Prominin-1+/CD133+ bone marrow-derived heart-resident cells suppress experimental autoimmune myocarditis

AIMS: Experimental autoimmune myocarditis (EAM) is a CD4(+) T cell-mediated mouse model of inflammatory heart disease. Tissue-resident bone marrow-derived cells adopt different cellular phenotypes depending on the local milieu. We expanded a specific population of bone marrow-derived prominin-1-expressing progenitor cells (PPC) from healthy heart tissue, analysed their plasticity, and evaluated their capacity to protect mice from EAM and heart failure. METHODS AND RESULTS: PPC were expanded from healthy mouse hearts. Analysis of CD45.1/CD45.2 chimera mice confirmed bone marrow origin of PPC. Depending on in vitro culture conditions, PPC differentiated into macrophages, dendritic cells, or cardiomyocyte-like cells. In vivo, PPC acquired a cardiac phenotype after direct injection into healthy hearts. Intravenous injection of PPC into myosin alpha heavy chain/complete Freund's adjuvant (MyHC-alpha/CFA)-immunized BALB/c mice resulted in heart-specific homing and differentiation into the macrophage phenotype. Histology revealed reduced severity scores for PPC-treated mice compared with control animals [treated with phosphate-buffered saline (PBS) or crude bone marrow at day 21 after MyHC-alpha/CFA immunization]. Echocardiography showed preserved fractional shortening and velocity of circumferential shortening in PPC but not PBS-treated MyHC-alpha/CFA-immunized mice. In vitro and in vivo data suggested that interferon-gamma signalling on PPC was critical for nitric oxide-mediated suppression of heart-specific CD4(+) T cells. Accordingly, PPC from interferon-gamma receptor-deficient mice failed to protect MyHC-alpha/CFA-immunized mice from EAM. CONCLUSION: Prominin-1-expressing, heart-resident, bone marrow-derived cells combine high plasticity, T cell-suppressing capacity, and anti-inflammatory in vivo effect

Appropriateness of antibiotic treatment in intravenous drug users, a retrospective analysis

BACKGROUND: Infectious disease is often the reason for intravenous drug users being seen in a clinical setting. The objective of this study was to evaluate the appropriateness of treatment and outcomes for this patient population in a hospital setting. METHODS: Retrospective study of all intravenous drug users hospitalized for treatment of infectious diseases and seen by infectious diseases specialists 1/2001-12/2006 at a university hospital. Treatment was administered according to guidelines when possible or to alternative treatment program in case of patients for whom adherence to standard protocols was not possible. Outcomes were defined with respect to appropriateness of treatment, hospital readmission, relapse and mortality rates. For statistical analysis adjustment for multiple hospitalizations of individual patients was made by using a generalized estimating equation. RESULTS: The total number of hospitalizations for infectious diseases was 344 among 216 intravenous drug users. Skin and soft tissue infections (n = 129, 37.5% of hospitalizations), pneumonia (n = 75, 21.8%) and endocarditis (n = 54, 15.7%) were most prevalent. Multiple infections were present in 25%. Treatment was according to standard guidelines for 78.5%, according to an alternative recommended program for 11.3%, and not according to guidelines or by the infectious diseases specialist advice for 10.2% of hospitalizations. Psychiatric disorders had a significant negative impact on compliance (compliance problems in 19.8% of hospitalizations) in multiple logistic regression analysis (OR = 2.4, CI 1.1-5.1, p = 0.03). The overall readmission rate and relapse rate within 30 days was 13.7% and 3.8%, respectively. Both non-compliant patient behavior (OR = 3.7, CI 1.3-10.8, p = 0.02) and non-adherence to treatment guidelines (OR = 3.3, CI 1.1-9.7, p = 0.03) were associated with a significant increase in the relapse rate in univariate analysis. In 590 person-years of follow-up, 24.6% of the patients died: 6.4% died during hospitalization (1.2% infection-related) and 13.6% of patients died after discharge. CONCLUSION: Appropriate antibiotic therapy according to standard guidelines in hospitalized intravenous drug users is generally practicable and successful. In a minority alternative treatments may be indicated, although associated with a higher risk of relapse

CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis

Experimental autoimmune myocarditis (EAM) represents a Th17 T cell-mediated mouse model of postinflammatory heart disease. In BALB/c wild-type mice, EAM is a self-limiting disease, peaking 21 days after alpha-myosin H chain peptide (MyHC-alpha)/CFA immunization and largely resolving thereafter. In IFN-gammaR(-/-) mice, however, EAM is exacerbated and shows a chronic progressive disease course. We found that this progressive disease course paralleled persistently elevated IL-17 release from T cells infiltrating the hearts of IFN-gammaR(-/-) mice 30 days after immunization. In fact, IL-17 promoted the recruitment of CD11b(+) monocytes, the major heart-infiltrating cells in EAM. In turn, CD11b(+) monocytes suppressed MyHC-alpha-specific Th17 T cell responses IFN-gamma-dependently in vitro. In vivo, injection of IFN-gammaR(+/+)CD11b(+), but not IFN-gammaR(-/-)CD11b(+), monocytes, suppressed MyHC-alpha-specific T cells, and abrogated the progressive disease course in IFN-gammaR(-/-) mice. Finally, coinjection of MyHC-alpha-specific, but not OVA-transgenic, IFN-gamma-releasing CD4(+) Th1 T cell lines, together with MyHC-alpha-specific Th17 T cells protected RAG2(-/-) mice from EAM. In conclusion, CD11b(+) monocytes play a dual role in EAM: as a major cellular substrate of IL-17-induced inflammation and as mediators of an IFN-gamma-dependent negative feedback loop confining disease progression

Neue Technologien fuer hocheffiziente Silicium-Solarzellen Schlussbericht

The general difference between Cz-grown Si and the more expensive FZ-grown Si is in the content of impurities, especially interstitial oxygen. Avoiding the impurities in the crystal growing process is a task that requires a relatively large effort. The Cz-grown silicon has yet another disadvantage, namely occurrence of an unwanted and hitherto unexplained effect: The photodegradation of the solar cell efficiency sets in, from a high initial efficiency achieved immediately after processing down to a stable final efficiency, about 1-2% below the initial value. This effect, or rather removal of this effect, is of great technological significance. The tasks defined for this project therefore were: 1. Characterisation of the metastable defect underlying the degradation of the efficiency. 2. Development of technology aimed at reducing the effect. 3. Development of an optimised process for Czochralski-grown silicon solar cells. The tree tasks could be carried out successfully, and a material could be achieved with top efficiencies of 22.0%, which is a value very close to the expensive FZ-grown silicon. (orig./CB)Der generelle Unterschied von Cz-Silicium gegenueber dem teureren zonengezogenen FZ-Si ist die Verunreinigung insbesondere mit interstitiellem Sauerstoff. Die Vermeidung dieser Sauerstoffkontamination bei der Kristallherstellung ist relativ aufwendig. Zusaetzlich tritt in Cz-Silicium der unerwuenschte und bislang unverstandene Effekt auf, dass durch Beleuchtung eine Degradation des Solarzellenwirkungsgrades von einem hohen Ausgangswert unmittelbar nach der Prozessierung auf einen stabilen Endwert ausgeloest wird. Da der Wirkungsgrad durch die Degradation absolut um 1-2% sinkt, ist dieser Effekt und insbesondere seine technologische Beseitigung von groesster praktischer Bedeutung, da dies eine deutliche Erhoehung der Wirtschaftlichkeit bewirken wuerde. Die Aufgaben in diesem Arbeitspunkt waren daher folgende: 1. Die Charakterisierung des metastabilen Defektes der der Wirkungsgraddegradation zugrunde liegt. 2. Die Entwicklung technologischer Verfahren zur Reduzierung dieses Degradationseffektes. 3. Die Entwicklung eines fuer Cz-Si optimierten Solarzellenprozesses. Alle drei Punkte konnten sehr erfolgreich bearbeitet werden und fuehrten letztendlich zu Spitzenwirkungsgraden von 22.0%, einem Wert der dem von teurem FZ-Si sehr nahe kommt. (orig.)Available from TIB Hannover: F99B1332+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Silicium-Solarzellen mit hoechsten Wirkungsgraden Abschlussbericht

In this report the basic activities for the development of the silicon high efficiency solar cell technology are described. The project had two main goals: (i) The improvement of efficiencies using a systematic optimization of all cell parameters and technology steps and (ii) the simplification of the technology towards the possibilities of an industrial production, keeping the cell efficiency at a high level. Starting from the LBSF technology, developed at Fraunhofer ISE, the reduction of all loss mechanisms led to efficiencies up to 22.5% on FZ-silicon. Using a modification of this technology efficiencies of up to 21.7% have been reached on Cz-silicon. Even after the reduction of the number of photolithographic steps from six to three efficiencies up to 21.6% on FZ- and 19.5% on Cz-silicon have been obtained. These are best values in an international comparison. (orig.)In diesem Projektbericht werden grundlegende Arbeiten zur Entwicklung der Silicium-'Highefficiency'-Solarzellentechnologie beschrieben. Das Projekt hatte zwei Hauptziele: (i) Die Erhoehung der Wirkungsgrade durch eine systematische Optimierung aller Zellparameter und aller Technologieschritte und (ii) die Vereinfachung der Technologie unter Beibehaltung sehr hoher Wirkungsgrade mit dem Ziel einer Annaeherung an die Moeglichkeiten der Industriefertigung. Ausgehend von der im Fraunhofer ISE entwickelten LBSF-Technologie gelang es durch Reduzierung aller Verlustmechanismen, Wirkungsgrade bis zu 22.5% auf FZ-Silicium zu erreichen. Nach Anpassung der Technologie wurden auf Cz-Silicium Wirkungsgrade bis 21.7% erzielt. Ein von sechs auf drei Fotomaskenschritte reduzierter Prozess erzielte immerhin noch Werte bis 21.6% auf FZ- und 19.5% auf Cz-Material. Alle dieser Werte stellen im internationalen Vergleich Spitzenleistungen dar. (orig.)Available from TIB Hannover: F96B1115+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

