Search

Your search keyword '"Targan, S"' showing total 584 results
Start Over Author "Targan, S"
584 results on '"Targan, S"'

51. Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy

Author

Sandborn, W. J., primary, Rutgeerts, P., additional, Gasink, C., additional, Jacobstein, D., additional, Zou, B., additional, Johanns, J., additional, Sands, B. E., additional, Hanauer, S. B., additional, Targan, S., additional, Ghosh, S., additional, de Villiers, W. J. S., additional, Colombel, J.-F., additional, and Feagan, B. G., additional

Published
2018
Full Text
View/download PDF

52. Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population.

Author

Williams, SM, Rivas, MA, Avila, BE, Koskela, J, Huang, H, Stevens, C, Pirinen, M, Haritunians, T, Neale, BM, Kurki, M, Ganna, A, Graham, D, Glaser, B, Peter, I, Atzmon, G, Barzilai, N, Levine, AP, Schiff, E, Pontikos, N, Weisburd, B, Lek, M, Karczewski, KJ, Bloom, J, Minikel, EV, Petersen, B-S, Beaugerie, L, Seksik, P, Cosnes, J, Schreiber, S, Bokemeyer, B, Bethge, J, International IBD Genetics Consortium, NIDDK IBD Genetics Consortium, T2D-GENES Consortium, Heap, G, Ahmad, T, Plagnol, V, Segal, AW, Targan, S, Turner, D, Saavalainen, P, Farkkila, M, Kontula, K, Palotie, A, Brant, SR, Duerr, RH, Silverberg, MS, Rioux, JD, Weersma, RK, Franke, A, Jostins, L, Anderson, CA, Barrett, JC, MacArthur, DG, Jalas, C, Sokol, H, Xavier, RJ, Pulver, A, Cho, JH, McGovern, DPB, Daly, MJ, Williams, SM, Rivas, MA, Avila, BE, Koskela, J, Huang, H, Stevens, C, Pirinen, M, Haritunians, T, Neale, BM, Kurki, M, Ganna, A, Graham, D, Glaser, B, Peter, I, Atzmon, G, Barzilai, N, Levine, AP, Schiff, E, Pontikos, N, Weisburd, B, Lek, M, Karczewski, KJ, Bloom, J, Minikel, EV, Petersen, B-S, Beaugerie, L, Seksik, P, Cosnes, J, Schreiber, S, Bokemeyer, B, Bethge, J, International IBD Genetics Consortium, NIDDK IBD Genetics Consortium, T2D-GENES Consortium, Heap, G, Ahmad, T, Plagnol, V, Segal, AW, Targan, S, Turner, D, Saavalainen, P, Farkkila, M, Kontula, K, Palotie, A, Brant, SR, Duerr, RH, Silverberg, MS, Rioux, JD, Weersma, RK, Franke, A, Jostins, L, Anderson, CA, Barrett, JC, MacArthur, DG, Jalas, C, Sokol, H, Xavier, RJ, Pulver, A, Cho, JH, McGovern, DPB, and Daly, MJ

Abstract

As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10-100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel con

Published
2018

54. Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

Author

Feagan, BG, Sandborn, WJ, Gasink, C, Jacobstein, D, Lang, Y, Friedman, JR, Blank, MA, Johanns, J, Gao, L-L, Miao, Y, Adedokun, OJ, Sands, BE, Hanauer, SB, Vermeire, S, Targan, S, Ghosh, S, de Villiers, WJ, Colombel, J-F, Tulassay, Z, Seidler, U, Salzberg, BA, Desreumaux, P, Lee, SD, Loftus, EV, Dieleman, LA, Katz, S, and Rutgeerts, P

Abstract

BACKGROUND\ud Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.\ud METHODS\ud We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed \ud these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score

Published
2016

58. LONG-TERM EFFICACY AND SAFETY OF USTEKINUMAB FOR CROHN’S DISEASE: RESULTS FROM IM-UNITI LONG-TERM EXTENSION THROUGH 2 YEARS

Author

Sandborn, W., primary, Rutgeerts, P., additional, Gasink, C., additional, Jacobstein, D., additional, Gao, L., additional, Johanns, J., additional, Sands, B., additional, Hanauer, S., additional, Targan, S., additional, Ghosh, S., additional, Villiers, W., additional, Colombel, J., additional, Feagan, B., additional, and Silva, Bruno, additional

