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1.
Objectives To formulate an equation for fine mapping of disease loci under complex conditio ns and determine the marker- disease distance in a specific case using this equa tion.Methods Lewontin’s linkage disequilibrium (LD) measure D’ was used to formulate an e quation for mapping disease genes in the presence of phenocopies, locus heterogeneit y, gene- gene and gene- environment interactions, incomplete penetrance, uncerta in liability and threshold, incomplete initial LD, natural selection, recurrent mutation, high disease allele frequency and unknown mode of inheritance.This e quation was then used to determine the distance between a marker (ε4 within the apolipoprotein E gene, APOE) and Alzheimer’s disease (AD) loci using published data.Results An equation was formulated for mapping disease genes under the above conditions .If these conditions are present but ignored, then recombination fraction θ between marker and disease loci will be either overestimated or estimated with little bias.Therefore, an upper limit of θ can be obtained.AD has been foun d to be associated with the marker allele ε4 in Africans, Asians, and Caucasian s.This suggests that the AD- ε4 allelic LD predates the divergence of peoples occurring 100 000 years ago.With the age of AD- ε4 allelic LD so estima ted, the maximal distance was calculated to be 23. 2 kb (mean 5. 8 kb).Conclusions (1) A method is developed for LD mapping of susceptibility genes.(2) A mutatio n within the APOE gene itself, among others, is responsible for the susceptibili ty to AD, which is supported by recent evidence from studies using transgenic mice.   相似文献   

2.
Myasthenia gravis in pediatric and elderly patients   总被引:4,自引:0,他引:4  
Liu W  Liu G  Fan Z  Gai X 《中华医学杂志(英文版)》2003,116(10):1578-1581
Objective To determine whether the clinical and pathologic characteristics and prognoses of myasthenia gravis (MG) patients below 15 years differ from those patients over 50 years after thymectomy. Methods We reviewed the registry material of 30 pediatric and 32 elderly MG patients after thymectomy, including their age, sex, clinical classification, pathological types, and prognoses. The Chi-square test or Wilcoxon’s rank-sum test was used to determine the statistical differences between the children and elderly groups.Results No significant difference was seen in sex distribution between the two groups (Chi-square test, P=0.625), but there were differences in clinical classification: more type Ⅰ was observed in the pediatric group than in the elderly group, but more type Ⅱor Ⅲ was seen in the elderly group (Wilcoxon’s rank-sum test, P<0.001). As to pathological types, the pediatric group was also significantly different from the elderly group (Chi-square test, P<0.01). All of the patients (100%) in the pediatric group had thymus hyperplasia, but in the elderly group more than half (56.26%) were found to have thymoma (benign or malignant). The prognoses after thymectomy were better in the pediatric group than in the elderly group (Wilcoxon’s rank-sum test, P<0.001). Conclusions Because the prognoses are generally better than those of the elderly patients, we should be careful when operating on pediatric patients of ocular type. The elderly patients tend to receive more aggressive treatment because of more severe generalized types often associated with thymoma and poor prognoses. Both pediatric and elderly patients are seldom associated with other autoimmune disease.  相似文献   

3.
Management of cerebral ischemia due to Takayasu''''s arteritis   总被引:2,自引:0,他引:2  
Aortoarteritis ,alsocalledTakayasu’sarteritis ,isachronicidiopathicinflammatorydiseasethataffectslargeandmediumsizearteries Clinicalfeaturesreflectlimbororganischemiaresultingfromstenosistoobliterationofinvolvedarteries Thisdisease ,describedbyTakayasuin…  相似文献   

4.
Objective To study the human dystrophin gene molecular deletion mechanism, we analyzed breakpoint regions within junction fragments of deletion-type patients and investigated whether the dystrophin gene’s intron structure might be related to intron instability.Methods Junction fragments corresponding to exon 46 and 51 deletions were cloned. The breakpoint regions were sequenced, and the features of introns with available Genebank sequences were analyzed.Results An analysis of junction fragment sequences corresponding to exon 46 and 51 deletions showed that all 5’ and 3’ breakpoints are located within repeat sequences. No small insertions, small deletions, or point mutations are located near the breakpoint junctions. By analyzing the secondary structure of the junction fragments, we demonstrated that all junction fragment breakpoints are located in non-matching regions of single-stranded hairpin loops. A high concentration of repetitive elements is found to be a key feature of many dystrophin introns. In total, 34.8% of the overall dystrophin intron sequences is composed of repeat sequences.Conclusion Repeat elements in many dystrophin gene introns are the key to their structural bases and reflect intron instability. As a result of the primary DNA sequences, single-stranded hairpin loops form, increasing the instability of the gene, and forming the base for breaks in the DNA. The formation of the single-stranded hairpins can result in reattachment of two different breakpoints, producing a deletion.  相似文献   

