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R J Miller

Publications and source records attributed to R J Miller.

At least 19 recordsLinked to original sources
PubMed1992

Picosecond phase grating spectroscopy of hemoglobin and myoglobin: energetics and dynamics of global protein motion.

Phase grating spectroscopy has been used to follow the optically triggered tertiary structural changes of carboxymyoglobin (MbCO) and carboxyhemoglobin (HbCO). Probe wavelength and temperature dependencies have shown that the grating signal arises from nonthermal density changes induced by the protein structural changes. The material displaced through the protein structural changes leads to the excitation of coherent acoustic modes of the surrounding water. The coupling of the structural changes to the fluid hydrodynamics demonstrates that a global change in the protein structure is occurring in less than 30 ps. The global relaxation is on the same time scale as the local changes in structure in the vicinity of the heme pocket. The observed dynamics for global relaxation and correspondence between the local and global structural changes provides evidence for the involvement of collective modes in the propagation of the initial tertiary conformational changes. The energetics can also be derived from the acoustic signal. For MbCO, the photodissociation process is endothermic by 21 +/- 2 kcal/mol, which corresponds closely to the expected Fe-CO bond enthalpy. In contrast, HbCO dissipates approximately 10 kcal/mol more energy relative to myoglobin during its initial tertiary structural relaxation. The difference in energetics indicates that significantly more energy is stored in the hemoglobin structure and is believed to be related to the quaternary structure of hemoglobin not present in the monomeric form of myoglobin. These findings provide new insight into the biomechanics of conformational changes in proteins and lend support to theoretical models invoking stored strain energy as the driving force for large amplitude correlated motions.

Carboxyhemoglobin↗
PubMed1992

5-Hydroxytryptamine-3 receptors modulate synaptic activity in the rat nucleus tractus solitarius in vitro.

Whole-cell patch clamp recordings were made from neurons in the rat nucleus tractus solitarius (NTS) in transverse brainstem slices. 5-Hydroxytryptamine (5-HT, 100 microM) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-CH3-5-HT, 100 microM) depolarized 86% of NTS neurons at resting membrane potential (Vm). This response was resistant to tetrodotoxin (TTX) and Co2+ application. In addition, 2-CH3-5-HT (500 nM-100 microM) increased the amplitude and frequency of both excitatory and inhibitory spontaneous synaptic potentials. This effect was also TTX-resistant, but was abolished by Co2+. The effects of 2-CH3-5-HT on EPSPs and IPSPs evoked by electrical stimulation of the tractus solitarius (TS) were analyzed separately in the presence of bicuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. Concentrations of 2-CH3-5-HT between 500 nM and 1 microM decreased the amplitude of evoked EPSPs and IPSPs with similar potency. The selective 5-HT3 receptor antagonists ICS 205-930 (10 nM) and MDL 72222 (10 microM) reversibly blocked the effects of 2-CH3-5-HT at all doses examined. It is concluded that 5-HT3 receptors can mediate both pre- and postsynaptic responses in the NTS.

Animals↗
PubMed1992

Activation of endothelin receptors by sarafotoxin regulates Ca2+ homeostasis in cerebellar astrocytes.

We carried out experiments designed to investigate the effects of sarafotoxin-6B (SFTx) on [Ca2+]i in cerebellar astrocytes using the Ca2+ indicator fura-2. Both endothelin-1 and sarafotoxin-6B increased [Ca2+]i in individual cerebellar astrocytes in cell culture. The shape of the response was variable but usually consisted of an initial peak of [Ca2+]i followed by an extended plateau increase in [Ca2+]i. In Ca(2+)-free medium only the initial peak was observed. If Ca2+ was subsequently readmitted to the external medium a plateau was now formed. When external Ca2+ was removed during a plateau, [Ca2+]i rapidly declined; replacing the external Ca2+ reversed this decline. The plateau was also reversibly reduced by addition of Ni2+ (5 mM) to the external medium. Addition of 50 mM K+ produced a small increase in [Ca2+]i in most cells. This response was blocked by nimodipine. However, nimodipine only slightly blocked the plateau increase in [Ca2+]i that was formed following activation of endothelin receptors. Furthermore, perfusion of cells with 50 mM K+ during the plateau portion of a response to SFTx reduced [Ca2+]i. In some cells addition of a phorbol ester produced a sustained increase in [Ca2+]i that was blocked by nimodipine. In conclusion, activation of endothelin receptors by SFTx in cerebellar astrocytes produces both Ca2+ mobilization and Ca2+ influx. The pathway for Ca2+ influx is predominantly a non-voltage-dependent one, although some entry through a dihydropyridine-sensitive pathway also appears to occur. Furthermore, activation of protein kinase C in cerebellar astrocytes activates voltage-sensitive Ca2+ channels.