Published
2017
Full Text
View/download PDF

59. OC-043 Long term efficacy and safety of ustekinumab for crohn’s disease: results from im-uniti long-term extension through 2 years

Author

Sandborn, WJ, primary, Rutgeerts, P, additional, Gasink, C, additional, Jacobstein, D, additional, Gao, L, additional, Johanns, J, additional, Sands, B, additional, Hanauer, S, additional, Targan, S, additional, Ghosh, S, additional, Villiers, WJS de, additional, Colombel, JF, additional, and Feagan, BG, additional

Published
2017
Full Text
View/download PDF

60. OC-005 A Multicenter, Double-Blind, Placebo (PBO)-Controlled Ph3 Study of Ustekinumab (UST), A Human IL-12/23P40 MAB, in Moderate-Severe Crohn’s Disease (CD) Refractory to anti-TNFΑ: UNITI-1

Author

Rutgeerts, P, primary, Gasink, C, additional, Blank, M, additional, Lang, Y, additional, Johanns, J, additional, Gao, L-L, additional, Sands, B, additional, Hanauer, S, additional, Feagan, B, additional, Targan, S, additional, Ghosh, S, additional, de Villiers, W, additional, Colombel, J-F, additional, Lee, SD, additional, Desreumaux, P, additional, Loftus, EV, additional, Vermeire, S, additional, and Sandborn, WJ, additional

Published
2016
Full Text
View/download PDF

62. OC-007 A Multicenter, Double-Blind, Placebo (PBO)-Controlled Ph3 Study of Ustekinumab (UST), A’Human MAB to IL-12/23P40, IN PTS with Moderately-Severely Active Crohn’s Disease (CD) Who are Naïve or not Refractory to anti-TNFΑ: UNITI-2: Abstract OC-007 Table 1

Author

Feagan, B, primary, Gasink, C, additional, Lang, Y, additional, Friedman, JR, additional, Johanns, J, additional, Gao, L-L, additional, Sands, B, additional, Hanauer, S, additional, Rutgeerts, P, additional, Targan, S, additional, Ghosh, S, additional, de Villiers, W, additional, Colombel, J-F, additional, Tulassay, Z, additional, Seidler, U, additional, and Sandborn, WJ, additional

