A Promoter Polymorphism of the Alpha 8 Integrin Gene and the Progression of Autosomal-Dominant Polycystic Kidney Disease

Background/Aims: Dysregulation of integrins is a feature of tissue remodeling in autosomal-dominant polycystic kidney disease (ADPKD). The alpha 8 beta 1 integrin ( _ 8 _ 1) affects kidney development and the susceptibility to renal injury in mice. We investigated whether the –414 T/C polymorphism in the promoter region of the alpha 8 integrin chain gene (ITGA8) is associated with the progression of renal disease in ADPKD. Methods: Genotyping for the –414 T/C polymorphism was performed by allelic separation using RT-PCR in 294 patients with ADPKD. Alpha 8 integrin expression was detected by RT-PCR and immunohistochemistry. Results: 41% of the study population reached end stage renal disease at a mean age of 51 8 12 years. The frequency of the –414 C allele was 0.194 in ADPKD. C allele carriers (CC and TC genotypes) were compared with patients homozygous for the T allele (TT genotype). Kaplan-Meier analysis revealed that end-stage renal failure occurred at a significantly younger age in TT homozygotes (median age, 47 years; 95% CI, 46–49 years) than in C allele carriers (median age, 51 years; 95% CI, 49–53 years; p = 0.046 by the log-rank test). When parameters of ADPKD patients were compared between genotype by analysis of variance, only age at onset of end-stage renal failure was significantly different (p = 0.026) whereas age at onset of hypertension, body surface area, 24-hour systolic and diastolic blood pressure did not differ. In kidneys of ADPKD, expression of alpha 8 integrin is increased and found de novo in cystic epithelia. Conclusion: A polymorphism of the ITGA8 promoter modifies the progression of renal failure in ADPKD

Технологическая подготовка производства изготовления детали «Корпус функционной муфты» на станках с ЧПУ

Выпускная квалификационная работа 72 страницы, 13 рисунков, 23 таблицы, 15 источников, страниц альбомной документации. Ключевые слова: крышка, крышка для выходного вала, машиностроение, технологический процесс. Объектом исследования является деталь типа «Крышка». Цель работы – разработка технологии производства детали “Крышка”. В процессе работы проведены теоретические исследования существующих технологических процессов, используемых в машиностроительном производстве, сделан сравнительный анализ их достоинств и недостатков. Результатом данной работы является технологический процесс изготовление детали “Крышка”, применимого для реального производства, где есть необходимые оборудование.Abschlusstraining Arbeit beträgt 72 Seiten, 13 Abbildungen, 23 Tabellen, 15 Quellen der Landschafts Seiten der Dokumentation. Stichworte: Abdeckung, Abdeckung für die Abtriebswelle, Maschinenbau, Verfahrenstechnik. Das Ziel der Forschung ist Teil der "Deckel". Ziel - zu Produktionstechnologie Details "Deckel" zu entwickeln. In dem Verfahren der theoretischen Forschung der bestehenden technologischen Prozessen in der Maschinenbauindustrie verwendet wird, aus einer vergleichenden Analyse ihrer Stärken und Schwächen. Das Ergebnis dieser Arbeit ist es, die Produktion von Teilen "Deckel", die für die reale Produktion zu verarbeiten, die die notwendige Ausrüstung

Detection of autosomal dominant polycystic kidney disease by NMR spectroscopic fingerprinting of urine

Autosomal dominant polycystic kidney disease (ADPKD) is a frequent cause of kidney failure; however, urinary biomarkers for the disease are lacking. In a step towards identifying such markers, we used multidimensional-multinuclear nuclear magnetic resonance (NMR) spectroscopy with support vector machine-based classification and analyzed urine specimens of 54 patients with ADPKD and slightly reduced estimated glomerular filtration rates. Within this cohort, 35 received medication for arterial hypertension and 19 did not. The results were compared with NMR profiles of 46 healthy volunteers, 10 ADPKD patients on hemodialysis with residual renal function, 16 kidney transplant patients, and 52 type 2 diabetic patients with chronic kidney disease. Based on the average of 51 out of 701 NMR features, we could reliably discriminate ADPKD patients with moderately advanced disease from ADPKD patients with end-stage renal disease, patients with chronic kidney disease of other etiologies, and healthy probands with an accuracy of >80%. Of the 35 patients with ADPKD receiving medication for hypertension, most showed increased excretion of proteins and also methanol. In contrast, elevated urinary methanol was not found in any of the control and other patient groups. Thus, we found that NMR fingerprinting of urine differentiates ADPKD from several other kidney diseases and individuals with normal kidney function. The diagnostic and prognostic potential of these profiles requires further evaluation

PKHD1, the Polycystic Kidney and Hepatic Disease 1 Gene, Encodes a Novel Large Protein Containing Multiple Immunoglobulin-Like Plexin-Transcription–Factor Domains and Parallel Beta-Helix 1 Repeats

Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease that presents primarily in infancy and childhood and that is characterized by enlarged kidneys and congenital hepatic fibrosis. We have identified PKHD1, the gene mutated in ARPKD. PKHD1 extends over ⩾469 kb, is primarily expressed in human fetal and adult kidney, and includes a minimum of 86 exons that are variably assembled into a number of alternatively spliced transcripts. The longest continuous open reading frame encodes a 4,074-amino-acid protein, polyductin, that is predicted to have a single transmembrane (TM)-spanning domain near its carboxyl terminus, immunoglobulin-like plexin-transcription–factor domains, and parallel beta-helix 1 repeats in its amino terminus. Several transcripts encode truncated products that lack the TM and that may be secreted if translated. The PKHD1-gene products are members of a novel class of proteins that share structural features with hepatocyte growth-factor receptor and plexins and that belong to a superfamily of proteins involved in regulation of cell proliferation and of cellular adhesion and repulsion

The effect of spironolactone on diastolic function in haemodialysis patients

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e'. Changes in the frequency of HFpEF were analysed using the comprehensive 'HFA-PEFF score'. Complete echocardiographic assessment was available in 65 individuals (59.5 ± 13.0 years, 21.5% female) with preserved left ventricular ejection fraction (LVEF > 50%). At baseline, mean E/e' was 15.2 ± 7.8 and 37 (56.9%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e' between the spironolactone group and the placebo group (+ 0.93 ± 5.39 vs. + 1.52 ± 5.94, p = 0.68) or in mean change of left atrial volume index (LAVi) (1.9 ± 12.3 ml/