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131.
Linkage studies have identified a large (>60-Mb) region on chromosome 10q that segregates with Alzheimer Disease (AD). Within the region, the gene for insulin degrading enzyme (IDE) represents a notable biological candidate given that it degrades amyloid beta-protein (one of the major constituents of senile plaques) and the intracellular amyloid precursor protein (APP) domain released by gamma-secretase processing. We have used a single nucleotide polymorphism (SNP) genetic association strategy to investigate AD in relation to a 480-kb region encompassing IDE. A 276-kb linkage disequilibrium block was revealed that spans three genes (IDE, KNSL1, and HHEX). Assessing this block in several independent sets of case-control materials (early- and late-onset AD) and focusing also upon quantitative measures that are pertinent to AD diagnosis and severity (MMSE scores, microtubule-associated protein Tau [MAPT] levels in CSF, degree of brain pathology, and age-at-onset) produced extensive evidence for significant AD association. Signals (p-values ranging from 0.05 to <1x10(-9)) were generally stronger when examining haplotypes rather than individual SNPs, and quantitative trait tests most uniformly revealed the detected associations. Consistent risk alleles and haplotypes were apparent across the study, with effects in some cases as large as that of the epsilon4 allele of APOE. A subsequent mutation screen of exons in all three suspect genes provided no evidence for common causative mutations. These results provide substantial evidence that genetic variation within or extremely close to IDE impacts both disease risk and traits related to the severity of AD. 相似文献
132.
Biomechanical Properties of Esophagus during Systemic Treatment with Epidermal Growth Factor in Rats
Zhao J Yang J Vinter-Jensen L Zhuang F Gregersen H 《Annals of biomedical engineering》2003,31(6):700-709
The epidermal growth factor (EGF) is a growth factor with effects on many cell types and tissue. Morphometric and passive biomechanical properties were studied in isolated segments of the esophagus in 22 EGF-treated rats and 12 control rats. The rats were divided into groups with EGF treatment for 2, 4, 7, and 14 days (n=6 for each group except n=4 for the 14 days EGF-treatment group) or saline treatment (n=3 for each group). The mechanical test was performed as a distension experiment in vitro where the whole esophagus was stretched to its in situ length and distended with pressures up to 10 cm H2O using a ramp distension protocol. The pressure and outer diameter were recorded. Circumferential stress (force per area) and strain (deformation) were computed from the diameter and pressure data using the zero-stress state as reference. The zero-stress state was obtained by cutting esophageal rings radially. This caused the rings to open up into a sector. EGF induced pronounced morphometric changes, e.g., the wall thickness, wall cross-sectional area, and inner and outer circumferential lengths significantly increased during the EGF treatment. Histological analysis showed mucosa and submucosa growth during EGF treatment. The opening angle and residual strains increased with the highest value in the 14 days EGF-treated group (P < 0.05). The change in opening angle depended largely on the change in mucosa thickness. Furthermore, the circumferential stiffness of the esophagus reached a maximum after 7 days EGF treatment (P < 0.01). © 2003 Biomedical Engineering Society.
PAC2003: 8719Rr, 8717Ee 相似文献
133.
134.
Rudy G E van Eijsden Mike Gerards Lars M T Eijssen Alexandra T M Hendrickx Roselie J E Jongbloed John H J Wokke Rogier Q Hintzen Maria E Rubio-Gozalbo Irenaeus F M De Coo Egill Briem Valeria Tiranti Hubert J M Smeets 《Genetics in medicine》2006,8(10):620-627
PURPOSE: Oxidative phosphorylation is under dual genetic control of the nuclear and the mitochondrial DNA (mtDNA). Oxidative phosphorylation disorders are clinically and genetically heterogeneous, which makes it difficult to determine the genetic defect, and symptom-based protocols which link clinical symptoms directly to a specific gene or mtDNA mutation are falling short. Moreover, approximately 25% of the pediatric patients with oxidative phosphorylation disorders is estimated to have mutations in the mtDNA and a standard screening approach for common mutations and deletions will only explain part of these cases. Therefore, we tested a new CHIP-based screening method for the mtDNA. METHODS: MitoChip (Affymetrix) resequencing was performed on three test samples and on 28 patient samples. RESULTS: Call rates were 94% on average and heteroplasmy detection levels varied from 5-50%. A genetic diagnosis can be made in almost one-quarter of the patients at a potential output of 8 complete mtDNA sequences every 4 days. Moreover, a number of potentially pathogenic unclassified variants (UV) were detected. CONCLUSIONS: The availability of long-range PCR protocols and the predominance of single nucleotide substitutions in the mtDNA make the resequencing CHIP a very fast and reliable method to screen the complete mtDNA for mutations. 相似文献
135.
136.