Published
2016
Full Text
View/download PDF

64. Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis

Author

Beaudoin, Melissa, Goyette, Philippe, Goel, Gautam, Louis, E., Mansfield, J. C., Mathew, C. G., McGovern, D. P., Mitrovic, M., Montgomery, G. W., Mowat, C., Newman, W., Palmieri, O., Panés, J., Lagace, Caroline, Parkes, M., Phillips, A., Ponsioen, C. Y., Potocnik, U., Prescott, N. J., Proctor, D. D., Radford-Smith, G. L., Regueiro, M., Rioux, J. D., Roberts, R., Annese, Vito, Rotter, J. I., Rutgeerts, P., Sanderson, J., Sans, M., Satsangi, J., Schreiber, S., Schumm, P., Seibold, F., Sharma, Y., Silverberg, M. S., Bitton, Alain, Simms, L. A., Steinhart, A., Targan, S. R., Taylor, K. D., Torkvist, L., Vermeire, S., Halfvarson, J., Verspaget, H. W., De Vos, M., Walters, T., Begun, Jakob, Wang, K., Weersma, R. K., Whiteman, D., Wijmenga, C., Brant, Steven R., Bresso, Francesca, Cho, Judy H., Duerr, Richard H., Halfvarson, Jonas, Boucher, Gabrielle, McGovern, Dermot P. B., Radford-Smith, Graham, Schreiber, Stefan, Schumm, Philip L., Sharma, Yashoda, Silverberg, Mark S., Weersma, Rinse K., Quebec IBD Genetics Consortium, NIDDK IBD Genetics Consortium, International IBD Genetics Consortium (IIBDGC), Lo, Ken Sin, D'Amato, Mauro, Vermeire, Severine, Franke, Andre, Lettre, Guillaume, Xavier, Ramnik J., Daly, Mark J., Rioux, John D., Aumais, G., Bernard, E. J., Bitton, A., Rivas, Manuel A., Cohen, A., Deslandres, C., Lahaie, R., Paré, P., Brant, S. R., Cho, J. H., Duerr, R. H., Stevens, Christine, Ahmad, T., Anderson, C. A., Annese, V., Baldassano, R. N., Balschun, T., Barclay, M., Barrett, J. C., Bayless, T. M., Bis, J. C., Alikashani, Azadeh, Brand, S., Bumpstead, S., Buning, C., Colombel, J. F., Cottone, M., D'Amato, M., D'Inca, R., Ladouceur, Martin, Daly, M. J., Denson, T., Dubinsky, M., Edwards, C., Ellinghaus, D., Florin, T., Franchimont, D., Franke, A., Gearry, R., Ellinghaus, David, Georges, M., Glas, J., Van Gossum, A., Griffiths, A. M., Guthery, S. L., Hakonarson, H., Haritunians, T., Hugot, J. P., de Jong, D. J., Jostins, L., Torkvist, Leif, Kugathasan, S., Kullak-Ublick, G., Latiano, A., Laukens, D., Lawrance, I., Lee, J., Lees, C. W., Lemann, M., Levine, A., Libioulle, C., and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Cancer Research, Génétique clinique, LIVER, Genome-wide association study, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, GENETIC-VARIANTS, Medicine and Health Sciences, Ethnicity, UBIQUITIN LIGASES, Genetics(clinical), Genetics (clinical), Genetics, 0303 health sciences, Ecology, High-Throughput Nucleotide Sequencing, CROHN-DISEASE, CROHNS-DISEASE, 3. Good health, 030220 oncology & carcinogenesis, Medical genetics, Biologie, Research Article, EXPRESSION, medicine.medical_specialty, Canada, lcsh:QH426-470, SUSCEPTIBILITY LOCI, Evolution, Ubiquitin-Protein Ligases, Ethnic Groups, Evolution des espèces, Biology, Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2], Polymorphism, Single Nucleotide, 03 medical and health sciences, Behavior and Systematics, medicine, Humans, Genetic Predisposition to Disease, Ligase activity, MODULATION, Allele, GENOME-WIDE ASSOCIATION, Molecular Biology, Genotyping, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, Ecologie, Biologie moléculaire, Receptors, Interleukin, medicine.disease, NUCLEAR FACTOR 4-ALPHA, Genetic architecture, Cancérologie, CARD Signaling Adaptor Proteins, lcsh:Genetics, CELLS, Colitis, Ulcerative, INTESTINAL EPITHELIAL-CELLS, Genome-Wide Association Study, INFLAMMATORY-BOWEL-DISEASE
Abstract

Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (~14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. © 2013 Beaudoin et al., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2013
Full Text
View/download PDF

