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N T Thompson

Publications and source records attributed to N T Thompson.

28 records · Page 2Linked to original sources
PubMed1986

Synergistic responses in human platelets. Comparison between aggregation, secretion and cytosolic Ca2+ concentration.

Synergistic interaction between ADP, adrenaline, 5-hydroxytryptamine (5HT) and [8-arginine]vasopressin is not observed for the aggregatory response of aspirin-treated human platelets when this response is estimated directly from the decrease in the number of single platelets in the suspension. This finding is in marked contrast with prior reports of synergistic interaction between these agonists when the rate and extent of the aggregometer response is estimated from the increase in the light transmittance of the suspension, using a platelet aggregometer. We propose that the apparent synergistic response detected using the aggregometer results from the inability of this instrument to respond during the initial phase of aggregation. Significant synergistic interaction is observed for the increase in cytosolic [Ca2+] induced by addition of the ADP/5HT and, to a lesser extent, of the ADP/vasopressin agonist pairs as compared with that caused by addition of the individual agonists. This effect is not, however, typical of the system since increases in cytosolic [Ca2+] induced by addition of the ADP/thrombin or 5HT/vasopressin agonist pairs are no greater than the sum of the responses to these agonists added separately. Addition of collagen prior to ADP or 11,9-epoxymethanoprostaglandin H2 (U46619) fails to enhance the increase in cytosolic [Ca2+] induced by these latter agonists. Adrenaline, when added prior to non-saturating concentrations of U46619, thrombin, vasopressin or ADP, significantly enhances the increase in cytosolic [Ca2+] induced by these agonists in platelets suspended in media containing less than 0.1 microM or 1 mM Ca2+. However, adrenaline fails to enhance the increase in cytosolic [Ca2+] induced by the divalent cation ionophore, ionomycin. Enhancement by adrenaline of Ca2+ influx induced by U46619, thrombin and ADP has been shown by using Mn2+ as probe. Adrenaline also enhances the extent of [3H]5HT secretion induced by U46619, thrombin and vasopressin but fails to increase that induced by ADP in this aspirin-treated preparation. These results are in part consistent with the postulate that adrenaline, acting via an alpha 2-adrenoceptor, modulates receptor--phospholipase-C coupling. However, such modulation does not appear to involve inhibition of adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Platelets↗
PubMed1986

Particle volume changes associated with light transmittance changes in the platelet aggregometer: dependence upon aggregating agent and effectiveness of stimulus.

The increase in light transmittance of aspirin-treated platelet-rich plasma caused by addition of non-saturating doses of ADP and, at earlier times, of adrenaline is correlated with formation of aggregates having a volume in the range 490-8580 fl. and containing 100-2000 platelets. The disappearance of single platelets and the formation of aggregates having volumes less than 490 fl. makes no significant contribution to the increase in light transmittance. Similar relationships are observed on addition of saturating doses of ADP and adrenaline except that the formation of aggregates larger than 8580 fl. contributes significantly to the initial phase of the increase in light transmittance and is more closely correlated with the overall change in this parameter.

Adenosine Diphosphate↗
PubMed1985

Inhibition by luciferin-luciferase reagents of aggregatory responses to excitatory agonists in washed platelet suspensions.

Addition of two commercial luciferin-luciferase reagents caused marked inhibition of the aggregatory response of washed human platelets to thrombin, ADP, vasopressin and platelet-activating factor (PAF). Analysis of the effects of the individual components of one of these reagents revealed that Mg2+, and to a lesser extent bovine serum albumin, was responsible for the observed inhibition. A modified luciferin/luciferase reagent has been designed on the basis of these data for use in washed platelet suspensions which causes minimal inhibition of the aggregatory and secretory responses to thrombin but which gives a near maximal luminescence yield.

Adenosine Diphosphate↗
PubMed1985

Intracellular calcium fluxes in human platelets.

Fluorescence changes and secretory responses have been measured on addition of various excitatory agonists to platelets loaded with the cytosolic Ca2+ probe, Quin 2 or with chlortetracycline as a probe for membrane-associated Ca2+. When extracellular [Ca2+] is decreased to less than 0.1 microM by addition of EGTA a linear correlation is observed between the extent of increase in cytosolic [Ca2+] and the extent of mobilisation of membrane-associated Ca2+ on stimulation by maximal doses of five excitatory agonists. A similar linear correlation between the increase in cytosolic [Ca2+] and the extent of ATP secretion is observed over the thrombin dose/response curve. Similar EC50 values are observed for ATP secretion, the increase in cytosolic [Ca2+] and the decrease in chlortetracycline fluorescence induced by thrombin. However, the decrease in chlortetracycline fluorescence shows a sigmoidal relationship with the increase in cytosolic [Ca2+] and a hyperbolic relationship with ATP secretion over this dose/response curve. Addition of prostaglandin D2 prior to thrombin causes parallel inhibition of the increase in cytosolic [Ca2+] and the decrease in chlortetracycline fluorescence induced by this agonist. However, addition of prostaglandin D2 after thrombin reverses the increase in cytosolic [Ca2+] induced by this agonist but fails to cause a similar reversal of the decrease in chlortetracycline fluorescence. The data provide further evidence supporting the proposal that chlortatracycline can be used as a probe to monitor mobilisation of membrane-associated Ca2+ but suggest that, in platelets stimulated in the effective absence of extracellular Ca2+, both Ca2+ mobilisation and Ca2+ removal can under some conditions involve sites which are not monitored by this probe.

