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R M Morgan

Publications and source records attributed to R M Morgan.

36 records · Page 2Linked to original sources

Ca2+ ion sequestration by guinea-pig tracheal cartilage: its influence on trachealis reactivity to KCl.

1. The contractile response of guinea-pig isolated trachealis to KCl has been studied in the presence and absence of cartilage. 2. Dissection of cartilage from the trachealis resulted in both a rightward displacement of the concentration-response curve to KCl (EC50 value: intact strip, 26.9 +/- 3.7 mM n = 5; dissected strip, 38.7 +/- 2.6 mM n = 5; P less than 0.05), and a reduction in the contractile response to KCl (30 mM) observed in a nominally Ca(2+)-free medium. 3. Removal of cartilage from the trachealis did not alter the responsiveness of the tissue to CaCl2 (2.5 mM) when added to K+ depolarized tissues. 4. Muscle-denuded cartilage rings were prepared by surgical removal of the trachealis muscle. Autoradiographic studies, and a direct comparison of Ca2+ (2.5 mM) uptake with that of sorbitol (2.5 mM) showed that cartilage per se had a high capacity to accumulate Ca2+ ions by a process which was resistant to iodoacetate (100 microM), diflunisal (100 microM) and boiling. 5. The uptake of 45Ca into isolated cartilage was unaltered by the addition of orthovanadate (500 microM), verapamil (10 microM), diltiazem (10 microM) or Bay K 8644 (10 microM), but was significantly reduced (P less than 0.05) in the presence of LaCl3 (1-10 mM). 6. We conclude, like previous studies, that cartilage may supply a pool of Ca2+ ions to airway smooth muscle during the generation of tension in a noninally Ca(2+)-free medium, and that LaCl3 may provide an experimental tool to elucidate further the role of non-muscle Ca(2+)-depots in smooth muscle contraction.

Animals↗

Bay K 8644, modifier of calcium transport and energy metabolism in rat heart mitochondria: a new intracellular site of action.

1. The dihydropyridine Ca2+ channel agonist Bay K 8644 (10-200 microM) produced a concentration-dependent increase in State 4 respiration in the rat heart mitochondria with the highest concentration (200 microM) increasing the rate from 33.1 +/- 0.7 to 187.0 +/- 13.3 ng atoms O2 consumed min-1 mg-1 protein. 2. Bay K 8644 (200 microM) reduced State 3 respiration from 247.2 +/- 11.7 to 174.4 +/- 0.06 ng atoms O2 min-1 mg-1 protein, reduced the respiratory control index (RCI) from 5.3 +/- 0.45 to 1.1 +/- 0.03 and reduced the ADP:O ratio from 2.75 +/- 0.03 to 1.3 +/- 0.15. 3. A similar, but smaller, stimulation of State 4 respiration was seen with nitrendipine (25-200 microM), the rate increasing from 22.6 +/- 1.0 to 33.1 +/- 1.8 ng atoms O2 consumed min-1 mg-1 protein in the presence of 200 microM nitrendipine. 4. Bay K 8644 (10-60 microM) increased the total Ca2+ uptake into rat heart mitochondria, the total increasing from 248.8 +/- 8.4 to 406.9 +/- 17.6 ng Ca2+ mg-1 protein at 60 microM Bay K 8644 (EC50 = 18.9 +/- 1.4 microM). 5. Bay K 8644 (10-60 microM) produced a concentration-dependent reduction in the Ca2+ influx rate (IC50 = 52.5 +/- 2.8 microM). Similar effects were seen with (+)-Bay K 8644 and (-)-Bay K 8644. 6. Nitrendipine (40-120 microM) stimulated Ca2+ efflux from mitochondria preloaded with the ion; the efflux rate increasing from 2.9 +/- 0.05 to 114.2 +/- 6.2 nmol Ca2+ min-1 mg-1 protein (EC50 = 57.3 +/- 1.3 microM). 7. These data indicate dihydropyridine-induced changes in the activity of the mitochondrial Na+/Ca2 . antiporter pathway; nitrendipine causing stimulation and Bay K 8644 causing inhibition.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Determination of the extent of ischemic damage and the effect of the calcium antagonist, verapamil following coronary artery ligation in the rat.

