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61.
62.
Krüger S Bier A Plaschke J Höhl R Aust DE Kreuz FR Pistorius SR Saeger HD Rothhammer V Al-Taie O Schackert HK 《Human mutation》2004,24(4):351-352
Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer-susceptibility syndromes. Germline mutations in mismatch repair genes are associated with the clinical phenotype of HNPCC. We report ten novel germline mutations, three in MSH2 and seven in MLH1. All but one mutation have been found in families fulfilling criteria of the Bethesda guidelines; four of them additionally fulfilled the Amsterdam criteria I or II. Eight mutations were considered pathogenic and predictive diagnostics in healthy family members at risk shall be undertaken; these include five frameshift mutations leading to premature stop codons, in MSH2: c.1672delT (p.S558Xfs) and c.2466_2467delTG (p.C822X) and in MLH1: c.1023delG (p.R341Xfs), c.1127_1128dupAT (p.K377Xfs) and c.1310delC (p.P437Xfs); three mutations leading to splice aberrations, in MSH2: c.1661G>C (r.1511_1661del) and in MLH1: c.677+3A>C (r.589_677del) and c.1990-2A>G predicted to result in a splice site defect. The remaining two mutations are unclassified variants with assumed pathogenicity: one missense mutation in the highly conserved ATPase domain of MLH1 (c.122A>G [p.D41G]) and one in-frame insertion of twelve nucleotides in MLH1 (c.2155_2156insATGTGTTCCACA [p.I719delinsNVFHI]). These two mutations were not found in 102 alleles of healthy control individuals. The corresponding tumors from all patients showed a high level of microsatellite instability (MSI-H). Immunohistochemistry (IHC) revealed complete loss of expression of the affected protein in the tumor cells from all but three patients. The tumors from the patients with the mutations c.1127_1128dupAT and c.1990-2A>G showed a reduction of expression of the MLH1-protein, rather than complete loss. In the tumor from the patient with the missense mutation c.122A>G [p.D41G] a normal expression of the proteins coded by MLH1 and MSH2 was noticed. 相似文献
63.
Microsatellite instability and alteration of the expression of hMLH1 and hMSH2 in ovarian clear cell carcinoma 总被引:5,自引:0,他引:5
Cai KQ Albarracin C Rosen D Zhong R Zheng W Luthra R Broaddus R Liu J 《Human pathology》2004,35(5):552-559
Microsatellite instability (MSI) is commonly seen in tumors associated with the hereditary nonpolyposis colorectal cancer syndrome and is caused by defects in the DNA mismatch repair genes. MSI has also been observed in various sporadic cancers, including colorectal, gastric, and endometrial. The role and incidence of MSI in ovarian clear cell carcinoma remain unknown. This study was conducted to evaluate the frequency of MSI in ovarian clear cell carcinomas and to evaluate the sensitivity and specificity of immunohistochemistry in predicting mismatch-repair gene deficiency. A total of 42 ovarian clear cell carcinomas were analyzed for MSI using a panel of 5 microsatellite markers (BAT25, BAT26, D5S346, D2S123, and D17S250). Alterations in the expression of hMLH1 and hMSH2 proteins in these tumors were examined. Of the 42 ovarian clear cell tumors analyzed, 6 demonstrated a high level of MSI (MSI-H), 3 demonstrated a low level of MSI (MSI-L), and the remaining 33 exhibited microsatellite stability (MSS). No correlation was found between MSI level and patient age or tumor stage or size (P >0.05). Loss of expression of either hMLH1 or hMSH2 was observed in 4 of the 6 (67.7%) MSI-H tumors, whereas 34 of the 36 (94.4%) MSI-L or MSS tumors expressed both the hMLH1 and hMSH2 gene products. Our results indicate that MSI-H is involved in the development of a subset of ovarian clear cell carcinomas. A strong correlation exists between alterations in the expression of hMLH1 and hMSH2 and the presence of MSI-H in these tumors. However, immunohistochemical testing alone may miss a small fraction of cases with MSI-H. 相似文献
64.
The prognostic role of the extent of Y microdeletion on spermatogenesis and maturity of Sertoli cells 总被引:6,自引:0,他引:6
Kleiman SE Bar-Shira Maymon B Yogev L Paz G Yavetz H 《Human reproduction (Oxford, England)》2001,16(3):399-402
Substantial involvement of the Y chromosome in sexual development and spermatogenesis has been demonstrated. Over the last decade, varying extent of Y chromosome microdeletions have been identified among infertile patients with azoospermia or oligozoospermia. These microdeletions were clustered in three main regions named AZFa, AZFb, and AZFc. Analysis of the Y chromosome microdeletion was found to be of prognostic value in cases of infertility, both in terms of clinical management as well as for understanding the aetiology of the spermatogenesis impairment. However, the accumulated data are difficult to analyse, due to the variable extent of these deletions, the different sequence-tagged sites (STS) used to detect the microdeletions, and the non-uniformity of the histological terminology used by different investigators. This debate discusses the chances of finding testicular spermatozoa in men with a varying extent of Y chromosome microdeletions. The genotype and germ cell findings in men with AZFa microdeletions as well as those that include more than a single AZF region are reviewed, as is the effect of Y chromosome AZF microdeletions on the maturity of the Sertoli cells. 相似文献
65.
