Complexity of IL-1β induced gene expression pattern in human articular chondrocytes

SummaryThe mRNA fingerprinting technique, differential display reverse transcription polymerase chain (DDRT-PCR), was used to detect changes in the overall pattern of gene expression in human articular knee chondrocytes induced by interleukin-1β (IL-1β), the prototypical inducer of catabolic responses in degenerate joint diseases. One hundred different primer combinations generated approximately 10 000 different PCR fragments for IL-1β treated, as well as for untreated human chondrocytes, cultivated in alginate beads. This represented 53% of all expressed chondrocyte genes as based on statistical considerations. Side by side comparisons of differential display patterns originating from two different donor tissues yielded 44 reproducibly, differentially-displayed cDNA fragments, which were subcloned and sequenced. Sequence homology searches revealed sequence identities to the human necrosis factor α (TNF-α) and IL-1 regulated gene TSG-6, fibronectin, osteopontin, calnexin, and the DNA repair enzyme ERCC5. The differential expression was confirmed with Northern and quantitative PCR analyses. The known function of these genes and their known IL-1 responsiveness indicate that the employed model system reflects the pleiotropic effects of IL-1 on the overall gene expression in human articular chondrocytes and identifies genes involved in very different biochemical pathways. Twenty-seven cDNAs lacked sequence homologies to known genes and may represent novel genes

Decreasing hospital mortality between 1994 and 1998 in patients with acute myocardial infarction treated with primary angioplasty but not in patients treated with intravenous thrombolysis Results from the pooled data of the maximal individual therapy in acute myocardial infarction (MITRA) registry and the myocardial infarction registry (MIR)

AbstractOBJECTIVESWe investigated changes in the clinical outcome of primary angioplasty and thrombolysis for the treatment of acute myocardial infarction (AMI) from 1994 to 1998.BACKGROUNDPrimary angioplasty for the treatment of AMI is a sophisticated technical procedure that requires experienced personnel and optimized hospital logistics. Growing experience with primary angioplasty in clinical routine and new adjunctive therapies may have improved the outcome over the years.METHODSThe pooled data of two German AMI registries: the Maximal Individual Therapy in AMI (MITRA) study and the Myocardial Infarction Registry (MIR) were analyzed.RESULTSOf 10,118 lytic eligible patients with AMI, 1,385 (13.7%) were treated with primary angioplasty, and 8,733 (86.3%) received intravenous thrombolysis. Patients characteristics were quite balanced between the two treatment groups, but there was a higher proportion of patients with a prehospital delay of >6 h in those treated with primary angioplasty. The proportion of an in-hospital delay of more than 90 min significantly decreased in patients treated with primary angioplasty over the years (p for trend = 0.015, multivariate odds ratio [OR] for each year of the observation period = 0.84, 95% confidence interval [CI]: 0.73– 0.96) but did not change significantly in patients treated with thrombolysis. Hospital mortality decreased significantly in the primary angioplasty group (p = 0.003 for trend; multivariate OR for each year = 0.73, 95% CI: 0.58– 0.93). However, for patients treated with thrombolysis, hospital mortality did not change significantly (p for trend 0.175, multivariate OR for each year: 1.02, 95% CI: 0.94– 1.11).CONCLUSIONSCompared with thrombolysis the clinical results of primary angioplasty for the treatment of AMI improved from 1994 to 1998. This indicates a beneficial effect of the growing experience and optimized hospital logistics of this technique over the years

Role of Two Cell Wall Amidases in Septal Junction and Nanopore Formation in the Multicellular Cyanobacterium Anabaena sp PCC 7120

Work in the Tübingen lab was supported by Deutsche Forschungsgemeinschaft (SFB766). RP was supported by Deutsche Forschungsgemeinschaft (GRK1708). Work in Seville was supported from Plan Nacional de Investigación, Spain, co-financed by the European Regional Development Fund (grant no. BFU2014-56757-P)

Конкурентоспособность фирм в условиях рыночной экономики

Анализ эффективности организации коммерческой деятельности предприятия и оценка конкурентоспособности фирмы. Исследование и разработка системы повышения конкурентоспособности предприятия рынка рекламных услуг.Analysis of the effectiveness of the organization of commercial activities of the enterprise and evaluation of the firm's competitiveness. Research and development of a system for increasing the competitiveness of a service enterprise

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Marsch ins Bett

MARSCH INS BETT Marsch ins Bett ( - ) Einband ( - ) Titelseite ( - ) Leidwort ( - ) Humor - medizinisch gesehen (6) Über die Gefahren der Diät und anderer ungesunder Ernährungsweisen (7) Über die Nachteile des Nichtrauchens (13) Über das Wohl von Alkohol (20) Über merkwürdige Wirkungen von frischer Luft (22) Über die Schädlichkeit des Sports (26) Über die besten Wege zum Herzinfarkt (30) Über die Notwendigkeit, Arbeitsschutzbestimmungen nicht zu beachten (35) Über Möglichkeiten, etwas gegen seine Gesundheit zu tun (42) Über widersprüchliche Erfahrungen von und mit Ärzten (45) Über Herzkläpse, Erkältungskrankheiten, Massagen und ähnlichen Zeitvertreib (66) Über die Zähne sowie das Stochern in denselben (78) Über Bandwürmer und Blinddärme (82) Über die Freuden eines Krankenhausaufenthaltes (84) Über die Tatsache, daß Nerven eine Krankheit sind,desgleichen auch die Psychoanalyse (95) Über Methoden zur vollen Ausnutzung der Sozialversicherungsbeiträge (102) Über den nutzbringenden Umgang mit Medikamenten (106) Über Licht und Schatten von Kuren (115) Über geeignete Mittel, hundert Jahre alt zu werden (121) Über das Widersinnige unseres Buchtitels ... (125) Lassen Sie sich beraten ... ( - ) Die Autoren und ihre Seitenlage ( - ) Nachwort ( -

