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Biomedical subjects

D J Henry

Publications and source records attributed to D J Henry.

18 recordsLinked to original sources
PubMed1998

Adaptations in the mesoaccumbens dopamine system resulting from repeated administration of dopamine D1 and D2 receptor-selective agonists: relevance to cocaine sensitization.

The mesoaccumbens dopamine (DA) system is intricately involved in sensitization to the locomotor stimulant effects of cocaine. Among the adaptations implicated in cocaine sensitization are transient subsensitivity of impulse-regulating DA D2 autoreceptors on ventral tegmental area (VTA) DA neurons leading to hyperactivity of the mesoaccumbens DA pathway, and persistently enhanced DA D1 receptor responses of nucleus accumbens (NAc) neurons. We have tested the hypothesis that both of these adaptations are necessary to produce cocaine sensitization. We injected rats twice daily for 2 weeks with the selective DA D1 class receptor agonist SKF 38393, the DA D2 class receptor agonist quinpirole, or both. We then used single-cell recording procedures to determine possible alterations in VTA DA autoreceptor sensitivity and NAc D1 receptor sensitivity at three withdrawal times: 1 day, 1 week and 1 month. We also tested whether these treatments produced cross-sensitization to cocaine at each withdrawal time. Repeated quinpirole treatment produced a reduction in VTA autoreceptor sensitivity and cross-sensitization to cocaine, but these effects lasted for less than 1 week. Repeated SKF 38393 treatment produced enhanced NAc D1 responses which lasted for 1 week and cross-sensitization to cocaine which was only evident after 1 week of withdrawal. Repeated treatment with the combination of the two agonists transiently down-regulated autoreceptor sensitivity, enhanced and prolonged D1 receptor supersensitivity (lasting 1 month), and produced enduring cross-sensitization to cocaine. These results suggest that neuroadaptations within both the VTA and NAc may be necessary for the induction of enduring cocaine sensitization.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Computer-based patient education: observations on effective communication in the clinical setting.

Computer-based patient education materials are becoming more widely used in an attempt to increase the efficacy and efficiency of the delivery of health care. This paper discusses the authors' experiences in designing and implementing interactive multimedia presentations for patient education in an orthopaedic surgery office setting. Content must be chosen carefully to effectively educate without alienating the patient; simple graphics and animation are best for conveying complex medical and surgical concepts. The interface must be simple; both mouse input and touchscreen have proven acceptable and require minimal instruction. Improvements in program design will result in task-oriented evaluation systems that allow the patient to use the information gained to demonstrate understanding.

Communication↗
PubMed1995

Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes.

The neuronal cannabinoid receptor clone was expressed of saturable [3H]WIN 55,212-2 binding sites. Co-expression of the cannabinoid receptor with cRNA coding for the G-protein-gated inwardly rectifying K+ channel (GIRK1) resulted in oocytes exhibiting large inward K+ currents in response to the cannabinoid agonist WIN 55,212-2. The activation of the potassium current by WIN 55,212-2 was dose-dependent with an EC50 of 630 nM. These results suggest that activation of inwardly rectifying K+ channels may be an additional effector mechanism for brain cannabinoid receptors.

Analgesics↗
PubMed1995

Agonist-induced desensitization of the mu opioid receptor-coupled potassium channel (GIRK1).

In Xenopus oocytes expressing the rat mu receptor and the G protein-gated, inwardly rectifying K+ channel (known as KGA or GIRK1), application of [D-Ala2,MePhe4,Glyol5]enkephalin) a mu opioid agonist, evoked a dose-dependent increase in K+ conductance. With sustained agonist exposure, the amplitude of the response decayed with a t1/2 of 8 +/- 2 min. In oocytes coexpressing the mu and 5HT1A receptors with GIRK1, stimulation of either receptor resulted in heterologous desensitization of the subsequent response to the other. Injection of guanosine 5'-O-(thiotriphosphate) (1 mM) increased the basal GIRK1 activity and the total response to the application of agonist, but did not affect the rate of desensitization. Basal channel activity in the absence of agonist also desensitized at the same rate when the oocytes were exposed to high K+ (96 mM) solution. The above results indicate that the desensitization of the response occurred at a site downstream of the receptor, possibly at the channel. The rate of desensitization was not significantly altered by any of the following treatments: removal of external Ca2+, preloading the oocytes with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-tetra-(acetoxymethyl)-ester (0.5-1 mM), elevation of cAMP levels, treatment with phorbol esters (1 microM), staurosporine (0.5 microM), okadaic acid (1 microM), or cytochalasin B (0.5 microM). These results suggest that desensitization may not involve a calcium or phosphorylation-dependent mechanism.

