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3. Gene therapy for glioblestome multiforme: in vivo tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir

Author

Stockhammer, G., Brotchi, J., Leblanc, R., Bernstein, M., Schackert, G., Weber, F., Ostertag, C., Mulder, N. H., Mellstedt, H., Seiler, R., Yonekawa, Y., Twerdy, K., Kostron, H., Witte, O. De, Lambermont, M., Velu, T., Laneuville, P., Villemure, J.-G., Rutka, J. T., Warnke, P., Laseur, M., Mooij, J. J. A., Boëthius, J., Mariani, L., Meyer, M., Brändli, C., Frei, K., Könu, D., and Gianella-Borradori, A.

Published
1997
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9. Protective Effect of a 21-Aminosteroid during Experimental Pneumococcal Meningitis

Author

Lorenzi, S, Koedel, U, Frei, K, Bernatowicz, A, Fontana, A, Pfister, H-W, and University of Zurich

Subjects
2723 Immunology and Allergy, 570 Life sciences, biology, 610 Medicine & health, 2725 Infectious Diseases, 142-005 142-005
Abstract

This study investigated whether the 21-aminosteroid U74389F, an inhibitor of lipid peroxidation, attenuates pathophysiologic changes in experimental pneumococcal meningitis. Infected rats injected intravenously with vehicle and U74389F developed increases in regional cerebral blood flow (rCBF), intracranial pressure (ICP), brain water content, and white blood cells (WBC) in cerebrospinal fluid (CSF) within 8 h after intracisternal challenge. Pretreatment with or administration of U74389F 4 h after infection significantly reduced the increase in ICP but had no effect on rCBF increase. Moreover, U74389F pretreatment significantly reduced brain water content and CSF WBC count. In vitro, U74389F inhibited iron-dependent lipid peroxidation of astrocyte cultures and the production of tumor necrosis factor-a, interleukin-6, and nitric oxide by stimulated macrophages. These data suggest that U74389F modulates early pathophysiologic alterations in experimental pneumococcal meningitis

Published
2017

10. Prospective navigator-echo-based real-time triggering of fetal head movement for the reduction of artifacts

Author

Bonel, H., Frei, K., Raio, L., Meyer-Wittkopf, M., Remonda, L., Wiest, R., Bonel, H., Frei, K., Raio, L., Meyer-Wittkopf, M., Remonda, L., and Wiest, R.

Abstract

The purpose of this study was to evaluate the neuroimaging quality and accuracy of prospective real-time navigator-echo acquisition correction versus untriggered intrauterine magnetic resonance imaging (MRI) techniques. Twenty women in whom fetal motion artifacts compromised the neuroimaging quality of fetal MRI taken during the 28.7 ± 4week of pregnancy below diagnostic levels were additionally investigated using a navigator-triggered half-Fourier acquired single-shot turbo-spin echo (HASTE) sequence. Imaging quality was evaluated by two blinded readers applying a rating scale from 1 (not diagnostic) to 5 (excellent). Diagnostic criteria included depiction of the germinal matrix, grey and white matter, CSF, brain stem and cerebellum. Signal-difference-to-noise ratios (SDNRs) in the white matter and germinal zone were quantitatively evaluated. Imaging quality improved in 18/20 patients using the navigator echo technique (2.4 ± 0.58 vs. 3.65 ± 0.73 SD, p < 0.01 for all evaluation criteria). In 2/20 patients fetal movement severely impaired image quality in conventional and navigated HASTE. Navigator-echo imaging revealed additional structural brain abnormalities and confirmed diagnosis in 8/20 patients. The accuracy improved from 50% to 90%. Average SDNR increased from 0.7 ± 7.27 to 19.83 ± 15.71 (p < 0.01). Navigator-echo-based real-time triggering of fetal head movement is a reliable technique that can deliver diagnostic fetal MR image quality despite vigorous fetal movement

Published
2018

13. Extensive oxidative weathering in the aftermath of a late Neoproterozoic glaciation - Evidence from trace element and chromium isotope records in the Urucum district (Jacadigo Group) and Puga iron formations (Mato Grosso do Sul, Brazil)

Author

Frei, R., Døssing, L. N., Gaucher, C., Boggiani, P. C., Frei, K. M., Árting, T. Bech, Crowe, S. A., Freitas, B. T., Frei, R., Døssing, L. N., Gaucher, C., Boggiani, P. C., Frei, K. M., Árting, T. Bech, Crowe, S. A., and Freitas, B. T.

Published
2017

14. Erythropoietin reduces experimental autoimmune encephalomyelitis severity via neuroprotective mechanisms

Author

Moransard, M, Bednar, M, Frei, K, Gassmann, M, Ogunshola, O O, Moransard, M, Bednar, M, Frei, K, Gassmann, M, and Ogunshola, O O

Abstract

Treatment with erythropoietin (Epo) in experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis (MS), has consistently been shown to ameliorate disease progression and improve overall outcome. The effect has been attributed to modulation of the immune response and/or preservation of the central nervous system (CNS) tissue integrity. It remains unclear, however, if (a) Epo acts primarily in the CNS or the periphery and if (b) Epo’s beneficial effect in EAE is mainly due to maintaining CNS tissue integrity or to modulation of the immune response. If Epo acts primarily by modulating the immune system, where is this modulation required? In the periphery, the CNS or both?

Published
2017

15. Infusion of [Alpha]-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease

Author

Schiffmann, R., Murray, G. J., Treco, D., Daniel, P., Sellos-Moura, M., Myers, M., Quirk, J. M., Zirzow, G. C., Borowski, M., Loveday, K., Anderson, T., Gillespie, F., Oliver, K. L., Jeffries, N. O., Doo, E., Liang, T. J., Kreps, C., Gunter, K., Frei, K., Crutchfield, K., Selden, R. F., and Brady, R. O.

Subjects
Fabry's disease -- Research, Lysosomes -- Health aspects, Metabolic diseases -- Research, Science and technology
Abstract

Fabry disease is a lysosomal storage disorder caused by a deficiency of the lysosomal enzyme [Alpha]-galactosidase A ([Alpha]-gal A). This enzymatic defect results in the accumulation of the glycosphingolipid globotriaosylceramide ([Gb.sub.3]; also referred to as ceramidetrihexoside) throughout the body. To investigate the effects of purified [Alpha]-gal A, 10 patients with Fabry disease received a single i.v. infusion of one of five escalating dose levels of the enzyme. The objectives of this study were: (i) to evaluate the safety of administered [Alpha]-gal A, (ii) to assess the pharmacokinetics of i.v.-administered [Alpha]-gal A in plasma and liver, and (iii) to determine the effect of this replacement enzyme on hepatic, urine sediment and plasma concentrations of [Gb.sub.3]. [Alpha]-Gal A infusions were well tolerated in all patients. Immunohistochemical staining of liver tissue approximately 2 days after enzyme infusion identified [Alpha]-gal A in several cell types, including sinusoidal endothelial cells, Kupffer cells, and hepatocytes, suggesting diffuse uptake via the mannose 6-phosphate receptor. The tissue half-life in the liver was greater than 24 hr. After the single dose of [Alpha]-gal A, nine of the 10 patients had significantly reduced [Gb.sub.3] levels both in the liver and shed renal tubular epithelial cells in the urine sediment. These data demonstrate that single infusions of [Alpha]-gal A prepared from transfected human fibroblasts are both safe and biochemically active in patients with Fabry disease. The degree of substrate reduction seen in the study is potentially clinically significant in view of the fact that [Gb.sub.3] burden in Fabry patients increases gradually over decades. Taken together, these results suggest that enzyme replacement is likely to be an effective therapy for patients with this metabolic disorder.