Apart from pharmacological interventions, four methods can be used to induce myocardial damage in the isolated, perfused heart. These are (i) total global ischemia, where perfusion is stopped completely; (ii) partial ischemia where perfusion is restricted; (iii) regional ischemia, produced by occlusion of the coronary circulation, and (v) hypoxia where the oxygenated buffer is replaced with a buffer bubbled with nitrogen. Using rat hearts, coronary artery occlusion was found to have potential as a screening device for antiischemic compounds. In these studies 45Ca uptake and enzyme release were found to increase with ligation time. The inclusion of the Ca2+ antagonist verapamil (0.01 to 1 microM) resulted in a concentration-dependent inhibition of 45Ca uptake (IC50 = 68 nM); however the proportion of tissue damaged remained unchanged. Similar findings were obtained in the presence of the dihydropyridine Ca2+ antagonist nicardipine (0.1 or 1 microM). Measurement of enzyme release during the reperfusion period confirmed significant correlations between levels of either lactate dehydrogenase (LDH) or creatine kinase (CK) and 45Ca uptake. Studies involving LDH show that cation uptake precedes enzyme release (r = 0.93; p = less than 0.001).

Animals↗

Palmitoyl carnitine: an endogenous promotor of calcium efflux from rat heart mitochondria.

The effects of the fatty acid ester palmitoyl carnitine (PC) on mitochondrial Ca2+ handling and ATP synthesis are described. At low concentrations (5-40 microM) PC was found to produce changes in mitochondrial Ca2+ handling, the most significant effect (P less than 0.05) being the promotion of Ca2+ efflux (EC25 = 1.19 +/- 0.11 microM). Studies on mitochondrial substrate oxidation in the presence of either glutamate plus malate, or succinate, confirmed the ability of PC (10-100 microM) to cause loss of respiratory control as shown by reductions in the Respiratory Control Index for each substrate. It was concluded that the effect of PC on Ca2+ transport was due to a direct action on the Na+-Ca2+ antiporter system, whilst the effect on respiration was due to an uncoupling action.

Animals↗

The effects of cadmium on succinate and NADH-linked substrate oxidations in rat hepatic mitochondria.

Low concentrations of cadmium (3.3-40 microM) inhibited State 3 NADH-linked respiration in rat hepatic mitochondria, but failed to release oligomycin (1 microgram) inhibited State 3 respiration, or to significantly change the State 4 rate. In the presence of succinate, 40 microM cadmium inhibited State 3 respiration by 89%, while concentrations between 3.3 and 13.3 microM stimulated State 4 respiration. Higher concentrations caused marked inhibition. In the presence of succinate, cadmium released oligomycin inhibited State 3 respiration. Cadmium (0.001-1.0 mM) did not stimulate mitochondrial ATPase activity or inhibit ferricyanide reduction, but stimulated NAD+ linked mitochondrial dehydrogenase activities and NADH oxidation. These results indicate that cadmium interacts with either the NADH dehydrogenase complex or other NADH-dependent enzymes and not solely by an uncoupling action.

Adenosine Triphosphate↗

Cadmium content in selected rat tissues following treatments with cadmium chloride and/or gamma radiation.

This study was conducted to determine concentrations of cadmium (Cd) in various rat tissues; radiation effectiveness on Cd concentrations in rat tissues; and Cd effectiveness when radiation was applied as the second insult. Animals were subjected to Cd over a 29-day period and on Day 30 were exposed to an acute dose of 60Co gamma-ray. Rats were killed on Day 1, 7, or 21 following irradiation. Cd concentrations were determined by flame spectroscopy. Rats injected with Cd alone or Cd in combination with radiation showed a dose-dependent accumulation and retention of the metal in the liver and kidney over the intervals to sacrifice. Significantly smaller amounts of the metal were seen in the spleen, intestine, stomach, heart, testis, lung, blood, brain, and muscle. Generally, Cd did not afford protection against radiation in the tissues studied. Radiation, when used singly or as a coinsult with Cd, did not significantly alter the concentrations of Cd in any of the tissues studied except the heart, in which it contributed to the clearance of Cd. No synergistic or antagonistic effects were observed between Cd and ionizing radiation in any of the other tissues studied.

Animals↗

Interaction of cadmium chloride and gamma irradiation on blood parameters of the young adult rat.

