bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informed choice and the widespread use of antiinflammatory drugs
Authors: Fraenkel Liana , Wittink Dick R. , Concato John , Fried Terri 
Published: April 2004

AbstractObjectiveTo examine whether the current widespread use of antiinflammatory drugs may reflect a lack of informed choice (i.e., unawareness of adverse effects or potential treatment alternatives) among older patients with knee osteoarthritis (OA).MethodsConsecutive patients with symptomatic knee OA (n = 100) completed a questionnaire to assess their awareness of drug toxicity. Patients also completed an Adaptive Conjoint Analysis task so that the influence of providing an additional treatment alternative on patient preferences for nonselective nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase‐2 (COX‐2) inhibitors could be assessed.ResultsFifty‐four percent of the patients surveyed were unaware of any adverse effects related to NSAIDs and 80% were unaware of any toxicity related to COX‐2 inhibitors. When given a choice between NSAIDs and COX‐2 inhibitors, 57% of patients preferred COX‐2 inhibitors over NSAIDs. When presented with a third less effective, but safer alternative, 100% of patients switched preferences to the safer, albeit less effective, option.ConclusionsOur findings suggest that the widespread use of NSAIDs may reflect lack of informed choice among older patients with OA.
The clinical effect of glucocorticoids in patients with rheumatoid arthritis may be masked by decreased use of additional therapies
Authors: Van Everdingen Amalia A. , Siewertsz Van Reesema Dirk R. , Jacobs Johannes W. G. , Bijlsma Johannes W. J. 
Published: April 2004

AbstractObjectiveOur previous analysis of patients with early active rheumatoid arthritis (RA) treated with prednisone or placebo revealed the following discrepancy: although a significant retardation of joint damage was observed in the prednisone group compared with the placebo group, no differences in clinical variables between the 2 groups were observed, due to greater use of additional therapy in the placebo group. We sought to investigate whether this descrepancy would extend to variables of well‐being.MethodsWe conducted a double‐blind, randomized, placebo‐controlled clinical trial of prednisone (10 mg) in patients with RA; the duration of the study was 2 years. Following the placebo‐controlled trial, a 1‐year open‐label followup study was conducted in 81 patients with early (≤1 year) active, previously untreated RA. Forty‐one patients were allocated to receive oral prednisone, 10 mg/day, and 40 patients were assigned to the placebo group. Analgesics, nonsteroidal antiinflammatory drugs (NSAIDs), local injections of a glucocorticoid (only when absolutely necessary), and use of physiotherapy were allowed in both groups. After 6 months, sulfasalazine (2 gm/day) could be prescribed as rescue therapy in both groups. At the beginning of the study and every 6 months thereafter, 2 questionnaires (the VDF [Dutch version of the Health Assessment Questionnaire] and the IRGL [Dutch version of the Arthritis Impact Measurement Scales]) were administered. A visual analog scale (VAS) for morning pain was administered every 3 months. Disease activity and radiologic scores were assessed.ResultsVDF scores in the 2 groups were not statistically significantly different. No statistically significant differences between groups were observed in almost all parameters of the IRGL. In the prednisone group (and only at 6 months), the VAS scores for morning pain and general well‐being showed improvement comparable with the transient improvement in some of the disease activity variables. In the prednisone group, use of NSAIDs, analgesics, local injections of glucocorticoids, and physiotherapy sessions was ∼50% that in the placebo group.ConclusionAlthough significant retardation of joint damage in the prednisone group indicates better disease control, no differences between the groups for variables of well‐being were found. This discrepancy may be attributed to greater use of additional therapy in the placebo group. In future clinical trials, the use of additional therapies should be taken into account when analyzing the differences in effect between drugs.