Animals↗
PubMed1992

The prevalence of carpal tunnel syndrome in patients with basal joint arthritis of the thumb.

Basal joint arthritis of the thumb and carpal tunnel syndrome are common conditions with an acknowledged coexistence. This article attempts to quantify the prevalence of carpal tunnel syndrome in patients with basal joint arthritis and to examine some of the etiologic factors that affect the coexistence of the two disorders. Of 246 patients who had surgery about the basal joint, 95 patients (39%) were identified by chart review as having carpal tunnel syndrome. Eleven of 122 remaining patients contacted had symptomatic carpal tunnel syndrome confirmed by nerve-conduction studies, bringing the total to 106 (43%). The prevalence was higher in worker's compensation patients and those with diabetes mellitus. The prevalence was lower in men than in women, and patients with inflammatory joint disease were at less risk than those with osteoarthritis. Given this high association, great care should be taken to diagnose or exclude coexistent carpal tunnel syndrome in patients scheduled for basal joint surgery so that, if present, it can be treated at the same time, diminishing the risk of postoperative morbidity and delayed symptoms.

Arthritis↗
PubMed1992

Inhibition of quantal transmitter release in the absence of calcium influx by a G protein-linked adenosine receptor at hippocampal synapses.

Spontaneous miniature excitatory postsynaptic currents (MEPSCs) were recorded by whole-cell voltage-clamp techniques in cultured rat hippocampal pyramidal neurons. The specific adenosine A1 receptor agonist cyclopentyladenosine (CPA) reduced the frequency of MEPSCs without affecting their amplitude distribution or kinetic properties. This action was blocked by pretreatment of the cells with pertussis toxin. In the presence of divalent cation Ca2+ channel blockers, CPA was still effective in reducing the frequency of MEPSCs. It was shown that this effect cannot be explained by changes in basal Ca2+ influx. These results suggest that neurotransmitters that produce presynaptic inhibition at hippocampal synapses utilize several mechanisms, one of which may involve inhibition of some component of the quantal release apparatus that occurs independently of inhibition of Ca2+ influx.

Adenosine↗
PubMed1992

Investigations into neuropeptide Y-mediated presynaptic inhibition in cultured hippocampal neurones of the rat.

1. We have examined the effects of neuropeptide Y (NPY) on synaptic transmission and [Ca2+]i signals in rat hippocampal neurones grown in culture. [Ca2+]i in individual neurones displayed frequent spontaneous fluctuations often resulting in an elevated plateau [Ca2+]i. These fluctuations were reduced by tetrodotoxin (1 microM) or combinations of the excitatory amino acid antagonists 6-cyano-7-dinitro-quinoxaline (CNQX) (10 microM) and aminophosphonovalerate (APV) (50 microM), indicating that they were the result of glutamatergic transmission occurring between hippocampal neurones. 2. [Ca2+]i fluctuations were also prevented by Ni2+ (200 microM), by the GABAB receptor agonist, baclofen (10 microM) and by NPY (100 nM) or Y2 receptor-selective NPY agonists. Following treatment of cells with pertussis toxin, NPY produced only a brief decrease in [Ca2+]i fluctuations which rapidly recovered. 3. Perfusion of hippocampal neurones with 50 mM K+ produced a large rapid increase in [Ca2+]i. This increase was slightly reduced by NPY or by a combination of CNQX and APV. The effects of CNQX/APV occluded those of NPY. NPY had no effect on Ba2+ currents measured in hippocampal neurones under whole cell voltage-clamp even in the presence of intracellular GTP-gamma-S. On the other hand, Ba2+ currents were reduced by both Cd2+ (200 microM) and baclofen (10 microM). 4. Current clamp recordings from hippocampal neurones demonstrated the occurrence of spontaneous e.p.s.ps and action potential firing which were accompanied by increases in [Ca2+]i. This spontaneous activity and the accompanying [Ca2+]i signals were prevented by application of NPY (100 nM). When hippocampal neurones were induced to fire trains of action potentials in the absence of synaptic transmission, these were accompanied by an increase in cell soma [Ca2+]j. NPY (100 nM) had no effect on these cell soma [Ca2+], signals. NPY (100 nM) also had no effect on inward currents generated in hippocampal neurones by micropipette application of glutamate (50 microM).5. Thus, NPY is able to abolish excitatory neurotransmission in hippocampal cultures through a pertussis toxin-sensitive mechanism. However, no effect of NPY on Ca2+ influx into the cell soma of these hippocampal neurones could be discerned. These results are consistent with a localized presynaptic inhibitory effect of NPY on glutamate release in hippocampal neurones in culture.

