bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9
Authors: So Chi Wai , Karsunky Holger , Wong Piu , Weissman Irving L. , Cleary Michael L. 
Published: January 2004

AbstractDifferential expression of Hox genes is associated with normal hematopoiesis, whereas inappropriate maintenance of Hox gene expression, particularly Hoxa7 and Hoxa9, is a feature of leukemias harboring mixed-lineage leukemia (MLL) mutations. To understand the pathogenic roles of Hox genes in MLL leukemias, we assessed the impact of Hoxa7 or Hoxa9 nullizygosity on hematopoietic progenitor compartments and their susceptibility to MLL-induced leukemias. Selective reductions in the absolute numbers of committed progenitors, but not of hematopoietic stem cells, distinguished Hoxa7- and Hoxa9-deficient mice. Megakaryocytic/erythroid progenitor (MEP) reductions in Hoxa7-/-mice correlated with reticulocytosis and thrombocytopenia without anemia. Conversely, Hoxa9-/- mice displayed marked lymphopenia and substantial reductions of common lymphoid progenitors (CLPs) and lymphoid precursors, in addition to significant reductions of common myeloid progenitors (CMPs) and granulocyte/monocyte progenitors (GMPs). In retroviral transduction/transplantation assays, Hoxa7- and Hoxa9-deficient progenitors remained susceptible to transformation by MLL-GAS7, which activates MLL through a dimerization-dependent mechanism. However, Hoxa7-/- or Hoxa9-/-progenitors were less efficient in generating transformed blast colony-forming units (CFUs) in vitro and induced leukemias with longer disease latencies, reduced penetrance, and less mature phenotypes. Thus, Hoxa7 and Hoxa9 contribute to hematopoietic progenitor homeostasis but are not necessary for MLL-GAS7–mediated leukemogenesis, yet they appear to affect disease latency, penetrance, and phenotypes consistent with their critical roles as downstream targets of MLL fusion proteins. (Blood. 2004;103:3192-3199)
GRK6 deficiency is associated with enhanced CXCR4-mediated neutrophil chemotaxis in vitro and impaired responsiveness to G-CSF in vivo
Authors: Vroon Anne , Heijnen Cobi J , Raatgever Roel , Touw Ivo P , Ploemacher Rob E , Premont Richard T , Kavelaars Annemieke 
Published: January 2004

AbstractThe stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signaling pathway is thought to play an important role in the induction of neutrophil mobilization from the bone marrow in response to granulocyte-colony stimulating factor (G-CSF) treatment. CXCR4 belongs to the family of G protein-coupled receptors. Multiple members of this receptor family are desensitized by agonist-induced G protein-coupled receptor kinase (GRK)-mediated phosphorylation. Here, we demonstrate that in vitro SDF-1-induced chemotaxis of bone marrow-derived neutrophils from GRK6-deficient mice is significantly enhanced and that desensitization of the calcium response to SDF-1 is impaired in GRK6−/− neutrophils. CXCR4 activation by SDF-1 provides a key retention signal for hematopoietic cells in the bone marrow. It is interesting that we observed that in the absence of GRK6, the G-CSF-induced increase in circulating neutrophils is profoundly impaired. Three days after injection of pegylated-G-CSF, significantly lower numbers of circulating neutrophils were observed in GRK6−/− as compared with wild-type (WT) mice. In addition, early/acute neutrophil mobilization in response to G-CSF (3 h after treatment) was also impaired in GRK6−/− mice. However, blood neutrophil levels in untreated GRK6−/− and WT mice were not different. Moreover, the percentage of neutrophils in the bone marrow after G-CSF treatment was increased to the same extent in WT and GRK6−/− mice, indicating that neutrophil production is normal in the absence of GRK6. However, the increased chemotactic sensitivity of GRK6−/− neutrophils to SDF-1 was retained after G-CSF treatment. In view of these data, we suggest that the impaired G-CSF-induced neutrophil mobilization in the absence of GRK6 may be a result of enhanced CXCR4-mediated retention of PMN in the bone marrow.
Neutrophil chemoattractant genes KC and MIP-2 are expressed in different cell populations at sites of surgical injury
Authors: Armstrong David A , Major Jennifer A , Chudyk Alison , Hamilton Thomas A 
Published: January 2004

