bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tests of Stepping as Indicators of Mobility, Balance, and Fall Risk in Balance‐Impaired Older Adults
Authors: Cho Be‐long , Scarpace Diane , Alexander Neil B. 
Published: June 2004

Objectives: To determine the relationships between two tests of stepping ability (the maximal step length (MSL) and rapid step test (RST)) and standard tests of standing balance, gait, mobility, and functional impairment in a group of at‐risk older adults.Design: Cross‐sectional study.Setting: University‐based laboratory.Participants: One hundred sixty‐seven mildly balance‐impaired older adults recruited for a balance‐training and fall‐reduction program (mean age 78, range 65–90).Measurements: Measures of stepping maximally (MSL, the ability to maximally step out and return to the initial position) and rapidly (RST, the time taken to step out and return in multiple directions as fast as possible); standard measures of balance, gait, and mobility including timed tandem stance (TS), tandem walk (TW, both timing and errors), timed unipedal stance (US), timed up and go (TUG), performance oriented mobility assessment (POMA), and 6‐minute walk (SMW); measures of leg strength (peak knee and ankle torque and power at slow and fast speeds); self‐report measures of frequent falls (>2 per 12 months), disability (Established Population for Epidemiologic Studies of the Elderly (EPESE) physical function), and confidence to avoid falls (Activity‐specific Balance Confidence (ABC) Scale). Spearman and Pearson correlation, intraclass correlation coefficient, logistic regression, and linear regression were used for data analysis.Results: MSL consistently predicted a number of self‐report and performance measures at least as well as other standard balance measures. MSL correlations with EPESE physical function, ABC, TUG, and POMA scores; SMW; and peak maximum knee and ankle torque and power were at least as high as those correlations seen with TS, TW, or US. MSL score was associated with the risk of being a frequent faller. In addition, the six MSL directions were highly correlated (up to 0.96), and any one of the leg directions yielded similar relationships with functional measures and a history of falls. Relationships between RST and these measures were relatively modest.Conclusion: MSL is as good a predictor of mobility performance, frequent falls, self‐reported function, and balance confidence as standard stance tests such as US. MSL simplified to one direction may be a useful clinical indicator of mobility, balance, and fall risk in older adults.
Short-Term Effects of Practice With Trunk Restraint on Reaching Movements in Patients With Chronic Stroke
Authors: Michaelsen Stella M. , Levin Mindy F. 
Published: June 2004

Background and Purpose—In prehension tasks with objects placed within arm’s reach, patients with hemiparesis caused by stroke use excessive trunk movement to compensate for arm motor impairments. Compensatory trunk movements may improve motor function in the short term but may limit arm recovery in the long term. Previous studies showed that restriction of trunk movements during reach-to-grasp movements results in immediate increases in active arm joint ranges and improvement in interjoint coordination. To evaluate the potential of this technique as a therapeutic intervention, we compared the effects of short-term reach-to-grasp training (60-trial training session) with and without physical trunk restraint on arm movement patterns in patients with chronic hemiparesis.Methods—A total of 28 patients with hemiparesis were assigned to 2 groups: 1 group practiced reach-to-grasp movements during which compensatory movement of the trunk was prevented by a harness (trunk restraint), and the second group practiced the same task while verbally instructed not to move the trunk (control). Kinematics of reaching and grasping an object placed within arm’s length were recorded before, immediately after, and 24 hours after training.Results—The trunk restraint group used more elbow extension, less anterior trunk displacement, and had better interjoint coordination than the control group after training, and range of motion was maintained 24 hours later in only the trunk restraint group.Conclusions—Restriction of compensatory trunk movements during practice may lead to greater improvements in reach-to-grasp movements in patients with chronic stroke than practice alone, and longer-term effects of this intervention should be evaluated.
Gain Scheduling Feedback Control of Tower Cranes with Friction Compensation
Authors: Omar Hanafy M , Nayfeh Ali H 
Published: June 2004

