bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia
Authors: Mayr Christine , Speicher Michael R. , Kofler David M. , Buhmann Raymund , Strehl John , Busch Raymonde , Hallek Michael , Wendtner Clemens-Martin 
Published: September 2005

AbstractIn chronic lymphocytic leukemia (CLL), chromosomes usually evade detailed cytogenetic analyses because cells poorly respond to the traditionally used set of mitogens. We applied novel technologies, such as stimulation of CLL cells either with CD40 ligand or with a combination of CpG-oligodeoxynucleotides and IL-2, to increase the freequncy of metaphase spreads for detailed chromosome analysis in 96 patients with CLL. This approach revealed that translocations occurred in 33 of 96 (34%) of our patients with CLL. The presence of translocations defined a new prognostic subgroup because these patients have significantly shorter median treatment-free survival (24 months vs 106 months; P < .001) and significantly inferior overall survival (OS; median, 94 months) than patients without translocations (346 months; P < .001). In multivariate analysis—including Binet stage, complex karyotype, CD38 expression, and 17p deletions—translocation proved to be the prognostic marker with the highest impact for an unfavorable clinical outcome (P < .001). In summary, we identified a new subgroup of patients with CLL defined by chromosomal trans-locations and poor prognosis. Our data may facilitate the identification of molecular events crucial for transforming activity in this disease and should have implications for risk-adapted clinical management of patients with CLL. (Blood. 2006;107:742-751)
β-Glucan enhances complement-mediated hematopoietic recovery after bone marrow injury
Authors: Cramer Daniel E. , Allendorf Daniel J. , Baran Jarek T. , Hansen Richard , Marroquin Jose , Li Bing , Ratajczak Janina , Ratajczak Mariusz Z. , Yan Jun 
Published: September 2005

AbstractMyelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony-stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stroma-iC3b interacts with hematopoietic progenitor cells (HPCs) and the role of complement (C) and complement receptor 3 (CR3) in BM injury/repair. We demonstrate here that stroma-iC3b tethers HPCs via the inserted (I) domain of HPC complement receptor 3 (CR3, CD11b/CD18, Mac-1). Following irradiation, stroma-iC3b was observed in the presence of purified IgM and normal mouse serum (NMS), but not serum from Rag-2-/- mice, implicating a role for antibody (Ab) and the classic pathway of C activation. Furthermore, a novel role for soluble yeast β-glucan, a ligand for the CR3 lectin-like domain (LLD), in the priming of CR3+ HPC is suggested. Soluble yeast β-glucan could enhance the proliferation of tethered HPCs, promote leukocyte recovery following sublethal irradiation, and increase the survival of lethally irradiated animals following allogeneic HPC transplantation in a CR3-dependent manner. Taken together, these observations suggest a novel role for C, CR3, and β-glucan in the restoration of hematopoiesis following injury. (Blood. 2006;107:835-840)
Key role of the p110δ isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110δ function in B cells
Authors: Bilancio Antonio , Okkenhaug Klaus , Camps Montserrat , Emery Juliet L. , Ruckle Thomas , Rommel Christian , Vanhaesebroeck Bart 
Published: September 2005

AbstractMouse gene–targeting studies have documented a central role of the p110δ isoform of phosphoinositide 3-kinase (PI3K) in B-cell development and function. A defect in B-cell antigen receptor (BCR) signaling is key to this B-cell phenotype. Here we further characterize this signaling defect and report that a p110δ-selective small molecule inhibitor mirrors the effect of genetic inactivation of p110δ in BCR signaling. p110δ activity is indispensable for BCR-induced DNA synthesis and phosphorylation of Akt/protein kinase B (PKB), forkhead transcription factor/forkhead box O3a (FOXO3a), and p70 S6 kinase (p70 S6K), with modest effects on the phosphorylation of glycogen synthase kinase 3 α/β (GSK3α/β) and extracellular signal-regulated kinase (Erk). The PI3K-dependent component of intracellular calcium mobilization also completely relies on p110δ catalytic activity. Resting B cells with inactive p110δ fail to enter the cell cycle, correlating with an incapacity to up-regulate the expression of cyclins D2, A, and E, and to phosphorylate the retinoblastoma protein (Rb). p110δ is also critical for interleukin 4 (IL-4)–induced phosphorylation of Akt/PKB and FOXO3a, and protection from apoptosis. Taken together, these data show that defects observed in p110δ mutant mice are not merely a consequence of altered B-cell differentiation, and emphasize the potential utility of p110δ as a drug target in autoimmune diseases in which B cells play a crucial role.
An easy approach to the Robins-Breslow-Greenland variance estimator
Authors: Silcocks Paul 
Published: September 2005