Animals↗
PubMed1995

The persistence of behavioral sensitization to cocaine parallels enhanced inhibition of nucleus accumbens neurons.

The mesoaccumbens dopamine system is intricately involved in the locomotor stimulation produced by cocaine and sensitization of this effect following repeated cocaine administration. The mechanisms responsible for the expression of sensitized locomotion appear to involve alterations in both presynaptic (increased dopamine release) and postsynaptic (increased responsiveness of dopamine D1 receptors) aspects of dopamine neurotransmission within the nucleus accumbens. The present experiments used behavioral and single-cell electrophysiological techniques to determine the persistence of sensitization and of enhanced postsynaptic responses to cocaine within the nucleus accumbens following various periods of withdrawal from repeated cocaine treatment (10 mg/kg i.p., twice daily, 14 d). Behavioral sensitization to the locomotor stimulant effects of cocaine was evident after 1 d, 1 week, and 1 month, but not 2 months of withdrawal. A similar time course was observed for the enhanced efficacy of cocaine-induced inhibition of nucleus accumbens neurons, whether cocaine was administered systemically or locally by microiontophoresis. Nucleus accumbens neurons also exhibited sensitized inhibitory responses to iontophoretically applied GABA after 1 d of withdrawal, but not later times. These findings suggest that cocaine sensitization is relatively persistent, but not necessarily permanent, and support the hypothesis that expression of behavioral sensitization to cocaine involves actions within the NAc, particularly those mediated by dopamine D1 receptors.

Animals↗
PubMed1995

Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes.

Xenopus oocytes expressed kappa-opioid specific binding sites after injection of cRNA prepared from a clone of the rat kappa-opioid receptor. Coinjection of kappa receptor cRNA with cRNA coding for a G protein-linked, inwardly rectifying, K+ channel (GIRK1, or KGA) resulted in oocytes that responded to the kappa agonist U-69593 by activating a large (1.0-1.5-microA) K+ current. U-69593 exhibited an EC50 of 260 +/- 50 nM and was blocked by the opioid antagonists norbinaltorphimine and naloxone. The kappa agonist bremazocine was 200-fold more potent than U-69593 in eliciting K+ current but exhibited a partial agonist profile in this expression system. The present results indicate that stimulation of inwardly rectifying K+ channels may be a potential effector mechanism for kappa-opioid receptors.

Amino Acid Sequence↗
PubMed1994

Conducting states of a mammalian serotonin transporter.

We have studied permeation at a cloned rat 5-HT transporter expressed in Xenopus oocytes. [3H]5-HT uptake and [125I]RTI-55 binding yield a turnover rate of approximately 1/s that does not depend on membrane potential. However, in voltage-clamp experiments, three distinct currents results from 5-HT transporter expression. First, a steady-state, voltage-dependent transport-associated current is induced by 5-HT application. Second, a transient inward current is activated by voltage jumps to high negative potentials in the absence of 5-HT and is blocked by 5-HT itself. Third, a small leakage current is observed in the absence of 5-HT. All the observed currents are blocked by inhibitors of 5-HT uptake but are differentially affected by Na+, Li+, K+, Ba2+, Cs+, Cl-, and amiloride. The conducting states of the 5-HT transporter may reflect the existence of a permeation pathway similar to that of ionic channels.