65. Ustekinumab induction and maintenance therapy in refractory Crohn's disease

Author

Sandborn, Wj, Gasink, C, Gao, Ll, Blank, Ma, Johanns, J, Guzzo, C, Sands, Be, Hanauer, Sb, Targan, S, Rutgeerts, P, Ghosh, S, de Villiers WJ, Panaccione, R, Greenberg, G, Schreiber, S, Lichtiger, S, Feagan, Bg, Haas, T, Kaser, A, Vogelsang, H, Brown, S, Florin, T, Gibson, Pg, Hetzel, D, Leong, R, Pavli, P, Radford-Smith, G, Sparrow, M, Baert, F, D'Haens, G, D'Heygere, F, Franchimont, D, Louis, E, Mana, F, Moreels, T, Vermeire, S, Anderson, F, Axler, J, Greenbloom, S, Bitton, A, Fedorak, Rn, Larkai, E, Marshall, J, Singh, R, Abitbol, V, Allez, M, Lemann, M, Bonaz, B, Colombel, Jf, Dupas, Jl, Hebuterne, X, Laharie, D, Lerebours, E, Moreau, J, Bokemeyer, B, Holler, B, Howaldt, Sp, Krummenerl, T, Kucharzik, T, Ochsenkühn, T, Raedler, A, Schiefke, I, Seidler, U, Sturm, A, Zeitz, M, Eliakim, A, Fishman, S, Konikoff, Fm, Lavy, A, Niv, Y, Nussinson, E, Rachmilewitz, D, Andriulli, A, Annese, V, Biancone, L, Corazza, Gr, Danese, S, Sturniolo, Gc, Terrosu, G, Sorrentino, D, Hommes, Dw, Jansen, Jm, Otten, Mh, Pierik, M, Ponsioen, Cy, Stokkers, P, van Bodegraven AA, Van der Woude, J, Calvet Calvo, X, Casellas, F, Garcia López, S, Garcia-Planella, E, Ginard-Vincens, D, López San Román, A, Muñoz Nuñez, F, Pérez Gisbert, J, Vera, Mi, Rodrigo, J, Riestra-Menendez, S, Arnott, I, Bloom, S, Campbell, Ss, Harbord, Mw, Mansfield, Jc, Nwokolo, C, Parkes, M, Probert, Cs, Aberra, Fn, Abraham, Bp, Abreu, Mt, Amontree, Js, Barish, Cf, Barto, Ae, Behm, B, Birbara, Ca, Bologna, S, Dryden GW Jr, Eisner, Ms, Ertan, A, Fogel, R, Gagneja, Hk, Ginsburg, P, Goff, Js, Gordon, G, Hamilton, Jw, Hanson, Js, Hardi, R, Hemaidan, A, Higgins, P, Holderman, W, Hornbuckle, K, Ibegbu, E, Isaacs, Kl, Katz, Ja, Katz, S, Kaufman, Bp, Kavanaugh, Af, Khurana, Sk, Lashner, B, Lawrence, S, Hansen, Rn, Lee, S, Leighton, Ja, Leman, Bi, Levenson, Sd, Lowe, Je, Marcuard, Sp, Matsuyama, Rm, Mcnair, Ae, Melmed, G, Miller, Km, Miner PB Jr, Mutlu, Ea, Keshavarzian, A, Narayen, V, Noar, Md, Patel, Ph, Patrick, Tj, Peck, A, Peterson, Ka, Phillips, Rw, Picco, Mf, Randall, C, Richards, Rj, Safdi, Ma, Scherl, Eh, Schwartz, Da, Schwartz, Hi, Schwartz, Jl, Sedghi, S, Shafran, I, Siegel, Ca, Sninsky, Ca, Stern, M, Suiter, D, Swaminath, A, Terdiman, Jp, Mahadevan, U, Thomson, C, Valentine, J, Vasudeva, R, Vecchio, Ja, Wolf, Dc, Yajnik, V, Yabkowski, J, Yen, E., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Other departments

Subjects
Male, Oncology, MONOCLONAL-ANTIBODY, Drug Resistance, Disease, Severity of Illness Index, Crohn Disease, Maintenance therapy, IL-23, Adult, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Double-Blind Method, Female, Humans, Induction Chemotherapy, Maintenance Chemotherapy, Middle Aged, Remission Induction, Tumor Necrosis Factors, Ustekinumab, Monoclonal, Humanized, Settore MED/12 - Gastroenterologia, Crohn's disease, EXPERIMENTAL COLITIS, General Medicine, medicine.drug, medicine.medical_specialty, MONOCLONAL-ANTIBODY, RANDOMIZED-TRIAL, EXPERIMENTAL COLITIS, CERTOLIZUMAB PEGOL, INFLAMMATION, IL-23, INTERLEUKIN-12, ADALIMUMAB, INFLIXIMAB, DISCOVERY, Antibodies, CERTOLIZUMAB PEGOL, INFLAMMATION, Refractory, Internal medicine, INFLIXIMAB, medicine, business.industry, Induction chemotherapy, medicine.disease, RANDOMIZED-TRIAL, INTERLEUKIN-12, Clinical trial, DISCOVERY, Immunology, Tumor Necrosis Factor Inhibitors, business, ADALIMUMAB
Abstract

BACKGROUND In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown. METHODS We evaluated ustekinumab in adults with moderate-to-severe Crohn's disease that was resistant to anti-tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks. RESULTS The proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P = 0.005 for the comparison with the 6-mg group). The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4%, P = 0.03) and response (69.4% vs. 42.5%, P < 0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal-cell carcinoma developed in 1 patient receiving ustekinumab. CONCLUSIONS Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.)

