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Biomedical subjects

J B Smith

Publications and source records attributed to J B Smith.

At least 253 records · Page 14Linked to original sources
PubMed1986

Erythrocyte cation transport activities as a function of cell age.

Erythrocyte cation transport systems were evaluated on cell fractions from 17 subjects. Density centrifugation was used to separate washed red cells into fractions enriched with younger and older cells; the cell age differences in these fractions were verified by reticulocyte counts (means are 3.5% for younger cell fractions and 0.7% for older cell fractions). Red cell age has a pronounced effect on several cation transport activities. The older cell fractions had increases in lithium-potassium cotransport (p less than 0.001), the rate constant for the lithium-potassium cotransport (p less than 0.001) and cellular cation permeability. The older cells had decreases in the number of ouabain binding sites (p less than 0.001), the rate constant for sodium efflux via the sodium-potassium adenosine triphosphatase pumps (p less than 0.001) and the sodium-lithium countertransport (p less than 0.025). In subjects with markedly different cell ages, these effects should be considered when evaluating red cell cation transport activities.

Adolescent↗
PubMed1986

Determination of basal and stimulated levels of inositol triphosphate in [32P]orthophosphate-labeled platelets.

Previous studies indicated that thrombin-stimulation of platelets prelabeled with [3H]inositol or [32P]orthophosphate results in an increase of radioactive inositol triphosphate, a substance thought to modulate the levels of free intracellular calcium. In the present study, we improved the method of resolution of inositol triphosphate from other compounds that are also labeled with [32P]orthophosphate using a combination of enzyme treatment and electrophoresis. We have further demonstrated that the specific activities of metabolic ATP and phosphatidylinositol diphosphate (the precursor of inositol triphosphate) are identical in [32P]orthophosphate-labeled platelets. It follows that the amount of inositol triphosphate is proportional to its radioactivity in the metabolic compartment of the cells. Using this protocol, the concentration of inositol triphosphate in resting and thrombin-stimulated platelets were determined to be 1-4 and 10-30 pmol/10(8) cells, respectively.

Adenosine Triphosphate↗
PubMed1986

Role of platelet-activating factor-acether in mediating guinea pig anaphylaxis.

The pathophysiology of anaphylaxis is very complex, and the sequelae of events are not fully explained in terms of the effects of histamine and peptide leukotrienes alone. Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, PAF-acether) has been detected in animals undergoing anaphylaxis. Injection of synthetic PAF-acether induces similar effects, including bronchoconstriction, respiratory arrest, systemic hypotension, neutropenia, and thrombocytopenia. The results reported here demonstrate that the histamine- and leukotriene-independent component of guinea pig anaphylaxis in vivo and in isolated lung parenchymal strips in vitro is mediated by PAF-acether. However, PAF-acether is not responsible for the anaphylaxis-induced thrombocytopenia.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

Effects of chronically administered d-amphetamine on spaced responding maintained under multiple and single-component schedules.

Key pressing by rats was maintained under spaced-responding and random-ratio schedules of food delivery, and rates of responding were reliably different for each schedule. When responding was maintained under a multiple schedule, appropriate doses of d-amphetamine (1.0 and 1.7 mg/kg) markedly increased low rates of spaced responding while markedly decreasing high rates of ratio responding. These drug-produced changes in response rate resulted in decreased food presentation during both schedule components. When 1.0 mg/kg d-amphetamine was given daily, tolerance developed to initially decreased ratio responding in six to nine sessions, but did not develop to initially increased spaced responding. However, when the ratio schedule was removed, tolerance developed very quickly to increases under the spaced-responding schedule, and associated food frequency returned to control levels. When the ratio schedule was reinstated, spaced responding was once again increased, and its associated frequency of food delivery was again decreased. The development of tolerance to the behavioral effects of d-amphetamine was influenced more by global changes in response consequences during entire experimental sessions than by local changes in response consequences in single components of those sessions. Whenever the concept of "response cost" is used, it should be understood in terms of total "cost".

