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M L Stefano

Publications and source records attributed to M L Stefano.

5 recordsLinked to original sources
PubMed1996

Morphine stimulates nitric oxide release from invertebrate microglia.

Morphine stimulates nitric oxide (NO) release in human endothelial cells. To determine whether this mechanism also occurs in invertebrates, the mussel Mytilus edulis was studied. Exposure of excised ganglia to morphine for 24 h resulted in a significant dose-dependent decrease in microglial egress that was naloxone sensitive. In coincubating the excised ganglia with morphine and the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), an increase in microglial egress was observed, suggesting that morphine may stimulate microglia to release NO. Morphine exposure to these cells in vitro resulted in NO release (39.4 +/- 4.9 nM), a phenomenon found to be naloxone sensitive (10(-6) M; NO level = 5.9 +/- 2.6 nM) and L-NAME sensitive (10(-4) M; NO level = 2.8 +/- 1.8 nM). Opioid peptides did not stimulate NO release, indicating that the process was mediated by the opiate alkaloid selective mu 3 receptor. Coincubation of microglia with L-arginine or the superoxide scavenger, superoxide dismutase, resulted in significantly higher NO levels observed following morphine stimulation. Taken together, the data demonstrate that morphine can stimulate NO release in cells obtained from an invertebrate that represents an animal 500 million years divergent in evolution from man, underscoring the significance of this process and further substantiating the critical importance of morphine as a naturally occurring signal molecule.

Animals↗
PubMed1994

Microglia in invertebrate ganglia.

The results of this study lend strong support to the concept of the existence in insects and molluscs of a distinctive class of neuroglial cells comparable to vertebrate microglia. The evidence presented is as valid as that used in reference to the separate status of vertebrate microglia--i.e., the demonstration of a close structural and functional relationship of these cells with cells of the immune system. As in vertebrates, the excision of ganglia from three invertebrate species (the molluscs Planorbarius corneus and Mytilus edulis and the insect Leucophaea maderae) and their maintenance in incubation media led to an exodus of small cells and their accumulation in the culture dish. During this process, they underwent conformational changes from stellate to rounded, and then to more or less ameboid, comparable to those indicative of the process of activation in the animals' immunocytes. Functional characteristics which these translocated microglia-like cells share with immunocytes are motility, phagocytotic activity, and adherence to the culture dish. Furthermore, the two cells have certain biochemical features in common--e.g., the presence of certain cytokines and (at least in Planorbarius) that of corticotropin. An additional phenomenon of particular interest for the classification of microglial elements is their response to morphine. At 10(-6) M, this drug decreases not only the number of cells emerging from the excised ganglia but also the degree of their transformation to the "active" ameboid form. This dose-dependent and naloxone-sensitive effect of morphine on microglial cells parallels that on activated immunocytes of the same species. Corresponding results demonstrating an inhibitory effect of morphine on mobilized microglial cells of the frog Rana pipiens indicate that this relationship between the two cell types under consideration also exists in vertebrates. Binding and displacement experiments with membrane homogenates of microglial cells as well as immunocytes of Mytilus have shown that the effects of morphine on both cell types are mediated by the same special opiate receptor (mu 3).

Animals↗
PubMed1993

Left ventricular systolic and diastolic function measurements using an ambulatory radionuclide monitor: effects of different time averaging on accuracy.

The accuracy of an ambulatory radionuclide detector (VEST) for left ventricular systolic (ejection fraction, EF) and diastolic (peak filling rate, PFR) measurements was assessed at different time averaging of the nuclear and electrocardiographic data. Fifty-one patients, in a total of 67 studies, underwent equilibrium radionuclide angiography (RNA) immediately before a VEST study. VEST data were analyzed using single-beat analysis and different time averaging of 5, 10, 15, 30 and 60 sec. Agreement between VEST and RNA in estimating EF and PFR was evaluated by computing limits of agreement (LA). These were computed as 1.96 times the s.d. of the mean differences between the two methods, expressed in the same unit as EF and PFR. Differences between the two methods were plotted against their mean, allowing investigation of any possible relationship between measurement error and the true value (whose best estimate is the mean between the two methods). The entire statistical analysis was repeated at each different time averaging. LAs for EF measurement by VEST were -10.4:8.8 (single-beat analysis), -11.2:9.9 (5-sec averaging), -5.4:4.8 (10-sec averaging), -4.9:4.5 (15-sec averaging), -6.2:5.6 (30-sec averaging), -6.9:4.5 (60-sec averaging). Results indicate good agreement between VEST and RNA in measuring EF, at least for time averaging > or = 10 sec. LAs for PFR ranged from -0.6:0.6 (single beat) to -1.0:0.6 (60-sec averaging), which was considered a clinically acceptable agreement between VEST and RNA. No relationship between measurement error and true value was found either for EF and PFR.

Electrocardiography, Ambulatory↗