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61.
ASTROCYTE-CONDITIONED MEDIUM INDUCES BLOOD-BRAIN BARRIER PROPERTIES IN ENDOTHELIAL CELLS 总被引:6,自引:0,他引:6
62.
The aim of laboratory screening in Phase I is to exclude subjects with subclinical illness, who might be at increased risk in the study, and who might also adversely influence interpretation of the results. A new method for laboratory screening, based on Bayesian probability theory, is proposed, which consists of: 1. Drawing up a list of diseases to be excluded. 2. Defining for each disease, the maximum acceptable risk that an included subject could be affected by it. 3. Identifying one test for each disease. 4. Using a contingency table to calculate the specificity of the test and integrating the estimated prevalence of the disease from epidemiological data. 5. Applying the percentage obtained by the calculation of specificity to the previously determined distribution of values in the volunteer population to identify the threshold value for inclusion. Use of this deductive method in screening volunteers for Phase I trials affords increased security of selection, while reducing the number of non-pertinent exclusions because of laboratory findings. 相似文献
63.
Heterogeneous proteolytic specificity and activity of the house dust mite proteinase allergen Der p I 总被引:3,自引:0,他引:3
C. R. A. HEWITT H. HORTON R. M. JONES D. I. PRITCHARD† 《Clinical and experimental allergy》1997,27(2):201-207
Background Exposure of the skin or respiratory tract to proteinases is frequently associated with allergic sensitization. This is of particular significance in the domestic indoor environment where the proteolytic activity of Der p I, the group I allergen of the house dust mite Dermatophagoides pteronyssinus, may influence the allergenicity of mites. Using class-specific proteinase inhibitors and active-site affinity chromatography, we have previously shown that Der p I exhibits a mixed cysteine-serine proteinase activity. Measurement of the amount of cleavage, however, did not determine whether the inhibitors used were targeting exactly the same proteolytic mechanism. Objective To resolve this issue, we have examined whether the cleavage specificity of the cysteine and serine proteinase activities of Der p I was the same. Methods HPLC and mass spectrometry were used to analyse and identify the products of a Der p I-digested peptide substrate and thus identify the peptide bonds cleaved. Results Der p I cleaves different peptide bonds, depending upon the class of proteolytic mechanism used. In the model peptide substrate insulin B chain, the cysteine and serine proteinase activities of Der p I showed preference for glutamic acid and arginine respectively in the P1 position. Conclusion These data suggest the existence of more than one mechanistic form of the allergen immunologically identified as Der p I. If proteolytic activity is indeed a function of allergenicity, this information may have important implications for the pathogenicity of Der p I and the ability of innate antiproteinase defences in the respiratory tract to prevent immune sensitization. 相似文献
64.
R. DE BOER W. A. D. VAN DER HOEVEN S. O. STAPEL 《Clinical and experimental allergy》1995,25(8):765-770
Background: Fluctuations in the level of mite allergens in domestic house dust are the result of changes in the balance between synthesis, removal and decay. Purely physical forces as well as enzymatic degradation, mediated by house dust inhabiting microbes, may contribute to the decay of allergens in domestic dust. Knowledge about the speed of decay is essential for an understanding of the dynamics of allergen levels. Objective: The present study is a quantitative assessment of the speed of decay at nine combinations of temperature (15°C, 20°C and 25°C) and relative humidity (33%, 55% and 75%). Methods: Samples of mite infested material of an old rug were stored at these temperature/relative humidity-combinations for 6, 12 or 18 months, after the mites were killed by cither a freezing treatment or an acaricide (lindane). The microbes living in the rug presumably survive these treatments. Concentrations of Der p I and Der p II + Der f II. in extracts of the rug material, were measured by a radio immunoassay. Results: No significant changes in the levels of Der p I and Der p II +Der f II, could be detected even after 11/2 year at a high temperature and humidity. Conclusion: These findings incidate that mite allergens can be extremely stable under normal domestic circumstances. 相似文献
65.
BACKGROUND: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management. AIM: To evaluate structured TTP for geriatric patients with impaired cognitive function. PATIENTS AND METHODS: A neuropsychological examination was performed on all patients over 54 years [n=102, age 68.6 +/- 8.7 years, diabetes duration 10.3 (0.03-35.4) years, HbA1c 10.3 +/- 1.7% (HPLC, Diamat, NR 4.5-6.3%), cognitive function 87.7 +/- 12.3 IQ points] who took part in TTP for insulin therapy. Patients with impaired cognitive function participated either in the standard TTP of Berger [n = 35, age 67.6 +/- 8.9 years, diabetes duration 9.9 (0.04-35.4) years, HbA1c 10.3 +/- 2.0%] or in the specialized structured geriatric DICOF-TTP [n=33, age 70.4 +/- 8.2 years, diabetes duration 10.4 (0.03-24.9) years, HbA1c 10.7 +/- 1.8%]. RESULTS: After TTP there were no differences in knowledge and ability for diabetes self-management (standard/DICOF: knowledge 11.0 +/- 2.6 vs. 12.2 +/- 2.7 points, P = 0.11; handling 14.9 +/- 3.3 vs. 15.9 +/- 2.5 points, P = 0.18). However, patients who took part in the DICOF programme showed better scores in satisfaction with the education programme [standard/DICOF 44.7 (31-57) vs. 52.5 (45-59) points, P < 0.001]. Six months later the DICOF participants showed better results regarding diabetes self-management (standard/DICOF: handling 12.5 +/- 4.1 vs. 15.9 +/- 3.1 points, P = 0.001). Both groups showed HbA1c decrease (8.3 +/- 1.4 vs. 8.5 +/- 1.3%, P=0.62) and similar incidence of acute complications. CONCLUSIONS: Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management. 相似文献
66.
