@article{RauchSalzwedelBjarnasonWehrensetal.2021, author = {Rauch, Bernhard and Salzwedel, Annett and Bjarnason-Wehrens, Birna and Albus, Christian and Meng, Karin and Schmid, Jean-Paul and Benzer, Werner and Hackbusch, Matthes and Jensen, Katrin and Schwaab, Bernhard and Altenberger, Johann and Benjamin, Nicola and Bestehorn, Kurt and Bongarth, Christa and D{\"o}rr, Gesine and Eichler, Sarah and Einwang, Hans-Peter and Falk, Johannes and Glatz, Johannes and Gielen, Stephan and Grilli, Maurizio and Gr{\"u}nig, Ekkehard and Guha, Manju and Hermann, Matthias and Hoberg, Eike and H{\"o}fer, Stefan and Kaemmerer, Harald and Ladwig, Karl-Heinz and Mayer-Berger, Wolfgang and Metzendorf, Maria-Inti and Nebel, Roland and Neidenbach, Rhoia Clara and Niebauer, Josef and Nixdorff, Uwe and Oberhoffer, Renate and Reibis, Rona and Reiss, Nils and Saure, Daniel and Schlitt, Axel and V{\"o}ller, Heinz and K{\"a}nel, Roland von and Weinbrenner, Susanne and Westphal, Ronja}, title = {Cardiac rehabilitation in German speaking countries of Europe — evidence-based guidelines from Germany, Austria and Switzerland LLKardReha-DACH — Part 1}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, number = {10}, issn = {2077-0383}, doi = {10.3390/jcm10102192}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239709}, year = {2021}, abstract = {Background: Although cardiovascular rehabilitation (CR) is well accepted in general, CR-attendance and delivery still considerably vary between the European countries. Moreover, clinical and prognostic effects of CR are not well established for a variety of cardiovascular diseases. Methods: The guidelines address all aspects of CR including indications, contents and delivery. By processing the guidelines, every step was externally supervised and moderated by independent members of the "Association of the Scientific Medical Societies in Germany" (AWMF). Four meta-analyses were performed to evaluate the prognostic effect of CR after acute coronary syndrome (ACS), after coronary bypass grafting (CABG), in patients with severe chronic systolic heart failure (HFrEF), and to define the effect of psychological interventions during CR. All other indications for CR-delivery were based on a predefined semi-structured literature search and recommendations were established by a formal consenting process including all medical societies involved in guideline generation. Results: Multidisciplinary CR is associated with a significant reduction in all-cause mortality in patients after ACS and after CABG, whereas HFrEF-patients (left ventricular ejection fraction <40\%) especially benefit in terms of exercise capacity and health-related quality of life. Patients with other cardiovascular diseases also benefit from CR-participation, but the scientific evidence is less clear. There is increasing evidence that the beneficial effect of CR strongly depends on "treatment intensity" including medical supervision, treatment of cardiovascular risk factors, information and education, and a minimum of individually adapted exercise volume. Additional psychologic interventions should be performed on the basis of individual needs. Conclusions: These guidelines reinforce the substantial benefit of CR in specific clinical indications, but also describe remaining deficits in CR-delivery in clinical practice as well as in CR-science with respect to methodology and presentation.}, language = {en} } @article{MoussetBuchheidtHeinzetal.2014, author = {Mousset, Sabine and Buchheidt, Dieter and Heinz, Werner and Ruhnke, Markus and Cornely, Oliver A. and Egerer, Gerlinde and Kr{\"u}ger, William and Link, Hartmut and Neumann, Silke and Ostermann, Helmut and Panse, Jens and Penack, Olaf and Rieger, Christina and Schmidt-Hieber, Martin and Silling, Gerda and S{\"u}dhoff, Thomas and Ullmann, Andrew J. and Wolf, Hans-Heinrich and Maschmeyer, Georg and B{\"o}hme, Angelika}, title = {Treatment of invasive fungal infections in cancer patients—updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)}, series = {Annals of Hematology}, volume = {96}, journal = {Annals of Hematology}, doi = {10.1007/s00277-013-1867-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121340}, pages = {13-32}, year = {2014}, abstract = {Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. Early antifungal treatment is mandatory to improve survival. Today, a number of effective and better-tolerated but more expensive antifungal agents compared to the former