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W Martin

Publications and source records attributed to W Martin.

At least 19 recordsLinked to original sources
PubMed1992

A comparison of maximal exercise and dipyridamole thallium-201 planar gated scintigraphy.

Both symptom-limited maximal exercise and intravenously given dipyridamole stress (0.56 mg/kg over 4 min with a 2 min walk) gated thallium scans were performed in 22 patients undergoing coronary arteriography for the assessment of chest pain. All scans were acquired gated to the electrocardiogram in 3 projections and were reported for the presence and extent of defects in 5 myocardial segments in each view. In addition, left and right ventricular myocardial uptake and estimates of right and left lung and liver to left ventricular uptake were assessed relative to the injected dose of thallium-201. Overall, 190/310 segments were abnormal with exercise compared with 169/310 with dipyridamole. Segments were scored greater in extent in 90/310 cases with exercise, compared with 46/310 in which the defect was more extensive with dipyridamole (P less than 0.0005). Non-attenuation corrected percentage myocardial thallium uptakes were similar for both stresses: anterior percentage uptakes, 0.785% +/- 0.230% with exercise versus 0.870% +/- 0.217% with dipyridamole (NSD). Left and right lung and liver to left ventricle ratios were all significantly higher with dipyridamole than with exercise (1.587 +/- 0.408 versus 1.446 +/- 0.518, P less than 0.02; 1.78 +/- 0.479 versus 1.46 +/- 0.502, P less than 0.002; 2.598 +/- 0.788 versus 1.265 +/- 0.386, P less than 0.001, respectively). High right and left lung uptakes with dipyridamole were strongly correlated with high exercise values (r = 0.756, P less than 0.001; r = 0.809, P less than 0.001). The liver uptake was weakly correlated between the 2 different stress tests (r = 0.483, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Suppression of transformed phenotype in hybrids of v-fgr and v-raf transformed rat-1 cells with rat embryonic fibroblasts is due to transcriptional inactivation of viral oncogenes.

Rat-1 cells that had been transformed to tumorigenicity by transfection with the retroviral oncogenes v-raf from 3611-murine sarcoma virus, or v-fgr from Gardner-Rasheed feline sarcoma virus were fused with rat embryonic fibroblasts at an early passage. In both fusion experiments hybrid cells were isolated that exhibited normal morphology, anchorage requirement for proliferation, and either no tumorigenicity (v-fgr) or extended latency periods for tumor growth (v-raf) in nude mice. Transcription of viral oncogenes is drastically reduced in hybrid cells (at least 30-fold compared to their transformed parental cells), while the half-life of the corresponding transcripts is not effected. In the chromatin of hybrid cells the integrated retroviral oncogenes are as sensitive to degradation with pancreatic DNase I as the endogenous actin gene. Thus the observed down regulation of proviral transcript levels does not correlate with changes in chromatin structure. We conclude that in hybrids of (v-fgr)- and (v-raf)-transformed Rat-1 cells with embryonic fibroblasts, transcription of the retroviral oncogenes appears to be repressed by trans-acting factors of the normal parental cell.

Animals↗
PubMed1992

The influence of arm position and cardiac output on bolus clearance from the arm.

The importance of arm position and cardiac output on the clearance of a bolus injection from the arm was assessed in 63 patients using technetium-99m. Injections were made in the left arm which was either adducted, abducted or adducted with the forearm flexed over the lower chest. The clearance of isotope was assessed by measuring the amount of radioactivity remaining in the arm at 10 s intervals and calculating it as a fraction of the injected dose. The clearance of Tc-99m was significantly faster and more complete from the abducted arm than from the adducted arm. There was no correlation between clearance and cardiac output.

Arm↗
PubMed1992

Modulation of barrier function of bovine aortic and pulmonary artery endothelial cells: dissociation from cytosolic calcium content.