Two hundred and sixteen male Sprague-Dawley (S-D) rats, 80 +/- 5 days old and weighing 220-250 g each, were assigned at random to nine groups of 24 rats each. Rats were injected with cadmium (Cd) intraperitoneally every 3 days for 29 days for a total of nine injections. Injections doses were 0, 1.0, or 2.5 mg Cd kg-1 body wt. Twenty-four hours after the last Cd injection (Day 30), each rat received an acute whole-body 60Co gamma radiation dose of 0, 3.62, or 5.43 Gray (Gy) at a dose rate of 33.04 Gy min-1. The irradiated groups exhibited significant decreases in the total number of white blood cells (WBCs) and the percentage of lymphocytes. Significant increases were seen in the percentage of polyneutrophils, serum triacylglycerols (TG), serum iron, and serum lactate dehydrogenase (LDH). Cd-treated groups had increased total WBCs, percentage of polyneutrophils, and serum glutamate oxaloacetate transaminase (SGOT). Significant decreases were observed in the percentage of lymphocytes, hemoglobin, total number of red blood cells (RBCs), and hematocrit. In the co-insult, significant decreases were seen in the total number of WBCs and RBCs, the percentage of lymphocytes, hemoglobin, and hematocrit. Significant increases were observed in the percentage of polyneutrophils and serum iron. In general, Cd acted as a debilitator which enhanced the overall effect of ionizing radiation when applied as the second insult. On the other hand, Cd also provided protection against radiation; that is, some parameters such as total WBCs, serum TG, serum iron, and serum LDH were not as adversely affected by the co-insult as when radiation only was used. The mechanism of this Cd anomaly is not known.

Analysis of Variance↗

Sediment fingerprints: a forensic technique using quartz sand grains.

The analyses of 738 soil and sediment samples taken during the investigation of 20 forensic cases are combined in a database for retrospective comparisons. Quartz sand grain surface textures are combined into grain types which are analysed at one of five orders of classification. This classification also provides frequency data on the number of grain types found in a sample, the individuality of the quartz grain type assemblages and quartz grain type ratios. The technique, developed primarily as an exclusion mechanism, suggests possibilities, in some circumstances, that significant interpretations can be achieved at different orders of classification. The technique provides excellent exclusionary results and, when combined with other independent lines of analysis, is a powerful tool in forensic interpretation because it uses quartz as its discriminatory mineral. The technique also highlights the potential for computer image recognition analysis.

Dermatoglyphics↗

Serum vitamin A and E concentrations in pediatric total parenteral nutrition patients.

There is uncertainty as to optimal doses of fat soluble vitamins required by pediatric total parenteral nutrition (TPN) patients. We compared serum vitamin A (A) and E (E) concentrations analyzed by HPLC in chronic (greater than 2 weeks) TPN patients aged 1 month to 12 years to values obtained in out-patient surgery patients of the same age. TPN patients received 1500 micrograms of retinol and 2.5 IU of E as alpha-tocopheryl acetate (2.5 ml LyphoMed Multi Vitamin Concentrate). These doses were 214% of the recommended dose of A and 36% for E. Oral intake was minimal in most patients. The results of our study revealed a mean serum A level for TPN patients (N = 29) of 26.0 +/- 15.0 (SD) micrograms/dl vs 25.0 +/- 10.0 (SD) micrograms/dl in controls (N = 52). Mean serum E was 0.63 +/- 0.24 (SD) mg/dl vs 0.89 +/- 0.31 (SD) mg/dl for TPN patients and controls, respectively. There was no consistent trend related to duration of TPN for 23 patients with serial values. Seven (24%) TPN patients had serum A greater than mean + 2 SD of control (p less than 0.01). No values were less than mean - 2 SD. Infants on TPN had a significantly lower mean serum A (22.3 +/- 10.9 micrograms/dl) than TPN patients greater than 1 year of age (34.1 +/- 16.0 micrograms/dl; p less than 0.001). Fifty-two percent of TPN patients vs 26% of control had serum A less than 20 micrograms/dl (p greater than 0.1). For E, one patient had a high value and two patients low values relative to control.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Multi-technique comparison of source and primary transfer soil samples: an experimental investigation by D Croft and K Pye. A comment.

The Croft and Pye paper has a story to tell about the differentiation capabilities of four analytical techniques. It is not however, the whole story. This may be due in part to the lack of reproducibility in the generation of results, and also in the effort to match soil samples and thus infer that the results provide stronger conclusions than is possible to make with this sort of analysis. More research must be done to establish in what instances these techniques and others provide reliable, reproducible, representative and accurate results, and in what capacity such results can be presented. As they stand, the results from this paper should be treated with great caution and not extrapolated to any other forensic case work until greater reliability of these and other techniques has been established.

Comment↗