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81.
M van der Neut Kolfschoten R J Dirven S R Poort R van Wijk H L Vos F R Rosendaal R M Bertina 《Journal of thrombosis and haemostasis》2004,2(6):910-917
BACKGROUND: During the study of a family with hereditary factor (F)V deficiency (FV Amersfoort, 1102 A > T in exon 7) we identified an individual with 5% FV heavy chain antigen (FV(HC)) and 50% FV light chain antigen (FV(LC)). Further testing revealed that apart from the FV Amersfoort allele a second variant FV allele was segregating in this family, which encodes for a FV molecule with a reduced affinity for mAb V-23 used in the FV heavy chain ELISA (ELISA(HC)). OBJECTIVE: Identification and characterization of the molecular basis responsible for the reduced affinity of the variant FV for mAb V-23. METHODS: Family members of the proband were screened for mutations in the exons coding for the heavy chain of FV, after which the recombinant variant FV could be generated and characterized. Next, the cases and controls of the Leiden Thrombophilia Study (LETS) were genotyped for carriership of the variant FV. RESULTS: In the variant FV allele a polymorphism in exon 3 (409G > C) was identified, which predicts the replacement of aspartic acid 79 by histidin (D79H). Introduction of this mutation in recombinant FV confirmed that it reduces the affinity for binding to mAb V-23. The substitution has no effect on FV(a) stability and Xa-cofactor activity. In Caucasians the frequency of the FV-79H allele is approximately 5%. Analysis of the LETS revealed that the FV-79H allele is not associated with FV levels (FV(LC)), activated protein C sensitivity (using an activated partial thromboplastin time-based test) or risk of venous thrombosis (OR 1.07, CI 95: 0.7-1.7). CONCLUSION: The D79H substitution in FV should be considered as a neutral polymorphism. The monoclonal antibody V-23, which has a strongly reduced affinity for FV-79H, is not suitable for application in diagnostic tests. 相似文献
82.
Insulin resistance Type A and short 5th metacarpals. 总被引:1,自引:0,他引:1
BACKGROUND/AIMS: Insulin resistance is associated with a number genetic syndromes and a variety of defects of insulin action. METHODS: We describe three members of an extended family spanning two generations with insulin resistance Type A and short 5th metacarpals. The proband had secondary amenorrhoea, male pattern hair distribution, acne, hirsutism, deep voice, acanthosis nigricans, polycystic ovaries, diabetes, features of acromegaly, raised creatine kinase and triglyceride levels and short 5th metacarpals. Her growth hormone, adrenal steroid and testosterone levels were normal. The proband's daughter had severe acne, hirsutism, acanthosis nigricans, polycystic ovaries, raised triglyceride, glucose and testosterone level short metacarpals and normal insulin receptor gene. The proband's son had a muscular build, raised creatine kinase, hypertriglyceridaemia and short 5th metacarpals. His fasting insulin levels were normal but pro-insulin was raised. RESULT/CONCLUSION: There are many familial and genetic syndromes associated with insulin resistance. This family was diagnosed as having insulin resistance Type A. This family does not conform entirely to any of the previously described syndromes and a number of family members have the phenotype of short 5th metacarpals, which appears to be associated with the features of insulin resistance Type A. 相似文献
83.
颅脑损伤与胰岛素抵抗的相关性研究 总被引:2,自引:0,他引:2
目的分析颅脑损伤的严重性、血糖与胰岛素水平三者之间的关系。方法92例颅脑损伤患者按入院时GCS评分分为轻度、中度及重度颅脑损伤三组,分别于伤后24h、48h、72h测定空腹血糖、血清胰岛素值,并计算稳态模式中的胰岛素抵抗指数(HOMA—IR)。患者出院时按GOS标准评估预后。采用SPSS11.5统计软件对数据进行处理,分析GCS、空腹血糖、胰岛素水平的关系。结果出院时按GOS标准.良好72例,差12例,死亡8例.死亡率8.7%。92例颅脑损伤患者伤后连续3d空腹血糖及胰岛素水平在轻度、中度、重度颅脑损伤三组患者中有显著差异(P〈0.01或P〈0.05)。颅脑损伤程度越重.血糖和HOMA—IR越高。结论空腹血糖值和HOMA—IR值可作为评估颅脑损伤严重程度的参考指标。 相似文献
84.
