bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surveys on attitudes towards legalisation of euthanasia: importance of question phrasing
Authors: Hagelin J , Nilstun T , Hau J , Carlsson H-E 
Published: December 2004

Aim:To explore whether the phrasing of the questions and the response alternatives would influence the answers to questions about legalisation of euthanasia.Methods:Results were compared from two different surveys in populations with similar characteristics. The alternatives “positive”, “negative”, and “don’t know” (first questionnaire) were replaced with an explanatory text, “no legal sanction”, four types of legal sanctions, and no possibility to answer “don’t know” (second questionnaire). Four undergraduate student groups (engineering, law, medicine, and nursing) answered.Results:In the first questionnaire (n = 684) 43% accepted euthanasia (range 28–50%), 14% (8–33%) did not, and 43% (39–59%) answered “don’t know”. Two per cent of the respondents declined to answer. In comparison with previous surveys on attitudes to euthanasia the proportion of “don’t know” was large. The results of the second questionnaire (n = 639), showed that 38% favoured “no legal prosecution” (26–50%). However, 62% (50–74%) opted for different kinds of legal sanctions, and two of four groups expressed significantly different views in the two surveys. A proportion of 10% declined to answer the second questionnaire.Conclusion:An introduction of an explanatory text and a wider range of response alternatives produced differences between the results of the two surveys conducted.
Attitudes of healthcare professionals and parents regarding genetic testing for violent traits in childhood
Authors: Campbell E , Ross L F 
Published: December 2004

Objectives:Although no genetic tests for violent behaviour are currently available, research is ongoing to isolate genes related to a propensity for violence. We explored the attitudes of parents and healthcare professionals toward behavioural genetic testing for violence.Design:The attitudes of healthcare professionals and the lay public about genetic testing of children were elicited for a range of conditions through interviews with healthcare professionals and focus groups with parents. All participants were informed that behavioural genetic testing was the only hypothetical genetic test in our script and it was presented as the last condition.Participants:The healthcare professionals included both genetic professionals and paediatricians. Focus group participants were recruited through various community institutions in the southside of Chicago and nearby suburbs.Results:The healthcare professionals tended to medicalise behavioural genetics, and were opposed to testing unless treatment was available. They were also uniformly concerned about the potential harms of this information, including unintentional adverse effects from environmental changes. In contrast, parents wanted genetic testing for behavioural traits to be available even in the absence of proved medical treatments. Not all parents wanted to test their own children, and some parents were concerned about self-fulfilling prophecies. Some parents, however, felt the information was important for their understanding, and could be used to support environmental changes.Conclusions:While healthcare professionals medicalised behavioural genetics, parents focused on environmental causes and influences. Consequently, healthcare professionals do not want to offer testing if there is no clear treatment, while parents may want this information to shape environmental influences.
A role for bone marrow–derived cells in the vasculature of noninjured CNS
Authors: Galimi Francesco , Summers Robert G. , van Praag Henriette , Verma Inder M. , Gage Fred H. 
Published: December 2004

AbstractThe contribution of hematopoietic cells to the formation of blood vessels is currently the focus of intense scrutiny. Bone marrow–derived endothelial progenitor cells are thought to generate endothelial cells in many tissues, including myocardium, muscle, and certain tumors. In the central nervous system (CNS), however, the possible role of bone marrow–derived angiocompetent cells remains unclear. Here we have investigated the long-term involvement of bone marrow–derived cells in the maintenance of endothelial structures in the brain, spinal cord, and retina. Using hematopoietic chimeras stably expressing green fluorescent protein (GFP) in bone marrow–derived tissues, we found large numbers of hematopoietic cells closely associated with vessels in the CNS. None of these cells, however, showed an endothelial phenotype. They were positive for monocytic and microglial surface markers and demonstrated active phagocytosis of neighboring endothelial elements. Bone marrow–derived, vasculature-associated cells in the noninjured adult CNS are distinct from endothelial cells, but play an active role in vascular structures.
Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose
Authors: Cao Thai M. , Shizuru Judith A. , Wong Ruby M. , Sheehan Kevin , Laport Ginna G. , Stockerl-Goldstein Keith E. , Johnston Laura J. , Stuart Monic J. , Grumet F. Carl , Negrin Robert S. , Lowsky Robert 
Published: December 2004

