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Biomedical subjects

C M Chesney

Publications and source records attributed to C M Chesney.

34 records · Page 2Linked to original sources
PubMed1982

Muscle calcium and magnesium content in Duchenne muscular dystrophy.

Calcium (Ca) and magnesium (Mg) content were determined in muscle of 27 patients with Duchenne muscular dystrophy, 36 with other neuromuscular diseases, and 22 whose muscle biopsy specimens were histochemically normal. Muscle Ca was significantly elevated in all diseases studied but was about 50% higher in Duchenne dystrophy patients (p less than 0.0001). Mg was decreased by 44% in Duchenne dystrophy, compared with less striking deficits in other diseases (p less than 0.005). In older, nonambulatory Duchenne dystrophy patients, Mg was significantly lower than in younger, ambulatory patients (p less than 0.001); muscle Ca was the same in both groups. On the basis of noncollagen nitrogen concentration, muscle MG depletion could not be attributed solely to reduced muscle mass. These findings strengthen arguments for a role of Ca in the pathogenesis of muscular dystrophy and may implicate Mg depletion as another pathogenetic factor.

Adolescent↗
PubMed1982

Effect of platelet-activating factor (PAF) on human platelets.

The effect of pure synthetic PAF (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) was studied in human platelets. PAF (0.2--2.0 micrograms/ml) produced a dose-dependent aggregation in human platelet-rich plasma (PRP) or platelet suspension obtained by gel-filtration (GFP). In addition, PAF (0.8 microgram/ml) induced secretion of 14C-serotonin (45% +/- 10%; mean +/- SD, n = 9) and platelet factor 4 (PF4) (12.89 +/- 3.81 micrograms/10(9) platelets; n = 9) in PRP. Similar results were obtained in GFP. Aggregation and release of 14C-serotonin and PF4 were inhibited by the metabolic inhibitors 2-deoxyglucose (16.7 mM) and antimycin-A (8.3 micrograms/ml), by the membrane-active drugs mepacrine (10 microM) and chlorpromazine (0.025 mM), by PGI2 (5.34 nM), which elevates intracellular c-AMP, by indomethacin (10 microM) or aspirin (100 microM). The ADP scavengers, creatine phosphate and creatine phosphokinase (CP/CPK), inhibited the second wave of aggregation but not secretion. These data suggest that the major effect of PAF on human platelets is mediated through the cyclo-oxygenase pathway and not through a third pathway.

Animals↗
PubMed1981

Stability of prostaglandin I2 in human blood.

Prostaglandin I2 (PGI2) is hydrolyzed more slowly in human plasma than in buffer at the same pH; this stabilization appears to be due to binding of PGI2 to albumin. The stability of the antiaggregatory potency of PGI2 is similar in human blood and in plasma buffered to pH 7.55. No measurable conversion of [3H]-PGI2 to radioactive or nonradioactive metabolites occurred during incubation with blood.

Alprostadil↗
PubMed1981

Subcellular localization and secretion of factor V from human platelets.

Factor V, a plasma protein cofactor necessary for optimal conversion of prothrombin to thrombin, is also present in considerable concentration in blood platelets (9.9 units per 10(9) platelets). Subcellular fractionation by two methods has localized factor V in the alpha granules of unstimulated platelets. ADP and epinephrine cause release of 4.6% and 6.4%, respectively, of the total factor V, a process completely inhibited by cyclooxygenase alkylation by aspirin. In contrast, collagen causes release of 25% of platelet factor V, a process only partially suppressed by aspirin. Secretion of factor V depends on the availability of metabolic energy, because antimycin A, an inhibitor of aerobic metabolism, and 2-deoxyglucose, an inhibitor of anaerobic glycolysis, together almost totally inhibited the secretion of factor V induced by collagen. The data establish that factor V is not normally available on unstimulated platelets but can be secreted from alpha granules upon stimulation with physiological agents such as ADP, epinephrine, and collagen. Because factor V is known to serve as a receptor for factor Xa, the exposure of factor V on platelets consequent to release would accelerate the process of blood coagulation.

Adenosine Diphosphate↗
PubMed1980

Effect of synthetic estrogen on platelet aggregation and vascular release of PGI2-like material in the rabbit.

Treatment of adult female New Zealand white rabbits with ethinyl estradiol, the synthetic estrogen used in many oral contraceptives, results in a significant increase in in vivo aggregation. This alteration in platelet behavior is accompanied by diminished vascular release of antiaggregatory PGI2 (prostacyclin)-like material. Addition of a progestin prevents the change in platelet aggregation seen with the estrogen alone. Diminished vascular PGI2 release may be an important factor in the pathogenesis of thrombotic occurrences experienced by some oral contraceptive users. In vivo platelet aggregation may be of value in identifying individuals at risk of developing thrombotic disturbances while taking oral contraceptives.

Adenosine Diphosphate↗
PubMed1977

Adenylate cyclase and phosphodiesterase activity in the platelet release abnormality.