5.
Zafirlukast,aleukotriene (LT)receptorantagonist,wasconsideredasanalternativetotreattheasthmainrecentyears Ithasbeendemonstratedthatleukotrienereceptorsexistnotonlyinairwaybutalsoinpulmonaryvasocular 1Pangetal’sstudyshowedthatZafirlukastcanloweranoxicpulmonaryhypertensioninrats 2  ToinvestigatethepossibleclinicaltherapeuticefficacyofZafirlukastonchronicobstructivepulmonarydisease (COPD )inducedanoxicpulmonaryhypertension ,westudiedthehemodynamic ,oxygen dynamicandventilativeeffectsofZafir…  相似文献   

6.
Posterior chamber phakic intraocular lens implantation for high myopia   总被引:5,自引:1,他引:4  
Shen Y  Du C  Gu Y  Wang J 《中华医学杂志(英文版)》2003,116(10):1523-1526
Objective To evaluate the efficacy, safety and stability of posterior chamber phakic intraocular lens (PIOLs) implantation for the correction of high myopia.Methods Thirty-nine eyes of twenty patients with high myopia (between-11.75 and-25.75 diopters) had a posterior chamber PIOL (Staar ICL) implanted. During 6-48 months’ follow-up, visual acuity, refraction, intraocular pressure (IOP), corneal reaction and space between crystal lens and intraocular lens (IOLs) were tested.Results Successful implantation was achieved in all patients. Visual acuity without correction greater than 0.5 was found in 34 eyes at 1 day and 3 months postoperatively. Thirty-five eyes maintained a low negative power of refraction (-1.42±1.32 doipters), which did not prevent the patients from most of their daily activities. During 3-48 months’ follow-up, refraction was stable and no cornea edema and glaucoma was found. Two eyes of one patient had corticosteroid glaucoma and another eye showed cataractogenesis under anterior capsular membrane.Conclusion Posterior chamber PIOL implantation is predictable, safe, and effective in the correction of high myopia, and its indications should be carefully selected.  相似文献   

7.
Objective To delineate the influence of transcutaneous electrical nerve stimulation (TENS) on heat pain threshold and vibration threshold in human. Methods Twenty healthy, young subjects, aged from 20 to 39, participated in the study. They were randomly allocated into either TENS or placebo group. Thirty minutes of conventional TENS (200 μs pulses at 100 Hz and 2-3 times sensory threshold) or placebo stimulation was applied to the acupuncture points (LI4) on each subject’s left hand. Heat pain and vibration thresholds were measured using Medoc TSA-2001 and VSA-3000 respectively on the thenar eminence of each subject’s left hand. These assessments were done at 30, 20 and 10 minutes before and 0, 10, 20, 30, 40 and 50 minutes after 30 minutes of TENS or placebo treatment. Results This study showed a significant increase in heat pain threshold by 0.81℃ and 1.54℃ respectively at 0 (P=0.002) and 20 minutes (P=0.004) after 30 minutes of TENS application to the LI4 acupoint of young healthy subjects, compared with placebo stimulation. Interestingly, no significant difference in vibration threshold was found between the TENS and placebo groups. Conclusion The effect of TENS on the acupoint is to reduce pain but not tactile (specifically vibration) sensibility.  相似文献   

8.
Objective To clone the full-length of a differentially expressed cDNA fragment, LC27, and study its biological function tentatively. Methods Northern blot was used to analyze the expression pattern of LC27 in hepatocellular carcinoma, matched nontumor liver tissues, fetal liver and normal adult liver tissues, as well as BEL-7402 hepatocellular carcinoma cell line ESTs splicing and 5’ rapid amplification of cDNA ends (5’ RACE) were used to clone the full-length of LC27 cDNA.An antisense oligodeoxynucleotide approach was used to investigate the biological role of the gene in the proliferation of BEL-7402 cells. Results A 2186 bp novel cDNA with an open reading frame encoding a 283 amino acid protein was cloned.Analysis of the deduced amino acid sequence indicated that it is 38% (88/229) identical to human Golgi 4-transmembrane spanning transporter MTP.The gene and the encoded protein was termed hepatocellular carcinoma overexpressed transmembrane protein (hotp) and HOTP, respectively.Hotp mRNA was almost undetectable in normal adult liver and fetal liver tissues.However, it was significantly up-regulated in hepatocellular carcinoma and some matched nontumor liver tissues, as well as BEL-7402 cells.The proliferation of BEL-7402 cells was suppressed by an antisense oligodeoxynucleotide against hotp mRNA at a concentration of 50 μg/ml. Conclusion HOTP may be an integral membrane transporter protein.The overexpression of the gene in hepatocellular carcinoma may play an important role in hepatocarcinogenesis and disease progression.  相似文献   

