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Biomedical subjects

R W Turner

Publications and source records attributed to R W Turner.

At least 37 records · Page 2Linked to original sources
PubMed1994

Modulation of ion channels in rod photoreceptors by nitric oxide.

Subcellular compartments in the outer retina of the larval tiger salamander were identified as likely sites of production of nitric oxide (NO), a recently recognized intercellular messenger. NADPH diaphorase histochemistry and NO synthase immunocytochemistry labeled photoreceptor ellipsoids and the distal regions of bipolar and glial cells apposing photoreceptor inner segments, suggesting a role for NO in visual processing in the outer retina. We investigated the actions of NO on several rod photoreceptor ion channels. Application of the NO-generating compound S-nitrosocysteine increased Ca2+ channel current and a voltage-independent conductance, but had no affect on voltage-gated K+ or nonspecific cation currents. Given the steep relation between voltage-dependent Ca2+ influx and photoreceptor synaptic output, these results indicate that NO could modulate transmission of the photoresponse to second order cells.

Amino Acid Oxidoreductases↗
PubMed1994

Specific diagnosis of progressive multifocal leukoencephalopathy by polymerase chain reaction.

Using polymerase chain reaction (PCR), 34 cerebrospinal fluid (CSF) samples from 28 patients with progressive multifocal leukoencephalopathy (PML) were analyzed. As controls, 116 samples were evaluated from 82 human immunodeficiency virus type 1 (HIV-1)-infected patients and 1 HIV-1-negative patient. Of the HIV-1-positive patients, 23 had cerebral toxoplasmosis, 10 had HIV leukoencephalopathy, and 49 had other neurologic complications. Detection of JC virus (JCV) DNA in CSF was increased 10-fold by the addition of carrier DNA before phenol-chloroform-isoamyl alcohol extraction. The primer pair JC 26/29, from the VP1/large T region, had a limit of detection of 10(5) JCV DNA molecules/100 microL. The primer pair JC 36/39, located in the large T gene region, had a 100-fold lower limit of detection. With JC 26/29, the sensitivity was 43% (12/28) and specificity was 100%. Using JC 36/39, sensitivity increased to 82% (23/28), and false-positive results were not observed. Diagnosis of PML is greatly aided by PCR analysis of CSF.

Base Sequence↗
PubMed1994

Progressive multifocal leukoencephalopathy diagnosed by amplification of JC virus-specific DNA from cerebrospinal fluid.

OBJECTIVE: To study the diagnostic sensitivity and specificity of polymerase chain reaction (PCR) for the non-invasive diagnosis of progressive multifocal leukoencephalopathy (PML) in HIV-1-infected individuals. DESIGN: Retrospective analysis of stored cerebrospinal fluid (CSF) samples by PCR of HIV-1-infected patients. METHODS: Results of the PCR analysis of the CSF of three AIDS patients with autopsy-proven PML were compared with the results in 15 neurologically asymptomatic HIV-1-infected patients and with 15 AIDS patients with other opportunistic infections of the central nervous system (CNS). A polyclonal antiserum to simian virus 40 (SV40) cross-reacting with JC virus (JCV) late antigens was used for immunocytochemical confirmation of the diagnosis. Two different primer pairs, one taken from the VP1/large T gene and the other from the large T gene, were used to amplify JCV-specific DNA sequences from CSF. RESULTS: Five CSF samples were analysed and JCV-specific DNA found in three patients with autopsy-proven PML. No JCV-specific DNA was detected in 47 CSF samples, including serial samples from 14 of the 30 non-PML patients. The diagnosis of PML was confirmed in all three cases by immunocytochemistry. CONCLUSION: PML can be diagnosed by PCR analysis of CSF. The sensitivity and specificity of the method depends on the sensitivity of the primers used for amplification. Using a primer pair from the large T gene, JCV-specific DNA was amplified in three cases with PML as early as the day of presentation with the first neurological symptom of PML.