Published
2012

66. A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables

Author

Siegel, C. A., primary, Horton, H., additional, Siegel, L. S., additional, Thompson, K. D., additional, Mackenzie, T., additional, Stewart, S. K., additional, Rice, P. W., additional, Stempak, J. M., additional, Dezfoli, S., additional, Haritunians, T., additional, Levy, A., additional, Baek, M., additional, Milgrom, R., additional, Dulai, P. S., additional, Targan, S. R., additional, Silverberg, M. S., additional, Dubinsky, M. C., additional, and McGovern, D. P., additional

Published
2015
Full Text
View/download PDF

67. Detection of Antisynthetic Mannoside Antibodies (AΣMA) Reveals Heterogeneity in the ASCA Response of Crohn's Disease Patients and Contributes to Differential Diagnosis, Stratification, and Prediction

Author

Khoury, P. V. E, Colombel, J.F., Sofie Joossens, Ph.D., Standaert-Vitse, A., Collot, M., Halfvarson, J., Ayadi, A., Landers, C.J., Vermeire, S., Rutgeerts, P., Targan, S. R., Chamaillard, M., Mallet, Jean-Maurice, Sendid, B., Poulain, D., Physiopathologie des Candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Physiopathologie des Maladies Inflammatoires de l'Intestin, Division of Gastroenterology, University Hospital Gasthuisberg, Biomolécules : synthèse, structure et mode d'action (UMR 8642) (BIOSYMA), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Örebro University Hospital [Örebro, Sweden], Laboratoire de Parasitologie et Mycologie, École de Médecine, École de Médecine, Inflammatory Bowel Disease Center,, Cedars-Sinai Medical Center, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
[CHIM.ORGA]Chemical Sciences/Organic chemistry, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

70. International collaboration provides convincing linkage replication in complex disease through analysis of a large pooled data set: Crohn disease and chromosome 16

Author

Cavanaugh, J. A., Bryce, M. E., Stanford, P. M., Pavli, P., Vermeire, S., Peeters, M., Vlietinck, R., Rutgeerts, P., Rioux, J. D., Silverberg, M. S., Steinhart, A. H., Siminovitch, K. A., Hugot, J. P., Lesage, S., Zouali, H., Paavola, P., Halme, L., Färkkilä, M., Kontula, K., Annese, V., Forabosco, P., Fortina, P., Latiano, A., Van Heel, D., Parkes, M., Lench, N., Jewell, D., Brant, S. R., Bailey-Wilson, J. E., Panhuysen, C. I. M., Bayless, T. M., Cho, J. H., Bonen, D. K., Kirschner, B. S., Hanauer, S. B., Yang, H., Taylor, K., Targan, S. R., Rotter, J. I., Silver, J., Gulwani-Akolkar, B., Akolkar, P., Lin, X. -Y., Duerr, R. H., Zhang, L., Achkar, J. P., Baldassano, R. N., Daly, M. J., and Risch, N.

Subjects
Male, Genetic Linkage, International Cooperation, Ulcerative, 0302 clinical medicine, Chromosome Mapping, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 16, Colitis, Ulcerative, Crohn Disease, European Continental Ancestry Group, Family Characteristics, Female, Genetic Heterogeneity, Genetic Markers, Genetic Predisposition to Disease, Genotype, Humans, Jews, Lod Score, Microsatellite Repeats, Models, Genetic, Nuclear Family, Reproducibility of Results, Statistics, Nonparametric, Genetics, Genetics (clinical), Models, Pair 12, Genetics(clinical), 0303 health sciences, Statistics, Articles, Colitis, 3. Good health, symbols, Microsatellite, 030211 gastroenterology & hepatology, Human, Locus (genetics), Biology, White People, Chromosomes, 03 medical and health sciences, symbols.namesake, Chromosome 16, Genetic, Genetic linkage, Nonparametric, Genotyping, Chromosome 12, 030304 developmental biology, Genetic heterogeneity, Pair 16, Mendelian inheritance
Abstract

Numerous familial, non-Mendelian (i.e., complex) diseases have been screened by linkage analysis for regions harboring susceptibility genes. Except for rare, high-penetrance syndromes showing Mendelian inheritance, such as BRCA1 and BRCA2, most attempts have failed to produce replicable linkage findings. For example, in multiple sclerosis and other complex diseases, there have been many reports of significant linkage, followed by numerous failures to replicate. In inflammatory bowel disease (IBD), linkage to two regions has elsewhere been reported at genomewide significance levels: the pericentromeric region on chromosome 16 (IBD1) and chromosome 12q (IBD2). As with other complex diseases, the subsequent support for these localizations has been variable. In this article, we report the results of an international collaborative effort to investigate these putative localization by pooling of data sets that do not individually provide convincing evidence for linkage to these regions. Our results, generated by the genotyping and analysis of 12 microsatellite markers in 613 families, provide unequivocal replication of linkage for a common human disease: a Crohn disease susceptibility locus on chromosome 16 (maximum LOD score 5.79). Despite failure to replicate the previous evidence for linkage on chromosome 12, the results described herein indicate the need to further investigate the potential role of this locus in susceptibility to ulcerative colitis. This report provides a convincing example of the collaborative approach necessary to obtain the sample numbers required to achieve statistical power in studies of complex human traits.

