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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 289 records · Page 16Linked to original sources
PubMed1985

Methodological considerations of epidemiological diagnoses in respiratory diseases.

Since epidemiological research depends extensively on questionnaire responses, a comparison of such responses with a standardized medical evaluation was conducted. It was found that standardized questionnaires do well in comparison for certain kinds of information on chronic conditions. However, clinical evaluations will elicit more information, specifically of a milder nature. It was concluded that standardized epidemiological questionnaires are satisfactory for survey of chronic conditions.

Adolescent↗
PubMed1985

An electrophysiological analysis of the actions of the 3-PPP enantiomers on the nigrostriatal dopamine system.

Extracellular single unit recording and microiontophoretic studies were carried out in chloral hydrate-anesthetized gallamine-paralyzed rats to investigate the actions of the enantiomers of the dopamine (DA) analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, on the nigrostriatal DA system. Intravenously administered (+)- or (-)-3-PPP consistently inhibited nigral DA neuronal activity; these actions were readily antagonized by haloperidol but were not affected by a pretreatment of reserpine plus alpha-methyltyrosine. In contrast to (+)-3-PPP, the (-)-enantiomer produced only partial inhibition of the majority of cells studied and was also capable of partially reversing the inhibitory action of apomorphine. A prior hemitransection of the brain did not alter the inhibitory action of either enantiomer. Whereas iontophoretically ejected (+)-3-PPP consistently reduced DA cell firing rate, similarly applied (-)-3-PPP reduced the activity of only some DA cells, while the majority were not influenced. In addition, iontophoresis of (-)-3-PPP could reduce the inhibitory effect of similarly applied DA or (+)-3-PPP. The (+)-enantiomer reduced caudate neuronal activity both after intravenous administration and iontophoresis. Intravenously administered (-)-3-PPP failed to influence or increased the activity of these neurons and reversed the inhibitory action of apomorphine. However, iontophoretically ejected drug reduced caudate cell activity and did not influence the inhibitory action of DA. The activity of non-DA zona reticulata neurons was inconsistently influenced by the 3-PPP enantiomers. It is concluded that (+)-3-PPP is a directly acting DA agonist, stimulating both DA autoreceptors and postsynaptic DA receptors. In contrast, (-)-3-PPP appears to be a partial agonist at nigral DA autoreceptors, whereas the action of the drug at putative postsynaptic DA receptors in the caudate remains to clarified.

Animals↗
PubMed1985

Dopamine receptor agonists: mechanisms underlying autoreceptor selectivity. II. Theoretical considerations.

In a companion article, we extensively reviewed the pharmacological actions of the enantiomers of the dopamine analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP. The profiles of action exhibited by transdihydrolisuride (TDHL) and the trans-fused 7-OH-1,2,3,4,4a,5,6,10-octahydrobenzo(f)quinoline (HW 165) were also described. These latter agents, along with (-)-3-PPP, exert a variety of effects at different DA receptors depending on the anatomical location of these receptor sites and the experimental conditions. In the first part of the present article, it is suggested that the intrinsic activity of these agents in different pharmacological models is dependent on the responsiveness of the relevant DA-receptors which, in turn, is related to the degree of previous agonist occupancy of these sites. In situations where these agents exhibit partial agonist activity, their pharmacological effect is also dependent on the relative concentrations of drug and endogenous DA competing for common receptor sites. A number of theoretical implications will be discussed relevant to the suggestion that DA receptors exist in various adaptational states which can influence drug action. In the second part of this review, we will consider the behavioural profile exhibited by (-)-3-PPP in relation to that observed with classical DA antagonists. In addition, the potential clinical application of (-)-3-PPP and similar-acting agents will be discussed.

Animals↗
PubMed1985

Sub-chronic administration of (-)-3-PPP and central dopamine receptor sensitivity changes.

