bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective binding of factor XI–N248 to activated human platelets
Authors: Sun Mao-Fu , Baglia Frank A. , Ho David , Martincic Danko , Ware Russell E. , Walsh Peter N. , Gailani David 
Published: July 2002

AbstractVariants of factor XI containing Gln226 to Arg (Q226 to R) and Ser248 to Asn (S248 to N) substitutions were first identified in an African American family with a history of excessive bleeding. The substitutions have recently been identified in unrelated individuals, suggesting they are relatively common. Both amino acids are located in the third apple domain of factor XI, an area implicated in binding interactions with factor IX and activated platelets. Recombinant factor XI–R226 and factor XI–N248 were compared with wild-type factor XI in assays for factor IX activation or platelet binding. Factor XI–R226 activates factor IX with a Michaelis-Menten constant (Km) about 5-fold greater than wild-type protein. The catalytic efficiency of factor IX activation is similar to wild-type protein, however, due to an increase in the turnover number (kcat) for the reaction. Iodinated factor XI–N248 binds to activated platelets with a dissociation constant (Kd) more than 5-fold higher than wild-type protein (55 nM and 10 nM, respectively). Activation of factor XI–N248 by thrombin in the presence of activated platelets is slower and does not progress to the same extent as activation of the wild-type protein under similar conditions. Factor XI–N248 activates factor IX normally in a purified protein system and has relatively normal activity in activated partial thromboplastin time (aPTT) assays. Factor XI–N248 is the first factor XI variant described with a clear functional difference compared with wild-type protein. Importantly, the defect in platelet binding would not be detected by routine clinical evaluation with an aPTT assay.
Expression of CCR-7, MIP-3β, and Th-1 chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities
Authors: Parlato Stefania , Santini Stefano M. , Lapenta Caterina , Di Pucchio Tiziana , Logozzi Mariantonia , Spada Massimo , Giammarioli Anna Maria , Malorni Walter , Fais Stefano , Belardelli Filippo 
Published: July 2002

AbstractThe migration capability of dendritic cells (DCs) is regulated by their response to factors, namely chemokines, that characterize maturation stage and shape their functional activities. This study examines the morphology, expression of chemokines/chemokine receptors, and migration properties of DCs generated after treatment of monocytes with type I interferon (IFN) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (IFN-DCs). IFN-DCs showed phenotypical and morphologic features undetectable in DCs generated in the presence of interleukin 4 (IL-4) and GM-CSF, such as expression of CD83 and CD25 and the presence of CD44+, highly polarized, thin, and long dendrites. IFN-DCs markedly migrated in response to β-chemokines (especially MIP-1β) and expressed the Th-1 chemokine IP-10. Notably, IFN-DCs showed an up-regulation of CCR7 as well as of its natural ligand MIP-3β, characteristics typical of mature DCs. Of interest, IFN-DCs exhibited a marked chemotactic response to MIP-3β in vitro and strong migratory behavior in severe combined immunodeficient (SCID) mice. In SCID mice reconstituted with human peripheral blood leukocytes, IFN-DCs induced a potent primary human antibody response and IFN-γ production, indicative of a Th-1 immune response. These results define the highly specialized maturation state of IFN-DCs and point out the existence of a “natural alliance” between type I IFN and monocyte/DC development, instrumental for ensuring an efficient connection between innate and adaptive immunity.
Identification of poor prognostic features among patients requiring mechanical ventilation after hematopoietic stem cell transplantation
Authors: Bach Peter B. , Schrag Deborah , Nierman David M. , Horak David , White Peter , Young James W. , Groeger Jeffrey S. 
Published: July 2002

Abstract
Patients who develop respiratory failure requiring mechanical ventilation after hematopoietic stem cell transplantation (HSCT) have very high mortality. Several investigators have identified prognostic features that can be used to identify a subset of these patients who are virtually certain to die, yet these have never been prospectively assessed. The objectives of this study were to determine the accuracy of published prognostic features for mortality and to determine the survival of patients who recover from respiratory failure. A systematic review of the literature was undertaken to identify reported poor prognostic features and survival rates. The study validated the reported poor prognostic features on a prospective, multicenter inception cohort of 226 patients with respiratory failure requiring mechanical ventilation after HSCT. The main outcome measures were determination of a baseline probability of death, drawn from literature review; likelihood ratio of mortality for each prognostic feature determined from the validation cohort; conditional probability of death in the presence of each feature; and 6-month survival of those who recover. Patients requiring mechanical ventilation after HSCT have a baseline probability of death of 82% to 96%. In the setting of combined hepatic and renal dysfunction, the probability of death rises to 98% to 100%. Other previously reported prognostic features are less strongly associated with mortality. For patients who recover from respiratory failure, the proportion surviving 6 months or longer ranges from 27% to 88%. It was concluded that in patients requiring mechanical ventilation after HSCT, the presence of combined hepatic and renal dysfunction is highly predictive of death. The presence of this feature may justify the recommendation to withdraw life-sustaining measures.
Origins of “late” relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes
Authors: Ford Anthony M. , Fasching Karin , Panzer-Grümayer E. Renate , Koenig Margit , Haas Oskar A. , Greaves Mel F. 
Published: July 2002

