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Biomedical subjects

J Diamond

Publications and source records attributed to J Diamond.

At least 181 records · Page 10Linked to original sources
PubMed1983

Comparison of the effects of forskolin and isoproterenol on cyclic AMP levels and tension in bovine coronary artery.

The effects of isoproterenol and forskolin on cyclic AMP levels and tension were compared in helical strips of bovine coronary artery. Both compounds produced time- and dose-dependent increases in cyclic AMP levels and both compounds relaxed potassium-contracted arteries. However, in contrast to the results with isoproterenol, cyclic AMP elevation and relaxation were not well correlated at lower concentrations of forskolin. For example, 0.1 microM forskolin increased cyclic AMP levels in the arteries by approximately 5.5-fold but did not relax the muscles. A smaller elevation of cyclic AMP produced by 1.0 microM isoproterenol, on the other hand, was accompanied by an almost complete relaxation of the arteries. These results suggest that either cyclic AMP is not responsible for the relaxation caused by these agents, or some form of functional compartmentalization of cyclic AMP exists in this tissue.

Animals↗
PubMed1983

Peripheral hepatic artery embolization for primary and secondary hepatic neoplasms.

Eighteen patients underwent peripheral arterial embolization with Gelfoam powder for treatment of primary or metastatic hepatic neoplasms. Except for two cases in which the patients could not undergo long-term arterial infusion, all cases were treatment failures from intravenous chemotherapy, intra-arterial chemotherapy, or, in some cases, intra-arterial chemotherapy plus radiation therapy. Fourteen patients had good symptomatic relief from the procedure. Four of these patients are alive at 3, 5, 6, and 18 months following the procedure. Four patients died within 2 weeks following embolization, three of progression of disease and one of aspiration pneumonia. Of the patients showing symptomatic relief, 10 died of progression of cancer 2 to 14 months following embolization, with a median survival of 5 months. Based on the results in this small group of patients, it would seem that transcatheter hepatic dearterialization is often successful palliative therapy in patients who are not responsive to traditional therapies. Because of the low procedural morbidity, transcatheter embolization is superior to surgical dearterialization.

Carcinoma, Hepatocellular↗
PubMed1983

Lack of correlation between cyclic GMP elevation and relaxation of nonvascular smooth muscle by nitroglycerin, nitroprusside, hydroxylamine and sodium azide.

Recent reports have suggested that the smooth muscle relaxant effects of drugs such as nitroprusside and nitroglycerin are mediated by increases in tissue levels of cyclic GMP. This hypothesis was examined by comparing the effects of nitroprusside, nitroglycerin, hydroxylamine and sodium azide on tension and cyclic GMP levels in rat vas deferens, rat myometrium and guinea-pig taenia coli. All four of the agents were capable of increasing cyclic GMP levels in these tissues but there did not appear to be a good correlation between cyclic GMP elevation and muscle relaxation in any of the tissues studied. For example, nitroprusside markedly elevated cyclic GMP levels in rat vas deferens and myometrium but had no relaxant effect on either tissue. Nitroglycerin was less effective than nitroprusside in elevating cyclic GMP levels, but was an effective relaxant in both tissues. Significant increases in myometrial cyclic GMP were seen with 0.1, 1 and 5 mM concentrations of hydroxylamine but only the highest concentration had a definite relaxant effect on the muscles. A similar concentration of nitroprusside produced a greater elevation of cyclic GMP than did hydroxylamine, but had no relaxant effect in this preparation. In guinea-pig taenia coli, significant increases in cyclic GMP levels were obtained with concentrations of sodium azide and hydroxylamine which had no effect on the contractile activity of the preparations. These results, together with previous results from this laboratory, suggest that the relaxant effects of this group of drugs in rat vas deferens, rat myometrium and guinea-pig taenia coli are not mediated by increases in tissue levels of cyclic GMP. Further experiments are necessary to determine whether a causal relationship exists between cyclic GMP elevation and relaxation in other types of smooth muscle.

Animals↗
PubMed1983

Possible role for cyclic GMP in endothelium-dependent relaxation of rabbit aorta by acetylcholine. Comparison with nitroglycerin.