AIDS-Related Opportunistic Infections↗
PubMed1994

TTX-sensitive dendritic sodium channels underlie oscillatory discharge in a vertebrate sensory neuron.

Immunocytochemical and electrophysiological techniques were used to localize TTX-sensitive sodium channels (NaChs) over the soma-dendritic axis of basilar and nonbasilar pyramidal cells of the electrosensory lateral line lobe (ELL) of weakly electric fish (Apteronotus leptorhynchus). Dense NaCh-like immunolabel was detected on the membranes of basilar and nonbasilar pyramidal cell somata. Punctate regions of immunolabel (approximately 15 microns) were separated by nonlabeled expanses of membrane over the entire extent of basal dendrites. Similar punctate immunolabel was observed over the apical dendrites, and frequently on membranes of afferent parallel fiber boutons in the distal apical dendritic region. Intracellular recordings from pyramidal cell somata or proximal apical dendrites (75-200 microns) were obtained using an in vitro ELL slice preparation. TTX-sensitive potentials were identified by focal pressure ejection of TTX. Somatic recordings demonstrated both TTX-sensitive fast spike discharge and a slow prepotential; similar but lower amplitude potentials were recorded in apical dendrites. Dendritic spikes were composed of at least two active components triggered by a fast prepotential (FPP) generated by the somatic spike. TTX-sensitive spikes propagated in a retrograde fashion over at least the proximal 200 microns of the apical dendrites, as determined by the conduction of an antidromic population spike and focal TTX ejections. Somatic spikes were followed by a depolarizing afterpotential (DAP) that was similar in duration and refractory period to that of proximal dendritic spikes. During repetitive spike discharge, the DAP could increase in amplitude and attain somatic spike threshold, generating a high-frequency spike doublet and a subsequent hyperpolarization that terminated spike discharge. Repetition of this process gave rise to an oscillatory burst discharge (2-6 spikes/burst) with a frequency of 40-80 Hz. Both the DAP and oscillatory discharge were selectively blocked by TTX ejections restricted to the proximal apical dendritic region. The present study demonstrates an immunolocalization of NaChs over somatic and dendritic membranes of a vertebrate sensory neuron that correlates with the distribution of TTX-sensitive potentials. The interaction of somatic and dendritic action potentials is further shown to underlie an oscillatory discharge believed to be important in electrosensory processing.

Animals↗
PubMed1993

Fast pre-potential generation in rat hippocampal CA1 pyramidal neurons.

Small all-or-none pre-potentials have been shown under some conditions to underlie antidromic and orthodromic spike discharge in somatic recordings of hippocampal pyramidal neurons [Andersen P. and Lomo T. (1966) Expl Brain Res. 2, 247-260; Kandel E. R. et al. (1961) J. Neurophysiol. 24, 225-242; Schwartzkroin P. A. (1977) Brain Res. 128, 53-68; Spencer W. A. and Kandel E. R. (1961) J. Neurophysiol. 24, 272-285]. These potentials are taken to reflect spike discharge in distant regions of the cell (axonal or dendritic) [Andersen P. and Lomo T. (1966) Expl Brain Res. 2, 247-260; Kandel E. R. and Spencer W. A. (1961) Ann. N. Y. Acad. Sci. 94, 570-603; Schwartzkroin P. A. (1977) Brain Res. 128, 53-68] or electronic spike conduction across a gap junction between neighboring pyramidal cells [Dudek F. E. et al. (1983) In Basic Mechanisms of Neural Hyperexcitability, pp. 31-73]. The present study compared pre-potentials recorded at the somatic and dendritic levels and used restricted applications of tetrodotoxin to examine the relationship between pre-potentials and Na+ spike discharge. Intrasomatic and intradendritic recordings were obtained from CA1 pyramidal neurons of rat hippocampal slices maintained in vitro. Orthodromic and antidromic spike discharge was evoked by stimulation of afferent fibers in stratum radiatum and pyramidal cell axons in the alveus, respectively. Focal pressure application of tetrodotoxin in the immediate vicinity of somatic or dendritic recordings uncovered pre-potentials following blockade of antidromic spike discharge. Blockade of these pre-potentials required the diffusion of tetrodotoxin to a location remote from the recording site. Focal application of tetrodotoxin in the cell body layer reliably uncovered orthodromic pre-potentials at the soma only when stimulus intensity was raised beyond threshold for somatic spike discharge; e.g. to intensities shown to initiate spike discharge in apical dendritic locations [Turner R. W. et al. (1991) J. Neurosci. 11, 2270-2280]. These data provide evidence that propagation of a Na+ spike over the pyramidal cell axis is preceded by a depolarization in the form of a pre-potential. The uncovering of orthodromic somatic pre-potentials by tetrodotoxin during suprathreshold activation further supports the proposal [Spencer W. A. and Kandel E. R. (1961) J. Neurophysiol. 24, 272-285] that dendritic spike discharge [Turner R. W. et al. (1991) J. Neurosci. 11, 2270-2280] can underlie fast pre-potential generation in pyramidal cell somata.

