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Biomedical subjects

S Noble

Publications and source records attributed to S Noble.

At least 91 records · Page 5Linked to original sources
PubMed1989

Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury.

Cyclic variations in coronary blood flow (CFVs) in dogs with experimental coronary artery stenosis and endothelial injury appear to result primarily from the aggregation of platelets at the site of stenosis followed by dislodgement and distal embolization. Using this canine model, we tested the hypotheses: (a) that thrombin is an important mediator of CFVs in dogs with coronary stenoses and endothelial injury; (b) that inhibition of thrombin with heparin, or MCI-9038, a selective thrombin inhibitor, abolishes CFVs in this model; and (c) that abolition of CFVs by thrombin inhibition is time dependent. CFVs, produced in open-chest dogs by placing a flow-reducing plastic constrictor around the left anterior coronary artery, were monitored for either 30 min (group I) or 3 h (group II) before treatment with either heparin or 4-methyl-1-(N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl (MCI-9038). In group I, cyclic flow variations were abolished by heparin in 12 of 18 dogs and by MCI-9038 in 5 of 7 dogs. In group II, cyclic flow variations were not abolished by heparin in any of seven dogs and were abolished by MCI-9038 in only one of seven dogs. Thus, (a) thrombin appears to be an important mediator of cyclic flow variations in dogs with coronary artery stenosis and endothelial injury and (b) inhibition of thrombin abolishes CFVs after short but not prolonged periods of CFVs.

Animals↗
PubMed1989

Relapses after multidrug therapy for leprosy: a preliminary report of 22 cases in west Nepal.

The WHO recommended multidrug therapy regimens for leprosy patients were implemented in Nepal from 1982. Therefore a considerable number of both paucibacillary (PB) and multibacillary (MB) patients have been on observation after release from MDT, for as long as 4-5 years. A retrospective study was done considering the patients who relapsed during this period and who were registered at the Out-patients Department of Green Pastures Hospital in Pokhara, Nepal. A total of 22 patients relapsed out of 927 who were released from MDT.

Drug Therapy, Combination↗
PubMed1988

Similarities between behavior of respiratory muscles in breath-holding and in elastic loading.

Breath-holding subjects often exhibit involuntary contractions of respiratory muscles which are much stronger and faster than the efforts they would make during unrestricted breathing at the same level of CO2 and O2. To gain a better understanding of the genesis of these contractions, we compared them with the respiratory response to external elastic loading. Normal men rebreathed a mixture of 8% CO2 in oxygen against no load, elastic loads of 25 and 75 cm H2O/L, and held their breath, equivalent to an elastic load of 226 cm H2O/L. At iso-CO2, increasing loads led to progressively smaller tidal volumes, inspiratory flow rates and ventilation. However, respiratory muscles were progressively activated by the loads, as indicated by increasing occlusion pressure, so that inspiratory flow rate and ventilation were defended much better than could be expected if no neural compensation occurred. The pattern of respiratory muscle activity in breath-holding was qualitatively similar to that in elastic loading, and seemed quantitatively to be an extreme form of reaction to a large load. The reduction in inspiratory time and therefore of peak inspiratory pressure and ratio of inspiratory to total time with very large loads could be viewed as an adaptive response to limit respiratory muscle fatigue.

Adult↗
PubMed1988

A seasoned practice.

Explore the source record for details and available documents.

Practice Management, Dental↗
PubMed1986

Effect of L-thyroxine on serum angiotensin converting enzyme activity in sheep.

The effect of L-thyroxine on serum angiotensin converting enzyme activity using a sheep model was examined. Following two weeks of L-thyroxine treatment, the activity of serum angiotensin converting enzyme was increased from 6.92 U/ml to 8.65 U/ml (s.e.m. = 0.40, n = 13, P less than 0.01). Discontinuation of L-thyroxine treatment resulted in lowering the activity of serum angiotensin converting enzyme within three weeks to values close to those observed during the control period. It was concluded that L-thyroxine modulates serum angiotensin converting enzyme activity. The sheep is an appropriate animal model for the study of the factors that control serum angiotensin converting enzyme activity.