NO-1886对高糖高脂饲料喂养新西兰兔糖代谢的影响 总被引:6,自引:0,他引:6
合成药NO-1886是脂蛋白脂肪酶(LPL)的激动剂,能降低血浆甘油三酯(TG)并升高高密度脂蛋白胆固醇(HDL-c)水平。我们曾发现NO-1886还具有降低血糖的作用。本研究主要观察NO-1886对糖尿病兔胰岛素抵抗及β-细胞功能方面的影响。用高糖高脂饲料诱导,使新西兰兔血浆葡萄糖升高,发生胰岛素抵抗。在高糖高脂饲料中添加1%NO-1886进行治疗。结果:发现NO-1886可抑制血清葡萄糖升高,经糖耐量和胰岛素敏感性试验检测,NO-1886可保护胰岛素的急性相分泌,增强胰岛素对葡萄糖的清除能力。研究结果提示NO-1886具有改善胰岛素抵抗、降低血糖的作用。 相似文献
85.
高果糖诱导IR大鼠模型血清脂质代谢的改变及意义 总被引:4,自引:0,他引:4
目的: 评估高果糖膳食对机体胰岛素敏感性及血清脂质代谢的影响及意义.方法:以高果糖膳食(果糖占总热量34.5%)诱导并经钳夹技术证实建立胰岛素抵抗(IR)大鼠模型,生化比色法测定血清游离脂肪酸(FFA),生化酶法测定血清甘油三酯(TG)及总胆固醇(TC).结果:高果糖膳食喂养4周后,实验组大鼠葡萄糖输注率由(11.5±0.6)mg/kg·min-1下降至(6.6±0.4)mg/kg·min-1(P<0.01);血清FFA由(0.45±0.09)mmol/L增至(0.78±0.19)mmol/L(P<0.01);TG由(0.54±0.10)mmol/L增至(0.96±0.22)mmol/L(P<0.01);TC由(1.96±0.32)mmol/L增至(2.42±0.21)mmol/L(P<0.01).结论:高果糖膳食可导致机体严重IR,是建立IR大鼠模型的有效手段;该模型同时伴有血清脂代谢各相关指标的明显异常,血脂的变化既是IR的结果,也是IR向纵深发展的原因和必要条件. 相似文献
86.
代谢综合征患者瘦素抵抗的研究 总被引:8,自引:3,他引:5
目的 :研究代谢综合征 (MS)患者瘦素抵抗的状况。 方法 :选取 5 0例MS患者 (MS组 )和 30例正常人 (正常对照组 ) ,分别测定体重指数 (BMI)、腰臀比 (WHR)、收缩压 (SBP)、舒张压 (DBP)、血清瘦素水平 (leptin)、空腹血糖(FPG)、空腹胰岛素 (FIns)、血清总胆固醇 (TC)、三酰甘油 (TG)、低密度脂蛋白胆固醇 (LDL C)、高密度脂蛋白胆固醇(HDL C)以及脂蛋白 (a)〔LP(a)〕 ,并计算HOMA胰岛素抵抗指数 (HOMA IR)。 结果 :与正常对照组相比 ,MS组血清瘦素水平显著上升 [(2 3.82± 1 5 .6 3) μg/Lvs(1 1 .2 0± 4 .70 ) μg/L ,P <0 .0 1 ],BMI、WHR、SBP、DBP、HOMA IR、TC、TG、LDL C、HDL C亦明显升高 ,而两组间LP(a)差异无显著性意义 (P >0 .0 5 )。 结论 :MS患者血清瘦素水平显著升高 ,可能由于该患者群存在一定程度的瘦素抵抗 ,使正常的脂肪 胰岛素轴反馈机制受到破坏、瘦素抑制胰岛素分泌的能力下降 ,从而导致MS的发生 相似文献
87.