The effects of sub-chronic treatment with (-)-3-PPP (8 mg/kg, s.c., b.i.d. for 21 days), a dopaminergic agent with mixed agonist/antagonist properties, were investigated by means of behavioural and in vivo biochemical methods. There was no change in basal locomotor activity and central dopamine (DA) synthesis after 24 hours withdrawal. A slight, though significant reduction of the locomotor suppressive effect and of the DA synthesis-stimulating effect of acute (-)-3-PPP challenge doses of 0.125 and 1.0 mg/kg (s.c.), respectively, were demonstrated in (-)-3-PPP-pretreated as compared to vehicle-pretreated rats. No change in either action was evident after acute challenge with 8.0 mg/kg (s.c.) of the drug. The plasma levels of (-)-3-PPP were virtually unchanged by pretreatment with active drug. The findings are discussed in terms of a modest down- and up-regulation of DA autoreceptors and postsynaptic receptors, respectively, induced by the subchronic (-)-3-PPP treatment.

Animals↗
PubMed1985

Dopamine-receptor agonists: mechanisms underlying autoreceptor selectivity. I. Review of the evidence.

The behavioural, biochemical, neuroendocrinological and electrophysiological actions of the enantiomers of the dopamine (DA) analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, are extensively reviewed. (+)-3-PPP acts in a fashion similar to classical direct-acting DA agonists, stimulating both DA autoreceptors and postsynaptic DA receptors, although in some situations the drug appears to exhibit partial agonist activity. (-)-3-PPP exerts a variety of actions in different pharmacological models. Either agonistic, antagonistic or both agonistic and antagonistic activity are observed depending on the anatomical location of the relevant DA receptors and the experimental conditions. The actions of transdihydrolisuride (TDHL) and the trans-fused 7-OH-1,2,3,4,4a,5,6,10b-octahydrobenzo(f)quinoline (HW 165) are also discussed. These agents possess a similar spectrum of action to (-)-3-PPP suggesting a new generation of DA agonists which exhibit variable intrinsic activity at different DA receptors. Finally, evidence is presented indicating that the 3-PPP enantiomers display selectivity for DA receptors.

Acetylcholine↗
PubMed1985

The psycho-social consequences of intermittent husband absence: an epidemiological study.

This paper examines the psycho-social effects on wives of their husbands' intermittent absence on off-shore oil rigs. It is based on data gathered from a random sample of wives living in the Aberdeen area, and it proceeds in three stages. The analysis begins with a comparison between wives whose husbands work on- and off-shore, it goes on to examine differential reaction to husband absence in the off-shore group and concludes with an attempt to estimate prevalence of the 'intermittent husband syndrome'. All the available evidence suggests that the psycho-social effects of intermittent husband absence have been exaggerated. The mental and physical health of wives of men working off-shore was similar in most respects to the health of wives whose husbands work on-shore. Within the sample of wives whose husbands worked off-shore those most affected by intermittent husband absence were 'Novices' (newly married wives with preschool children and no previous experience of husband absence), those with outside employment and those experiencing irregular absences. But even among such groups with fairly pronounced mood and behaviour changes there was little evidence of raised levels of morbidity. When defined in terms of specified levels of reactivity, marital conflict and morbidity prevalence of the 'intermittent husband syndrome' was found to be around 10%.

Adjustment Disorders↗
PubMed1985

Novel dopamine receptor agonists and antagonists with preferential action on autoreceptors.

The enantiomers of cis-5-hydroxy-1-methyl-2-(di-n-propylamino)tetralin and its methyl ether have been synthesized. The compounds were tested for central dopamine (DA) receptor activity, by using biochemical and behavioral tests in rats. The (1R,2S)-(-) enantiomers of 1 and 2 are characterized as centrally acting DA-receptor agonists while the corresponding (1S,2R)-(+) enantiomers are characterized as centrally acting DA-receptor antagonists. Compounds (+)-1 and (+)-2 differ from classical neuroleptics in being able to increase DA synthesis rate in a wide dose range without reducing locomotor activity, suggesting a pronounced selectivity for DA autoreceptors. Also the (-) enantiomers seem to act preferentially on DA autoreceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

Masculinity, femininity, type A behavior, and psychosocial adjustment in medical students.