Abstract
Approximately 20% of childhood B-precursor acute lymphoblastic leukemia (ALL) has a TEL-AML1 fusion gene, often in association with deletions of the nonrearranged TEL allele.TEL-AML1 gene fusion appears to be an initiating event and usually occurs before birth, in utero. This subgroup of ALL generally presents with low- or medium-risk features and overall has a very good prognosis. Some patients, however, do have relapses late or after the cessation of treatment, at least on some therapeutic protocols. They usually achieve sustained second remissions. Posttreatment relapses, or even very late relapses (5-20 years after diagnosis), in childhood ALL are clonally related to the leukemic cells at diagnosis (by IGH or T-cell receptor [TCR] gene sequencing) and are considered, therefore, to represent a slow re-emergence or escape of the initial clone seen at diagnosis. Microsatellite markers and fluorescence in situ hybridization identified deletions of the unrearranged TEL allele and IGH/TCR gene rearrangements were analyzed; the results show that posttreatment relapse cells in 2 patients with TEL-AML1–positive ALL were not derived from the dominant clone present at diagnosis but were from a sibling clone. In contrast, a patient who had a relapse while on treatment with TEL-AML1 fusion had essentially the sameTEL deletion, though with evidence for microsatellite instability 5′ of TEL gene deletion at diagnosis, leading to extended 5′ deletion at relapse. It is speculated that, in some patients, combination chemotherapy for childhood ALL may fail to eliminate a fetal preleukemic clone with TEL-AML1 and that a second, independent transformation event within this clone after treatment gives rise to a new leukemia masquerading as relapse.
TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: therapeutic applications
Authors: Mitsiades Constantine S. , Treon Steven P. , Mitsiades Nicholas , Shima Yoshihito , Richardson Paul , Schlossman Robert , Hideshima Teru , Anderson Kenneth C. 
Published: July 2002

AbstractMultiple myeloma (MM) remains incurable and novel treatments are urgently needed. Preclinical in vitro and in vivo evaluations were performed to assess the potential therapeutic applications of human recombinant tumor necrosis factor (TNF)–related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) in MM. TRAIL/Apo2L potently induced apoptosis of MM cells from patients and the majority of MM cell lines, including cells sensitive or resistant to dexamethasone (Dex), doxorubicin (Dox), melphalan, and mitoxantrone. TRAIL/Apo2L also overcame the survival effect of interleukin 6 on MM cells and did not affect the survival of peripheral blood and bone marrow mononuclear cells and purified B cells from healthy donors. The status of the TRAIL receptors (assessed by immunoblotting and flow cytometry) could not predict TRAIL sensitivity of MM cells. The anti-MM activity of TRAIL/Apo2L was confirmed in nu/xid/bg mice xenografted with human MM cells; TRAIL (500 μg intraperitoneally daily for 14 days) was well tolerated and significantly suppressed the growth of plasmacytomas. Dox up-regulated the expression of the TRAIL receptor death receptor 5 (DR5) and synergistically enhanced the effect of TRAIL not only against MM cells sensitive to, but also against those resistant to, Dex- or Dox-induced apoptosis. Nuclear factor (NF)-κB inhibitors, such as SN50 (a cell-permeable inhibitor of the nuclear translocation and transcriptional activity of NF-κB) or the proteasome inhibitor PS-341, enhanced the proapoptotic activity of TRAIL/Apo2L against TRAIL-sensitive MM cells, whereas SN50 reversed the TRAIL resistance of ARH-77 and IM-9 MM cells. Importantly, normal B lymphocytes were not sensitized to TRAIL by either Dox, SN50, or PS-341. These preclinical studies suggest that TRAIL/Apo2L can overcome conventional drug resistance and provide the basis for clinical trials of TRAIL-based treatment regimens to improve outcome in patients with MM.
Phase 1 study of polyethylene glycol formulation of interferon α-2B (Schering 54031) in Philadelphia chromosome–positive chronic myelogenous leukemia
Authors: Talpaz Moshe , O'Brien Susan , Rose Esther , Gupta Samir , Shan Jianqin , Cortes Jorge , Giles Francis J. , Faderl Stefan , Kantarjian Hagop M. 
Published: July 2002

