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D Clark

Publications and source records attributed to D Clark.

At least 37 records · Page 2Linked to original sources
PubMed1991

Role of dopamine D1 and D2 receptors in mediating the d-amphetamine discriminative cue.

The role of D1 and D2 dopamine (DA) receptors in mediating the discriminative cue produced by d-amphetamine (0.5 mg/kg) in rats has been assessed by using compounds which exert strong selectivity for each of these DA receptor subtypes. The D2 agonists quinpirole and RU 24213 substituted completely for d-amphetamine, while the D1 agonists SKF 38393 and SKF 81297 failed to exert such effects. On the other hand, the D2 antagonists raclopride and YM 09151-2, and D1 antagonists SCH 23390 and SKF 83566, all completely blocked d-amphetamine discrimination. The D2 antagonists produced more pronounced inhibitory effects on response rate than did D1 antagonists. Quinpirole substitution for d-amphetamine was blocked by YM 09151-2, but not by SCH 23390, while the locomotor stimulatory effect of quinpirole was inhibited by both drugs. The present findings confirm that D2 receptors play a primary role in the d-amphetamine discriminative cue, while the precise role of D1 receptors remains to be disclosed.

Animals↗
PubMed1991

N-methyl-D-aspartate increases the excitability of nigrostriatal dopamine terminals.

The terminal excitability of nigrostriatal dopamine cells was measured before and after i.v. administration of N-methyl-D-aspartate (NMDA; 1 or 4 mg/kg), the competitive NMDA antagonist AP-7 (2-amino-7-phosphonoheptanoic acid) (4 mg/kg) or saline. NMDA produced a dose-dependent increase in terminal excitability, in the absence of an effect on the somal membrane, whereas AP-7 and saline were without effect. These data provide convergent in vivo evidence that glutamate can enhance striatal dopamine release via the NMDA receptor.

2-Amino-5-phosphonovalerate↗
PubMed1991

Localization of [3H]GABA-labelled nerve fibre networks in the rat intestinal mucosa.

Laminar preparations of the rat colonic mucosa were treated for [3H]GABA (5 x 10(-8) M) autoradiography. Under conditions specific for high-affinity labelling of neuronal elements, a network of fibres overlying the base of the mucosal crypts and a second network coursing in close association with the crypts, were intensely labelled. Along the course of the overlying network of fibres, were dense accumulations of silver grains reminiscent of junctions for fibres projecting into the mucosa. All labelling could be prevented by the specific neuronal uptake inhibitor, L-DABA (10(-3) M).

Aminobutyrates↗
PubMed1991

Differential agonist profile of the enantiomers of 3-PPP at striatal dopamine autoreceptors: dependence on extracellular dopamine.

The effects of the enantiomers of 3-hydroxyphenyl-N-n-propylpiperidine (3-PPP) at dopamine (DA) synthesis modulating autoreceptors, measured as DOPA accumulation after decarboxylase inhibition, were assessed in vivo and in rat striatal slices. In vivo, (+)-3-PPP inhibited DOPA accumulation in the striatum, nucleus accumbens, and medial prefrontal cortex, whereas (-)-3-PPP either increased (striatal) or had no effect (accumbens, prefrontal cortex), on DOPA accumulation. In vitro, both (+)- and (-)-3-PPP reduced basal DOPA accumulation with a similar order of potency (apparent EC50 = 2.1 and 1.0 microns, respectively) and maximal effect, although they were less potent than the D2 DA receptor agonist quinpirole (EC50 = 0.15 microM). The inhibition of tyrosine hydroxylation was also observed in slices obtained from reserpine-pretreated rats and was blocked by the selective D2 DA antagonist (-)-sulpiride. This suggests that 3-PPP inhibition of DOPA accumulation was mediated directly by stimulation of DA D2 receptors. Increasing the amount of extracellular DA by depolarizing slices with 30 mM K+ did not alter the qualitative effects of either quinpirole or (+)-3-PPP. However, the stimulation of DA autoreceptors by (-)-3-PPP was no longer apparent under conditions of elevated extracellular DA. Under these depolarizing conditions, (-)-3-PPP actually antagonized the inhibitory effect afforded by either quinpirole or pergolide. A similar switch in profile was observed with transdihydrolisuride (TDHL). The data support the notion that (-)-3-PPP and TDHL are partial agonists at synthesis modulating DA autoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of low, autoreceptor selective doses of dopamine agonists on the discriminative cue and locomotor hyperactivity produced by d-amphetamine.