Animals↗
PubMed1992

Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients.

Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I [HTLV-I] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-I DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-I infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Deltaretrovirus Antibodies↗
PubMed1991

Apical dendritic depolarizations and field interactions evoked by stimulation of afferent inputs to rat hippocampal CA1 pyramidal cells.

The relationship between orthodromic extracellular field potentials and intradendritic depolarizations in apical dendrites of CA1 pyramidal neurons was investigated using the in vitro slice preparation of rat hippocampus. Orthodromic synaptic field potentials evoked by stimulation of afferent inputs in stratum radiatum or stratum oriens were used to measure extracellular voltage gradients generated over the pyramidal cell axis. Extracellular gradients were of opposite polarity over the region of pyramidal cell apical dendrites in stratum radiatum. The stratum radiatum-evoked gradient was negative towards the apical dendrites and the stratum oriens-evoked gradient negative towards the cell body layer, with gradients reaching values of up to 50 mV/mm over the apical dendritic axis. Intradendritic recordings obtained greater than 150 microns from stratum pyramidale directly measured the subthreshold apical dendritic excitatory postsynaptic potentials evoked by stratum radiatum or stratum oriens stimulation. These ground-referenced recordings were then compared to the transmembrane potential calculated by subtraction of the corresponding extradendritic field potential. Both stratum radiatum and stratum oriens stimulation evoked graded excitatory postsynaptic potentials that could be recorded in apical dendritic impalements up to 265 microns from stratum pyramidale. The calculated transmembrane potential of the stratum radiatum-evoked excitatory postsynaptic potential had a significantly greater rate of rise, peak amplitude, and rate of decay than that of the ground-referenced excitatory postsynaptic potential. In contrast, the rates of rise and decay of the transmembrane potential of the stratum oriens-evoked excitatory postsynaptic potential were reduced with respect to the ground-referenced recording. The peak amplitude of the stratum oriens-evoked transmembrane potential, however, varied according to the polarity of the corresponding extradendritic population spike response recorded in stratum radiatum. These data reveal that synaptic activation of either basal or apical dendrites of CA1 pyramidal cells evokes a depolarization that can be recorded over a substantial region of the apical dendritic arbor. Furthermore, extradendritic field potentials evoked by stimulation of these inputs produce opposite effects on the transmembrane potential of apical dendrites. The magnitude of the accompanying extracellular voltage gradients suggest that these shifts in transmembrane potential reflect ephaptic interactions at the apical dendritic level of pyramidal cells.

Animals↗
PubMed1991

Complex mixtures in industrial workspaces: lessons for indoor air quality evaluations.

