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Biomedical subjects

George Chen

Publications and source records attributed to George Chen.

9 recordsLinked to original sources
PubMed2006

Polycythemia vera and its molecular basis: an update.

The molecular basis of polycythemia vera is discussed in the context of the JAK2 V617F mutation, in our view the most important advance in understanding the pathogenesis of polycythemia vera. This chapter discusses the nature of the JAK2 V617F mutation including the studies demonstrating its role in erythropoietin independence and hypersensitivity and endogenous erythroid colony formation. The evolving evidence that JAK2 V617F is not specific for polycythemia vera pathogenesis and the development of disease phenotype is presented as well as alternative candidates for pathogenic mutations such as the protein tyrosine phosphatases and SOCS-3. Finally, the clinical correlations and implications of the JAK2 V617F mutation are discussed.

Humans↗
PubMed2005

Induced acceleration contributions to locomotion dynamics are not physically well defined.

Induced acceleration analysis quantifies the contributions of individual moments and forces to the accelerations, reaction forces, and powers produced during a task. The analysis has been advocated in the assessment of muscle and joint moment function during locomotion. However, results and interpretations drawn from the analysis have differed considerably between studies. The purpose of this paper is to assess whether induced acceleration contributions to locomotion dynamics are physically well defined. The assessment was facilitated by the analyses of a simple, theoretical locomotor task using different models. The task was based on a planar, rigid-body simulation in which joint moments at the hip, knee, and ankle posturally supported the configuration of the body as it rolled forward in a pendular motion. Induced acceleration analyses were performed using four models that completely described the simulated dynamics of the task but represented progressively fewer degrees of freedom. The contributions of each joint moment to the ground reaction force and trunk and leg powers differed between models, even though the net contributions were identical for all models and consistent with the simulation. Moreover, when all body degrees of freedom were represented in the model, large power redistributions between the trunk and leg were attributed to individual joint moments. However, these redistributions mostly cancelled such that the net redistribution was modest. In a single-segment model, this net redistribution was attributed entirely to gravity, without any cancellation of power flows. To conclude, induced acceleration contributions to the dynamics of a task are not physically well defined. The application of the analysis in the assessment of muscle and joint moment function during locomotion should be critically reevaluated.

Acceleration↗
PubMed2005

Gait deviations associated with post-stroke hemiparesis: improvement during treadmill walking using weight support, speed, support stiffness, and handrail hold.

By comparing treadmill walking in hemiparetic and non-disabled individuals at matched speeds, Chen et al. [Chen G, Patten C, Kothari DH, Zajac FE. Gait differences between individuals with post-stroke hemiparesis and non-disabled controls at matched speeds. Gait Posture (2004)] identified gait deviations that were consistent with impaired swing initiation and single limb support in the paretic limb and related compensatory strategies. Treadmill training with harness support is a promising, task-oriented approach to restoring locomotor function in individuals with post-stroke hemiparesis. To provide a rationale for the proper selection of training parameters, we assessed the potential of body weight support, treadmill speed, support stiffness, and handrail hold to improve the identified gait deviations associated with hemiparesis during treadmill walking. In the six hemiparetic subjects studied, the adjustment of each training parameter was found to improve a specific set of the gait deviations. With increased body weight support or the addition of handrail hold, percentage single limb support time on the paretic limb increased and temporal symmetry improved. With increased treadmill speed, leg kinetic energy at toe-off in the paretic limb increased but remained low relative to values in the non-paretic limb. With increased support stiffness, the exaggerated energy cost associated with raising the trunk during pre-swing and swing of the paretic limb was improved. We conclude that the proper selection of training parameters can improve the gait pattern practiced by individuals with hemiparesis during treadmill training and may improve treatment outcome.

Body Weight↗
PubMed2005

Gait differences between individuals with post-stroke hemiparesis and non-disabled controls at matched speeds.

Treadmill walking was used to assess the consistent gait differences between six individuals with post-stroke hemiparesis and six non-disabled, healthy controls at matched speeds. The hemiparetic subjects walked on the treadmill at their comfortable speeds, while each control walked at the same speed as the hemiparetic subject with whom he or she was matched. Kinematic and insole pressure data were collected from multiple, steady-state gait cycles. A large set of gait differences found between hemiparetic and non-disabled subjects was consistent with impaired swing initiation in the paretic limb (i.e., inadequate propulsion of the leg during pre-swing, increased percentage swing time, and reduced knee flexion at toe-off and mid-swing in the paretic limb) and related compensatory strategies (i.e., pelvic hiking and swing-phase propulsion and circumduction of the paretic limb). Exaggerated positive work associated with raising the trunk during pre-swing and swing of the paretic limb, consistent with pelvic hiking, contributed to increased mechanical energetic cost during walking. A second set of gait differences found was consistent with impaired single limb support on the paretic limb (i.e., shortened support time on the paretic limb) and related compensatory strategies (i.e., exaggerated propulsion of the non-paretic limb during pre-swing to shorten its swing time). Other significant gait differences included asymmetry in step length and increased step width. We conclude that consistent gait differences exist between hemiparetic and non-disabled subjects walking at matched speeds. The differences provide insights, concerning hemiparetic impairment and related compensatory strategies, that are in addition to the observation of slow walking speed.