1. Barrier function and cytosolic free calcium content [Ca2+]i was measured in monolayers of bovine pulmonary artery endothelial cells (BPAEC) and bovine aortic endothelial cells (BAEC). 2. Thrombin (1 u ml-1) increased albumin transfer across monolayers of BPAEC but not BAEC, yet induced biphasic increases in [Ca2+]i in both endothelial cell types, consisting of a rapid, initial phasic component which decayed to a lower, more sustained plateau phase. 3. 4 beta-Phorbol 12-myristate 13-acetate (PMA; 0.3-3000 nM) increased albumin transfer across monolayers of BPAEC and BAEC, but had no effect on basal levels of [Ca2+]i in either endothelial cell type. 4. Treatment of BPAEC and BAEC with forskolin (30 microM), an activator of adenylate cyclase, had no effect on resting transfer of albumin, but inhibited that stimulated by PMA (600 nM). It also inhibited the thrombin (1 u ml-1)-induced increase in albumin transfer across monolayers of BPAEC, but enhanced the plateau phase of the associated increase in [Ca2+]i. 5. Treatment of BPAEC and BAEC with either atriopeptin II (100 nM), an activator of particulate guanylate cyclase, or 8 bromo cyclic GMP (30 microM) had no effect on resting or PMA (600 nM)-stimulated transfer of albumin. Both agents did, however, inhibit the thrombin (1 u ml-1)-induced increase in albumin transfer across monolayers of BPAEC, but had no effect on the associated increase in [Ca2+]i. 6. These data suggest a dissociation between the ability of agents that increase or decrease albumin transfer and their effects on [Ca2+]i. Consequently, activation of protein kinase C may be the major stimulus for trans-endothelial transfer of macromolecular solutes. Endothelial barrier function is enhanced by elevation of either cyclic AMP or cyclic GMP content. Cyclic AMP appears to act by inhibiting the actions of protein kinase C, while cyclic GMP may act to inhibit a key step proximal to activation of this enzyme.

Animals↗
PubMed1992

Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN: Cross sectional study. SETTING: University department of medical cardiology. PATIENTS: 90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS: 48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). RESULTS: 43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. CONCLUSIONS: Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.

Adult↗
PubMed1992

Thallium scans in syndrome X.

OBJECTIVE: To review thallium scans in patients with angina and normal coronary arteriograms. DESIGN: Retrospective review of data. SETTING: Regional cardiac centre in Glasgow. PATIENTS: 100 patients selected from those undergoing diagnostic angiography for typical angina who had normal arteriograms (around 10%), no other cardiovascular abnormality, and available thallium scans (performed routinely before angiography). MAIN OUTCOME MEASURES: Coronary arteriography, exercise tests, and gated thallium scans at peak exercise. RESULTS: The exercise test was positive in 30 and negative in 70 patients. Thallium defects were found in 98 patients, but no consistent pattern and no significant correlation existed between the extent of thallium defect and positive exercise test or exercise tolerance. CONCLUSIONS: Thallium defects described in 98 of 100 patients with angina and normal coronary arteriograms suggest that microvascular angina may be commoner than is generally appreciated.

Adult↗
PubMed1992

The future of podiatric medical education. Cautious optimism.

The leadership of the Pennsylvania College of Podiatric Medicine sets forth the following treatise on the outlook for podiatric medical education into the 21st century. Despite the seemingly impossible challenges facing the profession and its students, it is their opinion that the future is bright and with dedicated effort the profession will become stronger in the years ahead.

Education, Medical↗
PubMed1992

Balanced triple-vessel disease: enhanced detection by estimated myocardial thallium uptake.

Maximal stress thallium scans may prove to be 'normal' in some patients with triple-vessel disease due to global reduction in flow resulting in no focal perfusion defect. The aim of this study was to attempt to identify patients with global reduction in flow by estimating total thallium delivery to the left ventricle. Myocardial thallium uptake was calculated as a percentage of injected dose as a mean of three projections in 90 patients undergoing diagnostic arteriography and in 10 normal volunteers. These volunteers and nine patients who proved to have normal coronary arteries established a normal range. Values for myocardial thallium uptake were: 1.166 +/- 0.352% in normals (n = 19); 0.671 +/- 0.184% in patients with single- or double-vessel disease (n = 26); 0.708 +/- 0.245% in patients with triple-vessel disease (n = 55). Thallium scans were normal in 11 of 55 patients with triple-vessel disease and eight of 26 with single- or double-vessel disease. However, eight of these 11 and 5 of the eight proved to have abnormal myocardial thallium uptake. Thus combining the tests improved sensitivity from 76.5% for the scan alone to 94.5% for the scan and myocardial thallium uptake, with no reduction in specificity. Measurement of myocardial thallium uptake is a readily and reliably quantified parameter from a thallium scan which leads to enhanced detection of coronary artery disease.

Adult↗
PubMed1991

Growth inhibition of oncogene-transformed rat fibroblasts by cocultured normal cells: relevance of metabolic cooperation mediated by gap junctions.