AbstractInterferon α (IFN-α) therapy improves prognosis in Philadelphia chromosome (Ph)–positive chronic myelogenous leukemia (CML). Polyethylene glycol (PEG) attached to IFN-α prolongs its half-life and may offer better therapy. The aims of this phase 1 study were to define the maximal tolerated dose (MTD), dose-limiting toxicities (DLTs), and response with PEG IFN-α-2b. Twenty-seven adults with Ph+ CML in chronic or accelerated phases, in whom IFN-α treatment had failed, were studied. Patients had hematologic (9 patients) or cytogenetic resistance (12 patients) or intolerance to IFN-α (6 patients). PEG IFN-α-2b was given as a weekly subcutaneous injection starting at 0.75 μg/kg weekly and escalating to 1.5, 3, 4.5, 6, 7.5, and 9.0 μg/kg. The MTD was defined at 7.5 to 9 μg/kg; DLT included severe fatigue, neurotoxicity, liver function abnormalities, and myelosuppression. Longer administration of PEG IFN-α-2b resulted in chronic side effects not observed earlier, which defined the MTD and DLT. The proposed phase 2 dose of PEG IFN-α-2b was 6 μg/kg weekly. Among 19 patients with active disease, 7 (37%) achieved complete hematologic response (CHR); 2 (11%) had a cytogenetic response (complete). Among 8 patients treated in CHR, 7 (87%) improved cytogenetic response to complete (4 patients) or partial (3 patients). All 6 patients intolerant to IFN-α tolerated PEG IFN-α-2b; 4 improved their cytogenetic response. The results show that PEG IFN-α-2b is easier to deliver (once weekly), better tolerated, and perhaps more effective than IFN-α.
Molecular pathways in bone marrow homing: dominant role of α4β1 over β2-integrins and selectins
Authors: Papayannopoulou Thalia , Priestley Gregory V. , Nakamoto Betty , Zafiropoulos Vivian , Scott Linda M. 
Published: July 2002

AbstractThe specific retention of intravenously administered hemopoietic cells within bone marrow is a complex multistep process. Despite recent insights, the molecular mechanics governing this process remain largely undefined. This study explored the influence of β2-integrins on the homing to bone marrow and repopulation kinetics of progenitor cells. Both antifunctional antibodies and genetically deficient cells were used. In addition, triple selectin-deficient mice were used as recipients of either deficient (selectin or β2) or normal cells in homing experiments. The homing patterns of either β2 null or selectin null cells into normal or selectin-deficient recipients were similar to those of normal cells given to normal recipients. Furthermore, spleen colony-forming units and the early bone marrow repopulating activity for the first 2 weeks after transplantation were not significantly different from those of control cells. These data are in contrast to the importance of β2-integrin and selectins in the adhesion/migration cascade of mature leukocytes. The special bone marrow flow hemodynamics may account for these differences. Although early deaths after transplantation can be seen in recipients deficient in CD18 and selectin, these are attributed to septic complications rather than homing defects. However, when β2- or selectin-null donor cells are treated with anti-α4 antibodies before their transplantation to normal or selectin-deficient recipients, a dramatic inhibition of homing (&gt;90%) was found. The data suggest that the α4β1/vascular cell adhesion molecule-1 pathway alone is capable of providing effective capture of cells within the bone marrow, but if its function is compromised, the synergistic contribution of other pathways, that is, β2-integrins or selectins, is uncovered.
In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome
Authors: Cassinat Bruno , Chevret Sylvie , Zassadowski Fabien , Balitrand Nicole , Guillemot Isabelle , Menot Marie-Laurence , Degos Laurent , Fenaux Pierre , Chomienne Christine 
Published: July 2002

Abstract
Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.
Ef” cacy of two forms of electrical stimulation in increasing quadriceps strength: a randomized controlled trial
Authors: Bircan Cigdem , Senocak Ozlem , Peker Ozlen , Kaya Aylin , Tamc Sebnem Akgol , Gulbahar Selmin , Akalin Elif 
Published: July 2002

Objective: To investigate whether electrical stimulation is effective in improving quadriceps strength in healthy subjects and to compare interferential and low-frequency current in terms of the effects on quadriceps strength and perceived discomfort. Design: Randomized, controlled study. Setting: Physical Medicine and Rehabilitation Department in a university hospital. Subjects: Thirty medical faculty students, divided into three groups, participated in the study. Interventions: Group A received electrical stimulation with bipolar interferential current while group B received electrical stimulation with lowfrequency current (symmetrical biphasic). Group C served as the control group. Electrical stimulation was given for 15 minutes, ”ve days a week for three weeks, at a maximally tolerated intensity with the knee fully extended in the sitting position. Main outcome measures: Before and after the study, quadriceps strength was measured with a Cybex dynamometer isokinetically at the angular velocities of 60°/s and 120°/s. The perceived discomfort experienced with each type of electrical stimulation was quantified by the use of a visual analogue scale (VAS). Results: Statistically significant increase in isokinetic strength was observed after training in group A and group B. Increase in strength did not differ between the stimulation groups. No significant change in strength occurred in group C. Perceived discomfort by the stimulation groups was not significantly different. Conclusion: Both interferential and low-frequency currents can be used in strength training with the parameters used in this study.
The immediate effect of handling technique on range of movement in the hemiplegic shoulder
Authors: Tyson S F , Chissim C 
Published: July 2002