Aged↗
PubMed2005

Acute respiratory distress syndrome after rituximab infusion.

Rituximab, a humanized monoclonal antibody approved for malignant lymphoma, is being increasingly, effectively, and safely used for immune thrombocytopenic purpura (ITP) and other humoral autoimmune disorders. We report the case of a 43-year-old man with ITP refractory to steroids and intravenous immunoglobulin who developed acute respiratory distress syndrome (ARDS) after a single infusion of rituximab. Dyspnea, hypoxemia, and pleuritic chest pain occurred within 24 hours of rituximab administration, and there was no other apparent explanation. Progressive hypoxemia mandated endotracheal intubation 1 week after rituximab administration and led to death 4 weeks after admission. ARDS has been associated with the administration of other monoclonal antibodies, such as infliximab, gemtuzumab ozogamicin, and OKT3 and is believed to be directly mediated by release of proinflammatory cytokines. ARDS is rarely associated with rituximab infusion for lympho-proliferative disorders, but it should be considered by those administering rituximab, especially when a patient develops severe pulmonary symptoms soon after infusion.

Adult↗
PubMed2003

Expression and localization of AT1 receptors in hepatic Kupffer cells: its potential role in regulating a fibrogenic response.

Previous studies have showed that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of liver cirrhosis. The localization of angiotensin II receptor in hepatic stellate cells opens up a new research direction of RAS in the regulation of liver fibrosis. However, the potential role of angiotensin II on Kupffer cells remains unexplored. As Kupffer cells are actively involved in the fibrotic process, the present study aimed, specifically, to demonstrate the presence of key RAS components, with particular reference to the AT(1) receptor, and its potential role in hepatic Kupffer cells. The expression of key RAS components in rat liver and isolated hepatic Kupffer cells was analyzed by RT-PCR. The expression and precise localization of AT(1) receptors in hepatic Kupffer cells were investigated by Western blot analysis and immunofluorescent double staining, respectively. The effect of angiotensin-stimulated Kupffer cells on the expression of the fibrogenic factors, i.e. transforming growth factor-beta (TGF-beta) and fibronectin, was examined by semi-quantitative RT-PCR. RT-PCR analysis showed that mRNA of several key RAS components-angiotensin II receptors, angiotensinogen, renin and angiotensin-converting enzyme, particularly the AT(1) receptors, was expressed in the liver and isolated hepatic Kupffer cells. The AT(1) receptor protein was consistently expressed in hepatic Kupffer cells as evidenced by Western blot analysis. Double immunostaining confirmed that the AT(1) receptors were specifically localized to the Kupffer cells from the liver and isolated hepatic Kupffer cells. On the other hand, angiotensin II stimulated mRNA expression of TGF-beta and fibronectin, which could be inhibitable by saralasin and losartan, the nonselective and specific antagonists for AT(1) receptors, respectively. The present findings clearly demonstrated the expression, localization and potential role of local RAS components with particular emphasis on the AT(1) receptors in hepatic Kupffer cells. The intimate interaction of angiotensin II with its AT(1) receptor located in the Kupffer cells and its fibrogenic action may represent a regulatory mechanism in the development of liver fibrosis such as inflammation and cirrhosis.

Angiotensin II↗
PubMedDate not supplied

Treadmill training with harness support: selection of parameters for individuals with poststroke hemiparesis.

Locomotor training with a treadmill and harness support is a promising, task-oriented approach to restoring gait function in individuals with poststroke hemiparesis. However, a scientific basis for the proper selection of training parameters is lacking. Considerable latitude exists in the application of locomotor training, and training protocols vary widely between experimenters and clinical settings. Recent studies indicate that the prescription of certain parameters, including body-weight support (BWS) and treadmill speed, can affect treatment outcome in hemiparetic individuals. As an initial step toward developing a basis for selection of parameters, we reviewed the literature for studies that quantified the immediate (i.e., within session) biomechanical effects of adjusting BWS, treadmill speed, support stiffness, and handrail hold during treadmill walking in hemiparetic and nondisabled subjects. We then summarized results from personal investigations of these parameters. Based on the currently available evidence, we discuss the scientific rationale for selecting certain training parameters for individuals with poststroke hemiparesis and outline future directions for research.

Exercise Therapy↗