We have studied the proliferation of rat 208F cells (a derivative of Rat-1 cells) transformed by activated c-Ha-ras, v-fgr, v-raf, v-fms, or v-src oncogenes during cocultivation with an excess of early passage rat embryonic fibroblasts or immortal 208F cells. The total number and size of foci formed by oncogene-transformed 208F cells were strongly reduced by cocultured normal fibroblasts. The extent of growth suppression of transformed foci appears to be dependent on the type of transforming oncogene and on the type of normal fibroblasts rather than on the extent of gap-junctional communication between transformed and normal cells. Total inhibition of fluorescent dye transfer between normal and transformed cells by the 3 beta-O-hemisuccinate of 18 alpha-glycyrrhetinic acid (18 alpha-carbenoxolone), an inhibitor of gap-junctional communication in human fibroblasts, did not prevent growth inhibition of transformed cells in the cocultivation assay. Since adjacent cells remained electrically coupled in the presence of this inhibitor it is possible that the strongly reduced metabolic cooperation, as indicated by the lack of fluorescent dye transfer, is sufficient for mediating the growth-inhibitory effect of normal fibroblasts. 208F cell-conditioned medium, however, also caused strong growth inhibition of transformed derivatives, suggesting that the effect is in part mediated by release of stable growth inhibitor(s) from 208F cells.

Animals↗
PubMed1991

Bradykinin induces elevations of cytosolic calcium through mobilisation of intracellular and extracellular pools in bovine aortic endothelial cells.

1. In the presence of 1.8 mM extracellular calcium, bradykinin (0.3 nM-100 nM) induced a biphasic elevation of intracellular calcium ([Ca2+]i) in bovine aortic endothelial cells, consisting of an initial, large transient component followed by a lower sustained component. 2. When endothelial cells were bathed in nominally calcium-free solution containing 0.5 mM EGTA, bradykinin induced only a transient elevation of [Ca2+]i: the magnitude of this was significantly smaller than that obtained in the presence of extracellular calcium and the sustained phase was abolished. In the continued presence of bradykinin, re-addition of extracellular calcium to achieve a level of around 1.8 mM resulted in the induction of a biphasic elevation of [Ca2+]i consisting of a large initial component followed by a lower sustained component. 3. In the presence of 1.8 mM extracellular calcium, caffeine (5 mM) induced a small elevation of [Ca2+]i. When endothelial cells were bathed in nominally calcium-free solution containing 0.5 mM EGTA, the caffeine-induced elevation of [Ca2+]i was almost completely abolished. 4. In the presence of 1.8 mM extracellular calcium, treatment of endothelial cells with the calcium influx blocker, nickel chloride (4 mM), had no effect on resting [Ca2+]i or on the magnitude of the bradykinin-induced initial transient elevation of [Ca2+]i but abolished the sustained component. 5. In the presence of 1 mM extracellular calcium, treatment with the calcium chelator EGTA (2 mM; 1 min) had no effect on resting [Ca2+]i but the magnitude of the bradykinin-induced initial transient elevation of [Ca2+]i was significantly reduced. Increasing the exposure time or concentration of EGTA resulted in no further reduction in the magnitude of the bradykinin-induced transient component. 6. Treatment of endothelial cells with the putative inhibitor of intracellular calcium release, 3,4,5-trimethoxybenzoic acid 84diethylamino)octyl ester (TMB-8, 0.1 mM) increased resting [Ca21]i slightly but had no effect on the magnitude of the bradykinin-stimulated elevation of [Ca22ji. 7. These findings suggest that, in bovine aortic endothelial cells, the bradykinin-induced initial transient elevation of [Ca21]i is completely dependent upon release of calcium from intracellular stores and the sustained component is due to calcium influx. They further suggest the possible existence of two intracellular calcium pools, one which is rapidly depleted in the absence of extracellular calcium and a second which is resistant to such depletion.

Animals↗
PubMed1991

Effects of cyclic nucleotides and phorbol myristate acetate on proliferation of pig aortic endothelial cells.

