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204. Campylobacter jejuni impairs sodium transport and epithelial barrier function via cytokine release in human colon

Author

Bucker, R., Krug, S. M., Moos, V., Bojarski, C., Schweiger, M. R., Kerick, M., Fromm, A., Janssen, S., Fromm, M., Hering, N. A., Siegmund, B., Schneider, T., Barmeyer, C., Schulzke, J. D., Bucker, R., Krug, S. M., Moos, V., Bojarski, C., Schweiger, M. R., Kerick, M., Fromm, A., Janssen, S., Fromm, M., Hering, N. A., Siegmund, B., Schneider, T., Barmeyer, C., and Schulzke, J. D.

Abstract

Campylobacter jejuni is the most prevalent cause of foodborne bacterial enteritis worldwide. Patients present with diarrhea and immune responses lead to complications like arthritis and irritable bowel syndrome. Although studies exist in animal and cell models, we aimed at a functional and structural characterization of intestinal dysfunction and the involved regulatory mechanisms in human colon. First, in patients' colonic biopsies, sodium malabsorption was identified as an important diarrheal mechanism resulting from hampered epithelial ion transport via impaired epithelial sodium channel (ENaC) beta- and gamma-subunit. In addition, barrier dysfunction from disrupted epithelial tight junction proteins (claudin-1, -3, -4, -5, and -8), epithelial apoptosis, and appearance of lesions was detected, which cause leak-flux diarrhea and can perpetuate immune responses. Importantly, these effects in human biopsies either represent direct action of Campylobacter jejuni (ENaC impairment) or are caused by proinflammatory signaling (barrier dysfunction). This was revealed by regulator analysis from RNA-sequencing (cytometric bead array-checked) and confirmed in cell models, which identified interferon-gamma, TNF alpha, IL-13, and IL-1 beta. Finally, bioinformatics' predictions yielded additional information on protective influences like vitamin D, which was confirmed in cell models. Thus, these are candidates for intervention strategies against C. jejuni infection and post-infectious sequelae, which result from the permissive barrier defect along the leaky gut.

Published
2018

205. Validation of the 'United Registries for Clinical Assessment and Research' [UR-CARE], a European online registry for clinical care and research in inflammatory bowel disease

Author

Burisch, J., Gisbert, J.P., Siegmund, B., Bettenworth, D., Thomsen, S.B., Cleynen, Isabelle, Cremer, Anneline, Sheng Ding, N.J., Furfaro, F., Galanopoulos, M., Grunert, P.C., Hanzel, J., Ivanovski, T.K., Krustins, E., Noor, N., O'Morain, N., Rodríguez-Lago, I., Scharl, M., Tua, J., Uzzan, M., Yassin, N.A., Baert, Filip, Langholz, E., Burisch, J., Gisbert, J.P., Siegmund, B., Bettenworth, D., Thomsen, S.B., Cleynen, Isabelle, Cremer, Anneline, Sheng Ding, N.J., Furfaro, F., Galanopoulos, M., Grunert, P.C., Hanzel, J., Ivanovski, T.K., Krustins, E., Noor, N., O'Morain, N., Rodríguez-Lago, I., Scharl, M., Tua, J., Uzzan, M., Yassin, N.A., Baert, Filip, and Langholz, E.

Abstract

Background: The 'United Registries for Clinical Assessment and Research' [UR-CARE] database is an initiative of the European Crohn's and Colitis Organisation [ECCO] to facilitate daily patient care and research studies in inflammatory bowel disease [IBD]. Herein, we sought to validate the database by using fictional case histories of patients with IBD that were to be entered by observers of varying experience in IBD. Methods: Nineteen observers entered five patient case histories into the database. After 6 weeks, all observers entered the same case histories again. For each case history, 20 key variables were selected to calculate the accuracy for each observer. We assumed that the database was such that = 90% of the entered data would be correct. The overall proportion of correctly entered data was calculated using a beta-binomial regression model to account for inter-observer variation and compared to the expected level of validity. Re-test reliability was assessed using McNemar's test. Results: For all case histories, the overall proportion of correctly entered items and their confidence intervals included the target of 90% (Case 1: 92% [88-94%]; Case 2: 87% [83-91%]; Case 3: 93% [90-95%]; Case 4: 97% [94-99%]; Case 5: 91% [87-93%]). These numbers did not differ significantly from those found 6 weeks later [NcNemar's test p > 0.05]. Conclusion: The UR-CARE database appears to be feasible, valid and reliable as a tool and easy to use regardless of prior user experience and level of clinical IBD experience. UR-CARE has the potential to enhance future European collaborations regarding clinical research in IBD., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