100例2型糖尿病患者交感神经皮肤反应研究 总被引:1,自引:0,他引:1
目的探讨交感神经皮肤反应(SSR)检测在评价2型糖尿病(T2DM)自主神经损害中的价值.方法对100例T2DM患者进行SSR检测,30例健康志愿者作为对照.结果2组SSR的起始潜伏期、N波潜伏期、波幅、面积比较差异有显著性意义(P<0.05),P波潜伏期差异无显著性意义(P>0.05).T2DM组72例(72%)患者至少有一肢SSR异常.血糖控制满意组和血糖控制不良组比较,起始和N波潜伏期差异有统计学意义(P<0.05),波幅和面积无显著性意义(P>0.05).T2DM组病程<5年与病程≥5年比较,潜伏期、波幅、面积差异均无统计学意义(P>0.05).结论SSR可作为评价T2DM自主神经损害的客观电生理指标;T2DM患者SSR与血糖控制水平相关,与病程无关. 相似文献
67.
K. F. Tait J. E. Collins J. M. Heward I. Eaves H. Snook J. A. Franklyn A. H. Barnett J. A. Todd M. Maranian A. Compston S. Sawcer S. C. L. Gough 《Diabetic medicine》2004,21(3):267-270
Aims The Type 1 diabetes susceptibility locus, IDDM2, has been mapped to a variable number of tandem repeats (VNTR) region 5′ upstream of the insulin (INS) and insulin‐like growth factor (IGF2) genes on chromosome 11p15. The function of the VNTR is uncertain; however, it may influence the thymic expression of the insulin gene and affect the development of immune self‐tolerance. The aim of this study was to investigate whether the INS VNTR region is a Type 1 diabetes‐specific locus or acting as a general autoimmunity gene. Methods We genotyped the INS‐IGF2 VNTR [using the surrogate INS?23 HphI single nucleotide polymorphism (SNP)] in 823 Graves’ disease (GD)/multiple sclerosis (MS) families, 1433 GD/MS patients and 837 healthy control subjects. Results We found no evidence of excess transmission of the allele associated with Type 1 diabetes to individuals affected by GD or MS within the families. Analysis of the case–control dataset showed no genotypic or allelic difference between the two populations. Conclusions These data suggest that the INS‐IGF2 VNTR is acting as a Type 1 diabetes‐specific susceptibility gene rather than as an influence on general autoimmunity. 相似文献
68.
目的:明确氟对人牙乳头细胞合成 I型胶原的影响。 方法:对人牙乳头细胞进行体外培养 ,分别给予0 .0、0 .2× 10 - 6、1.0× 10 - 6、5 .0× 10 - 6、2 5 .0× 10 - 6 g/ L 氟处理 ,采用免疫细胞化学方法染色 ,图象分析氟对细胞合成 I型胶原的影响。 结果:I型胶原在对照组和 4种氟浓度处理组细胞表达均为阳性。图象分析结果表明 ,4种氟浓度对体外培养的人牙乳头细胞合成 I型胶原量与对照组相比差异无统计学意义 (P>0 .0 5 )。结论:过量氟对牙本质基质 型胶原的影响可能不是通过影响成牙本质细胞内合成实现的 相似文献
69.
本文报告胰岛细胞脑内移植治疗I型糖尿病共3例,分别经过3个月、4个月、6个月的临床观察,其临床症状明显改善或消失,空腹血糖由移植前平均12.38mmol/L下降至7.77mmol/L;3例患者普通胰岛素用量平均每日62.3~u,移植后第21~30天均完全停用胰岛素,其中1例已持续撤离胰岛素治疗达5个月。观察结果提示:胰岛移植物在患者的脑内成活,并具有良好的内分泌功能。 相似文献
70.
J. Scott Tonigan 《Alcoholism, clinical and experimental research》2007,31(S3):55s-56s
The statistical search for mechanisms of change involves multiple inferential tests, ones that generally follow a fixed sequence designed to demonstrate mediation. While there are several popular approaches to conducting such tests, e.g., SEM and MRA, the inflated Type I error rate problem associated with conducting these tests has received little, if any, attention. This paper offers 2 solutions to avoid committing Type I errors associated with mediational tests. Most straightforward, investigators may choose to use a Bonferroni adjustment. In contrast, a design-based approach can be used that tests rival explanations for the observed effects. Examples drawn from addiction research are provided. 相似文献