AbstractThe influence of graft composition on clinical outcomes after reduced-intensity conditioning is not well-characterized. In this report we prospectively enumerated CD34+, CD3+, CD4+, and CD8+ cell doses in granulocyte colony-stimulating factor–mobilized peripheral blood mononuclear cell (G-PBMC) allografts in 63 patients who received transplants following non-myeloablative conditioning with total body irradiation 200 cGy plus fludarabine as treatment for malignant diseases. Donors were HLA-identical siblings (n = 38) or HLA-matched unrelated individuals (n = 25). By univariate analyses G-PBMC CD8+ T-cell dose in at least the 50th percentile favorably correlated with full donor blood T-cell chimerism (P = .03), freedom from progression (P = .001), and overall survival (P = .01). No G-PBMC cell dose influenced grade II to IV acute or extensive chronic graftversus-host disease. In multivariate analysis only G-PBMC CD8+ T-cell dose (P = .003; RR = 0.2, 95% CI = 0.1-0.6) was associated with improved freedom from progression. Infusion of low G-PBMC CD8+ T-cell dose for reduced-intensity allografting may adversely affect T-cell engraftment and survival outcome.
Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)–producing dendritic cells: too much ado about IDO?
Authors: Terness Peter , Chuang Jing-Jing , Bauer Thomas , Jiga Lucian , Opelz Gerhard 
Published: December 2004

AbstractAlthough dendritic cells (DCs) strongly stimulate the immune response, they can also induce unresponsiveness. Recently, a human monocyte-derived DC subpopulation was described that constitutively expresses indoleamine 2,3-dioxygenase (IDO). These DCs were defined as nonadherent CD123+/CC chemokine receptor 6+ (CCR6+) cells that suppress the allogeneic T-cell response. In the present study, we generated nonadherent, mature DCs from human blood monocytes. As expected, in addition to the classic markers, these cells expressed CD123 and CCR6. Reverse transcription–polymerase chain reaction (RT-PCR), however, did not show IDO gene transcription, nor did we detect enzymatic IDO activity. Treating the cells with interferon-γ (IFN-γ) resulted in significant IDO production. Subsequently, we studied the regulatory properties of IDO-producing DCs on autologous and allogeneic T-cell responses. Neither OKT3-stimulated T cells of healthy donors nor myelin basic protein (MBP)–specific T cells of patients with multiple sclerosis (MS) were suppressed by autologous IDO DCs. However, whereas IDOneg DCs supported further stimulation of preactivated MBP-specific T cells of an MS patient, IDOpos DCs had lost this capacity. The allogeneic T-cell response was only marginally suppressed by IDO DCs. Our findings show that nonadherent CD123+/CCR6+ human DCs do not constitutively express IDO, and, even if they express the enzyme after IFN-γ treatment, they possess only limited T-cell regulatory function.
Imatinib mesylate therapy may overcome the poor prognostic significance of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia
Authors: Quintas-Cardama Alfonso , Kantarjian Hagop , Talpaz Moshe , O'Brien Susan , Garcia-Manero Guillermo , Verstovsek Srdan , Rios Mary Beth , Hayes Kimberly , Glassman Armand , Bekele B. Nebiyou , Zhou Xian , Cortes Jorge 
Published: December 2004

AbstractDeletions of derivative chromosome 9 [der(9)] can be identified by fluorescence in situ hybridization (FISH) in 10% to 15% of patients with chronic myeloid leukemia (CML). Patients with der(9) deletions have been reported to have an adverse outcome when treated with chemotherapy, interferon, and possibly imatinib mesylate. We investigated the frequency and prognostic significance of der(9) deletions among 352 patients with CML treated with imatinib mesylate at our institution, in whom a deletion status of der(9) was determined. Thirty-three patients (9%; 95% CI 0.07, 0.13) (30 in chronic phase, 3 in accelerated phase) had der(9) deletions. The rates of major (82% vs 79%, P = 0.82) and complete cytogenetic response (76% vs 66%, P = .33) with imatinib mesylate therapy were similar in patients with and without der(9) deletions, respectively. After a median follow-up of 28 months, there was no difference in overall survival (P = .30) or response duration (P = .49) in patients with and without deletions. In a multivariate analysis, der(9) deletions had no significant impact on response, survival, or response duration. We conclude that treatment with imatinib mesylate overcomes the adverse prognostic significance of der(9) deletions in patients with CML.
Isolation and characterization of human antigen-specific TCRαβ+ CD4-CD8- double-negative regulatory T cells
Authors: Fischer Karin , Voelkl Simon , Heymann Jana , Przybylski Grzegorz K. , Mondal Krishna , Laumer Monika , Kunz-Schughart Leoni , Schmidt Christian A. , Andreesen Reinhard , Mackensen Andreas 
Published: December 2004