Acceptable occupational exposure levels for hundreds of airborne concentrations of dusts, vapors, fumes, and gases have been set by consensus organizations and regulatory bodies for decades. These levels have established tremendous precedent and are tempting reference values in the relatively new field of indoor air quality evaluations where validated criteria are greatly needed. The American Conference of Government Industrial Hygienists (ACGIH) has been the most visible and productive group setting these guidelines for industrial exposure. The ACGIH Chemical Substances Committee has published an annual list of threshold limit values (TLVs) for more than 40 years. Currently the list covers more than 400 substances. In 1989, the Occupational Safety and Health Administration (OSHA) published updated permissible exposure limits (PELs) for approximately 600 substances. Most PELs before this update were adopted from the 1968 ACGIH list of TLVs and consensus standards of the American Standards Association. This OSHA update has resulted in reductions of 212 PELs and the addition of 164 new levels. The magnitude of the problem of protecting workers can be seen by the small fraction that the OSHA PELs represent of the more than 60,000 entries in the National Institute for Occupational Safety and Health's Registry of Toxic Effects of Chemical Substances. None of these levels, whether guidelines or regulatory requirements, are established based on any possible synergistic effect with other chemicals. The only guidance given by the ACGIH for synergistic effects is that such cases must be determined individually. Clearly, there are major drawbacks in using occupational standards and guidelines for evaluating the health effects of chemical agents that can be found in office settings, often in concentrations orders of magnitude less than what is routinely measured in the workplace. These guidelines are even less valuable when the concern is the complex mixing of chemicals in nonoccupational environments.

Air Pollutants, Occupational↗
PubMed1991

The site for initiation of action potential discharge over the somatodendritic axis of rat hippocampal CA1 pyramidal neurons.

Early electrophysiological studies in the mammalian hippocampus reported that orthodromic depolarization of pyramidal cells evoked action potential discharge (presumed Na+ dependent) both at the axon hillock and at one or more sites in the dendritic arborization (Cragg and Hamlyn, 1955; Andersen, 1959, 1960; Spencer and Kandel, 1961; Andersen and Lomo, 1966). Although tetrodotoxin (TTX)-sensitive spikes have been recorded at the dendritic level (Wong et al., 1979; Benardo et al., 1982; Miyakawa and Kato, 1986; Turner et al., 1989), the site for initiation of these potentials has not yet been determined. In this study, we examine the site for initiation of Na+ spike discharge over the cell axis of rat hippocampal CA1 pyramidal neurons. Intrasomatic and intradendritic recordings were obtained from pyramidal neurons of hippocampal slices maintained in vitro. Spike discharge was evoked by alvear (antidromic) stimulation or orthodromically by stimulation of afferent inputs in stratum oriens (SO) or stratum radiatum (SR). Antidromic and orthodromic spikes were greatest in amplitude in somatic recordings and declined over the apical dendritic axis, while spike half-width was shortest at the cell body and increased with distance from stratum pyramidale. Measurements of orthodromic spike threshold revealed that the only location at which spikes discharged at a consistent membrane potential at threshold intensity (voltage threshold) was the cell body region. Finally, at threshold intensity, SR-evoked intradendritic spikes were blocked by local application of TTX in stratum pyramidale, while spike blockade at suprathreshold intensity required the diffusion of TTX into the apical dendritic region. These results indicate that, for threshold intensities of stimulation, antidromic and orthodromic spike discharge in CA1 pyramidal cells is initiated in the region of the cell body layer, subsequently conducting over the apical dendrites in a retrograde fashion. In contrast, SR-evoked orthodromic spike discharge exhibits an intensity-dependent shift in the site of origin up to 200 microns within the apical dendritic arborization.

Action Potentials↗
PubMed1989

Localization of tetrodotoxin-sensitive field potentials of CA1 pyramidal cells in the rat hippocampus.

