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Biomedical subjects

R C Lee

Publications and source records attributed to R C Lee.

At least 109 records · Page 6Linked to original sources
PubMed1990

Genetically determined alcohol preference and cyclic AMP binding proteins in mouse brain.

Free-choice consumption of alcohol by mice with differing phenotypic alcohol preferences caused uniformly large decreases in brain cyclic AMP-dependent protein kinase activity toward an exogenous substrate (histone 2b) but the effect of alcohol on brain cyclic AMP binding activity was strain-specific. Furthermore, particulate kinase phosphorylating activity toward an endogenous protein (kinase regulatory subunit, RII) was altered by alcohol consumption in a strain-specific manner. The changes in cyclic AMP binding and phosphorylating activity appeared to result from phenotypic differences in the brain's response to alcohol. Thus, low preference animals were sensitive to alcohol and showed a large decrease in cyclic AMP binding and an increase in phosphorylation of regulatory subunit in response to alcohol. In contrast, high preference strain had only a small decrease in cyclic AMP binding and a decrease in phosphorylation, even though these animals consumed a significantly larger dose of alcohol. These data suggest that changes in cyclic AMP binding and/or phosphorylation of kinase regulatory subunit may be phenotypic markers of alcohol preference in inbred mice.

Alcoholism↗
PubMed1990

Evolving clinical and scientific concepts of upper extremity electrical trauma.

In conclusion, the pathogenesis of electrical injury is more complex than previously thought. Cellular damage occurs both by heating and electroporation. The relative contributions of heat and electroporation depend on the duration of electric current passage, the orientation of the cells, their location, and other factors. If the contact is brief, nonthermal mechanisms of cell damage may be most important. If the contact is much longer, heat damage will be most destructive. The characteristic time before heat damage predominates is probably a function of the electrical field strength in the tissue. If heat damage predominates, the injury may not be limited just to the plasma membrane but to other cell membranes as well. This is unlikely to be reversible. These parameters should also determine the pattern of injury. Damage by Joule heating is not known to be dependent on cell size, whereas larger cells are more vulnerable to membrane breakdown by electroporation. Cells do survive transient plasma membrane rupture under appropriate circumstances. Thus, if electroporation is the mechanism of damage, injured tissue may be salvageable; the challenge is to identify a technique that promptly reseals the damaged membranes. Current therapy requires a fully staffed and equipped intensive care unit, available operating suites, and the full range of available medical specialists. Major teaching hospitals are usually the prime candidates for operating an electric trauma unit. After initial resuscitation, efforts should be directed primarily toward preventing additional tissue loss mediated through a compartment syndrome. Renal and cardiac failure resulting from the release of intracellular muscle contents into the circulation must be prevented. Attention can then be directed toward maximizing tissue salvage and preventing late skeletal and neuromuscular complications. Finally, complex reconstructive procedures are needed to optimize the functional value of the remaining tissue. The eventual reconstructive goals should be kept in mind throughout the acute care of the patient.

Arm Injuries↗
PubMed1989

Kinetics of the chondrocyte biosynthetic response to compressive load and release.

To gain insight regarding the rate at which cartilage tissue can sense and respond to a dynamic mechanical stimulus, we have examined the time-course of changes in biosynthetic activity following both the application and release of a static compressive stress. Cartilage harvested from the reserve zone of calf epiphyseal plate was subjected to unconfined static compressive stresses of 0, 0.25 and 0.5 MPa. Incorporation of [35S]sulfate and [3H]proline was measured during loading periods of less than 1 to 26 h and after preloading periods of 0.5, 2 or 12 h. During loading, total incorporation decreased to steady levels with time constants estimated to be 0.25-4 h (proline) and 1-5 h (sulfate). Proline incorporation exceeded control levels for 3 h after release of a 2 or 12 h preload. Sulfate incorporation remained depressed for at least 4 h after release of a 12 h preload and remained at control levels following release of 0.5 and 2 h preloads. We conclude that the modulation of proline incorporation by both loading and load release is faster than the modulation of sulfate incorporation. Furthermore, the response to unloading is not just the inverse of the response to loading; this nonlinearity suggests that the response to dynamic loading would not be determined simply by the time average component of the dynamic load.

Animals↗
PubMed1988

Significance of cell size and tissue structure in electrical trauma.

High-voltage electrical trauma frequently leads to extensive and selective destruction of muscle and nerve tissue. In this paper, the mechanism of plasma membrane disruption due to the large transmembrane potentials imposed during electrical trauma is used to explain the particular susceptibility of muscle and nerve cells to damage. It is proposed that this vulnerability is partially due to the relatively large size of these cells. A distributed-parameter electric cable model of an elongated cell is used to examine the alteration of the transmembrane potential caused by a 60 Hz electric field applied parallel to the long axis of the cell. The maximum predicted transmembrane potential occurs at the ends of the cell and is strongly cell-size dependent. Theories are discussed which illustrate how this could explain the predisposition of skeletal muscle to cell membrane breakdown and rupture. The predicted effect of either close-neighboring cells in a tissue or cell contact with cortical bone is even greater induced transmembrane potentials and increased probability of rupture. This is the first hypothesis which explains the clinically-observed pattern of tissue damage resulting from electrical trauma.