Published
2000

16. Impact of endothelial tight junction alterations on cavernous malformation bleeding propensity

Author

Jakimovski, D, Schneider, H, Frei, K, Kennes, LN, and Bertalanffy, H

Subjects
bleeding propensity, ddc: 610, tight junction, 610 Medical sciences, Medicine, cavernous malformation
Abstract

Objective: Endothelial tight junction (TJ) expression in cerebral cavernous malformations (CCM) is mostly absent, which causes increased perilesional erythrocyte and fluid oozing. However, in a subset of CCM lesions, foci of preserved TJ staining are observed along endothelial cell contacts. We evaluated[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2014
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17. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

Author

Nalls, M.A. Pankratz, N. Lill, C.M. Do, C.B. Hernandez, D.G. Saad, M. Destefano, A.L. Kara, E. Bras, J. Sharma, M. Schulte, C. Keller, M.F. Arepalli, S. Letson, C. Edsall, C. Stefansson, H. Liu, X. Pliner, H. Lee, J.H. Cheng, R. Ikram, M.A. Ioannidis, J.P.A. Hadjigeorgiou, G.M. Bis, J.C. Martinez, M. Perlmutter, J.S. Goate, A. Marder, K. Fiske, B. Sutherland, M. Xiromerisiou, G. Myers, R.H. Clark, L.N. Stefansson, K. Hardy, J.A. Heutink, P. Chen, H. Wood, N.W. Houlden, H. Payami, H. Brice, A. Scott, W.K. Gasser, T. Bertram, L. Eriksson, N. Foroud, T. Singleton, A.B. Plagnol, V. Sheerin, U.-M. Simón-Sánchez, J. Lesage, S. Sveinbjörnsdóttir, S. Barker, R. Ben-Shlomo, Y. Berendse, H.W. Berg, D. Bhatia, K. de Bie, R.M.A. Biffi, A. Bloem, B. Bochdanovits, Z. Bonin, M. Bras, J.M. Brockmann, K. Brooks, J. Burn, D.J. Charlesworth, G. Chinnery, P.F. Chong, S. Clarke, C.E. Cookson, M.R. Cooper, J.M. Corvol, J.C. Counsell, C. Damier, P. Dartigues, J.-F. Deloukas, P. Deuschl, G. Dexter, D.T. van Dijk, K.D. Dillman, A. Durif, F. Dürr, A. Edkins, S. Evans, J.R. Foltynie, T. Dong, J. Gardner, M. Gibbs, J.R. Gray, E. Guerreiro, R. Harris, C. van Hilten, J.J. Hofman, A. Hollenbeck, A. Holton, J. Hu, M. Huang, X. Wurster, I. Mätzler, W. Hudson, G. Hunt, S.E. Huttenlocher, J. Illig, T. Jónsson, P.V. Lambert, J.-C. Langford, C. Lees, A. Lichtner, P. Limousin, P. Lopez, G. Lorenz, D. McNeill, A. Moorby, C. Moore, M. Morris, H.R. Morrison, K.E. Mudanohwo, E. O’sullivan, S.S. Pearson, J. Pétursson, H. Pollak, P. Post, B. Potter, S. Ravina, B. Revesz, T. Riess, O. Rivadeneira, F. Rizzu, P. Ryten, M. Sawcer, S. Schapira, A. Scheffer, H. Shaw, K. Shoulson, I. Sidransky, E. Smith, C. Spencer, C.C.A. Stefánsson, H. Bettella, F. Stockton, J.D. Strange, A. Talbot, K. Tanner, C.M. Tashakkori-Ghanbaria, A. Tison, F. Trabzuni, D. Traynor, B.J. Uitterlinden, A.G. Velseboer, D. Vidailhet, M. Walker, R. van de Warrenburg, B. Wickremaratchi, M. Williams, N. Williams-Gray, C.H. Winder-Rhodes, S. Stefánsson, K. Hardy, J. Factor, S. Higgins, D. Evans, S. Shill, H. Stacy, M. Danielson, J. Marlor, L. Williamson, K. Jankovic, J. Hunter, C. Simon, D. Ryan, P. Scollins, L. Saunders-Pullman, R. Boyar, K. Costan-Toth, C. Ohmann, E. Sudarsky, L. Joubert, C. Friedman, J. Chou, K. Fernandez, H. Lannon, M. Galvez-Jimenez, N. Podichetty, A. Thompson, K. Lewitt, P. Deangelis, M. O'brien, C. Seeberger, L. Dingmann, C. Judd, D. Marder, K. Fraser, J. Harris, J. Bertoni, J. Peterson, C. Rezak, M. Medalle, G. Chouinard, S. Panisset, M. Hall, J. Poiffaut, H. Calabrese, V. Roberge, P. Wojcieszek, J. Belden, J. Jennings, D. Marek, K. Mendick, S. Reich, S. Dunlop, B. Jog, M. Horn, C. Uitti, R. Turk, M. Ajax, T. Mannetter, J. Sethi, K. Carpenter, J. Dill, B. Hatch, L. Ligon, K. Narayan, S. Blindauer, K. Abou-Samra, K. Petit, J. Elmer, L. Aiken, E. Davis, K. Schell, C. Wilson, S. Velickovic, M. Koller, W. Phipps, S. Feigin, A. Gordon, M. Hamann, J. Licari, E. Marotta-Kollarus, M. Shannon, B. Winnick, R. Simuni, T. Videnovic, A. Kaczmarek, A. Williams, K. Wolff, M. Rao, J. Cook, M. Fernandez, M. Kostyk, S. Hubble, J. Campbell, A. Reider, C. Seward, A. Camicioli, R. Carter, J. Nutt, J. Andrews, P. Morehouse, S. Stone, C. Mendis, T. Grimes, D. Alcorn-Costa, C. Gray, P. Haas, K. Vendette, J. Sutton, J. Hutchinson, B. Young, J. Rajput, A. Klassen, L. Shirley, T. Manyam, B. Simpson, P. Whetteckey, J. Wulbrecht, B. Truong, D. Pathak, M. Frei, K. Luong, N. Tra, T. Tran, A. Vo, J. Lang, A. Kleiner-Fisman, G. Nieves, A. Johnston, L. So, J. Podskalny, G. Giffin, L. Atchison, P. Allen, C. Martin, W. Wieler, M. Suchowersky, O. Furtado, S. Klimek, M. Hermanowicz, N. Niswonger, S. Shults, C. Fontaine, D. Aminoff, M. Christine, C. Diminno, M. Hevezi, J. Dalvi, A. Kang, U. Richman, J. Uy, S. Sahay, A. Gartner, M. Schwieterman, D. Hall, D. Leehey, M. Culver, S. Derian, T. Demarcaida, T. Thurlow, S. Rodnitzky, R. Dobson, J. Lyons, K. Pahwa, R. Gales, T. Thomas, S. Shulman, L. Weiner, W. Dustin, K. Singer, C. Zelaya, L. Tuite, P. Hagen, V. Rolandelli, S. Schacherer, R. Kosowicz, J. Gordon, P. Werner, J. Serrano, C. Roque, S. Kurlan, R. Berry, D. Gardiner, I. Hauser, R. Sanchez-Ramos, J. Zesiewicz, T. Delgado, H. Price, K. Rodriguez, P. Wolfrath, S. Pfeiffer, R. Davis, L. Pfeiffer, B. Dewey, R. Hayward, B. Johnson, A. Meacham, M. Estes, B. Walker, F. Hunt, V. O'neill, C. Racette, B. Swisher, L. Dijamco, C. Conley, E.D. Dorfman, E. Tung, J.Y. Hinds, D.A. Mountain, J.L. Wojcicki, A. Lew, M. Klein, C. Golbe, L. Growdon, J. Wooten, G.F. Watts, R. Guttman, M. Goldwurm, S. Saint-Hilaire, M.H. Baker, K. Litvan, I. Nicholson, G. Nance, M. Drasby, E. Isaacson, S. Burn, D. Pramstaller, P. Al-Hinti, J. Moller, A. Sherman, S. Roxburgh, R. Slevin, J. Perlmutter, J. Mark, M.H. Huggins, N. Pezzoli, G. Massood, T. Itin, I. Corbett, A. Chinnery, P. Ostergaard, K. Snow, B. Cambi, F. Kay, D. Samii, A. Agarwal, P. Roberts, J.W. Higgins, D.S. Molho, E. Rosen, A. Montimurro, J. Martinez, E. Griffith, A. Kusel, V. Yearout, D. Factor, S. Zabetian, C. Clark, L.N. Liu, X. Lee, J.H. Cheng Taub, R. Louis, E.D. Cote, L.J. Waters, C. Ford, B. Fahn, S. Vance, J.M. Beecham, G.W. Martin, E.R. Nuytemans, K. Pericak-Vance, M.A. Haines, J.L. Destefano, A. Seshadri, S. Choi, S.H. Frank, S. Bis, J.C. Psaty, B.M. Rice, K. Longstreth, W.T., Jr. Ton, T.G.N. Jain, S. van Duijn, C.M. Uitterlinden, A.G. Verlinden, V.J. Koudstaal, P.J. Singleton, A. Cookson, M. Gibbs, J.R. Hernandez, D. Nalls, M. Zonderman, A. Ferrucci, L. Johnson, R. Longo, D. O'brien, R. Traynor, B. Troncoso, J. van der Brug, M. Zielke, R. Weale, M. Ramasamy, A. Dardiotis, E. Tsimourtou, V. Spanaki, C. Plaitakis, A. Bozi, M. Stefanis, L. Vassilatis, D. Koutsis, G. Panas, M. Hadjigeorgiou, G.M. Lunnon, K. Lupton, M. Powell, J. Parkkinen, L. Ansorge, O. International Parkinson's Disease Genomics Consortium (IPDGC) Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI) 23andMe GenePD NeuroGenetics Research Consortium (NGRC) Hussman Institute of Human Genomics (HIHG) The Ashkenazi Jewish Dataset Investigator Cohorts for Health Aging Research in Genetic Epidemiology (CHARGE) North American Brain Expression Consortium (NABEC) United Kingdom Brain Expression Consortium (UKBEC) Greek Parkinson's Disease Consortium Alzheimer Genetic Analysis Group