gold standard amphotericin B deoxycholate are available. Clinical decision-making must consider results from numerous studies and published guidelines, as well as licensing status and cost pressure. New developments in antifungal prophylaxis improving survival rates result in a continuous need for actualization. The treatment options for invasive Candida infections include fluconazole, voriconazole, and amphotericin B and its lipid formulations, as well as echinocandins. Voriconazole, amphotericin B, amphotericin B lipid formulations, caspofungin, itraconazole, and posaconazole are available for the treatment of invasive aspergillosis. Additional procedures, such as surgical interventions, immunoregulatory therapy, and granulocyte transfusions, have to be considered. The Infectious Diseases Working Party of the German Society of Hematology and Oncology here presents its 2008 recommendations discussing the dos and do-nots, as well as the problems and possible solutions, of evidence criteria selection.}, language = {en} } @article{RuckBittnerAfzalietal.2015, author = {Ruck, Tobias and Bittner, Stefan and Afzali, Ali Maisam and G{\"o}bel, Kerstin and Glumm, Sarah and Kraft, Peter and Sommer, Claudia and Kleinschnitz, Christoph and Preusse, Corinna and Stenzel, Werner and Wiendl, Heinz and Meuth, Sven G.}, title = {The NKG2D-IL-15 signaling pathway contributes to T-cell mediated pathology in inflammatory myopathies}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {41}, doi = {10.18632/oncotarget.6462}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136047}, year = {2015}, abstract = {NKG2D is an activating receptor on T cells, which has been implicated in the pathogenesis of autoimmune diseases. T cells are critically involved in idiopathic inflammatory myopathies (IIM) and have been proposed as specific therapeutic targets. However, the mechanisms underlying T cell-mediated progressive muscle destruction in IIM remain to be elucidated. We here determined the involvement of the NKG2D - IL-15 signaling pathway. Primary human myoblasts expressed NKG2D ligands, which were further upregulated upon inflammatory stimuli. In parallel, shedding of the soluble NKG2D ligand MICA (sMICA) decreased upon inflammation potentially diminishing inhibition of NKG2D signaling. Membrane-related expression of IL-15 by myoblasts induced differentiation of naive CD8\(^+\) T cells into highly activated, cytotoxic \(CD8^+NKG2D^{high}\) T cells demonstrating NKG2D-dependent lysis of myoblasts in vitro. \(CD8^+NKG2D^{high}\) T cell frequencies were increased in the peripheral blood of polymyositis (PM) patients and correlated with serum creatinine kinase concentrations, while serum sMICA levels were not significantly changed. In muscle biopsy specimens from PM patients expression of the NKG2D ligand MICA/B was upregulated, IL-15 was expressed by muscle cells, CD68\(^+\) macrophages as well as CD4\(^+\) T cells, and \(CD8^+NKG2D^+\) cells were frequently detected within inflammatory infiltrates arguing for a local signaling circuit in the inflammatory muscle milieu. In conclusion, the NKG2D - IL-15 signaling pathway contributes to progressive muscle destruction in IIM potentially opening new therapeutic avenues.}, language = {en} } @article{FrankeKartenbeckZentgrafetal.1971, author = {Franke, Werner W. and Kartenbeck, J{\"u}rgen and Zentgraf, Hanswalter and Scheer, Ulrich and Falk, Heinz}, title = {Membrane-to-membrane cross-bridges. A means to orientation and interaction of membrane faces}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32122}, year = {1971}, abstract = {No abstract available}, language = {en} } @article{FrankeBergerFalketal.1974, author = {Franke, Werner W. and Berger, S. and Falk, Heinz and Spring, H. and Scheer, Ulrich and Trendelenburg, Michael F. and Schweiger, H. G. and Herth, W.