P-glycoprotein (Pgp) is a plasma membrane protein that was first characterised in multidrug resistant cell lines. The occurrence of Pgp in clinical tumors has been widely studied. Recent investigations have begun to focus on the relationship between Pgp detection in tumors and treatment outcome. In several types of tumors, detection of Pgp correlates with poor response to chemotherapy and shorter survival. P-glycoprotein overexpression often occurs upon relapse from chemotherapy but may also occur at the time of diagnosis. Studies of experimental rat liver carcinogenesis have shown that Pgp expression increases in late stages of carcinogenesis, suggesting that Pgp may be involved in tumor progression. While some of the Pgp isoforms are known to transport hydrophobic chemotherapeutic drugs out of tumor cells, the biologic effects of Pgp overexpression in tumor cells are not fully understood, because the spectrum of substrates for Pgp-mediated transport has not been determined. In the rat liver carcinoma model, strong expression of Pgp is associated with a highly vascular stroma, suggesting that Pgp in tumor cells may affect the connective tissue stroma. The regulation of Pgp appears to be complex, and little is known about how it is up-regulated during carcinogenesis. Further studies of the role of Pgp in malignancy may contribute to our understanding of molecular mechanisms which underlie tumor progression. 相似文献
88.
The value of different resistance parameters in distinguishing biopsy-proved dysfunction of renal allografts 总被引:3,自引:2,他引:1
Frauchiger B.; Bock A.; Eichlisberger R.; Landmann J.; Thiel G.; Mihatsch M. J.; Jager K. 《Nephrology, dialysis, transplantation》1995,10(4):527-532
The data concerning the value of duplex sonography in diagnosingparenchymatous renal allograft dysfunction are controversial.Most early studies did not take into consideration the manyfactors influencing resistance parameters. We therefore performeda prospective, biopsy-controlled study with exclusion of allknown sources of error regarding resistance parameters. Furthermorewe investigated the value of a new resistance parameter, thesystolic deceleration percentage. Forty-seven duplex sonographicstudies were performed on 43 patients (30 male, 13 female, medianage 47 years, range 770). Fourteen studies were doneon normally functioning grafts (control group) an average of33 days after transplantation. Thirty-three studies were performedon dysfunctional grafts immediately prior to biopsy. Graftswhich had been transplanted more than a year previously or withvascular findings or any other clinical or sonographic pathologyprobably explaining function deterioration were excluded. Inall patients, the resistive index (RI), pulsatility index (PI)and systolic deceleration percentage (DP) were calculated inthe main renal artery and in the interlobar artery. Of the 33grafts with dysfunction, nine had vascular rejection (VR), 11interstitial rejection (IR), 11 cyclosporin A toxicity (CAT)and two other histologies (OR). The mean RI in normal grafts(NO) was 0.71±0.06 in the main artery and 0.68±0.06in the interlobar artery, in VR 0.86±0.12 and 0.80±0.18,in IR 0.72±0.05 and 0.70±0.07, in CAT 0.67±0.06and 0.65±0.07 and in OR 0.64±0.07 and 0.60±0.01.For PI, the values were 1.45±0.23 and 1.41±0.28(NO), 3.5±2.13 and 2.92±2.16 (VR), 1.55±0.26and 1.46±0.33 (IR), 1.32±0.25 and 1.27±0.26(CAT) and 1.30±0.34 and 1.13±0.04 (OR). For DPwe calculated 28±5% and 29±6% (NO), 43±14%and 36±6% (VR), 29±9% and 27±9% (IR), 31±8%and 32±7% (CAT ) and 32±4% and 28±3% (OR).The sensitivity/specificity for VR with a cutoff mean+2 SD was0.44/1 for RI, 0.55/0.97 for PI and 0.33/0.89 for DP. It wasconcluded that:(1) despite the high selection of our patientgroup, diagnostic accuracy of duplex sonography for diagnosingparenchymatous function disorder in renal allograft remainsinsufficient; (2) in vascular rejection only, the resistanceparameters differ significantly from the values of normal allografts;(3) the higher the cutoff of resistance parameters, the betterthe specificity and the worse the sensitivity for diagnosingvascular rejection; (4) of all investigated resistance parameters,the RI is the most practical due to a simple measurement technique. 相似文献
89.