Amiloride↗
PubMed1993

Electrophysiological effects of cocaine in the rat nucleus accumbens: microiontophoretic studies.

The nucleus accumbens (NAc) is intricately involved in maintaining cocaine self-administration. Cocaine inhibits the firing of most NAc cells due to its ability to prevent the reuptake of dopamine (DA) and 5-hydroxytryptamine (5-HT), both of which predominantly inhibit NAc cell discharge in vivo. The present studies investigated the roles of DA and 5-HT in the effects of iontophoretically applied cocaine. Most NAc cells exhibited negative/positive waveforms (Type I cells). These cells were significantly more sensitive to cocaine than Type II cells (positive/negative waveforms), apparently due to differences in the actions of 5-HT. Whereas DA was equipotent at inhibiting Type I and Type II cells, 5-HT inhibited Type I cells but, primarily excited Type II cells. Thus the ability of cocaine to potentiate the effects of both DA and 5-HT resulted in a pronounced inhibition of Type I cells, whereas the 5-HT-mediated excitation of Type II cells appeared to reduce DA-mediated inhibition. Combined administration of selective DA (GBR 12909) and 5-HT (fluoxetine) uptake inhibitors was required to mimic the effects of cocaine on Type I and Type II NAc cells. Acute depletion of DA (86%) produced by alpha-methyl-p-tyrosine (AMPT) significantly reduced the inhibitory effects of cocaine on all NAc cells. Acute depletion of 5-HT (74%) produced by p-chlorophenylalanine (PCPA) significantly reduced the inhibitory effect of cocaine on Type I cells, but it significantly enhanced the inhibition of Type II cells. Simultaneous reduction of DA and 5-HT levels produced a significantly greater reduction of cocaine-induced inhibition of Type I neurons than did AMPT or PCPA alone. These findings are discussed in relation to proposed roles of DA and 5-HT in cocaine self-administration.

Animals↗
PubMed1992

Acute depolarization block of A10 dopamine neurons: interactions of morphine with dopamine antagonists.

Extracellular single-unit recording techniques were used to determine the effects of morphine, administered either systematically (intravenous) or locally (microiontophoresis), on ventral tegmental area (A10) dopamine (DA) neuronal activity in animals pretreated with D1 (SCH 23390) or D2 (pimozide) DA receptor antagonists. In rats pretreated with the D2 antagonist pimozide, A10 DA neurons readily entered a state of apparent depolarization block in response to either i.v. or iontophoretically applied morphine. Whether the inactivation of DA neurons was induced by systemic or local morphine, it was reversed in 22 of 27 cases by iontophoretic administration of the inhibitory amino acid transmitter gamma-aminobutyric acid (GABA), suggesting depolarization block as the underlying mechanism. Pretreatment of rats with the D1 antagonist SCH 23390 did not significantly alter the tendency of A10 DA neurons to enter apparent depolarization block in response to morphine. These data support recent behavioral evidence suggesting that the combination of systemic pimozide and ventral tegmental area morphine can result in depolarization inactivation of the mesoaccumbens DA reward system.

Analysis of Variance↗
PubMed1991

Maximising the sensitivity and specificity of non-contact tonometry in glaucoma screening.

Data from a glaucoma screening study involving 88.5% of the population age 50 and over of a single handed general practitioner were reanalysed to determine the effect of altering the protocol for intraocular pressure assessment and the effect of changing the referral threshold. The predictive power of the Keeler Pulsair noncontact tonometer was found to decrease from 22.5% at four pulses per eye to 12.3% when only one pulse per eye was used, with a reduction of sensitivity from 91.7% to 75%. The sensitivity of the same device fell from 91.7% if all patients with an IOP greater than 21 mmHg were deemed as having a positive screen, to 41.6% when only patients with an IOP greater than 26 mmHg were considered for referral. To create a balance between high sensitivity and acceptable predictive power of a positive result in a population where 50% of glaucoma sufferers are known prior to screening, we advise that four pulses per eye should be used with an IOP of greater than 22 mmHg used as the significant finding indicating that the patient required referral.