AbstractThe Mantel-Haenszel estimate for the odds ratio (and its logarithm) in stratified case control studies lacked a generally acceptable variance estimate for many years. The Robins-Breslow-Greenland estimate has met this need, but standard textbooks still do not provide an explanation of how it is derived. This article provides an accessible derivation which demonstrates the link between the Robins-Breslow-Greenland estimate and the familiar Woolf estimate for the variance of the log odds ratio, and which could easily be included in Masters level courses in epidemiology. The relationships to the unconditional and conditional maximum likelihood estimates are also reviewed.
Idiopathic chronic cough: a real disease or a failure of diagnosis?
Authors: McGarvey LPA 
Published: September 2005

AbstractDespite extensive diagnostic evaluation and numerous treatment trials, a number of patients remain troubled by a chronic and uncontrollable cough. Eosinophilic bronchitis, atopic cough and non-acid reflux have been recently added to the diagnostic spectrum for chronic cough. In some cases, failure to consider these conditions may explain treatment failure. However, a subset of patients with persisting symptoms may be regarded as having an idiopathic cough. These individuals are most commonly female, of postmenopausal age and frequently report viral upper respiratory tract infections as an initiating event. This paper seeks to explore the validity of idiopathic cough as a distinct clinical entity.
Positive association between mammographic breast density and bone mineral density in the Postmenopausal Estrogen/Progestin Interventions Study
Authors: Crandall Carolyn , Palla Shana , Reboussin Beth A , Ursin Giske , Greendale Gail A 
Published: September 2005

Abstract
Introduction
Mammographic breast density is a strong independent risk factor for breast cancer. We hypothesized that demonstration of an association between mammographic breast density and bone mineral density (BMD) would suggest a unifying underlying mechanism influencing both breast density and BMD.

Methods
In a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions Study (PEPI), participants were aged 45 to 64 years and were at least 1 year postmenopausal. Mammographic breast density (percentage of the breast composed of dense tissue), the outcome, was assessed with a computer-assisted percentage-density method. BMD, the primary predictor, was measured with dual-energy X-ray absorptiometry. Women quitting menopausal hormone therapy to join PEPI were designated recent hormone users.

Results
The mean age of the 594 women was 56 years. The average time since menopause was 5.6 years. After adjustment for age, body mass index, and cigarette smoking, in women who were not recent hormone users before trial enrollment (n = 415), mammographic density was positively associated with total hip (P = 0.04) and lumbar (P = 0.08) BMD. Mammographic density of recent hormone users (n = 171) was not significantly related to either total hip (P = 0.51) or lumbar (P = 0.44) BMD. In participants who were not recent hormone users, mammographic density was 4% greater in the highest quartile of total hip BMD than in the lowest. In participants who were not recent hormone users, mammographic density was 5% greater in the highest quartile of lumbar spine BMD than in the lowest.