Abstract

We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10-16). We also show six risk loci associated with proximal gene expression or DNA methylation. © 2014 Nature America, Inc. All rights reserved.

Published
2014

18. Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib - a phase II trial

Author

Hegi, M E, Diserens, A C, Bady, P, Kamoshima, Y, Kouwenhoven, M C M, Delorenzi, M, Lambiv, W L, Hamou, M F, Matter, M S, Koch, A, Heppner, F L, Yonekawa, Y, Merlo, A, Frei, K, Mariani, L, Hofer, S, and University of Zurich

Subjects
10180 Clinic for Neurosurgery, 10032 Clinic for Oncology and Hematology, 610 Medicine & health, 2730 Oncology, 1306 Cancer Research
Published
2011

19. Novel human pathological mutations. Gene symbol: THAP1. Disease: dystonia 6

Author

Xiao, J., Zhao, Y., Bastian, R. W., Perlmutter, J. S., Racette, B. A., Tabbal, S. D., Karimi, M., Paniell, R., Blitzer, A., Batish, S. D., Wszolek, Z. K., Uitti, R. J., Gerpen, J. A., Peter Hedera, Simon, D. K., Tarsy, D., Truong, D. D., Frei, K. P., Pfeiffer, R. F., Gong, S., and Ledoux, M. S.

Subjects
DNA-Binding Proteins, Amino Acid Substitution, Base Sequence, Dystonia Musculorum Deformans, Mutation, Missense, Humans, Nuclear Proteins, Apoptosis Regulatory Proteins, Codon
Published
2011

21. Tracing the dynamic life story of a bronze age female

Author

Margarita Frei, K., Mannering, U., Kristiansen, K., Allentoft, M.E., Wilson, A.S., Skals, I., Tridico, S., Louise Nosch, M., Willerslev, E., Clarke, L., Frei, R., Margarita Frei, K., Mannering, U., Kristiansen, K., Allentoft, M.E., Wilson, A.S., Skals, I., Tridico, S., Louise Nosch, M., Willerslev, E., Clarke, L., and Frei, R.

Abstract

Ancient human mobility at the individual level is conventionally studied by the diverse application of suitable techniques (e.g. aDNA, radiogenic strontium isotopes, as well as oxygen and lead isotopes) to either hard and/or soft tissues. However, the limited preservation of coexisting hard and soft human tissues hampers the possibilities of investigating high-resolution diachronic mobility periods in the life of a single individual. Here, we present the results of a multidisciplinary study of an exceptionally well preserved circa 3.400-year old Danish Bronze Age female find, known as the Egtved Girl. We applied biomolecular, biochemical and geochemical analyses to reconstruct her mobility and diet. We demonstrate that she originated from a place outside present day Denmark (the island of Bornholm excluded), and that she travelled back and forth over large distances during the final months of her life, while consuming a terrestrial diet with intervals of reduced protein intake. We also provide evidence that all her garments were made of non-locally produced wool. Our study advocates the huge potential of combining biomolecular and biogeochemical provenance tracer analyses to hard and soft tissues of a single ancient individual for the reconstruction of high-resolution human mobility.

