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532 results on '"Frei, K."'

55. 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

59. 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

60. 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

61. 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

62. 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

63. 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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64. 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

Published
2013
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65. 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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71. Novel THAP1 sequence variants in primary dystonia

Author

Xiao, J., primary, Zhao, Y., additional, Bastian, R. W., additional, Perlmutter, J. S., additional, Racette, B. A., additional, Tabbal, S. D., additional, Karimi, M., additional, Paniello, R. C., additional, Wszolek, Z. K., additional, Uitti, R. J., additional, Van Gerpen, J. A., additional, Simon, D. K., additional, Tarsy, D., additional, Hedera, P., additional, Truong, D. D., additional, Frei, K. P., additional, Dev Batish, S., additional, Blitzer, A., additional, Pfeiffer, R. F., additional, Gong, S., additional, and LeDoux, M. S., additional

Published
2010
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73. Granulocyte-macrophage colony-stimulating factor (GM-CSF) production by glioblastoma cells. Despite the presence of inducing signals GM-CSF is not expressed in vivo

Author

Frei K, Piani D, Uv, Malipiero, Erwin G. Van Meir, de Tribolet N, and Fontana A

Subjects
Chemotactic Factors, Transforming Growth Factor beta, Immunology, Cyclic AMP, Tumor Cells, Cultured, Immunology and Allergy, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Glioma, RNA, Messenger, Dinoprostone, Interleukin-1
Abstract

One of the morphologic hallmarks of human gliomas are inflammatory infiltrates with accumulation of macrophages in the tumor site. The signals leading to the macrophage response are only at the beginning of being understood. Novel chemotactic factors that have recently been characterized as secretory products of glioblastoma cells may attract mononuclear cells from the blood. Within the tumor tissue blood-derived monocytes and macrophages of the brain tissue, the microglial cells, may increase in cell numbers due to tumor-derived growth factors. Both astrocytoma cell lines and cultured astrocytes have been shown recently to produce granulocyte-macrophage (GM)-CSF. We show that in vitro not only astrocytoma but also glioblastoma cell lines secrete GM-CSF when stimulated with TNF-alpha or IL-1. However, there is no evidence for GM-CSF production by glioblastoma cells in vivo: fresh tumor samples lack the mRNA for GM-CSF and the protein is not detectable in the tumor cyst fluids or the cerebrospinal fluids of glioblastoma patients. This contrasts IL-1 and IL-6 that are detectable in the tumor cyst fluids and IL-6 also in the cerebrospinal fluids of the patients. Unlike GM-CSF, transforming growth factor-beta 2 mRNA is expressed in ex vivo tested glioblastoma tissues. Absence of GM-CSF in vivo may be explained by the presence of tumor-derived inhibitory factors, such as transforming growth factor-beta 2 and PGE which suppress GM-CSF production by glioblastoma cells in vitro. The accumulation of macrophages at the tumor site may be due to local elaboration of chemoattractants and/or not yet defined growth factors rather than due to GM-CSF production.

Published
1992

75. 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

82. The neurogenetics of mucolipidosis type IV

Author

Altarescu, G., primary, Sun, M., additional, Moore, D. F., additional, Smith, J. A., additional, Wiggs, E. A., additional, Solomon, B. I., additional, Patronas, N. J., additional, Frei, K. P., additional, Gupta, S., additional, Kaneski, C. R., additional, Quarrell, O. W., additional, Slaugenhaupt, S. A., additional, Goldin, E., additional, and Schiffmann, R., additional

Published
2002
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87. 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

89. Mucolipidosis type IV

Author

Frei, K. P., primary, Patronas, N. J., additional, Crutchfield, K. E., additional, Altarescu, G., additional, and Schiffmann, R., additional

Published
1998
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96. Experimental Listeria meningoencephalitis. Macrophage inflammatory protein-1 alpha and -2 are produced intrathecally and mediate chemotactic activity in cerebrospinal fluid of infected mice.

Author

Seebach, J, primary, Bartholdi, D, additional, Frei, K, additional, Spanaus, K S, additional, Ferrero, E, additional, Widmer, U, additional, Isenmann, S, additional, Strieter, R M, additional, Schwab, M, additional, Pfister, H, additional, and Fontana, A, additional

Published
1995
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