The ability of low doses of the dopamine (DA) agonists quinpirole and (+)-3-PPP to reduce the discriminative stimulus properties and locomotor hyperactivity produced by d-amphetamine (0.5 mg/kg) was assessed in two groups of rats. Quinpirole (0.0125-0.05 mg/kg) and (+)-3-PPP (1.0-2.0 mg/kg) completely antagonized d-amphetamine-induced locomotor hyperactivity. In contrast, only single doses of quinpirole (0.025 mg/kg) and (+)-3-PPP (2.0 mg/kg) were effective in the drug discrimination paradigm; the antagonisms were small (18-47%), but significant. The inhibitory effects of quinpirole and (+)-3-PPP in these behavioural models are probably due to their ability to selectively stimulate DA autoreceptors in the nucleus accumbens and reduce the increase in DA release produced by d-amphetamine. It is suggested that the much weaker effects of the drugs in the discrimination paradigm are due to changes produced by the long-term periodic administration of d-amphetamine to these animals, such as a down-regulation in the sensitivity of DA autoreceptors.

Animals↗
PubMed1991

Behavioural profile of partial D2 dopamine receptor agonists. 1. Atypical inhibition of d-amphetamine-induced locomotor hyperactivity and stereotypy.

The effects of partial D2 dopamine (DA) receptor agonists on the behavioural activation produced by 1.5 and 8.0 mg/kg d-amphetamine were compared with the changes produced by the classical DA antagonist haloperidol. Alterations in behaviour were assessed in standard activity monitoring cages by direct observation of the rats using a rapid time sampling procedure. Haloperidol blocked d-amphetamine (1.5 mg/kg)-induced increases in photocell counts, ambulation, rearing and sniffing up, and after the highest dose of the DA antagonist the animals were mainly inactive. The partial D2 DA agonist SDZ 208-911 was equipotent to haloperidol in blocking the increase in photocell counts and rearing produced by d-amphetamine. However, even high doses of the drug did not reduce the incidence of sniffing or induce inactivity, but qualitative changes in the form of sniffing did occur. Although considerably less potent, preclamol exerted similar effects to SDZ 208-911. The profiles of SDZ 208-912 and terguride were intermediary to those of SDZ 208-911 and haloperidol. All compounds blocked the repetitive sniffing down produced by 8.0 mg/kg d-amphetamine. After a low dose of haloperidol, these stereotyped behaviours were replaced by a behavioural syndrome similar to that observed with low dose d-amphetamine, but inactivity was observed following a further small increase in antagonist dose. The blockade of stereotypy by SDZ 208-911, preclamol and terguride was accompanied only by the low dose d-amphetamine behavioural syndrome; no inhibition of sniffing or induction of inactivity occurred. SDZ 208-912 exhibited a profile with features very similar to that noted with haloperidol. These findings suggest that partial D2 agonists exert similar, but not identical, behavioural effects to classical DA antagonists when dopaminergic function in increased by d-amphetamine. The differences in behavioural profile are discussed in relation to variations in the intrinsic efficacy of the dopaminergic compounds and to differences in the response capability of D2 receptor populations underlying the different behaviours produced by d-amphetamine.

Animals↗
PubMed1991

The sequence of the Arbacia punctulata bindin cDNA and implications for the structural basis of species-specific sperm adhesion and fertilization.

Bindin is the major protein component of the acrosome granule of sea urchin sperm which mediates the species-specific adhesion of sperm to the egg surface during fertilization. Bindin isolated from both Arbacia punctulata and Strongylocentrotus purpuratus sperm demonstrate a distinct adhesive preference for eggs of the same species although a significant amount of cross-species reactivity is observed. Here we describe the isolation and sequence of A. punctulata bindin cDNA clones and a comparison of the predicted protein sequence with the sequence previously reported for S. purpuratus bindin (Gao et al., 1986, Proc. Natl. Acad. Sci., USA 83, 8634-8638). Bindins from these genera show substantial sequence similarity in both the mature bindin domain and the probindin precursor region. The most striking identity is a region of 42 conserved amino acids in the central part of the mature bindins. This conserved domain may be responsible for conserved functions of bindin. Regions flanking this conserved element on both the amino and carboxyl side are more highly divergent, suggesting that they are responsible for the species-specific properties of bindin. The mature A. punctulata sequence contains a putative transmembrane segment between residues 431 and 451 that is absent from S. purpuratus bindin. This structural element may account for the previous observation that isolated A. punctulata bindin uniquely forms multilamellar structures reminiscent of lipid bilayers and binds significant amounts of phospholipid and detergent. The structure of this hydrophobic segment also displays a number of similarities to viral fusion peptides.

