MAST and adrenergic-resistant anaphylaxis.
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Anaphylaxis↗
Biomedical subjects
R B Low
Publications and source records attributed to R B Low.
Control of intraabdominal hemorrhage and shock: a comparison of fluid resuscitation, MAST, and balloon occlusion.
Our study examined the efficacy of four treatment modalities in controlling hemorrhage and achieving hemodynamic stabilization in hemorrhagic shock: intravenous fluid replacement (IV); military antishock trousers used concomitantly with fluids (MAST); balloon occlusion at the level of the diaphragm with concomitant fluid replacement (balloon); and a combination of MAST inflation, balloon occlusion, and fluid resuscitation (MAST and balloon). Twenty-eight mongrel dogs were anesthetized, and the spleen was exposed and completely crushed. The abdomen was closed, and treatment was initiated and continued for four hours or until the dog died. For all conditions the hematocrit dropped during the course of the experiment; balloon occlusion was effective at slowing this drop (P less than .0001), but MAST had no statistically significant effect. Animals with balloons bled more slowly into the abdominal cavity than did animals in the other two groups (P less than .0001). MAST also were effective at slowing the bleeding (P less than .05). Of the balloon and the MAST and balloon dogs, all except one survived the entire four hours; this difference between balloon and nonballoon dogs is significant (P = .002). MAST did not have a statistically significant effect on survival. Perfusion pressure (PP) declined during the course of the experiment, and the balloon was effective at slowing this decline (P less than .0001); none of the other comparisons was statistically significant.
Analysis of Variance↗
Synthesis of cytoskeletal and contractile proteins by cultured IMR-90 fibroblasts.
Models of the assembly of cytoskeletal and contractile proteins of eukaryotic cells require quantitative information about the rates of synthesis of individual component proteins. We applied the dual isotope technique of Clark and Zak (1981, J. Biol. Chem., 256:4863-4870) to measure the synthesis rates of cytoskeletal and contractile proteins in stationary and growing cultures of IMR-90 fibroblasts. Fibroblast proteins were labeled to equilibrium with [14C]leucine over several days, at the end of which there was a 4-h pulse with [3H]leucine. Fractional synthesis rates (percent per hour) were calculated from the 3H/14C ratio of cell protein extracts or protein purified by one- or two-dimensional polyacrylamide gel electrophoresis and the 3H/14C ratio of medium-free leucine. The average fractional synthesis rate for total, SDS- or urea-soluble; Triton-soluble; and cytoskeletal protein extracts in stationary cells each was approximately 4.0%/h. The range of values for the synthesis of individual proteins from total cell extracts or cytoskeletal extracts sliced from one-dimensional gels was similar, though this range was greater than that for major proteins of Triton-soluble protein extracts. Three specific cytoskeletal proteins--actin, vimentin, and tubulin--were synthesized at similar rates that were significantly slower than the average fractional synthesis rate for total protein. Myosin, on the other hand, was synthesized faster than average. Synthesis rates were the same for beta-and gamma-actin and polymerized (cytoskeletal extract) vs. Triton-soluble actin. The same was true for alpha- and beta-tubulin and two different forms of vimentin. Synthesis rates were uniformly higher in growing cells, though the same pattern of differential rates was observed as for stationary cells. Synthesis rates in growing cells were higher than the rate necessary to maintain the growth rate, even for those cytoskeletal proteins being synthesized slowly. Therefore, there appears to be some turnover of these cytoskeletal elements even during growth. We conclude that proteins in cytoskeletal extracts may have nonuniform rates of synthesis, but at least one important subclass of cytoskeletal proteins that comprise filament subunits have the same synthesis rates.
Actins↗
Heterogeneity of myosin isozyme content of rabbit heart.
