification by 16S rRNA did not play a role in the management of patients infected with these bacteria. From 32 patients, 33 “difficult‐to‐identify” gram‐positive bacilli were identified; the organisms were mycobacteria, Nocardia, Tsukamurella, Rhodococcus, and Gordonia. In 24 patients for whom clinical data were available, results from the 16S rRNA sequencing method led to treatment change in 14 immunocompromised patients (including 7 hematopoietic stem cell recipients and 1 liver transplant recipient). Therapy was modified in 9 patients, initiated in 3 patients, and discontinued in 2 patients. Most patients’ therapy was switched to oral antibiotics with discontinuation of intravascular catheters, facilitating early hospital discharge. All 14 patients were alive 30 days after infection onset. The present study demonstrates the clinical application of 16S rRNA sequencing method to identify “difficult‐to‐identify” mycobacteria and other gram‐positive bacilli in clinical specimens, particularly in immunocompromised hosts. 相似文献
878.
目的 观察2型糖尿病(T2DM)下肢血管病变患者血管新生相关因子的变化,探讨血管新生在糖尿病下肢血管病变发展中的作用.方法 测定31例T2DM无下肢血管病变患者(T2DM 组)、49例T2DM下肢血管病变患者(下肢血管病变组)及40例正常对照者(对照组)血清CXCL16、碱性成纤维细胞生长因子(bFGF)、血小板源性内皮细胞生长因子(PD-ECGF)水平和外周血内皮祖细胞(EPCs)数量.应用多普勒超声测定踝臂指数(ABI),左、右足背动脉及左、右腘动脉内径,血流流速.结果 T2DM组和对照组相比,血清bFGF、PD-ECGF水平升高(P均<0.01),外周血EPCs数量下降(P <0.001).下肢血管病变组与T2DM组和对照组相比,血清CXCL16、bFGF、PD-ECGF水平升高(P均<0.001),外周血EPCs数量下降(P<0.01).下肢血管病变组和T2DM组、对照组相比,ABI下降(P<0.01),左、右足背动脉,左、右胭动脉内径减小(P<0.01或P<0.05),下肢血管病变组和对照组相比,左、右足背动脉,左、右胭动脉血流流速减低(P<0.05).结论 T2DM下肢血管病变患者存在血管新生障碍,血管新生相关因子的升高和EPCs数量下降在糖尿病下肢血管病变发生中可能起重要作用. 相似文献
879.
880.
Ioannis Griveas George Visvardis George Sakellariou Ploumis Passadakis Ilias Thodis Vasilios Vargemezis 《Renal failure》2013,35(6):493-499
The immune defect in hemodialysis (HD) patients is associated with a monocyte dysfunction, including an increase in the production of proinflammatory cytokines. Blood membrane contact leads to an increase in cellular activation and sequestration into the capillary bed of the lung. The influence of the sequestration on the number of mature monocytes was studied by analyzing the fate of monocytes, particularly, the CD14+CD16+ subpopulation, during HD treatment.In thirty stable HD patients, the distinct cell populations were determined by differential blood counts and flow cytometry. Patients with diabetes or systemic vasculitis, those showing evidence of infectious complications or malignancy, or those taking immunosuppressive medications were excluded from the study. Cells from this study population were analyzed before the start, 30 min thereafter, and at the end of HD treatment, each time using a different dialyzer: hemophan, methylmethacrylate (PMMA), triacetate membrane, cuprophane/vitamin E, acrylonitrile, and sodium methallylsulfonate polymer (AN69).The CD14+CD16+ subset decreased at 30 min and remained suppressed for the course of dialysis. To examine whether currently used biocompatible membranes differ in their effect on the sequestration of monocyte subpopulations, temporal monocytic changes were comparatively analyzed during HD with a different dialyzer. The drop in the first 30 min until the end of HD treatment was significant (p<0.05), very uniform, and sharp in all patients, and was independent upon membrane type.The CD14+CD16+ monocyte subpopulation showed increased and longer margination from the blood circulation during HD. Given the fact that CD14+CD16+ monocytes represent a sensitive marker for inflammation or cellular activation, the depletion of these cells may offer an easily accessible parameter that is more sensitive than complement activation for biocompatibility studies on forthcoming, improved dialyzer membranes. 相似文献