耐药性癫(癎)患者颞叶中细胞周期依赖性蛋白激酶5的表达

目的 研究细胞周期依赖性蛋白激酶5(cyclin dependent kinases 5,CDK5)在耐药性癫(癎)患者颞叶中的表达,探索其在耐药性癫(癎)发病机制中的作用.方法 收集耐药性癫(癎)患者术后脑组织,用荧光定量PCR、免疫组化和Western blot 3种检测方法从基因和蛋白水平分别测定CDK5在耐药性癫(癎)患者颞叶中的表达,并与对照组进行比较.结果 荧光定量PCR发现CDK5 mRAN比对照组明显增加,免疫组化检测显示这种基因的蛋白表达产物主要分布在神经元轴突和胶质细胞中,Western blot检测在相对分子质量35 000处有一蛋白条带,并且可见实验组(颞叶和海马中分别为1.4293±0.1839和2.0733±0.4738)高于对照组(颞叶和海马中分别为0.9680±0.4147和1.403±0.6163,P＜0.05).结论 CDK5在耐药性癫(癎)患者颞叶中表达增强,提示他们可能参与了耐药性癫(癎)的形成.     

RNA干扰及其在胶质瘤基因治疗中的应用

RNA干扰（RNA interference。RNAi）是双链RNA（double—stranded RNA，dsRNA）降解特异性靶基因转录出的mRNA。从而抑制靶蛋白表达的现象。自从二十世纪九十年代发现RNAi这一现象以来，RNAi已被广泛应用于研究基因功能、信号转导通路和基因治疗等方面。随着分子生物学、分子遗传学等学科的发展．发现了许多与肿瘤发生、发展和预后密切相关的基因。经过大量临床前期试验表明，针对特异性靶基因的小干扰RNA（short／small interfering RNA．siRNA）治疗胶质瘤是行之有效的。为基因治疗胶质瘤提供了新的思路。[第一段]     

载脂蛋白E基因多态性与脑梗死的相关性分析

目的　探讨载脂蛋白 E基因多态性与脑梗死的关系。方法　通过聚合酶链反应 -限制性片段长度多态性 (PCR- RFL P)分析结合 DNA直接银染技术检测 6 6例脑梗死 (CI)患者的载脂蛋白 E(Apo E)基因型 (其中家系中有明确脑梗死先证者的家族聚集性脑梗死 (FMACI)亚组 2 6例 ,家系中无脑卒中史的非家族聚集性脑梗死 (NF-MACI)亚组 4 0例 ) ,并与 90例健康对照组比较 ,同时检测血脂、脂蛋白 (a) [L P(a) ]及部分载脂蛋白。结果　脑梗死组ε3/4基因型频率明显高于对照组 (P<0 .0 1) ,ε3/3基因型频率明显低于对照组 (P<0 .0 1) ;两脑梗死亚组之间的ε3/4/ε3/3基因型频率虽有上升 /下降趋势 ,但未发现明显的统计学差异 ;FMACI组高密度脂蛋白 (HDL )水平明显低于 NFMACI组 (P<0 .0 5 )。结论　 Apo E基因多态性与脑梗死的发生有关 ,ε4等位基因是脑梗死的易感因子 ,ε3等位基因对脑梗死的发生有保护作用 ;Apo E基因多态性和 HDL水平双重作用于家族聚集性脑梗死的发生。     

Discovery of potent and selective inhibitors of procollagen C-proteinase for the treatment of fibrotic disorders

Introduction   Fibrosis is a component of many tissue pathologies leading to loss of normal tissue function, primarily due to excessive collagen deposition. Collagen is deposited following cleavage of the C- and N- terminal peptides from the pro-collagen molecule. The cleavage of the globular C-peptide by PCP reduces solubility of the fibrillar collagen molecule, resulting in deposition of insoluble collagen. Increased insoluble collagen deposition is a feature of all organ fibroses, with inhibition of this process, a key potential anti-fibrotic mechanism. The aim of this work was to discover potent and selective PCP inhibitors as experimental, topically applied, anti-fibrotic drugs for clinical evaluation.
Materials and methods   PCP was cloned from human osteosarcoma cells and enzymatic activity demonstrated using a PCP-specific peptide cleavage assay. Activities were confirmed by measuring cleavage of [³H]C-peptide from type-I pro-collagen. A cell-based fibroplasias model was employed to demonstrate compound efficacy using collagen deposition, liberated C-peptide and histological endpoints. The activities of PCP inhibitors in fibroblast and epithelial in vitro cell proliferation and migration assays, and selectivity vs. a panel of MMPs were also determined.
Discussion   In summary, we have identified and characterized potent and selective inhibitors of PCP for progression to clinical studies for investigation as a treatment paradigm for fibrotic disease.  

  Results     

5.