Glaucoma↗
PubMed1991

Repeated cocaine administration causes persistent enhancement of D1 dopamine receptor sensitivity within the rat nucleus accumbens.

The rewarding effects of cocaine are mediated primarily by the mesoaccumbens dopamine (DA) system, which projects from A10 DA cell bodies within the ventral tegmental area to the nucleus accumbens (NAc). This pathway is also intricately involved in the locomotor stimulating effect of cocaine and the progressive increases (sensitization) in this behavior observed after repeated administration of cocaine and other psychomotor stimulants. By using single-cell electrophysiological recording and microiontophoretic techniques, we demonstrated previously that repeated cocaine administration (10 mg/kg i.p., twice daily, 14 days) renders impulse-regulating somatodendritic A10 DA autoreceptors subsensitive, thereby increasing impulse flow within the mesoaccumbens DA system. In striking contrast, inhibitory responses of NAc neurons to iontophoretic DA were significantly increased in cocaine-treated rats tested 16 to 24 hr after the last cocaine injection. In the present study, iontophoretic application of selective D1 (SKF 38393) and D2 (quinpirole) DA receptor agonists was utilized to determine the extent to which each of these DA receptor subtypes is altered by repeated cocaine administration. After 2 weeks of twice daily cocaine (10 mg/kg i.p.) injections, significant increases in the inhibitory responses of NAc neurons to SKF 38393, but not quinpirole, were observed. In addition, this D1 receptor sensitization was still evident when animals were tested either 7 days or 1 month after the final cocaine injection. After 2 months of withdrawal from cocaine treatment, D1 receptor sensitivity in the NAc had returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Screening for glaucoma in the community by non-ophthalmologically trained staff using semi automated equipment.

Eighty-nine and a half per cent of the population of a general practice over the age of 49 years were screened for glaucoma and high risk ocular hypertension requiring treatment. Screening took place using semi-automated intraocular pressure and visual field equipment operated by non-ophthalmologically trained staff. An experienced ophthalmologist examined all patients in a single blind manner to reduce false negatives to a minimum. Patients suspected of requiring treatment on the grounds of raised intraocular pressure, abnormal visual fields or suspicious optic discs were subsequently examined in a hospital clinic. Treatment criteria, as commonly practiced, were carefully defined and the sensitivities and specificities of the methods of screening used were calculated. One and three tenths per cent of the practice population were known to be receiving treatment prior to the study and a further 1.4% were found to require treatment after screening. The sensitivity and specificity of the non-contact tonometer were 91.7% and 95.6% respectively with a predictive power of 22.5% for a positive result. The mean time taken to perform the test in both eyes was two minutes. Seventy per cent of the patients with pressures over 22 mmHg in both eyes on screening were found to require treatment. The routine use of the field screener did not increase either the sensitivity or specificity of the screening process but its use in cases with raised intraocular pressure is advised to indicate the degree of urgency of the referral. An algorithm based on the results of the study is suggested when planning the use of semi-automated equipment to screen for ocular disease related to raised intraocular pressure.

Aged↗
PubMed1990

Costing a community based screening programme for the detection of glaucoma.

The cost of detecting a case of glaucoma in a community based screening programme was calculated using data from a pilot study on a population aged 50 and over. The cost per screen was estimated at 3.35 pounds with a total cost of 311 pounds per case detected. These estimates include the cost of both the algorithmically based screening programme and the hospital assessment of true and false positives. These costs are considered to compare favourably with the potential costs incurred by paying optometrists to screen high risk groups whilst providing the opportunity to detect over twice the number of cases of occult glaucoma.

Community Health Services↗
PubMed1990

Calculating the predictive power of the Henson field screener in a population at risk of glaucomatous field loss.