Animals↗
PubMed1986

Effects of fixed-ratio length on the development of tolerance to decreased responding by l-nantradol.

Key pecking of pigeons was maintained under either a 100-response or a 300-response fixed-ratio schedule of food presentation, and animals received 0.03 mg/kg/day l-nantradol prior to experimental sessions. Tolerance developed for initial rate decreases under fixed ratio 100 in 10-12 sessions, but tolerance did not develop under fixed ratio 300 for up to 30 sessions. When the fixed ratio was changed from 300 back to 100, tolerance developed in three to four sessions, and when the fixed ratio was changed from 100 back to 300, tolerance diminished in two to three sessions. The importance of fixed-ratio parameter for the observation of tolerance extends the generality of the influence of reinforcement processes on tolerance.

Analgesics↗
PubMed1986

Antibodies to phospholipids and nuclear antigens in patients with repeated abortions.

The frequency of positive tests for antibodies to nuclear antigens (antinuclear, deoxyribonucleic acid, Ro, La, Smith, and ribonucleoprotein) or to phospholipids was investigated in 82 patients with isolated repeated abortions. Patients with a positive antibody test (positive or negative deoxyribonucleic acid antibodies) appeared to be a separate subgroup of those with unexplained repeated abortions from those with antibodies to cardiolipin. A total of 13.1% of the 61 patients with unexplained repeated abortions had elevated levels of IgM and/or IgG anticardiolipin antibody, while none were found in patients with explained abortions (p less than 0.1). Enzyme-linked immunosorbent assays for antibodies binding to other phospholipids suggested that sera from patients with repeated abortions who had the lupus anticoagulant contained antibodies that were most often of the IgG class with affinity for negatively charged phospholipids. Binding of IgG but not IgM antibodies to cardiolipin correlated closely with that to other negatively charged phospholipids. The use of clotting tests for the lupus anticoagulant to screen patients with repeated abortions for associated autoantibodies is likely to significantly underestimate the extent of this clinical problem.

Abortion, Habitual↗
PubMed1986

Hospital deaths in a high risk obstetric population: Karawa, Zaire.

Three thousand four hundred thirteen consecutive deliveries at a rural hospital in Zaire are examined. 85% of patients had goiters and 5% were cretins. Twenty maternal deaths occurred, or 5.9 per 1000 deliveries. Risk factors for maternal death included late presentation, advanced age (greater than or equal to 35 years), no education and presence of goiter or cretinism. Ninety percent of women who died were in critical condition at admission, 45% had labored greater than or equal to 48 h and 70% had uterine rupture.

Adolescent↗
PubMed1986

Modulation of receptor mediated leukotriene release in the perfused heart.

The chemotactic peptide n-formyl-methionyl-leucyl-phenylalanine (FMLP) induces peptide leukotriene release at concentrations of 20-25 pmol/ml 3 min after the start of FMLP infusion. FMLP-induced leukotriene release in rabbit hearts is not blocked by the leukotriene receptor antagonist FPL-55712 at concentrations that totally antagonize the hemodynamic effects of exogenously infused peptide leukotrienes. Moreover, propyl gallate, a lipoxygenase inhibitor, does not block FMLP-induced leukotriene release. However, the chemotactic peptide antagonist (Boc-Phe-Leu-Phe-Leu-Phe-OH) totally antagonized FMLP-induced leukotriene release suggesting that the release is via a different mechanism, possibly a receptor mediated event.

Animals↗
PubMed1986

Asymmetric space closure.

In a vertically slotted 0.022 X 0.028 inch edgewise system, the use of a two-dimensional ribbon arch--0.022 X 0.016 inch from lateral incisor to lateral incisor and 0.016 X 0.022 inch from the canine to the molars--plus an uprighting spring on the canine maintained incisor position while unilaterally protracting a molar-premolar unit by means of sliding mechanics. Five degrees of labial crown torque was placed in the incisor portion of the wire and the uprighting spring exerted a force of 200 to 250 g. The intra-arch force applied to protract the molar--premolar unit was 300 to 350 g.