2-Amino-5-phosphonovalerate↗
PubMed1992

The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro.

1. Intracellular and whole-cell patch recordings were made from sixty-seven neurones located in the nucleus tractus solitarii (NTS) in transverse slices of rat brainstem. 2. Baclofen at concentrations of 2-20 microM caused hyperpolarization from normal resting membrane potentials (Vm). This response was associated with a decrease in input resistance (Rm) tested by current pulses in discontinuous current clamp mode when membrane potential was restored to control level by current injection. In single electrode discontinuous voltage clamp mode, baclofen at these concentrations caused a small (< 50 pA) outward current associated with increased membrane conductance measured by voltage steps from holding potentials (Vh) of -50 or -60 mV. Current-voltage relations at these Vhs and the results of varying Vh between -50 and -110 mV during responses to baclofen gave a reversal potential of -73 mV. The amplitudes of baclofen responses were related to K+ concentration tested by comparing responses in media containing 1-24 mM extracellular K+, indicating that postsynaptically baclofen acts via a K+ conductance. 3. These effects were still apparent in the presence of tetrodotoxin (which did not abolish all spontaneous synaptic activity) and also in medium containing a combination of Co2+, the excitatory amino acid antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and the GABAA antagonist bicuculline which blocked synaptic activity. 4. The amplitude and frequency of spontaneous postsynaptic potentials (spPSPs) and spontaneous postsynaptic currents (spPSCs) were reduced by baclofen at concentrations (1 microM or less) which had no effect on membrane potential or holding current in current or voltage clamp recordings respectively. 5. The amplitude of evoked excitatory (evEPSPs/evEPSCs) and inhibitory (evIPSPs/evIPSCs) synaptic events elicited by electrical stimulation in the vicinity of the tractus solitarius (TS) was reduced by low concentrations of baclofen (250 nM-1 microM) which did not produce discernible postsynaptic responses. 6. In order to examine the effects of baclofen on excitatory synaptic events without contamination with inhibitory events, stimulation of the TS was carried out in the presence of bicuculline. Conversely to investigate actions on purely inhibitory synaptic responses experiments were carried out with CNQX in the bathing solution. Inhibitory synaptic responses could still be evoked, presumably by stimulation of interneurones in the vicinity of the TS. IPSPs/IPSCs were more sensitive to baclofen than EPSPs/EPSCs. 7. The effects of baclofen on membrane potential or holding current and PSP/PSCs were antagonized by 2-hydroxysaclofen (400 microM) confirming that baclofen was acting at gamma-aminobutyric acid (GABA)B receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Role of metabotropic glutamate (ACPD) receptors at the parallel fiber-Purkinje cell synapse.

1. The role of metabotropic glutamate receptors at the parallel fiber (PF)-Purkinje cell synapse in cerebellum was studied by examining the actions of the active stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [1S,3R-ACPD (25-50 microM)] on fura-2-loaded, patch-clamped rat Purkinje cells in thin slices. 2. The bath application of 1S,3R-ACPD evoked a direct post-synaptic depolarization that readily desensitized during prolonged (> 1 min) applications of the drug. This depolarizing response to 1S,3R-ACPD differed from the slow depolarization to 1S,3R-ACPD observed in cortical neurons mediated via closure of potassium channels in that it was not associated with an obvious change in membrane conductance and was not blocked by external barium. Similarly, slow inward rectifier currents were not affected during the 1S,3R-ACPD-induced depolarization. 3. The direct depolarization induced by 1S,3R-ACPD was not mediated by N-methyl-D-aspartate (NMDA) or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid kainate (AMPA)-KA excitatory amino acid (EAA) receptor subtypes, because the response was not blocked in the presence of antagonists of these receptors. 4. The EAA antagonist L-2-amino-3-phosphonopropionic acid, which blocks 1S,3R-ACPD-induced inositide synthesis in other cell types, had no effect on the depolarizing response. 5. Fura-2 measurements of somatic [Ca2+]i revealed that [Ca2+]i was not elevated during the 1S,3R-ACPD-induced depolarization unless the cell fired calcium-dependent action potentials. 6. In addition to the direct depolarization induced by 1S,3R-ACPD, the amplitude of PF-evoked excitatory postsynaptic potentials (EPSPs) was profoundly and reversibly reduced. This effect was observed in all cells regardless of whether a direct depolarization was produced by 1S,3R-ACPD. This reduction of the PF EPSP generally preceded the onset of depolarizing responses, did not desensitize during prolonged applications of 1S,3R-ACPD, and was reversible. 7. The reversible reduction of the PF EPSP by 1S,3R-ACPD was not related to a postsynaptic blocking action of the drug, because responses of Purkinje cells to AMPA, an agonist of the EAA receptor subtype mediating the EPSP, were reversibly potentiated in the presence of 1S,3R-ACPD. 8. The nitric oxide synthesis promoter sodium nitroprusside (1-3 nM) had no effect on the amplitude of PF EPSP or the membrane properties of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

Interwoven threads: occupational therapy, feminism, and holistic health.