Published
2015

25. How stemlike are sphere cultures from long-term cancer cell lines? Lessons from mouse glioma models

Author

Ahmad, M, Frei, K, Willscher, E, Stefanski, A, Kaulich, K, Roth, P, Stühler, K, Reifenberger, G, Binder, H, Weller, M, Ahmad, M, Frei, K, Willscher, E, Stefanski, A, Kaulich, K, Roth, P, Stühler, K, Reifenberger, G, Binder, H, and Weller, M

Abstract

Cancer stem cells may mediate therapy resistance and recurrence in various types of cancer, including glioblastoma. Cancer stemlike cells can be isolated from long-term cancer cell lines, including glioma lines. Using sphere formation as a model for cancer cell stemness in vitro, we derived sphere cultures from SMA-497, SMA-540, SMA-560, and GL-261 glioma cells. Gene expression and proteomics profiling demonstrated that sphere cultures uniformly showed an elevated expression of stemness-associated genes, notably including CD44. Differences in neural lineage marker expression between nonsphere and sphere cultures were heterogeneous except for a uniform reduction of β-III-tubulin in sphere cultures. All sphere cultures showed slower growth. Self-renewal capacity was influenced by medium conditions but not nonsphere versus sphere culture phenotype. Sphere cultures were more resistant to irradiation, whereas both nonsphere and sphere cultures were highly resistant to temozolomide. Nonsphere cells formed more aggressive tumors in syngeneic mice than sphere cells in all models except SMA-560. There were no major differences in vascularization or infiltration by T cells or microglia/macrophages between nonsphere and sphere cell-derived tumors implanted in syngeneic hosts. Together, these data indicate that mouse glioma cell lines may be induced in vitro to form spheres that acquire features of stemness, but they do not exhibit a uniform biologic phenotype, thereby challenging the view that they represent a superior model system.

Published
2014

29. Identification of a novel neuroligin in humans which binds to PSD-95 and has a widespread expression

Author

Bolliger, M F, Frei, K, Winterhalter, K H, and Gloor, S M

Subjects
Base Sequence, Sequence Homology, Amino Acid, Cell Adhesion Molecules, Neuronal, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Brain, Chromosome Mapping, Gene Expression, Membrane Proteins, Nerve Tissue Proteins, Rats, COS Cells, Animals, Humans, Amino Acid Sequence, RNA, Messenger, Carrier Proteins, Disks Large Homolog 4 Protein, Research Article, DNA Primers, Protein Binding
Abstract

Neuroligins, first discovered in rat brain, form a family of three synaptically enriched membrane proteins. Using reverse transcription-PCR of human brain polyadenylated RNA and extensive database searches, we identified the human homologues of the three rat neuroligins and a cDNA encoding a fourth member, which we named neuroligin 4. Neuroligin 4 has 63-73% amino acid identity with the other members of the human neuroligin family, and the same predicted domain structure. DNA database analyses, furthermore, indicated that a possible fifth neuroligin gene may be present in the human genome. Northern-blot analysis revealed expression of neuroligin 4 in heart, liver, skeletal muscle and pancreas, but barely at all in brain. Overexpression of neuroligin 4 cDNA in COS-7 cells led to the production of a 110 kDa protein. Immunofluorescence analysis demonstrated that the protein was integrated into the plasma membrane. Overexpression of cDNAs encoding neuroligin 4 and the PDZ-domain protein, PSD-95, in COS-7 cells resulted in the formation of detergent-resistant complexes. Neuroligin 4 did not bind to ZO-1, another PDZ-domain protein. Together, our data show that the human neuroligin family is composed of at least one additional member, and suggest that neuroligin 4 may also be produced outside the central nervous system.

Published
2001

30. Expression of nogo-a is decreased with increasing gestational age in the human fetal brain

Author

Haybaeck, J, Lienos, I C, Dulay, R J, Bettermann, K, Miller, C L, Wälchli, T, Frei, K, Virgintino, D, Rizzi, M, Weis, S, Haybaeck, J, Lienos, I C, Dulay, R J, Bettermann, K, Miller, C L, Wälchli, T, Frei, K, Virgintino, D, Rizzi, M, and Weis, S

Abstract

Nogo is a member of the reticulon family. Our understanding of the physiological functions of the Nogo-A protein has grown over the last few years, and this molecule is now recognized as one of the most important axonal regrowth inhibitors present in central nervous system (CNS) myelin. Nogo-A plays other important roles in nervous system development, epilepsy, vascular physiology, muscle pathology, stroke, inflammation, and CNS tumors. Since the exact role of Nogo-A protein in human brain development is still poorly understood, we studied its cellular and regional distribution by immunohistochemistry in the frontal lobe of 30 human fetal brains. Nogo-A was expressed in the following cortical zones: ependyma, ventricular zone, subventricular zone, intermediate zone, subplate, cortical plate, and marginal zone. The number of positive cells decreased significantly with increasing gestational age in the subplate and marginal zone. Using different antibodies, changes in isoform expression and dimerization states could be shown between various cortical zones. The results demonstrate a significant change in the expression of Nogo-A during the development of the human brain. The effects of its time- and region-specific regulation have to be further studied in detail.

Published
2012

31. Patupilone (Epothilone B) for recurrent glioblastoma: Clinical outcome and translational analysis of a single-institution phase I/II trial

Author

Oehler, C, Frei, K, Rushin, E J, McSheehy, P M J, Weber, D, Allegrini, P R, Weniger, D, Lütolf, U M, Knuth, A, Yonekawa, Y, Barath, K, Broggini-Tenzer, A, Pruschy, M, Hofer, S, Oehler, C, Frei, K, Rushin, E J, McSheehy, P M J, Weber, D, Allegrini, P R, Weniger, D, Lütolf, U M, Knuth, A, Yonekawa, Y, Barath, K, Broggini-Tenzer, A, Pruschy, M, and Hofer, S

Abstract

Background: Patients with glioblastoma (GBM) inevitably develop recurrent or progressive disease after initial multimodal treatment and have a median survival of 6-9 months from time of progression. To date, there is no accepted standard treatment for GBM relapse or progression. Patupilone (EPO906) is a novel natural microtubule-stabilizing cytotoxic agent that crosses the blood-brain barrier and has been found to have preclinical activity in glioma models. Methods: This is a single-institution, early-phase I/II trial of GBM patients with tumor progression who qualified for second surgery with the goal of evaluating efficacy and safety of the single-agent patupilone (10 mg/m(2), every 3 weeks). Patients received patupilone 1 week prior to second surgery and every 3 weeks thereafter until tumor progression or toxicity. Primary end points were progression-free survival (PFS) and overall survival (OS) at 6 months as well as patupilone concentration in tumor tissue. Secondary end points were toxicity, patupilone concentration in plasma and translational analyses for predictive biomarkers. Results: Nine patients with a mean age of 54.6 ± 8.6 years were recruited between June 2008 and April 2010. Median survival and 1-year OS after second surgery were 11 months (95% CI, 5-17 months) and 45% (95% CI, 14-76), respectively. Median PFS was 1.5 months (95% CI, 1.3-1.7 months) and PFS6 was 22% (95% CI, 0-46), with 2 patients remaining recurrence-free at 9.75 and 22 months. At the time of surgery, the concentration of patupilone in tumor tissue was 30 times higher than in the plasma. Tumor response was not predictable by the tested biomarkers. Treatment was generally well tolerated with no hematological, but cumulative, though reversible sensory neuropathy grade ≤3 was seen in 2 patients (22%) at 8 months and grade 4 diarrhea in the 2nd patient (11%). Non-patupilone-related peri-operative complications occurred in 2 patients resulting in discontinuation of patupilone therapy. Th