Cell Membrane↗
PubMed1988

Mechanical and physiochemical determinants of the chondrocyte biosynthetic response.

The relation between mechanical loading of cartilage and chondrocyte activity in vivo may be mediated by several physical transduction mechanisms including: cell deformation, hydrostatic pressure gradients, fluid flow, streaming currents, and physicochemical changes. We have developed an organ culture system designed to study chondrocyte biosynthetic response to such physical stimuli. This study focuses on the effects of static compression and physicochemical changes. Cartilage disks harvested from the reserve zone of the epiphyseal plate of 1-2-week-old calves were subjected to static compressive stresses of 0-3 MPa in unconfined compression and the incorporation of [35S]sulfate and [3H]proline was measured during the 12-h loading period. Incorporation of both proline and sulfate decreased monotonically with increasing stress. Compressive loading also produces physicochemical changes including a decreased water content and increased matrix fixed-charge density, with a concomitant increase in interstitial counterion concentrations (e.g., K+, H+) and decreased coion concentrations (e.g., SO4(2-). We therefore examined the possibility that specific changes in interstitial mobile ion concentrations may be linked to chondrocyte response to static compression by measuring biosynthesis in the absence of mechanical compression while independently altering the SO4(2-), K+, and H+ composition of the bathing medium. We found that proline and sulfate incorporation were strongly dependent on pH, but independent of [SO4(2-)] and [K+] in the range studied. These results suggest that compression-induced changes in local, interstitial pH may account for the observed biosynthetic response to static compression.

Animals↗
PubMed1988

Role of cell membrane rupture in the pathogenesis of electrical trauma.

Heating due to current flow may not always be the primary cause of tissue damage in electrical injury. We have demonstrated that electric field strengths relevant to the clinical electrical injury problem are capable of permanently disrupting isolated skeletal muscle cells and altering the electrical properties of intact skeletal muscle in the absence of Joule heating effects. The field strengths used in these experiments are theoretically representative of fields at sites distant from the surface entry and exit points in many cases of electrical injury. These results provide further evidence that cell membrane disruption by large induced transmembrane potentials may explain the changes in the electrical properties of muscle observed in experimental electrical trauma (M. Chilbert, et al., J. Trauma 25: 209, 1985) and thus may contribute significantly to the extensive tissue destruction associated with electrical trauma.

Animals↗
PubMed1987

Frequency dependence of electric field modulation of fibroblast protein synthesis.

The effect of electric current on protein biosynthesis in mammalian fibroblasts was investigated with neonatal bovine fibroblast-populated collagen matrices. The field strength dependence of electric field modulation of proline incorporation into extracellular and intracellular protein was measured over a frequency range from 0.1 to 1000 hertz. A frequency- and amplitude-dependent reduction in the rate of incorporation was observed. In tissues containing cells aligned either parallel or perpendicular to the electric field, this response was dependent on the orientation of the cells relative to the direction of the applied electric field. This study demonstrates that currents of physiological strength can stimulate alterations in biosynthesis and thereby may influence tissue growth, remodeling, and repair.

Animals↗
PubMed1987

Electrical injury mechanisms: electrical breakdown of cell membranes.

Electric fields are capable of damaging cells through both thermal and nonthermal mechanisms. While joule heating is generally recognized to mediate tissue injury in electrical trauma, the possible role of electrical breakdown of cell membranes has not been thoroughly considered. Evidence is presented suggestive that in many instances of electrical trauma the local electrical field is of sufficient magnitude to cause electrical breakdown of cell membranes and cell lysis. In theory, large cells such as muscle and nerve cells are more vulnerable to electrical breakdown. To illustrate the significance of cell size and orientation, a geometrically simple model of an elongated cell is analyzed.

Arm↗
PubMed1987

Electrical injury mechanisms: dynamics of the thermal response.

The thermal response of the human upper extremity to large electric currents was examined using an axisymmetric unidimensional model containing bone, skeletal muscle, fat, and skin in coaxial cylindrical geometry. Appropriate thermal and electrical properties were assigned to each tissue, and the tissue response to joule heating was determined by a finite-element numerical technique. We found that when the tissues are electrically in parallel, skeletal muscle sustained the largest temperature rise and then heated adjacent tissues. Thus, when bone is not in series with other tissues, joule heating of bone is unlikely to be responsible for thermal damage to adjacent tissue. In addition, the effect of tissue perfusion on the thermal response was found to be essential for rapid cooling of the centrally located tissues.

Adipose Tissue↗
PubMed1984

Use of hyperimmune serum, vaccination, and certain management procedures for control of pseudorabies in swine.