The freshman class of a midwestern medical school completed measures of masculinity and femininity, Type A behavior, and a variety of dependent variables concerning psychological well-being, adjustment, and interpersonal satisfaction. Appropriate statistical treatment of the data revealed strong and consistent masculinity effects on neuroticism, depression, self-esteem, confidence, hedonic capacity, locus of control, and relationship satisfaction. Femininity main effects varied in number as a function of the statistical method employed and involved a more diverse group of variables than is typically reported. Additive androgyny formulations of mental health were supported; balance androgyny formulations were not. No evidence for a Type A X Masculinity effect on adjustment was found. Discussion focuses on the correct interpretation of masculinity and femininity scales, comparability of analysis of variance (ANOVA) and multiple regression statistical analyses, and the viability of the concept of androgyny.

Adult↗
PubMed1985

Acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on dopamine metabolism in mouse and rat striatum.

Monoamines and metabolites in mouse striatum were measured at intervals (0-6 h) after injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 50 mg kg-1 subcutaneously). In addition, the accumulation of 3,4-dihydroxyphenylalanine (dopa), induced by inhibition of the aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015), was assessed during every 15 min (0-135 min) after MPTP administration. The alterations induced by MPTP during the first hour after injection were a transient acceleration followed by a marked retardation of dopa synthesis, a decrease in 3,4-dihydroxyphenylacetic acid (DOPAC; -55%) and an increase in 3-methoxytyramine (3-MT; +400%). Between 60 and 75 min after administration, some dramatic changes took place: a 40% reduction of dopamine (DA), a marked additional increase in 3-MT (to 1300% of control) and an increase in homovanillic acid (HVA; +50%). The period after 75 min was characterized by a further depletion of DA, a decrease in 3-MT and a transient increase in HVA (max. 240% of control). Six hours after the administration, all concentrations of DA and its metabolites were subnormal, i.e. DA (30% of control), 3-MT (10%), DOPAC (10%) and HVA (65%). The MPTP-induced retardation of dopa synthesis was not antagonized by haloperidol or by reserpine pretreatment. MPTP (25 or 50 mg kg-1 s.c.) produced similar acute changes in the levels of DA and its metabolites in rat as in mouse striatum, though much less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Oil wives and intermittent husbands.

An investigation was conducted in the Aberdeen area on wives of oil men working either off-shore or on-shore. No differences were found in measures of general health; but 'off-shore wives' were shown to experience mood and behavioural changes, linked to the pattern of swiftly recurring partings and reunions. While a majority of such wives appeared to tolerate or even thrive on their style of life, 10% had reactions sufficiently pronounced to deserve the label of Intermittent Husband Syndrome or 'caseness'. Many others would have benefited from more effective preventive and support services.

Adult↗
PubMed1985

Investigations into the relations between respiratory illness in children, gas cooking and nitrogen dioxide in the U.K.

In 1977 an association was reported between the prevalence of respiratory illness and use of gas for cooking at home in a national sample of six to 11 year olds living in England and Scotland (p less than .10). Other variables such as social class and number of cigarette smokers at home did not seem to explain the association. As the gas cooker is an unflued appliance emitting a variety of pollutants during gas combustion it was suggested that indoor air pollution might explain the finding. Nitrogen dioxide (NO2) was suspected so a series of studies was conducted to investigate the distribution of levels of NO2 in the home, the relative contribution of sources of NO2 to indoor exposure and the relation between respiratory illness in six to 11 year olds and levels of NO2 in the home. The gas cooker was found to be one of the main sources of NO2 in the home. Winter weekly averages in kitchens with gas cookers had a mean of 112.2 ppb (n = 428, range 5-317 ppb). Levels in electric cooking kitchens were significantly lower (n = 87, mean 18 ppb, range 6-188 ppb). Studies of health indicated a relation between respiratory illness and bedroom levels of NO2 over the range 4-169 ppb (p .10). Results for living room levels of NO2 suggested a similar but non-significant relationship (p greater than .10). No relation was found for kitchen levels of NO2. For schoolchildren any effect on health from indoor NO2 is likely to be weak. However other sections of the population such as infants and the elderly who may spend more time indoors and are particularly susceptible to respiratory illness need to be studied to assess fully the impact that NO2 may be having on health.