AbstractKC and macrophage-inflammatory protein-2 (MIP-2) are CXC chemokines that exhibit distinct temporal patterns of expression in the skin following surgical injury. In situ hybridization analysis demonstrates that these two chemokines are expressed by distinct cell types at different times following injury. Dermal fibroblasts and endothelial cells are primarily responsible for KC expression in the skin 6 h following surgery. In contrast, MIP-2 production appears to be restricted to infiltrating inflammatory leukocytes including neutrophils and monocytes, which appear later in the response. This cell type-specific pattern of chemokine expression is recapitulated in vitro using isolated primary- and long-term-cultured cell types. Primary dermal fibroblasts stimulated with interleukin-1α express predominantly KC and very little MIP-2, and peritoneal exudate neutrophils produce as much or more MIP-2 as KC following stimulation in vitro. Although a collection of exogenous stimuli can induce expression of KC and MIP-2, the quantitative ratio for expression reflects the cell type and not the stimulus. The selective expression of KC over MIP-2 in endothelial cells results from markedly greater KC gene transcription and not from alterations in the rate of mRNA decay. These results demonstrate that distinct CXC chemokines show restricted expression in myeloid versus nonmyeloid cell types and that patterns of chemokine expression at sites of inflammation in vivo reflect the temporally ordered contribution of these distinct cell types.
The receptor tyrosine kinase MerTK activates phospholipase C γ2 during recognition of apoptotic thymocytes by murine macrophages
Authors: Todt Jill C , Hu Bin , Curtis Jeffrey L 
Published: January 2004

AbstractApoptotic leukocytes must be cleared efficiently by macrophages (Mø). Apoptotic cell phagocytosis by Mø requires the receptor tyrosine kinase (RTK) MerTK (also known as c-Mer and Tyro12), the phosphatidylserine receptor (PS-R), and the classical protein kinase C (PKC) isoform βII, which translocates to Mø membrane and cytoskeletal fractions in a PS-R-dependent manner. How these molecules cooperate to induce phagocytosis is unknown. As the phosphatidylinositol-specific phospholipase (PI–PLC) γ2 is downstream of RTKs in some cell types and can activate classical PKCs, we hypothesized that MerTK signals via PLC γ2. To test this hypothesis, we examined the interaction of MerTK and PLC γ2 in resident, murine peritoneal (P)Mø and in the murine Mø cell line J774A.1 (J774) following exposure to apoptotic thymocytes. We found that as with PMø, J774 phagocytosis of apoptotic thymocytes was inhibited by antibody against MerTK. Western blotting and immunoprecipitation showed that exposure to apoptotic cells produced three time-dependent changes in PMø and J774: tyrosine phosphorylation of MerTK; association of PLC γ2 with MerTK; and tyrosine phosphorylation of PLC γ2. Cross-linking MerTK using antibody also induced phosphorylation of PLC γ2 and its association with MerTK. A PI–PLC appears to be required for phagocytosis of apoptotic cells, as the PI–PLC inhibitor Et-18-OCH3 and the PLC inhibitor U73122, but not the inactive control U73343, blocked phagocytosis without impairing adhesion. On apoptotic cell adhesion to Mø, MerTK signals at least in part via PLC γ2.
Combined activation of innate and T cell immunity for recognizing immunomodulatory properties of therapeutic agents
Authors: Rose Bettina , Herder Christian , Löffler Heike , Kolb Hubert , Martin Stephan 
Published: January 2004