Amino Acid Sequence↗
PubMed1991

High-affinity uptake of [3H]GABA by submucous ganglion cells, nerve fibres and peri- and para-vascular fibres in guinea-pig and rat intestine.

Segments of the intestinal wall from the guinea-pig and rat were dissected, and laminae from the submucous layer subjected to light microscopic [3H]GABA autoradiography. The laminae were carefully prepared so that their planar arrangement could be easily viewed. Intense labelling of fine processes by [3H]GABA was found in the different laminae of the submucous including Henle's or Schabadasch's plexus, the vascular nerve plexus, and a network of fibres subjacent to the muscularis mucosae. This labelling was extensive and represented neuronal-specific high-affinity uptake of radiolabelled GABA. The pattern of labelling was different between the laminae; however, within individual laminae, the distribution of labelled fibres was characteristic of the local nerve networks. Ganglia displayed intense labelling of neuropil and ganglion cells. These results provide strong evidence for the presence of GABAergic nerve cells and processes in the mammalian intestinal submucosa.

Animals↗
PubMed1991

Contradictions in the development of new hospices: a case study.

Despite a decade of concern about the 'mushrooming' of new hospice developments within the British Isles, we remain remarkably ignorant about the processes which lead to the initiation of new hospice projects and the factors which affect their progress. Three inter-related issues appear important: (1) policy and resource implications; (2) changing models of hospice care; (3) 'community' factors. This paper explores the interconnections between these, using a case study approach and describes in detail the efforts of a single local voluntary group to establish a programme of community care for dying people. It shows that: (1) local 'communities' are likely to make continued demands for hospice type care, despite official scepticism about proliferation; but also that these communities should not be seen as homogeneous in their aspirations and demands; (2) new models of community care will interact with wider policy changes in the NHS and Social Services to raise questions about how terminal care services can be further developed; (3) shifts away from traditional in-patient models of care are likely to high-light divisions between 'lay' and 'professional' groups in their perceptions of how services can be delivered.

Community Participation↗
PubMed1991

Disseminated pneumocystis carinii infection in AIDS.

Eight patients with AIDS and Pneumocystis carinii infection were studied. Protean manifestations were a feature not untypical of disseminated pneumocystosis. Aerosolised pentamidine as prophylaxis against P carinii pneumonia was ineffective at suppressing dissemination. The knowledge that extrapulmonary infection can occur has implications for the detection and treatment of, and prophylaxis against, P carinii infection. The survival of patients with disseminated pneumocystosis is particularly poor, and may be due to a lack of clinical awareness and consequent delay in diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1991

MR imaging in hydatid disease.

Hydatid cysts may develop anywhere in the body as a result of the presence of a viable parasite (Echinococcus granulosus). Depending on the condition of the parasite, the host reaction, and therapy, the hydatid cyst will degenerate and may eventually collapse, leaving an area of calcification in the host tissue. The purpose of this pictorial essay is to demonstrate the use of MR imaging in the diagnosis of the various stages of hydatid disease and in monitoring response to therapy.

Albendazole↗
PubMed1991

Treatment of antenatal myasthenia gravis.

Maternal myasthenia gravis has been associated with the presence of neonatal myasthenia and sometimes fatal congenital anomalies. As a result, antenatal therapy directed at fetal sequelae may be indicated. We present the case of a pregnant myasthenic woman whose two previous pregnancies had ended in neonatal deaths from fetal deformations that were presumably due to maternal myasthenia. Serial plasmaphereses and oral prednisone therapy were used in an attempt to depress maternal anti-acetylcholine receptor antibody titers. As anti-acetylcholine receptor antibody titers fell, fetal breathing movements became apparent by ultrasound, and as these titers rose, no fetal breathing movements were apparent. Our patient delivered an infant with transient neonatal myasthenia but normal pulmonary development and no deformations. We suggest that the therapy given may have improved the outcome of this pregnancy compared with her two previous pregnancies.

Administration, Oral↗
PubMed1990

Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins.

The MDR1 gene, responsible for multidrug resistance in human cells, encodes a broad specificity efflux pump (P-glycoprotein). P-glycoprotein consists of two similar halves, each half including a hydrophobic transmembrane region and a nucleotide-binding domain. On the basis of sequence homology between the N-terminal and C-terminal halves of P-glycoprotein, we have previously suggested that this gene arose by duplication of a primordial gene. We have now determined the complete intron/exon structure of the MDR1 gene by direct sequencing of cosmid clones and enzymatic amplification of genomic DNA segments. The MDR1 gene includes 28 introns, 26 of which interrupt the protein-coding sequence. Although both halves of the protein-coding sequence are composed of approximately the same number of exons, only two intron pairs, both within the nucleotide-binding domains, are located at conserved positions in the two halves of the protein. The other introns occur at different locations in the two halves of the protein and in most cases interrupt the coding sequence at different positions relative to the open reading frame. These results suggest that the P-glycoprotein arose by fusion of genes for two related but independently evolved proteins rather than by internal duplication.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Aggressive jejunal lymphoma of large granular lymphocytes. Immunohistochemical, ultrastructural, molecular, and DNA content analysis.