Published
2012

32. Impairment of tight junctions and glucose transport in endothelial cells of human cerebral cavernous malformations

Author

Schneider, H, Errede, M, Ulrich, N H, Virgintino, D, Frei, K, Bertalanffy, H, Schneider, H, Errede, M, Ulrich, N H, Virgintino, D, Frei, K, and Bertalanffy, H

Abstract

Cerebral cavernous malformations (CCMs) often cause hemorrhages that can result in severe clinical manifestations, including hemiparesis and seizures. The underlying mechanisms of the aggressive behavior of CCMs are undetermined to date, but alterations of vascular matrix components may be involved. We compared the localization of the tight junction proteins (TJPs) in 12 CCM specimens and the expression of glucose transporter 1 (GLUT-1), which is sensitive to alterations in TJP levels, in 5 CCM specimens with those in 5 control temporal lobectomy specimens without CCM by immunofluorescence microscopy. The TJPs occludin, claudin-5, and zonula occludens ZO-1 were downregulated at intercellular contact sites and partly redistributed within the surrounding tissue in the CCM samples; there was also a marked reduction of GLUT-1 immunoreactivity compared with that in control specimens. Corresponding analysis using quantitative real-time reverse transcription polymerase chain reaction on 8 CCM and 8 control specimens revealed significant downregulation of mRNA expression of occludin, claudin-5, ZO-1, and GLUT-1. The altered expression and localization of the TJPs at interendothelial contact sites accompanied by a reduction of GLUT-1 expression in dilated CCM microvessels likely affect vascular matrix stability and may contribute to hemorrhages of CCMs.

Published
2011

33. STEM CELLS

Author

Cheng, L., primary, Huang, Z., additional, Zhou, W., additional, Wu, Q., additional, Rich, J., additional, Bao, S., additional, Baxter, P., additional, Mao, H., additional, Zhao, X., additional, Liu, Z., additional, Huang, Y., additional, Voicu, H., additional, Gurusiddappa, S., additional, Su, J. M., additional, Perlaky, L., additional, Dauser, R., additional, Leung, H.-c. E., additional, Muraszko, K. M., additional, Heth, J. A., additional, Fan, X., additional, Lau, C. C., additional, Man, T.-K., additional, Chintagumpala, M., additional, Li, X.-N., additional, Clark, P., additional, Zorniak, M., additional, Cho, Y., additional, Zhang, X., additional, Walden, D., additional, Shusta, E., additional, Kuo, J., additional, Sengupta, S., additional, Goel-Bhattacharya, S., additional, Kulkarni, S., additional, Cochran, B., additional, Cusulin, C., additional, Luchman, A., additional, Weiss, S., additional, Wu, M., additional, Fernandez, N., additional, Agnihotri, S., additional, Diaz, R., additional, Rutka, J., additional, Bredel, M., additional, Karamchandani, J., additional, Das, S., additional, Day, B., additional, Stringer, B., additional, Al-Ejeh, F., additional, Ting, M., additional, Wilson, J., additional, Ensbey, K., additional, Jamieson, P., additional, Bruce, Z., additional, Lim, Y. C., additional, Offenhauser, C., additional, Charmsaz, S., additional, Cooper, L., additional, Ellacott, J., additional, Harding, A., additional, Lickliter, J., additional, Inglis, P., additional, Reynolds, B., additional, Walker, D., additional, Lackmann, M., additional, Boyd, A., additional, Berezovsky, A., additional, Poisson, L., additional, Hasselbach, L., additional, Irtenkauf, S., additional, Transou, A., additional, Mikkelsen, T., additional, deCarvalho, A. C., additional, Emlet, D., additional, Del Vecchio, C., additional, Gupta, P., additional, Li, G., additional, Skirboll, S., additional, Wong, A., additional, Figueroa, J., additional, Shahar, T., additional, Hossain, A., additional, Lang, F., additional, Fouse, S., additional, Nakamura, J., additional, James, C. D., additional, Chang, S., additional, Costello, J., additional, Frerich, J. M., additional, Rahimpour, S., additional, Zhuang, Z., additional, Heiss, J. D., additional, Golebiewska, A., additional, Stieber, D., additional, Evers, L., additional, Lenkiewicz, E., additional, Brons, N. H. C., additional, Nicot, N., additional, Oudin, A., additional, Bougnaud, S., additional, Hertel, F., additional, Bjerkvig, R., additional, Barrett, M., additional, Vallar, L., additional, Niclou, S. P., additional, Hao, X., additional, Rahn, J., additional, Ujack, E., additional, Lun, X., additional, Cairncross, G., additional, Senger, D., additional, Robbins, S., additional, Harness, J., additional, Lerner, R., additional, Ihara, Y., additional, Santos, R., additional, Torre, J. D. L., additional, Lu, A., additional, Ozawa, T., additional, Nicolaides, T., additional, James, D., additional, Petritsch, C., additional, Higgins, D., additional, Schroeder, M., additional, Ball, B., additional, Milligan, B., additional, Meyer, F., additional, Sarkaria, J., additional, Henley, J., additional, Flavahan, W., additional, Hitomi, M., additional, Rahim, N., additional, Kim, Y., additional, Sloan, A., additional, Weil, R., additional, Nakano, I., additional, Li, M., additional, Lathia, J., additional, Hjelmeland, A., additional, Kaluzova, M., additional, Platt, S., additional, Kent, M., additional, Bouras, A., additional, Machaidze, R., additional, Hadjipanayis, C., additional, Kang, S.-G., additional, Kim, S.-H., additional, Huh, Y.-M., additional, Kim, E.-H., additional, Park, E.-K., additional, Chang, J. H., additional, Kim, S. H., additional, Hong, Y. K., additional, Kim, D. S., additional, Lee, S.-J., additional, Kim, E. H., additional, Kang, S. G., additional, Deleyrolle, L., additional, Sinyuk, M., additional, Goan, W., additional, Otvos, B., additional, Rohaus, M., additional, Oli, M., additional, Vedam-Mai, V., additional, Schonberg, D., additional, Lee, S.-T., additional, Chu, K., additional, Lee, S. K., additional, Kim, M., additional, Roh, J.-K., additional, Griveau, A., additional, Reichholf, B., additional, McMahon, M., additional, Rowitch, D., additional, Nitta, R., additional, Mitra, S., additional, Agarwal, M., additional, Bui, T., additional, Lin, J., additional, Adamson, C., additional, Martinez-Quintanilla, J., additional, Choi, S.-H., additional, Bhere, D., additional, Heidari, P., additional, He, D., additional, Mahmood, U., additional, Shah, K., additional, Gholamin, S., additional, Feroze, A., additional, Achrol, A., additional, Kahn, S., additional, Weissman, I., additional, Cheshier, S., additional, Sulman, E. P., additional, Wang, Q., additional, Mostovenko, E., additional, Liu, H., additional, Lichti, C. F., additional, Shavkunov, A., additional, Kroes, R. A., additional, Moskal, J. R., additional, Conrad, C. A., additional, Lang, F. F., additional, Emmett, M. R., additional, Nilsson, C. L., additional, Osuka, S., additional, Sampetrean, O., additional, Shimizu, T., additional, Saga, I., additional, Onishi, N., additional, Sugihara, E., additional, Okubo, J., additional, Fujita, S., additional, Takano, S., additional, Matsumura, A., additional, Saya, H., additional, Saito, N., additional, Fu, J., additional, Wang, S., additional, Yung, W. K. A., additional, Koul, D., additional, Schmid, R. S., additional, Irvin, D. M., additional, Vitucci, M., additional, Bash, R. E., additional, Werneke, A. M., additional, Miller, C. R., additional, Shinojima, N., additional, Takezaki, T., additional, Fueyo, J., additional, Gumin, J., additional, Gao, F., additional, Nwajei, F., additional, Marini, F. C., additional, Andreeff, M., additional, Kuratsu, J.-I., additional, Singh, S., additional, Burrell, K., additional, Koch, E., additional, Jalali, S., additional, Vartanian, A., additional, Sulman, E., additional, Wouters, B., additional, Zadeh, G., additional, Spelat, R., additional, Singer, E., additional, Matlaf, L., additional, McAllister, S., additional, Soroceanu, L., additional, Spiegl-Kreinecker, S., additional, Loetsch, D., additional, Laaber, M., additional, Schrangl, C., additional, Wohrer, A., additional, Hainfellner, J., additional, Marosi, C., additional, Pichler, J., additional, Weis, S., additional, Wurm, G., additional, Widhalm, G., additional, Knosp, E., additional, Berger, W., additional, Kuratsu, J.-i., additional, Tam, Q., additional, Tanaka, S., additional, Nakada, M., additional, Yamada, D., additional, Todo, T., additional, Hayashi, Y., additional, Hamada, J.-i., additional, Hirao, A., additional, Tilghman, J., additional, Ying, M., additional, Laterra, J., additional, Venere, M., additional, Chang, C., additional, Summers, M., additional, Rosenfeld, S., additional, Luk, S., additional, Iafrate, J., additional, Cahill, D., additional, Martuza, R., additional, Rabkin, S., additional, Chi, A., additional, Wakimoto, H., additional, Wirsching, H.-G., additional, Krishnan, S., additional, Frei, K., additional, Krayenbuhl, N., additional, Reifenberger, G., additional, Weller, M., additional, Tabatabai, G., additional, Man, J., additional, Shoemake, J., additional, and Yu, J., additional

