bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Assessment of Glenohumeral Translation after Anterior Shoulder Dislocation and Subsequent Arthroscopic Bankart Repair
Authors: Marquardt Björn , Hurschler Christof , Schneppendahl Johannes , Witt Kai-Axel , Pötzl Wolfgang , Steinbeck Jörn 
Published: July 2006

Background During the past decade, developments in arthroscopic technology have made arthroscopic repair of labral lesions feasible. However, results with the use of the transglenoid suture technique, or with the use of bioabsorbable tacks, have remained variable in the literature, and the recurrence rates are still inferior to those of open Bankart repair. Hypothesis Arthroscopic Bankart repair with suture anchors can re-create translational and rotational range of motion of the intact glenohumeral joint, and the number of preoperative dislocations has an influence on the result. Study Design Controlled laboratory study. Materials Twelve cadaveric shoulders were tested in a robot-assisted shoulder simulator. Anterior and posterior translation and external rotation were measured for intact, dislocated (shoulders were randomly selected to 1 of 3 groups, which were dislocated 1, 3, or 7 times), and repaired conditions at 0° and 90° of glenohumeral elevation. Results After shoulder dislocation, a significant increase was found in translation and rotation, confirming the creation of a traumatic shoulder instability model. Further testing of the specimen revealed that translational and rotational ranges of motion were reduced by arthroscopic Bankart repair at both testing positions. External rotation was decreased significantly at 0° and 90° of abduction. No significant differences were found between the 3 dislocation groups. Conclusion The results demonstrate a sufficient biomechanical performance of arthroscopic Bankart repair using suture anchors in a traumatic anterior shoulder instability model. With the numbers available, no relationship was found between the number of dislocations and the postoperative result concerning translational or rotational motion. Clinical Relevance Glenohumeral translation and rotation after arthroscopic Bankart repair with use of suture anchors approached near normal values, confirming the clinical success of this technique.
Solute transport via the new permeability pathways in Plasmodium falciparum–infected human red blood cells is not consistent with a simple single-channel model
Authors: Staines Henry M. , Ashmore Stephanie , Felgate Hannah , Moore Jessica , Powell Trevor , Ellory J. Clive 
Published: July 2006

AbstractAfter infection of a red blood cell (RBC), the malaria parasite, Plasmodium falciparum, increases the permeability of the host's plasma membrane by inducing new permeability pathways (NPPs). Single-channel patch-clamp experiments have shown the presence in infected RBCs of novel anion-selective channel types with low open-state probabilities at positive membrane potentials. These channels have been postulated to form the NPPs. Here, we have used a range of transport techniques to study whether electroneutral solutes use these channels or altered/separate pathways. Transport of the electroneutral solute sorbitol via the NPPs was found to increase by a small but significant amount after gross membrane depolarization. This is inconsistent with transport via a channel with a reduced open-state probability at positive membrane potentials. As has been demonstrated previously for parasite-induced anion currents, sorbitol transport in infected RBCs was found to be sensitive to the presence of bovine serum albumin (BSA). However, it remains to be shown whether the effect is due to serum/BSA altering a single channel type or activating a new pathway. In addition, the study highlights problems that can occur when using different transport techniques to study the NPPs.
Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: a study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression
Authors: Dicker Frank , Schnittger Susanne , Haferlach Torsten , Kern Wolfgang , Schoch Claudia 
Published: July 2006