}, title = {Morphology of the nucleo-cytoplasmic interactions during the development of Acetabularia cells. I. The vegetative phase}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32363}, year = {1974}, abstract = {The ultrastructure of th e growin g and ma turing primary nucleus of Acetabularia medite rranea and Acetabularia major has been studied with the use of various fi xation procedures. Particular interest has been focused on the deta ils of the nuclear periphery and the perinuclear region. It is demonstrated that early in nuclear grow th a characteristic perinucl ear structura l complex is formed which is, among the eukaryotic cells, unique to Acetabularia and re lated genera. This perinuclear system consists essentially of a) the nuclear envelope with a very hi gh pore frequency and various pore complex assoc iat ion s w ith granular and/or threadlike structures some of which are continuous with the nucleolus; b) an approx imate ly 100 nm thick intermediate zone densely filled with a filam entOus material and occasional sma ll membraneous structures from which the typical cytOplasmic and nuclear organe lles and particles are excl ud ed ; c) an adjacent Iacunar labyrinthum which is interrupted by many plasmatic junction channels between the intermed iate zone and the free cytOplasm; d) numerous dense perinuclear bodies in the juxtanuclear cytOplasm which a re especia lly frequent at the junction channels and reveal a composition of aggregated fibrillar and granul ar structures; e) very dense exclusively fibrill ar agg regates which occur either in assoc iation with t he perinuclear region of the lacunar labyrinthum or, somewhat further out, in the cytOplasmic strands between the bra nches of the lacun ar labyrinthum in the form of slender, characteristic rods or "sausages".}, language = {en} } @article{ScheerMessnerHazanetal.1987, author = {Scheer, Ulrich and Messner, Karin and Hazan, Rachel and Raska, Ivan and Hansmann, Paul and Falk, Heinz and Spiess, Eberhard and Franke, Werner W.}, title = {High sensitivity immunolocalization of double and single-stranded DNA by a monoclonal antibody}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-41063}, year = {1987}, abstract = {A monoclonal antibody (AK 30-10) is described which specifically reacts with DNA both in double and single-stranded forms but not with other molecules and structures, including deoxyribonucleotides and RNAs. When used in immunocytochemical experiments on tissue sections and permeabilized cultured cells, this antibody detects DNA-containing structures, even when the DNA is present in very small amounts. Examples of high resolution detection include the DNA present in amplified extrachromosomal nucleoli, chromomeres of lampbrush chromosomes, mitochondria, chloroplasts and mycoplasmal particles. In immunoelectron microscopy using the immunogold technique, the DNA was localized in distinct substructures such as the "fibrillar centers" of nucleoli and certain stromal centers in chloroplasts. The antibody also reacts with DNA of chromatin of living cells, as shown by microinjection into cultured mitotic cells and into nuclei of amphibian oocytes. The potential value and the limitations of immunocytochemical DNA detection are discussed.}, subject = {Cytologie}, language = {en} } @phdthesis{Heinz2001, author = {Heinz, Werner J.}, title = {Identifikation und Charakterisierung von PHR3, einem zu der PHR/GAS-Familie homologen Gen bei Candida albicans}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1179719}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2001}, abstract = {Es konnte mit PHR3 bei Candida albicans ein drittes GAS-homologes Gen nachgewiesen werden. Dieses weist {\"u}berzeugende {\"U}bereinstimmungen der Nuklein- und Aminos{\"a}urensequenz und mit der fehlenden GPI-Verankerungsstelle und der pH-konstitutiven Expression auch interessante Unterschiede zu den bisher bekannten Genen der PHR-Familie auf. Eine funktionelle Homologie zu den weiteren PHR-Genen bei Candida albicans konnte nicht belegt werden. Es sind bisher in verschiedenen Spezies mehrere homologe Gene dieser Familie nachgewiesen worden. So sind auch bei Candida albicans weitere m{\"o}glich und die endg{\"u}ltige Zahl der PHR-Gene wird erst nach Abschluß des Candida albicans-Genomprojektes bestimmt werden k{\"o}nnen. Der Zweck mehrerer homologer Gene ist insbesondere f{\"u}r die bei unterschiedlichen pH-Werten vorliegenden Proteine Phr1p und Phr2p noch nicht bekannt. Eine m{\"o}gliche Erkl{\"a}rung ist, dass ihre Translation auf unterschiedliche Weise die Expression anderer Gene oder die Prozessierung und Funktion von Proteinen beeinflusst. Eine solche feine Regulation von Wachstums- und Virulenzfaktoren und somit eine Anpassung an Umweltbedingungen und Infektionswege ist f{\"u}r die Pathogenit{\"a}t von Candida albicans von Bedeutung. Die spezifischen Faktoren f{\"u}r die Induktion von PHR3 sind, sollte eine differenzierte Regulation vorliegen, dagegen ebenso wenig wie f{\"u}r GAS4, als n{\"a}hestes verwandtes Gen, und f{\"u}r die weiteren GAS-Gene bekannt. Zum