A possible role for cyclic GMP as a mediator of the endothelium-dependent relaxation of rabbit aorta by acetylcholine has been investigated using rabbit aortic rings with and without intact endothelium. In the presence of intact endothelial cells, acetylcholine caused marked increases in tissue levels of cyclic GMP accompanied by relaxation of the muscles. In aortic rings from which the endothelium had been removed, acetylcholine caused neither cyclic GMP elevation nor relaxation of the muscles. Acetylcholine-induced relaxation and cyclic GMP elevation in preparations with intact endothelium were both blocked by atropine. Reasonably good temporal and dose-response correlations between cyclic GMP elevation and relaxation were obtained with acetylcholine. Thus, although a causal relationship has not been definitely established, these results are consistent with the proposed role for cyclic GMP as a mediator of the endothelium-dependent relaxation of rabbit aorta by acetylcholine. In contrast to the results with acetylcholine, elevation of cyclic GMP and relaxation of aortic rings by nitroglycerin were not dependent on the presence of endothelial cells. Lower doses of nitroglycerin relaxed the muscles without elevating cyclic GMP levels. At higher concentrations of nitroglycerin, greater relaxation was obtained for a given degree of cyclic GMP elevation than was the case with acetylcholine. These results suggest that at least part of nitroglycerin's relaxant effect in this tissue is independent of cyclic GMP elevation.

Acetylcholine↗
PubMed1982

Effect of species pool size on species occurrence frequencies: Musical chairs on islands.

If species interactions affect species distributions, then species occurrence frequencies (nu(i)), defined as the fraction of an archipelago's islands that species i inhabits, should vary with species pool size. A "natural experiment" approximating this test is provided by the Bismarck, Solomon, and New Hebrides archipelagoes, whose bird species pools decrease in that order, the species of each archipelago being mostly a subset of those of the next richer archipelago. The average nu for an archipelago's species decreases with archipelago pool size. In the archipelago with the largest pool, most species are on few islands and few species are on most islands, whereas the reverse is true in the archipelago with the smallest pool. For species shared between two or more archipelagoes, nu(i) decreases with pool size or number of species in the same guild. These interarchipelagal differences in nu(i) or average nu reflect differences in level of interspecific competition, which reduces nus in species-rich archipelagoes in two ways: usually, by reducing a species' incidence on small islands and restricting the species to larger islands; less often (for so-called supertramps), by restricting a species to small islands.

Journal Article↗
PubMed1981

Regenerating axons reclaim sensory targets from collateral nerve sprouts.

There is a critical period for the sprouting of intact low-threshold mechanosensory cutaneous nerves in rats; functional invasion of adjacent denervated skin does not occur in animals older than about 20 days of age, and it is largely confined to denervated skin within the "domain" of the parent dermatome. These nerves can regenerate readily in the adult, however, and such regenerating nerves do not respect domain borders; moreover, they functionally displace endings of intact nerves that earlier had sprouted into denervated skin.

Aging↗
PubMed1981

High-K+-induced inhibition of cAMP accumulation in smooth muscle.

This study examines a possibility that high-K+ depolarization induced inhibition of cAMP accumulation by beta-adrenoceptor stimulation (observed in our previous studies) is mediated by depolarization induced release of acetylcholine. Rat uterine strips were depolarized by high-K+ solution with or without atropine. Isoproterenol produced similar degrees of relaxation and increases in cAMP levels in depolarized smooth muscle with or without atropine. It is suggested that the release, if any, of acetylcholine from smooth muscle depolarization is not the primary cause of the observed inhibition of cAMP accumulation.

Acetylcholine↗
PubMed1981

Merkel cells as targets of the mechanosensory nerves in salamander skin.

Previous investigations showed that the morphological basis of the low-threshold rapidly adapting mechanoreceptors in the salamander skin is neurite-Merkel cell complex located in the epidermis. We have now examined whether sensory nerves are required for the appearance of Merkel cells, and whether these cells act as specific targets for ingrowing sensory axons. Electronmicroscopic examination of denervated skin shows that Merkel cells survive in normal density and appearance in the epidermis for at least six months without nerves. In addition, mechanosensory function of such skin is restored when the skin become reinnervated either by collaterally sprouting (intact) nerves or by regenerating ones, and Merkel cells are then found to have nerve terminals associated with them. These experiments suggest that Merkel cells do act as targets for ingrowing nerves in these circumstances. Further experiments were done on skin that had regenerated in the total absence of any innervation to the limb; such new skin contained nerve-free Merkel cells that were normal in appearance, density and location. When nerves were allowed to innervate this new skin the sensory axons grew to the "new" Merkel cells and established typical neurite-Merkel cell complexes, and normal mechanosensory function. Since the new skin had developed without nerves, the sensory axons were not following "old" pathways to the Merkel cells. We conclude that the Merkel cells are the true targets for the mechanosensory axons; these cells attract the sensory axons to them and/or contain specific markers that allow the ingrowing axons to recognize them. Once a Merkel cell becomes innervated it loses this "target cell" quality. In addition, mechanosensory function of the sensory endings appears to occur only when the endings have developed a morphological association with a Merkel cell.

