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171.
Ketterling RP Drost JB Scaringe WA Liao DZ Liu JZ Kasper CK Sommer SS 《Human mutation》1999,13(3):221-231
Small consensus sequences have been defined for RNA splicing, but questions about splicing in humans remain unanswered. Analysis of germline mutations in the factor IX gene offers a highly advantageous system for studying the mutational process in humans. In a sample of 860 families with hemophilia B, 9% of independent mutations are likely to disrupt splicing as their primary mode of action. This includes 26 splicing mutations reported herein. When combined with the factor IX splice mutations reported by others, at least 104 independent mutations have been observed, 80 of which are single base substitutions within the splice donor and splice acceptor consensus sequences. After analysis of these mutations, the following inferences emerge: (1) the susceptibility of a splice donor sequence to deleterious mutation depends on the degree of similarity with the donor consensus sequence, suggesting a simple "5-6 hypothesis" for predicting deleterious vs. neutral mutations; (2) the great majority of mutations that disrupt the splice donor or splice acceptor sequences result in at least a 100-fold decrement in factor IX coagulant activity, indicating that the mutations at these sites generally function as an on/off switch; (3) mutations that create cryptic splice junctions or that shorten but do not interrupt the polypyrimidine tract in the splice acceptor sequence can reduce splicing by a variable amount; and (4) there are thousands of potential donor-acceptor consensus sequence combinations in the 38-kb factor IX gene region apparently not reduced by evolutionary selective pressure, presenting an apparent paradox; i.e., mutations in the donor and acceptor consensus sequences at intron/exon splice junctions can dramatically alter normal splicing, yet, appropriately spaced, good matches to the consensus sequences do not predispose to significant amounts of alternative splicing. 相似文献
172.
为探讨使用博莱霉素的患者产生肺炎样症状和肺纤维化样症状的机理,给动物从气管内注入博莱霉素A_5,观察其对肺脏的作用。发现该药到达肺组织后,可引起明显的肺损伤。早期先引起肺泡炎,后期可导致肺纤维化。实验从病理学上揭示了博莱霉素引起肺炎样和肺纤维化样症状的原因。提示在给患者使用博莱霉素时,一旦其出现了肺炎样症状,就应及时停药并进行胸部X线检查,及时给予适当处理,以防止肺纤纤维化的发生。 相似文献
173.
目的:探讨顺铂作用于卵巢癌细胞的作用机理。方法:通过电镜、光镜、流式细胞仪等方法观察顺铂诱导人亲代和耐药卵巢癌细胞COC1 、COC1/DDP凋亡,进行细胞周期分析及计算凋亡率。结果:顺铂引起细胞S期增多、S期细胞凋亡,COC1 、COC1/DDP细胞凋亡率不同。结论:顺铂药理机制之一是诱导细胞凋亡,耐药与凋亡减少有关。 相似文献
174.
应用荧光试剂(33258Hoechst)微量测定细胞内DNA含量,应用荧光胺(Fluorescamine)微量测定细胞内蛋白质含量。结果:荧光试剂与DNA的A-T碱基形成复合物后,其激发波长(EX)由320nm移至350nm,发射波长(EM)由480nm移至460nm,且荧光强度大为增强。荧光胺与蛋白质反应生成强荧光化合物,在EX390nm,EM475nm条件下最低检测限为0.5μg/μl。该法操作简便,微量快速,重复性好。可用于荧光微量测定DNA与蛋白质含量,还可用于观察细胞的增殖。 相似文献
175.
为了能够精确地建立轻、中、重液压冲击分级脑损伤动物模型,我们设计了侧位液压冲击脑损伤装置。该装置由不锈钢储液管、压缩空气、减压设备及计算机等组成,可以精确地控制冲击气压的大小、记录冲击时脑组织所承受的压力、显示压力曲线、液压冲击后可以迅速释放系统内的压力,国内、外均未见报道。侧位液压冲击脑损伤随冲击压力的增加而加重,以冲击侧大脑半球为最重,也可波及对侧及脑底部。 相似文献
176.
目的:探讨骨肉瘤保肢治疗中肿瘤大小、临床分期、手术方式、术前、术后化疗以及肿瘤多药耐药基因(mdr)表达产物P糖蛋白(P-170)对术后生存时间的影响。方法:统计分析近7年47例骨肉瘤保肢术患者的病理、临床资料及生存时间,并用链菌素生物素标记法(LSAB)免疫组织化学法回顾性检测肿瘤标本中P-170糖蛋白。结果:临床分期为ⅡB期患者1~5年生存率分别是974%,760%,463%,389%和340%;ⅡA期患者相应的生存率为100%,800%,800%,800%和800%;ⅠB期患者相应的生存率皆为100%;各临床分期间的生存率有统计学差异(P<01)。术前有化疗的患者1~5年生存率分别是975%,845%,674%,571%和530%;术前无化疗的患者相应的生存率分别为857%,429%和0%;两组生存率有统计学意义(P<001)。术后有化疗的患者1~5年生存率分别是971%,942%,727%,616%和572%;术后无化疗的患者相应的生存率分别是90%,200%和0%;差异有统计学意义(P<001)。P-糖蛋白阳性组1~5年生存率分别是974%,733%,471%,359%和307%;P-糖蛋白阴性组的相应值皆为100%,差异有统计学意义(P<001)。此外,在不同保肢术式中人工关节置换术患者1~5年生存率最高,分别是967%,930%,700%,631%和520%,差异有统计学意义(P<001)。结论:肿瘤临床分期、肿瘤大小、保肢术式、术前、术后化疗及P-17 相似文献
177.
