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  • 1
    Abstract: Analysis of biological processes is frequently performed with the help of phenotypic assays where data is mostly acquired in single end-point analysis. Alternative phenotypic profiling techniques are desired where time-series information is essential to the biological question, for instance to differentiate early and late regulators of cell proliferation in loss-of-function studies. So far there is no study addressing this question despite of high unmet interests, mostly due to the limitation of conventional end-point assaying technologies. We present the first human kinome screen with a real-time cell analysis system (RTCA) to capture dynamic RNAi phenotypes, employing time-resolved monitoring of cell proliferation via electrical impedance. RTCA allowed us to investigate the dynamics of phenotypes of cell proliferation instead of using conventional end-point analysis. By introducing data transformation with first-order derivative, i.e. the cell-index growth rate, we demonstrate this system suitable for high-throughput screenings (HTS). The screen validated previously identified inhibitor genes and, additionally, identified activators of cell proliferation. With the information of time kinetics available, we could establish a network of mitotic-event related genes to be among the first displaying inhibiting effects after RNAi knockdown. The time-resolved screen captured kinetics of cell proliferation caused by RNAi targeting human kinome, serving as a resource for researchers. Our work establishes RTCA technology as a novel robust tool with biological and pharmacological relevance amenable for high-throughput screening.
    Type of Publication: Journal article published
    PubMed ID: 21765947
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  • 2
    ISSN: 0168-9002
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1076
    Keywords: Type I Hyperlipoproteinemia ; Lipiduria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An Hand des Krankheitsverlaufes eines $$2{\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle 2$}}$$ jährigen Knaben mit exogener (fettinduzierter) Hyperlipoproteinämie (Typ I nach Fredrickson) wird auf diagnostische und therapeutische Schwierigkeiten bei dieser seltenen Erkrankung eingegangen. Besonders bemerkenswert sind eine mehrfach beobachtete Lipidurie, ein Extremwert der Serumtriglyceride von 30200 mg% und eine gesteigerte TmPAH. Letztere wurde auch beim Kindesvater beobachtet. Der Kindesvater hatte bereits bei üblicher, 2 seiner 4 Schwestern nach fettreicher Kost einen hohen Triglyceridspiegel. Eine verminderte Lipoproteinlipase und ein Chylomikronenband konnten beim Kindesvater nachgewiesen werden. Die Fettmenge in der Kost mußte bei unserem Patienten mit 7 g/Tag sehr niedrig gehalten werden. Therapieversuche mit mittelkettigen Triglyceriden, mit Heparin und Clofibrat blieben erfolglos.
    Notes: Abstract A $$2{\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle 2$}}$$ -year-old boy with excessive hyperlipemia type I could be observed. In a fat rich diet period elevation of plasma triglycerides up to 30200 mg% with severe abdominal symptoms was induced. The level of lipoprotein-lipase, typical lipidelectrophoresis and fat induction of hyperglyceridemia confirmed the diagnosis. A reduction of heparin induced lipoproteinlipase could be also found in the father of the child. Both father and child had an elevation of PAH-clearance to nearly threefold. The boy several times had fat floating on the urine. Medium chain triglycerides did not give an improvement, dietary management could be achieved by reduction of dietary fats to 10 g per day.