Biomedical subjects
Publications and source records attributed to C M Smith.
Eight patients with chronic obstructive bronchitis and moderate disability entered a pilot study of the effects of controlled diaphragmatic breathing. They received three weeks of placebo physiotherapy (shoulder exercises) followed by three weeks of instruction on controlled diaphragmatic breathing. No beneficial effects were observed on exercise performance or the perceived strain of exercise.
The characteristics of irreversibly sickled cells (ISC) are reviewed in relationship to their potential significance in the initiation of sickle cell vaso-occlusion. Although ISC are implicated in the shortened red cell survival of sickle cell anemia, there is no direct correlation to the frequency or severity of sickle crisis. ISC are heterogeneous in their physical properties suggesting the possibility that a subpopulation may be disproportionately important in causing vaso-occlusion. Study of their deformability heterogeneity of ISC showed that filtration-separated hard ISC are similar in morphology and intracellular composition to soft ISC, and would not be distinguished on blood smear.
The phospholipase A2 from Crotalus adamanteus venom has been shown to be active as the dimer or 30 000 molecular weight species, at concentrations used for enzyme assay (0.1--10 microgram/ml). Gel filtration of the enzyme in the presence of Ca2+ and monomeric concentrations of the substrate dihexanoylphosphatidylcholine showed that all the protein migrated as a 30 000 molecular weight species. Active enzyme sedimentation velocity experiments using the same conditions gave s020,W=2.85 +/- 0.05 S, which compares favorably with the value obtained at mg/ml concentrations (3.11 S). These results confirm the results of Shen et al. (Shen, B.W., Tsao, F.H.C, Law, J.H. and Kézdy, F.J. (1975) J. Am. Chem. Soc. 97, 1205--1208).
Specific antibody responses to influenza virus were obtained in vitro from human blood mononuclear cells (PBM). The response was T cell-dependent, as shown by separation of PBM into E rosette-positive (E+) and -negative (E-) populations. The histocompatibility requirements for T-B cells interactions in this response were analyzed by recombining E- and E+ fractions from donors with varying degrees of HLA compatibility. No antibody formation was obtained from any allogeneic combination except for the special case of HLA identical siblings. As these experiments included combinations with shared or identical HLA-DR specificities, it was unlikely that genetic restriction alone could account for the failure of T-B cell collaboration. Evidence that suppression was responsible for the lack of antibody formation was obtained from experiments in which allogeneic E+ cells profoundly depressed specific antibody responses of intact PBM. In contrast, no such suppression was seen in pokeweed mitogen-driven polyclonal Ig synthesis for which there are no major histocompatibility complex requirements for T cell help. The suppressor activity of allogeneic E+ cells was found to be radiation-sensitive. By irradiating E+ cells, it was, therefore, possible to test for T cell help across an HLA barrier without unwanted suppressor effects. Under these conditions, (irradiated) E+ cells were able to collaborate with allogeneic E- cells even with no HLA alleles in common. This was true even when autologous monocytes were depleted from the helper E+ population. Supernatants collected from antigen-driven cultures of allogeneic E- and E+ cells were able to replace helper T cells in the specific antibody response to influenza virus. The apparent lack of genetic restriction in these responses might, therefore, be explained by the production of a nonrestricted helper factor.
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Human lymphocytes obtained from peripheral blood or spleen were cultured with influenza virus in a microculture system to produce strain specific antibody which was detected by the enzyme linked immunosorbent assay (ELISA). Nanogram amounts of specific antibody could be detected in cultures of 4 x 10(5) cells.
A characteristic withdrawal syndrome appears following the interruption of chronic heavy consumption of alcoholic beverages. The pathophysiological elaborations of the various withdrawal signs and symptoms are considered. Among the unlikely, although plausible, pathophysiologic mechanisms of the tremulousness and skeletal muscle hyperreactivity of withdrawal is the accumulation or the sustained production of one or more circulating "toxic substances." Evidence consistent with such a mechanism includes the reported alleviation by dialysis of an impending withdrawal syndrome in alcoholic patients, the appearance of reflex hyperreactivity in withdrawing animals below the level of a chronic section of the spinal cord, and the time course of the appearance and disappearance of withdrawal syndromes. The various potential pathophysiological and neurochemical manifestations of the withdrawal illness are discussed--alterations in neural inhibition, in alpha-aminobutyric acid, catecholamines, acetylcholine, dopamine, prostaglandin, and in peptides. Experimental tests whereby a "toxic substance hypothesis" of withdrawal can be ruled in or out are proposed.