Reduction of adhesion formation in rabbits by intraperitoneal administration of lazaroid formulations     

Rodgers  KE; Girgis  W; St Amand  K; Campeau  J; diZerega  GS 《Human reproduction (Oxford, England)》1998,13(9):2443-2451

Adhesion formation is a major source of postoperative morbidity and mortality. In this study, the ability of a variety of lazaroid formulations [the antioxidant 21-aminosteroid PNU74006F (tirilazad) and the non-steroidal 2-methylaminochroman derivative PNU83,836E] to reduce i.p. adhesion formation in three rabbit models was examined. In initial studies, PNU83836E was administered via Alzet miniosmotic pump to the site of injury. In the sidewall and double uterine horn models, PNU83,836E was administered via Alzet miniosmotic pump for the entire postoperative interval. In the sidewall model, there was a dose- dependent reduction in the area of the sidewall injury that was involved in adhesions. In the double uterine horn model, PNU83,836E was administered via Alzet miniosmotic pump to the area of injury for 1, 2, 3 or 7 days. Administration for as little as 24 h after surgery significantly reduced the extent of adhesion formation and the reduction was increased if it was administered for longer. Further studies were conducted in which various lazaroid formulations were administered as a bolus at the end of surgery. In both the sidewall and double uterine horn models, administration of either PNU83,386E (in citrate buffer) or PNU74006F (in cyclodextrin or lipid emulsion vehicles) at the end of surgery reduced adhesion formation. Administration of a bolus of PNU74006F 10 min prior to initiation of surgery with or without additional treatment at the end of surgery further increased its efficacy in the reduction of adhesion formation. Administration of a minimum of 1.5 mg before and after surgery (3 mg total) was required for maximal efficacy. These studies demonstrate that pre- and postoperative administration of either a steroidal (PNU74006F) or non-steroidal (PNU83,836E) lazaroid intraperitoneally reduced the formation and reformation of postoperative adhesions in three animal models.      

6.

难治性便秘综合治疗及影响因素的评价   总被引：1，自引：0，他引：1  

许琳  宋志强  王智凤  柯美云 《基础医学与临床》2008,28(4):387-390

目的评价综合治疗对难治性便秘的疗效及影响因素。方法将84例难治性便秘分为非重叠组和重叠组。应用个体化综合治疗4周,观察便秘症状评分变化及总有效率,分析IC患者的重叠症状和心理障碍状态对疗效的影响。结果(1)84例便秘患者中,重叠组和非重叠组分别占40.5%和59.5%。(2)重叠组和非重叠组的总有效率分别为50.0%和78.0%(P<0.05)。(3)对37例IC患者的心理测试调查显示,59.4%(22/37)有心理障碍状态,重叠组和非重叠组伴有心理障碍状态对治疗的总有效率分别为4.8%和31.5%(P<0.05)。结论适合个体化的综合治疗使多数难治性便秘缓解症状,但伴有重叠症状,尤其心理障碍状态则影响疗效。     

7.

Joan of Arc, creative psychopath: is there another explanation?          下载免费PDF全文

Whitlock FA 《Journal of the Royal Society of Medicine》1987,80(2):129

     

8.

Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors   总被引：3，自引：0，他引：3  

克晓燕  杨玉花  赵昕  王良绪 《中华医学杂志(英文版)》2001,114(2):196-199

Objective To evaluate the long-term therapeutic effects of autologous peripheral blood st em cell transplantation (auto-PBSCT) on the treatment of hematological and soli d tumors. Methods Fifty-one patients were recruited in this auto-PBSCT study, in which several p otentially important parameters were studied including the optimal time for stem cell co llection, the dose of stem cell reinfusion, the time of hematopoietic reconsti tution, the disease free survival (DFS) and overall survival (OS), complication s related to transplantation, and maintenance chemotherapy after auto-PBSCT. Results After APBSCT, 3-year and 5-year survival rates of NHL were 83.3%; those of AM L were 74.7%; those of MM were 37.9% and 19%; those of ALL were 40% and 0% res pectively. Hematopoietic reconstitution was greatly promoted by granulocyte col ony stimulating factor (G-CSF). The mean time for patients’ neutrophil to reco ver up to &gt;0.5×10(9) /L after APBSCT was 11.14 days in the group of the patien ts receiving G-CSF in contrast to 17.6 days in the group receiving no G-CSF. The most common complications of transplantation were fever, liver dysfunction and hypokalaemia, which were curable. No death was due to transplantation related complications.Conclusion Comparing with conventional chemotherapy, our study suggests that auto-PBSCT i s a very important therapeutic option that can significantly improve the prognos is in the patients with hematological and solid tumors, especially in the patien ts with AML and NHL.     

9.

国人无综合征性耳聋患者的线粒体基因组7445A→G突变263例调查     

刘玉和  柯肖枚  戚豫  徐海波  顾之平  刘晓晨  刘洁芬 《临床耳鼻咽喉头颈外科杂志》2000,14(4)

目的 :探讨国人无综合征性耳聋 ( NSD)患者的线粒体 DNA 744 5 A→ G( m t DNA744 5 A→ G)突变的发生情况。方法 :对 32个 NSD家系 12 8例和 135例散发的 NSD患者 ,10 0例正常人 ,以 PCR法检测 mt DNA 744 5 A→ G突变情况。结果 :全部受检者无 mt DNA744 5 A→ G突变发生。结论 :国人 NSD患者的 m t DNA744 5 A→ G突变的发生率较低 ,且明显低于 mt DNA15 5 5 A→ G的突变发生率     

10.

