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Biomedical subjects

R C Lee

Publications and source records attributed to R C Lee.

At least 19 recordsLinked to original sources
PubMed2001

Skeletal muscle mass and aging: regional and whole-body measurement methods.

Skeletal muscle is a large compartment that can now be quantified using research and clinically applicable regional and whole-body methods. The most important advances are the two imaging methods, computed tomography (CT) and magnetic resonance imaging (MRI). Both CT and MRI can serve as regional and whole-body reference methods when evaluating other approaches for estimating skeletal muscle mass. Imaging methods also afford the opportunity to quantify both anatomic skeletal muscle and the smaller adipose-tissue free skeletal muscle component. Other available methods for estimating skeletal muscle, either regional or at the whole body level, include dual-energy x-ray absorptiometry, in vivo neutron activation analysis-whole body counting, anthropometry, ultrasound, bioimpedance analysis, and urinary metabolite markers. Each method is reviewed in the context of the aging process, cost, availability, practicality, and desired accuracy. New insights should be possible when skeletal muscle mass, measured using these methods, is combined with other descriptors of muscle biochemical and mechanical function.

Absorptiometry, Photon↗
PubMed2000

Total-body skeletal muscle mass: development and cross-validation of anthropometric prediction models.

BACKGROUND: Skeletal muscle (SM) is a large body compartment of biological importance, but it remains difficult to quantify SM with affordable and practical methods that can be applied in clinical and field settings. OBJECTIVE: The objective of this study was to develop and cross-validate anthropometric SM mass prediction models in healthy adults. DESIGN: SM mass, measured by using whole-body multislice magnetic resonance imaging, was set as the dependent variable in prediction models. Independent variables were organized into 2 separate formulas. One formula included mainly limb circumferences and skinfold thicknesses [model 1: height (in m) and skinfold-corrected upperarm, thigh, and calf girths (CAG, CTG, and CCG, respectively; in cm)]. The other formula included mainly body weight (in kg) and height (model 2). The models were developed and cross-validated in nonobese adults [body mass index (in kg/m(2)) < 30]. RESULTS: Two SM (in kg) models for nonobese subjects (n = 244) were developed as follows: SM = Ht x (0.00744 x CAG(2) + 0.00088 x CTG(2) + 0.00441 x CCG(2)) + 2.4 x sex - 0.048 x age + race + 7.8, where R:(2) = 0.91, P: < 0.0001, and SEE = 2.2 kg; sex = 0 for female and 1 for male, race = -2.0 for Asian, 1.1 for African American, and 0 for white and Hispanic, and SM = 0.244 x BW + 7.80 x Ht + 6.6 x sex - 0.098 x age + race - 3.3, where R:(2) = 0.86, P: < 0.0001, and SEE = 2.8 kg; sex = 0 for female and 1 for male, race = -1.2 for Asian, 1.4 for African American, and 0 for white and Hispanic. CONCLUSION: These 2 anthropometric prediction models, the first developed in vivo by using state-of-the-art body-composition methods, are likely to prove useful in clinical evaluations and field studies of SM mass in nonobese adults.

Adult↗
PubMed2000

Use of quality-adjusted life year weights with dose-response models for public health decisions: a case study of the risks and benefits of fish consumption.

Risks associated with toxicants in food are often controlled by exposure reduction. When exposure recommendations are developed for foods with both harmful and beneficial qualities, however, they must balance the associated risks and benefits to maximize public health. Although quantitative methods are commonly used to evaluate health risks, such methods have not been generally applied to evaluating the health benefits associated with environmental exposures. A quantitative method for risk-benefit analysis is presented that allows for consideration of diverse health endpoints that differ in their impact (i.e., duration and severity) using dose-response modeling weighted by quality-adjusted life years saved. To demonstrate the usefulness of this method, the risks and benefits of fish consumption are evaluated using a single health risk and health benefit endpoint. Benefits are defined as the decrease in myocardial infarction mortality resulting from fish consumption, and risks are defined as the increase in neurodevelopmental delay (i.e., talking) resulting from prenatal methylmercury exposure. Fish consumption rates are based on information from Washington State. Using the proposed framework, the net health impact of eating fish is estimated in either a whole population or a population consisting of women of childbearing age and their children. It is demonstrated that across a range of fish methylmercury concentrations (0-1 ppm) and intake levels (0-25 g/day), individuals would have to weight the neurodevelopmental effects 6 times more (in the whole population) or 250 times less (among women of child-bearing age and their children) than the myocardial infarction benefits in order to be ambivalent about whether or not to consume fish. These methods can be generalized to evaluate the merits of other public health and risk management programs that involve trade-offs between risks and benefits.