Fast and learnable behavioral and cognitive modeling for virtual character animation
Authors: Dinerstein Jonathan , Egbert Parris K , Garis Hugo de , Dinerstein Nelson 
Published: April 2004

AbstractBehavioral and cognitive modeling for virtual characters is a promising field. It significantly reduces the workload on the animator, allowing characters to act autonomously in a believable fashion. It also makes interactivity between humans and virtual characters more practical than ever before. In this paper we present a novel technique where an artificial neural network is used to approximate a cognitive model. This allows us to execute the model much more quickly, making cognitively empowered characters more practical for interactive applications. Through this approach, we can animate several thousand intelligent characters in real time on a PC. We also present a novel technique for how a virtual character, instead of using an explicit model supplied by the user, can automatically learn an unknown behavioral/cognitive model by itself through reinforcement learning. The ability to learn without an explicit model appears promising for helping behavioral and cognitive modeling become more broadly accepted and used in the computer graphics community, as it can further reduce the workload on the animator. Further, it provides solutions for problems that cannot easily be modeled explicitly. Copyright © 2004 John Wiley & Sons, Ltd.
On Copper‐tetrahydrogen‐decaoxo‐diperiodate‐hexahydrate CuH4I2O10×6H2O: Crystal Structure, Vibrational Spectroscopy and Thermal Analysis.
Authors: Botova M. , Nagel R. , Haeuseler H. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Structural and Electrical Behavior of the Pyrochlores: Sm2‐xMxTi2O7‐x/2 (M: Mg, Co, Ni).
Authors: Daidouh A. , Pico C. , Veiga M. L. , Almontassir A. , Abboudi M. , Hanebali L. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Chiral Germanium Zeotype with Interconnected 8‐, 11‐, and 11‐Ring Channels. Catalytic Properties.
Authors: Medina M. E. , Iglesias M. , Snejko N. , Gutierrez‐Puebla E. , Monge M. A. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
[N2C6H14]2 [(UO2)6(H2O)2F2 (PO4)2(HPO4)4] ×4H2O: A New Microporous Uranium Phosphate Fluoride.
Authors: Doran Michael B. , Stuart Clair L. , Norquist Alexander J. , O'Hare Dermot 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
An Easy and Convenient Synthesis of Optically Active β‐Amino Alcohols and 1,2‐Diamines. Applications in Enantioselective Deprotonation of Cyclohexene Oxide.
Authors: Shin Sung Hye , Kang Sang Kyu , Cho Byung Tae 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Preparation of Chiral Organochalcogeno‐α‐methylbenzyl Alcohols via Biocatalysis. The Role of Daucus carota Root.
Authors: Comasseto Joao V. , Omori Alvaro T. , Porto Andre L. M. , Andrade Leandro H. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Regioselective Synthesis of Bis(silyl enol ethers) and Bis(conjugated Enones) Through Electron Transfer from Mg Metal.
Authors: Maekawa Hirofumi , Sakai Manabu , Uchida Tetsuro , Kita Yoshio , Nishiguchi Ikuzo 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Regioselective Substitution in α‐Bromo‐β‐butoxyvinyl Trifluoromethyl Ketone by N‐Nucleophiles.
Authors: Rulev A. Yu. , Fedorov S. V. , Nenajdenko V. G. , Balenkova E. S. , Voronkov M. G. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Organic Reactions in Ionic Liquids: Ionic Liquid‐Accelerated Nucleophilic Substitution Reaction of α‐Tosyloxyketones with Potassium Salts of Aromatic Acids.
Authors: Liu Zhi , Chen Zhen‐Chu , Zheng Qin‐Guo 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Kinetic Resolution of Epoxides by a C—C Bond‐Forming Reaction: Highly Enantioselective Addition of Indoles to cis, trans, and meso Aromatic Epoxides Catalyzed by [Cr(salen)] Complexes.
Authors: Bandini Marco , Cozzi Pier Giorgio , Melchiorre Paolo , Umani‐Ronchi Achille 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Control of Product Distribution in the Domino Metathesis Reactions of N‐Alkynyl 2‐Azabicyclo[2.2.1]hept‐5‐en‐3‐ones. A Convenient Synthesis of Functionalized γ‐Lactams and Indolizidinones.