Published
2013
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34. EXPERIMENTAL THERAPEUTICS AND PHARMACOLOGY

Author

Aaberg-Jessen, C., primary, Fogh, L., additional, Halle, B., additional, Jensen, V., additional, Brunner, N., additional, Kristensen, B. W., additional, Abe, T., additional, Momii, Y., additional, Watanabe, J., additional, Morisaki, I., additional, Natsume, A., additional, Wakabayashi, T., additional, Fujiki, M., additional, Aldaz, B., additional, Fabius, A. W. M., additional, Silber, J., additional, Harinath, G., additional, Chan, T. A., additional, Huse, J. T., additional, Anai, S., additional, Hide, T., additional, Nakamura, H., additional, Makino, K., additional, Yano, S., additional, Kuratsu, J.-i., additional, Balyasnikova, I. V., additional, Prasol, M. S., additional, Kanoija, D. K., additional, Aboody, K. S., additional, Lesniak, M. S., additional, Barone, T., additional, Burkhart, C., additional, Purmal, A., additional, Gudkov, A., additional, Gurova, K., additional, Plunkett, R., additional, Barton, K., additional, Misuraca, K., additional, Cordero, F., additional, Dobrikova, E., additional, Min, H., additional, Gromeier, M., additional, Kirsch, D., additional, Becher, O., additional, Pont, L. B., additional, Kloezeman, J., additional, van den Bent, M., additional, Kanaar, R., additional, Kremer, A., additional, Swagemakers, S., additional, French, P., additional, Dirven, C., additional, Lamfers, M., additional, Leenstra, S., additional, Balvers, R., additional, Kleijn, A., additional, Lawler, S., additional, Gong, X., additional, Andres, A., additional, Hanson, J., additional, Delashaw, J., additional, Bota, D., additional, Chen, C.-C., additional, Yao, N.-W., additional, Chuang, W.-J., additional, Chang, C., additional, Chen, P.-Y., additional, Huang, C.-Y., additional, Wei, K.-C., additional, Cheng, Y., additional, Dai, Q., additional, Morshed, R., additional, Han, Y., additional, Auffinger, B., additional, Wainwright, D., additional, Zhang, L., additional, Tobias, A., additional, Rincon, E., additional, Thaci, B., additional, Ahmed, A., additional, He, C., additional, Lesniak, M., additional, Choi, Y. A., additional, Pandya, H., additional, Gibo, D. M., additional, Fokt, I., additional, Priebe, W., additional, Debinski, W., additional, Chornenkyy, Y., additional, Agnihotri, S., additional, Buczkowicz, P., additional, Rakopoulos, P., additional, Morrison, A., additional, Barszczyk, M., additional, Hawkins, C., additional, Chung, S., additional, Decollogne, S., additional, Luk, P., additional, Shen, H., additional, Ha, W., additional, Day, B., additional, Stringer, B., additional, Hogg, P., additional, Dilda, P., additional, McDonald, K., additional, Moore, S., additional, Hayden-Gephart, M., additional, Bergen, J., additional, Su, Y., additional, Rayburn, H., additional, Edwards, M., additional, Scott, M., additional, Cochran, J., additional, Das, A., additional, Varma, A. K., additional, Wallace, G. C., additional, Dixon-Mah, Y. N., additional, Vandergrift, W. A., additional, Giglio, P., additional, Ray, S. K., additional, Patel, S. J., additional, Banik, N. L., additional, Dasgupta, T., additional, Olow, A., additional, Yang, X., additional, Mueller, S., additional, Prados, M., additional, James, C. D., additional, Haas-Kogan, D., additional, Dave, N. D., additional, Desai, P. B., additional, Gudelsky, G. A., additional, Chow, L. M. L., additional, LaSance, K., additional, Qi, X., additional, Driscoll, J., additional, Ebsworth, K., additional, Walters, M. J., additional, Ertl, L. S., additional, Wang, Y., additional, Berahovic, R. D., additional, McMahon, J., additional, Powers, J. P., additional, Jaen, J. C., additional, Schall, T. J., additional, Eroglu, Z., additional, Portnow, J., additional, Sacramento, A., additional, Garcia, E., additional, Raubitschek, A., additional, Synold, T., additional, Esaki, S., additional, Rabkin, S., additional, Martuza, R., additional, Wakimoto, H., additional, Ferluga, S., additional, Tome, C. L., additional, Forde, H. E., additional, Netland, I. A., additional, Sleire, L., additional, Skeie, B., additional, Enger, P. O., additional, Goplen, D., additional, Giladi, M., additional, Tichon, A., additional, Schneiderman, R., additional, Porat, Y., additional, Munster, M., additional, Dishon, M., additional, Weinberg, U., additional, Kirson, E., additional, Wasserman, Y., additional, Palti, Y., additional, Gramatzki, D., additional, Staudinger, M., additional, Frei, K., additional, Peipp, M., additional, Weller, M., additional, Grasso, C., additional, Liu, L., additional, Berlow, N., additional, Davis, L., additional, Fouladi, M., additional, Gajjar, A., additional, Huang, E., additional, Hulleman, E., additional, Hutt, M., additional, Keller, C., additional, Li, X.-N., additional, Meltzer, P., additional, Quezado, M., additional, Quist, M., additional, Raabe, E., additional, Spellman, P., additional, Truffaux, N., additional, van Vurden, D., additional, Wang, N., additional, Warren, K., additional, Pal, R., additional, Grill, J., additional, Monje, M., additional, Green, A. L., additional, Ramkissoon, S., additional, McCauley, D., additional, Jones, K., additional, Perry, J. A., additional, Ramkissoon, L., additional, Maire, C., additional, Shacham, S., additional, Ligon, K. L., additional, Kung, A. L., additional, Zielinska-Chomej, K., additional, Grozman, V., additional, Tu, J., additional, Viktorsson, K., additional, Lewensohn, R., additional, Gupta, S., additional, Mladek, A., additional, Bakken, K., additional, Carlson, B., additional, Boakye-Agyeman, F., additional, Kizilbash, S., additional, Schroeder, M., additional, Reid, J., additional, Sarkaria, J., additional, Hadaczek, P., additional, Ozawa, T., additional, Soroceanu, L., additional, Yoshida, Y., additional, Matlaf, L., additional, Singer, E., additional, Fiallos, E., additional, Cobbs, C. S., additional, Hashizume, R., additional, Tom, M., additional, Ihara, Y., additional, Santos, R., additional, Torre, J. D. L., additional, Lepe, E., additional, Waldman, T., additional, James, D., additional, Huang, X., additional, Yu-Jen, L., additional, Gupta, N., additional, Solomon, D., additional, Zhang, Z., additional, Hayashi, T., additional, Adachi, K., additional, Nagahisa, S., additional, Hasegawa, M., additional, Hirose, Y., additional, Gephart, M. H., additional, Su, Y. S., additional, Hingtgen, S., additional, Kasmieh, R., additional, Nesterenko, I., additional, Figueiredo, J.-L., additional, Dash, R., additional, Sarkar, D., additional, Fisher, P., additional, Shah, K., additional, Horne, E., additional, Diaz, P., additional, Stella, N., additional, Huang, C., additional, Yang, H., additional, Wei, K., additional, Huang, T., additional, Hlavaty, J., additional, Ostertag, D., additional, Espinoza, F. L., additional, Martin, B., additional, Petznek, H., additional, Rodriguez-Aguirre, M., additional, Ibanez, C., additional, Kasahara, N., additional, Gunzburg, W., additional, Gruber, H., additional, Pertschuk, D., additional, Jolly, D., additional, Robbins, J., additional, Hurwitz, B., additional, Yoo, J. Y., additional, Bolyard, C., additional, Yu, J.