Adolescent↗
PubMed2000

Integrin-dependent human macrophage migration induced by oscillatory electrical stimulation.

Electrical stimulation has been used to promote wound healing. The mechanisms by which such stimulation could interact with biological systems to accelerate healing have not been elucidated. One potential mechanism could involve stimulation of macrophage migration to the site of a wound. Here we report that oscillatory electric fields induce human macrophage migration. Macrophages exposed to a 1 Hz, 2 V/cm field show an induced migration velocity of 5.2+/-0.4 x 10(-2) microm/min and a random motility coefficient of 4.8+/-1.4 x 10(-2) microm2/min on a glass substrate. Electric field exposure induces reorganization of microfilaments from ring-like structures at the cell periphery to podosomes that are confined to the contact sites between cell and substrate, suggesting that the cells are crawling on glass. Treatment of cells with monoclonal antibodies directed against beta2-integrins prior to field exposure prevents cell migration, indicating that integrin-dependent signaling pathways are involved. Electric fields cause macrophage migration on laminin or fibronectin coated substrates without inducing podosome formation or changes in cellular morphology. The migration velocity is not significantly altered but the random movement is suppressed, suggesting that cell movements on a laminin- or fibronectin-coated surface are not mediated by cell crawling. It is suggested that electric field-induced macrophage migration utilizes several modes of cell movement, including cell crawling and possibly cell rolling.

Cell Movement↗
PubMed2000

Structure and function analysis of LIN-14, a temporal regulator of postembryonic developmental events in Caenorhabditis elegans.

During postembryonic development of Caenorhabditis elegans, the heterochronic gene lin-14 controls the timing of developmental events in diverse cell types. Three alternative lin-14 transcripts are predicted to encode isoforms of a novel nuclear protein that differ in their amino-terminal domains. In this paper, we report that the alternative amino-terminal domains of LIN-14 are dispensable and that a carboxy-terminal region within exons 9 to 13 is necessary and sufficient for in vivo LIN-14 function. A transgene capable of expressing only one of the three alternative lin-14 gene products rescues a lin-14 null mutation and is developmentally regulated by lin-4. This shows that the deployment of alternative lin-14 gene products is not critical for the ability of LIN-14 to regulate downstream genes in diverse cell types or for the in vivo regulation of LIN-14 level by lin-4. The carboxy-terminal region of LIN-14 contains an unusual expanded nuclear localization domain which is essential for LIN-14 function. These results support the view that LIN-14 controls developmental timing in C. elegans by regulating gene expression in the nucleus.

Amino Acid Sequence↗
PubMed2000

Surfactant sealing of membranes permeabilized by ionizing radiation.

Acute tissue injury and subsequent inflammation, including tissue edema and erythema, can be caused by sufficiently high levels of exposure to gamma radiation. The mechanism of this tissue injury is related to the generation of reactive oxygen intermediates (ROI) which chemically alter biological molecules and cell physiology. Cell membrane lipids are vulnerable to ROI-mediated lipid peroxidation that then leads to many of the acute tissue effects. We hypothesize that increased cell membrane permeability leading to osmotic swelling and vascular transudation is one of these effects. Thus we used adult postmitotic rhabdomyocytes in culture and microscopic fluorescence techniques to quantify radiation-induced changes in cell membrane permeability. Based on time-resolved dye flux measurements, a characteristic lag time of 34 +/- 3 min was determined between exposure to 160 Gy of gamma radiation and the decrease in membrane permeability. Administration of 0.1 mM nonionic surfactant Poloxamer 188 added to the cell medium after irradiation completely inhibited the dye loss over the time course of 2 h. Thus a reproducible model was developed for studying the mechanism of acute radiation injury and the efficacy of membrane-sealing agents. As only supportive measures now exist for treating the acute, nonlethal injuries from high-dose radiation exposure, agents that can restore cell membrane function after radiation damage may offer an important tool for therapy.

Animals↗
PubMed2000

Upper extremity electrical injury.

Electrical injuries to the upper extremity are far ranging in extent and vary in magnitude. Proper management requires an appreciation for the pathophysiology, clinical manifestations, and therapeutic options. Persistent neurologic and psychiatric problems further impact the high incidence of disability in the electrical injury patient. Loss is significant for victims, their families, and employers, in part because of the relative youth of those injured.

Arm Injuries↗
PubMed2000

Cecal volvulus: report of seven cases and literature review.