AbstractDown-regulation of immune responses by regulatory T (Treg) cells is an important mechanism involved in the induction of tolerance to allo-antigens (Ags). Recently, a novel subset of Ag-specific T-cell receptor (TCR)αβ+ CD4-CD8- (double-negative [DN]) Treg cells has been found to be able to prevent the rejection of skin and heart allografts by specifically inhibiting the function of antigraft-specific CD8+ T cells. Here we demonstrate that peripheral DN Treg cells are present in humans, where they constitute about 1% of total CD3+ T cells, and consist of both naïve and Ag-experienced cells. Similar to murine DN Treg cells, human DN Treg cells are able to acquire peptide–HLA-A2 complexes from antigen-presenting cells by cell contact-dependent mechanisms. Furthermore, such acquired peptide-HLA complexes appear to be functionally active, in that CD8+ T cells specific for the HLA-A2–restricted self-peptide, Melan-A, became sensitive to apoptosis by neighboring DN T cells after acquisition of Melan-A–HLA-A2 complexes and revealed a reduced proliferative response. These results demonstrate for the first time that a sizable population of peripheral DN Treg cells, which are able to suppress Ag-specific T cells, exists in humans. DN Treg cells may serve to limit clonal expansion of allo-Ag–specific T cells after transplantation.
The origins of age-related proinflammatory state
Authors: Ferrucci Luigi , Corsi Annamaria , Lauretani Fulvio , Bandinelli Stefania , Bartali Benedetta , Taub Dennis D. , Guralnik Jack M. , Longo Dan L. 
Published: December 2004

AbstractWe hypothesized that the rising levels of inflammatory markers with aging is explained by cardiovascular risk factors and morbidity becoming progressively more prevalent in older persons. Information on inflammatory markers, cardiovascular risk factors, and diseases was collected in 595 men and 748 women sampled from the general population (age, 20-102 years). In both men and women, older age was associated with higher levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra), IL-18, C-reactive protein (CRP), and fibrinogen, while soluble IL-6 receptor (sIL-6r) increased significantly with age only in men. Adjusting for cardiovascular risk factors and morbidity, the age regression coefficients became substantially smaller in models predicting IL-6, IL-1ra, IL-18, and fibrinogen and larger in the model predicting sIL6r. Adjustment for cardiovascular morbidity substantially reduced the effect of age on CRP in men but not in women. Findings were confirmed in a subgroup of 51 men and 45 women with low risk profile and no cardiovascular morbidity. Part of the “proinflammatory state” in older persons is related to the high prevalence of cardiovascular risk factor and morbidity.
z-VAD-fmk augmentation of TNFα-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species
Authors: Cowburn Andrew S. , White Jessica F. , Deighton John , Walmsley Sarah R. , Chilvers Edwin R. 
Published: December 2004