Animals↗
PubMed1984

Mechanisms of rat pancreatic islet allograft rejection.

Since the mechanisms of rat islet allograft rejection are unknown, metabolic, histologic, and immunologic parameters were characterized during rejection. Syngeneic intraportal islet transplants in diabetic Lewis rats normalize glucose values without islet cellular infiltrates; after Wistar-Furth allografts, glucose values rapidly return to diabetic levels and infiltration of islets by mononuclear cells occurs. Using lymphocyte proliferative assays, allogeneic islets induce a 3-fold stimulation of lymphocytes derived from nondiabetic allograft recipients. Using cytotoxicity assays, cell-mediated cytotoxicity of allogeneic islet target cells although inefficient is 2-fold greater in diabetic allograft recipients than in syngeneic recipients. Antibody-dependent cellular cytotoxicity is not observed, whereas 14 days after allotransplantation, complement-dependent antibody-mediated cytotoxicity is elevated. These data suggest that islet allograft rejection using metabolic, histopathologic and immunologic methods is associated primarily with cell-mediated cytotoxicity related to histocompatibility antigens.

Animals↗
PubMed1984

Trial of vindesine, etoposide, and cisplatin in patients with previously treated, advanced-stage, non-small cell bronchogenic carcinoma.

Twenty-two patients with advanced-stage, non-small cell bronchogenic carcinoma were treated in a pilot study with a combination of vindesine, etoposide, and cisplatin (VEDDP). All patients had been previously treated with a non-cisplatin-containing regimen and had documentation of progressive disease. Median duration of VEDDP therapy was 2.6 months. Only one patient had a minor response. Median survival from start of protocol therapy was 3.7 months; the overall survival from start of primary therapy was 13.5 months. The only significant variable possibly affecting survival was achieving a minor response or stable disease (5.0 months for minor response/stable disease from start of VEDDP vs 3.2 months for progressive disease, P = 0.016). Hematologic toxicity was moderate to severe in 14 patients and prevented completion of two full cycles in seven patients. We conclude that VEDDP is ineffective in inducing a response in patients with refractory, advanced-stage non-small cell bronchogenic carcinoma in the dose and kinetic schema used in this pilot study.

Adolescent↗
PubMed1981

The calcium and frequency dependence of the slow inward current 'staircase' in frog atrium.

1. Changes in the magnitude of the slow inward current in the frog atrium were monitored at different stimulation frequencies, using a double sucrose-gap technique. 2. After short rest periods (1.5-3.0 min), repetitive clamp depolarizations applied at frequencies ranging from 0.33 to 1 Hz (20-60/min) resulted in a progressive increase in the slow inward current towards a new level. Action-potential amplitudes and plateau levels usually showed similar increases under these conditions. 3. Changes in the magnitude of the slow inward current were also found when the frequency was changed during constant stimulation. 4. Replacement of calcium ions by strontium or barium ions led to an augmentation or reduction, respectively, of the 'staircase' effect, relative to the effect in calcium-containing solutions. Barium ions were found to greatly increase the slow inward channel 'recovery' time. 5. The results suggest that calcium influx into amphibian atrial fibres contributes to the regulation of the slow inward conductance mechanism. Progressively increasing currents may underlie positive tension staircases.

Animals↗
PubMed1981

Voltage-dependent potentiation of the slow inward current in frog atrium.