Conclusion
Mammographic density and BMD are positively associated in women who have not recently used postmenopausal hormones. A unifying biological mechanism may link mammographic density and BMD. Recent exogenous postmenopausal hormone use may obscure the association between mammographic density and BMD by having a persistent effect on breast tissue.
Prognostic Analysis for Survival in Adult Solid Organ Transplant Recipients With Post-Transplantation Lymphoproliferative Disorders
Authors: Ghobrial Irene M. , Habermann Thomas M. , Maurer Matthew J. , Geyer Susan M. , Ristow Kay M. , Larson Timothy S. , Walker Randall C. , Ansell Stephen M. , Macon William R. , Gores Gregory G. , Stegall Mark D. , McGregor Christopher G. 
Published: September 2005

Purpose The objective of this study was to determine prognostic factors for overall survival in patients with post-transplantation lymphoproliferative disorders (PTLDs). Patients and Methods This study focused on the 107 adult solid organ transplantation patients who were diagnosed with PTLDs at Mayo Clinic (Rochester, MN) between December 1970 and May 2003. Results The median age at the time of diagnosis was 48 years (range, 15 to 75 years). Extranodal disease including grafted organ involvement was present in 85 patients (80%). The graft organ was involved in 30 patients (28%). At the time of these analyses, 62 patients (58%) had died. The median survival for the entire cohort was 31.5 months (95% CI, 10.7 to 72.5 months). The median follow-up of living patients was 51.8 months (range, 5.6 to 202.6 months). In univariate analyses for overall survival from the time of PTLD diagnosis, the following poor prognostic factors were identified: poor performance status with Eastern Cooperative Oncology Group levels 3 and 4 (P < .0001), grafted organ involvement (P = .0005), the presence of one or more extranodal sites (P = .005), both nodal and extranodal disease (P = .002), high International Prognostic Index (P = .006), advanced stage (P = .001), and elevated lactate dehydrogenase (P = .03). A final multivariable model for survival was constructed using three factors: poor performance status (3 to 4), monomorphic disease, and graft organ involvement. Conclusion A prognostic model has been developed for PTLD patients using one center's 30 years of experience. We propose additional confirmation and validation of these prognostic factors in larger prospective studies.
Phase I to II Multicenter Study of Oblimersen Sodium, a Bcl-2 Antisense Oligonucleotide, in Patients With Advanced Chronic Lymphocytic Leukemia
Authors: O'Brien Susan M. , Cunningham Charles C. , Golenkov Anatoliy K. , Turkina Anna G. , Novick Steven C. , Rai Kanti R. 
Published: September 2005

Purpose To determine the maximum-tolerated dose (MTD), efficacy, safety, and pharmacokinetics of oblimersen sodium in patients with advanced chronic lymphocytic leukemia (CLL). Patients and Methods Eligible patients had relapsed or refractory CLL after treatment with fludarabine. Oblimersen was administered at doses ranging from 3 to 7 mg/kg/d as a 5-day continuous intravenous infusion in cycle 1 and as a 7-day continuous intravenous infusion in subsequent cycles every 3 weeks in stable or responding patients. Results Forty patients were enrolled and treated (14 patients in phase I and 26 patients in phase II). Dose-limiting reactions in phase I included hypotension and fever, and the MTD for phase II dosing was established at 3 mg/kg/d. Two (8%) of 26 assessable patients achieved a partial response. Other evidence of antitumor activity included ≥ 50% reduction in splenomegaly (seven of 17 patients; 41%), complete disappearance of hepatomegaly (two of seven patients; 29%), ≥ 50% reduction of lymphadenopathy (seven of 22 patients; 32%), and ≥ 50% reduction in circulating lymphocyte counts (11 of 22 patients; 50%). Adverse events included transient hypotension, fever, fatigue, night sweats, diarrhea, nausea, vomiting, hypokalemia, and cough. Plasma concentrations of oblimersen (parent drug) and its major metabolites were variable. Renal clearance represented only a small portion of total parent drug clearance. Conclusion Dosing with oblimersen sodium in patients with CLL is limited by development of a cytokine release syndrome that is characterized by fever, hypotension, and back pain. Oblimersen sodium has modest single-agent activity in heavily pretreated patients with advanced CLL, and further evaluation of its activity in combination with cytotoxic drugs is warranted.
Epstein-Barr Virus As a Marker of Survival After Hodgkin's Lymphoma: A Population-Based Study
Authors: Keegan Theresa H.M. , Glaser Sally L. , Clarke Christina A. , Gulley Margaret L. , Craig Fiona E. , DiGiuseppe Joseph A. , Dorfman Ronald F. , Mann Risa B. , Ambinder Richard F. 
Published: September 2005