9.
Themorbidityandmortalityofgastriccancerhavedecreasedmarkedlysincethe 1930’s 1 Althoughthisdecreasehasoccurredworldwide ,themorbidityandmortalityofgastriccancerarestillcomparativelyhigherinJapan ,China ,Chile ,andIreland Gastriccancerisstilltheleadingcauseofc…  相似文献   

10.
Objective To investigate the occurrence and extent of apoptosis in the course of restenosis. Methods The experimental models of vessel narrowness and intima thickness were established in minipigs’ iliac arteries by balloon injury and specimens were retrieved on the 1st, 3rd, 6th,12th and 30th days for dynamic observation. Apoptotic smooth muscle cells (SMCs) were detected by terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling (TUNEL). Results Apoptotic SMCs occurred only in the thickened intima 12 days after injury accompanied with the proliferative SMCs, the percentage of apoptosis was 1. 94%±0. 42% on the 12th day and 1. 36%±0. 31% on the 30th day respectively. The low frequency of apoptosis compared with the proliferative SMCs was a feature in the restenotic pathology. Conclusions Apoptosis participates in the pathogenetic process of intimal thickening and its level was low compared with proliferation. The findings suggest that attempts to modulate apoptosis after vessel injury constitute a theoretical approach to the prevention of restenosis.  相似文献   

11.
A VASCULAR necrosis of the femoral head usually leads to destruction of the hip joint, increasing musculoskeletal morbidity in young and middle aged patients. Total joint replacement is commonly used to treat disabling secondary osteoarthrosis. Although most recent improvements in total hip replacement may decrease the failure, patients are usually young and the current hip prothesis function would not fulfill purpose for the remaining life ex-pectancy for these patients. So it is necessary…  相似文献   

12.
脱蛋白骨联合VEGF基因转染治疗股骨头缺血坏死   总被引:2,自引:0,他引:2  
目的探索一种新的方法治疗股骨头早期缺血性坏死(avascular necrosis of the femoral head,AVNFH)。方法69只AVNFH造模成功后的新西兰大白兔随机分成3组。第1组,将脱蛋白骨(deproteinized bone,DPB)复合pcDNA3.1/VEGF165质粒植入坏死的股骨头内,第2组植入DPB,第3组仅在股骨头内钻一隧道。术后3d,1、2、4、8和16周获取标本。RT—PCR、Western blot和免疫组化技术分别检测VEGF165 mRNA、蛋白的表达及安全性。X线大体观察成骨情况,组织形态学分析血管发生和股骨头修复。结果第1组VEGF165 mRNA和蛋白表达术后1周达到高峰,时间持续超过3周,第1组动物术后远膈脏器未检测到VEGF165的表达。血管形成术后2,4周增加,骨形成术后2,4和8周增加,与另两组相比差异有显著性(P〈0.01)。结论VEGF165基因转染可促进局部血管的早期形成,DPB-VEGF复合物可增加骨形成,VEGF基因治疗兔AVNFH有效、安全,脱蛋白骨联合VEGF165基因治疗为骨坏死的修复提供了理论基础。  相似文献   

13.
Ad-huVEGF121基因转染对兔坏死股骨头血流的影响   总被引:3,自引:1,他引:3  
目的探讨一种治疗股骨头缺血坏死的新方法.方法重组腺病毒Ad-hVEGF121注射入坏死的股骨头,应用RT-PCR和免疫组织化学技术检测VEGF121的表达,观察股骨头内新生血管数量,用SPECY技术观察坏死股骨头的动脉灌注情况.结果转染后的股骨头内VEGF121表达增高,新生血管数量增多,SPECT观察发现坏死股骨头血流量明显增加.结论转染VEGF1:1基因可以增加坏死股骨头新生血管数量和血流量.  相似文献   