Krausse-Opatz B Schmidt C Fendrich U Bialowons A Kaever V Zeidler H Kuipers J Köhler L 《Microbial pathogenesis》2004,37(3):155-161
Chlamydia trachomatis (CT) as well as Chlamydophila pneumoniae (CP) cause chronic inflammatory diseases in humans. Persistently infected monocytes are involved in the pathogenesis by inducing mediators of inflammation. An in vitro system of chlamydial persistence in human peripheral blood monocytes (HPBM) was used to investigate prostaglandin E(2) (PGE(2)) production and the expression of the key enzyme for prostaglandin production, cyclooxygenase-2 (COX-2). PGE(2) production was determined by PGE(2)-ELISA of HPBM-culture supernatants. Cox-2 mRNA expression was measured by real-time RT-PCR of total RNA isolated from HPBM. Both, CT and CP, stimulated PGE(2) production of HPBM in vitro. Equivalent numbers of CT per host cell induced a higher PGE(2)-response compared to CP. The amount of synthesized PGE(2) depended on the chlamydial multiplicity of infection (MOI). Even at an MOI of 10 the amount of CT- and CP-induced prostaglandin, respectively, was lower than the amount of prostaglandin induced by E. coli lipopolysaccharide (LPS) at a concentration of 10microg/ml. In contrast to stimulation with LPS, Chlamydia-induced PGE(2) production as well as cox-2 mRNA decreased after day 1 post infection (p.i.). These data indicate that Chlamydia stimulate PGE(2) production in human monocytes. Since Chlamydia are often contaminated by mycoplasma, the influence of mycoplasma on the prostaglandin production was investigated additionally. Mycoplasma fermentans (MF) also stimulated PGE(2) production. The co-infection of mycoplasma and Chlamydia resulted in an additive effect in the production of PGE(2). Thus it is important to use host cells and Chlamydia free of mycoplasma contamination for the analysis of Chlamydia-induced prostaglandin production. 相似文献
137.
138.
Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas. 总被引:5,自引:0,他引:5
Tone I. Andersen Astrid Gaustad Anne-Lise Brresen George W. Farrants Jahn M. Nesland Lars Ottestad Kjell M. Tveit 《Genes, chromosomes & cancer》1992,4(2):113-121
Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival. 相似文献
139.
Blood components can be prepared either by separation of ordinary whole blood units or, selectively, by apheresis techniques. In recent years, new methods for improvement of quality and length of storage have been developed. The additive solution approach is now being applied increasingly. Its advantages and the difference between some available systems are described. Blood component therapy must be integrated into the patients' water/electrolyte balance and nutrition schedule. An outline is given of the role of blood components in the treatment of shock. The question of excessive bleeding, the possibilities of making the diagnosis of its cause(s) in the individual case, and the use of blood components is described. Coronary pulmonary bypass is used as an example of a complicated situation that can be handled effectively by a limited number of diagnostic and therapeutic tools.
Resumen Los componentes sanguíneos pueden ser preparados bien por separación de unidades ordinarias de sangre total o, selectivamente, por técnicas de aferesis. Estas últimas tienen la ventaja de permitir la selección de donantes particularmente apropiados en relación a compatibilidad inmunológica o a la ausencia de agentes infecciosos transmisibles, así como a la posibilidad de que un mismo donante pueda ser usado en forma repetida dentro de un período de tiempo corto. Nuevos métodos de mejoramiento y prolongación del período de almacenamiento han sido desarrollados. El enfoque de las soluciones aditivas es empleado con creciente frecuencia; se describen sus ventajas y las diferencias con otros métodos disponibles en la actualidad.La terapia con componentes sanguíneos debe ser parte integral del manejo del equilibrio de agua y electrolitos y del programa de soporte nutricional. Se provee una guía sobre el uso de componentes sanguíneos en el tratamiento del shock.Se describe el problema del sangrado excesivo, la posibilidad de establecer el diagnóstico de su causa en cada caso individual, y el uso de los componentes sanguíneos. El bypass coronario es presentado como ejemplo de una situación compleja que puede ser manejada en forma efectiva por medio de un número limitado de métodos de diagnóstico y tratamiento.
Résumé Les constituants du sang peuvent être isolés soit par séparation des unités de sang total ordinaire, soit sélectivement par techniques d'apharèse. Au cours des récentes années des méthodes pour améliorer la qualité et la durée du stockage ont été mises au point. Pour ce faire, l'emploi d'additifs est largement répandu. Les avantages et les différences entre quelques méthodes disponibles sont décrits par les auteurs. Le traitement par constituants du sang doit être associé à l'équilibre hydroélectrolytique et nutritif. Le rôle des différentes parties constituantes du sang dans le traitement du choc est souligné. La question de l'hémorragie excessive, les possibilités de faire le diagnostic de ses causes dans les cas individuels et l'emploi des parties constituantes adéquates du sang sont décrits. A titre d'exemple le By pass pulmo-coronarien, situation particulièrement délicate, peut être contrôlé efficacement par un nombre limité de méthodes diagnostiques et thérapeutiques.相似文献
140.
Lars Camner Rolf Sandell Per-Östen Söder 《Community dentistry and oral epidemiology》1986,14(1):31-33
In a previous study the concept "patient involvement" was found to be strongly predictive of therapy outcome. On the basis of a questionnaire concerning patients' background and motivation, 82 patients were interviewed before treatment. To cover the concept "patient involvement" 16 variables were considered as relevant measures. In a factor analysis four factors accounted for 90% of the common variance. The factors were interpreted in terms of: initial attitudes, attendance, self-confidence and teeth-mindedness. 相似文献