-G., additional, Wojton, J., additional, Zhang, J., additional, Bailey, Z., additional, Eaves, D., additional, Cripe, T., additional, Old, M., additional, Kaur, B., additional, Serwer, L., additional, Le Moan, N., additional, Ng, S., additional, Butowski, N., additional, Krtolica, A., additional, Cary, S. P. L., additional, Johns, T., additional, Greenall, S., additional, Donoghue, J., additional, Adams, T., additional, Karpel-Massler, G., additional, Westhoff, M.-A., additional, Kast, R. E., additional, Dwucet, A., additional, Wirtz, C. R., additional, Debatin, K.-M., additional, Halatsch, M.-E., additional, Merkur, N., additional, Kievit, F., additional, Stephen, Z., additional, Wang, K., additional, Kolstoe, D., additional, Ellenbogen, R., additional, Zhang, M., additional, Kitange, G., additional, Haefner, E., additional, Knubel, K., additional, Pernu, B. M., additional, Sufit, A., additional, Pierce, A. M., additional, Nelson, S. K., additional, Keating, A. K., additional, Jensen, S. S., additional, Lachowicz, J., additional, Demeule, M., additional, Regina, A., additional, Tripathy, S., additional, Curry, J.-C., additional, Nguyen, T., additional, Castaigne, J.-P., additional, Davis, T., additional, Davis, A., additional, Tanaka, K., additional, Keating, T., additional, Getz, J., additional, Kapp, G. T., additional, Romero, J. M., additional, Lee, S., additional, Ramisetti, S., additional, Slagle-Webb, B., additional, Sharma, A., additional, Connor, J., additional, Lee, W.-S., additional, Kluk, M., additional, Aster, J. C., additional, Ligon, K., additional, Sun, S., additional, Lee, D., additional, Ho, A. S. W., additional, Pu, J. K. S., additional, Zhang, Z.-q., additional, Lee, N. P., additional, Day, P. J. R., additional, Leung, G. K. K., additional, Liu, Z., additional, Liu, X., additional, Madhankumar, A. B., additional, Miller, P., additional, Webb, B., additional, Connor, J. R., additional, Yang, Q. X., additional, Lobo, M., additional, Green, S., additional, Schabel, M., additional, Gillespie, Y., additional, Woltjer, R., additional, Pike, M., additional, Lu, Y.-J., additional, Luchman, H. A., additional, Stechishin, O., additional, Nguyen, S., additional, Cairncross, J. G., additional, Weiss, S., additional, Lun, X., additional, Wells, J. C., additional, Hao, X., additional, Grinshtein, N., additional, Kaplan, D., additional, Luchman, A., additional, Senger, D., additional, Robbins, S., additional, Madhankumar, A., additional, Rizk, E., additional, Payne, R., additional, Park, A., additional, Pang, M., additional, Harbaugh, K., additional, Wilisch-Neumann, A., additional, Pachow, D., additional, Kirches, E., additional, Mawrin, C., additional, McDonell, S., additional, Liang, J., additional, Piao, Y., additional, Nguyen, N., additional, Yung, A., additional, Verhaak, R., additional, Sulman, E., additional, Stephan, C., additional, Lang, F., additional, de Groot, J., additional, Mizobuchi, Y., additional, Okazaki, T., additional, Kageji, T., additional, Kuwayama, K., additional, Kitazato, K. T., additional, Mure, H., additional, Hara, K., additional, Morigaki, R., additional, Matsuzaki, K., additional, Nakajima, K., additional, Nagahiro, S., additional, Kumala, S., additional, Heravi, M., additional, Devic, S., additional, Muanza, T., additional, Knubel, K. H., additional, Neuwelt, A., additional, Wu, Y. J., additional, Donson, A., additional, Vibhakar, R., additional, Venkatamaran, S., additional, Amani, V., additional, Neuwelt, E., additional, Rapkin, L., additional, Foreman, N., additional, Ibrahim, F., additional, New, P., additional, Cui, K., additional, Zhao, H., additional, Chow, D., additional, Stephen, W., additional, Nozue-Okada, K., additional, Nagane, M., additional, McDonald, K. L., additional, Ogawa, D., additional, Chiocca, E., additional, Godlewski, J., additional, Patel, A., additional, Pasupuleti, N., additional, Gorin, F., additional, Valenzuela, A., additional, Leon, L., additional, Carraway, K., additional, Ramachandran, C., additional, Nair, S., additional, Quirrin, K.-W., additional, Khatib, Z., additional, Escalon, E., additional, Melnick, S., additional, Phillips, A., additional, Boghaert, E., additional, Vaidya, K., additional, Ansell, P., additional, Shalinsky, D., additional, Zhang, Y., additional, Voorbach, M., additional, Mudd, S., additional, Holen, K., additional, Humerickhouse, R., additional, Reilly, E., additional, Parab, S., additional, Diago, O., additional, Ryken, T., additional, Agarwal, S., additional, Al-Keilani, M., additional, Alqudah, M., additional, Sibenaller, Z., additional, Assemolt, M., additional, Sai, K., additional, Li, W.-y., additional, Li, W.-p., additional, Chen, Z.-p., additional, Saito, R., additional, Sonoda, Y., additional, Kanamori, M., additional, Yamashita, Y., additional, Kumabe, T., additional, Tominaga, T., additional, Sarkar, G., additional, Curran, G., additional, Jenkins, R., additional, Scharnweber, R., additional, Kato, Y., additional, Lin, J., additional, Everson, R., additional, Soto, H., additional, Kruse, C., additional, Liau, L., additional, Prins, R., additional, Semenkow, S., additional, Chu, Q., additional, Eberhart, C., additional, Sengupta, R., additional, Marassa, J., additional, Piwnica-Worms, D., additional, Rubin, J., additional, Shai, R., additional, Pismenyuk, T., additional, Moshe, I., additional, Fisher, T., additional, Freedman, S., additional, Simon, A., additional, Amariglio, N., additional, Rechavi, G., additional, Toren, A., additional, Yalon, M., additional, Shimazu, Y., additional, Kurozumi, K., additional, Ichikawa, T., additional, Fujii, K., additional, Onishi, M., additional, Ishida, J., additional, Oka, T., additional, Watanabe, M., additional, Nasu, Y., additional, Kumon, H., additional, Date, I., additional, Sirianni, R. W., additional, McCall, R. L., additional, Spoor, J., additional, van der Kaaij, M., additional, Geurtjens, M., additional, Veiseh, O., additional, Fang, C., additional, Leung, M., additional, Strohbehn, G., additional, Atsina, K.-K., additional, Patel, T., additional, Piepmeier, J., additional, Zhou, J., additional, Saltzman, W. M., additional, Takahashi, M., additional, Valdes, G., additional, Inagaki, A., additional, Kamijima, S., additional, Hiraoka, K., additional, Micewicz, E., additional, McBride, W. H., additional, Iwamoto, K. S., additional, Gruber, H. E., additional, Robbins, J. M., additional, Jolly, D. J., additional, McCully, C., additional, Bacher, J., additional, Thomas, T., additional, Murphy, R., additional, Steffen-Smith, E., additional, McAllister, R., additional, Pastakia, D., additional, Widemann, B., additional, Chen, P., additional, Hua, M., additional, Liu, H., additional, Woolf, E. C., additional, Abdelwahab, M. G., additional, Fenton, K. E., additional, Liu, Q., additional, Turner, G., additional, Preul, M. C., additional, Scheck, A. C., additional, Shen, W., additional, Brown, D., additional, Pedersen, H., additional, Hariono, S., additional, Yao, T.-W., additional, Sidhu, A., additional, Weiss, W. A., additional, Nicolaides, T. P., additional, and Olusanya, T., additional