Abstract
Compared with fluorescence in situ hybridization (FISH), conventional metaphase cytogenetics play only a minor prognostic role in chronic lymphocytic leukemia (CLL) so far, due to technical problems resulting from limited proliferation of CLL cells in vitro. Here, we present a simple method for in vitro stimulation of CLL cells that overcomes this limitation. In our unselected patient population, 125 of 132 cases could be successfully stimulated for metaphase generation by culture with the immunostimulatory CpG-oligonucleotide DSP30 plus interleukin 2. Of 125 cases, 101 showed chromosomal aberrations. The aberration rate is comparable to the rate detected by parallel interphase FISH. In 47 patients, conventional cytogenetics detected additional aberrations not detected by FISH analysis. A complex aberrant karyotype, defined as one having at least 3 aberrations, was detected in 30 of 125 patients, compared with only one such case as defined by FISH. Conventional cytogenetics frequently detected balanced and unbalanced translocations. A significant correlation of the poor-prognosis unmutated IgVH status with unbalanced translocations and of the likewise poor-prognosis CD38 expression to balanced translocations and complex aberrant karyotype was found. We demonstrate that FISH analysis underestimates the complexity of chromosomal aberrations in CLL. Therefore, conventional cytogenetics may define subgroups of patients with high risk of progression.
Continuous signaling via PI3K isoforms β and γ is required for platelet ADP receptor function in dynamic thrombus stabilization
Authors: Cosemans Judith M. E. M. , Munnix Imke C. A. , Wetzker Reinhard , Heller Regine , Jackson Shaun P. , Heemskerk Johan W. M. 
Published: July 2006

Abstract
Signaling from collagen and G protein–coupled receptors leads to platelet adhesion and subsequent thrombus formation. Paracrine agonists such as ADP, thromboxane, and Gas6 are required for platelet aggregate formation. We hypothesized that thrombi are intrinsically unstable structures and that their stabilization requires persistent paracrine activity and continuous signaling, maintaining integrin αIIbβ3 activation. Here, we studied the disassembly of human and murine thrombi formed on collagen under high shear conditions. Platelet aggregates rapidly disintegrated (1) in the absence of fibrinogen-containing plasma; (2) by blocking or inhibiting αIIbβ3; (3) by blocking P2Y12 receptors; (4) by suppression of phosphoinositide 3-kinase (PI3K) β. In murine blood, absence of PI3Kγ led to formation of unstable thrombi, leading to dissociation of multiplatelet aggregates. In addition, blocking PI3Kβ delayed initial thrombus formation and reduced individual platelet-platelet contact. Similarly without flow, agonist-induced aggregation was reversed by late suppression of P2Y12 or PI3K isoforms, resulting in single platelets that had inactivated αIIbβ3 and no longer bound fibrinogen. Together, the data indicate that continuous outside-in signaling via P2Y12 and both PI3Kβ and PI3Kγ isoforms is required for perpetuated αIIbβ3 activation and maintenance of a platelet aggregate. This novel concept of intrinsic, dynamic thrombus instability gives possibilities for the use of antiplatelet therapy.
Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection
Authors: van Leeuwen Ester M. M. , Remmerswaal Ester B. M. , Heemskerk Mirjam H. M. , ten Berge Ineke J. M. , van Lier Rene A. W. 
Published: July 2006

Abstract
To obtain insight into human CD4+ T cell differentiation and selection in vivo, we longitudinally studied cytomegalovirus (CMV)–specific CD4+ T cells after primary infection. Early in infection, CMV-specific CD4+ T cells have the appearance of interferon γ (IFNγ)–producing T-helper 1 (TH1) type cells, whereas during latency a large population of CMV-specific CD4+CD28– T cells emerges with immediate cytotoxic capacity. We demonstrate that CD4+CD28– T cells could lyse CMV antigen–expressing target cells in a class II–dependent manner. To clarify the clonal relationship between early and late CMV-specific CD4+ T cells, we determined their Vβ usage and CDR3 sequences. The T-cell receptor β (TCRβ) diversity in the early CMV-specific CD4+ T-cell population was high in contrast to the use of a very restricted set of TCRβ sequences in latent infection. T-cell clones found in the late CMV-specific CD4+ T-cell population could not be retrieved from the early CD4+ T-cell population, or were present only at a low frequency. The observation that dominant CMV-specific CD4+ clones during latency were only poorly represented in the acute phase suggests that after the initial control of the virus strong selection and/or priming of novel clones takes place in persistent infections in humans.
Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation
Authors: Bozza Silvia , Bistoni Francesco , Gaziano Roberta , Pitzurra Lucia , Zelante Teresa , Bonifazi Pierluigi , Perruccio Katia , Bellocchio Silvia , Neri Mariella , Iorio Anna Maria , Salvatori Giovanni , De Santis Rita , Calvitti Mario , Doni Andrea , Garlanda Cecilia , Mantovani Alberto , Romani Luigina 
Published: July 2006

AbstractReactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. Pentraxin 3 (PTX3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hematopoietic transplantation. We assessed here whether PTX3 binds HCMV and murine virus (MCMV) and the impact on viral infectivity and superinfection in vivo. We found that PTX3 bound both viruses, reduced viral entry and infectivity in vitro, and protected from MCMV primary infection and reactivation as well as Aspergillus superinfection. This occurred through the activation of interferon (IFN) regulatory factor 3 (IRF3) in dendritic cells via the TLR9/MyD88-independent viral recognition sensing and the promotion of the interleukin-12 (IL-12)/IFN-γ–dependent effector pathway.
Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B
Authors: Fröhling Stefan , Schlenk Richard F. , Kayser Sabine , Morhardt Martina , Benner Axel , Döhner Konstanze , Döhner Hartmut ,   for the German-Austrian AML Study Group
Published: July 2006

AbstractTo assess the prognostic impact of cytogenetics in elderly patients with acute myeloid leukemia (AML) receiving intensive induction and consolidation treatment according to a single protocol specifically designed for patients above age 60, pretreatment samples from 361 patients registered for the AML HD98-B trial of the German-Austrian AML Study Group were analyzed by chromosome banding and fluorescence in situ hybridization, and cytogenetic findings were correlated with outcome. Using a proportional hazards model with backward selection, 3 prognostic subgroups were identified based on the influence of cytogenetic abnormalities on overall survival (OS): low-risk, t(15;17), and inv(16) in 25 of 361 patients (7%); standard-risk, normal karyotype, t(8;21), t(11q23), +8 within a noncomplex karyotype, and +11 within a noncomplex karyotype in 208 of 361 patients (58%); high-risk, all other aberrations in 128 of 361 patients (35%). On multivariate analysis, high-risk cytogenetics (hazard ratio [HR], 2.24) and age above 70 years (HR, 2.34) were independent prognostic factors affecting OS, and stratification according to these parameters demonstrated that a large subgroup of patients (55%), characterized by age 70 or older or high-risk cytogenetics, or both, had very unfavorable treatment results despite intensive chemotherapy. Thus, karyotype and age are major determinants of outcome in elderly patients with AML.
A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma
Authors: Richardson Paul G. , Blood Emily , Mitsiades Constantine S. , Jagannath Sundar , Zeldenrust Steven R. , Alsina Melissa , Schlossman Robert L. , Rajkumar S. Vincent , Desikan K. Raman , Hideshima Teru , Munshi Nikhil C. , Kelly-Colson Kathleen , Doss Deborah , McKenney Mary L. , Gorelik Svetlana , Warren Diane , Freeman Andrea , Rich Rebecca , Wu Anfang , Olesnyckyj Marta , Wride Kenton , Dalton William S. , Zeldis Jerome , Knight Robert , Weller Edie , Anderson Kenneth C. 
Published: July 2006

AbstractThis multicenter, open-label, randomized phase 2 study evaluated 2 dose regimens of lenalidomide for relapsed, refractory myeloma. Seventy patients were randomized to receive either 30 mg once-daily or 15 mg twice-daily oral lenalidomide for 21 days of every 28-day cycle. Patients with progressive or stable disease after 2 cycles received dexamethasone. Analysis of the first 70 patients showed increased grade 3/4 myelo-suppression in patients receiving 15 mg twice daily (41% versus 13%, P = .03). An additional 32 patients received 30 mg once daily. Responses were evaluated according to European Group for Blood and Marrow Transplantation (EBMT) criteria. Overall response rate (complete, partial, or minor) to lenalidomide alone was 25% (24% for once-daily and 29% for twice-daily lenalidomide). Median overall survival in 30-mg once-daily and twice-daily groups was 28 and 27 months, respectively. Median progression-free survival was 7.7 months on once-daily versus 3.9 months on twice-daily lenalidomide (P = .2). Dexamethasone was added in 68 patients and 29% responded. Time to first occurrence of clinically significant grade 3/4 myelosuppression was shorter in the twice-daily group (1.8 vs 5.5 months, P = .05). Significant peripheral neuropathy and deep vein thrombosis each occurred in only 3%. Lenalidomide is active and well tolerated in relapsed, refractory myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone.
Hematopoietic origin of fibroblasts/myofibroblasts: its pathophysiologic implications
Authors: Ogawa Makio , LaRue Amanda C. , Drake Christopher J. 
Published: July 2006