1 The role of cyclic nucleotides and protein kinase C in controlling proliferation of pig aortic endothelial cells (PAEC) in culture was investigated. 2 Dibutyryl cyclic AMP (30 microM), added twice daily, inhibited proliferation but 8 bromo cyclic GMP (30 microM) had no effect. Two other stimuli known to increase PAEC cyclic GMP content by stimulating particulate and soluble guanylate cyclase respectively, atriopeptin II (10 nM) and sodium nitroprusside (1 microM), were also without effect on proliferation. 3 Two agents known to inhibit soluble guanylate cyclase and lower intercellular cyclic GMP content, haemoglobin (10 microM) and methylene blue (10 microM), each inhibited proliferation of PAEC. 4 The inhibitory effect of haemoglobin (10 microM) was mediated by inhibition of soluble guanylate cyclase since it was reversed by agents known to increase cyclic GMP content, i.e. atriopeptin II (10 nM), 8 bromo cyclic GMP (30 microM) or sodium nitroprusside (1 microM). The inhibitory effect of methylene blue (10 microM) was not reversed by these agents. 5 Phorbol 12-myristate 13-acetate (PMA, 0.1 nM-1 microM), which activates protein kinase C, inhibited proliferation in a concentration-dependent manner. No early stimulation of proliferation was seen with PMA. The inactive isomer, 4 alpha-phorbol 12,13-didecanoate (0.3 microM), lacked the ability of PMA to inhibit proliferation of PAEC. 6. PMA-induced inhibition of proliferation appeared not to be due to stimulated production of destructive oxygen-derived free radicals since it was unaffected by the radical scavengers, vitamin E (30 microM) or butylated hydroxytoluene (30 microM). The antiproliferative actions of paraquat (10 microM), an agent which generates free radicals intracellularly, was, in contrast, inhibited by vitamin E or butylated hydroxytoluene. Furthermore, neither dibutyryl cyclic AMP (30 microM) nor 8 bromo cyclic GMP (30 microM) had any effect on the ability of PMA to inhibit proliferation. 7. This study suggests that cyclic AMP, cyclic GMP and protein kinase C play a role in controlling the proliferation of PAEC.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Effects of metabolic inhibitors on endothelium-dependent and endothelium-independent vasodilatation of rat and rabbit aorta.

1. Basal release of endothelium-derived relaxing factor (EDRF) rendered endothelium-containing rings of rat aorta 4.7 fold less sensitive to the contractile actions of phenylephrine and depressed the maximum response when compared with endothelium-denuded rings. The responsiveness and maximum response to phenylephrine was, however, similar in rings of rabbit aorta with or without endothelium. 2. Rotenone (1 nM-0.1 microM), an inhibitor of oxidative phosphorylation, induced a profound, irreversible blockade of phenylephrine-induced tone in endothelium-containing and endothelium-denuded rings of rat aorta, but induced only slight inhibition of tone in rings of rabbit aorta. 3. 2-Deoxy glucose (10 mM), an inhibitor of glycolysis, had no effect on phenylephrine-induced contraction in endothelium-denuded rings of rat aorta, but inhibited reversibly the endothelium-dependent depression of contraction in endothelium containing rings. 2-Deoxy glucose had no effect on phenylephrine-induced contraction in rings of rabbit aorta with or without endothelium. 4. Rotenone (0.1 microM) inhibited acetylcholine-induced, endothelium-dependent relaxation of phenylephrine-contracted rings or rat and rabbit aorta. In endothelium-denuded rings of rat aorta, relaxation induced by glyceryl trinitrate of isoprenaline was also inhibited, but relaxation induced by 8-bromo cyclic GMP or dibutyryl cyclic AMP was not. Relaxation induced by verapamil on KCl-contracted, endothelium-denuded rings of rat aorta was also unaffected. 5. 2-Deoxy glucose (10 mM) inhibited acetylcholine-induced, endothelium-dependent relaxation of phenylephrine-contracted rings of rat and rabbit aorta. In endothelium-denuded rings of rat aorta, relaxation induced by glyceryl trinitrate and by isoprenaline was also inhibited, but relaxation induced by 8-bromo cyclic GMP or dibutyryl cyclic AMP was not. Relaxation induced by verapamil on KCIcontracted, endothelium-denuded rings of rat aorta was also unaffected. 6. These data suggest that in rabbit and in rat aorta, rotenone inhibits acetylcholine-induced relaxation by inhibiting EDRF production, and by depressing smooth muscle sensitivity to EDRF, respectively. They further suggest that 2-deoxy glucose inhibits acetylcholine-induced relaxation in both tissues by depressing the sensitivity to EDRF, probably as a result of reduced synthesis of cyclic GMP. The additional possibility that 2-deoxy glucose inhibits EDRF production warrants further investigation. 7. The blockade by 2-deoxy glucose of the endothelium-dependent depression of phenylephrine-induced tone in rat aorta probably reflects blockade of the actions of spontaneously released EDRF.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Effects of hypoxia and metabolic inhibitors on production of prostacyclin and endothelium-derived relaxing factor by pig aortic endothelial cells.