206. Frequenz familiärer Merkmale bei Adenokarzinomen des gastroösophagealen Übergangs und Magens in Berlin (EpihiB-Studie)

Author

Schölzchen, J, additional, Treese, C, additional, Thuß-Patience, P, additional, Mrózek, A, additional, Rau, B, additional, Weizsäcker, F, additional, Seeliger, H, additional, Hartmann, D, additional, Estévez-Schwarz, L, additional, Siegmund, B, additional, Horn, D, additional, Nassir, M, additional, and Daum, S, additional

Published
2018
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213. Liver fibrosis and metabolic alterations in adults with homozygous alpha1-antitrypsin deficiency (PiZZ genotype)

Author

Hamesch, K., primary, Woditsch, V., additional, Mandorfer, M., additional, Moeller, L.S., additional, Pereira, Vítor, additional, Delgado, M.P., additional, Reichert, M.C., additional, Heimes, C.V., additional, Voss, J., additional, Spivak, I., additional, Gueldiken, N., additional, Arslanow, A., additional, Schaefer, B., additional, Zoller, H., additional, Aigner, E., additional, Reiberger, T., additional, Martin, W., additional, Siegmund, B., additional, Eray, Y., additional, Danilo, B., additional, Stolk, J., additional, Gleiber, W., additional, Knipel, V., additional, Windisch, W., additional, Bals, R., additional, Koczulla, A.R., additional, Miravitlles, M., additional, Janciauskiene, S., additional, Genesca, J., additional, Lammert, F., additional, Trauner, M., additional, Krag, A., additional, Trautwein, C., additional, and Strnad, P., additional

Published
2018
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214. Erratum: Campylobacter jejuni impairs sodium transport and epithelial barrier function via cytokine release in human colon

Author

Bücker, R., primary, Krug, S.M., additional, Moos, V., additional, Bojarski, C., additional, Schweiger, M.R., additional, Kerick, M., additional, Fromm, A., additional, Janßen, S., additional, Fromm, M., additional, Hering, N.A., additional, Siegmund, B., additional, Schneider, T., additional, Barmeyer, C., additional, and Schulzke, J.D., additional

Published
2018
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215. High prevalence and functional effects of serum antineuronal antibodies in patients with gastrointestinal disorders

Author

Lütt, A., primary, Michel, K., additional, Krüger, D., additional, Volz, M. S., additional, Nassir, M., additional, Schulz, E., additional, Poralla, L., additional, Tangermann, P., additional, Bojarski, C., additional, Höltje, M., additional, Teegen, B., additional, Stöcker, W., additional, Schemann, M., additional, Siegmund, B., additional, and Prüss, H., additional

Published
2018
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220. Liver Fibrosis and Metabolic Alterations in Adults with Homozygous Alpha1-antitrypsin Deficiency (PiZZ Genotype)

Author

Hamesch, K, additional, Heimes, C, additional, Mandorfer, M, additional, Moeller, L, additional, Pereira, V, additional, Pons, M, additional, Reichert, M, additional, Woditsch, V, additional, Voß, J, additional, Bretag, T, additional, Spivak, I, additional, Arslanow, A, additional, Krawczyk, M, additional, Wetzel, M, additional, Siegmund, B, additional, Aigner, E, additional, Schaefer, B, additional, Zoller, H, additional, Reiberger, T, additional, Yagmur, E, additional, Gleiber, W, additional, Bals, R, additional, Koczulla, A, additional, Miravittles, M, additional, Janciauskiene, S, additional, Bzdok, D, additional, Genesca, J, additional, Lammert, F, additional, Trauner, M, additional, Krag, A, additional, Trautwein, C, additional, and Strnad, P, additional