Authors: Arjona Odon , Csaky Aurelio G. , Leon Vanessa , Medel Rocio , Plumet Joaquin 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Intramolecular Hydroamination/Cyclization of Conjugated Aminodienes Catalyzed by Organolanthanoid Complexes. Scope, Diastereo‐ and Enantioselectivity, and Reaction Mechanism.
Authors: Hong Sukwon , Kawaoka Amber M. , Marks Tobin J. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
An Efficient Synthesis of N3,4‐Diphenyl‐5‐(4‐fluorophenyl)‐2‐isopropyl‐1H‐3‐pyrrolecarboxamide, a Key Intermediate for Atorvastin Synthesis.
Authors: Pandey Pramod S. , Rao T. Srinivasa 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis of Indolo[1,2‐b]indazole Derivatives.
Authors: Zhu Yong‐ming , Kaneko Kimiyoshi , Kato Osamu , Kiryu Yoshimitsu , Takatsu Noriyuki , Shiono Kazuhiko , Katayama Hajime 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Antimicrobial Activities of Some Imidazole Substituted Indoles.
Authors: Benkli Kadriye , Demirayak Seref , Gundogdu‐Karaburun Nalan , Kiraz Nuri , Iscan Gokalp , Ucucu Umit 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Phenolic Thiazoles as Novel Orally‐Active Neuroprotective Agents.
Authors: Harnett Jeremiah J. , Roubert Veronique , Dolo Christine , Charnet Christelle , Spinnewyn Brigitte , Cornet Sylvie , Rolland Alain , Marin Jean‐Gregoire , Bigg Dennis , Chabrier Pierre‐E. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis, Characterization and Antiinflammatory‐Analgesic Properties of 6‐(α‐Amino‐4‐chlorobenzyl)thiazolo[3,2‐b]‐1,2,4‐triazol‐5‐ols.
Authors: Tozkoparan Birsen , Goekhan Nesrin , Kuepeli Esra , Yesilada Erdem , Ertan Mevluet 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
An Efficient Chemical Fixation of Nitric Oxide: Convenient and Practical Synthesis of 1,2,3‐Oxadiazole 3‐Oxides.
Authors: Sugihara Takumichi , Kuwahara Kimiko , Wakabayashi Akihito , Takao Hiroko , Imagawa Hiroshi , Nishizawa Mugio 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Stereochemistry of Nucleophilic Substitution Reactions Depending upon Substituent: Evidence for Electrostatic Stabilization of Pseudoaxial Conformers of Oxocarbenium Ions by Heteroatom Substituents.
Authors: Ayala Leticia , Lucero Claudia G. , Romero Jan Antoinette C. , Tabacco Sarah A. , Woerpel K. A. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Spectroscopic Properties of Cross‐Conjugated Ketones and meso‐Substituted Tridecamethine Salts Containing the Pyran or Pyridone Fragment.
Authors: Krasnaya Zh. A. , Smirnova Yu. V. , Shvedova L. A. , Tatikolov A. S. , Kuz'min V. A. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Pyridazines. Part 36. Synthesis and Antiplatelet Activity of 5‐Substituted‐6‐phenyl‐3(2H)‐pyridazinones.
Authors: Coelho Alberto , Sotelo Eddy , Fraiz Nuria , Yanez Matilde , Laguna Reyes , Cano Ernesto , Ravina Enrique 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
A Facile Synthesis of New 3‐Substituted‐2,3‐dihydropyrido[3,2‐d]pyrimidine‐2,4‐diones.
Authors: Mamouni R. , Akssira M. , Aadil M. , Elhakmaoui A. , Lasri J. , Zaballos‐Garcia E. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Spiropyrans and Spirooxazines. Part 2. Synthesis, Structures, and Photochromic Properties of 6′‐Cyano‐Substituted Spironaphthooxazines.
Authors: Voloshin N. A. , Metelitsa A. V. , Micheau J. C. , Voloshina E. N. , Besugliy S. O. , Shelepin N. E. , Minkin V. I. , Tkachev V. V. , Safoklov B. B. , Aldoshin S. M. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Nitration of the 6‐Methyl‐1,3,5‐triazine Derivatives, 6‐Methyl‐1,3,5‐triazine‐2,4(1H,3H)‐dione and 2,4‐Dimethoxy‐6‐methyl‐1,3,5‐triazine.