Abstract
In most cell types constitutive and ligand-induced apoptosis is a caspase-dependent process. In neutrophils, however, the broad-spectrum caspase inhibitor z-VAD-fmk enhances tumor necrosis factor-α (TNFα)-induced cell death, and this has been interpreted as evidence for caspase-dependent and -independent cell death pathways. Our aim was to determine the specificity of the effect of z-VAD-fmk in neutrophils and define the potential mechanism of action. While confirming that z-VAD-fmk (&gt; 100 μM) enhances TNFα-induced neutrophil apoptosis, lower concentrations (1-30 μM) completely blocked TNFα-stimulated apoptosis. Boc-D-fmk, a similar broad-spectrum caspase inhibitor, and z-IETD-fmk, a selective caspase-8 inhibitor, caused a concentration-dependent inhibition of only TNFα-stimulated apoptosis. Moreover, the caspase-9 inhibitor, Ac-LEHD-cmk, had no effect on TNFα-induced apoptosis, and z-VAD-fmk and Boc-D-fmk inhibited TNFα-stimulated reactive oxygen species (ROS) generation. These data suggest that TNFα-induced apoptosis in neutrophils is fully caspase dependent and uses a mitochondrial-independent pathway and that the proapoptotic effects of z-VAD-fmk are compound specific and ROS independent.
Transfusion-related acute lung injury
Authors: Silliman Christopher C. , Ambruso Daniel R. , Boshkov Lynn K. 
Published: December 2004

AbstractTransfusion-related acute lung injury (TRALI) is a life-threatening adverse effect of transfusion that is occurring at increasing incidence in the United States and that, in the past 2 reporting years, has been the leading cause of transfusion-related death. TRALI and acute lung injury (ALI) share a common clinical definition except that TRALI is temporally and mechanistically related to the transfusion of blood/blood components. In prospective studies, 2 patient groups, 1 requiring cardiac surgery and 1 with hematologic malignancies and undergoing induction chemotherapy, were predisposed. Two different etiologies have been proposed. The first is a single antibody-mediated event involving the transfusion of anti-HLA class I and class II or antigranulocyte antibodies into patients whose leukocytes express the cognate antigens. The second is a 2-event model: the first event is the clinical condition of the patient resulting in pulmonary endothelial activation and neutrophil sequestration, and the second event is the transfusion of a biologic response modifier (including lipids or antibodies) that activates these adherent polymorphonuclear leukocytes (PMNs), resulting in endothelial damage, capillary leak, and TRALI. These hypotheses are discussed, as are the animal models and human studies that provide the experimental and clinical relevance. Prevention, treatment, and a proposed definition of TRALI, especially in the context of ALI, are also examined.
The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL)
Authors: Palladini Giovanni , Perfetti Vittorio , Perlini Stefano , Obici Laura , Lavatelli Francesca , Caccialanza Riccardo , Invernizzi Rosangela , Comotti Benedetto , Merlini Giampaolo 
Published: December 2004

AbstractBased on the efficacy of thalidomide in multiple myeloma and on its synergy with dexamethasone on myeloma plasma cells, we evaluated the combination of thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary amyloidosis (AL) whose disease was refractory to or had relapsed after first-line therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall, 15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5-8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic bradycardia was a common (26%) adverse reaction. The combination of thalidomide and dexamethasone is rapidly effective and may represent a valuable second-line treatment for AL.
Imatinib-Induced Regression of AIDS-Related Kaposi's Sarcoma
Authors: Koon Henry B. , Bubley Glenn J. , Pantanowitz Liron , Masiello David , Smith Brad , Crosby Katherine , Proper JoAnn , Weeden Will , Miller Thomas E. , Chatis Pamela , Egorin Merrill J. , Tahan Steven R. , Dezube Bruce J. 
Published: December 2004

Purpose Activation of the platelet-derived growth factor (PDGF) and c-kit receptors has been proposed as important in mediating the growth of AIDS-related Kaposi's sarcoma (KS). We investigated the response of KS to the PDGF receptor (PDGFR)/c-kit inhibitor, imatinib mesylate, and investigated the effect of this therapy on critical signal transduction intermediates. Patients and Methods Ten male patients with AIDS-related cutaneous KS, which progressed despite chemotherapy and/or highly active antiretroviral therapy, received imatinib mesylate administered orally, 300 mg twice daily. Clinical response was determined by serial tumor measurements. To determine biologic and histologic response, skin lesion biopsies were obtained at baseline and following 4 weeks of therapy. Results Five of 10 participants had a partial response by tumor measurements. Biopsies after 4 weeks of therapy demonstrated histologic regression in four of six patients. Four patients' tumor biopsies were assessable for immunohistochemistry end points pre- and post-therapy. These demonstrated inhibition of PDGFR and its downstream effector, extracellular receptor kinase, which is a member of the mitogen-activated protein kinase family. The most common adverse event was diarrhea, which led to dose reduction in six patients. Conclusion Imatinib mesylate administered orally twice daily for AIDS-related KS results in clinical and histologic regression of cutaneous KS lesions within 4 weeks. These promising results demonstrate that inhibition of the c-kit and/or PDGF receptors may represent an effective strategy for treating KS.
Long-Term Survival Rates of Patients With Prostate Cancer in the Prostate-Specific Antigen Screening Era: Population-Based Estimates for the Year 2000 by Period Analysis
Authors: Brenner Hermann , Arndt Volker 
Published: December 2004