AbstractComplex syndromes such as atherosclerosis and type 2 diabetes are disorders that are associated with inflammatory processes involving innate and adaptive immunity. Emerging knowledge about the pathological consequences of immune imbalances in a wide range of disease settings is expected to help to identify novel therapeutic targets. However, current test systems for immunomodulatory drugs tend to be too simplistic, as they rely only on cells of the innate- or the adaptive-immune system, or they are complex, in vivo models, which are not suitable for screening purposes. Using a modified mixed lymphocyte culture (MMLC) assay for combined analysis of innate and adaptive immunity, we show that this assay is very sensitive for the presence of low concentrations of immunomodulatory agents. Low-dose lipopolysaccharide stimulation of cells from two unrelated donors yields a strong cytokine response including interleukin (IL)-12 and IL-18, which induce interferon-γ as a potential analysis parameter. As the MMLC assay is based on the mutual interaction of cells of the innate and adaptive immunity, it enables the monitoring of cytokine release under almost physiological conditions and might be of interest for the characterization of known and novel drugs concerning their immunomodulatory potency.
The validity of questionnaire measures for assessing depression after stroke
Authors: Lincoln N B , Nicholl C R , Flannaghan T , Leonard M , Van der Gucht E 
Published: January 2004

Objective: Depression has been reported to occur frequently after stroke. The aim of the study was to assess the validity of questionnaire measures for screening for depression after stroke. Design: Cross-sectional correlational study between questionnaire measures of mood and psychiatric interview. Setting: Hospital and community. Participants: Stroke patients were recruited from hospital wards and from a randomized controlled trial of cognitive behavioural therapy. Main measures: Beck Depression Inventory, Wakefield Depression Inventory, General Health Questionnaire 28 and Schedules for Clinical Assessment in Neuropsychiatry. Results: Poor agreement was found between psychiatric diagnosis and questionnaire measures of mood. The sensitivity of the questionnaire measures was high, but specificity was low. No cut-off points with satisfactory sensitivity and specificity could be identified from ROC curves. Conclusions: Although questionnaire assessments of depression provide a satisfactory screening method, specificity values are too low to provide a basis for the diagnosis of depression. Measures need to be developed with higher specificity to facilitate screening for depression after stroke.
A post-discharge quality of life outcome measure for lower limb amputees: test–retest reliability and construct validity
Authors: Callaghan B G , Condie M E 
Published: January 2004

Objective: To adapt the Patient Generated Index (PGI) quality of life measure for use with lower limb amputees and to conduct a test–retest reliability and construct validity study on the adapted measure. Design: Repeat questionnaire interviews with a four-week interval administered by trained peers. Setting: Participants' homes. Subjects: Forty-two unilateral lower limb transfemoral amputees, 16 years of age or older and fluent in English, fitted with a prosthesis and discharged into the community for at least one year following postoperative rehabilitation therapy. Main results: An intraclass correlation coefficient of 0.48 ( p < 0.001) was achieved for the index reliability analyses. Intraclass correlation (ICC) values for the seven most commonly mentioned areas of life affected by the amputation and its treatment ranged from 0.40 to 0.92. Comparing the PGI with the SF-12 Health Survey physical and mental component summaries gave Pearson's correlation coefficients of 0.12 ( p < 0.5) and 0.56 ( p < 0.001) respectively. Multiple linear regression analysis showed the SF-12 physical and mental component scores explained 31.5% of the variability in PGI scores, however, the mental component scores alone explained 31.2%. Conclusions: The PGI was adapted and found to be moderately reliable in terms of repeatability during successive follow-up interviews. Testing its construct validity supported a stronger relationship between mental health and quality of life than between physical health and quality of life.
Defining and using quality of life: a survey of health care professionals
Authors: McKevitt C , Redfern J , La-Placa V , Wolfe C DA 
Published: January 2004

Objective: ‘Quality of life’ is an important but poorly defined outcome in health and health care research. We sought to identify stroke professionals' definitions of quality of life and views of the purpose of its assessment. Design: Using issues identified during in-depth interviews with stroke care professionals, we designed a postal survey questionnaire. Participants were asked to define quality of life, identify the purposes of assessing it and report experiences of measuring patient quality of life. Comparisons between professional groups were analysed using chi-squared tests of significance. Subjects: Care of the elderly physicians, physiotherapists and occupational therapists in the UK. Results: Of 2793 questionnaires distributed, 1572 were returned (56% response rate). Quality of life was defined in terms of ‘happiness’ by 72%; 25% included social well-being; 25% included physical abilities. Most (91%) identified ‘asking patients’ as an effective way to assess quality of life; 40% using standardized measures. Half those who reported using quality of life measures experienced difficulties, including being unsure about which measure to use and concerns about validity. Conclusions: The idea of quality of life as happiness dominated responders' definitions. We argue that the term may be used in both a technical sense (an outcome) and in a broad colloquial sense, without necessarily distinguishing between the two. Clarification of the concept and its uses is required if recent calls to introduce quality of life assessment in clinical care are to be feasible.
Muscle strength in patients with chronic pain
Authors: Van Wilgen C P , Akkerman L , Wieringa J , Dijkstra P U 
Published: January 2004