We have designed a controller based on gain-scheduling feedback to move a load from point to point within one oscillation cycle and without inducing large swings. The settling time of the system is taken to be equal to the period of oscillation of the load. This criterion enables us to calculate the controller feedback gains for varying load weight and cable length. First, we designed the controller for gantry cranes and then extended it to tower cranes by considering the coupling between the translational and rotational motions. Numerical simulations show that the controller is effective for reducing load oscillations and transferring the load in a reasonable time compared with that of optimal control. To experimentally validate the theory, we had to compensate for friction. To this end, we estimated the friction, then applied an opposite control action to cancel it. To estimate the friction force, we assumed a mathematical model, then we estimated the model coefficients using an off-line identification technique, the least-squares method. First, the process of identification was applied to a theoretical model of a dc motor with known friction coefficients. From this example, some guidelines and rules were deduced for the choice of the least-squares parameters. Then, the friction coefficients of the gantry crane model were estimated and validated.
Variables that Affect/Control High-Density Polyethylene Film Oxygen–Moisture Barrier
Authors: Todd William G. 
Published: June 2004

Multiple layer polyolefin-based films continue to be one of the preferred packages for both the food and medical industries. The technology of these films has advanced over the years from simple monolayer structures to multilayer hybrid structures. These affordable packages not only provide tamper proof evidence, but also protection from insects, bacteria, germs, and dust and are very effective in providing moisture and oxygen barrier. This paper will discuss these latter two properties, moisture and oxygen barrier, when polyethylene is used as the primary film component. Many variables affect high-density polyethylene (HDPE) film’s oxygen transmission rates (OTR), and water vapor transmission rates (WVTR). These variables include film crystalline structure, relaxation rates of molten polyethylene, polyethylene manufacturing technology, polyethylene resin physical properties, atmospheric conditions, and film fabrication technology and structure. This paper will describe how permeation rates are measured and how each of the above variables affects the permeation rates.
Platelet-associated CD154 in immune thrombocytopenic purpura
Authors: Solanilla Anne , Pasquet Jean-Max , Viallard Jean-François , Contin Cécile , Grosset Christophe , Déchanet-Merville Julie , Dupouy Maryse , Landry Marc , Belloc Francis , Nurden Paquita , Blanco Patrick , Moreau Jean-François , Pellegrin Jean-Luc , Nurden Alan T. , Ripoche Jean 
Published: June 2004

AbstractCD40-ligand (CD154) is expressed on activated CD4+ T lymphocytes and is essential for the T cell–dependent activation of B lymphocytes. CD154 is also expressed at the activated platelet surface. In this study, we show that platelet-associated CD154 is increased in immune thrombocytopenic purpura (ITP), a disease characterized by an autoimmune response against proteins of the platelet membrane. CD154 and its messenger RNA were also present in increased amounts in the megakaryocytes of patients with ITP. We found that platelet-associated CD154 is competent to induce the CD40-dependent proliferation of B lymphocytes, and we observed an in vitro CD154-dependent production of antibodies to the GPIIb/IIIa complex (integrin αIIbβ3) when platelets and peripheral blood B lymphocytes from ITP patients with circulating anti-GPIIb/IIIa antibody were cultured together. Therefore, platelet-associated CD154 expression is increased in ITP and is able to drive the activation of autoreactive B lymphocytes in this disease.
Neuromedin U: a Myb-regulated autocrine growth factor for human myeloid leukemias
Authors: Shetzline Susan E. , Rallapalli Ravikumar , Dowd Kelley J. , Zou Shaomin , Nakata Yuji , Swider Cezary R. , Kalota Anna , Choi John K. , Gewirtz Alan M. 
Published: June 2004

AbstractThe c-myb proto-oncogene has been implicated in leukemogenesis, but possible mechanisms remain ill defined. To gain further insight to this process, we used transcript profiling in K562 cells expressing a dominant-negative Myb (MERT) protein. A total of 105 potential Myb gene targets were identified. Neuromedin U (NmU), a peptide affecting calcium transport, underwent the greatest expression change (∼ 5-fold decrease). To verify a linkage between c-myb and NmU, their mRNA levels were quantitated using real-time polymerase chain reaction in primary acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), as well as normal hematopoietic cells. We found that c-myb was elevated in AML and ALL samples, but NmU expression was increased only in AML cells. Significantly, only AML cells expressed the cognate receptor of NmU, NMU1R, suggesting the presence of a novel autocrine loop. We examined this possibility in detail. Exogenous NmU “rescued” growth suppression in K562-MERT cells and stimulated the growth of primary AML cells. Short interfering RNA “knockdown” of NmU in K562 cells arrested cell growth. Exposing Indo-1–labeled K562 cells to NmU induced an intracellular Ca++ flux consistent with engagement of the NMU1R. Combined, these results suggest that NmU expression is related to Myb and that the NmU/NMU1R axis constitutes a previously unknown growth-promoting autocrine loop in myeloid leukemia cells.
Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion
Authors: Abe Masahiro , Hiura Kenji , Wilde Javier , Shioyasono Atsushi , Moriyama Keiji , Hashimoto Toshihiro , Kido Shinsuke , Oshima Takashi , Shibata Hironobu , Ozaki Shuji , Inoue Daisuke , Matsumoto Toshio 
Published: June 2004