Published
2018
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221. Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A

Author

Eckhardt, C.L., Velzen, A.S. van, Peters, M., Astermark, J., Brons, P.P., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Hay, C.R.M., Haya, S., Heerde, W.L. van, Hermans, C., Holmstrom, M., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Gorkom, B.A.P., Leebeek, F.W.G., Liesner, R., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., Mcrae, S., Meijer, K., Mitchell, M., Morfini, M., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Smiers, F.J., Siegmund, B., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., INSIGHT Study Grp, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de malformations vasculaires congénitales, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), RS: CARIM School for Cardiovascular Diseases, Biochemie, Interne Geneeskunde, Pediatrics, Hematology, Epidemiology, Other departments, Paediatric Infectious Diseases / Rheumatology / Immunology, ACS - Amsterdam Cardiovascular Sciences, and AII - Amsterdam institute for Infection and Immunity

Subjects
Invasive mycoses and compromised host Translational research [N4i 2], Adult, medicine.medical_specialty, Age-related aspects of cancer [ONCOL 2], Time Factors, Adolescent, Genotype, Immunology, Mutation, Missense, Kaplan-Meier Estimate, Hemophilia A, DIAGNOSIS, Biochemistry, Gastroenterology, Young Adult, Interquartile range, Risk Factors, Internal medicine, medicine, Missense mutation, Humans, Cumulative incidence, Desmopressin, Genotyping, POLYMORPHISMS, Retrospective Studies, Hematology, Factor VIII, Cardiovascular diseases [NCEBP 14], business.industry, Incidence (epidemiology), DESMOPRESSIN, Cell Biology, Middle Aged, MILD, Antibodies, Neutralizing, Confidence interval, Treatment Outcome, business, medicine.drug, Follow-Up Studies
Abstract

Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 non-severe hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A. ( Blood . 2013; 122(11):1954-1962) © 2013 by The American Society of Hematology.

Published
2013

222. A guiding map for inflammation

Author

Netea, M.G., Balkwill, F., Chonchol, M., Cominelli, F., Donath, M.Y., Giamarellos-Bourboulis, E.J., Golenbock, D., Gresnigt, M.S., Heneka, M.T., Hoffman, H.M., Hotchkiss, R., Joosten, L.A.B., Kastner, D.L., Korte, M., Latz, E., Libby, P., Mandrup-Poulsen, T., Mantovani, A., Mills, K.H., Nowak, K.L., O'Neill, L.A., Pickkers, P., Poll, T. van der, Ridker, P.M., Schalkwijk, J., Schwartz, D.A., Siegmund, B., Steer, C.J., Tilg, H., Meer, J.W.M. van der, Veerdonk, F.L. van de, Dinarello, C.A., Netea, M.G., Balkwill, F., Chonchol, M., Cominelli, F., Donath, M.Y., Giamarellos-Bourboulis, E.J., Golenbock, D., Gresnigt, M.S., Heneka, M.T., Hoffman, H.M., Hotchkiss, R., Joosten, L.A.B., Kastner, D.L., Korte, M., Latz, E., Libby, P., Mandrup-Poulsen, T., Mantovani, A., Mills, K.H., Nowak, K.L., O'Neill, L.A., Pickkers, P., Poll, T. van der, Ridker, P.M., Schalkwijk, J., Schwartz, D.A., Siegmund, B., Steer, C.J., Tilg, H., Meer, J.W.M. van der, Veerdonk, F.L. van de, and Dinarello, C.A.

