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Biomedical subjects

J F Mustard

Publications and source records attributed to J F Mustard.

At least 163 records · Page 9Linked to original sources
PubMed1977

Inhibition of platelet adhesion to rabbit aorta by sulphinpyrazone and acetylsalicylic acid.

A technique for the isolation of rabbit thoracic aorta in a form in which it can withstand normal pressure and a new in vitro system in which it was tested is described. Segments of aorta were selectively damaged with a balloon catheter by the Baumgartneer technique and supensions of washed platelets, labelled with 51Cr, were perfused through them. More platelets adhered to the damaged surface than to the undamaged surface. Suophinpyrazone was more effective than aspirin in inhibiting platelet adherence to both the damaged and undamaged surface.

Animals↗
PubMed1977

Effects of cephalothin and penicillin G on platelet function in vitro.

High concentrations of cephalothin or penicillin G inhibit a number of the functions of human or rabbit platelets in citrated platelet-rich plasma (PRP) and in suspensions of washed platelets. The reactions shown to be inhibited are: ADP-induced shape change and the primary and secondary phases of aggregation and release induced by ADP or adrenaline in human cirtated PRP; release and aggregation of washed human platelets exposed to collagen, thrombin, vasopressin, or the ionophore A 23,187; aggregation of washed human platelets exposed to phytohaemagglutinin from Phaseolus vulgaris (PHA) or polylysine; release induced by concanavalin A or PHA in suspensions of washed platelets from rabbits; platelet adherence to a collagen-coated surface or to the damaged intimal surface of the rabbit aorta; platelet factor 3 availability; lysis of rabbit platelets by an antiserum directed against them; and clot retraction. Neither antibiotic affected serotonin-induced aggregation; a high concentration of cephalothin slightly inhibited the initial rate of serotonin uptake. Penicilloic acid showed about half the inhibitory effect of penicillin G on ADP-induced aggregation. In citrated human platelet-rich plasma, ampicillin and oxacillin inhibited ADP-induced aggregation to the same extent as similar concentrations of penicillin G; in suspensions of washed platelets, however, ampicillin was less inhibitory than penicillin G or oxacillin. Platelet ultrastructure, assessed by transmission electron microscopy, was not visibly altered. Evidence that the antibiotics become bound to platelets is the finding that platelets incubated with the antibiotics ans resuspended in fresh media showed less response to aggregating agents compared with control platelets. Penicillin G and related antibiotics may be inhibitory because they coat the platelet surface. Their effects on platelet functions are probably responsible for excessive bleeding and increased bleeding times observed in patients and volunteers receiving high doses of these antibiotics.

Antibodies↗
PubMed1977

Incorporation of 32PO4 into phospholipids of blood platelets.

Human or rabbit platelets in an artificial medium without phosphate were incubated with carrier-free [32P] orthophosphate for I h, washed and resuspended in Tyrode-albumin solution containing unlabelled phosphate. Aliquots of platelet suspension were subjected to lipid extraction at various times and the extracted phospholipids were separated by thin layer chromatography. The specific radioactivities of triphosphoinositide (TPI) and diphosphoinositide (DPI) were highest during the labelling period and then declined rapidly after the platelets were resuspended in the medium containing unlabelled phosphate. The percentage of total phospholipid 32P in TPI and DPI decreased from over 95% at 1 h to less than 50% at 12 h with either rabbit or human platelets. The specific radioactivity of monophosphoinositide (MPI) reached its greatest value 6-8 h after labelling. In the in vitro incubation studies, phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE) were negligibly labelled in the initial hours but at 12 h (rabbit or human platelets) PC contained more than 30% of the radioactivity. PE and PS contained less than 10% of the total phospholipid-bound radioactivity at the end of the incubation period. The pattern of incorporation of [32P]orthophosphate into the inositol phospholipids, PC, PS and PE that had been found in the in vitro studies was confirmed by an in vivo study in which rabbit platelets labelled with 32P in vitro were infused into rabbits and harvested after 35 h. These findings indicate that the phosphates of all the phospholipids studied in these experiments turn over in vitro and in vivo but the phosphates of the inositol phospholipids turn over most rapidly.

Animals↗
PubMed1977

Labeling of the releasable adenine nucleotides of washed human platelets.