Adenosine Triphosphate↗
PubMed1984

The role of cytoplasmic free calcium in the responses of quin2-loaded human platelets to vasopressin.

Responses to vasopressin were studied in human platelets loaded with the fluorescent Ca2+ indicator, quin2. In the presence of 1 mM external Ca2+, vasopressin caused a transient rise in [Ca2+]i from the basal level near 100nM to about 700 nM; peak [Ca2+]i was reached in a few seconds and the level then declined towards resting over several minutes. In the absence of external Ca2+ there was a much smaller rise of similar time-course, suggesting that vasopressin increases [Ca2+]i mainly by stimulated-influx across the plasma membrane but also by partly releasing internal Ca2+. Inhibition of thromboxane A2 formation somewhat reduced the peak [Ca2+]i in the presence of external Ca2+, but had no effect on the response attributed to release of internal Ca2+. With external Ca2+, vasopressin stimulated shape-change, secretion and aggregation. Secretion and aggregation were decreased by about half following blockage of thromboxane production. The ability of vasopressin to induce shape-change and secretion even at near basal [Ca2+]i suggests that activators other than Ca2+ are involved.

Aminoquinolines↗
PubMed1984

Effects of alpha 2-adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets.

A range of 2-(,5-dihydroimidazolyl)-benzene, -quinoline, and -quinoxaline derivatives and 2-morpholino-4-catechol have been characterized as agonists or partial agonists for human platelet aggregation; and for inhibition of adenylate cyclase by measurement of their effect on platelet [cyclic-3',5'-AMP]. Antagonist activity for these compounds versus adrenaline as agonist has also been assessed for these two responses. The compounds can be divided into 4 groups. Group I contains compounds that are agonists for both responses; group II, compounds that are agonists for inhibition of adenylate cyclase but antagonists for the aggregatory response; group III, compounds that are agonists for the aggregatory response but are antagonists for inhibition of adenylate cyclase by adrenaline; and group IV, compounds that are antagonists for both responses. In group I the EC50 values for induction of aggregation are not significantly different from the EC50 values for inhibition of adenylate cyclase except for 2-morpholino-4-catechol which is significantly more potent as an inhibitor of adenylate cyclase. In group IV a linear correlation is observed between the K1 values for the two responses for 8 compounds but 2 other compounds do not conform to this correlation. The data are not consistent with a model in which a single chi 2-adrenoceptor mediates both the aggregatory response and inhibition of adenylate cyclase and hence support a model in which unique chi 2-adrenoceptors mediate these two responses.

Adenosine Diphosphate↗
PubMed1975

The variable fine structure of elastin visualized with Verhoeff's iron hematoxylin.

Verhoeff's iron hematoxylin (VIH) followed by lead citrate (LC) applied to epoxy thin sections stained the dense component of elastic fibers heavily and the peripheral microfibrillar component lightly in guinea pig trachea and mouse testis fixed with a glutaraldehyde-osmium tetroxide sequence. This method stained large fimbriated fibers beneath tracheal epithelium, small fibers and stacked aggregates thereof in the deep lamina propria, cartilage and adventitia of the trachea and large stacked fibers in the fibroelastic band of the trachea. Fibers of the fetus differed from those of the adult, especially in the subepithelial elastic lamina of the trachea. Elastic fibers were intimately associated with fibroblasts and particularly slender fibroblast processes in tracheal stroma and with chondrocytes in tracheal cartilage. Fibroblasts associated with elastic fibers in the tracheal subepithelial lamina propria were often closely bordered by eosinophils, mast cells, or monocytes. Occasional mast cells extended slender processes around elastic fibers in the subepithelial lamina propria. In mouse testis and in many regions of the trachea, small elastic fibers were identified which were below the limits of resolution for the light microscope and were not apparent at the ultrastructural level in routinely stained thin sections.

Animals↗
PubMed1975

Variability of dermal elastin visualized ultrastructurally with iron hematoxylin.

The Verhoeff iron hematoxylin-lead citrate (VIH-LC) method demonstrated vertical elastic fibers that were often composed only of microfibrillar component extending into the epidermal basement membrane in human skin. These fibers connected with a network of trabeculae composed of microfibrils and elastin fibrils in varying proportions. The large elastic fibers in the deep two thirds of the dermis consited mainly of compact bundles of small elstin fibrils in infants and of solid elastin cores with a fimbriated periphery in adults; Dermis of a 6-month-old fetus contained very few small elastic fibrils except around blood vessels. Skin of an elderly subject revealed exteme proliferation of unusual reticulated elastic fibers in various areas and disclosed abnormal nodules of elastin or collagen fibrils in finely particulate matter. Small elastin fibrils, abundant microfibrils, and intermixed individual collagen fibrils comprised an adventitial collar between sweat glands and fibroblasts. Elastin fibrils were absent from this collar in the fetus and increased with the subject's age. A permanganate-high iron diamine sequence appeared to impart density to the microfibrillar component of elastic fibers.

Adolescent↗