Adolescent↗
PubMed1986

Knee problems in children.

The paper describes physical examination of the knee and some of the knowledge functional anatomy necessary for diagnosis and management of knee disorders that occur in children. It includes brief descriptions of the diagnostic features of these conditions, as well as principles of conservative and surgical management.

Cartilage Diseases↗
PubMed1986

Direct evidence for the existence of a neutrophil-derived platelet activator (neutrophilin).

Human neutrophils and platelets were loaded with the intracellular calcium indicator fura-2. The chemotactic peptide N-formyl-Met-Leu-Phe (fMet-Leu-Phe) induced a rapid elevation of cytosolic free calcium in cytochalasin B-treated neutrophils but failed to increase the cytosolic calcium in platelets. On the other hand, when unloaded neutrophils were incubated together with autologous fura-2-loaded platelets, fMet-Leu-Phe stimulated a 6-fold increase in platelet cytosolic calcium subsequent to a brief lag. Parallel experiments demonstrated that the addition of fMet-Leu-Phe to neutrophil/platelet incubates also elicited platelet aggregation and serotonin release. Platelet activation showed a positive correlation with the concentration of fMet-Leu-Phe added to the mixed cell population. Cell-free supernatants prepared from fMet-Leu-Phe-stimulated neutrophils were capable of inducing platelet calcium mobilization, aggregation, and secretion. The amount of platelet-activating material present in the supernatant was proportional to the number of activated neutrophils. Preincubation of platelets with BN 52021, acetylsalicylic acid, SQ-29,548, or hirudin did not modify the aggregation response induced by the supernatant collected from fMet-Leu-Phe-activated neutrophils, suggesting that the material was not 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (paf-acether), arachidonic acid, thromboxane A2, or thrombin. Pretreatment of the neutrophil supernatant with an ADP (creatine phosphate/creatine phosphokinase) or a superoxide/peroxide (superoxide dismutase/catalase) scavenging system also had no effect on aggregation or secretion, indicating that these substances did not participate in platelet activation. The biological activity present in the neutrophil supernatant was destroyed by heat and inactivated by treatment with phenylmethylsulfonyl fluoride, indicating that it is a protein and most probably an enzyme with serine protease activity. These data provide the direct observation of secondary signal transmission to platelets following primary activation of neutrophils. We propose the name neutrophilin for the neutrophil-derived mediator.

Blood Platelets↗
PubMed1986

Bryostatin, an activator of the calcium phospholipid-dependent protein kinase, blocks phorbol ester-induced differentiation of human promyelocytic leukemia cells HL-60.

Phorbol esters bind to and activate a calcium phospholipid-dependent protein kinase (C kinase). Some researchers believe that activation of C kinase is necessary for the induction of phorbol ester biologic effects. Our research indicates that bryostatin, a macrocyclic lactone that binds to the phorbol ester receptor in human polymorphonuclear leukocytes, also binds to this receptor in the human promyelocytic leukemia cell line, HL-60. Bryostatin activates partially purified C kinase from HL-60 cells in vitro, and when applied to HL-60 cells in vivo, it decreases measurable cytoplasmic C kinase activity. Unlike the phorbol esters, bryostatin is unable to induce a macrophage-like differentiation of HL-60 cells; however, bryostatin, in a dose-dependent fashion, blocks phorbol ester-induced differentiation of HL-60 cells and, if applied within 48 hr of phorbol esters, halts further differentiation. These results suggest that activation of the C kinase by some agents is not sufficient for induction of HL-60 cell differentiation and imply that some of the biologic effects of phorbol esters may occur through a more complex mechanism than previously thought.

Binding, Competitive↗
PubMed1986

Angiotensin-receptor signaling in cultured vascular smooth muscle cells.