Purpose Epstein-Barr virus (EBV) in Hodgkin's lymphoma (HL) cells has been considered as a prognostic marker for this heterogeneous disease, but studies have yielded mixed findings, likely because of selected patient series and failure to acknowledge an effect of age on outcome. This study assessed survival after HL in a population-based cohort large enough to examine the joint effects of EBV with other factors including age, sex, and histologic subtype. Patients and Methods Included were 922 patients with classical HL diagnosed between mid-1988 and 1997 in the Greater San Francisco Bay Area, with archived biopsy specimens assayed for EBV with immunohistochemistry and in situ hybridization. Vital status was followed through December 30, 2003 (median follow-up time, 97 months). Overall and disease-specific survival were analyzed with the Kaplan-Meier method and Cox proportional hazards regression models. Results In children less than 15 years old, EBV presence was suggestively associated (P = .07) with favorable survival. In adults aged 15 to 44 years, EBV did not affect HL outcome, although a protective effect was suggested. In older adults (45 to 96 years), EBV presence nearly doubled the risk of overall and HL-specific mortality but only for patients with nodular sclerosis (NS) histologic subtype (hazard ratio for death = 2.5; 95% CI, 1.5 to 4.3). Conclusion In HL, EBV tumor cell presence is associated with better survival in young patients and poorer survival in older patients with NS, independent of other factors. Variation in outcome by age and histology could indicate biologically distinct disease entities. Evidence that EBV is a meaningful prognostic marker may have therapeutic relevance.
Bleomycin Pulmonary Toxicity Has a Negative Impact on the Outcome of Patients With Hodgkin's Lymphoma
Authors: Martin William G. , Ristow Kay M. , Habermann Thomas M. , Colgan Joseph P. , Witzig Thomas E. , Ansell Stephen M. 
Published: September 2005

Purpose Bleomycin pulmonary toxicity (BPT) has been well described in Hodgkin's lymphoma (HL) patients treated with bleomycin-containing chemotherapy regimens. The influence of this pulmonary complication, along with the omission of bleomycin from further chemotherapy, on overall survival (OS) and progression-free survival (PFS) in HL remains unclear. We reviewed our experience with BPT in HL to better delineate outcome and appropriate treatment in these patients. Patients and Methods One hundred forty-one patients who were treated with bleomycin-containing chemotherapy for newly diagnosed HL between January 1986 and February 2003 were eligible for this retrospective review. BPT was defined by the presence of pulmonary symptoms, bilateral interstitial infiltrates, and no evidence of an infectious etiology. Results BPT was observed in 18% of patients. Increasing age, doxorubicin, bleomycin, vinblastine, and dacarbazine as initial therapy, and granulocyte colony-stimulating factor use were associated with the development of BPT. Patients with BPT had a median 5-year OS rate of 63% v 90% (P = .001) in unaffected patients. The mortality rate from BPT was 4.2% in all patients and 24% in patients who developed the pulmonary syndrome. BPT incidence and mortality were highest in patients older than 40 years. The omission of bleomycin had no impact on obtaining a complete remission, PFS, or OS. Conclusion BPT results in a significant decrease in 5-year OS in patients who are treated for HL. Age ≥ 40 years seems to add substantially to the risk. In patients who do not die from acute pulmonary toxicity, both OS and PFS seem equal, despite the omission of bleomycin.
Differential Recruitment of p160 Coactivators by Glucocorticoid Receptor between Schwann Cells and Astrocytes
Authors: Grenier Julien , Trousson Amalia , Chauchereau Anne , Cartaud Jean , Schumacher Michael , Massaad Charbel 
Published: September 2005