1. The role of tetrodotoxin (TTX)-sensitive (Na+) channels in the generation of antidromic and orthodromic field potentials of the CA1 pyramidal cell population was examined by local application of TTX in the in vitro rat hippocampal slice preparation. 2. The sensitivity of alvear (antidromic) and stratum oriens (SO)-evoked potentials to TTX application (10-100 microM) was tested in stratum pyramidale and over the entire extent of pyramidal cell apical dendrites in stratum radiatum. Stratum radiatum (SR)-evoked potentials were examined at the level of pyramidal cell bodies and over the proximal 200 microns of the apical dendritic region. 3. Pressure application of TTX confined to stratum pyramidale or regions of stratum radiatum selectively blocked the negative component of antidromic and SO-evoked population discharge in the cell body layer and over the initial 200 microns of stratum radiatum. 4. SR stimulation evoked a complex field potential in the proximal stratum radiatum (less than 150 microns) composed of at least three components: 1) A short-duration (approximately 3 ms) negativity of shorter peak latency than the population spike recorded simultaneously in stratum pyramidale. This potential was highly sensitive to TTX and appeared to be instrumental in the generation of the cell body population response. 2) A long-duration negativity (approximately 20 ms) evoked at stimulation strengths that were subthreshold for both the short-duration negativity in proximal stratum radiatum and the cell body population spike. Although apparently less sensitive to TTX, this potential was reduced in amplitude with repeated TTX application; and 3) a slow (approximately 12 ms) positive-going potential that was only observed after eliminating all TTX-sensitive conductance mechanisms in the proximal stratum radiatum. 5. The latency difference between the SR-evoked short-duration negativity of proximal stratum radiatum and the population spike in stratum pyramidale decreased or reversed during the course of multiple discharge induced by the addition of bicuculline or picrotoxin (5-10 microM) to the perfusate. 6. These data indicate the presence of TTX-sensitive presumed Na+ channels over the initial 200 microns of pyramidal cell apical dendrites capable of supporting active conduction of population discharge evoked by antidromic or SO stimulation. The sensitivity of SR-evoked potentials to TTX suggests that a synaptic potential generated in the distal apical dendrites is capable of triggering both a slow active depolarization and a fast spike-like discharge in the proximal apical dendritic region.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Anxiety and depression in a primary care clinic. Comparison of Diagnostic Interview Schedule, General Health Questionnaire, and practitioner assessments.

Over one half of all persons seen in a primary care clinic were identified as having anxiety or depressive disorder by the primary care provider, the General Health Questionnaire (GHQ), or the Diagnostic Interview Schedule (DIS). In only about 5% of all patients were findings positive on all three assessments concurrently. Both the GHQ and the practitioners identified over 30% of all patients as having a disorder, while about 8% had one or more of five DIS anxiety or depressive disorders (major depression, dysthymia, panic disorder, generalized anxiety disorder, or obsessive-compulsive disorder). Of the patients with DIS disorders 83% had positive GHQ scores, and 73% were identified by the practitioner as having a mental disorder.

Adolescent↗
PubMed1987

An experiment to change detection and management of mental morbidity in primary care.

A randomized clinical trial was conducted in a group practice for the primary care of adult patients to address the effect of feedback to providers of information from a psychiatric screening questionnaire, the General Health Questionnaire (GHQ). The practice is staffed by faculty, residents, and health care extenders of The Johns Hopkins University School of Medicine's Division of Internal Medicine. The patient population was drawn mainly from the inner city community in Baltimore that surrounds the hospital, where the practice is physically based. The GHQ was administered at the time of a regular visit to the practice and results made available to the clinicians for randomly allocated subsamples of their patients. The study results showed that feedback of GHQ information led to only marginal effects on overall detection of mental health problems among the patients in general. However, marked increases in detection occurred among the elderly, blacks, and men, subgroups that ordinarily have relatively low rates of detection of mental morbidity by primary care practitioners. Feedback of GHQ information did not affect management.

Adolescent↗
PubMed1987

Action-potential discharge in hippocampal CA1 pyramidal neurons: current source-density analysis.