Objective: To analyse the in‘uence of chronic pain on muscle strength. Design: Muscle strength of patients with unilateral nonspecific chronic pain, in an upper or lower limb, were measured according to a standardized protocol using a hand-held dynamometer. Before and after muscle strength measurement, a visual analogue scale for pain intensity was assessed. Results: Forty patients were measured and the muscle strength of the painful side was 20–30% less than that of the nonpainful side. Strength reduction was seen in the whole limb. A significant correlation between pain intensity and reduced muscle strength in the painful limb existed for hip ‘exion, knee ‘exion, knee extension and three-point grip. Conclusions: A strength reduction of 20–30% in a painful limb seems to be ‘normal’ in chronic pain patients.
Falls in community-dwelling older persons following hip fracture: impact on self-efficacy, balance and handicap
Authors: Whitehead Craig , Miller Michelle , Crotty Maria 
Published: January 2004

Objective: To compare the four-month outcomes of fallers and nonfallers as well as those with slow gait speed in patients with hip fracture successfully discharged back to the community. Design: Prospective study with four-month follow-up data. Setting: Community sample of survivors of hip fracture who have completed their rehabilitation programme. Subjects: A consecutive sample of 73 community-dwelling, cognitively intact older adults admitted to hospital following a fall-related hip fracture and available to complete a follow-up assessment at four months. Main outcome measures: At baseline, data collection consisted of the Modified Barthel Index (MBI), Mini Mental State Examination (MMSE), sociodemographics and medical history. At four months follow-up, data collection consisted of the MBI, London Handicap Scale (LHS), Berg Balance Scale (BBS), a 10-metre timed walk test, Falls Efficacy Scale (FES) and the Activities Balance Confidence (ABC) scale. Participants were also asked to recall if they had fallen in the four months since their fracture. Results: Seventy-three participants had complete data for evaluation. There was minimal disability with a mean MBI of 91.2 but there was some residual handicap with a mean LHS of 0.67. Those who had fallen had lower selfefficacy (FES) and greater handicap (LHS). Those with slower gait speed were more handicapped (LHS), had lower self-efficacy (FES and ABC) and lower balance scores (BBS). Conclusions: Measuring ADL disability alone loses valuable information in community-dwelling survivors of hip fracture. Falls after hip fracture should be a target for treatment and our data give some weight to the idea of a fall fracture cycle. Gait speed, which may re‘ect lower limb strength, is also a target for therapeutic interventions. These measures should be included in clinical practice.
An Intercultural Nursing Perspective on Autonomy
Authors: Hanssen Ingrid 
Published: January 2004

This article is based on an empirical study regarding ethical challenges in intercultural nursing. The focus is on autonomy and disclosure. Autonomy is a human capacity that has become an important ethical principle in nursing. Although the relationship between autonomy and patients’ possibly harmful choices is discussed, the focus is on ‘forced’ autonomy. Nurses seem to equate respect with autonomy; it seems to be hard to cope with the fact that there are patients who voluntarily undergo treatment but who actively participate neither in the treatment offered nor in making choices regarding that treatment. Nurses’ demand for patients to be autonomous may in some cases jeopardize the respect, integrity and human worth that the ethical principle of autonomy is meant to ensure. Even though respect for a person’s autonomy is also respect for the person, one’s respect for the person in question should not depend on his or her capacity or aptitude to act autonomously. Is autonomy necessarily a universal ethical principle? This article negates this question and, through the issues of culture, individualism versus collectivism, first- and second- order autonomy, communication and the use of family interpreters, and respect, an attempt is made to explain why.
A Monomeric, Donor-free Lithium Complex with a New Overcrowded β-Diketiminato Ligand
Authors: Takeda Nobuhiro , Hamaki Hirofumi , Tokitoh Norihiro 
Published: January 2004