AbstractMultiple myeloma (MM) expands in the bone marrow and causes devastating bone destruction by enhancing osteoclastic bone resorption in its vicinity, suggesting a close interaction between MM cells and osteoclasts (OCs). Here, we show that peripheral blood mononuclear cell-derived OCs enhanced growth and survival of primary MM cells as well as MM cell lines more potently than stromal cells, and that OCs protected MM cells from apoptosis induced by serum depletion or doxorubicin. OCs produced osteopontin (OPN) and interleukin 6 (IL-6), and adhesion of MM cells to OCs increased IL-6 production from OCs. In addition, IL-6 and OPN in combination enhanced MM cell growth and survival. However, the effects of OCs on MM cell growth and survival were only partially suppressed by a simultaneous addition of anti–IL-6 and anti-OPN antibodies and were completely abrogated by inhibition of cellular contact between MM cells and OCs. These results demonstrate that OCs enhance MM cell growth and survival through a cell-cell contact-mediated mechanism that is partially dependent on IL-6 and OPN. It is suggested that interactions of MM cells with OCs augment MM growth and survival and, thereby, form a vicious cycle, leading to extensive bone destruction and MM cell expansion.
Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium
Authors: Göthert Joachim R. , Gustin Sonja E. , van Eekelen J. Anke M. , Schmidt Uli , Hall Mark A. , Jane Stephen M. , Green Anthony R. , Göttgens Berthold , Izon David J. , Begley C. Glenn 
Published: June 2004

AbstractTumor growth is dependent in part on “neoangiogenesis.” Functional involvement of bone marrow (BM)-derived cells in this process has been demonstrated. However, it remains controversial as to whether tumor endothelium itself is BM derived. Here we sought to address this issue with an endothelial-specific, inducible transgenic model. We generated Cretransgenic mice (endothelial-SCL-Cre-ERT) using the tamoxifen-inducible Cre-ERT recombinase driven by the 5′ endothelial enhancer of the stem cell leukemia (SCL) locus. These mice were intercrossed with Cre reporter strains in which β-galactosidase (LacZ) or enhanced yellow fluorescent protein (EYFP) are expressed upon Cre-mediated recombination. After tamoxifen administration, endothelial LacZ staining was observed in embryonic and adult tissues. Cre-mediated recombination was also observed in newly generated tumor endothelium. In adult BM cells we could only detect trace amounts of recombination by flow cytometry. Subsequently, BM from endothelial-SCL-Cre-ERT;R26R mice was transplanted into irradiated recipients. When tumors were grown in recipient mice, which received tamoxifen, no tumor LacZ staining was detected. However, when tumors were grown in endothelial-SCL-Cre-ERT;R26R mice 3 weeks after the cessation of tamoxifen treatment, there was widespread endothelial LacZ staining present. Thus, this genetic model strongly suggests that BM cells do not contribute to tumor endothelium and demonstrates the lineage relation between pre-existing endothelium and newly generated tumor endothelial cells. (Blood. 2004;104:1769-1777)
New anticoagulants
Authors: Hirsh Jack , O'Donnell Martin , Weitz Jeffrey I. 
Published: June 2004

AbstractAnticoagulants are pivotal agents for prevention and treatment of thromboembolic disorders. Limitations of existing anticoagulants, vitamin K antagonist and heparins, have led to the development of newer anticoagulant therapies. These anticoagulants have been designed to target specific coagulation enzymes or steps in the coagulation pathway. New anticoagulants that are under evaluation in clinical trials include: (1) inhibitors of the factor VIIa/tissue factor pathway; (2) factor Xa inhibitors, both indirect and direct; (3) activated protein C and soluble thrombomodulin; and (4) direct thrombin inhibitors. Although most of these are parenteral agents, several of the direct inhibitors of factor Xa and thrombin are orally active. Clinical development of these therapies often starts with studies in the prevention of venous thrombosis before evaluation for other indications, such as prevention of cardioembolism in patients with atrial fibrillation or prosthetic heart valves. At present, the greatest clinical need is for an oral anticoagulant to replace warfarin for long-term prevention and treatment of patients with venous and arterial thrombosis. Ximelagatran, an oral direct thrombin inhibitor, is the first of a series of promising new agents that might fulfill this need. Large phase 3 trials evaluating ximelagatran for the secondary prevention of venous thromboembolism and prevention of cardioembolic events in patients with atrial fibrillation have been completed.
Notch4-induced inhibition of endothelial sprouting requires the ankyrin repeats and involves signaling through RBP-Jκ
Authors: MacKenzie Farrell , Duriez Patrick , Larrivée Bruno , Chang Linda , Pollet Ingrid , Wong Fred , Yip Calvin , Karsan Aly 
Published: June 2004