A program involving use of hyperimmune serum, vaccination, and certain management procedures for the control of pseudorabies was evaluated on several farms on which the disease was enzootic. Neonatal mortality and reproductive failures on farms utilizing the program were compared with death losses and reproductive failures on farms not utilizing the program. The reduction in preweaning mortality and reproductive failures between the treated and nontreated groups were 42.1% and 39.6%, respectively.

Abortion, Veterinary↗
PubMed1982

A comparison of in vitro cellular responses to mechanical and electrical stimulation.

In the last several decades, enormous interest has been generated toward understanding the cell as it is controlled by its external physical environment. The purpose of this study was to determine the effects of well-defined applied mechanical stress and time-varying electric fields on the cellular synthesis of connective tissue macromolecules. Chondrocytes harvested by trypsin digestion of 15-day-old chick embryo sternae were randomly dispersed and cultured on elastin membranes in a humidified atmosphere with 10 per cent CO2 and 90 per cent air. Following five days of growth in F12 media and 5 per cent fetal calf serum, the membranes underwent either 1) a 10 per cent cyclic mechanical stretch or 2) 60 Hz A.C. electrical stimulation with current densities of 1 to 1,000 nA/mm2 or 3) control without stimulation, each for an eight-hour period. C14-hydroxyproline incorporation into collagen, and H2 35 SO4 incorporation into glycosaminoglycans (GAGs) were measured by liquid scintillation techniques. Scanning and transmission electron microscopy analysis of control and stimulated cells demonstrated discernable differences. Both mechanically and electrically stimulated chondrocytes showed a two- to three-fold increase in GAG synthesis and a general depression in protein and collagen synthesis over controls. The general similarity in response to both mechanical and electrical stress suggests common processes by which they modulate cellular synthesis of cartilage connective tissue proteins.

Animals↗
PubMed1981

Oscillatory compressional behavior of articular cartilage and its associated electromechanical properties.

The compressive stiffness of articular cartilage was examined in oscillatory confined compression over a wide frequency range including high frequencies relevant to impact loading. Nonlinear behavior was found when the imposed sinusoidal compression amplitude exceeded a threshold value that depended on frequency. Linear behavior was attained only by suitable control of the compression amplitude. This was enabled by real time Fourier analysis of data which provided an accurate assessment of the extent of nonlinearity. For linear viscoelastic behavior, a stiffness could be defined in the usual sense. The dependence of the stiffness on ionic strength and proteoglycan content showed that electrostatic forces between matrix charge groups contribute significantly to cartilage's compressive stiffness over the 0.001 to 20 Hz frequency range. Sinusoidal streaming potentials were also generated by oscillatory compression. A theory relating the streaming potential field to the fluid velocity field is derived and used to interpret the data. The observed magnitude of the streaming potential suggests that interstitial fluid flow is significant to cartilage behavior over the entire frequency range. The use of simultaneous streaming potential and stiffness data with an appropriate theory appears to be an important tool for assessing the relative contribution of fluid flow, intrinsic matrix viscoelasticity, or other molecular mechanisms to energy dissipation in cartilage. This method is applicable in general to hydrated, charged polymers.

Action Potentials↗
PubMed1980

Placental lesions caused by pseudorabies virus in pregnant sows.

Pathologic and viral investigations were done on 13 fetal placentas and 23 aborted fetuses associated with naturally occurring pseudorabies in swine. Of the 13 fetal placentas examined, 7 (53.8%) had various degrees of necrotizing placentitis. The lesions were characterized by coagulative necrosis of the chorionic fossae and by intranuclear inclusions in degenerating trophoblasts and occasionally in mesenchymal cells. In addition, a mild inflammatory cell reaction was observed in the mesenchyma. Numerous viral particles, ultrastructurally indistinguishable from herpesvirus, were observed by electron microscopy in the affected chorionic membrane. Large aggregates of herpesvirus virions were demonstrated in the nucleus and cytoplasm of degenerated trophoblasts and mesenchymal cells. Of the 23 aborted fetuses examined, 22 (95.6%) had typical coagulative necrosis in the liver, spleen, adrenal glands, and visceral lymph nodes. Inclusions similar to those in the chorionic placenta were observed in the parenchymal cells of those organs, on the margins of necrotic areas. Pseudorabies virus was isolated from various organs of the aborted fetuses, but virus isolation from the placentas was not attempted. In a survey of 52 affected sows, sera from 49 (94.2%) neutralized the isolated virus. The findings indicated that the placental lesions caused by the virus were primary. The study also indicated the merit of routine examination of aborted fetal placentas and fetuses for diagnosis of pseudorabies.

Animals↗
PubMed1973

Applications of artificial intelligence: relationships between mass spectra and pharmacological activity of drugs.

The possibility that the mass spectrum and pharmacological activity of a compound may be directly related has been explored with the help of various computer-based pattern-recognition techniques. The relationship appears to hold at least for tranquilizers and sedatives, and compounds with one or the other of these two pharmacological activities can thus be classified from their mass spectra with a high degree of accuracy.

Computers↗