14.
目的:构建pcDNA3.1/VEGF165质粒及联合脱蛋白骨基因治疗早期股骨头缺血性坏死.方法:将含人VEGF165全长cDNA序列的克隆载体pUC18/VEGF165与pcDNA3.1( )载体构建成重组真核表达质粒pcDNA3.1/VEGF165;69只AVNFH造模成功后的新西兰大白兔随机分成3组.第一组,将脱蛋白骨复合pcDNA3.1/VEGF165质粒植入坏死的股骨头内;第二组植入DPB;第三组仅在股骨头内钻一隧道.股骨头标本术后3天,1,2,4,8和16周获取.RT-PCR检测VEGF165mRNA的表达,Western blot检测VEGF165蛋白的表达,组织形态学分析血管发生和股骨头修复.结果:成功构建pcDNA3.1/VEGF165;第一组VEGF165 mRNA和蛋白表达术后1周达到高峰,时间持续超过3周.血管形成术后2,4周增加,骨形成术后2,4和8周增加,与另两组相比差异呈显著性(P<0.01).结论:VEGF165基因转染可促进局部血管的早期形成,DPB-VEGF复合物可增加骨形成.脱蛋白骨联合VEGF165基因治疗为骨坏死的修复提供了理论基础.  相似文献   

15.
Avascularnecrosisofthefemoralheadisanin creasingcauseofmusculoskeletalmorbidityinyoungandmiddleagedpersons It’sadebilitatingdiseasethatusuallyleadstodestructionofthehipjoint To taljointreplacementiscommonlyusedtotreatdis ablingsecondaryosteoarthrosis Althoughthemostrecentimprovementsintotalhipreplacementmayde creasethefailure ,thepatientsareusuallyyoungandthecurrenthipprothesiswouldn’tfunctionwellfortheremaininglifeexpectancyforthesepatients Forthisreason ,it’snecessarytodelayoreliminatethe…  相似文献   

16.
目的以hVEGF165基因转染的骨髓间充质干细胞移植治疗兔激素性股骨头坏死模型,通过影像学观察、病理学及免疫组织化学检查等方法评价疗效。方法使用马血清与醋酸泼尼松龙制备兔激素性股骨头缺血性坏死动物模型后分为4组,分别进行以下治疗:A组(不作任何处理);B组(髓心减压+自体骨移植);C组(髓心减压+骨髓间充质干细胞+自体骨移植);D组(髓心减压+Ad-VEGF165转染骨髓间充质干细胞+白体骨移植)。术后3周处死行病理学、免疫组织化学检查及Western Blot检测股骨头内VEGF的表达,比较各组间的差异。结果D组在软骨下血管、VEGF阳性面积百分比、股骨头内VEGF的相对浓度均高于其他各组;在VEGF平均灰度值、空骨陷窝率低于其他各组,且各组间差异有统计学意义。结论转染了Ad—VEGF165的骨髓间充质干细胞在宿主股骨头局部可以表达VEGF蛋白,且较单纯的骨髓间充质干细胞移植表达的强度更高,对激素性股骨头坏死进行早期治疗具有确切疗效。  相似文献   

17.
刘保一  赵德伟 《中华医学杂志》2009,89(37):2629-2633
目的 检测rAAV-2-hVEGF-165转染骨髓基质干细胞后的基因表达,研究髓芯减压关节镜监视下hVEGF基因转染骨髓基质干细胞在治疗股骨头缺血性坏死中的作用及价值.方法 制备rAAV-2-hVEGF-165,将病毒以感染被率(MOI)为1×10~5v.g./cell转染兔骨髓基质干细胞,应用腺相关病毒介导绿荧光蛋白转染兔骨髓基质干细胞检测转染情况.应用RT-PCR和免疫印迹检测转染BMSCs外源hVEGF基因的转录与表达,得出最佳的转染时间.关节镜监视并对坏死骨清除后植入骨髓基质干细胞,术后2、4、8周分别对各组兔股骨头行X线分析,生物力学分析,切片血管计数并行免疫组化检查,观察疗效.结果 rAAV-2-hVEGF-165转染的兔骨髓基质干细胞可有效表达hVEGF-165,RT-PCR和免疫印迹检测可见转染MSCs中外源hVEGF基因的转录与表达.转染后48 h即可有表达,10 d时表达最强.免疫组化检测发现植入转染的骨髓基质干细胞2周后出现阳性表达,8周后强阳性表达.生物力学分析显示植入转染细胞组股骨头强度接近正常股骨头.结论 hVEGF-165基因转染的兔骨髓基质干细胞可有效表达具有生物活性的hVEGF-165蛋白.通过关节镜监视可以彻底清除死骨,使hVEGF-165基因修饰的骨髓基质干细胞准确的回植入股骨头坏死处,可使股骨头缺血性坏死的修复加强.回植入兔股骨头的hVEGF-165基因可有效表达.  相似文献   