Functional receptors for angiotensin II (ANG II) are present in smooth muscle cells cultured from rat aorta. These cells are especially suitable for investigating transmembrane signaling events, since ANG II-receptor function is consistently expressed for many population doublings in culture. Cytoplasmic free Ca, measured with quin 2 or fura-2, transiently increases after receptor stimulation. ANG II releases Ca that is sequestered intracellularly, since the removal of extracellular Ca does not prevent the hormone from increasing intracellular free Ca. Angiotensin provokes both polyphosphoinositide hydrolysis and phosphatidate-phosphoinositide synthesis. Purified inositol trisphosphate (IP3) releases Ca from a nonmitochondrial organelle, presumably the sarcoplasmic reticulum or a specialized region therein. IP3 probably opens an intracellular Ca channel by a ligand-binding reaction rather than a metabolic reaction. The accumulation of IP3 in intact cells in response to ANG II seems fast enough to cause Ca mobilization. ANG II increases a fast and a slow component of 45Ca2+ efflux from the intact cells. The rapid stimulation of Ca2+ efflux from the cell via a Na-Ca antiporter probably accounts at least in part for the short duration of the increase in cytoplasmic free Ca elicited by angiotensin. ANG II has no effect on a fast component of 45Ca2+ influx but does increase a slow component of 45Ca2+ influx; that increase would help to sustain the elevation in free Ca and the refilling of the sarcoplasmic reticulum. Additionally, ANG II-receptor stimulation depolarizes the cell membrane and increases the specific activities of the Na-K pump, the Na-H antiporter, the Na-Ca antiporter, and the Na-K-Cl cotransporter. Ca and/or 1,2-diacylglycerol, the lipophilic activator of protein kinase C, which is concomitantly produced along with IP3, may mediate the effects of ANG II on Na and K transport. Investigations of cultured vascular smooth muscle support the inositol-signaling hypothesis of hormone action.

Amiloride↗
PubMed1986

Inhibition of the platelet activating factor mediated component of guinea pig anaphylaxis by receptor antagonists.

The role of platelet activating factor (PAF) and its inhibition by specific receptor antagonists was studied in hypersensitivity reactions in guinea pig lung parenchymal strips and in guinea pigs in vivo. Immunological challenge of isolated lung parenchymal strips with ovalbumin resulted in a contractile response of 184 +/- 16 mg (n = 38). Pretreatment of the strips with a combination of the antihistamine diphenhydramine, the dual lipoxygenase and cyclooxygenase product synthesis inhibitor BW-755C, and the PAF receptor antagonist kadsurenone totally inhibited the increase in tension. The bronchoconstrictor effects induced by immunological challenge were also totally inhibited when the leukotriene receptor antagonist FPL-55,712 was used to replace BW-755C or another PAF receptor antagonist, alprazolam was used to replace kadsurenone. Ovalbumin challenge in sensitized guinea pigs in vivo resulted in airway constriction, circulatory failure and an abrupt fall in continuously measured platelet count by 75 +/- 12%, followed by death of all animals within 5-8 min. Pretreatment with diphenhydramine, BW-755C and kadsurenone (or alprazolam) improved survival to 64% (i.e., 7 of 11 animals) compared to a survival rate of 0% (i.e., 0 of 8 vehicle treated controls). Despite the improved survival, the severe thrombocytopenia was unaltered with the combined therapy. PAF, histamine and peptide leukotrienes appear to act in concert in mediating the anaphylaxis-induced airway constriction and circulatory failure in guinea pigs, but are not apparently responsible for the accompanying thrombocytopenia.

Alprazolam↗
PubMed1986

Associations of three erythrocyte cation transport systems with plasma lipids in Utah subjects.