Published
2001

71. Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease

Author

Kleoudis, C. S., Hanauer, S. B., Targan, S. R., Feagan, B. G., Tremaine, W. J., Fedorak, R. N., Wolf, D. C., McDonald, J. W.D., Isaacs, K. L., Sutherland, L. R., Lipsky, J. J., Murdock R.H., Jr, Sandborn, W. J., Gordon, S., Pike, M. G., Sninsky, C. A., and Mays, D. C.

Abstract

Background & Aims: Azathioprine is effective for Crohn's disease but acts slowly. A loading dose may decrease the time to response. Methods: A placebo-controlled study was conducted in patients with active Crohn's disease despite prednisone treatment. Patients were randomized to a 36-hour infusion of azathioprine, 40 mg/kg (51 patients), or placebo (45 patients) followed by oral azathioprine, 2 mg/kg, for 16 weeks. Prednisone was tapered over 5 weeks. The primary outcome measure was complete remission at week 8, defined by discontinuation of prednisone and a Crohn's Disease Activity Index of ≤150 points. Erythrocyte concentrations of the azathioprine active metabolite, 6-thioguanine nucleotide, were measured. Results: At week 8, 13 patients (25%) were in complete remission in the azathioprine-loaded group compared with 11 patients (24%) in the placebo group. The frequency of complete remission did not increase after 8 weeks in either group. Both groups achieved steady state of 6-thioguanine nucleotide by week 2, and no differences were found in mean concentrations between the groups. There were no significant differences in the frequency of adverse events between the groups. Conclusions: A loading dose does not decrease the time to response in patients with steroid-treated Crohn's disease beginning azathioprine therapy. Steady state of erythrocyte 6-thioguanine nucleotide and complete response occurred earlier than previously reported.GASTROENTEROLOGY 1999;117:527-535

Published
1999
Full Text
View/download PDF

73. P300 Health related quality of life results through week 22 from the CERTIFI study, a multicenter, randomized, double-blind, placebo-controlled Phase2b study of ustekinumab in patients with moderately to severely active Crohn's disease

Author

Feagan, B., primary, Gasink, C., additional, Gao, L.-L., additional, Blank, M., additional, Johanns, J., additional, Guzzo, C., additional, Chiou, C.-F., additional, Sandborn, W., additional, Hanauer, S.B., additional, Targan, S., additional, Rutgeerts, P., additional, Ghosh, S., additional, De Villiers, W., additional, Panaccione, R., additional, Greenberg, G., additional, Schreiber, S., additional, Lichtiger, S., additional, and Sands, B., additional

Published
2012
Full Text
View/download PDF

74. Health related quality of life results through week 22 from the CERTIFI study, a multicenter, randomized, double-blind, placebo-controlled phase2b study of Ustekinumab in patients with moderately to severely active Crohnʼs disease

Author

Sands, BE, primary, Gasink, C, additional, Gao, L-L, additional, Blank, MA, additional, Johanns, J, additional, Guzzo, C, additional, Chiou, C-F, additional, Sandborn, WJ, additional, Hanauer, SB, additional, Targan, S, additional, Rutgeerts, P, additional, Ghosh, S, additional, de Villiers, W, additional, Panaccione, R, additional, Greenberg, G, additional, Schreiber, S, additional, Lichtiger, S, additional, and Feagan, BG, additional

Published
2011
Full Text
View/download PDF

75. A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 2b Study of Ustekinumab, a Human Monoclonal Antibody to Il-12/23p40, in Patients with Moderately to Severely Active Crohnʼs Disease: Results through Week 36 from the CERTIFI Trial: 2011 ACG Presidential Poster

Author

Feagan, Brian, primary, Gasink, C., additional, Gao, L., additional, Blank, M., additional, Johanns, J., additional, Guzzo, C., additional, Sands, B., additional, Hanauer, Stephen, additional, Targan, S., additional, Rutgeerts, P., additional, Ghosh, S., additional, de Villiers, W., additional, Panaccione, R., additional, Greenberg, G., additional, Schreiber, S., additional, Lichtiger, S., additional, and Sandborn, William, additional

