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991.
Screening for mutations in candidate genes for hypospadias   总被引:2,自引:0,他引:2  
Hypospadias, a condition with a frontally placed urethral orifice on the penis, is the most common malformation in males. During fetal development several components are necessary for normal male genital development. Testosterone and dihydrotestosterone act via the androgen receptor but a defective receptor function results in different degrees of genital malformations. Testosterone-5α-reductase converts testosterone to dihydrotestosterone, which is crucial for normal differentiation, and a total lack of this enzyme results, in syndromes with hypospadias. The Wilms' tumour 1 (WT1) gene is expressed in the fetal gonad and genital malformations can occur due to WT1 gene mutations. These genes are therefore strong candidate genes for hypospadias. We have analysed 35 boys with hypopadias and one girl diagnosed as with complete androgen insensitivity syndrome, using exon by exon polymerace chain reaction (PCR) amplification of the AR, WT1 and 5α-reductase genes and screened for point mutations and performed subsequent DNA sequencing. No mutations in any of these genes were found in the 26 patients with isolated hypospadias. Two patients with severe hypospadias with cryptorchidism were found to carry mutations in the androgen receptor gene. Also the girl with clinically diagnosed complete androgen insensitivity was found to be homozygous for a splice mutation in the 5α-reductase gene. In summary, mutations in the WT1, AR and 5α-reductase genes are not common causes of isolated hypospadias. Received: 1 October 1997 / Accepted: 4 May 1998  相似文献   
992.
c-fos基因在乐果中毒后肌无力大鼠肌组织中的表达   总被引:4,自引:0,他引:4  
采用RT-PCR、WesternBlot技术,检测了有机磷农药乐果对大鼠骨骼肌细胞中即刻早期反应基因c-fos表达的影响。结果表明,在乐果作用下,骨骼肌细胞c-fos基因表达在mRNA以及蛋白质水平均明显增高。然而骨骼肌细胞c-fos的表达是否与毒物刺激有关,其在农药中毒机制上的生物学意义有待深入研究。  相似文献   
993.
免疫状态对Fv—4基因抗Friend MuLV作用的影响   总被引:1,自引:0,他引:1  
通过检测免疫抑制的F1小鼠和杂合子F2裸鼠对Friend小鼠白血病病毒(Fr.MuLV)感染的敏感性,探讨免疫状态对Fv-4基因(特别是对Fv-4基因杂合子)抗FriendMuLV作用的影响,经腹腔接种Fr.MuLV病毒液攻击小鼠或F2裸鼠后,检查其计中Fr.MuLV的增主其发病情况,结果表明,免疫抑制的F1小鼠和杂合子F1裸鼠都可被Fr.MuLV脾脏中有病毒增殖,并用约2/3的杂合子F2裸鼠与B  相似文献   
994.
氯化甲基汞对大鼠脑神经细胞凋亡及P^53基因表达的影响   总被引:6,自引:0,他引:6  
选用Wistar系雄性大鼠,经皮下注射给予10mg/Kg体重氯化甲基汞(CH3HgCl),连续7天,第15天取其脑组织,利用细胞和分子生物学技术进行DNA电泳和流式细胞术(FCM)分析。实验结果,染毒组大鼠脑组织DNA电泳呈现特征性梯形电泳带;FCM分析染毒组大鼠脑神经细胞的凋亡率、P53基因表达率显著高于对照组(P<0.05)。结果表明:CH3HgCl以诱导凋亡方式导致脑神经细胞损伤,P53基因参与CH3HgCl诱导脑神经细胞凋亡的基因调控过程。  相似文献   
995.
宋诗铎  张同海 《天津医药》1999,27(10):602-604
目的:为获得与天然鲑鱼生长激素一致的基因工程产物,对已构建的鲑鱼生长激素基因分泌型表达质粒pOsGH153进行改造,删除所编码表达产物氨基端多余的9个碱基,方法:采用PALTER系统进行寡聚核苷酸指导下的基因定点缺失突变。突变质粒pOsGH158经限制性酶切图谱及Southern印迹杂交分析加以证,结果:含有表达质粒pOsGH158的大肠杆菌株经IPTG诱导后提取周质帽白,经SDS-PAGE及免疫  相似文献   
996.
张敬  张云亭 《天津医药》1999,27(11):668-670
目的:动态观察大鼠C6胶质瘤模型的自然生长过程及反义IGF-1mRNA对胶质瘤的治疗效果和治疗机制。方法:将32只Wistar大鼠分成4组,每组8只,(1)对照组(C组)于右尾状核接种C6鼠胶质瘤细胞。(2)治疗组(T组):于右尾状核接种C6细胞后的第7、10天在接种点注射脂质体包裹的质粒P-anti-IGF-1,对胶质瘤进行治疗于右尾状核接种经反义IGF-1mRNA转染的C6胶质瘤细胞。(4)K  相似文献   
997.
998.
A case of synchronous squamous cell carcinomas in the soft palate,larynx and esophagus is reported, along with findings of molecular-pathologicalanalysis. A biopsy sample from the aryngeal carcinoma revealedwell differentiated squamous cell carcinoma harboring two pointmutations at codons 144 and 148 of the p53 gene but not at codon299, and more than 50% of the cancer cells showed accumulationof p53 protein immunohistochemically. The esophageal tumor,which was moderately differentiated squamous cell carcinoma,showed immunoreactivity for p53 within the nuclei of 25–50%of cancer cells with a missense mutation at codon 299 but notat codon 144 or 148. This cancer also showed immunoreactivityfor transforming growth factor alpha. On the other hand, thepoorly differentiated squamous cell carcinoma in the soft palateshowed negative immunoreactivity for p53 and no point mutationin exons 5 to 8 of the gene. These results suggest that thethree synchronous squamous cell carcinomas arose as independentevents.  相似文献   
999.
Summary Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGF1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suraminin vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize.New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.  相似文献   
1000.
Summary A new method of measuring gene copy number in small samples of DNA was used to measure amplification of theerbB-2 gene and of chromosome 20q in breast cancers. This method, termed differentially competitive polymerase chain reaction (DC-PCR) combines the advantages of two other techniques for measuring amplification by PCR, namely differential PCR and competitive PCR. The DC-PCR methodology was evaluated for sensitivity and specificity by comparing amplification oferbB-2 measured by DC-PCR with that obtained by fluorescencein situ hybridization (FISH) for 42 cases or Southern blotting and/or slot blot analysis for 34 cases. There was over 90 percent concordance with both FISH and Southern blotting and/or slot blot analysis.DC-PCR was used to further characterize the newly described amplicon at chromosome 20q. By analyzing DNA from 10 breast cancer cell lines at 7 different loci, we identified a potential common region of amplification of approximately 5 centimorgans at chromosome 20q13 bordered by loci D20S52 and RMC20C001-S1. One hundred and seventeen cases of primary breast cancer were evaluated for amplification at these two loci. Amplification at one or more loci, defined as > 1.5 fold higher copy number than that of normal DNA, was found in 25 cases (21%). Sixteen cases were amplified at only one of the two probes (12 cases for RMC20C001-S1 and 4 cases for D20S52), suggesting that the target gene lies between the two markers or that there are two independent target genes within a small chromosome region.  相似文献   
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