AbstractNotch proteins comprise a family of transmembrane receptors. Ligand activation of Notch releases the intracellular domain of the receptor that translocates to the nucleus and regulates transcription through the DNA-binding protein RBP-Jκ. Previously, it has been shown that the Notch4 intracellular region (N4IC) can inhibit endothelial sprouting and angiogenesis. Here, N4IC deletion mutants were assessed for their ability to inhibit human microvascular endothelial cell (HMEC) sprouting with the use of a quantitative endothelial sprouting assay. Deletion of the ankyrin repeats, but not the RAM (RBP-Jκ associated module) domain or C-terminal region (CT), abrogated the inhibition of fibroblast growth factor 2 (FGF-2)- and vascular endothelial growth factor (VEGF)-induced sprouting by Notch4, whereas the ankyrin repeats alone partially blocked sprouting. The ankyrin repeats were also the only domain required for up-regulation of RBP-Jκ-dependent gene expression. Interestingly, enforced expression of the ankyrin domain alone was sufficient to up-regulate some, but not all, RBP-Jκ-dependent genes. Although N4IC reduced VEGF receptor-2 (VEGFR-2) and vascular endothelial (VE)-cadherin expression, neither of these events is necessary and sufficient to explain N4IC-mediated inhibition of sprouting. A constitutively active RBP-Jκ mutant significantly inhibited HMEC sprouting but not as strongly as N4IC. Thus, Notch4-induced inhibition of sprouting requires the ankyrin repeats and appears to involve RBP-Jκ-dependent and -independent signaling. (Blood. 2004;104:1760-1768)
Puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) binds and catalyzes PDK1, allowing VEGF-stimulated activation of S6K for endothelial cell proliferation and angiogenesis
Authors: Yamazaki Tohru , Akada Tetsuya , Niizeki Osamu , Suzuki Takahiro , Miyashita Hiroki , Sato Yasufumi 
Published: June 2004

Abstract
Puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) plays an important role in angiogenesis by regulating the proliferation and migration of endothelial cells (ECs). Here we characterize the mechanism by which PILSAP regulates the vascular endothelial growth factor (VEGF)–stimulated proliferation of ECs. The specific elimination of PILSAP expression or its enzymatic activity inhibited VEGF-stimulated G1/S transition in ECs. This G1 arrest correlated with reduced cyclin dependent kinase 4/6 (CDK4/6) activity and retinoblastoma (Rb) protein phosphorylation. Analyses of signaling molecules upstream of CDK4/6 revealed that S6 kinase (S6K) activation was affected by PILSAP, whereas that of phosphatidylinositol-3 kinase (PI3K), Akt, and extracellular signal-related kinase 1/2 (ERK1/2) was not. We further demonstrated that PILSAP bound phosphatidylinositol-dependent kinase 1 (PDK1) and removed 9 amino acids from its N-terminus, which allowed S6K to associate with PDK1 and PILSAP upon VEGF stimulation. We constructed mutant PILSAP, which lacked the aminopeptidase activity but bound PDK1. Mutant PILSAP abrogated S6K activation upon VEGF stimulation in a dominant-negative manner. An N-terminal truncated form of PDK1 abolished the dominant-negative effect of mutant PILSAP. Finally, the introduction of a mutated PILSAP gene in ECs inhibited angiogenesis and retarded tumor growth in vivo. These results indicate that PILSAP plays a crucial role in the cell cycle progression of ECs and angiogenesis via the binding and modification of PDK1.
In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis
Authors: Saudemont Aurore , Quesnel Bruno 
Published: June 2004