1. Slow inward currents, isi, were measured using a double sucrose-gap voltage-clamp technique during experiments involving different depolarization protocols. 2. Following short rest periods, repetitive stimulation gave rise to slow inward currents which changed progressively in a voltage-dependent manner. Small voltage depolarizations gave rise to initial small decreases in current (negative 'staircase'). The current usually then showed a secondary increase but still remained, in most cases, below the control amplitude. Larger depolarizations produced increasingly larger and more rapidly rising positive current 'staircases'. 3. The amount of increase in current magnitude during repetitive depolarization was more strongly dependent on the size of the voltage step than on the amplitude of the initial current. 4. Twin-pulse experiments having a fixed interval between pulses (usually 1.0 sec), showed that 'test' pulses produced more slow inward current than preceding 'conditioning' depolarizations. The augmentation was larger following conditioning pulses of longer duration. Current augmentation was larger during 'staircase' obtained with longer pulses. 5. Following constant duration 'conditioning' depolarizations, varying the interpulse interval showed that the slow inward current flowing during the 'test' pulse could be augmented following intervals of as long as 6-8 sec. 6. Small pre-pulses also augmented the slow inward currents obtained in response to 'tet' pulses. 7. Experiments in calcium-free solutions (with EGTA) showed qualitatively similar 'staircase' effects and current augmentation following preceding depolarizations. 8. Experiments in which sodium was replaced by lithium gave rise to larger slow inward currents. The 'staircase' for such currents developed in a similar manner to that seen under control conditions. 9. It is concluded that slow inward current augmentation is produced by membrane depolarization in a fashion which is at least partially independent of calcium or sodium ion influx.

Animals↗
PubMed1980

The contribution of potassium accumulation to outward currents in frog atrium.

1. Voltage-clamp experiments on frog atrial muscle were designed to distinguish effects due to K accumulation in extracellular spaces from those due to activation of K conductance mechanisms in the membrane. 2. The set of instantaneous current-voltage relations obtained at various external K concentrations following depolarization to about -10 mV for several seconds was found to be quite different from that obtained before the depolarization. Hence the process of increasing the extracellular K concentration cannot account for all the time-dependent changes in outward current during depolarization. 3. Although the instantaneous current-voltage relations obtained at different values of external K concentration before prolonged depolarization show the cross-over phenomenon (Noble, 1965), those obtained at the end of the depolarization did not show this feature. It is concluded that the current-voltage relations for the channels conducting the time-dependent K current do not show cross-over. 4. These results were used to construct a model involving both K activation and K accumulation. This model successfully reproduces the appearance of a very slow component in outward current decay tails which, when subtracted by semi-exponential curve-stripping leaves a component with the real time constant of conductance change. The model does not however reproduce the appearance of a fast decaying component without adding a second conductance mechanism, or assuming non-exponential decay of a single conductance mechanism. 5. It is therefore suggested that i chi, fast is not a perturbation of i chi, slow or of iK1 by the process of K accumulation. This conclusion is reinforced by the results of experiments showing that the relative magnitude of i chi, fast is not greatly changed by substantially increasing the external K concentration in order to reduce the proportionate effect of K accumulation on the K concentration.

Animals↗
PubMed1979

Cardiac pacemaker oscillation and its modulation by autonomic transmitters.

1. A scheme is presented which summarizes the activation and deactivation of the membrane currents which underlie pacemaking in the natural pacemaker of the heart. 2. Experimental evidence (mostly obtained using the voltage-clamp technique) for the properties of the time-dependent membrane currents in pacemaking tissue of the frog and the rabbit is discussed. 3. The mode of the inhibitory action of acetylcholine on pacemaker cells is considered. In the amphibian pacemaker cell, acetylcholine probably reduces slow inward current (as it certainly does in amphibian atrium) but in mammalian sino-atrial node it seems that such action, if present at all, is much less marked. In the pacemakers of both amphibian and mammal, acetylcholine greatly increases outward potassium current and there is recent evidence that it may do so by opening up a special acetylcholine-activated potassium channel. 4. Adrenaline greatly increases the slow inward current in pacemaker as in other cardiac tissues. This increase, together with (in mammal at least) an increased change of an additional pacemaking current, overrides an adrenaline-induced increase in outward current and leads to acceleration of the pacemaking rate. 5. The Appendix contains a brief consideration of the experimental and theoretical basis for the method of exponential separation of outward current components in the presence of the extracellular potassium accumulation that inevitably accompanies the flow of outward membrane current.

Acetylcholine↗