Occupational therapy is a predominantly female profession; 93% to 95% of occupational therapists are women. The implications and ramifications of this reality have seldom been directly addressed. In this article, beliefs about balance, activity, environment, and autonomy are explored from the perspectives of occupational therapy, feminism, holistic health, and medicine. The assertion that occupational therapy has more in common philosophically with feminism and holistic health than it does with medicine is supported. This awareness provides a new framework for examining current issues of concern to the profession, such as support for purposeful activity, existence outside the mainstream of power holders, and problems and powers inherent in being seen as a women's profession. Recommendations are made that occupational therapists commit more money and energy to encourage, facilitate, and support female leadership; develop innovative strategies for keeping members who take time out to raise families informed; support more holistic and feminist reorganization of work settings; instill awareness of these issues in our students; and address our strengths as a women's profession. All occupational therapists must also confront their own anti-women prejudice.

Curriculum↗
PubMed1992

Metabotropic glutamate receptors mediate excitatory transmission in the nucleus of the solitary tract.

Following microinjection into the nucleus tractus solitarius (NTS), the effects of glutamate on the baroreceptor reflex are poorly antagonized by kynurenic acid and DL-2-amino-5-phosphonovaleric acid, suggesting the possible involvement of metabotropic glutamate receptors in this response. The metabotropic glutamate receptor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) depolarized neurons located medial to the tractus solitarius (TS) at the level of the area postrema in coronal sections of the rat NTS. This effect was mimicked by glutamate and was not blocked by antagonists at alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate or NMDA receptors. 1S,3R-ACPD also produced an inward current under voltage clamp that was not accompanied by a rise in [Ca2+]i, monitored with the Ca(2+)-sensitive dye fura-2. Conversely, the muscarinic agonist carbachol produced an outward current and a rise in [Ca2+]i. 1S,3R-ACPD reduced both the excitatory and the inhibitory postsynaptic current resulting from single electrical stimuli in the region of the TS. High-frequency stimulation of the TS produced an inward current in the presence of AMPA/kainate and NMDA receptor blockers. This current had similar properties to that produced by 1S,3R-ACPD. Thus, metabotropic glutamate receptors may mediate a component of excitatory transmission in the NTS.

2-Amino-5-phosphonovalerate↗
PubMed1992

Calcium directly permeates kainate/alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptors in cultured cerebellar Purkinje neurons.

In cultures of rat cerebellar neurons that were enriched in Purkinje cells, the non-N-methyl-D-aspartate glutamate receptor agonist kainate (KA) stimulated Ca2+ influx into all neurons in Na(+)-containing solutions. A large Ca2+ influx was also observed in most neurons when KA was applied in Na(+)-free solutions, even when the cells were voltage-clamped at negative potentials. KA also stimulated Co2+ uptake into both Purkinje and non-Purkinje neurons. The KA-induced Ca2+ influx was insensitive to pharmacological antagonists of voltage-sensitive Ca2+ channels and antagonists of N-methyl-D-aspartate receptors. Thus, different types of cerebellar neurons possess KA-gated ionophores that are permeable to Ca2+. This Ca2+ conductance may play an important role in glutamate-mediated physiological and pathological events in the cerebellum.

Animals↗
PubMed1992

Metabotropic glutamate receptors potentiate ionotropic glutamate responses in the rat dorsal horn.

The effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] were examined on responses mediated by the ionotropic glutamate receptor agonists N-methyl D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), and kainic acid (KA), in neurons acutely isolated from the dorsal horn of the rat spinal cord. (1S,3R)-ACPD produced an increase in the intracellular Ca2+ concentration in 50% of acutely isolated dorsal horn neurons, which could be prevented by blockers of voltage-sensitive Ca2+ channels. (1S,3R)-ACPD markedly potentiated increases in the intracellular Ca2+ concentration induced by NMDA, AMPA, and KA but not by 10-50 mM KCl. This potentiation occurred in all cells, required the simultaneous presence of both agonists, and was rapidly reversible. In the spinal cord slice preparation, (1S,3R)-ACPD potentiated the inward currents evoked by pressure application of AMPA, NMDA, and KA, an effect that was also rapidly reversible. These short term effects of (1S,3R)-ACPD may play an important role in the regulation of ionotropic responses mediated by glutamate in the spinal cord.

Animals↗