An unusual large cell lymphoma of the proximal jejunum with large granular lymphocyte (LGL) morphologic characteristics and T-helper/inducer cell phenotype is described. Although the cells strongly expressed Leu-7 (HNK-1), studies with antibodies directed against the more specific natural killer (NK) antigens, CD16 (Leu-11) and Leu-19, were negative. Ultrastructural analysis of the neoplastic cells demonstrated substantial numbers of electron-dense granules and rare parallel tubular arrays. Clonal rearrangement of the T-cell receptor beta chain gene and germline configuration of the immunoglobulin heavy chain gene confirmed the T-cell origin of the neoplastic cells. This lymphoma pursued an aggressive clinical course, with rapid dissemination to the lungs and central nervous system. DNA content analysis indicated that a similar DNA aneuploid population was present in the jejunal primary and lung tissue at recurrence. There was no evidence of nodal, peripheral blood, splenic, or bone marrow involvement. Morphologic and functional similarities between the lymphoid tissues of the gastrointestinal tract and lung have previously prompted a classification of the immune system into distinct peripheral somatic and mucosal components. Based on the distribution and migratory properties of the tumor cells in this case, the authors propose that this lymphoma arose from a minor mucosa-associated LGL subset that may be unrelated to circulating LGLs. In addition, these observations emphasize that prominent granulated cytomorphologic features may be seen in neoplastic disorders with the T-helper/inducer phenotype, as well as in the more widely recognized lymphoproliferative disorders of NK and cytotoxic/suppressor cell types.

Aged↗
PubMed1990

Cardiovascular and symptomatic reduction effects of alprazolam and imipramine in patients with panic disorder: results of a double-blind, placebo-controlled trial.

Seventy-nine patients with panic disorder were randomized to an 8-week double-blind treatment with alprazolam, imipramine, or placebo. Patients kept daily records of panic attacks, activity, anxiety, sleep, and medication use. Weekly measures of anxiety, depression, somatic symptoms, fears, avoidance, disability, and improvement were obtained. All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures. By physician and patient global assessment, patients receiving alprazolam or imipramine were significantly better than patients on placebo. The alprazolam effects were apparent by week 1; the imipramine effects by week 4. All groups showed significant reductions in anxiety, depression, somatic measures, and panic attack frequency. At 8 weeks, patients in the alprazolam group reported significantly less fear than patients in the other two groups. Subjects in the imipramine group showed a significant increase in heart rate and blood pressure.

Adult↗
PubMed1990

Identification and catabolic activity of well-derived gasoline-degrading bacteria from a contaminated aquifer.

Approximately 300 gasoline-degrading bacteria were isolated from well water and core material from a shallow coastal aquifer contaminated with unleaded gasoline. Identification of 244 isolates revealed four genera: Pseudomonas, Alcaligenes, Nocardia, and Micrococcus, with pseudomonads making up 86.9% of bacteria identified. A total of 297 isolates was sorted into 111 catabolic groups on the basis of aerobic growth responses on 15 gasoline hydrocarbons. Each test hydrocarbon was degraded by at least one isolate. Toluene, p-xylene, ethylbenzene, and 1,2,4-trimethylbenzene were most frequently utilized as growth substrates, whereas cyclic and branched alkanes were least utilized. Most isolates were able to grow on 2 or 3 different hydrocarbons, and nearly 75% utilized toluene as a sole source of carbon and energy. Isolates were remarkably specific for hydrocarbon usage, often catabolizing only one of several closely related compounds. A subset of 220 isolates was sorted into 51 groups by polyacrylamide gel electrophoresis. Pseudomonas aeruginosa was partitioned into 16 protein-banding groups (i.e., subspecies) whose catabolic activities were largely restricted to substituted aromatics. Different members of subspecies groups defined by protein-banding pattern analysis often exhibited different growth responses on the same hydrocarbon, implying marked strain diversity. The catabolic activities of well-derived, gasoline-degrading bacteria associated with this contaminated aquifer are consonant with in situ adaptation at the site.

Bacteria, Aerobic↗