PubMed Health⌕ Search

Biomedical subjects

P Cech

Publications and source records attributed to P Cech.

10 recordsLinked to original sources
PubMed1987

High- and low-affinity receptors regulate platelet responses to phorbol diesters and teleocidin.

We examined binding of 3H-phorbol dibutyrate (3H-PDBu) to gel filtered human platelets (GFP) and discovered that GFP possess two classes of receptors for phorbol diesters (PDE). High-affinity (HA) receptors, approximately 5000/GFP, bound 3H-PDBu with an apparent dissociation constant (KD) of approximately 12 nM. Low-affinity receptors were approximately 5 times more numerous (2.4 X 10(4)/GFP) and had a 10-fold lower affinity for 3H-PDBu (apparent KD = 115 nM). The potencies of phorbol myristate acetate (PMA) and PDBu paralleled their binding affinities to the PDE receptors. Teleocidin (Tel), although structurally distinct from PDE, competed with 3H-PDBu for its HA-receptors (KI Tel = 1.9 nM). Binding of PDE to HA- or LA- receptors was rapid, reversible, saturable and stereospecific. The HA- and LA-receptors modulated different platelet responses. HA-receptors regulated the secretion of beta-thromboglobulin from alpha-granules and the release of N-acetyl-beta-D-hexosaminidases from lysosomes. LA-receptors mediated both platelet aggregation and the release of serotonin from dense granules. This is the first demonstration of two physiologically active classes of PDE/Tel receptors in human platelets, and demonstrates that particular platelet responses may be directed by distinct classes of receptors for specific agonists.

Binding, Competitive↗
PubMed1986

Effects of phorbol diesters and teleocidin on normal human platelets.

Teleocidins are newly described indole alkaloid tumor promoters that are structurally distinct from phorbol diesters (PDE). We compared the effects of teleocidin and selected PDE on platelet aggregation, secretion and aspects of arachidonate metabolism. Three tumor-promoting PDE (phorbol myristate acetate (PMA), phorbol dibutyrate (PDBu) and 4-beta-phorbol didecanoate (4-beta-PDD] and a non-tumor promoting PDE (4-alpha-phorbol didecanoate (4-alpha-PDD] were used. Teleocidin and tumor promoting PDE caused platelet aggregation after a delay that was inversely related to tumor promoter concentration and also triggered secretion of alpha- and dense granules and selective release of lysosomal enzymes. Aggregation and its associated 125I-fibrinogen binding to platelets were both inhibited by Na2EDTA. 4-alpha-PDD was ineffective. Analysis of platelet aggregation responses and activation kinetics revealed that PDBu was 11.7 times less potent than teleocidin PMA, or 4-beta-PDD. Neither PDE nor teleocidin stimulated 14C-arachidonate release from normal human platelets, and both aggregated aspirin-treated platelets. These results show that representatives of two structurally distinct classes of tumor promoters, phorbol diesters and indole alkaloids, are potent activators of platelet aggregation, fibrinogen binding, and granule/lysosomal secretion, by a mechanism that bypasses arachidonate release and formation of cyclooxygenase-dependent arachidonate metabolites.

Arachidonic Acids↗
PubMed1979

[Effect of the sun on circulating 25-hydroxycalciferol levels in normal subjects in Switzerland].

The principal source of human natural vitamin D is cholecalciferol produced in skin by the action of ultraviolet light. Plasma levels of 25-hydroxyvitamin D (25-OH-D), the hepatic metabolite of cholecalciferol, increased by 39.3% in 20 healthy young Swiss subjects after a 3-week holiday in the sun. Significant increases of circulating 25-OH-D (p smaller than 0.001) were found as much as 2 months later when compared with a group not deliberately exposed to sunshine. A short vacation in the sun therefore appears to be beneficial in replenishing vitamin D body stores.

Adult↗
PubMed1979

Hereditary myeloperoxidase deficiency.

The functional properties of granulocytes in a diabetic patient deficient in myeloperoxidase (MPO) were compared with those of granulocytes in healthy subjects. The granulocytes of this patient had normal phagocytic activity. The microbicidal activity of the granulocytes was partially diminished with regard to Staphylococcus aureus and was almost nil with regard to Candida albicans. Fungicidal activity of normal granulocytes was shown to be impaired during the in vitro artificial hyperglycemic condition. The relationship among diabetes mellitus, MPO deficiency, and serious C. albicans infection was examined. Genetic investigation was carried out in 28 members of the proband's family. In close relatives of the patient, MPO values were found to be diminshed to a greater or lesser degree, thus suggesting variable expressivity of the heterozygote state of MPO deficiency.

Adult↗
PubMed1977

[Hereditary myeloperoxidase deficiency. Clinical, biological and genetic study].

A case is reported of hereditary myeloperoxidase deficiency in a diabetic patient suffering from a Candida albicans hepatic abscess. Myeloperoxidase (MPO) is completely absent from the neutrophils and monocytes, although it is present in the eosinophils. Functional granulocyte studies have revealed normalchemotactic and phagocytic activity, although the bacterial activity is partially diminished with regard to Staphylococcus aureus and is almost nil with regard to Candida albicans. The granulocytic metabolism, when stimulated by zymosan, is characterized by greatly increased oxygen consumption. Genetic investigations have been conducted in 28 members of the patient's family. Cyto- and biochemical determination of MPO is clearly diminished in close relatives of the patient. Genetic analysis indicates recessive autosomal transmission with variable expressivity of the gene for the heterozygote state.

Adult↗
PubMed1977

[Potassium chloride and non-specific ulcers in the small intestine].

Gut toxicity due to potassium chloride preparations is well known, but there is little information concerning side effects of the newer slow release preparations. Small bowel ulceration due to the new slow release formulation is described. As far as the authors are aware this is the first such case published in Switzerland.

Administration, Oral↗