R. A. Adegbola S. Sabally T. Corrah B. West & D. Mabey 《Tropical medicine & international health : TM & IH》1997,2(5):428-432
Summary One hundred and three strains of Neisseria gonorrhoeae isolated from a periurban STD clinic in The Gambia were studied for antimicrobial susceptibility, plasmid profile, and serogroup using standard procedures. Seventy-nine (77%) were penicillinase producers (PPNG) and fully resistant to penicillin (MIC ≥8 mg/l). One isolate showed chromosomally induced resistance to penicillin (MIC 2 mg/l). None of the isolates was sensitive to tetracycline; 16 (16%) showed intermediate resistance (MICs 1–8 mg/l) and 87 (84%) showed high-level plasmid-mediated resistance (TRNG) (MICs >10 mg/l). This is the first report of TRNG in The Gambia. Only 6 (6%) strains were fully sensitive to trimethoprim-sulphamethoxazole (MIC <8 mg/l); 78 (76%) showed intermediate level resistance (MICs 8–16 mg/l) and 19 (18%) were fully resistant (MIC >32 mg/l). Indications of an increase in MIC to ciprofloxacin and ceftriaxone were found in 6 (6%) and 1 (1%) strains, respectively, although all remained fully sensitive (MICs 0.004–0.03 mg/1 and 0.001–0.015 mg/l). All PPNG and TRNG strains carried the 3.2 MDa and 25.2 MDa plasmids, respectively. All isolates carried the 2.6 MDa cryptic plasmid and 9 (3 PPNG and 6 non-PPNG) carried the 24.5 MDa conjugative plasmid. Forty-four (43%) strains were typed group W1, 58 (56%) W11/111 and 1 had cross-reacting antigens. Because PPNG are frequently encountered and high-level TRNG is now prevalent, the newer cephalosporins and quinolones must now be considered as first-line drugs for the treatment of gonorrhoea in The Gambia. 相似文献
90.
A. J. Pope P. J. R. Shaw M. J. Coptcoat P. H. L. Worth 《Neurourology and urodynamics》1990,9(5):503-508
The changes in bladder function occurring after a surgical alteration in bladder outflow resistance were studied in 20 males undergoing transurethral prostatectomy (TURP) and in 20 females undergoing an endoscopic bladder neck suspension (EBNS). Serial cystometrograms (CMG) were performed before operation, and on alternate days after spontaneous micturition was re-established, for 5 days in the males and for 21 days in the females. CMGs were repeated at 3 months and 1 year after operation. After TURP voiding pressures (Pdet) fell rapidly from a mean of 118 cm H2O before operation to 57 cm H2O at 5 days, with an increase in flow rate during this time from 10.5 ml/s to 24 ml/s. Detrusor instability that had been present in 14 patients resolved within 2 days in 12. There was no further significant urodynamic change over the 1-year study period. After EBNS, there was an early rise in voiding pressure (Pdet rose from 26 cm H2O before operation to 42 cm H2O at 3 days). This continued to increase up to 21 days particularly in those patients with initial large residuals. Three patients developed detrusor instability. Flow rates were greatly reduced at first (27 ml/s before operation and 13 ml/s at 3 days), and gradually increased in line with voiding pressures, yet were still diminished 1 year after operation. The urodynamic changes following a reduction in bladder outflow resistance by TURP are immediate and sustained and unlikely to be the result of structural changes within the bladder wall. EBNS produces an increase in outflow resistance and it can be several weeks before balanced voiding is achieved, with significantly increased detrusor pressures needed to achieve complete bladder emptying at a reduced flow rate. 相似文献