High-efficiency-Solarzellen-Technikum, HESTEC Abschlussbericht

The project comprised the following activities and results: (1) Acquisition of new supplementary process equipment. (2) Testing and preparation of the new pilot line equipment. (3) Measurement of the mean efficiency of RP-PERC cells on (float zone) FZ silicon in pilotline operation. (4) Measurement of the mean efficiency of RP-PERC cells on (Czochralski) Cz silicon in pilot line operation. (5) Development of a SiN_x film with excellent passivation characteristics. (6) Achievement of the maximum efficiency world-wide so far for a SiN_x passivated solar cell. (7) Development of a strongly simplified process for preparation of the point-contacted rear side. (8) Optimisation of the RP-PERC cell for very low luminance. (9) Development of emitter-wrap-through solar cells (EWT). (10) Development of rear contact cells with an efficiency of 21.5 %. (11) Prevention of light-induced degradation of Cz silicon by using gallium as doping material. (12) Reduction of degradation of boron-doped Cz-Si solar cells by using an optimized solar cell process. (13) Strong reduction of the cell cost by introduction of the pilot line equipment. (14) Introduction of PV moduels with RP-PERC cells in the telecommunications market. (orig.)Im folgenden sind die wichtigsten Aktivitaeten und Ergebnisse, die im Rahmen dieses Projektes erarbeitet wurden, dargestellt: (1) Erweiterung des Prozessequipments. Es wurden folgende Geraete angeschafft, um den Durchsatz bei der Herstellung hocheffizienter RP-PERC (Random Pyramids - Passivated Emitter and Rear Cell) Zellen stark zu erhoehen: (a) Automatische Photolackstation (b) Automatischer Maskaligner (c) Plasmareaktor zur Entfernung von Photolackresten ('Resist Ashing') (d) Chemiebank fuer 6'' Wafer (e) Produktionsnahe Metallaufdampfanlage (f) Halbautomatische Galvanikapparatur. (2) Einfahren des neuen Pilotlinienequipments. (3) Mittlerer Wirkungsgrad von RP-PERC-Zellen auf (Float Zone) FZ-Silicium im Pilotlinienbetrieb: 21.3#+-#0.5%. (4) Mittlerer Wirkungsgrad von RP-PERC-Zellen auf (Czochralski) Cz-Silicium im Pilotlinienbetrieb: 18.2#+-#0.4%. (5) Entwicklung einer sehr gut passivierenden SiN_x-Schicht. (6) Bester Wirkungsgrad (21.5%) weltweit fuer eine SiN_x-passivierte Solarzelle. (7) Entwicklung eines stark vereinfachten Prozesses zur Herstellung der punktkontaktierten Rueckseite. (8) Optimierung der RP-PERC-Zelle fuer sehr geringe Beleuchtungsstaerken. Schon bei voller Sonnenbestrahlung liegt der Wirkungsgrad von RP-PERC-Zellen etwa um 40% hoeher als der kommerzieller Zellen. (9) Entwicklung von Emitter-Wrap-Through Solarzellen (EWT). (10) Entwicklung von Rueckseitenkontaktzellen mit 21.5% Wirkungsgrad. (11) Vermeidung der lichtinduzierten Degradation in Cz-Silicium durch Verwendung von Gallium als Dotierstoff. (12) Reduzierung der Degradation in bordotierten Cz-Si-Solarzellen durch Verwendung eines optimierten Solarzellenprozesses. (13) Starke Reduzierung der Zellkosten durch Einfuehrung des Pilotlinienequipments. (14) Einfuehrung von PV-Modulen mit RP-PERC-Zellen in den Telekommunikationsmarkt. (orig.)Available from TIB Hannover: F03B1235 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman

Lipid-Intervention und koronare Herzkrankheit bei Mannern unter 56 Jahren. Die Coronare Interventions-Studie: CIS. [Lipid intervention and coronary heart disease in men less than 56 years of age. The Coronary Intervention Study: CIS]

The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously. RESULTS: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C g