To investigate the pathophysiology of essential hypertension, detailed biochemical and clinical variables were collected and analyzed for 2091 Utah subjects aged 3 to 83 years. Three different measurements of erythrocyte cation transport were obtained: Na+-Li+ countertransport, Li+-K+ cotransport, and furosemide-insensitive Li+ efflux into MgCl2. Total plasma cholesterol, triglycerides, and high density lipoprotein cholesterol levels were obtained from fasting subjects. Levels of high density lipoprotein subfractions 2 and 3 were also obtained from 350 subjects. Standardized data collection also included blood pressure, height, weight, and presence or absence of a diagnosis or treatment of essential hypertension. In univariate analyses of all 1420 adults, each of the three transport systems showed the same significant correlations with triglyceride levels (r = 0.33-0.35, p less than 0.0001), high density lipoprotein concentration (r = -0.19 to -0.21, p less than 0.001), and weight (r = 0.22-0.28, p less than 0.0001). In multivariate regression analyses, values for each transport system were significantly higher in hypertensive subjects; values for triglycerides, high density lipoprotein, and usually, the high density lipoprotein subfractions continued to have strong significant independent associations with all three transport systems; and weight remained significantly related only to Na+-Li+ countertransport. In separate logistic regressions, plasma triglyceride levels (positively, p less than 0.001) and high density lipoprotein subfraction 3 levels (inversely, p less than 0.03) were associated with hypertension itself. In multivariate analyses among 671 children, high density lipoprotein and high density lipoprotein subfraction 3 levels showed significant (p less than 0.05) inverse correlations with Na+-Li+ countertransport and furosemide-insensitive Li+ efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Sodium pump parameters of red blood cells in men, women and women taking oral contraceptives.

Three parameters of the sodium pump, the sodium efflux rate, the intracellular sodium content (Nai) and the number of sodium, potassium ATPase sites per red blood cell (sites/rbc) were measured simultaneously on erythrocytes from normal men and women and from women taking oral contraceptives. Significant (p less than 0.002) differences were obtained between normal men and women for sodium efflux (1.68 +/- 0.15 vs 1.52 +/- 0.12 mmoles/L rbc/hr). Among the three measured parameters, there was an inverse relationship (r = -0.74) between Nai and sites/rbc and a linear correlation (r = 0.89) between efflux per site and Nai. A positive correlation (r = 0.78) between the sites/rbc and a first-order rate constant for Na efflux/rbc suggests that one component of the rate constant is the number of sites/rbc. Values for a second-order rate constant, calculated from the assumption that efflux/rbc depends on both Nai and the number of sites/rbc, were similar for normal men and women but significantly (p less than 0.001) higher for women taking oral contraceptives.

Adult↗
PubMed1986

Effect of plasma storage on erythrocyte sodium pump measurements.

The possibility that sodium handling in red cells may be an indicator of abnormalities associated with hypertension has encouraged many investigators to study erythrocyte sodium transport. The results have often been in conflict, perhaps because of the variety of laboratory techniques and procedures employed. Investigation into the effect of storage of red cells in plasma showed larger changes when cells were stored at 0 degrees C than at room temperature (19 degrees). At 0 degrees C, sodium efflux via the pump increased 22.1% (p less than 0.001) after 2 hours storage and 54.2% (p less than 0.005) after 4 hrs of storage. At 19 degrees C, sodium efflux values were more scattered after storage, but the mean value was not significantly different even after 4 hours. Intracellular sodium increased 17.3% in cells stored 4 hrs at 0 degrees C; significant changes were not observed when cells were stored 2 hrs at 0 degrees C or 2-4 hours at 19 degrees C. The number of Na, K-ATPase sites per red blood cell did not change with either storage condition. For samples processed within one hour of drawing, or stored at room temperature, there were close correlations between the sodium efflux per site and the intracellular sodium concentration as well as between the intracellular sodium and the sites per red cell. These relationships were not evident for cells stored at 0 degrees C. These data indicate that red cells to be used in pump measurements should be stored at room temperature and should be processed within 2 hours.

Adult↗