Authors: Bellamy Anthony J. , Latypov Nikolaj V. , Goede Patrick 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Chalcogeno Morita—Baylis—Hillman Reaction of 2‐(Methylchalcogeno)phenyl Vinyl Ketones with Aldehydes, Ketones, and α‐Dicarbonyl Compounds.
Authors: Kinoshita Hironori , Kinoshita Sayaka , Munechika Yukari , Iwamura Tatsunori , Watanabe Shin‐ichi , Kataoka Tadashi 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
An Unprecedented N‐Transacylation Reaction of 2‐Acetamido‐2‐deoxy‐α‐D‐glucopyranosides.
Authors: Li Yingxia , Li Chunxia , Wang Peng , Chu Shidong , Guan Huashi , Yu Biao 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
The Selective Silylation of D‐Mannitol Assisted by Phenylboronic Acid and the Solid State and Solution Structures of the Intermediate 1,6‐Bis(silyl) Bis(phenylboronates).
Authors: Bhaskar Vijaya , D'Elia Angelo , Duggan Peter J. , Humphrey David G. , Krippner Guy Y. , Nhan Trang T. , Tyndall Edward M. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Efficacy of Methylenecyclopropane Analogues of Nucleosides Against Herpesvirus Replication in vitro.
Authors: Kushner Nicole L. , Williams Stephanie L. , Hartline Caroll B. , Harden Emma A. , Bidanset Deborah J. , Chen Xinchao , Zemlicka Jiri , Kern Earl R. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Novel Galbonolide Derivative as IPC Synthase Inhibitors: Design, Synthesis and in vitro Antifungal Activities.
Authors: Sakoh Hiroki , Sugimoto Yuichi , Imamura Hideaki , Sakuraba Shunji , Jona Hideki , Bamba‐Nagano Rie , Yamada Koji , Hashizume Terutaka , Morishima Hajime 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Cubic AgPbmSbTe2+m: Bulk Thermoelectric Materials with High Figure of Merit.
Authors: Hsu Kuei Fang , Loo Sim , Guo Fu , Chen Wei , Dyck Jeffrey S. , Uher Ctirad , Hogan Tim , Polychroniadis E. K. , Kanatzidis Mercouri G. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Early (Ti, Zr)‐late (Rh, Ir) Heteronuclear Complexes with Bridging Sulfido Ligands
Authors: Oro Luis A. , Ciriano Miguel A. , Perez‐Torrente Jesus J. , Casado Miguel A. , Hernandez‐Gruel Marc A. F. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
New Perspectives for Olefin Complexes: Synthesis and Characterization of Stable Rhodium(0) and Iridium(0) Complexes
Authors: Harmer J. , Frison G. , Rudolph M. , Schoenberg H. , Deblon S. , Maire P. , Boulmaaz S. , Breher F. , Boehler C. , Rueegger H. , et al. et al. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Ru Complexes Bearing Bidentate Carbenes: From Innocent Curiosity to Uniquely Effective Catalysts for Olefin Metathesis
Authors: Hoveyda Amir H. , Gillingham Dennis G. , Van Veldhuizen Joshua J. , Kataoka Osamu , Garber Steven B. , Kingsbury Jason S. , Harrity Joseph P. A. 