Animals↗
PubMed1981

Competitive reinnervation of salamander skin by regenerating and intact mechanosensory nerves.

We have investigated in the salamander the possibility that regenerating mechanosensory nerves might prefer the epidermal Merkel cells (their specific targets) that are located within their segmental domain to those within a "foreign" domain. Since regerating nerves cross domain boundaries with no evidence of the marked delay exhibited by intact sprouting nerves, we examined situations in which the regenerating axons of one segmental nerve were effectively in equal competition for denervated skin with those of another segmental nerve. Additionally, we investigated whether there were differences between regenerating axons and intact sprouting axons of the same segmental nerve, in their ability to innervate available skin both inside and outside the parent domain. No preference was detected of any type of nerve, regenerating or intact, for particular skin regions, or for Merkel cells as indicated by the numbers of mechanosensory thresholds of the touch spots that developed in reinnervated skin. Neither was there any indicating of displacement of "foreign" nerves from a particular region by appropriate axons. When regenerating and intact (sprouting) axons invaded denervated skin more or less simultaneously, the former appeared to have a slight advantage since a significantly greater proportion of skin was innervated by regenerated fibres. With this one exception, all the results were explained most simply by assuming that the axon that first arrives at a denervated Merkel cell establishes a permanent association with that cell and at the same time causes it to lose its "target character" for other axons.

Ambystoma↗
PubMed1981

Relationship between contraction and cyclic GMP levels of guinea pig taenia coli.

The relationship between isometric tension and the increase in cyclic GMP level associated with the initial phase of drug-induced contraction of taenia coli was studied. Maximal contraction induced by 100 micrometers carbachol or 124 mM KCl occurred in 30 sec and was associated with an increase in cyclic GMP levels of at least ten fold. However, 100 micrometers serotonin or low concentrations of carbachol (30 microM) produced nearly maximal contraction but only 10--20% of the maximal elevation in cyclic GMP induced by high concentrations of KCl. Furthermore, in the presence of a low concentration of Ca2+, or verapamil, both 124 mM KCl and 100 micrometers carbachol increased cyclic GMP with little elevation in isometric tension. Thus, large contractions were obtained with only small increases in cyclic GMP, and under other conditions, large increases in cyclic GMP were obtained with little increase in isometric tension. The results suggest that the initial increase in cyclic GMP level caused by these agents is not directly dependent on Ca2+ in the cellular pool containing the contractile proteins.

Animals↗
PubMed1980

Effects of hydralazine and verapamil on phosphorylase activity and guanosine cyclic 3',5'-monophosphate levels in guinea-pig taenia coli.

1 The roles of guanosine cyclic 3',5'-monophosphate (cyclic GMP) and calcium in the relaxation produced by hydralazine and verapamil in potassium-depolarized guinea-pig taenia coli have been investigated.2 Depolarization of isolated strips of guinea-pig taenia coli by 124 mM KCl caused sustained contractures and increases in tissue levels of cyclic GMP.3 The KCl-induced increases in cyclic GMP levels appeared to be calcium dependent. No increases in cyclic GMP levels were seen in strips of taenia coli depolarized in the absence of calcium. Readdition of calcium to the depolarizing solution contracted the muscles and increased cyclic GMP levels. When calcium was removed from the depolarizing solution during the sustained, tonic phase of a KCl-induced contracture, both tension and cyclic GMP levels returned to control values.4 Administration of 50 muM verapamil to KCl-contracted muscles completely relaxed the muscles and caused cyclic GMP levels to return to control values within 14 min. Hydralazine, 2 mM, on the other hand, relaxed the depolarized muscles without lowering cyclic GMP levels. No significant changes in cyclic AMP levels were seen in any of these experiments.5 Similar results were obtained in an analogous series of experiments in which glycogen phosphorylase activity was measured instead of cyclic GMP levels. Activation of phosphorylase during contractions of guinea-pig taenia coli had previously been reported to be a calcium-dependent phenomenon.6 It was concluded that increases in tissue levels of cyclic GMP (or of cyclic AMP) were not responsible for the relaxant effects of hydralazine or verapamil in these experiments. It was also suggested, based on our results, that verapamil exerted its relaxant effects in the depolarized taenia coli by lowering cytoplasmic calcium levels, whereas hydralazine relaxed the depolarized muscles without lowering intracellular calcium activity.

Animals↗