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The adrenocorticotropin fragment ACTH/MSH 4--10 (0.1 ug/kg IP) effectively modulates the neuromuscular responses of 9 to 15 day old rats. Muscle (extensor digitorum longus) contraction amplitude is increased, fatigue is delayed and muscle half-relaxation time is shortened during 20 min of continuous in situ stimulation of a branch of the deep peroneal nerve (square wave shocks 10 Hz, duration 0.5 msec, strength supermaximal). No effect on contraction time is seen. There is no facilitation or change in any contraction parameter in rats older than two weeks (16 to 40 days) indicating that these older animals, like normal adult rats, are unaffected by the peptide. Immature rats, however, are even more sensitive than hypophysectomized adult rats [29] to the ameliorative action of ACTH/MSH 4-10. This early sensitivity to ACTH/MSH 4--10 corresponds to important developmental changes occurring in nerve and muscle during the most critical period in postnatal development, the first two weeks.
A study of the effect of ingestion of lead on the metabolism and function of vitamin D was carried out in rats fed diets varying in calcium and phosphorus content. The ingestion of 0.82% lead as lead acetate suppressed plasma levels of 1,25-dihydroxycholecalciferol in rats fed either a low phosphorus or a low calcium diet while it had no effect on this parameter in rats fet either a high calcium diet or a normal phosphorus diet. Most important, the ingestion of lead totally blocked the intestinal calcium transport response to cholecalciferol, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. On the other hand, the ingestion of lead acetate had no influence on the mobilization of calcium from bone, the elevation of serum inorganic phosphorus and in the mineralization of rachitic bone in the same animals. Thus by the feeding of 0.82% lead on the intestinal responses to vitamin D and its metabolites was greatest in animals fed a low calcium or a low phosphorus diet, it was present with all diets tested.
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We have studied two patients, one with red cell aplasia and the other with neutropenia. Both showed lymphocytosis. In both cases, 90-100% of E rosetting cells were T cells as defined by the monoclonal antibodies UCHT1 and OKT3. The majority of these cells also carried the OKT8 suppressor/cytotoxic marker and were HLA-DR- and Fc gamma R-positive. In spite of the similarity of this phenotype to that reported for suppressor cells, these cells failed to suppress pokeweed mitogen-induced polyclonal Ig synthesis. Cells from both patients also failed to respond significantly to Con A and PHA. They were, however, unable to suppress the Con A responses of normal donors although cells from one patient were able to suppress completely a normal PHA response. These results demonstrate the existence of a genuine subset of T cells with Fc gamma receptors but suggest that not all such cells have typical suppressor function.
The relationship of altered deformability of irreversibly sickled cells (ISC) to their morphological and physiologic characteristics was evaluated in this study. ISC obtained by differential centrifugation and density gradient sedimentation were separated and enriched into hard and soft populations on the basis of their ability to pass through Nuclepore filters with an average pore size of 3.0 mu. Measurement of deformability by micropipette and Nuclepore elastimetry documented marked differences of erythrocyte rigidity in the two populations. Yet ISC morphology, intracellular viscosity determinants (mean cell hemoglobin concentration, density profile gradient, hemoglobin composition), and surface area geometry (mean cell volume, osmotic fragility) were similar in populations of hard and soft ISC. The similarity in intracellular viscosity and surface area geometry suggests that an intrinsic membrane alteration is responsible for the difference in deformability of filtration separated populations of ISC. Hard ISC may be more important to the pathophysiology of sickle cell disease than soft ISC, though ISC counts on peripheral blood smears would not be of help in distinguishing the two populations.
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We studied the effects of glucagon, dibutyryl cyclic AMP and dexamethasone on the rate of [(14)C]pantothenate conversion to CoA in adult rat liver parenchymal cells in primary culture. The presence of 30nm-glucagon increased the rate by about 1.5-fold relative to control cultures (range 1.4-2.3) and 2.4-fold relative to cultures containing 1-3m-i.u. of insulin/ml. The half-maximal effect was obtained at 3nm-glucagon. Dibutyryl cyclic AMP plus theophylline also enhanced the rate by about 1.5-fold. Dexamethasone acted synergistically with glucagon; glucagon at 0.3nm had no effect when added alone, but resulted in a 1.7-fold enhancement when added in the presence of dexamethasone (maximum effect at 50nm). The 1.4-fold enhancement caused by the addition of saturating glucagon concentrations was increased to a 3-fold overall enhancement by the addition of dexamethasone. However, dexamethasone added alone over the range 5nm to 5mum had no effect on the rate of [(14)C]pantothenate conversion to CoA. The stimulatory effect of dibutyryl cyclic AMP plus theophylline was also enhanced by the addition of dexamethasone. Changes in intracellular pantothenate concentration or radioactivity could not account for the stimulatory effects of glucagon, dibutyryl cyclic AMP or dexamethasone. Addition of 18mum-cycloheximide, an inhibitor of protein synthesis, decreased the rate of incorporation of [(14)C]pantothenate into CoA and the enhancement of this rate by glucagon and dibutyryl cyclic AMP plus theophylline in a reversible manner. These results demonstrate an influence of glucagon, dibutyryl cyclic AMP and glucocorticoids on the intracellular mechanism regulating total CoA concentrations in the liver.
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Explore the source record for details and available documents.