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2013
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35. Nettle as a distinct Bronze Age textile plant

Author

Bergfjord, C., primary, Mannering, U., additional, Frei, K. M., additional, Gleba, M., additional, Scharff, A. B., additional, Skals, I., additional, Heinemeier, J., additional, Nosch, M. -L, additional, and Holst, B., additional

Published
2012
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36. Moclobemide (Ro 11‐1163) in long‐term treatment

Author

Stefanis, C.N. Merz‐Frei, K.

Abstract

Patients requiring long‐term treatment of depression (at least 60 days) were followed up at monthly intervals under treatment with moclobemide. A total of 102 patients completed 1 year of treatment; the mean dose at the start of treatment was 340 mg daily, decreasing to 300 mg after a year. Three quarters of these patients were suffering from endogenous depression. The investigator's overall assessment of efficacy was good or very good for 96% of patients; efficacy judged together with tolerance was good or very good for 85% of patients. There were no noteworthy changes in safety parameters throughout the study, and adverse events were mainly minor and of short duration. The result of this analysis suggests that moclobemide is effective, safe and well tolerated in long‐term administration. Copyright © 1990, Wiley Blackwell. All rights reserved

Published
1990

39. Protective Effect of a 21-Aminosteroid during Experimental Pneumococcal Meningitis

Author

Lorenzi, S, Koedel, U, Frei, K, Bernatowicz, A, Fontana, A, Pfister, H-W, Lorenzi, S, Koedel, U, Frei, K, Bernatowicz, A, Fontana, A, and Pfister, H-W

Abstract

This study investigated whether the 21-aminosteroid U74389F, an inhibitor of lipid peroxidation, attenuates pathophysiologic changes in experimental pneumococcal meningitis. Infected rats injected intravenously with vehicle and U74389F developed increases in regional cerebral blood flow (rCBF), intracranial pressure (ICP), brain water content, and white blood cells (WBC) in cerebrospinal fluid (CSF) within 8 h after intracisternal challenge. Pretreatment with or administration of U74389F 4 h after infection significantly reduced the increase in ICP but had no effect on rCBF increase. Moreover, U74389F pretreatment significantly reduced brain water content and CSF WBC count. In vitro, U74389F inhibited iron-dependent lipid peroxidation of astrocyte cultures and the production of tumor necrosis factor-a, interleukin-6, and nitric oxide by stimulated macrophages. These data suggest that U74389F modulates early pathophysiologic alterations in experimental pneumococcal meningitis

Published
1995

49. Tumour necrosis factor-alpha in infectious meningitis.

Author

Nadal, D, Leppert, D, Frei, K, Gallo, P, Lamche, H, and Fontana, A

Abstract

During a one year period tumour necrosis factor-alpha (TNF-alpha) was prospectively determined in the cerebrospinal fluid of 49 patients with infectious meningitis. TNF-alpha was found in the cerebrospinal fluid of 15 of 18 patients with bacterial meningitis. In 11 patients who had cerebrospinal fluid positive for TNF-alpha it was detected in only one serum (in low concentration). There was no significant correlation between the concentration of TNF-alpha in cerebrospinal fluid and the patient's age, duration of illness and fever, body temperature, and serum C reactive protein. However, cerebrospinal fluid protein concentrations of greater than or equal to 2 g/l and leucocyte values of greater than or equal to 2.5 X 10(9)/l were more often associated with high TNF-alpha concentrations (greater than or equal to 500 pg/ml). In contrast with bacterial meningitis, none of the 31 samples of cerebrospinal fluid from patients with viral meningitis was positive for TNF-alpha. Thus this investigation supports the conclusion, drawn from animal studies on TNF-alpha in the cerebrospinal fluid, that the presence of TNF-alpha is indicative of bacterial meningitis. Absence of TNF-alpha cerebrospinal fluid, however, was found here not to exclude a bacterial aetiology of the infection. [ABSTRACT FROM AUTHOR]

Published
1989

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