Suprathreshold field screeners are in common use for the detection of glaucomatous field loss. The predictive power of a positive result (PP+) depends on the sensitivity and specificity of the screener in the population in which it is to be used. Using data from 755 normal individuals (1510 eyes), we calculated the PP+ of the Henson CFS2000 screening programme for a population aged 50 and over. 4.3% of normal eyes failed the screening programme. Ignoring one or two misses on the screening programme immediately adjacent to the disc reduced this figure to 1.3% and significantly improved the PP+ of the programme. Calculations of the PP+ at increasing glaucoma prevalence levels indicates this to be particularly relevant at low levels such as those encountered when screening middle aged and elderly populations. Optometrists should perform routine field analysis when screening for glaucoma provided they adhere to strict protocols.

Aged↗
PubMed1989

Do optometrists screen for glaucoma?

A survey of optometrists practising in Nottingham was undertaken to identify their methods of screening for glaucoma in the community. There was found to be great variation in all parameters examined including referral criteria. Although all of the respondents screened for glaucoma, 50% appeared not to be aware of subtle optic disc signs of the disease, 8% never measured intra-ocular pressures and 19% never performed visual field analysis. In a general practice population age 50 and over, 73% of patients had visited their optician within the last two years, 67% knew glaucoma was an eye disease, but only 15% remembered being screened for glaucoma.

False Positive Reactions↗
PubMed1989

Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: repeated administration.

Behavioral evidence indicates that the potent rewarding effects of cocaine are mediated, in part, by the mesoaccumbens dopamine (DA) system projecting from A10 DA cells in the ventral tegmental area (VTA) to the nucleus accumbens (NAc). Previous electrophysiological studies from our laboratory have indicated that cocaine (i.v.) exerts inhibitory effects on A10 DA neurons, due to enhanced stimulation by DA at DA autoreceptors are well as by activation of NAc-VTA feedback pathways. In the present experiments, extracellular single-unit recording and microiontophoretic techniques were used to determine the possible alterations in the mesoaccumbens DA system after repeated cocaine administration. Twice daily injections of cocaine (10 mg/kg i.p., 14 days) caused significant subsensitivity to the inhibitory effects of low i.v. doses of the DA agonist apomorphine in comparison to rats receiving similar treatments with saline or procaine. Iontophoretic application of DA to A10 DA neurons in rats treated repeatedly with cocaine (2X10 mg/kg, 14 days) also produced significantly less inhibition as compared to control rats. Cell population analysis of the VTA revealed that autoreceptor subsensitivity in cocaine-treated rats resulted in a significantly greater number of spontaneously active A10 DA neurons, and a significantly higher firing rate as compared to A10 DA neurons in control rats. In striking contrast to A10 DA cells, recordings from NAc neurons in cocaine-treated rats (2X10 mg/kg, 14 days) indicated that these cells were supersensitive to the inhibitory effects of iontophoretic DA. Although the mechanism underlying such supersensitivity remains unclear, the increased sensitivity of postsynaptic NAc DA receptors combined with the subsensitivity of A10 DA autoreceptors could lead to greatly enhanced DA transmission and may help to explain some aspects of cocaine-induced behavioral sensitization.

Animals↗
PubMed1985

Fluid inclusions in stony meteorites--a cautionary note.

Newly discovered fluid inclusions in thin sections of Bjurbole chondrules, shergottite EETA79001, lunar meteorite ALHA81005, and Apollo 16 glasses possess physical properties similar to those fluid inclusions found in thin sections of five stony meteorites recently described by Warner et al. (1983). The distribution and physical properties of these new fluid inclusions indicate they may be artifacts of thin section preparation; we suggest that saw coolant was sucked into vacuum vesicles in glasses and minerals through submicroscopic fractures produced during sawing. The similarities between these fluid inclusions and fluid inclusions previously described by Warner et al. (1983) lead us to conclude that many of the fluid inclusions reported earlier may be artifacts. Consequently, the origin of any fluid inclusions observed in thin sections of extraterrestrial materials must be interpreted with caution. The most probable true extraterrestrial fluid inclusions are those that have been observed in grains prepared without exposure to liquids of any kind.

Extraterrestrial Environment↗