HFE codon 63/282 (H63D/C282Y) dimorphism in German patients with genetic hemochromatosis

Abstract: Genetic hemochromatosis (GH) is closely associated with genes of the major histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for GH, with structural similarities to MHC class I genes, designated HLA-H and presently named HFE, has been cloned. The HFE gene is localized telomeric to the MHC and several reports have indicated that the HFE gene is mutated in GH patients. In the present study we have analyzed the relationship of HFE gene variants and disease manifestation in GH patients and family members. Fifty-seven patients with GH, 73 family members and 153 healthy blood donors were studied for the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr= C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR amplification of genomic DNA samples and restriction enzyme digestion using RsaI/SnaBI for C282Y and Bcll/Mbo 1 for H63D. Ferritin, transferrin serum levels and total iron-binding capacity were determined prior to therapeutic intervention. The Tyr-282 substitution occurred in 53 (93%) of patients compared with 8 (5.2%) of controls (OR=169, P >0.0001). Fifty-one (90%) patients were Tyr-282 homozygous. In contrast, the Asp-63 substitution was present in 5 (8.8%) of the patients compared with 34 (22%) of controls (OR=0.39, P =NS) with none of the patients being homozygous. In Tyr-282 homozygous GH patients serum ferritin levels, transferrin saturation, liver iron and liver iron index were elevated significantly compared to Tyr-282-negative patients, whereas no difference was observed between Tyr/Cys-282 heterozygous and Tyr-282-negative patients.     

Mutations in the androgen receptor gene of seven Chinese patients with complete androgen insensitivity syndromes

Androgenplaysanimportantroleinthenormaldevelopmentofmalephenotypeandtheregulationofvirilization.Theseactionsofandrogenaremediatedbytheintracellularandrogenreceptor(AR)containingN--terminal,DNAuandsteroidbindingdomains.MutationsintheARgenecancausevariousdegreesofandrogenInsensitivitysyndromes(AlS)inpatientswith46,XYkaryotype.ThephenotypeofpatientswithAlSrangesfromcompletefemaleexternalgenitalia(completeAlS,CAIS)overgenitalambiguity(partialAlS,PAlS)totheinfertilewithnormalmaleornearlys…     

核黄素等抗甲基苄基亚硝胺的致细胞突变作用

采用ＣＨＯ细胞ＨＧＰＲＴ位点突变测定系统观察了核黄素、尼克酰胺和锌等微量营养素对甲基苄基亚硝胺（ＭＢＮＡ）致细胞突变作用的影响。结果表明，在ＲＰＭＩ１６４０培养基中添加核黄素（２．６～１３．０μｍｏｌ／Ｌ）或尼克酰胺（４０～１２０μｍｏｌ／Ｌ）可显著抑制ＭＢＮＡ的致细胞突变作用。联合应用核黄素、尼克酰胺和锌效果更佳。提示：核黄素等微量营养素可能具有阻止细胞癌变的作用，为应用微量营养素干预治疗癌变过程提供了一定的理论依据。     

毛细管电泳技术快速检测p53基因点突变

目的：探讨利用毛细管电泳技术快速检测p53基因点突变的临床应用价值。方法：采用毛细管电泳作SSCP分析，检测20例结肠癌肿瘤标本p53基因第7外显子PCR扩增产物，并与传统的聚丙烯酰胺凝胶电泳结果进行比较，最后用DNA序列测定判断其准确性。结果：20例结肠癌标本中，毛细管电泳技术检测出5例标本(Ca4，Ca6，Ca7，Ca8，Ca14)有突变，而凝胶电泳结合银染技术仅检出4例标本(Ca4，Ca6，Ca7，Cal4)有突变，测序证实经毛细管电泳所检出的5例标本均存在点突变。结论：对于PCR产物的单链构象多态性分析，毛细管电泳技术是一种更加快速、简便、敏感的方法，可应用于临床筛查基因点突变。     