Purpose In the era of widespread prostate specific antigen (PSA) screening, a large proportion of older men have to live with a diagnosis of prostate cancer. In this study, we applied a new method for up-to-date analysis of long-term survival to evaluate if and to what extent these patients still have any excess mortality compared to the general population. Methods Five- and 10-year absolute and relative survival rates for the year 2000 were derived from the 1973 to 2000 database of the Surveillance, Epidemiology and End Results Program using the recently introduced period analysis methodology. Results Overall, 5- and 10-year relative survival rates were approximately 99% and 95%; that is, excess mortality compared with the general population was as low as 1% and 5% within 5 and 10 years following diagnosis, respectively. Two-thirds of patients were diagnosed with well or moderately differentiated localized/regional prostate cancer, and among these patients, 5- and 10-year relative survival rates were above 100% (indicating the lack of any excess mortality) at all ages. Conclusion While the value of PSA screening for lowering mortality due to prostate cancer remains to be shown by randomized clinical trials, the majority of patients diagnosed with prostate cancer in the PSA screening era do not have excess mortality compared to the general population under current patterns of medical care. This information may be important for both clinical management of, and for patients' coping with, the disease.
Modelling of loss mechanisms in a pushing metal V-belt continuously variable transmission. Part 3: Belt slip losses
Authors: Akehurst S , Vaughan N D , Parker D A , Simner D 
Published: December 2004

The power transmission efficiency of continuously variable transmissions (CVTs) based on the pushing metal belt is acknowledged to be lower than that of discrete ratio alternatives. This tends to negate the potential fuel economy benefits that are obtained by improved engine/load matching with a CVT. This series of three papers details an investigation into the loss mechanisms that occur within the belt drive as a first step to obtaining improvements in efficiency. This third paper follows on from two previous papers in which an analysis was performed modelling the torque losses that occur due to relative motion between the bands and segments of the belt, and between the pulleys and the belt due to pulley deflection effects. It describes additional experimental work, measuring the belt-slip speed tangentially about both of the pulleys in the variator. Additional loss models are proposed beyond those discussed in Parts 1 and 2 to describe the belt-slip phenomena, based on existing theory proposed by others. The analysis produced in this paper is validated against a range of experimental data and additionally through its close interaction with the torque-loss and torque-force distribution models proposed in Parts 1 and 2. The work takes into account new findings in other research and changes in the design of the current metal V-belt.
Modelling of loss mechanisms in a pushing metal V-belt continuously variable transmission. Part 1: Torque losses due to band friction
Authors: Akehurst S , Vaughan N D , Parker D A , Simner D 
Published: December 2004

The power transmission efficiency of continuously variable transmissions (CVTs) based on the pushing metal belt is acknowledged to be lower than that of discrete ratio alternatives. This tends to negate the potential fuel economy benefits that are obtained by improved engine/load matching with a CVT. This series of three papers details an investigation into the loss mechanisms that occur within the belt drive as a first step to obtaining improvements in efficiency. Experimental work has been undertaken to investigate the no-load and low-load torque losses associated with a pushing metal V-belt CVT. This first paper describes a new analysis of the principal torque losses occurring in the metal belt CVT due to relative motion occurring between the belt segments and bands. The work takes into account new findings in other research and changes in the design of the metal V-belt. The torque loss model proposed in this paper is supported by experimental data from several different test procedures. A number of additional torque loss mechanisms, due to pulley deflections, are described in Part 2 of the series. The findings from this current paper support an analysis of belt-slip losses, which is described in detail in Part 3.