Published: April 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Initially metastatic breast carcinoma has a distinct disease pattern but an equivalent outcome compared with recurrent metastatic breast carcinoma
Authors: Jimeno Antonio , Amador María Luz , González‐Cortijo Lucía , Tornamira María Victoria , Ropero Santiago , Valentín Vicente , Hornedo Javier , Cortés‐Funes Hernán , Colomer Ramón 
Published: April 2004

AbstractBACKGROUNDTo date, the clinical features and outcomes of patients with initially metastatic breast carcinoma (IMBC) have not been compared with the corresponding characteristics in patients with recurrent metastatic breast carcinoma (RBC). This issue may be particularly relevant to clinical research, as it may shed light on a potential bias with respect to the selection of patients for clinical trials.METHODSA retrospective analysis of the medical records of 1350 patients with breast carcinoma was performed. Outcome variables included overall survival, response rate, and progression‐free survival.RESULTSOne hundred nineteen of 370 patients with metastatic breast carcinoma had IMBC, whereas the remaining 251 had RBC. The median follow‐up duration was 39.4 months, and the median overall survival duration was 24 months. With regard to clinical characteristics, patients with IMBC were older than patients with RBC (61.7 years vs. 58.1 years; P < 0.001) and had a higher incidence of lobular carcinoma (15.9% vs. 7.7%; P = 0.018), a greater proportion of T3–4 tumors (58.8% vs. 27.9%; P < 0.001), a higher incidence of bone as the dominant metastatic site (41.2% vs. 21.5%; P < 0.001), a lower incidence of soft tissue as the dominant metastatic site (10.1% vs. 26.7%; P < 0.001), and a similar incidence of the viscera as the dominant metastatic site (48.7% vs. 51.8%; P = 0.78). Median overall survival duration was similar for patients with IMBC (25.1 months) and patients with RBC (23.3 months; P = 0.81). Statistical analyses also revealed nonsignificant differences between patients with IMBC and patients with RBC in terms of response rate (40.7% vs. 35.2%, respectively; P = 0.35) and median progression‐free survival duration (10.2 months vs. 9.0 months, respectively; P = 0.58).CONCLUSIONSAlthough patients with IMBC and patients with RBC exhibit distinct histologic and clinical characteristics, similar treatment efficacy results and survival outcomes are observed in these two groups. Cancer 2004. © 2004 American Cancer Society.
Myelin oligodendrocyte glycoprotein‐35–55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA‐DR2‐transgenic mice
Authors: Rich Cathleen , Link Jason M. , Zamora Alex , Jacobsen Helle , Meza‐Romero Roberto , Offner Halina , Jones Richard , Burrows Gregory G. , Fugger Lars , Vandenbark Arthur A. 
Published: April 2004

AbstractThe use of HLA class II‐transgenic (Tg) mice has facilitated identification of antigenic T cell epitopes that may contribute to inflammation in T cell‐mediated diseases such as rheumatoid arthritis and multiple sclerosis (MS). In this study, we compared the encephalitogenic activity of three DR2‐restricted myelin determinants [mouse (m) myelin oligodendrocyte glycoprotein (MOG)‐35–55, human (h)MOG‐35–55 and myelin basic protein (MBP)‐87–99] in Tg mice expressing the MS‐associated DR2 allele, DRB1*1501. We found that mMOG‐35–55 peptide was strongly immunogenic and induced moderatelysevere chronic experimental autoimmune encephalomyelitis (EAE) with white matter lesions after a single injection in Freund's complete adjuvant followed by pertussis toxin. hMOG‐35–55 peptide,which differs from mMOG‐35–55 peptide by a proline for serine substitution at position 42, was also immunogenic, but not encephalitogenic, and was only partially cross‐reactive with mMOG‐35–55. In contrast, MBP‐87–99, which can induce EAE in double‐Tg mice expressing both HLA‐DR2 and a human MBP‐specific TCR, was completely non‐encephalitogenic in HLA‐DR2‐Tg mice lacking the human TCR transgene. These findings demonstrate potent encephalitogenic activity of the mMOG‐35–55 peptide in association with HLA‐DR2, thus providing a strong rationale for further study of hMOG‐35–55 peptide as a potential pathogenic determinant in humans.