11 patients with histories of clinical bleeding were selected as examples of platelet release abnormality. Mean bleeding time was 18 +/- 2.6 min (normal +/- SEM; 6 +/- 0.44); mean platelet adhesiveness was 9.9 +/- 4.3% (normal +/- SEM; 30 +/- 2.2). Clot retraction and platelet factor 3 were normal. Platelet aggregation with adenosine diphosphate (ADP), epinephrine and collagen was decreased, as was 14C-serotonin release. Electron microscopic studies of platelets exposed to epinephrine showed 2 subgroups: one which failed to aggregate or have centralization of organelles and a second which developed pseudopodia and centralization of organelles, but rarely aggregated or degranulated. Measurements of activity of adenylate cyclase and phosphodiesterase under basal conditions were performed on platelets from patients and control subjects. Adenylate cyclase activity was significantly lower and phosphodiesterase activity significantly higher in the patient group. Prostaglandin E1 was a potent stimulator of adenylate cyclase in both groups, as was NaF. It was concluded that the causative defects with "platelt release abnormality" do not reside in either the activity of adenylate cyclase or of phosphodiesterase. Changes in formation and destruction of cyclic adenosinemonophosphate (AMP) may instead be regarded as a compensatory response to a defect in another effector system.

Adenylyl Cyclases↗
PubMed1975

Platelet hypersensitivity and intravascular coagulation in paroxysmal nocturnal hemoglobinuria.

The patient described had paroxysmal nocturnal hemoglobinuria associated with recurrent arterial as well as venous thrombosis. Study of platelet function revealed hypersensitivity to epinephrine, adenosine 5'phosphate (ADP) and collagen as judged by their ability to aggregate platelets as well as to release 14C serotonin. The release of total nucleotides was also markedly increased over normal with all aggregating agents. The abnormality was localized to the platelet since aggregation occurred when the patient's platelets were resuspended in normal plasma but not when normal platelets were incubated in the patient's plasma. Presumptive evidence for ongoing intravascular coagulation was an increase in fibrinogen derivatives of heavier molecular weight than the native protein presumably a result of thrombin action. However, factor XII was not activated and fibrinolysis was not increased. Complement component levels and antithrombin concentrations were also normal. The findings in this case suggest that hypersensitive platelets may contribute to the intravascular coagulation that is manifested by the increased incidence of thrombosis in patients with paroxysmal nocturnal hemoglobinuria.

Adenosine Diphosphate↗
PubMed1974

Human platelet collagenase.

The presence of proteolytic enzymes such as cathepsin and elastase in platelets and the important role of collagen in platelet aggregation suggested that collagenase might be present in platelets. Epinephrine, ADP, and collagen liberate collagenase from platelets in plasma as measured by the hydrolysis of [(14)C]glycine-labeled collagen fibrils. The collagenase activity appeared in an early phase of platelet aggregation and was not a part of the release reaction. However, only 50% of the total collagenase could be liberated by the aggregating agents used. Sucrose density gradient analysis of platelet homogenates using appropriate sub-cellular markers indicated that collagenase appeared in both the granule and membrane fractions. Gel-filtered platelets failed to show collagenase activity before exposure to aggregating agents but released more collagenolytic activity than was found in platelet-rich plasma. This observation was explained by the finding that collagenolytic activity was inhibited by normal human plasma. One of the inhibitors is alpha(1)-antitrypsin as demonstrated by decreased inhibition in plasma from a patient with homozygous alpha(1)-antitrypsin deficiency. Platelet collagenase activity could also be demonstrated by its ability to decrease the viscosity of collagen solutions and to produce collagen fragments similar to those produced by other mammalian collagenases on disk gel electrophoresis. The observation that partially purified platelet collagenase could destroy the platelet-aggregating activity of collagen suggests that the enzyme might function in a negative feedback mechanism limiting thrombus formation.

Acid Phosphatase↗
PubMed1972

Critical role of the carbohydrate side chains of collagen in platelet aggregation.

The reaction between human platelet membrane glucosyl transferase and collagen has recently been proposed as the mechanism for pletelet-collagen adhesion. Collagen contains glucosyl-galactose and galactose side chains linked through the galactose to hydroxylysine. Oxidation of the 6-hydroxymethyl position of the galactosyl residue to aldehydes with galactose oxidase completely abolishes platelet aggregation. This enzymatic modification of collagen can be fully reversed by reduction of the aldehydes formed by NaBH(4) with complete restoration of platelet aggregating ability. Limited digestion with bacterial collagenase abolishes the ability of collagen to aggregate platelets. Removal of the N-terminal telopeptides from collagen with trypsin does not affect platelet aggregation. Tertiary structure of soluble collagen is essential for platelet aggregation. Normal collagen is less effective than lathyritic collagen, which contains only a small number of cross-links. The decreased number of aldehyde groups in the lathyritic collagen are not responsible for the increase in aggregating ability, since reduction with NaBH(4) does not alter platelet aggregation. These results suggest that integrity and accessibility of the galactose receptor site may be crucial for the formation of a ternary collagenenzyme-platelet membrane complex which must precede platelet aggregation.

Alcohol Oxidoreductases↗