Abstract

Contains fulltext : 177132.pdf (publisher's version ) (Closed access), Biologists, physicians and immunologists have contributed to the understanding of the cellular participants and biological pathways involved in inflammation. Here, we provide a general guide to the cellular and humoral contributors to inflammation as well as to the pathways that characterize inflammation in specific organs and tissues.

Published
2017

225. Primary brain tumours and specific serum immunoglobulin E: a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort

Author

Schlehofer, B, Siegmund, B, Linseisen, J, Schüz, J, Rohrmann, S, Becker, S, Michaud, D, Melin, B, Bas Bueno-De-Mesquita, H, Peeters, P, Vineis, P, Tjonneland, A, Olsen, A, Overvad, K, Romieu, I, Boeing, H, Aleksandrova, K, Trichopoulou, A, Bamia, C, Lagiou, P, Sacerdote, C, Palli, D, Panico, S, Sieri, S, and Tumino, R

Abstract

Background: Case-control studies suggest that patients with allergic diseases have a lower risk of developing glioma but not meningioma or schwannoma. However, those data can be differentially biased. Prospective studies with objective measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood obtained before cancer diagnosis could help to clarify whether an aetiological association exists. Methods: The present case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) measured specific serum IgE as a biomarker for the most common inhalant allergens in 275 glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the ImmunoCAP specific IgE test. Subjects with an IgE level ≥0.35 kUA/l (kilo antibody units per litre) were classified as sensitized by allergens. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional logistic regression models for each tumour subtype. The effect of dose-response relationship was assessed in five increasing IgE level categories to estimate P-values for trend. Results: The risk of glioma was inversely related to allergic sensitization (OR = 0.73; 95% CI 0.51-1.06), especially pronounced in women (OR = 0.53; 95% CI 0.30-0.95). In dose-response analyses, for high-grade glioma, the lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04). No association was seen for meningioma and schwannoma. Conclusion: The results, based on serum samples prospectively collected in a cohort study, provide some support for the hypothesis that individuals with allergic sensitization are at reduced risk of glioma and confirm results from previous case-control studies. © 2011 John Wiley and Sons A/S.

Published
2016

226. Results of the fifth scientific workshop of the ECCO (II): Pathophysiology of perianal fistulizing disease

Author

Siegmund, B. Feakins, R.M. Bamias, G. Ludvig, J.C. Teixeira, F.V. Rogler, G. Scharl, M.

Abstract

The fifth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of fistulas to the disease course of patients with Crohn's disease (CD). The objectives were to reach a better understanding of the pathophysiological mechanisms underlying the formation of CD fistulas; to identify future topics in fistula research that could provide insights into pathogenesis; to develop novel therapeutic approaches; and to review current therapeutic strategies (with clarification of existing approaches to prevention, diagnosis and treatment). The results of the workshop are presented in two separate manuscripts. This manuscript describes current state-of-the-art knowledge about fistula pathogenesis, including the roles of epithelial-tomesenchymal transition and cytokine matrix remodelling enzymes, and highlights the common association between fistulas and stenosis in CD. The review also considers the possible roles that genetic predisposition and intestinal microbiota play in fistula development. Finally, it proposes future directions and needs for fistula research that might substantially increase our understanding of this complex condition and help unravel novel therapeutic strategies and specific targets for treatment. Overall, it aims to highlight unanswered questions in fistula research and to provide a framework for future research work. © 2015 European Crohn's and Colitis Organisation (ECCO).

Published
2016

231. CapsoCam SV-1 versus PillCam SB 3: Prospektive randomisierte Multicenter-Studie zum Vergleich beider Dünnarmkapseln bei obskurer gastrointestinaler Blutung

Author

Zwinger, LL, additional, Siegmund, B, additional, Stroux, A, additional, Adler, A, additional, Veltzke-Schlieker, W, additional, Wentrup, R, additional, Jürgensen, C, additional, Wiedenmann, B, additional, Wiedbrauck, F, additional, Hollerbach, S, additional, Liceni, T, additional, and Bojarski, C, additional