1. The site of origin of evoked action-potential discharge in hippocampal CA1 pyramidal neurons was investigated using the in vitro rat hippocampal slice preparation. 2. Action-potential discharge in pyramidal cells was evoked by stimulation of efferent pyramidal cell fibers in the alveus (antidromic) or afferent synaptic inputs in stratum oriens (SO) or stratum radiatum (SR). Laminar profiles of evoked extracellular field potentials were recorded at 25-micron intervals along the entire dendrosomatic axis of the pyramidal cell and a one-dimensional current source-density analysis was applied. 3. Suprathreshold stimulation of the alveus evoked an antidromic population spike response and current sink with the shortest peak latency in stratum pyramidale or proximal stratum oriens. A biphasic positive/negative potential associated with a current source/sink was recorded in dendritic regions, with both components increasing in peak latency with distance from the border of stratum pyramidale. 4. Suprathreshold stimulation of SO or SR evoked a population spike response superimposed upon the underlying synaptic depolarization at all levels of the dendrosomatic axis. The shortest latency population spike and current sink were recorded in stratum pyramidale or proximal stratum oriens. In dendritic regions, a biphasic positive/negative potential and current source/sink conducted with increasing latency from the border of stratum pyramidale. 5. A direct comparison of alvear- and SR-evoked responses revealed a basic similarity in population spike potentials and associated sink/source relationships at both the somatic and dendritic level and a similar shift in peak latency of spike components along the pyramidal cell axis. 6. It is concluded that the initial site for generation of a spike along the dendrosomatic axis of the pyramidal cell following antidromic or orthodromic stimulation is in the region of the cell body layer (soma or axon hillock). Action-potential discharge in dendritic regions then occurs as the result of a subsequent retrograde spike invasion of basal and apical dendritic arborizations.

Action Potentials↗
PubMed1986

The mode of antifungal action of tolnaftate.

The anti-dermatophyte agent tolnaftate was compared with the allylamine antifungal compounds naftifine and terbinafine. Tolnaftate was shown to inhibit sterol biosynthesis at the level of squalene epoxidation and squalene was shown to accumulate in dermatophytes grown in its presence. Biochemical studies in whole and broken cells supported this conclusion and showed that the compound was active against squalene epoxidation in broken C. albicans cells, but was much less potent against whole cells. These results suggested there was a barrier to penetration in these yeasts.

Allylamine↗
PubMed1984

Extracellular fields influence transmembrane potentials and synchronization of hippocampal neuronal activity.

The influence of extracellular fields on the transmembrane potential (TMP) of CA1 pyramidal neurons was investigated following both ortho- and antidromic stimulation in the in vitro hippocampal slice preparation. A short latency negative deflection on the intracellular potential coincided with the falling phase of the extracellular population spike. Subtraction of extracellular field potentials from ground referenced intracellular records revealed a sharp depolarizing wave of the TMP superimposed upon the underlying synaptic potential. This graded depolarization was capable of discharging CA1 cells and displayed a parallel shift in latency and amplitude with the extracellular population spike. A similar depolarizing wave was associated with the antidromically evoked population spike which persisted following blockade of synaptic activity. Finally, multiple population spike activity similar to that observed during epileptiform discharge was associated with repetitive depolarizing waves of the TMP. These data suggest that extracellular field potentials can ephaptically discharge CA1 neurons and may play a role in recruitment and synchronization of neuronal activity in the hippocampus.

Animals↗
PubMed1984

Ephaptic interactions contribute to paired pulse and frequency potentiation of hippocampal field potentials.

The contribution of ephaptic interactions to potentiation of the hippocampal CA1 extracellular population spike during paired pulse or frequency stimulation of stratum radiatum (SR) inputs was investigated using the in vitro hippocampal slice preparation. Records of the transmembrane potential revealed a depolarizing wave with an amplitude and latency that varied directly with that of the extracellular population spike. Paired pulse or repetitive stimulation of SR resulted in a potentiation of the population spike amplitude and a corresponding increase in the amplitude of the TMP depolarizing wave. Action potentials generated during the stimulus train consistently arose from the peak of the depolarizing wave. It is proposed that ephaptic interactions contribute to potentiation of the extracellular population spike through recruitment of subthreshold neurons within the population during repetitive afferent stimulation.

Animals↗