Tuberculosis versus lymphomas in the abdominal lymph nodes: evaluation with contrast-enhanced CT 总被引:24,自引:0,他引:24
Yang ZG Min PQ Sone S He ZY Liao ZY Zhou XP Yang GQ Silverman PM 《AJR. American journal of roentgenology》1999,172(3):619-623
OBJECTIVE: Tuberculosis in the abdominal lymph nodes may be difficult to distinguish from lymphomas. This study evaluated specific CT imaging criteria for differentiating these entities. MATERIALS AND METHODS: We retrospectively reviewed the anatomic distribution and CT enhancement patterns of disease in 69 patients, 26 (38%) with tuberculosis and 43 (62%) with untreated lymphomas involving abdominal lymph nodes. Of the patients with tuberculosis, five (19%) had disseminated disease and 21 (81%) had nondisseminated disease. Of the patients with lymphomas, 16 (37%) had Hodgkin's disease and 27 (63%) had non-Hodgkin's lymphoma. RESULTS: Disseminated and nondisseminated tuberculosis involved predominantly lesser omental, mesenteric, anterior pararenal, and upper paraaortic lymph nodes. Lower paraaortic lymph nodes were involved more often in Hodgkin's disease (15 patients [94%]), non-Hodgkin's lymphoma (24 patients [89%]), and disseminated tuberculosis (five patients [100%]) than in nondisseminated tuberculosis (one patient [5%]). Mesenteric lymph nodes were involved more often in disseminated tuberculosis (four patients [80%]) and nondisseminated tuberculosis (11 patients [52%]) than in Hodgkin's disease (one patient [6%]) (p < .01). Anatomic distribution was not different between disseminated tuberculosis and non-Hodgkin's lymphoma. Tuberculous lymphadenopathy commonly showed peripheral enhancement, frequently with a multilocular appearance, whereas lymphomatous adenopathy characteristically showed homogeneous attenuation (14 patients [87.5%] with Hodgkin's disease and 19 patients [70%] with non-Hodgkin's lymphoma [p < .01]). CONCLUSION: Our findings indicate that the anatomic distribution and specific enhancement patterns of lymphadenopathy seen on contrast-enhanced CT can be useful in differentiating between tuberculosis and untreated lymphomas of the abdominal lymph nodes. 相似文献
178.
R N Bryan J Cai G Burke R G Hutchinson D Liao J F Toole A P Dagher L Cooper 《AJNR. American journal of neuroradiology》1999,20(7):1273-1280
BACKGROUND AND PURPOSE: MR imaging has revealed putative evidence of subclinical cerebrovascular disease (CVD) as reflected by white matter signal changes and infarct-like lesions (ILLs). Nonetheless, the prevalence of this condition in the general population has been defined only to a limited extent. We herein report the prevalence and anatomic characteristics of ILLs seen on cranial MR images obtained as part of a population-based study of cardiovascular disease in middle-aged adults. These results are contrasted to those of previous similar studies, particularly those of an elderly population in the Cardiovascular Health Study (CHS). METHODS: This Atherosclerosis Risk in Communities (ARIC) cohort consists of a probability sample of community-living persons who were 55 to 72 years old at the time of MR examination. MR imaging of 1890 participants was performed at two ARIC field centers, based on a common protocol. MR studies were evaluated by trained readers at the MR Reading Center using original digital data displayed on a high-resolution workstation. The measures of lesion size, anatomic location, and signal intensity were collected. The definition for an ILL was a non-mass, hyperintense region with an arterial vascular distribution on spin-density and T2-weighted images. RESULTS: Two hundred ninety participants had ILLs, for an overall prevalence of 15.3%. Eighty-two percent of participants with ILLs had lesions that were 3 mm or larger in maximal dimension, although 87% of these lesions were 20 mm or smaller in maximal dimension. The prevalence of ILLs increased with age, from 7.9% in the 55- to 59-year-old age group to 22.9% in the 65- to 72-year-old age group (P < .001). Lesion prevalence was greater in black (20.7%) than in white persons (10.2% [P < .0001]), but did not differ significantly between male and female participants. The basal ganglia and thalamic region was the most commonly affected anatomic site, accounting for 78.9% of the lesions. CONCLUSION: Considering that the prevalence of self-reported stroke or transient ischemic attack in ARIC participants is 1.5%, these results suggest that there is significantly more subclinical than clinical CVD in the general population. Furthermore, the prevalence of this subclinical disease increases with age, and is greater in black persons. ILLs are dominated by "lacunae" in the basal ganglia and thalamus. These results are, in general, similar to those of a comparable study of elderly participants in the CHS, except for a 60% lower prevalence of ILLs in this younger population. 相似文献
179.