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes mellitus ; apo(a) gene ; apo(a) polymorphism ; Lp(a) ; susceptibility gene ; atherosclerosis ; risk factor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. High lipoprotein(a) [Lp(a)] plasma concentrations are a genetically determined risk factor for atherosclerotic complications. In healthy subjects Lp(a) concentrations are mostly controlled by the apolipoprotein(a) [apo(a)] gene locus which determines a size polymorphism with more than 30 alleles. Subjects with low molecular weight apo(a) phenotypes on average have higher Lp(a) concentrations than those with high molecular weight apo(a) phenotypes. There are many opinions about whether and why Lp(a) is raised in patients with Type I diabetes (insulin-dependent) mellitus. Methods. We investigated Lp(a) plasma concentrations and apo(a) phenotypes in 327 patients with Type I diabetes mellitus (disease duration 1–61 years) and in 200 control subjects matched for age and sex. Results. Patients with a disease duration of up to 15 years had significantly higher Lp(a) concentrations (24.3 ± 34.0 mg/dl vs 16.7 ± 22.6 mg/dl, p = 0.014) compared with control subjects. This increase can be explained by a considerably higher frequency of low molecular weight apo(a) phenotypes (38.9 % vs 23.5 %, p 〈 0.005). The frequency of low molecular weight apo(a) phenotypes decreased continuously with disease duration from 41.7 % in those with disease duration of up to 5 years to 18.2 % in those with the disease lasting more than 35 years. Conclusion/interpretation. Our data show that an increase of Lp(a) in Type I diabetic patients can only be observed in groups with short diabetes duration and that this elevation is genetically determined. Therefore, the apo(a) gene, located at 6q26–27, might be a susceptibility gene for Type I diabetes mellitus which is supported by recently published studies reporting evidence for linkage of this region (6q27) with Type I diabetes mellitus. Furthermore, the decreasing frequency of low molecular weight apo(a) phenotypes with disease duration suggests a survivor effect. [Diabetologia (1999) 42: 1021–1027]
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Acta neurochirurgica 11 (1963), S. 353-368 
    ISSN: 0942-0940
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Übersicht über die von Winiwarter-Buergersche Krankheit im Hinblick auf neuere Entwicklungen. Diese tendieren dahin, die Annahme, daß es sich bei der Buergerschen Krankheit um eine Krankheitseinheit eigener Genese handelt, zu verneinen und sie dem größeren Rahmen der Arteriosklerose zuzuordnen. Diese Ansicht wird gestützt durch die unerwartet große Häufigkeit, mit der sich stenosierende Atherome an den intracraniellen Gefäßen schon in relativ jungem Lebensalter finden. Es wird daraus geschlossen, daß es, unabhängig von den ätiologischen Beziehungen, eine besondere Form der cerebralen Gefäßverschlußkrankheiten gibt, die bevorzugt die Endabschnitte der Gefäße befällt und in klinischer und therapeutischer Hinsicht als eigengesetzlich zu betrachten ist. Ihr klinisches Bild ist im Vergleich mit dem ziemlich einförmigen Bild der gewöhnlichen cerebralen Arteriosklerose wechselnd, mit einem Schwerpunkt im Psychiatrischen.
    Abstract: Résumé La présente élude au sujet des variations cérébrales de la maladie de Von Winiwarter-Buerger est présentée à la lumière de récents développements. Ces derniers tendent à abolir le concepte de la thrombo-angéite de Buerger comme une entité pathologique spécifique et à la classer dans la large conception de l'artério-sclérose. Cet aspect est particulièrement démontré par le haut pourcentage, jusqu'alors insoupçonné d'athéromes sténosants des artères extracrâniennes survenant à un surprenant âge précoce. La conclusion proposée est quelles que puissent être les relations étiologiques du point de vue clinique et thérapeutique, une certaine forme de maladie artério sténosante cérébrale atteignant de préférence la partie terminale de l'arbre vasculaire, devrait être connue comme une condition ayant ses propres règles. Ce tableau clinique est variable si on le compare aux aspects uniformes de la commune artèriosclérose cérébrale avec une répercussion psychiatrique.