18.
目的探究葛根素对激素性股骨头坏死大鼠骨组织及PI3K/Akt信号转导通路的影响。方法将大鼠分为对照组、模型组和观察组,用臀肌注射甲泼尼龙琥珀酸钠方法复制激素性股骨头坏死大鼠模型。模型复制后观察组大鼠腹腔注射葛根素注射液。比较各组大鼠一般状态、股骨头病理切片和股骨头骨密度、血清血管内皮生长因子(VEGF)和一氧化氮(NO)水平、股骨头中Akt和p-Akt蛋白表达水平。结果观察组大鼠给药后活动程度显著提高,毛发有色泽,精神状态良好。模型组大鼠血清中的VEGF和NO水平低于对照组(P < 0.01);观察组大鼠血清中的VEGF和NO水平高于模型组(P < 0.01)。3组大鼠股骨头中Akt蛋白表达水平差异无统计学意义(P>0.05);模型组大鼠股骨头中p-Akt蛋白表达水平显著高于对照组(P < 0.01);观察组大鼠股骨头中p-Akt蛋白表达水平显著高于模型组(P < 0.01)。结论葛根素对激素性股骨头坏死模型大鼠有治疗作用,其作用机制可能为升高血清中促进血管新生活性因子水平的升高,进而促进血管新生,重建供血和血液循环,促进坏死部位新骨生成。  相似文献   

19.
目的研究hVEGF-165基因转染的犬骨髓间充质干细胞移植修复自体股骨头坏死的效果。方法用股骨颈截骨后克氏针再固定的方法建立犬股骨头坏死的动物模型,分为转基因间充质干细胞移植组、单纯间充质干细胞移植组和未治疗组,每组9只动物(18侧髋关节)。脂质体法将hVEGF-165基因转染进入骨髓间充质干细胞。造模后10周经大转子将细胞植入股骨头坏死区,转基因间充质干细胞和未转基因干细胞随机植入同一动物的左侧或右侧后肢。细胞移植后第2、8和12周取股骨头标本进行骨小梁定量分析,结合X线和同位素断层扫描分析3组间成骨修复的差别,并比较第12周时各组标本中截骨平面以上的血管数。结果①造模手术后10周,手术侧股骨颈骨折已愈合,但股骨头均出现典型的坏死。②骨小梁定量分析提示,在每一个时间点各组的成骨修复的差别有统计学意义:转基因间充质干细胞移植组的成骨修复好于单纯干细胞移植,未治疗组最差。X线和SPECT的表现与此相符。③12周时,转基因间充质干细胞移植组中血管数量最多,间充质干细胞移植组与未治疗组的血管数量没有统计差别。结论与未转基因的间充质干细胞移植相比,转染hVEGF-165基因后的间充质干细胞移植能够增加股骨头坏死区血管...  相似文献   

20.
目的:探讨血管内皮生长因子( vascular endothelial growth factor , VEGF)基因转染骨髓间充质干细胞( mesenchy-mal stem cells,MSCs)对慢性肾衰竭(chronic renal failure, CRF)大鼠肾小球内皮细胞修复和血管新生的影响。方法体外分离、培养大鼠MSCs,Ad5-hVEGF-EGFP转染MSCs并观察转染对细胞增殖,分泌VEGF的影响。50只雄性SD大鼠按数字表法随机分为假手术组、慢性肾衰竭组、MSCs移植组、Ad-VEGF注射组和VEGF基因转染的MSCs移植组,每组10只。采用分阶段5/6肾切除术制备大鼠慢性肾衰竭动物模型。假手术组与慢性肾衰竭组于切除右肾之前从该侧肾动脉注射不含血清的改良杜氏伊格尔(DMEM)培养液,其余3组分别给予MSCs,Ad-VEGF和VEGF基因转染的MSCs。8周后检测各组大鼠肾功能,并用免疫组化检测肾小球CD31表达情况。结果 Ad5-hVEGF-EGFP转染后对MSCs细胞增殖无影响,转染后分泌VEGF蛋白较空质粒转染组明显增加(P<0.05)。 MSCs移植组和VEGF基因转染的MSCs移植组血肌酐(Scr)和尿素氮(BUN)均较慢性肾衰竭组降低(P<0.05);与MSCs移植组比较,VEGF基因转染的MSCs移植组Scr和BUN降低更显著(P<0.05)。慢性肾衰竭组肾小球中CD31表达较假手术组显著降低(P<0.05),应用MSCs和VEGF165基因转染的MSCs干预后肾小球中CD31表达有所增加,VEGF基因转染的MSCs组增加更明显(P<0.05)。结论慢性肾衰竭大鼠给予转染VEGF基因的MSCs移植后毛细血管内皮细胞数量增多,肾脏功能改善;其作用可能与基因转染增加VEGF表达及有利于肾小球毛细血管内皮修复、血管新生有关。  相似文献   

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