Phenotypic variation in Waardenburg syndrome: mutational heterogeneity, modifier genes or polygenic background?

We have identified 11 mutational changes in the PAX3 gene in patients with type 1 Waardenburg syndrome (WS1) including three in the paired domain, six within or immediately adjacent to the homeodomain and two previously described polymorphic variants in exons 2 and 6. The affected members of one family carried substitutions involving two base pairs separated by one unaltered codon. Two of the deleterious mutations were identical and three others were identical to previously reported mutations. A comparison of clinical findings in families carrying substitutions in the same codon failed to reveal conspicuous similarities. Although subtle mutation-specific effects may well exist, allelic heterogeneity clearly cannot account for within family variation. However, the striking concordance of a pair of monozygotic twins with Waardenburg syndrome (WS) and previous reports of similar pairs indicate that phenotypic variation in WS has a genetic basis. If the genetic effects are mediated by oligogenic epistasis, as studies in the mouse suggest, it may ultimately be possible to predict clinically relevant aspects of the Waardenburg phenotype.      

纤维胆道镜临床应用160例

0　引言　纤维胆道镜 (下称胆道镜 )在肝内外胆道疾病中的应用 ,其诊治价值已得到充分肯定 .我院 1996 - 0 1/ 1999- 12 ,术中、术后使用胆道镜诊治胆道肿瘤及结石 16 0例 ,取得了较满意的效果 .1　对象和方法1.1　对象　术中应用胆道镜行胆道探查共 38(男 2 3,女 15 )例 ,其中胆总管结石 2 9例 ,肝内胆管多发结石 5例 ,胆管肿瘤4例 .术后经 T管瘘道取石或活检 12 2 (男 78,女 44 )例 ,年龄18～ 77岁 ,其中肝外胆管残余结石 114例 ,多发性肝内胆管残余结石 5例 ,胆总管下端肿瘤活检 2例 ,置管造影 1例 .1.2　方法　日本 Olympus CHP2 OQ…     

上消化道大出血122例的外科治疗

0　引言　上消化道大出血是内、外科医师临床工作的难题之一 ,我院 1985 / 1998因上消化道大出血而进行手术者共 12 2例 ,占同类疾病 10 13例的 12 .4% .1　临床资料　本组 12 2 (男 96 ,女 2 6 )例 .年龄 16～ 75岁 ,平均 45 .5岁 ,患者有呕血 ,柏油样便或两者兼有 .因出血过多可出现心悸 ,头晕 ,甚至休克 .病因与治疗结果见表 1.2　讨论　溃疡并发大出血是消化性溃疡常见的并发症 .此类病例术中首要问题是寻找出血灶 ,术前可做胃镜 .剖腹后首先探查常见出血部位如胃、十二指肠 ,然后探查肝胆、脾和空肠上段 ,未发现明确病灶者常规采用胃体…     

中药饮剂对大鼠降压和利尿的效果

0　引言　高血压病发病率高 ,其促发心脑血管病的危害越来越受到重视 .目前常用的化学药物多有各种副作用 ,为探索新的降压药物 ,我们开展了中药饮剂降压的动物药效观察 .1　材料和方法1.1　实验动物　由北京高血压病研究所动物室提供的 SD大鼠 48只 ,均为雌性 ,体质量 15 0～ 190 g,毛发光泽、精神、活动状况较好 .以北京京康饲料公司提供的混合料喂养 .实验期间饲养于自制代谢笼中 .48只大鼠随机分为实验组及对照组 ,各 2 4只 .两组同室饲养 ,室内温度、湿度、照明、噪音等环境相同 .1.2　中药饮剂组方及制备　中药饮剂组方原则以五皮饮…     

Immune privilege induced by cotransplantation of islet and allogeneic testicular cells

Objective To induce islet allograft long- term survival through cotransplantation of islet cells with sertoli cells. Methods Testicular sertoli cells were prepared by digestion with collagenase, trypsin an d DNase, and were cultured for 48 hours. Collagenase digested and Ficoll purifi ed donor (Wistar rat) islets were cotransplanted with allogeneic sertoli cells i n the absence of systemic immunosuppression. Terminal deoxynucleotidyl transfer ase- mediated X- dUTP nick- end labeling (TUNEL) was used to label apoptosis of lymphocytes surrounding the islet graft. Results Cotransplantation of islets and 1×10(7) sertoli cells reversed the diabetic sta te for more than 60 days in 100% (6/6) of the chemically diabetic Sprague Dawley rats. Grafts consisting of islets alone or islets plus 1×10(5) sertoli cells survived only for 5-6 days. Apoptosis of lymphocytes surrounding the islets was quite clear. Conclusion Cotransplantation of islets with FasL［+］ sertoli cells induces local immune priv ilege and allows long- term graft survival without systemic immunosuppression.     