A detailed study was carried out to measure the relative contents of V1 and V3 myosin isozymes in different regions of rabbit ventricle as a function of age, to assess animal-to-animal variability, and to compare different experimental approaches aimed at minimizing the effects of such variability. In addition, comparisons were made in normal developing hearts between ventricular isozyme composition and myofibrillar myosin calcium-stimulated adenosine triphosphatase. V1 isozyme predominated relative to V3 isozyme in the hearts of 2-week-old rabbits, decreasing to become a minor component in 10-week-old animals. Despite this trend, there was considerable variability in relative isozyme content of whole ventricular tissue among different rabbits of the same age. This variability was reduced in comparisons of littermates and by use of cardiac biopsies to measure changes in isozyme content in the same animal over time. Within different regions of a given heart, there also were small but significant differences in the percent V1 isozyme. The percent V1 was greatest for right ventricular papillary, followed by right ventricular free wall and then the left ventricle (free wall plus septum). There also were differences in the percent V1 within those regions, as exemplified by the significantly higher values for ventricular epicardium vs. endocardium. There was a linear correlation between the myofibrillar myosin calcium-stimulated adenosine triphosphatase and percent V1 of total isozyme for both right and left ventricles in normal and developing hearts. The regression lines for calcium-stimulated adenosine triphosphatase vs. percent V1 had a steeper slope in the left than in the right ventricle.
Aging↗
Biochemical, cytological, and histological alterations in rat lung following acute beryllium aerosol exposure.
Fischer 344 rats were exposed for 1 hr to an aerosol of BeO generated at a temperature of 560 degrees C. An initial lung burden of 500 +/- 4.1 ng Be was achieved. Animals were killed at 2.5 hr, and 2, 12, and 21 days postexposure. Bronchopulmonary lavage fluids were analyzed biochemically for enzymes, protein, lipids, and sialic acid, and cytologically to determine the composition of the free alveolar cell population. Nonspecific phagocytosis of yeast was measured in adherent macrophages. There were increases in all the biochemical parameters by 2 days postexposure, which peaked by Day 5 and then began to return to control levels. The cytological response on Days 2 and 5 was characterized by polymorphonuclear leucocyte infiltration and a depression in macrophage number and phagocytic activity. By Day 12, increased numbers of newly recruited macrophages with supranormal phagocytic activity populated the lung. During the same period, there was a reduction in lavage protein and lipid levels, perhaps due to a restoration of normal clearance mechanisms. Tissue morphological changes correlated well with the cytological and biochemical alterations.
Aerosols↗
Amino acid pools in cultured muscle cells.
Compartmentalization of cellular amino acid pools occurs in cultures of cardiac and skeletal muscle cells, but the factors involved in this are not clear. We have further defined this problem by analyzing the intracellular free leucine and the transfer-RNA-(tRNA)-bound leucine pool in cultures of skeletal and cardiac muscle incubated with 3H-leucine in the presence and absence of serum and amino acids. Withdrawal of nitrogen substrates caused substantial changes in leucine pool relationships--in particular, a change in the degree to which intracellular free leucine and tRNA-leucine were derived from the culture medium. In separate experiments, the validity of our tRNA measurements was confirmed by measurements of the specific activity of newly synthesized ferritin after iron induction. We discuss the implications of these findings with regard to factors involved in the control of amino acid flux through the cell, as well as with regard to design of experiments using isotopic amino acids to measure rates of amino acid utilization.
Amino Acids↗
The effect of d-amphetamine and ephedrine on smoking attitude and behavior.
Using a double blind, randomized, latin square design, 17 light smokers and 6 heavy smokers were given three times per day doses of placebo, 5 mg amphetamine sulfate, 7.5 mg amphetamine sulfate, 25 mg ephedrine hydrochloride or 50 mg ephedrine hydrochloride. Compared to placebo, active drug produced a statistically significant drop in feeling of addiction to cigarettes (p = 0.022). Ephedrine was reported to be more effective than amphetamine (p = 0.046). Subjects reported similar changes in feeling of enjoyment of smoking. Active drug produced a statistically significant drop in the actual amount of tobacco smoked in heavy smokers (p = 0.028), but not in light smokers. Only two smokers were able to quit completely during the experiment, and one of those people resumed smoking after she stopped taking medication. Possible explanations of these findings are discussed.
Attitude↗
Immunohistochemical identification of cell types in normal and in bleomycin-induced fibrotic rat lung. Cellular origins of interstitial cells.