Published
2017
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233. Europaweite Studie zur Leberbeteiligung beim Alpha1-Antitrypsin-Mangel offenbart die Leberfibrose und -steatose in Erwachsenen mit dem homozygoten PiZZ-Genotyp

Author

Hamesch, K, additional, Heimes, C, additional, Woditsch, V, additional, Voß, J, additional, Bretag, T, additional, Scholten, D, additional, Spivak, I, additional, Yagmur, E, additional, Wetzel, M, additional, Siegmund, B, additional, Reichert, M, additional, Arslanow, A, additional, Bals, R, additional, Lammert, F, additional, Stolk, J, additional, Janciauskiene, S, additional, Mandorfer, M, additional, Trauner, M, additional, Trautwein, C, additional, and Strnad, P, additional

Published
2017
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235. Prospektive Multi-Center-Studie zur Evaluation eines Point-of-Care-Tests (POCT) bei Zöliakie

Author

Tangermann, P, additional, Branchi, F, additional, Aschenbeck, J, additional, Schubert, S, additional, Schröder, A, additional, Heller, F, additional, Möhler, U, additional, Spitz, W, additional, Graefe, U, additional, Radke, M, additional, Trenkel, S, additional, Schmitt, M, additional, Siegmund, B, additional, Daum, S, additional, Bojarski, C, additional, and Schumann, M, additional

Published
2017
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237. Retrospektive Multicenter-Studie über die Indikationen, Komplikationen sowie das Outcome der modularen Cholangioskopie bei 250 Untersuchungen mit SpyGlassTMDS

Author

Turowski, F, additional, Hügle, U, additional, Dormann, A, additional, Bechtler, M, additional, Jakobs, R, additional, Gottschalk, U, additional, Nötzel, E, additional, Hartmann, D, additional, Lorenz, A, additional, Kolligs, F, additional, Veltzke-Schlieker, W, additional, Adler, A, additional, Becker, O, additional, Wiedenmann, B, additional, Bürgel, N, additional, Tröger, H, additional, Schumann, M, additional, Siegmund, B, additional, Daum, S, additional, and Bojarski, C, additional

Published
2017
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238. Multi-center study of liver disease in alpha1-antitrypsin deficiency: non-invasive evaluation of liver fibrosis in homozygous PiZZ patients

Author

Hamesch, K., primary, Scholten, D., additional, Spivak, I., additional, Voss, J., additional, Bretag, T., additional, Wetzel, M., additional, Siegmund, B., additional, Reichert, M., additional, Bals, R., additional, Lammert, F., additional, Mandorfer, M., additional, Trauner, M., additional, Stolk, J., additional, Janciauskiene, S., additional, Trautwein, C., additional, and Strnad, P., additional

Published
2017
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241. High-resolution microbiota flow cytometry reveals dynamic colitis-associated changes in fecal bacterial composition

Author

Zimmermann, J., Hübschmann, Thomas, Schattenberg, Florian, Schumann, Joachim, Durek, P., Riedel, R., Friedrich, M., Glauben, R., Siegmund, B., Radbruch, A., Müller, Susann, Chang, H.-D., Zimmermann, J., Hübschmann, Thomas, Schattenberg, Florian, Schumann, Joachim, Durek, P., Riedel, R., Friedrich, M., Glauben, R., Siegmund, B., Radbruch, A., Müller, Susann, and Chang, H.-D.

Abstract

Using high-resolution flow cytometry of bacterial shape (forward scatter) and DNA content (DAPI staining), we detected dramatic differences in the fecal microbiota composition during murine colitis that were validated using 16S rDNA sequencing. This innovative method provides a fast and inexpensive tool to interrogate the microbiota on the single-cell level.