Nachweis einer solchen signalspezifischen Transkription sind Experimente mit anderen Versuchsanordnungen, mit welchen sich komplexere Milieus und Infektionswege untersuchen lassen, wie DNA-Chips oder induktionsabh{\"a}ngige Signalkassetten (Morschh{\"a}user et al., 1999; Staib et al., 1999) hilfreich. Da eine fehlende C-terminale Region bei GAS1 zur Sekretion eines vergr{\"o}ßerten Proteins mit Hypermannosylierung der serinreichen Region f{\"u}hrt (Popolo et Vai, 1998), erscheint auch eine extrazellul{\"a}re Funktion von Phr3p, welches dieses hydrophobe 3' Ende nativ nicht besitzt, m{\"o}glich. Dabei ist eine zu Phr1p und Phr2p {\"a}hnliche oder gleiche enzymatische Funktion, welche in Diskussion 112 unterschiedlichen Kompartimenten oder von unterschiedlicher Lokalisation aus den Aufbau der Zellwand beeinflusst, denkbar.}, language = {de} } @article{SpinnerWilleSchwerdtfegeretal.2015, author = {Spinner, Christoph D and Wille, Florian and Schwerdtfeger, Christiane and Thies, Philipp and Tanase, Ursula and Von Figura, Guido and Schmid, Roland M and Heinz, Werner J and Klinker, Hartwig Hf}, title = {Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and MAI infection: some new conflicting data}, series = {AIDS Research and Therapy}, volume = {12}, journal = {AIDS Research and Therapy}, number = {1}, doi = {10.1186/s12981-014-0041-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144058}, year = {2015}, abstract = {Background: While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5'-diphosph-gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power. Methods: We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used. Results: High intra-personal variability in raltegravir serum levels was seen. Comparable C\(_{max}\) concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While C\(_{max}\) seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC(12) is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels. Conclusions: We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations.}, language = {en} } @article{MuellerGirardHopfneretal.2016, author = {M{\"u}ller, Stefanie H. and Girard, Simon L. and Hopfner, Franziska and Merner, Nancy D. and Bourassa, Cynthia V. and Lorenz, Delia and Clark, Lorraine N. and Tittmann, Lukas and Soto-Ortolaza, Alexandra I. and Klebe, Stephan and Hallett, Mark and Schneider, Susanne A. and Hodgkinson, Colin A. and Lieb, Wolfgang and Wszolek, Zbigniew K. and Pendziwiat, Manuela and Lorenzo-Betancor, Oswaldo and Poewe, Werner and Ortega-Cubero, Sara and Seppi, Klaus and Rajput, Alex and Hussl, Anna and Rajput, Ali H. and Berg, Daniela and Dion, Patrick A. and Wurster, Isabel and Shulman, Joshua M. and Srulijes, Karin and Haubenberger, Dietrich and Pastor, Pau and Vilari{\~n}o-G{\"u}ell, Carles and Postuma, Ronald B. and Bernard, Genevi{\`e}ve and Ladwig, Karl-Heinz and Dupr{\´e}, Nicolas and Jankovic, Joseph and Strauch, Konstantin and Panisset, Michel and Winkelmann, Juliane and Testa, Claudia M. and Reischl, Eva and Zeuner, Kirsten E. and Ross, Owen A. and Arzberger, Thomas and Chouinard, Sylvain and Deuschl, G{\"u}nther and Louis, Elan D. and Kuhlenb{\"a}umer, Gregor and Rouleau, Guy A.}, title = {Genome-wide association study in essential tremor identifies three new loci}, series = {Brain}, volume = {139}, journal = {Brain}, doi = {10.1093/brain/aww242}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186541}, pages = {3163-3169}, year = {2016}, abstract = {We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.}, language = {en} } @article{UllmannSchmidtHieberBertzetal.2016, author = {Ullmann, Andrew J. and Schmidt-Hieber, Martin and Bertz, Hartmut and Heinz, Werner J. and Kiehl, Michael and Kr{\"u}ger, William and Mousset, Sabine and Neuburger, Stefan and Neumann, Silke and Penack, Olaf and Silling, Gerda and Vehreschild, J{\"o}rg Janne and Einsele, Hermann and Maschmeyer, Georg}, title = {Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016}, series = {Annals of Hematology}, volume = {95}, journal = {Annals of Hematology}, number = {9}, organization = {Infectious Diseases Working Party of the German Society for Hematology and Medical Oncology (AGIHO/DGHO) and the DAG-KBT (German Working Group for Blood and Marrow Transplantation)}, doi = {10.1007/s00277-016-2711-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187587}, pages = {1435-1455}, year = {2016}, abstract = {Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria.}, language = {en} }