Abstract
In the nervous system, glucocorticoids can exert beneficial or noxious effects, depending on their concentration and the duration of hormonal stimulation. They exert their effects on neuronal and glial cells by means of their cognate receptor, the glucocorticoid receptor (GR), which recruits the p160 coactivator family members SRC-1 (steroid receptor coactivator 1), SRC-2, and SRC-3 after hormone binding. In this study, we investigated the molecular pathways used by the GR in cultured glial cells of the central and the peripheral nervous systems, astrocytes and Schwann cells (MSC80 cells), respectively. We performed functional studies based on transient transfection of a minimal glucocorticoid-sensitive reporter gene into the glial cells to test the influence of overexpression or selective inhibition by short interfering RNA of the three p160 coactivator family members on GR transactivation. We demonstrate that, depending on the glial cell type, GR differentially recruits p160 family members: in Schwann cells, GR recruited SRC-1a, SRC-1e, or SRC-3, whereas in astrocytes, SRC-1e and SRC-2, and to a lesser extent SRC-3, were active toward GR signaling. The C-terminal nuclear receptor-interacting domain of SRC-1a participates in its exclusion from the GR transcriptional complex in astrocytes. Immunolocalization experiments revealed a cell-specific intracellular distribution of the p160s, which was dependent on the duration of the hormonal induction. For example, within astrocytes, SRC-1 and SRC-2 were mainly nuclear, whereas SRC-3 unexpectedly localized to the lumen of the Golgi apparatus. In contrast, in Schwann cells, SRC-1 showed a nucleocytoplasmic shuttling depending on hormonal stimulation, whereas SRC-2 remained strictly nuclear and SRC-3 remained predominantly cytoplasmic. Altogether, these results highlight the cell specificity and the time dependence of p160s recruitment by the activated GR in glial cells, revealing the complexity of GR-p160 assembly in the nervous system.
Motility and growth of human bone-marrow mesenchymal stem cells during ex vivo expansion in autologous serum
Authors: Kobayashi T. , Watanabe H. , Yanagawa T. , Tsutsumi S. , Kayakabe M. , Shinozaki T. , Higuchi H. , Takagishi K. 
Published: September 2005

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures. Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.
The insertion geometry of the posterolateral corner of the knee
Authors: Brinkman J.-M. , Schwering P. J. A. , Blankevoort L. , Koolos J. G. , Luites J. , Wymenga A. B. 
Published: September 2005

We have quantitatively documented the insertion geometry of the main stabilising structures of the posterolateral corner of the knee in 34 human cadavers. The lateral collateral ligament inserted posterior (4.6 mm, sd 2) and proximal (1.3 mm, sd 3.6) to the lateral epicondyle of the femur and posterior (8.1 mm, sd 3.2) to the anterior point of the head of the fibula. On the femur, the popliteus tendon inserted distally (11 mm, sd 0.8) and either anterior or posterior (mean 0.84 mm anterior, sd 4) to the lateral collateral ligament. The popliteofibular ligament inserted distal (1.3 mm, sd 1.2) and anterior (0.5 mm, sd 2.0) to the tip of the styloid process of the fibula. The ligaments had a consistent pattern of insertion and, despite the variation between specimens, the standard deviations were less than the typical size of drill hole used in reconstruction of the posterolateral corner. The data provided in this study can be used in the anatomical repair and reconstruction of this region of the knee.
Metal-specific differences in levels of DNA damage caused by synovial fluid recovered at revision arthroplasty
Authors: Davies A. P. , Sood A. , Lewis A. C. , Newson R. , Learmonth I. D. , Case C. P. 
Published: September 2005

Previous research has shown an increase in chromosomal aberrations in patients with worn implants. The type of aberration depended on the type of metal alloy in the prosthesis. We have investigated the metal-specific difference in the level of DNA damage (DNA stand breaks and alkali labile sites) induced by culturing human fibroblasts in synovial fluid retrieved at revision arthroplasty. All six samples from revision cobalt-chromium metal-on-metal and four of six samples from cobalt-chromium metal-on-polyethylene prostheses caused DNA damage. By contrast, none of six samples from revision stainless-steel metal-on-polyethylene prostheses caused significant damage. Samples of cobalt-chromium alloy left to corrode in phosphate-buffered saline also caused DNA damage and this depended on a synergistic effect between the cobalt and chromium ions. Our results further emphasise that epidemiological studies of orthopaedic implants should take account of the type of metal alloy used.