There is substantial tissue reorganization in the interstitium in pulmonary fibrosis. In order to determine the origin of cells in the interstitium of normal or fibrotic rat lung, we stained lung tissue immunohistochemically with antiserums directed against intermediate filament proteins specific for cells of mesenchymal or muscle origin. Vimentin, specific for mesenchymal cells, was isolated from cultured 3T3 fibroblasts, and desmin, specific for muscle cells, was isolated from chicken gizzard and antiserums prepared in guinea pigs. Paraffin-embedded sections of normal or fibrotic rat lung from rats 28 days after treatment with bleomycin sulfate were reacted with each antiserum and stained by the peroxidase-antiperoxidase technique. Antivimentin antiserum stained discrete interstitial cells of both control and fibrotic lung. Smooth muscle surrounding large airways and vascular smooth muscle was not significantly stained with this antiserum but was heavily stained with antidesmin. However, antidesmin did not stain cells in the interstitium of normal or fibrotic rat lung. These results suggest that most cells in the normal as well as in the fibrotic interstitium, including contractile interstitial cells, are probably of mesenchymal (fibroblastic) rather than of smooth muscle origin.
Actins↗
Actin content of normal and of bleomycin-fibrotic rat lung.
A large proportion of parenchymal lung is composed of cells with an abundance of actin-containing cytoplasmic microfilaments. This may explain the substantial contractile capability of the tissue, which it appears cannot be ascribed totally to vascular or airway smooth muscle. Parenchymal contractility is increased in bleomycin-induced fibrosis, together with an increase in microfilaments and actin- and myosin-directed immunofluorescence. The present biochemical studies indicate that at least 10% of detergent-extractable protein from peripheral lung is actin. Approximately 71% of this actin is polymerized and 29% is monomeric, on the basis of differential ultracentrifugation. Isoelectric focusing and tryptic peptide analysis show that nonmuscle actin types predominate in the parenchyma, of which approximately 78% is beta-nonmuscle actin and 19% is gamma-nonmuscle actin, together with approximately 3% gamma-smooth muscle actin. Total actin as a percentage of extractable protein was not increased significantly in lungs of rats 4 or 8 wk after bleomycin instillation. Thus, actin per total lung is increased only in proportion to increased total lung weight. There is, in addition, no detectable shift in the beta/gamma actin ratio in the fibrotic lung or increase in percentage of smooth muscle actin. There is, however, a significant 16% decrease in monomeric G-actin and a commensurate significant increase in the percentage of polymerized or F-actin. Therefore, increased contractility and actin-specific immunofluorescence characteristic of fibrotic lung does not appear to be due to increases in total actin but rather to increases in its degree of polymerization, as is found in a variety of remodeling tissues. The consequence of these changes in contractile protein organization to lung function requires further investigation.
Actins↗
Control of intra-abdominal hemorrhage. A comparison of methods.
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Animals↗
Effects of insulin in vitro on protein turnover in rat epitrochlearis muscle.
Rates of protein synthesis and degradation were measured in the isolated rat epitrochlearis muscle by radiotracer techniques, by using the specific radioactivity of tRNA-bound amino acid as precursor for protein synthesis. The tissue maintained linear rates of protein synthesis for 3 h of incubation in the presence of amino acids and glucose and in the absence of insulin. Under these conditions, however, the muscles were in negative nitrogen balance, with rates of protein degradation exceeding rates of protein synthesis. Under steady-state conditions of labelling, the specific radioactivities of tRNA-bound leucine, phenylalanine and valine were significantly less than their respective values in the incubation medium, at concentrations in the medium varying from 1 to 10 times those in normal rat serum. Insulin caused a dose- and time-dependent increase in tRNA-based protein synthesis rates, more than doubling rates at 5 and 50 ng of insulin/ml. At the lower, physiological, concentration of insulin, the stimulation of protein synthesis was not observed until the third hour of incubation with the hormone, whereas the rate of protein synthesis at the higher concentration was elevated during the second hour. There were no delays in the stimulation by insulin of glucose conversion into glycogen. The delayed stimulatory effects of insulin on the rate of protein synthesis brought the tissue to a nitrogen balance near zero. The presence of the hormone also prevented the increase in the rate of protein degradation seen in the third hour of incubation in the absence of the hormone. These studies demonstrate the viability of the incubated rat epitrochlearis muscle with respect to protein metabolism and sensitivity to the protein anabolic effects of physiological concentrations of insulin, and indicate that the preparation is a suitable experimental model for the study of the control of protein metabolism in fast-twitch skeletal muscle.