Necrosis‐like cell death induced by bacteria in mouse macrophages
Authors: Kirschnek Susanne , Scheffel Julia , Heinzmann Ulrich , Häcker Georg 
Published: April 2004

AbstractThe death of individual cells is a frequent and physiological event in the mammalian immune system and most often occurs by apoptosis. It is becoming increasingly clear that cell death is alsoinduced during bacterial infections. Here we report that, in addition to the apoptotic form already established, a necrosis‐like form of cell death is induced by pyogenic bacteria (Enterobacteriaceae, Pseudomonas, enterococci) in mouse macrophages. Necrosis could be separated from apoptosis as it did not require phagocytosis of bacteria and occurred when apoptosis was inhibited by caspase blockade or by Bcl‐2. Furthermore, ligands that stimulate Toll‐like receptors were also found to have the capacity to induce necrosis. Strikingly, this form of cell death was sufficient for the uptake of dead cells by either mouse bone marrow‐derived DC or a cell line derived from DC, possibly by virtue of the externalization of phosphatidylserine. Since the loading with bacteria‐carrying cells is likely to impact on DC function, this form of necrosis may have a previously unsuspected role in the development of an immune response.
Differential usage of VLA‐4 and CXCR4 by CD3+CD56+ NKT cells and CD56+CD16+ NK cells regulates their interaction with endothelial cells
Authors: Franitza Suzanna , Grabovsky Valentin , Wald Ori , Weiss Ido , Beider Katia , Dagan Michal , Darash‐Yahana Merav , Nagler Arnon , Brocke Stefan , Galun Eithan , Alon Ronen , Peled Amnon 
Published: April 2004

AbstractThe mechanism that regulates the preferential accumulation of NKT cells in the BM is unknown. The BM endothelium constitutively expresses selectins, the integrin ligands VCAM‐1 and ICAM‐1, andthe chemokine CXCL12. Both NK and NKT subsets of cells exhibited similar tethering and rolling interactions on both P‐selectin and E‐selectin and expressed similar levels of the integrins, VLA‐4 and LFA‐1. Although NKT cells express higher levels of CXCR4 than NK cells, CXCL12 (the ligand for CXCR4) rapidly stimulates similar levels of adhesion of NK and NKT cells to VCAM‐1 and ICAM‐1. In both subsets, the arrest on VCAM‐1 was dependent on high affinity VLA‐4 and the homing of these cells to the BM of NOD/SCID was VLA‐4‐dependent. However, as opposed to the situation for NK cells, CXCL12 preferentially triggers, under shear flow, the rolling on VCAM‐1 and transendothelial migration of NKT cells. Moreover, over‐expression of high levels of CXCR4 on the YT NK cell line enables them to migrate in response to CXCL12. This study therefore suggests an important role for CXCR4 levels of expression and for VLA‐4 in regulating the accumulation of NKT cells in the BM.
Chronic graft‐versus‐host reaction is associated with a decrease in Ig light chain receptor editing in bone marrow self‐reactive B cells
Authors: Feuerstein Nili , DeSimone Dennis C. , Eisenberg Robert A. , Finkel Terri H. 
Published: April 2004

AbstractThe encounter of developing B cells in the bone marrow with soluble hen egg lysozyme (sHEL) self antigen induces anergy and endogenous κ light chain rearrangements (‘receptor editing’). We have previously shown that induction of chronic graft‐versus‐hostreaction (GVH) in tolerant Ig/sHEL mice results in prevention of B cell anergy in the bone marrow and the spleen. We now report that in chronic GVH, immature self‐reactive B cells also show reduced levels of receptor editing in the bone marrow. This is evidenced by the following observations: (a) a small population of‘receptor‐edited’ B cells, which is found in tolerant mice, is markedly reduced in mice that have lost tolerance in chronic GVH; (b) self‐reactive B cells in GVH mice have reduced levels of endogenous κ chain rearrangements; and (c) recombinase‐activating gene (RAG)‐2 expression is markedly decreased in immature self‐reactive B cells in the bone marrow of chronic GVH mice. These results suggest that in chronic GVH newly emerging B cells escape tolerance, in part because of decreased receptor editing in the bone marrow. Thus, the autoimmunity induced by chronic GVH may ultimately result from the failure of B cell tolerance at multiple checkpoints.