Published
2016

242. Determination of sulfur and nitrogen compounds during the processing of dry fermented sausages and their relation to amino acid generation

Author

Corral, Sara, Leitner, E., Siegmund, B., Flores Llovera, Mónica, Corral, Sara, Leitner, E., Siegmund, B., and Flores Llovera, Mónica

Abstract

© 2015 Elsevier Ltd. All rights reserved. The identification of odor-active sulfur and nitrogen compounds formed during the processing of dry fermented sausages was the objective of this study. In order to elucidate their possible origin, free amino acids (FAAs) were also determined. The volatile compounds present in the dry sausages were extracted using solvent assisted flavor evaporation (SAFE) and monitored by one and two-dimensional gas chromatography with different detectors: mass spectrometry (MS), nitrogen phosphorous (NPD), flame photometric (FPD) detectors, as well as gas chromatography-olfactometry. A total of seventeen sulfur and nitrogen compounds were identified and quantified. Among them, 2-acetyl-1-pyrroline was the most potent odor active compound, followed by methional, ethylpyrazine and 2,3-dihydrothiophene characterized by toasted, cooked potato, and nutty notes. The degradation of FAAs, generated during processing, was related to the production of aroma compounds, such as methionine forming methional and benzothiazole while ornithine was the precursor compound for 2-acetyl-1-pyrroline and glycine for ethylpyrazine.

Published
2016

243. Locally Increased Incidence of Periorbital Necrotizing Fasciitis.

Author

Schuh, A., Keidel, L., Siegmund, B., Otto,, S., Priglinger, S., and Hintschich, C.

Abstract

The article presents the case of five patients who were rushed to the eye hospital at Ludwig Maximilian University of Munich in Germany to discuss the locally increased incidence of periorbital necrotizing fasciitis (PNF) in the country. Also cited are the possible complications of PNF due to systemic toxicity like septicemia, cutaneous injuries, and multiorgan failures.

Published
2023
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244. Primary brain tumours andspecific serum immunoglobulin E: a case-control study nested in the EuropeanProspective Investigation into Cancer and Nutrition cohort

Author

Schlehofer B, Siegmund B, Linseisen J, Schüz J, Rohrmann S, Becker S, Michaud D, Melin B, Bas Bueno de Mesquita H, Peeters PH, Vineis P, Tjonneland A, Olsen A, Overvad K, Romieu I, Boeing H, Aleksandrova K, Trichopoulou A, Bamia C, Lagiou P, Sacerdote C, Palli D, Sieri S, Tumino R, Sanchez MJ, Rodriguez L, Dorronsoro M, Duell EJ, Chirlaque MD, Barricarte A, Borgquist S, Manjer J, Gallo V, Allen NE, Key TJ, Riboli E, Kaaks R, Wahrendorf J., PANICO, SALVATORE, Schlehofer, B, Siegmund, B, Linseisen, J, Schüz, J, Rohrmann, S, Becker, S, Michaud, D, Melin, B, Bas Bueno de Mesquita, H, Peeters, Ph, Vineis, P, Tjonneland, A, Olsen, A, Overvad, K, Romieu, I, Boeing, H, Aleksandrova, K, Trichopoulou, A, Bamia, C, Lagiou, P, Sacerdote, C, Palli, D, Panico, Salvatore, Sieri, S, Tumino, R, Sanchez, Mj, Rodriguez, L, Dorronsoro, M, Duell, Ej, Chirlaque, Md, Barricarte, A, Borgquist, S, Manjer, J, Gallo, V, Allen, Ne, Key, Tj, Riboli, E, Kaaks, R, and Wahrendorf, J.

Published
2011

245. Importance of bicarbonate transport for protection of cardiomyocytes against reoxygenation injury

Author

SCHAFER, C., LADILOV, Y. V., SIEGMUND, B., and PIPER, H. M.