AbstractTissue fibroblasts/myofibroblasts play a key role in growth factor secretion, matrix deposition, and matrix degradation, and therefore are important in many pathologic processes. Regarding the origin of tissue fibroblasts/myofibroblasts, a number of recent in vivo transplantation studies have suggested the bone marrow as the source of fibroblasts/myofibroblasts in liver, intestine, skin, and lung. Because bone marrow cells are thought to contain 2 types of stem cells (ie, hematopoietic stem cells [HSCs] and mesenchymal stem cells), it is important to determine which type of stem cells is the source of fibroblasts/myofibroblasts. To address this issue, we have carried out a series of studies of tissue reconstitution by single HSCs. By transplanting clones derived from single HSCs expressing transgenic enhanced green fluorescent protein, we found that fibroblasts/myofibroblasts in many organs and tissues are derived from HSCs. This brief note summarizes these findings and discusses clinical and experimental perspectives generated by this newly identified differentiation pathway of HSCs.
Newly identified c-KIT receptor tyrosine kinase ITD in childhood AML induces ligand-independent growth and is responsive to a synergistic effect of imatinib and rapamycin
Authors: Corbacioglu Selim , Kilic Mehtap , Westhoff Mike-Andrew , Reinhardt Dirk , Fulda Simone , Debatin Klaus-Michael 
Published: July 2006

AbstractActivating mutations of c-KIT lead to ligand-independent growth. Internal tandem duplications (ITDs) of exon 11, which encodes the juxtamembrane domain (JMD), are constitutively activating mutations found in 7% of gastrointestinal stromal tumors (GISTs) but have not been described in childhood acute myeloid leukemia (AML). DNA and cDNA from 60 children with AML were screened by polymerase chain reaction (PCR) for mutations of the JMD. A complex ITD (kit cITD) involving exon 11 and exon 12 was identified with a relative frequency of 7% (4/60). The human kit cITDs were inserted into the murine c-Kit backbone and expressed in Ba/F3 cells. KIT cITD induced factorindependent growth and apoptosis resistance, and exhibited constitutive autophosphorylation. KIT cITD constitutively activated the PI3K/AKT pathway and phosphorylated STAT1, STAT3, STAT5, and SHP-2. Imatinib (IM) or rapamycin (Rap) led to complete inhibition of growth, with IC50 values at nanomolar levels. IM and Rap synergistically inhibited growth and surmounted KIT cITD-induced apoptosis resistance. IM but not LY294002 inhibited phosphorylation of STAT3 and STAT5, suggesting aberrant cross talk between PI3K- and STAT-activating pathways. The findings presented may have immediate therapeutic impact for a subgroup of childhood AML-expressing c-KIT mutations.
EphB2 and EphB4 receptors forward signaling promotes SDF-1–induced endothelial cell chemotaxis and branching remodeling
Authors: Salvucci Ombretta , de la Luz Sierra Maria , Martina Jose A. , McCormick Peter J. , Tosato Giovanna 
Published: July 2006