BACKGROUND: Cecal volvulus is an abdominal emergency and delay in its diagnosis and treatment can result in severe complications. We reviewed these cases in order to increase the understanding of cecal volvulus (CV) to promote early diagnosis and better management. METHODS: In this retrospective study of seven patients (all male; mean age +/- standard deviation, 63.4 +/- 17.3 years) over a 16-year period, we reviewed radiographs, for diagnostic accuracy, and the results of surgical procedures for better future management. RESULTS: The symptoms of CV related to obstruction had a mean of duration of 6.85 days (range, 2-20 days). The preoperative diagnosis rate was 57.1%. Three types of CV (bascule, clockwise and counterclockwise) were found. There were three treatment failures resulting in two deaths. There were two cases of metachronous volvulus, one in the sigmoid colon and one in the small intestine. CONCLUSIONS: Resection is indicated for gangrene or perforation and is highly suggested in underlying bowel disease or recurrent operative procedures. For uncomplicated viable CV, cecopexy provides fair results. Metachronous volvulus should always be considered when obstruction recurs.

Adult↗
PubMed2000

Abdominal wall necrosis following transcatheter arterial chemoembolization for hepatocellular carcinoma.

A 76-year-old man, who had inoperable hepatocellular carcinoma, had been treated with transcatheter arterial chemoembolization (TACE) 11 times, percutaneous ethanol injection therapy three times and conformal radiotherapy once, all in other hospitals. At this admission, he developed myocutaneous necrosis in the right abdominal wall after TACE, via the collateral of the right internal mammary artery (IMA). Necrosis of the abdominal wall was due to ischemic changes caused by embolization of the distal branches of the IMA, which were aggravated by previous radiation therapy. We advise that embolization of the IMA in patients who have received radiotherapy should be avoided, if possible.

Abdominal Muscles↗
PubMed1999

Dynamics of membrane sealing in transient electropermeabilization of skeletal muscle membranes.

Large supraphysiologic transmembrane electrical potentials are known to alter the molecular organization of the bilayer lipid component of cell membranes, leading to ionic permeabilization or "electroporation". Typically, membrane electroporation is followed by several orders of magnitude increases in electrical conductance and diffusive permeability to low-molecular-weight solutes. Electroporation may be transient or stable depending on whether the membrane eventually seals or remains permeabilized. Factors that control sealing have not been well characterized. This paper describes the kinetics of membrane sealing following electroporation by pulses over a range of supraphysiologic potentials. The increase in membrane conductance is highly nonlinear during a -440-mV, 4-ms pulse and reaches two orders of magnitude greater than baseline. Electroporation and relaxation sealing kinetics are quite different, reflecting a significant hysteresis effect. Thus, it appears that the magnitude and duration of the field pulse are important factors in sealing.

Animals↗
PubMed1999

The use of collagen-GAG membranes in reconstructive surgery.

Porous collagen-glycosaminoglycan (PCG) membranes with a porous silicone elastomer coating have been useful as a scaffold for dermal replacement in burn victims. Critical physicochemical parameters of these membranes include pore size, cross-link density, the percentage of glycosaminoglycan, and the degree of banding of the collagen. These factors govern the immunobiological response. Optimizing these parameters can reduce inflammation, scarring, and contraction of wounds grafted with PCG membranes. PCG membranes are currently commercially manufactured (Integra, Integra Life Sciences, New Jersey) and available for clinical use. Because clinical outcomes have improved using these membranes for burn wound coverage, other skin reconstruction problems including scar resurfacing, keloids, treatment of donor sites, and treatment of chronic wounds can be considered as potential applications. This manuscript illustrates our early experience using Integra as a CG membrane for dermal replacement in reconstructive surgery. Our results indicate that CG membranes can lead to improved compliance and appearance compared to a meshed graft and may be sequentially placed in multiple layers to correct contour deformities. Also, in one case, we observed that, if placed on a wound bed with embedded skin epithelial cells, the PCG promotes epithelialization through the PCG matrix. The use of this material results in a supple integument with many similarities to normal skin.

Adult↗
PubMed1999

Pharmaceutical therapies for sealing of permeabilized cell membranes in electrical injuries.

Several years ago, we proposed that loss of cell membrane structural integrity by electroporation is a substantial cause of tissue necrosis in victims of electrical trauma. Specifically, this involves the permeabilization of the lipid bilayer by thermal and electrical forces. We further suggested that certain mild surfactants in low concentration could induce sealing of permeabilized lipid bilayers and salvage of cells that had not been extensively heat-damaged. Successful restoration of membrane transport properties using the surfactant poloxamer 188 was reported in 1992. The purpose of this study is to further examine the response of electroporated rat skeletal muscle membranes to poloxamer 188 (P188) therapy by direct assay of membrane transport properties. Experimental evidence accumulated to date suggests that P188 is effective in sealing permeabilized cell membranes both in vitro and in vivo.