Therapy of chronic metabolic acidosis among diabetologist

Hintergrund: Die chronische metabolischen Azidose (cmA) ist eine häufige Komplikation bei chronischer Niereninsuffizienz, deren Behandlung bei niereninsuffizienten Patienten mit Diabetes mellitus die Insulinresistenz verbessern kann. Um die aktuelle Therapiesituation der cmA im diabetologischen Umfeld abzubilden und mehr über die Zusammenarbeit von Diabetologen und Nephrologen zu erfahren, wurden diabetologisch tätige Haus- und Fachärzte zur cmA befragt. Methoden An 5863 Ärzten mit diabetologischer Zusatzqualifikation wurde postalisch ein Fragebogen versandt. Alle 97 erhaltenen Antwortbögen wurden deskriptiv ausgewertet. Ergebnisse Die meisten Teilnehmer sind Internisten mit diabetologischer Zusatzqualifikation (46 %) und behandeln im Median 50 (10; 112) Patienten mit Typ-1-Diabetes bzw. 210 (100; 450) Patienten mit Typ-2-Diabetes pro Quartal. Eine cmA wurde von 12 % der Teilnehmer in den letzten 12 Monaten bei median 4 (2; 6) Patienten mit Typ-1-Diabetes und 10 (3; 30) Patienten mit Typ-2-Diabetes beobachtet. Die cmA wird überwiegend durch Bestimmung des Serum-Bikarbonats (27; 28 %) und des Base Excess (19; 20 %) diagnostiziert. 38 (39 %) der Teilnehmer erhalten regelmäßig von Nephrologen die Empfehlung zur Behandlung der cmA. Sie wird von knapp 1 Drittel als relevant (29 %) und gut umsetzbar (27 %) betrachtet. Zur Behandlung der cmA wird vor allem orales Bikarbonat empfohlen (Bikarbonat: 39 %, Zitrat: 5 %, sonst: keine Angabe). Maßnahmen, die die Mehrheit der Diabetologen in der Verantwortung der Nephrologen sehen, sind ergänzende Diagnostik (87; 90 %) einschließlich Blutgasanalyse (59 %) sowie die Behandlung der cmA (62 %) und renalen Anämie (53 %). 34 % der Diabetologen gaben an, bisher noch keine cmA-Fälle in der Praxis behandelt zu haben. Die meisten Diabetologen überlassen die Behandlung und Überwachung der cmA dem Nephrologen (38 %). Dabei wird die Zusammenarbeit mit den Nephrologen als zufriedenstellend (81 %) bewertet. 38 % der Befragten haben in der täglichen Praxis beobachtet, dass die Einstellung der cmA auch die Insulinresistenz positiv beeinflusst. Eine CME-Fortbildung in der Diabetologie speziell zur cmA würden 76 (78 %) begrüßen. Diskussion Bei der Behandlung der cmA wird die Kooperation zwischen Diabetologen und Nephrologen generell gut bewertet, wobei die Diagnose, Behandlung und Überwachung einer cmA in der Verantwortung des Nephrologen gesehen werden. Da die Behandlung der cmA die Insulinresistenz verringern kann, sollte der Stellenwert der cmA-Therapie im diabetologischen Umfeld nicht unterschätzt werden. Um die cmA-Behandlung bei diabetischer Nephropathie zu optimieren, wären CME-Fortbildungen zur cmA geeignet. Zudem könnten Schulungen im Rahmen einer interdisziplinären Kooperation mit Diätberatern die Umsetzbarkeit diätetischer Interventionen zur Behandlung der cmA verbessern.Background Chronic metabolic acidosis (CMA) is a common complication of chronic kidney disease (CKD). Its treatment in patients with diabetes mellitus and CKD could also improve insulin resistance. We investigated the current therapeutic approaches in diabetes mellitus (DM) with CKD in a survey among diabetologic specialists and general practitioners with additional qualification in diabetology about their approach to CMA and cooperation with nephrologists. Methods 5863 practitioners were invited to complete a 27 item survey. 97 completed surveys were analysed descriptively. Results Most participants were internists with additional qualification in diabetology (46 %). They cared for median 50 (10; 112) patients with DM type I and 210 (100; 450) patients with diabetes m, type II per quarter. CMA was observed by 12 % of practitioners during the last 12 months in median 4 (2; 6) patients with DM type I and 10 (3; 30) with type II. CMA was mainly diagnosed via serum bicarbonate (28 %) or base excess (20 %). 39 % received a recommendation from the nephrologic colleagues about treatment of CMA. About one third of diabetologists rated this recommendation as highly relevant (29 %) and feasible (27 %). For treatment of CMA, oral bicarbonate is preferred (39 %). Most participants preferred their nephrological colleagues doing specialist diagnostics (90 %) including blood gas analysis, as well as taking care of the treatment of CMA (62 %) and anemia (53 %). 34 % had not treated CMA in their practice so far. The cooperation between the participants and nephrologists was evaluated good (81 %). Most participants (78 %) would appreciate further education with a focus on CMA. Discussion Cooperation between diabetologists and nephrologists works well. Nephrologists are mainly responsible for diagnosis and treatment of CMA. However, because CMA may worsen insulin resistance, its relevance for DM treatment appears to be underestimated. Further education may be required in this field