Abstract
The complex molecular mechanisms that drive endothelial cell movement and the formation of new vessels are poorly understood and require further investigation. Eph receptor tyrosine kinases and their membrane-anchored ephrin ligands regulate cell movements mostly by cell–cell contact, whereas the G-protein–coupled receptor CXCR4 and its unique SDF-1 chemokine ligand regulate cell movement mostly through soluble gradients. By using biochemical and functional approaches, we investigated how ephrinB and SDF-1 orchestrate endothelial cell movement and morphogenesis into capillary-like structures. We describe how endogenous EphB2 and EphB4 signaling are required for the formation of extracellular matrix–dependent capillary-like structures in primary human endothelial cells. We further demonstrate that EphB2 and EphB4 activation enhance SDF-1–induced signaling and chemotaxis that are also required for extracellular matrix–dependent endothelial cell clustering. These results support a model in which SDF-1 gradients first promote endothelial cell clustering and then EphB2 and EphB4 critically contribute to subsequent cell movement and alignment into cord-like structures. This study reveals a requirement for endogenous Eph signaling in endothelial cell morphogenic processes, uncovers a novel link between EphB forward signaling and SDF-1–induced signaling, and demonstrates a mechanism for cooperative regulation of endothelial cell movement.
Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications
Authors: Gonzalez-Paz Natalia , Chng Wee J. , McClure Rebecca F. , Blood Emily , Oken Martin M. , Ness Brian Van , James C. David , Kurtin Paul J. , Henderson Kimberly , Ahmann Gregory J. , Gertz Morie , Lacy Martha , Dispenzieri Angela , Greipp Philip R. , Fonseca Rafael 
Published: July 2006

Abstract
The biological and clinical implications of p16 gene methylation in multiple myeloma (MM) are still unclear despite previous studies. In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in monoclonal gammopathy of undetermined significance (MGUS; n = 17), smoldering multiple myeloma (SMM; n = 40), and MM (n = 522) at a prevalence of 24%, 28%, and 34%, respectively. However, p16 methylation does not appear to affect gene expression level. In a large cohort of patients with long-term follow-up information (n = 439), there was no difference in overall survival between patients with or without p16 methylation. We also found no association between p16 methylation and the main cytogenetic categories, although it was more common among patients with 17p13.1 deletions (p53 locus), a genetic progression event in MM. In addition, p16 methylation has no apparent effect on the cycle because there was also no difference in the plasma cell labeling index (a direct measurement of proliferation) between patients with and without p16 methylation. Our results question a major role for p16 methylation in the oncogenesis of the PC neoplasm, and we now believe p16 methylation may be a marker for overall epigenetic changes associated with disease progression, with no obvious direct biological or clinical consequences.
Upper airway dynamics during negative expiratory pressure in apneic and non-apneic awake snorers
Authors: Ferretti A , Giampiccolo P , Redolfi S , Mondini S , Cirignotta F , Cavalli A , Tantucci C 
Published: July 2006

Abstract

Background
The ability of negative expiratory pressure (NEP) technique to differentiate between awake snorers with and without obstructive sleep apnea-hypopnea (OSAH) was investigated.

Methods
Forty-eight subjects with sleep disordered breathing (SDB) and 7 healthy subjects, as non-snorer controls, underwent the NEP application of -5 and -7 cmH2O in the seated and supine position during wakefulness, after performing a sleep study. The upper airway collapsibility was assessed by computing the volume exhaled during the first 0.5 sec. (V,NEP0.5) and 1 sec. (V,NEP1) following the NEP start.

Results
Patients with severe (AHI ≥ 30) (n = 19) and mild-to-moderate (AHI <30 and >5) (n = 15) OSAH had lower V,NEP0.5 (340 ± 88 ml) as compared to snorers (AHI ≤ 5) (n = 14) (427 ± 101 ml; p < 0.01) and controls (n = 7) (492 ± 69 ml; p < 0.001) in the supine position with NEP -5 cmH2O. Less significant differences among the different groups were observed for V,NEP0.5 in the seated position with NEP -5 cmH2O and in both positions with NEP -7 cmH2O (only OSAH patients vs controls, p < 0.001). Similar results were obtained for V,NEP1 in either position by using both NEP -5 cmH2O and -7 cmH2O. In spite of this, a substantial overlapping of V,NEP0.5 and V,NEP1 between snorers and OSAH patients did not allow to identify a reliable diagnostic cut-off level. An inverse correlation with AHI was found for V,NEP0.5 in the supine position with NEP -5 cmH2O (rs = -0.46, p < 0.05) in severe OSAH patients.

Conclusion
The awake OSAH patients exhibit values of V,NEP0.5 and V,NEP1 lesser than those of awake snorers. The NEP technique, however, appears to have a limited usefulness as clinical tool for routine screening of the OSAH patients during wakefulness.