Purpose: To assess the immediate effect of two different handling techniques on range of ‘exion in the hemiplegic shoulder. Method: A randomized controlled design with within-subject comparison was used. Range of shoulder ‘exion was measured using a bubble goniometer. Range of passive movement was compared as the weak arm was lifted using an ‘axilla hold’ (when the gleno-humeral joint is supported and held in external rotation) and a ‘distal hold’ (when the arm is lifted at the forearm without shoulder support). Twenty-two people with arm weakness following stroke were recruited. They were inpatients or attending a day hospital in two NHS trusts, with no previous limitation of range or function of their arm. A paired t-test was used for analysis. Results: Mean shoulder ‘exion for the axilla hold was 115.2 degrees (SD 38.45), and 97.7 degrees (SD 44.7) for the distal hold. This difference was signi”cant at p < 0.001 (95% con”dence interval (95% CI) 7.96, 26.88). Conclusions: Lifting the hemiplegic arm by holding the humerus under the axilla and maintaining external rotation produces greater range of ‘exion at the hemiplegic shoulder than a ‘distal hold’.
Shoulder pain after stroke: a review of the evidence base to inform the development of an integrated care pathway
Authors: Turner-Stokes Lynne , Jackson Diana 
Published: July 2002

Background: Shoulder pain is a common complication of stroke. It can impede rehabilitation and has been associated with poorer outcomes and prolonged hospital stay. This systematic review was undertaken to inform the development of an evidence-based integrated care pathway (ICP) for the management of hemiplegic shoulder pain (HSP). Aims and objectives: 1) To provide a background understanding of the functional anatomy of the shoulder and its changes following stroke. 2) To review the literature describing incidence and causation of HSP and the evidence for factors contributing to its development. 3) To appraise the evidence for effectiveness of different interventions for HSP. Methods: Data sources comprised a computer-aided search of published studies on shoulder pain in stroke or hemiplegia and references to literature used in reviews (total references = 121). Main findings: Although a complex variety of physical changes are associated with HSP, these broadly divide into ‘flaccid’ and ‘spastic’ presentations. Management should vary accordingly; each presentation requiring different approaches to handling, support and intervention. (1) In the ‘accid stage, the shoulder is prone to inferior subluxation and vulnerable to soft-tissue damage. The arm should be supported at all times and functional electrical stimulation may reduce subluxation and enhance return of muscle activity. (2) In the spastic stage, movement is often severely limited. Relieving spasticity and maintaining range requires expert handling; overhead exercise pulleys should never be used. Local steroid injections should be avoided unless there is clear evidence of an in‘ammatory lesion. Conclusions: HSP requires co-ordinated multidisciplinary management to minimize interference with rehabilitation and optimize outcome. Further research is needed to determine effective prophylaxis and document the therapeutic effect of different modalities in the various presentations. Development of an integrated care pathway provides a reasoned approach to management of this complex condition, thus providing a sound basis for prospective evaluation of different interventions in the future.
Nursing as Vocation
Authors: White Karolyn 
Published: July 2002

In this article the author argues that nursing is best understood as a vocational occupation. Using Blum’s model of vocations it is argued that such occupations are socially expressed within practices embodying traditions, norms and a range of meanings: industrial, social, personal and moral. Vocational workers are those who identify in certain ways with these traditions, norms and meanings. One problem with the vocational model, as it has historically applied to nursing, is that it has been articulated through concepts of motherhood. Nursing was a vocation precisely because the character of the nurse was identified as feminine. The author argues that the vocational model for nursing can be conceptually disentangled from its identification with ideals of motherhood and femininity. It is nursing work and the identification with the moral and social meaning of nursing that give nursing its vocational status, not the feminized character of the nurse.
‘Tender Loving Care’ as a Relational Ethic in Nursing Practice
Authors: Kendrick Kevin David , Robinson Simon 
Published: July 2002

In the West, the term ‘tender, loving care’ (TLC) has traditionally been used as a defining term that characterizes nursing. When this expression informs practice, it can comfort the human spirit at times of fear and vulnerability. Such notions offer meaning and resonance to the ‘lived experience’ of giving and receiving care. This suggests that, in a nursing context, TLC is rooted firmly in relationship, that is, the dynamic that exists between carer and cared for. Despite this emphasis on relationship, there is a scarcity of literature that draws a connection between TLC and the moral challenge that is so much a part of human interaction. In this article we will address this deficit and present a narrative that places TLC at the centre of moral engagement between nurse and patient; in essence, we offer an alternative means of viewing relational ethics.