Published
2011
Full Text
View/download PDF

76. Variants in ZNF365 isoform D are associated with Crohn's disease

Author

Haritunians, T., primary, Jones, M. R., additional, McGovern, D. P. B., additional, Shih, D. Q., additional, Barrett, R. J., additional, Derkowski, C., additional, Dubinsky, M. C., additional, Dutridge, D., additional, Fleshner, P. R., additional, Ippoliti, A., additional, King, L., additional, Leshinsky-Silver, E., additional, Levine, A., additional, Melmed, G. Y., additional, Mengesha, E., additional, Vasilauskas, E. A., additional, Ziaee, S., additional, Rotter, J. I., additional, Targan, S. R., additional, and Taylor, K. D., additional

Published
2011
Full Text
View/download PDF

81. Linkage of Crohn's disease-related serological phenotypes: NFKB1 haplotypes are associated with anti-CBir1 and ASCA, and show reduced NF- B activation

Author

Takedatsu, H, primary, Taylor, K D, additional, Mei, L, additional, McGovern, D P B, additional, Landers, C J, additional, Gonsky, R, additional, Cong, Y, additional, Vasiliauskas, E A, additional, Ippoliti, A, additional, Elson, C O, additional, Rotter, J I, additional, and Targan, S R, additional

Published
2008
Full Text
View/download PDF

84. Natalizumab is effective without the concomitant use of immunosuppressants or corticosteroids for the induction and maintenance of response and remission in patients with Crohnʼs disease

Author

Wolf, D, primary, Feagan, B, additional, Fedorak, R, additional, Lashner, B, additional, Panaccione, R, additional, Present, D, additional, Rutgeerts, P, additional, Sandborn, W, additional, Spehlmann, M, additional, Tulassay, Z, additional, Volvofa, M, additional, and Targan, S, additional

Published
2008
Full Text
View/download PDF

86. Natalizumab Induces Sustained Response and Remission in the Absence of Concomitant Immunosuppressants in Patients with Crohnʼs Disease Who Failed Prior Anti-TNFα Therapy

Author

Lashner, B., primary, Colombel, J. F., additional, Enns, R., additional, Feagan, B. G., additional, Fedorak, R. N., additional, Hanauer, S. B., additional, Lawrance, I. C., additional, Panaccione, R., additional, Present, D., additional, Rutgeerts, P., additional, Sandborn, W. J., additional, Sanders, M., additional, Schreiber, S., additional, Spehlmann, M. E., additional, Tulassay, Z., additional, van Deventer, S., additional, Volfova, M., additional, Wolf, D. C., additional, and Targan, S., additional

Published
2007
Full Text
View/download PDF

87. Natalizumab Does Not Require the Concomitant Use of Immunosuppressants or Corticosteriods for the Induction of Sustained Response and Remission in Patients with Crohnʼs Disease

Author

Wolf, D. C., primary, Colombel, J. F., additional, Enns, R., additional, Feagan, B. G., additional, Fedorak, R. N., additional, Hanauer, S. B., additional, Lashner, B., additional, Lawrance, I. C., additional, Panaccione, R., additional, Present, D., additional, Rutgeerts, P., additional, Sandborn, W. J., additional, Sanders, M., additional, Schreiber, S., additional, Spehlmann, M. E., additional, Tulassay, Z., additional, van Deventer, S., additional, Volfova, M., additional, and Targan, S., additional

Published
2007
Full Text
View/download PDF

91. Natalizumab Maintains Remission for 2 Years in Patients with Moderately to Severely Active Crohnʼs Disease and in Those with Prior Infliximab Exposure

Author

Panaccione, R., primary, Colombel, J. F., additional, Enns, R., additional, Feagan, B., additional, Hanauer, S., additional, Lawrance, I., additional, Rutgeerts, P., additional, Sandborn, W. J., additional, Sanders, M., additional, Schreiber, S., additional, Targan, S., additional, and VanDeventer, S., additional

Published
2006
Full Text
View/download PDF

95. Preface

Author

DOMSCHKE, W. W, primary, KAGNOFF, M. F, additional, KUCHARZIK, T. F, additional, MAYER, L. F, additional, and Targan, S. R, additional

Published
2006
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results