In rabbit platelets, the metabolically active ATP pool equilibrates with the releasable ATP pool within 1 day. The studies showing this have now been extended to human platelets. Human platelets labeled with 14C-adenosine or 14C-adenine were incubated for up to 10 hr in vitro at 37 degrees C. After 10 hr, about 12% of the total platelet 14C-ATP and 14C-ADP had become releasable with thrombin (4.2 units/ml). Lysis of platelets did not occur, since less than 1% of the platelet-bound 51Cr from platelets labeled with this radioisotope appeared in the ambient fluid upon thrombin treatment. The 14C-ATP/14C-ADP ratio of the released adenine nucleotides (7.6) was similar to the 14C-ATP/14C-ADP ratio of the nonreleasable adenine nucleotides (7.1) 2 hr after the labeling with 14C-adenosine. However, upon prolonged incubation (10 hr) in vitro, the 14C-ATP/14C-ADP ratio of the releasable adenine nucleotides decreased to 2.7. The adenylate energy charge and the 14C-ATP/14C-ADP ratio of the metabolic adenine nucleotide pool did not change significantly during the time of observation. The 14C-ATP content of the platelets decreased by less than 1% hr of incubation at 37 degrees C. These observations are interpreted to mean that the 14C is transferred from the metabolically active, nonreleasable adenine nucleotide pool of human platelets into the releasable adenine nucleotide pool as ATP and is partially hydrolyzed there to yield ADP. The transfer of ATP across the storage organelle membrane of platelets may be similar to transport processes in the chromaffin cells of the adrenal medulla and may represent a general phenomenon in cells that possess storage organelles containing adenine nucleotides.

Adenosine Diphosphate↗
PubMed1977

Inhibition and potentiation of platelet function by lysolecithin.

The effects of lysolecithin (LPC) on aggregation, serotonin release, shape, and lysis of rabbit, pig, or human platelets in platelet-rich plasma (PRP) or Tyrode albumin solution were examined during prolonged incubation. LPC added to citrated or heparinized PRP from humans or rabbits at a final concentration above 100 muM caused instantaneous inhibition of platelet aggregation induced by adenosine diphosphate (ADP), epinephrine (human PRP only), collagen, or thrombin. The inhibitory effect of LPC was found to be partially reversible over a period of 60-90 min. LPC at final concentrations above 30 muM also caused inhibition of ADP-, collagen-, and thrombin-induced aggregation and collagen- and thrombin-induced release of serotonin in suspensions of rabbit, pig, or human platelets. With washed platelets, the inhibitory effect not only rapidly disappeared but was followed by transient potentiation of aggregation and serotonin release. This potentiating effect of LPC was most pronounced when thrombin was used as stimulus. Both inhibition and potentiation were observed at concentrations of LPC that did not cause a significant change in platelet shape or loss from platelets of lactic dehydrogenase. Inhibition and potentiation were also observed when platelets were added to suspending medium containing LPC, although considerably higher concentrations of LPC were required under these conditions. Potentiation was not observed when LPC was added to citrated or heparinized rabbit or human PRP or to washed rabbit platelets suspended in a medium containing 4% bovine serum albumin. It seemed likely that some or all of the observed effects of LPC on platelet function were due to structural modification of the platelet membrane insufficient to result in gross membrane damage or platelet lysis. In addition, the results of experiments using 14C-LPC seemed to indicate that the observed potentiating effect of LPC on platelet function may be related to its rapid uptake and metabolism by the platelets.

Adenosine Diphosphate↗
PubMed1977

Platelets, thrombosis and atherosclerosis.

The interaction of platelets with the vessel wall can contribute to the early stages in the development of atherosclerosis through effects on smooth muscle cell proliferation, endothelial permeability, and possibly by causing vessel wall injury. Platelets are involved in the development of thrombi in response to vessel injury, and the repeated formation of platelet emboli and platelet-fibrin emboli from the mural thrombi may be one of the factors that cause clinical complications of atherosclerosis. Drugs which inhibit platelet function, particularly those that prolong shortened platelet survival (sulfinpyrazone and dipyridamole) may prove to be important in inhibiting the response of blood to vessel injury and thereby modifying the extent of atherosclerosis and its complications.

Arteries↗
PubMed1976

Reactions of polylysine with human platelets in plasma and in suspensions of washed platelets.

The effects of polylysine on human platelets have been examined in citrated platelet-rich plasma (PRP) and in suspensions of washed platelets in various media. In PRP, polylysine caused aggregation after a lag phase. Heparin inhibited this completely. At certain concentrations of polylysine, two phases of aggregation occurred, the second being associated with release of 14C-serotonin from prelabelled platelets; this phase was inhibitable with prostaglandin E1, acetylsalicylic acid, sulphinpyrazone, adenosine, apyrase, or creatine phosphate/creatine phosphokinase. Polylysine-induced release also occurred in PRP with EDTA or hirudin as anticoagulant. In suspensions of washed platelets in Tyrode solution containing 0.35% or 4% albumin, or 1% gelatin, polylysine caused immediate platelet-to-platelet adherence and very little release of 14C-serotonin or platelet lysis. Heparin inhibited aggregation, but acetylsalicylic acid, prostaglandin E1, adenosine, apyrase, creatine phosphate/creatine phosphokinase or EDTA did not. In a modified Tyrode-albumin medium containing 1 mM magnesium but no calcium, polylysine-induced aggregation was associated with the release of 14C-serotonin which could be inhibited by acetylsalicylic acid or indomethacin; this is similar to the effect of ADP in this medium. In Tyrode solution without albumin or gelatin, polylysine-induced platelet aggregation was associated with release of a large percentage of 14C-serotonin, together with as much as 18% lysis; indomethacin inhibited this release reaction.

Albumins↗