    Notes: Summary The present view regarding the cerebral variant of von Winiwarter-Buerger's disease is presented in the light of recent developments. These tend to abolish the concept of Buerger's thromboangiitis as a disease entity sui generis and to classify it within the broader concept of arteriosclerosis. This view is adequately supported by the high incidence, hitherto unsuspected, of stenosing atheroma within the extracranial arteries occurring at a surprisingly early age. — The conclusion is drawn that, whatever the etiological relationship may be, from a clinical and therapeutic point of view a certain form of cerebral arterio-stenotic disease involving preferentially the terminal part of the vascular tree should be recognized as a condition in its own rights. Its clinical picture is variable as compared to the rather uniform picture of common arteriosclerosis cerebri, with the stress lying on the psychiatric rather than the neurological features. In addition, it may be complicated, in due course, by secondary symptoms due to proximal narrowing within the carotid and allied systems and/or involvement of the visceral vascular territories such as the myocardium. Both angiography and electrocardiography are imperative in differential diagnosis.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Applied physics 35 (1984), S. 9-12 
    ISSN: 1432-0630
    Keywords: 72.20 ; 73.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The kinetics of the Staebler-Wronski effect ina-Si:H were investigated experimentally. The rate of recovery from the illuminated state B to the annealed state A was observed at various temperatures in undoped,n- andp-dopeda-Si:H. The data can be characterized by a thermally activated relaxation time with an activation energy decreasing with increasing doping concentration. The results are compared with previous data and existing models.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Inspiratory muscle load ; cycle ergometer test ; diabetes mellitus ; exercise hyperpnea ; respiratory effort sensation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to evaluate the difference between Type 1 (insulin-dependent) diabetic patients and healthy control subjects regarding inspiratory muscle load during exercise hyperpnea. For this purpose an incremental progressive exercise test on a cycle ergometer was performed by 36 Type 1 diabetic patients and 40 healthy subjects. In order to determine the mechanical load on the inspiratory muscles breath by breath, we selected the following two parameters, which represent the pressure generated by the inspiratory muscles as well as the duration and velocity of their contraction: (1) the oesophageal tension time index, which is the product of the duty cycle (ratio of inspiratory time to total breath cycle duration) and the mean oesophageal pressure expressed as a percentage of the maximal oesophageal pressure and (2) the mean oesophageal pressure change per time unit during the inspiratory phase of each breathing manoeuver, which is expressed as a fraction of the subject's maximal oesophageal pressure. Comparison of the two groups revealed that at similar levels of ventilation the mechanical load on the inspiratory muscles was significantly higher in the Type 1 diabetic patients than in the control subjects. When the loading was stopped the maximal ventilation was lower in the patients. Nevertheless, they reported a degree of respiratory effort sensation comparable to the control group, which seems to have been caused by an increase of the mechanical load on the ventilatory muscles.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Diabetic nephropathy ; risk factors ; ACE polymorphism ; glycaemic control ; hypertension.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic nephropathy represents a major complication in patients with insulin-dependent diabetes mellitus (IDDM). Intervention trials using angiotensin-converting enzyme (ACE) inhibitors have pointed towards the important pathogenetic role of the renin-angiotensin system. Recently an insertion/deletion (I/D) polymorphism for the gene encoding the ACE has been described, the deletion type being associated with higher plasma ACE levels. As the intrarenal renin-angiotensin system might also be activated in this setting, we determined the ACE genotype together with other risk factors for the development of diabetic nephropathy in 122 patients with IDDM from a single centre with (n = 63) and without (n = 59) nephropathy. Long-term glycaemic control was evaluated using mean HbA1c values from the last 10 years. The two patient group were comparable with regard to duration of diabetes and glycaemic control as assessed by current HbA1c values. However, mean long-term HbA1c values were significantly higher in patients with diabetic nephropathy as was systemic blood pressure. The DD genotype was more prevalent in patients with renal disease. In the subgroup of patients who had had diabetes for more than 20 years (n = 90), the DD genotype was even more frequent in patients with nephropathy, and blood pressure and long-term HbA1c values were also higher in patients with renal disease. Logistic regression analysis revealed long-term glycaemic control, blood pressure and the ACE genotype to be independent risk factors for the prevalence of diabetic nephropathy. [Diabetologia (1997) 40: 327–331]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 23 (1982), S. 288-288 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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