Screening of H-ras Gene Point Mutations in 50 Cases of Bladder Carcinoma

Background Mutation converts the H-ras gene into an activated oncogene in about 10% of human bladder cancers. Codons 12 and 61 are the major "hot spots" for activation. A simple and accurate method to detect point mutations in these codons may be clinically useful for early diagnosis of bladder cancer.
Methods Bladder cancer samples from 50 patients, plus 10 samples of normal bladder mucosa, were analyzed for possible point mutation of the H-ras gene at either codon 12 or codon 61. The H-ras gene DNA segments that include these 2 codons were amplified by PCR methods, then the possible presence of a point mutation was evaluated at each codon by susceptibility of the respective DNA segments to digestion with the restriction enzyme and by dot blot hybridization assay. A bladder cancer patient who had an H-ras gene mutation was examined to see whether the mutation was also detectable in the cells released in the urine.
Results Definite or possible point mutations were found in 6 (1 2%) out of 50 bladder cancer patients, while no mutation was detected in normal mucosa. A point mutation could also be detected in cells isolated from the patient's urine sample.
Conclusion The prevalence of point mutations at codon 1 2 or codon 61 of the H-ras gene found in this study was similar to that previously estimated for human bladder cancer by DNA transfection assay. The method we have used for detecting point mutations of the H-ras gene provides a simple and highly accurate way to detect mutated cancer cells even in the urine. It may be clinically usable for early diagnosis of bladder cancer.     

远节指末端离断伤两种治疗方法的回顾性分析

①目的 旨在比较分析原位缝合与贯穿植入随意血管神经束加原位缝合治疗远节指末端离断伤的疗效及优缺点，更有针对性地为临床提供一种有效的治疗方法。②方法 对临床两种治疗方法的29例加以回顾性总结、比较分析，获得详细相关数据资料，并对数据资料进行统计学的分析和处理。③结果 原位缝合治疗远节指末端离断伤的总有效率远低于贯穿植入随意血管神经束加原位缝合法。④结论 贯穿植入随意血管神经束原位缝合治疗远节指末端离断伤，是一种比较理想的方法，值得临床推广使用。     

拉米夫定治疗慢性乙肝的疗效及乙肝病毒YMDD变异的研究

目的评价拉米夫定治疗慢性乙肝病人的1年疗效、乙肝病毒YMDD变异率、变异与治疗前HBV-DNA、ALT水平的联系。方法治疗组按入选标准随机选择32例慢性乙型肝炎患者给予拉米夫定100 mg/d并随访1年,并于治疗开始后3、6、9、12个月检测肝功能、HBV-M、HBV-DNA、YMDD变异。对照组随机选择36例从未接受抗病毒治疗的HBV-DNA阳性、ALT异常的慢性乙型肝炎患者,检测YMDD变异株。结果①拉米夫定治疗一年,HBV-DNA转阴率71.88%(23/32),HBeAg/HBeAb血清转换率18.52%(5/27),ALT复常率62.5%(20/32);治疗前及治疗12个月后ALT水平分别为132.59±66.07、49.78±27.94,治疗前后差别有统计学意义(P<0.001)。②治疗组在治疗前未发现YMDD变异,治疗6个月发现2例YMDD变异,变异率6.25%,治疗12个月发现5例YMDD变异,变异率15.63%;对照组36例从未接受抗病毒治疗的慢性乙型肝炎病人中检测出2例YVDD变异株与野生株共存。③治疗前ALT<3×ULN组及≥3×ULN组YMDD变异率分别为11.76%、20.00%,两组差别无统计学意义(P=0.645);治疗前HBV-DNA<106copies/mL组及≥106copies/mL组YMDD变异率分别为5.88%、26.67%,两组差别无统计学意义(P=0.161)。结论拉米夫定能迅速抑制乙肝病毒复制、改善肝功能;治疗前HBV-DNA水平及ALT水平不足以预见YMDD变异的发生;乙肝病毒YMDD变异株存在于未使用拉米夫定的慢性乙肝患者中,建议在抗病毒治疗前对YMDD变异进行常规检测。     

48例非霍奇金淋巴瘤中的p53基因突变

采用ＡＢＣ和ＰＣＲ－ＳＳＣＰ法在４８例ＮＨＬ中研究ｐ５３基因外显子５～８中发生突变的类型、频率与突变型ｐ５３蛋白的表达以及它们与病理分型、恶性程度的相关性。结果：突变型ｐ５３蛋白在ＮＨＬ中的阳性率为４１．７％，其中在弥漫型大细胞性淋巴瘤（ＤＬＣＬ）为７５％，在非ＤＬＣＬ为３５％，两者差异显著（Ｐ＜０．０５）；在ｐ５３蛋白表达阳性的ＮＨＬ中ＰＣＲＳＳＣＰ阳性主要见于ＤＬＣＬ，检出率为１５％，在非ＤＬＣＬ中ＰＣＲ－ＳＳＣＰ均为阴性（Ｐ＜０．０５）。表明国人ＮＨＬ，尤其在恶性程度很高的ＤＬＣＬ中存在ｐ５３基因突变，各型ＮＨＬ都有不同程度的突变型ｐ５３蛋白表达