AbstractIn tumor dormancy, tumor cells persist in the host over a long period of time but do not grow. We investigated in the DA1-3b mouse model of acute myeloid leukemia how leukemic cells could persist for months in spite of an effective antileukemic immune response. Mice were immunized with irradiated interleukin 12 (IL12)- or CD154-transduced DA1-3b cells, challenged with wild-type DA1-3b cells, and randomly killed during 1-year follow-up. Quantification of residual disease 1 year after challenge showed that persistent leukemic cells represented less than 0.02% of spleen cells in most animals. These residual cells were still able to kill naive hosts, even when isolated after 1 year of persistence. Persistent leukemic cells were more resistant to specific cytotoxic T-cell (CTL)-mediated killing and had enhanced B7-H1 and B7.1 expression proportional to the time they had persisted in the host. Blocking B7-H1 or B7.1/cytotoxic T-lymphocyte-associated antigen (CTLA-4) interaction enhanced CTL-mediated killing of the persistent cells, and blocking B7-H1, B7.1, or CTLA-4 in vivo prolonged survival of naive mice injected with persistent leukemic cells. Thus, escape of leukemic cells from tumor immunity via overexpression of B7-H1 or B7.1 might represent a new mechanism of tumor dormancy in acute leukemia. (Blood. 2004;104:2124-2133)
Translocation of the inhibitor of apoptosis protein c-IAP1 from the nucleus to the Golgi in hematopoietic cells undergoing differentiation: a nuclear export signal-mediated event
Authors: Plenchette Stéphanie , Cathelin Séverine , Rébé Cédric , Launay Sophie , Ladoire Sylvain , Sordet Olivier , Ponnelle Tibor , Debili Najet , Phan Thi-Hai , Padua Rose-Ann , Dubrez-Daloz Laurence , Solary Eric 
Published: June 2004

AbstractThe caspase inhibitor and RING finger-containing protein cellular inhibitor of apoptosis protein 1 (c-IAP1) has been shown to be involved in both apoptosis inhibition and signaling by members of the tumor necrosis factor (TNF) receptor family. The protein is regulated transcriptionally (eg, is a target for nuclear factor-κB [NF-κB]) and can be inhibited by mitochondrial proteins released in the cytoplasm upon apoptotic stimuli. The present study indicates that an additional level of regulation of c-IAP1 may be cell compartmentalization. The protein is present in the nucleus of undifferentiated U937 and THP1 monocytic cell lines. When these cells undergo differentiation under phorbol ester exposure, c-IAP1 translocates to the cytoplasmic side of the Golgi apparatus. This redistribution involves a nuclear export signal (NES)-mediated, leptomycin B-sensitive mechanism. Using site-directed mutagenesis, we localized the functional NES motif in the caspase recruitment domain (CARD) of c-IAP1. A nucleocytoplasmic redistribution of the protein was also observed in human monocytes as well as in tumor cells from epithelial origin when undergoing differentiation. c-IAP1 does not translocate from the nucleus of cells whose differentiation is blocked (ie, in cell lines and monocytes from transgenic mice overexpressing B-cell lymphoma 2 [Bcl-2] and in monocytes from patients with chronic myelomonocytic leukemia). Altogether, these observations associate c-IAP1 cellular location with cell differentiation, which opens new perspectives on the functions of the protein. (Blood. 2004;104:2035-2043)
Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells
Authors: Rajantie Iiro , Ilmonen Maritta , Alminaite Agne , Ozerdem Ugur , Alitalo Kari , Salven Petri 
Published: June 2004

Abstract
Bone marrow (BM)-derived cells are thought to participate in the growth of blood vessels during postnatal vascular regeneration and tumor growth, a process previously attributed to stem and precursor cells differentiating to endothelial cells. We used multichannel laser scanning confocal microscopy of whole-mounted tissues to study angiogenesis in chimeric mice created by reconstituting C57BL mice with genetically marked syngeneic BM. We show that BM-derived endothelial cells do not significantly contribute to tumor- or cytokine-induced neoangiogenesis. Instead, BM-derived periendothelial vascular mural cells were persistently detected at sites of tumor- or vascular endothelial growth factor-induced angiogenesis. Subpopulations of these cells expressed the pericyte-specific NG2 proteoglycan, or the hematopoietic markers CD11b and CD45, but did not detectably express the smooth muscle markers smooth muscle α-actin or desmin. Thus, the major contribution of the BM to angiogenic processes is not endothelial, but may come from progenitors for periendothelial vascular mural and hematopoietic effector cells. (Blood. 2004;104: 2084-2086)