66.
67.
目的 通过研究胃癌幽门螺杆菌(Hp)感染与微卫星不稳定性(MSI)的关系,探讨幽门螺杆菌在胃癌发生中的作用。方法 采用PCR为基础的方法对41例胃癌组织中Hp CagA基因以及4个微卫星位点BAT26,TP53,D2s123,D2s119进行检测,分析Hp感染与微卫星不稳定性之间的关系。结果 胃癌Hp和CagA的阳性率分别为63.4%(26/41),69.2%(18/26)。BAT26,TP53,D2s123,D2s119位点MSI的检出率分别为21.9%(9/41),29.3%(12/41),29.3%(12/41)和14.6%(6/41),Hp阳性组各位点MSI检出率与Hp阴性组比较无显著差异(P>0.05)。CagA^ Hp组与CagA^-Hp组各位点MSI检出率差异亦无显著性(P>0.05)。结论 Hp感染与MSI无显著相关,Hp可能并非通过MSI导致胃癌发生。 相似文献
68.
69.
Rafael Walker-Santiago Jason D. Tegethoff William M. Ralston James A. Keeney 《The Journal of arthroplasty》2021,36(2):653-656
BackgroundRevision total knee arthroplasty (rTKA) rates are increasing in younger patients. Few studies have assessed outcomes of initial aseptic rTKA performed for younger patients compared with traditional-aged patients.MethodsA detailed medical record review was performed to identify patient demographics, medical comorbidities, surgical rTKA indications, timing from index TKA to rTKA, subsequent reoperation rates, component rerevision rates, and salvage procedures for 147 young patients (158 knees) aged 55 years and younger and for a traditional older cohort of 276 patients (300 knees) between 60 and 75 years. Univariate analysis was performed to assess differences in these primary variables, and a log-rank test was used to estimate 5-year implant survival based on either reoperation or component revision and salvage procedures.ResultsYounger TKA patients were more likely to undergo initial aseptic rTKA within 2 years of their primary TKA (52.5% vs 29.0%, P < .001) and were more likely to undergo early reoperation (17.7% vs 9.7%, P = .02) or component rerevision (11.4% vs 6.0%, P < .05) after rTKA. Infection and extensor mechanism complications were more commonly noted in younger patients. Estimated 5-year survival was also lower for both reoperation (59.4% vs 65.7%, P = .02) and component rerevision or salvage (65.8% vs 80.1%, P = .02).ConclusionEarly reoperation and component re-rTKA were performed nearly twice as often in younger rTKA than traditional-aged TKA patients. Care should be given to reduce perioperative infection and extensor mechanism failures after rTKA in younger patients. 相似文献
70.
Mitzi S. Laughlin Emily A. Vidal Arin A. Drtil Robin N. Goytia Vasilios Mathews Anay R. Patel 《The Journal of arthroplasty》2021,36(7):2353-2358
BackgroundIn counseling patients about the complications of revision total hip arthroplasty (revTHA), it is imperative that mortality be considered. The actual mortality rate by indication of revision is ill-defined. The purpose of this study is to determine the mortality rate after revTHA.MethodsAn institutional database identified 596 patients who had undergone revTHA between 2012 and 2018. Medical records, national, state, and local death indexes were queried for mortality status and indication for revTHA. For survivors, the last clinical visit date was used for censoring in the mortality analysis. Mortality rates were calculated for all clinical patients and then by specific indication for revision.ResultsThe overall 2-year mortality rate following revTHA was 19.5 deaths per 1000 or 1 in 51 patients. Patients presenting with a periprosthetic fracture had a significantly higher 2-year mortality rate of 74.5 deaths per 1000 or 1 in 13 patients (P < .001), while an indication of dislocation or instability had a slightly higher 2-year mortality rate of 50.3 per 1000 (1 in 20) but this difference was not significant (P = .531). Other indications such as mechanical loosening or infection did not have a significantly different mortality rate.ConclusionThe overall 2-year mortality rate following revTHA was 19.5 deaths per 1000 which was largely attributed to patients with a periprosthetic fracture (74.5 per 1000) with other indications not significantly impacting mortality. Mortality rates and specific rates by indication for revision should be considered when counseling patients prior to revTHA. 相似文献