Amino Acids↗
Endocytosis: a review of mechanisms and plasma membrane dynamics.
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Animals↗
Altered rates of collagen synthesis in in vitro aged human lung fibroblasts.
Absolute rates of protein and collagen synthesis based on prolyl-tRNA as the precursor were determined in two age groups of IMR-90 human lung fibroblasts. Compared with midrange fibroblasts [population doubling level (PDL) = 20 to 30] aged fibroblasts (PDL greater than 40] were larger in size in terms of protein and RNA per cell, generally proliferated more slowly, exhibited different steady state [3H] proline transfer RNA (tRNA) precursor pool specific radioactivities, synthesized collagen at a substantially lower rate, and exhibited a reduction in the percent commitment to collagen synthesis. Total protein synthetic rates were reduced slightly in aged versus midrange fibroblasts but the difference was not statistically significant. Proliferative capacity (PDL/wk) correlated better with these changes than cumulative PDL. Cell size (protein/cell) was the variable that had the highest correlation with the reduction in collagen synthesis observed in human lung fibroblasts. Thus, an important differentiated function of human lung fibroblasts, collagen synthesis, is greatly diminished in vitro in large, slowly dividing fibroblasts.
Cell Line↗
Pinocytosis and intracellular degradation of exogenous protein: modulation by amino acids.
Intracellular degradation of exogenous (serum) proteins provides a source of amino acids for cellular protein synthesis. Pinocytosis serves as the mechanism for delivering exogenous protein to the lysosomes, the major site of intracellular degradation of exogenous protein. To determine whether the availability of extracellular free amino acids altered pinocytic function, we incubated monolayers of pulmonary alveolar macrophages with the fluid-phase marker, [14C]sucrose, and we dissected the pinocytic process by kinetic analysis. Additionally, intracellular degradation of endogenous and exogenous protein was monitored by measuring phenylalanine released from the cell monolayers in the presence of cycloheximide. Results revealed that in response to a subphysiological level of essential amino acids or to amino acid deprivation, (a) the rate of fluid-phase pinocytosis increased in such a manner as to preferentially increase both delivery to and size of an intracellular compartment believed to be the lysosomes, (b) the degradation of exogenously supplied albumin increased, and (c) the fraction of phenylalanine derived from degradation of exogenous albumin and reutilized for de novo protein synthesis increased. Thus, modulation of the pinosome-lysosome pathway may represent a homeostatic mechanism sensitive to the availability of extracellular free amino acids.
Amino Acids↗
The myofibroblast in pulmonary fibrosis.
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Acetylcholine↗
Active cellular control of alveolar compliance.
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Animals↗
Contractile proteins of the lung.
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Actins↗
Lavage type III procollagen N-terminal peptides in human pulmonary fibrosis and sarcoidosis.
Levels of type III procollagen N-terminal peptide were immunoassayed in sera and bronchoalveolar lavage fluids from healthy volunteers and patients with idiopathic pulmonary fibrosis or sarcoidosis. Peptide levels normalized to protein were higher than corresponding serum levels in all groups, suggesting that the lung is a producer of this peptide. Levels were significantly elevated in both patient groups, suggesting increased rates of type III collagen synthesis. Values were highest in idiopathic pulmonary fibrosis samples. Correlation of peptide levels with clinical severity of disease and lavage cell profiles was poor, perhaps because the latter reflects aspects of the disease process other than that stage in which type III collagen synthesis is altered. Lavage analyses of procollagen peptides may provide an important index of altered collagen synthesis in interstitial lung disease.
Amino Acid Sequence↗