1. The content of adenosine triphosphate (ATP) and basal and bradykinin-stimulated production of prostacyclin and endothelium-derived relaxing factor (EDRF) was measured in primary cultures of porcine aortic endothelial cells under normoxic (14.4% O2) and hypoxic (2.8% O2) conditions, and following treatment with rotenone and 2-deoxy glucose, which inhibit oxidative and glycolytic metabolism, respectively. 2. ATP content and basal and bradykinin-stimulated production of prostacyclin were similar under normoxic and hypoxic conditions. EDRF production, assessed as endothelial guanosine 3':5'-cyclic monophosphate (cyclic GMP) content, was also similar under both conditions. 3. Treatment with rotenone (0.3 microM) had no effect on ATP content or basal or bradykinin-stimulated production of prostacyclin or of EDRF, measured as endothelial cyclic GMP content. Elevation of cyclic GMP content by atriopeptin II was also unaffected. 4. Treatment with 2-deoxy glucose (20 mM) in glucose-free Krebs solution lowered ATP content, reduced bradykinin-stimulated production of prostacyclin and abolished the bradykinin-stimulated elevation of cyclic GMP content. Resting production of prostacyclin was unaffected but basal content of cyclic GMP was lowered in some experiments. Elevation of cyclic GMP content by atriopeptin II was abolished. 5. Combined treatment with rotenone (0.3 microM) and 2-deoxy glucose (20 mM) lowered ATP content more than with 2-deoxy glucose alone. Basal production of prostacyclin rose slightly and bradykinin-stimulated production was powerfully inhibited. Basal content of cyclic GMP was unaffected, but bradykinin-stimulated production was abolished. Elevation of cyclic GMP by atriopeptin II was also abolished. 6. Cascade bioassay experiments using endothelium-denuded rings of rabbit aorta as a detector system confirmed that bradykinin-stimulated production of EDRF was blocked by 2-deoxy glucose, but not by rotenone. 7. These data indicate that porcine aortic endothelial cells in culture operate under mainly glycolytic metabolism and this probably explains why production of prostacyclin and EDRF is unaffected under hypoxic conditions. They also indicate that glycolytic metabolism is required for agonist-stimulated production of prostacyclin and EDRF by these cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Effects of NG-substituted analogues of L-arginine on NANC relaxation of the rat anococcygeus and bovine retractor penis muscles and the bovine penile artery.

1. The effects of two inhibitors of nitric oxide synthase, NG-monomethyl L-arginine (L-NMMA) and NG-nitro L-arginine (L-NOARG), were examined on non-adrenergic non-cholinergic (NANC) inhibitory transmission in the rat anococcygeus, bovine retractor penis (BRP) and bovine penile artery. 2. In the rat anococcygeus, L-NMMA (10-1000 microM) produced a concentration-dependent augmentation of guanethidine (30 microM)-induced tone and inhibited NANC relaxation at all frequencies tested (0.1-20 Hz): the maximum inhibition obtained was 56 +/- 6% (n = 6). L-NOARG (0.3-30 microM) also augmented tone and inhibited NANC relaxation in a concentration-dependent manner, but unlike L-NMMA the maximum inhibition was 100%. 3. In the BRP, L-NMMA (10-100 microM) had no effect on tone or NANC-induced relaxation, but at 1000 microM tone was increased and NANC relaxation inhibited by 25 +/- 7% (n = 6). L-NOARG (0.3-30 microM) produced a concentration-dependent increase in tone and inhibition of NANC relaxation. As in the rat anococcygeus, inhibition of NANC relaxation was complete. 4. The effects of L-NMMA and L-NOARG were stereospecific since D-NMMA (10-1000 microM) and D-NOARG (1-1000 microM) had no effect on tone or NANC relaxation of the rat anococcygeus or BRP. 5. L-Arginine (10-300 microM) had no effect by itself on NANC-induced relaxation of the rat anococcygeus or BRP. It did, however, reverse the ability of L-NMMA (10-1000 microM) to augment tone and inhibit NANC relaxation in the rat anococcygeus and BRP. 6. On the bovine penile artery, both L-NMMA (100 microM) and L-NOARG (30 microM) augmented the tone induced by guanethidine (30 microM) and 5-hydroxytryptamine (0.2 microM) in an endothelium-dependent manner. L-NMMA had no effect on NANC-induced relaxation, but inhibited acetylcholine-induced endotheliumdependent relaxation. L-NOARG abolished NANC relaxation at all frequencies tested and inhibited acetylcholine-induced relaxation. D-NOARG (30 microM) had no effect on NANC or acetylcholine-induced relaxation. 7. The ability of L-NOARG to abolish NANC-induced relaxation in the rat anococcygeus, BRP and bovine penile artery suggests that the L-arginine-nitric oxide pathway mediates neurotransmission in all three tissues. The effectiveness of L-NMMA in blocking NANC relaxation-in the rat anococcygeus but not the BRP and bovine penile artery suggests a species difference in the neuronal nitric oxide synthase. The neuronal and endothelial nitric oxide synthases in the penile artery also appear to differ.