Subjects
Ischemia -- Research, Reperfusion (Physiology) -- Research, Muscle cells -- Research, Heart cells -- Research, Bicarbonates -- Physiological aspects, Biological sciences
Abstract

Importance of bicarbonate transport for protection of cardiomyocytes against reoxygenation injury. Am J Physiol Heart Circ Physiol 278: H1457-H1463, 2000.--Isolated cardiomyocytes from adult rats were incubated in anoxic bicarbonate-buffered media at extracellular pH ([pH.sub.o]) 6.4 until a cytosolic [Ca.sup.2+] overload and intracellular pH ([pH.sub.i]) of 6.4 were reached. On reoxygenation, the pH of the medium was changed to 7.4 to activate the [Na.sup.+]/[H.sup.+]exchanger (NHE) and the [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] symporter (NBS). The reoxygenation was performed in the absence or presence of the NHE inhibitor HOE-642 (3 [micro]mol/l) and/or the NBS inhibitor DIDS (0.5 mmol/l), as in bicarbonate-free media. In reoxygenated control cells [ph.sub.i] rapidly recovered to the preanoxic level, and a burst of spontaneous oscillations of cytosolic [Ca.sup.2+] occurred, accompanied by the development of hypercontracture. When NBS and NHE were simultaneously inhibited during reoxygenation, [ph.sub.i] recovery was prevented, [Ca.sup.2+] oscillations were attenuated, and hypercontracture was abolished. Sole inhibition of NBS or NHE showed no protection against hypercontracture. In the absence of cytosolic acidosis, HOE-642 or DIDS did not prevent hypercontracture induced by [Ca.sup.2+] overload. The results demonstrate that simultaneous inhibition of NHE and NBS is needed to protect myocardial cells against reoxygenation-induced hypercontracture. ischemia; reperfusion; myocytes

Published
2000

247. Von Willebrand Factor antigen and age explain variation in baseline FVIII:C among nonsevere hemophilia A patients with the same F8 genotype (Arg593Cys and Asn618Ser)

Author

Loomans, J.I., Velzen, A.S. van, Eckhardt, C.L., Peters, M., Astermark, J., Brons, P.P., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Hay, C.R.M., Haya, S., Heerde, W.L. van, Hermans, C., Holmstroom, M., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Konigs, C., Kruip, M.J.H.A., Laros-Van Gorkom, B.A.P., Leebeek, F.W.G., Liesner, R., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., Mcrae, S., Meijer, K., Mitchell, M., Morfini, M., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Rangarajan, S., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Smiers, F.J., Siegmund, B., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., and Insight Rise Study Grp

Published
2014

248. Clinical presentation of inhibitor development in non-severe hemophilia A: half of patients have high titer inhibitors and present with bleeding complications

Author

Eckhardt, C.L., Loomans, J.I., Velzen, A.S. van, Peters, M., Astermark, J., Brons, P.P., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Hay, C.R.M., Haya, S., Heerde, W.L. van, Hermans, C., Holmstrom, M., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Laros-Gorkom, B.A.P. van, Leebeek, F.W.G., Liesner, R., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., Mcrae, S., Meijer, K., Mitchell, M., Morfini, M., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Rangarajan, S., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Smiers, F.J., Siegmund, B., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., and Insight Study Grp

Published
2014

249. Inhibitors increase the burden of disease in nonsevere haemophilia A patients - treatment strategies to obtain hemostasis

Author

Velzen, A.S. van, Eckhardt, C.L., Streefkerk, N., Peters, M., Astermark, J., Brons, P.P., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Hay, C.R.M., Haya, S., Heerde, W.L. van, Hermans, C., Holmstrom, M., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Gorkom, B.A.P.L. van, Leebeek, F.W.G., Liesner, R., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., McRae, S., Meijer, K., Morfini, M., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Rangarajan, S., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Smiers, F.J., Siegmund, B., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., and INSIGHT Study Grp

Published
2014

250. Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study

Author

Stallmach, A., primary, Langbein, C., additional, Atreya, R., additional, Bruns, T., additional, Dignass, A., additional, Ende, K., additional, Hampe, J., additional, Hartmann, F., additional, Neurath, M. F., additional, Maul, J., additional, Preiss, J. C., additional, Schmelz, R., additional, Siegmund, B., additional, Schulze, H., additional, Teich, N., additional, von Arnim, U., additional, Baumgart, D. C., additional, and Schmidt, C., additional

Published
2016
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