Ambulatory urodynamic monitoring of external urethral sphincter behavior in chronic prostatitis patients 总被引:3,自引:0,他引:3
Aim: To study the behavior of external urethral sphincter in chronic prostatitis (CP) patient under natural filling.Methods: Twenty-one CP patients and 17 normal volunteers were involved in the study. Both the patients andvolunteers underwent ambulatory urodynamic monitoring (AM) and conventional medium filling cystometry (CMG).Urodec 500 was used for AM and Menuet for CMG. AM findings from CP patients were compared with those fromnormal volunteers, and the results from AM were compared with those from CMG. Results: In AM, the restingand voiding external urethral sphincter (EUS) pressures and maximum urethral closure pressures (MUCP) weresignificantly higher in CP patients [ ( 121.5 ±10.3) and (85.6±3.5) cm water, respectively ] than in normalvolunteers [ (77.6±11.4) and (10.3±1.6) cm water, respectively)]. Conclusion: The behavioral changes ofEUS in CP patients included spasm and instability of EUS, which were demonstrated using AM under natural filling;the findings were also in accord with the res 相似文献
180.
CD18-mediated neutrophil recruitment contributes to the pathogenesis of reperfused but not nonreperfused stroke 总被引:36,自引:0,他引:36
Prestigiacomo CJ Kim SC Connolly ES Liao H Yan SF Pinsky DJ 《Stroke; a journal of cerebral circulation》1999,30(5):1110-1117
BACKGROUND AND PURPOSE: Neutrophil (PMN) recruitment mediated by increased expression of intercellular adhesion molecule-1 expression (ICAM-1, CD54) in the cerebral microvasculature contributes to the pathogenesis of tissue injury in stroke. However, studies using blocking antibodies against the common beta2-integrin subunit on the PMN, the counterligand for ICAM-1 (CD18), have demonstrated equivocal efficacy. The current study tested the hypothesis that mice deficient in CD18 would be protected in the setting of reperfused but not nonreperfused stroke. METHODS: Two groups of mice were studied, those whose PMNs could express CD18 (CD18 +/+) and those mice hypomorphic for the CD-18 gene (CD18 -/-). PMNs obtained from CD18 -/- or CD18 +/+ mice were fluorescently labeled and tested for binding to murine brain endothelial monolayers. Using a murine model of focal cerebral ischemia in which an occluding suture placed in the middle cerebral artery (MCA) is removed after 45 minutes (transient ischemia, reperfused stroke) or left in place (permanent ischemia, nonreperfused stroke), cerebral infarct volumes (% ipsilateral hemisphere by TTC staining), cerebral blood flow (CBF, % contralateral hemisphere by laser-Doppler flowmetry), and survival (%) were examined 24 hours after the initial ischemic event. Adoptive transfer studies used 111In-labeled PMNs (from either CD18 +/+ or CD18 -/- mice) to examine the relative accumulation of PMNs in the ischemic region. RESULTS: PMNs obtained from CD18 -/- mice exhibit reduced adhesivity (compared with CD18 +/+ PMNs) for both quiescent and cytokine-activated endothelial monolayers. CD18 -/- mice (n=14) subjected to transient focal cerebral ischemia demonstrated a 53% decrease in infarct volumes versus CD18 +/+ mice (n=26, P<0.05), improved penumbral CBF at 24 hours (1.8-fold, P=0.02), and a 3.7-fold decrease in mortality (P=0.02). However, when CD18 -/- mice (n=12) were subjected to permanent focal cerebral ischemia, no differences were noted in infarct volume, mortality, or CBF versus similarly treated CD18 +/+ mice (n=10). There was a greater accumulation of CD18 +/+ PMNs in the ischemic zone of CD18 +/+ animals than CD18 -/- animals subjected to reperfused stroke (82% increase, P=0.02), although there was no difference between groups when subjected to permanent MCA occlusion. CONCLUSIONS: Deficiency for the CD18 gene confers cerebral protection in a murine model of reperfused stroke, but this benefit does not extend to CD18-deficient animals subjected to permanent MCA occlusion. These data suggest that anti-PMN strategies should be targeted to reperfused stroke and may perhaps be used in conjunction with thrombolytic therapy that establishes reperfusion. 相似文献