A PERSISTENT TRANSPLEURAL FISTULOUS COMMUNICATION BETWEEN LUNG AND CHEST WALL     

AK RAJPUT  VASU VARDHAN  KE RAJAN  SC TEWARI 《Medical Journal Armed Forces India》2000,56(3):259-261

     

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Reduction of adhesion formation in rabbits by intraperitoneal administration of lazaroid formulations

Adhesion formation is a major source of postoperative morbidity and mortality. In this study, the ability of a variety of lazaroid formulations [the antioxidant 21-aminosteroid PNU74006F (tirilazad) and the non-steroidal 2-methylaminochroman derivative PNU83,836E] to reduce i.p. adhesion formation in three rabbit models was examined. In initial studies, PNU83836E was administered via Alzet miniosmotic pump to the site of injury. In the sidewall and double uterine horn models, PNU83,836E was administered via Alzet miniosmotic pump for the entire postoperative interval. In the sidewall model, there was a dose- dependent reduction in the area of the sidewall injury that was involved in adhesions. In the double uterine horn model, PNU83,836E was administered via Alzet miniosmotic pump to the area of injury for 1, 2, 3 or 7 days. Administration for as little as 24 h after surgery significantly reduced the extent of adhesion formation and the reduction was increased if it was administered for longer. Further studies were conducted in which various lazaroid formulations were administered as a bolus at the end of surgery. In both the sidewall and double uterine horn models, administration of either PNU83,386E (in citrate buffer) or PNU74006F (in cyclodextrin or lipid emulsion vehicles) at the end of surgery reduced adhesion formation. Administration of a bolus of PNU74006F 10 min prior to initiation of surgery with or without additional treatment at the end of surgery further increased its efficacy in the reduction of adhesion formation. Administration of a minimum of 1.5 mg before and after surgery (3 mg total) was required for maximal efficacy. These studies demonstrate that pre- and postoperative administration of either a steroidal (PNU74006F) or non-steroidal (PNU83,836E) lazaroid intraperitoneally reduced the formation and reformation of postoperative adhesions in three animal models.      

难治性便秘综合治疗及影响因素的评价

目的评价综合治疗对难治性便秘的疗效及影响因素。方法将84例难治性便秘分为非重叠组和重叠组。应用个体化综合治疗4周,观察便秘症状评分变化及总有效率,分析IC患者的重叠症状和心理障碍状态对疗效的影响。结果(1)84例便秘患者中,重叠组和非重叠组分别占40.5%和59.5%。(2)重叠组和非重叠组的总有效率分别为50.0%和78.0%(P<0.05)。(3)对37例IC患者的心理测试调查显示,59.4%(22/37)有心理障碍状态,重叠组和非重叠组伴有心理障碍状态对治疗的总有效率分别为4.8%和31.5%(P<0.05)。结论适合个体化的综合治疗使多数难治性便秘缓解症状,但伴有重叠症状,尤其心理障碍状态则影响疗效。     

Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors

Objective To evaluate the long-term therapeutic effects of autologous peripheral blood st em cell transplantation (auto-PBSCT) on the treatment of hematological and soli d tumors. Methods Fifty-one patients were recruited in this auto-PBSCT study, in which several p otentially important parameters were studied including the optimal time for stem cell co llection, the dose of stem cell reinfusion, the time of hematopoietic reconsti tution, the disease free survival (DFS) and overall survival (OS), complication s related to transplantation, and maintenance chemotherapy after auto-PBSCT. Results After APBSCT, 3-year and 5-year survival rates of NHL were 83.3%; those of AM L were 74.7%; those of MM were 37.9% and 19%; those of ALL were 40% and 0% res pectively. Hematopoietic reconstitution was greatly promoted by granulocyte col ony stimulating factor (G-CSF). The mean time for patients’ neutrophil to reco ver up to &gt;0.5×10(9) /L after APBSCT was 11.14 days in the group of the patien ts receiving G-CSF in contrast to 17.6 days in the group receiving no G-CSF. The most common complications of transplantation were fever, liver dysfunction and hypokalaemia, which were curable. No death was due to transplantation related complications.Conclusion Comparing with conventional chemotherapy, our study suggests that auto-PBSCT i s a very important therapeutic option that can significantly improve the prognos is in the patients with hematological and solid tumors, especially in the patien ts with AML and NHL.     

国人无综合征性耳聋患者的线粒体基因组7445A→G突变263例调查

目的 :探讨国人无综合征性耳聋 ( NSD)患者的线粒体 DNA 744 5 A→ G( m t DNA744 5 A→ G)突变的发生情况。方法 :对 32个 NSD家系 12 8例和 135例散发的 NSD患者 ,10 0例正常人 ,以 PCR法检测 mt DNA 744 5 A→ G突变情况。结果 :全部受检者无 mt DNA744 5 A→ G突变发生。结论 :国人 NSD患者的 m t DNA744 5 A→ G突变的发生率较低 ,且明显低于 mt DNA15 5 5 A→ G的突变发生率