Animals↗
PubMed1991

Modulation of agonist-induced calcium mobilisation in bovine aortic endothelial cells by phorbol myristate acetate and cyclic AMP but not cyclic GMP.

1. In bovine aortic endothelial cells (BAEC), thrombin (1 mu ml-1), bradykinin (1-10 nM) and adenosine triphosphate (ATP) (0.3 microM-100 microM) each induced a biphasic elevation of cytosolic calcium ([Ca2+]i), consisting of an initial transient followed by a sustained plateau phase. 2. Pretreatment of BAEC with 4 beta-phorbol 12-myristate 13-acetate (PMA; 100 nM) reduced the magnitude of the initial transient elevation of [Ca2+]i, induced by thrombin (1 mu ml-1), low concentrations of bradykinin (1 nM) or ATP (0.3 microM, 3 microM), but not by higher concentrations of the latter two agonists. Addition of PMA (100 nM) during the plateau phase of the increase in [Ca2+]i induced by thrombin (1 mu ml-1), bradykinin (10 nM) or ATP (30 microM) resulted in a fall in [Ca2+]i. 3. The inhibitory effects of PMA (100 nM) were inhibited by staurosporine (100 nM) but not mimicked by the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD; 100 nM). Furthermore, staurosporine (100 nM) increased [Ca2+]i when added during the plateau phase of the increase in [Ca2+]i induced by thrombin or bradykinin. In contrast, staurosporine (100 nM) reduced [Ca2+]i when added during the plateau phase of the increase in [Ca2+]i induced by ATP (30 microM). 4. Pretreatment with forskolin (10 microM) had no effect on the magnitude of the initial transient elevation of [Ca2+]i induced by thrombin (1 mu ml-1), bradykinin (1 nM and 10 nM) or ATP (30 microM). In contrast, forskolin (10 microM) and isoprenaline (10 microM) each induced biphasic elevations of [Ca21]i when added during the plateau phase of the increase in [Ca2+]i induced by the three agonists. Furthermore, in the presence of the inhibitor of calcium influx, nickel chloride (4mM), these biphasic elevations were reduced to monophasic transient elevations. 5. 8 Bromo cyclic GMP (30 microM), a membrane-permeant analogue of guanosine 3': 5'-cyclic monophosphate (cyclic GMP), had no effect on the magnitude of the initial transient elevation of [Ca21]i induced by thrombin (1 u ml 1), bradykinin (10 nM) or ATP (3 microM). Furthermore, 8 bromo cyclic GMP (30 microM) and sodium nitroprusside (1 microM), had no effect when added during the plateau phase of the increase in [Ca2+]i induced by the three agonists. 6. NG nitro-L-arginine (50,microM), an inhibitor of nitric oxide synthase, had no effect on the magnitude of the initial transient elevation of [Ca21]i induced by thrombin (1 uml- ), bradykinin (1 nM) or ATP (3,microM), and had no effect on the plateau phase of the increase in [Ca2+]i induced by these agents. 7. These findings suggest that while activation of protein kinase C inhibits and elevation of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) augments calcium mobilisation in bovine aortic endothelial cells, elevation of cyclic GMP appears to have no effect.

Animals↗
PubMed1990

Laser desorption electron impact: application to a study of the mechanism of conjugation of glutathione and cyclophosphamide.

Toward the objective of producing ion radical species from involatile and thermally labile samples, we have combined laser desorption of neutral molecules with electron impact ionization on a time-of-flight mass analyzer with a delayed draw-out pulse. The analytical capabilities of this method are tested in the analysis of isotope labels in the involatile product in a mechanistic study of both the chemical and the enzyme catalyzed reactions of cyclophosphamide with glutathione.

Animals↗