Adhesion molecules expressed on platelets play important roles for in the interaction between platelets and vascular endothelial cells. However, little is known whether megakaryocytes bear the same ...adhesion molecules as those expressed on platelets. In this study, we have examined the expression of adhesion molecules, integrin family, immunoglobulin superfamily, selectin family and CD44 family on the purified megakaryocytes, in comparison with those on platelets. Megakaryocytes were purified by Percoll density centrifugation followed by albumin gravity sedimentation. Megakaryocytes doubly stained by anti-GP IIb/IIIa (Plt-1) and anti-adhesion molecule antibodies were analyzed by flowcytometer. All the adhesion molecules expressed on platelets were also expressed on megakaryocytes. In addition, among tested adhesion molecules, endothelial-leukocyte adhesion molecule-1 (ELAM-1) was detected on megakaryocytes whereas not on platelets. This study may help for understanding the expression of adhesion molecules during megakaryocytic maturation.
The pathogenesis of thrombocytopenia in patients with thrombocytopenia with absent radii (TAR) syndrome has not been clarified yet.
This is the first report of a Japanese patient with TAR syndrome. ...We studied his megakaryopoiesis in vitro and serum levels of thrombopoietin (TPO).
Serum levels of TPO in the patient with TAR syndrome were comparable with those of an age-matched control. The bone marrow cells from the patient with TAR syndrome actually generated megakaryocyte colonies in the presence of TPO and the numbers were significantly greater than those from the age-matched control marrow. However, megakaryocyte colonies from the marrow cells with TAR syndrome contained a much lower number of cells per colony and the size of the individual megakaryocytes appeared to be smaller.
These data suggest that megakaryocyte progenitors from patients with TAR syndrome may have decreased proliferative and differentiative capacity to respond to TPO, leading to thrombocytopenia.
This study was designed to examine the effect of hydroxyl radical (HO^・ ) on transmission at the sympathetic neurovascular junction. HO^・ was produced from Fentons reagent (H_2 O_2 plus FeSO_4 ). The ...canine superior mesenteric veins were removed surgically and cut into helical strips. Both basal norepinephrine (NE) release and release of NE induced by electrical stimulation (ES) were determined by superfusion technique. The vessels were superfused for a total of 190 min. ES was applied for three 10-min periods between 100 and 110 min (ES_1 ), between 140 and 150 min (ES_2 ), and between 170 and 180 min (ES_3 ). After ES_1 , superfusate solution containing Fentons reagent was applied for 30 min. The early exposure to HO^・ produced significant decrease in tension development caused by ES_2 , the contraction evoked by ES_3 decreased further. NE release in basal condition was significantly increased by exposure to HO^・ ,but NE release in response to ES was not. The observed increase in NE release was not dependent on Ca^2+ ion, ES-induced contractions in Ca^2+ -free solution were not affected by HO^・ exposure. These results suggest that HO^・ acts without inhibiting NE release mechanism at a postjunctional site where it inhibit NE-induced vascular contraction process. The existence of Ca^2+ independent NE release mechanism, which is senstive to HO^・ , also may be indicated by superfusion experiment in Ca^2+ -free solution.
This study was designed to examine the effect of hydroxyl radicals (HO^・ ) on peripheral transmission at the sympathetic neurovascular junction. For this study, HO^・ radicals were produced from ...Fentons reagent (H_2 O_2 plus FeSO_4 ). The canine superior mesenteric veins were removed surgically and were cleaned of adherent connective tissue and cut into helical strips. Both basal norepinephrine (NE) release and release of NE induced by electrical stimulation (ES) were determined by superfusion technique： the helical strips were suspended in jacketed (37 ℃) superfusion chambers, and superfused continuously with aerated(95% O_2 , 5% CO_2 ) Krebs.Ringer solution (pH 7.4) by a constant-flow pump. Two platinum wires were placed parallel to the helical strips for stimulating (9 V. 2 msec, 5 Hz) the adrenergic nerve terminals in the blood vessel wall. Sampling of superfusate started after a 90-min equilibration period. The vessels were superfused for a total of 190 min (including 90-min of equilibration). ES was applied for three 10-min periods between 100 and 110 min (ES_1 ), 140 and 150 min (ES_2 ), and between 170 and 180 min (ES_3 ). The superfusate samples were collected every 10 min among before, during and after each stimulation period. NE was determined by high-performance liquid chromatography with electrochemical detector; isometric tension changes evoked by ES were also recorded simultaneously. The generation of HO^・ radicals in the superfusate was monitored by ESR spectroscopy with DMPO as the spin trap throughout the experimental time course. After ES_1 , superfusate solution containing Fentons reagent was applied for 30 min. The exposure to HO^・ radicals produced significant decrease in tension development caused by ES_2 (when compared to the tension development elicited by ES_1 ); the contraction evoked by ES_3 decreased further. NE release induced by ES was not affected by exposure to HO^・ radicals; however, basal NE release was significantly increased after exposure to HO^・ radicals. The observed effect of HO^・ exposure on basal NE release was abolished in Ca^2+ free superfusion study. These results suggest that exposure to HO^・ radicals act at a postsynaptic sites where it inhibit the smooth muscle contraction process without affecting NE release mechanism. It is also postulated that the increase in basal NE release produced by HO^・ exposure may be due to increased influx of Ca^2+ into presynaptic nerve cells.
There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease.
In a multicenter, open-label trial ...conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority.
The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval CI, 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority).
As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).
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