Retroviral-mediated gene expression in human myelomonocytic cells: a comparison of hematopoietic cell promoters to viral promoters

Gene transfer into human hematopoietic stem cells with expression targeted to the maturing myelomonocytic progeny has applications for gene therapy of genetic diseases affecting granulocytes and macrophages. We hypothesized that promoters of myeloid-specific genes that are upregulated with myelomonocytic differentiation would also upregulate expression of an exogenous gene in a retroviral vector. Moloney murine leukemia virus (MoMuLV)-based retroviral vectors using promoters from hematopoietic genes (CD11b, CD18, and CD34) were compared with vectors with viral promoters (MoMuLV long terminal repeat [LTR], cytomegalovirus [CMV], and simian virus 40 [SV40]). Human glucocerebrosidase (GC) cDNA was the reporter gene. HL60 cells were transduced with these vectors and vector-derived GC activity was compared in undifferentiated HL-60 cells and the same cells differentiated into granulocytes using dimethyl sulfoxide or monocyte/macrophages using phorbol myristate acetate. In undifferentiated HL-60 cells, vector-derived GC activity was the highest when it was controlled by the MoMuLV LTR. In HL-60 cells differentiated into granulocytes, vector-derived GC activity transcribed from the CD11b, MoMuLV LTR, and CMV promoters was equivalent to 1.7, 1.5, and 1.5 times the normal endogenous GC activity, respectively, and 0.8, 2.0, and 3.6 times the normal GC activity, respectively, in those differentiated into macrophages. With granulocytic differentiation, the CD11b promoter showed maximal induction in GC activity (8-fold); with macrophage differentiation, the CD11b promoter showed a fourfold induction in GC expression. The CD11b promoter also generated significant levels of GC activity in the myelomonocytic progeny of transduced CD34+ cells. Expression from the CD11b promoter, unlike that from the CMV or the MoMuLV LTR promoters, was relatively myelomonocyte-specific, with minimal expression observed in Jurkat T cells or HeLa carcinoma cells. The induction of expression from the CD11b promoter with differentiation in HL-60 cells correlates with the developmental regulation of the CD11b gene. Retroviral vectors using the CD11b promoter have potential utility for gene therapy of disorders affecting the myelomonocytic lineage.     

大鼠蛛网膜下腔联合注射kappa受体激动剂和NMDA受体拮抗剂协同镇痛

以大鼠热辐射甩尾潜伏期为测痛指标,蛛网膜下腔(it)联合注射非镇痛剂量的kappa阿片受体激动剂强啡肽(dynorphin,Dyn)A-(1-13)5nmol或U50488H(trans-(±)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide)100nmol和N-methyl-D-aspartate(NMDA)受体拮抗剂DL-2-amino-5-phosphonovalericacid(APv)10 nmol 或 kynurenicacid (KYN) 50 nmol 有显著的协同镇痛效应,其效应与NMDA受体拮抗剂呈一定量效关系。Kappa阿片受体特异性拮抗剂nor-binaltorphi-mine(nor-BNI)15nmolit可完全翻转Dyn A-(1-13)5nmol和APv10nmol及U50488H100nmol和KYN50nmol的协同镇痛。说明协同作用是通过kappa受体和谷氨酸能神经元之间的相互作用实现的。     

蒿苯酯在大鼠的药物代谢动力学

大鼠ig蒿苯酯后吸收迅速,其药时曲线出现双峰现象。SPLI非房室模型统计矩计算结果表明,3剂量组平均驻留时间MRT约在12h,半衰期T_1/2约在8h,基本一致。将前8h第一峰血药浓度曲线用3P87程序拟合,药代动力学模型为一室模型。大鼠ig蒿苯酯后2h药物可广泛分布于各组织,6h后各组织中药物浓度均很低。ig蒿苯酯后主要经尿排出,48h经粪尿累积排出70.4%。蒿苯酯平均血浆蛋白结合率约为70%。提取物形式的鉴别结果表明,大鼠ig蒿苯酯后血中以蒿苯酯原型药为主,尿中蒿苯酯及还原青蒿素均有,粪中则以还原青蒿素为主。     

高龄冠心病行非心脏手术患者麻醉恢复室内的护理

0引言冠心病是高龄人群常见多发合并症.实施非心脏手术可因麻醉手术应激、疼痛、精神刺激等因素,常在围术期诱发或加重心绞痛、心肌梗死、心衰、心律失常等危险状况[1].     

丹参中抑制血小板聚集的活性成分

从中药丹参(Salvia miltiorrhiza Bunge)的根中获得5种成分,经鉴定3种为已知物即丹参新酮、铁锈醇及Ro-090680,另2种为新化合物,命名为△¹丹参新酮与△¹-丹参酮Ⅱ_A并观察了它们抑制血小板的聚集活性。