Animals↗
PubMed1999

Oxidative cell membrane alteration. Evidence for surfactant-mediated sealing.

Exposure to very intense ionizing irradiation produces acute tissue sequelae including inflammation, pain, and swelling that often results in tissue fibrosis and/or necrosis. Acute tissue necrosis occurs in hours when sufficiently rapid damage to membrane lipids and proteins leads to altered membrane structure, disrupting the vital electrochemical diffusion barrier necessary for cell survival. This damage mechanism is thought to underlie the interphase death of lethally irradiated postmitotic cells such as neurons, but it has also been implicated in the rapid cell death of lymphocytes and acute vascular changes due to capillary epithelium dysfunction. It is not known whether sealing of radiation-permeabilized cell membranes will prolong survival of lethally irradiated cells or perhaps lead to repair of damaged nucleic acids. The purpose of this study is to begin to address the first question.

Cell Membrane↗
PubMed1999

Management and coordination of postacute medical care for electrical trauma survivors.

The clinical spectrum of electrical injury ranges from the absence of any external physical signs to severe multiple trauma. Reported neuropsychiatric sequelae can vary from vague complaints, which may seem unrelated to the injury in their occurrence over time or by their apparent severity, to sequelae consistent with brain injury accompanying an electrical trauma. In this report, a case study and discussion are presented on the management and coordination of post-acute care of an electrical trauma survivor. Expertise and a multidisciplinary team are essential to cohesive patient care. Patient monitoring for progressive changes and prompt intervention are needed to address the potential difficulties experienced by trauma survivors as they rehabilitate to return to their work and their activities of daily living.

Adult↗
PubMed1999

Life after electrical injury. Risk factors for psychiatric sequelae.

Long-term cognitive and emotional deficits have been commonly reported in electrical injury (EI) survivors. However, it remains undetermined what factors may lead to the development of such effects in some patients and not in others. In this study, we hypothesized that certain elements of subjective EI experience may predict specific psychiatric sequelae. A group of 73 post-acute EI patients were included in this retrospective study. Statistical associations were examined between major psychiatric diagnoses (posttraumatic stress disorder and major depression) and such EI descriptors as having experienced "no-let-go" or having been knocked away on contact, as well as loss of consciousness or altered states of consciousness at the scene of the accident (including amnesia for the event). The study results will help physicians determine which patients may be at increased risk of developing psychiatric symptoms and address these issues as part of their total rehabilitation plan.

Adult↗
PubMed1999

Constitutive activation of the prolactin receptor results in the induction of growth factor-independent proliferation and constitutive activation of signaling molecules.

The ability to induce the oncogenic activation of the human prolactin receptor (PRLR) was examined by deleting 178 amino acids of the extracellular ligand-binding domain. Expression of this deletion mutant in the interleukin-3 (IL-3)-dependent murine myeloid cell line 32Dcl3 resulted in the induction of growth factor-independent proliferation. Parental 32Dcl3 cells proliferated only in the presence of exogenous murine IL-3 (mIL-3), while 32Dcl3 cells transfected with the long form of the human PRLR were able to proliferate in response to mIL-3, ovine prolactin, or human PRL. Cells expressing the Delta178 deletion mutant contained numerous phosphotyrosine-containing proteins in the absence of stimulation with either mIL-3 or ovine prolactin. Growth factor stimulation increased the number of proteins phosphorylated and the intensity of phosphorylation. These proteins included constitutively phosphorylated Janus kinase 2, signal transducer and activator of transcription 5, and SHC. Activated extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2) were observed in unstimulated 32Dcl3 cells expressing the Delta178 mutant. Likewise, transfection of Nb2 cells with the Delta178 deletion mutant induced growth factor-independent proliferation and constitutive activation of Janus kinase 2, ERK1, and ERK2. In addition to the induction of a growth factor-independent state, the expression of the Delta178 deletion mutant also suppressed the apoptosis that occurs when 32Dcl3 cells are cultured in the absence of growth factors such as IL-3. These data suggest that the constitutive activation of the PRLR can be achieved by deletion of the ligand binding domain and that this mutation leads to the oncogenic activation of the receptor as determined by the ability of the receptor to induce growth factor-independent proliferation of factor-dependent hematopoietic cells.

Caseins↗