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Biomedical subjects

M L Mayer

Publications and source records attributed to M L Mayer.

100 records · Page 6Linked to original sources
PubMed1976

Management of the multiproblem seductive patient.

A seductive gesture by a patient towards a physician is not uncommon in clinical practice, and presents a variety of problems in maintenance of the doctor-patient relationship and management of the patient's medical problems. Medical, psychological, and social factors must be considered in resolving these problems. This Grand Rounds presents such a case and discusses alternative approaches to patient management and the role of other health professionals in the care of such patients.

Adult↗
PubMedDate not supplied

The role of hydrophobic interactions in binding of polyamines to non NMDA receptor ion channels.

Block of kainate subtype glutamate receptor channels by internal polyamines was analysed using outside out patches from HEK 293 cells transiently transfected with GluR6(Q). Tetramines with different numbers and spacing of methylene groups between NH2 groups produced biphasic rectification well fit by the Woodhull model for a weakly permeable ion channel blocker. Such analysis revealed an increase in binding energy of 611 cal M(-1) for each methylene group added over the range 6-12 (CH2), suggesting that a major component of block by polyamines involves hydrophobic binding. Isomers with the same number of CH2 groups but different spacing between NH2 groups showed similar affinity. Due to differences in pKa values for protonation of NH2 groups, the average charge on the tetramines studied would be expected to vary from 3.98 to 2.22 at physiological pH; despite this, the voltage dependence of block was similar for all tetramines tested, with a mean value for ztheta of 1.82, similar to values for polyamines with five or six NH2 groups. In contrast, for 1,3-propane diamine (DA3 ztheta 0.83), and the N-propyl- (ztheta 1.42) and N,N'-diethyl- (ztheta 1.37) analogues of DA3, there was an increase in the voltage dependence of block on addition of hydrophobic groups.

Cell Line↗
PubMedDate not supplied

Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones.

Acidic amino acids are putative excitatory synaptic transmitters, the ionic mechanism of which is not well understood. Recent studies with selective agonists and antagonists suggest that neurones of the mammalian central nervous system possess several different receptors for acidic amino acids, which in turn are coupled to separate conductance mechanisms. N-methyl-D-aspartic acid (NMDA) is a selective agonist for one of these receptors. The excitatory action of amino acids acting at NMDA receptors is remarkably sensitive to the membrane potential and it has been suggested that the NMDA receptor is coupled to a voltage-sensitive conductance. Recently, patch-clamp experiments have shown the voltage-dependent block by Mg2+ of current flow through ion channels activated by L-glutamate. We now show using voltage-clamp experiments on mouse spinal cord neurones that the voltage-sensitivity of NMDA action is greatly reduced on the withdrawal of physiological concentrations (approximately 1 mM) of Mg2+ from the extracellular fluid. This provides further evidence that Mg2+ blocks inward current flow through ion channels linked to NMDA receptors.

Animals↗
PubMedDate not supplied

NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones.

Excitatory amino acids act via receptor subtypes in the mammalian central nervous system (CNS). The receptor selectively activated by N-methyl-D-aspartic acid (NMDA) has been best characterized using voltage-clamp and single-channel recording; the results suggest that NMDA receptors gate channels that are permeable to Na+, K+ and other monovalent cations. Various experiments suggest that Ca2+ flux is also associated with the activation of excitatory amino-acid receptors on vertebrate neurones. Whether Ca2+ enters through voltage-dependent Ca2+ channels or through excitatory amino-acid-activated channels of one or more subtype is unclear. Mg2+ can be used to distinguish NMDA-receptor-activated channels from voltage-dependent Ca2+ channels, because at micromolar concentrations Mg2+ has little effect on voltage-dependent Ca2+ channels while it enters and blocks NMDA receptor channels. Marked differences in the potency of other divalent cations acting as Ca2+ channel blockers compared with their action as NMDA antagonists also distinguish the NMDA channel from voltage-sensitive Ca2+ channels. However, we now directly demonstrate that excitatory amino acids acting at NMDA receptors on spinal cord neurones increase the intracellular Ca2+ activity, measured using the indicator dye arsenazo III, and that this is the result of Ca2+ influx through NMDA receptor channels. Kainic acid (KA), which acts at another subtype of excitatory amino-acid receptor, was much less effective in triggering increases in intracellular free Ca2+.

Animals↗
PubMedDate not supplied

Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons.

NMDA (N-methyl-D-aspartate) receptors serve as modulators of synaptic transmission in the mammalian central nervous system (CNS) with both short-term and long-lasting effects. Divalent cations are pivotal in determining this behaviour in that Mg2+ blocks the ion channel in a voltage-dependent manner, and Ca2+ permeates NMDA channels. Zn2+ could also modulate neuronal excitability because it is present at high concentrations in brain, especially the synaptic vesicles of mossy fibers in the hippocampus and is released with neuronal activity. Both proconvulsant and depressant actions of Zn2+ have been reported. We have found that zinc is a potent non-competitive antagonist of NMDA responses on cultured hippocampal neurons. Unlike Mg2+, the effect of Zn2+ is not voltage-sensitive between -40 and +60 mV, suggesting that Zn2+ and Mg2+ act at distinct sites. In addition, we have found that Zn2+ antagonizes responses to the inhibitory transmitter GABA (gamma-aminobutyric acid). Our results provide evidence for an additional metal-binding site on the NMDA receptor channel, and suggest that Zn2+ may regulate both excitatory and inhibitory synaptic transmission in the hippocampus.

Animals↗
PubMedDate not supplied

Barriers to care among racial/ethnic groups under managed care.

We describe barriers to care reported by racial/ethnic groups and explore the extent to which barriers vary between persons enrolled in managed care and those in non-managed care plans, using data from the 1996 Medical Expenditure Panel Survey (MEPS). Most respondents expressed satisfaction with their care; however, a substantial percentage reported experiencing barriers. Minorities, particularly Hispanics and Asian Americans, were more likely than non-Hispanic whites were to report barriers. Managed care enrollees across racial/ethnic groups faced different types of barriers than non-managed care enrollees did. Although managed care enrollees were more likely to report having a usual source of care and greater continuity of care, they also reported more difficulties obtaining care and less satisfaction with their care.

Continuity of Patient Care↗