Abstract
A monomeric, donor-free complex of lithium with a new overcrowded β-diketiminato ligand, [Li{TbtNC(Me)CHC(Me)NMes}] (Tbt = 2,4,6-[CH(SiMe3)2]3C6H2, Mes = mesityl), was synthesized and isolated as colorless crystals. Its unique structure was revealed by X-ray structural analysis to be compared with those of donor-coordinated lithium β-diketiminates.
Synthesis of the Boron Complex Composed of the Noncyclic Ligands Having Plural Hydroxy Groups and the Binding Ability Toward Lanthanoid Ions
Authors: Kameta Naohiro , Hiratani Kazuhisa , Houjou Hirohiko , Kanesato Masatoshi 
Published: January 2004

Abstract
The boron complex composed of the noncyclic ligand having plural hydroxy groups behaves as a complex ligand and a forms hetero-binuclear complex with a lanthanoid ion.
A Low-temperature Coreduction Route to Boron Nitride Flakes and Hollow Spheres
Authors: Chen Luyang , Gu Yunle , Shi Liang , Yang Zeheng , Ma Jianhua , Qian Yitai 
Published: January 2004

Abstract
Boron nitride flakes and hollow spheres were synthesized by coreduction of NH4Cl and BBr3 using sodium as reductant. X-ray powder diffraction (XRD) pattern could be indexed as hexagonal BN. The X-ray photoelectron spectra (XPS) were used to determine the composition ratio, which is B:N = 1:1.05. The transmission electron microscopy (TEM) images showed flake-like and hollow spherical morphology.
Consumer Sequential Search: Not Enough or Too Much?
Authors: Zwick Rami , Rapoport Amnon , Lo Alison King Chung , Muthukrishnan A. V. 
Published: January 2004

We study sequential search behavior in a generalized "secretary problem" in which a single object is to be selected from a set ofnalternatives. Alternatives are inspected in a random order, one at a time, and only the rank order of the current alternative relative to the ones that have already been observed can be ascertained. At each period, the consumer may either accept the current alternative, continue to search and pay a fixed cost, or recall an alternative that has already been inspected. A recalled alternative is assumed to be available with a known probability. The consumer's goal is to select the overall best alternative from the fixed set.We describe the results of an experiment designed to test the optimal model and compare it to a behavioral decision model that incorporates local patterns of the observed sequence. Both set size and search cost are manipulated experimentally in a 2x2 factorial design. Our results show that cost and set size affect the amount of search in the predicted direction. However, in the two no-cost conditions subjects search too little in comparison to the optimal model, whereas in the two cost conditions they search too much. The behavioral decision rule that we propose provides a possible account for the observed pattern of the behavioral regularities.
Commissioned Paper: Capacity Management, Investment, and Hedging: Review and Recent Developments
Authors: Van Mieghem Jan A. 
Published: January 2004

This paper reviews the literature on strategic capacity management concerned with determining the sizes, types, and timing of capacity investments and adjustments under uncertainty. Specific attention is given to recent developments to incorporate multiple decision makers, multiple capacity types, hedging, and risk aversion. Capacity is a measure of processing abilities and limitations and is represented as a vector of stocks of various processing resources, while investment is the change of capacity and includes expansion and contraction. After discussing general issues in capacity investment problems, the paper reviews models of capacity investment under uncertainty in three settings: The first reviews optimal capacity investment by single and multiple risk-neutral decision makers in a stationary environment where capacity remains constant. Allowing for multiple capacity types, the associated optimal capacity portfolio specifies the amounts and locations of safety capacity in a processing network. Its key feature is that it is unbalanced; i.e., regardless of how uncertainties are realized, one typically will never fully utilize all capacities. The second setting reviews the adjustment of capacity over time and the structure of optimal investment dynamics. The paper ends by reviewing how to incorporate risk aversion in capacity investment and contrasts hedging strategies involving financial versus operational means.