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Biomedical subjects

M B Ward

Publications and source records attributed to M B Ward.

8 recordsLinked to original sources
PubMed1987

Effect of human tumor cells on platelet aggregation: potential relevance to pattern of metastasis.

Tumor metastasis may be facilitated by interaction of tumor cells with platelets. It is not known, however, whether solid tumors which have predisposition to pulmonary metastasis affect platelets differently than lymphoid tumors, which rarely spread to lungs. We therefore examined the effects of cultured osteogenic sarcoma (MG-63, U2-OS), as well as leukemia (NALM-16, LAZ-221, K-562) and lymphoma (RAJI, MOlt 4) cells, on human platelet aggregation. Human osteogenic sarcoma (MG-63) cells alone induced platelet aggregation, whereas U2-OS cells induced platelet aggregation only after preincubation of platelets with subthreshold concentrations of epinephrine. In contrast, neither leukemia nor lymphoma cells affected platelet aggregation. These observations suggest that the platelet proaggregatory potential of tumor cells is variable and that the platelet stimulatory effects of osteogenic sarcoma cells may relate to their high risk of pulmonary metastasis.

Adenosine Diphosphate↗
PubMed1987

Spontaneous platelet aggregation: observations on potential mechanisms.

We identified SPA in three young apparently healthy women. SPA was associated with release of TXA2 and was only partially inhibited by ADP-inhibitor apyrase and alpha 2-adrenoceptor blocker yohimbine. In vitro incubation of aspirin (90 micrograms/ml) or selective TXA2 synthetase inhibitor OKY-046 (0.1 uM) with platelet rich plasma (PRP) did not abolish SPA, although platelet generation of TXA2 was markedly inhibited. In contrast, oral administration of large amounts of aspirin in one subject or in vitro incubation of PRP with TXA2 -endoperoxide receptor blocker SQ 29,548 (20-100 nM) significantly inhibited SPA. These studies suggest that SPA is associated with TXA2 release. Since TXA2 -endoperoxide receptor blocker completely abolishes the secondary wave, agents like this may be of therapeutic value in individuals with SPA and evidence of tissue ischemia.

Adult↗
PubMed1987

Reduction in myocardial neutrophil accumulation and infarct size following administration of thromboxane inhibitor U-63,557A.

We examined the effects of a new selective thromboxane A2 (TXA2) synthetase inhibitor, U-63,557A, on myocardial infarct size 48 hours following left coronary ligation in rats. With a single 8 mg/kg dose of U-63,557A (furegrelate) administered prior to coronary ligation, platelet aggregation and serum TXA2 formation declined significantly (p less than 0.02) for up to 48 hours. Myocardial infarct size, as measured by planimetry of serial left ventricular sections, was decreased from 44 +/- 3% (saline-treated control rats) to 34 +/- 4% (p less than 0.05). Left ventricular creatine kinase (CK) following coronary ligation was also preserved in U-63,557A vs saline-treated control animals (p less than 0.05). These beneficial effects of U-63,557A were not accompanied by reduction in the indices of myocardial oxygen demand (heart rate and arterial pressure). Furthermore, neutrophil accumulation in the infarcted myocardium was significantly decreased by U-63,557A (26 +/- 6 vs 96 +/- 3/high-power field [p less than 0.01]). These data suggest that administration of a single dose of selective TXA2 synthetase inhibitor prior to coronary ligation modulates platelet function for up to 48 hours and reduces the extent of myocardial injury, which may, in part, relate to decrease in neutrophil accumulation.

Animals↗
PubMed1987

Inhibition of human platelet and neutrophil function by piriprost (U-60,257).

Platelets and neutrophils are important in determining the extent of myocardial injury following coronary occlusion. The detrimental effects of these blood elements are mediated in part via release of arachidonate metabolites and oxidative species. A new selective inhibitor of leukotriene formation, piriprost (U-60,257), has been observed to decrease both neutrophil accumulation in the myocardium and infarct size following coronary ligation in experimental animals. Since piriprost may have clinical use, we examined its effects on human platelet and neutrophil functions. This compound was found to exert potent inhibitory effects on epinephrine-induced human platelet aggregation and TXA2 biosynthesis (IC50 0.04 microM). Piriprost also inhibited human neutrophil chemotaxis, oxidative species release, aggregation, and LTB4 synthesis with IC50 of 0.1, 0.04, 10 and 14 microM, respectively. Thus, piriprost inhibits a variety of human platelet and neutrophil functions. Because of its suppressive effects on human platelet and neutrophil functions and protective effects in experimental myocardial infarction, this agent may have clinical applications.

Blood Platelets↗
PubMed1986

Effects of thromboxane A2 inhibition on osteogenic sarcoma cell-induced platelet aggregation.

There is evidence that tumors may stimulate platelet aggregation, causing release of thromboxane A2. Thromboxane A2 may potentiate tumor metastasis by stimulating tumor cell growth and proliferation and by enhancing platelet-tumor cell aggregate formation. Despite potential significance of thromboxane A2 in tumor metastasis, agents which inhibit thromboxane A2 synthesis have not been uniformly effective in reducing tumor metastasis. We, therefore, evaluated the effects of a thromboxane A2 receptor antagonist SQ-29,548 compared to those of a thromboxane A2 synthetase inhibitor OKY-046 on osteogenic sarcoma-induced platelet aggregation and thromboxane A2 release. Osteogenic sarcoma cells added to platelet-rich plasma caused complete and irreversible platelet aggregation as well as thromboxane A2 release. Preincubation of platelet-rich plasma with SQ-29,548 (2 to 20 nM) decreased platelet aggregation induced by tumor cells, but it had no effect on thromboxane A2 release. In contrast, preincubation of platelet-rich plasma with OKY-046 (0.1 to 10 microM) had no effect on platelet aggregation despite a decrease in thromboxane A2 synthesis. These results suggest that thromboxane A2 receptor blockers, rather than synthetase inhibitors, may prevent tumor cell-induced platelet aggregation.

Blood Platelets↗