Child↗
PubMed1984

(+)- and (-)-3-PPP exhibit different intrinsic activity at striatal dopamine autoreceptors controlling dopamine synthesis.

Both enantiomers of the dopamine analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP; 0.5-32 mg/kg s.c.) dose dependently reduced the increase in striatal dopamine (DA) synthesis rate produced by gamma-butyrolactone (GBL). Whereas (+)-3-PPP completely prevented the action of GBL, (-)-3-PPP was only partially effective. In addition, (-)-3-PPP partially antagonised the inhibitory action of apomorphine on the GBL-induced increase in DA synthesis rate. These findings suggest that (+)- and (-)-3-PPP act as full and partial agonists respectively, at striatal DA autoreceptors controlling DA synthesis.

4-Butyrolactone↗
PubMed1984

Obstetric aspects of the use in pregnancy-associated hypertension of the beta-adrenoceptor antagonist atenolol.

The obstetric implications of the use of the beta-adrenoceptor antagonist atenolol have been evaluated in a prospective, randomized, double-blind, and placebo-controlled study involving 120 women with pregnancy-associated hypertension. The clinical interpretation of antenatal and intrapartum cardiotocographs was uninfluenced by atenolol. Human placental lactogen concentration fell in the atenolol group, but this was not an indicator of subsequent fetal distress. Other obstetric indices, such as urinary estriol excretion, were the same in both groups. Spontaneous premature labor occurred in five women receiving placebo but in none who received atenolol. Together with previously reported findings on pregnancy outcome, our study leads us to conclude that beta-blockers such as atenolol can appropriately be used in the management of hypertension during pregnancy.

Atenolol↗
PubMed1984

Synergistic effects of antigen and soluble T-cell factors in B-lymphocyte activation.

Supernatants from phorbol 12-myristate 13-acetate-activated cultures of the mouse EL4 thymoma, or of several mouse T-cell hybridomas stimulated either by their specific antigen or by concanavalin A, induced primary splenic B cells to proliferate and differentiate to antibody-secreting cells. This effect was not due to interleukin 2 and did not require the presence of macrophages. The antibody response was polyclonal, including antibodies specific for 2,4-dinitrophenyl and pigeon cytochrome c, present in amounts of 1% or less of the total immunoglobulin produced. The addition of either of these antigens increased the amount of the corresponding specific antibody. At very high concentrations of dinitrophenyl-hemocyanin the specific response could be depressed. These observations were taken to demonstrate that soluble T-cell factors are sufficient to activate a portion of naive B cells to antibody secretion and that under these conditions in vitro the presence of antigen merely enhances the specific response.

2,4-Dinitrophenol↗
PubMed1984

Efficient transformation of previously activated and dividing T lymphocytes by human T cell leukemia-lymphoma virus.

Modifying previously reported techniques, we attempted to increase the efficiency of human T cell leukemia-lymphoma virus (HTLV) transformation of human T lymphocytes. Lethally irradiated donor cells (DCs) were cultured with target mononuclear cells (TMCs). DCs included ten HTLV+ T cell lines with varying degrees of virus expression or seven cell lines that do not express HTLV. TMCs were prepared from 20 cord and 16 adult peripheral blood samples, including eight patients with acquired immunodeficiency syndrome (AIDS). TMCs were either added directly to the DCs or were first stimulated with phytohemagglutinin (PHA) (5 micrograms/mL) and grown in T cell growth factor (TCGF) prior to exposure to DCs. The presence of integrated HTLV proviral DNA in the transformed cells was determined by dot blot hybridization, utilizing a cloned probe to the HTLV-I genome. HTLV production by transformed TMCs was assessed for HTLV p19, reverse transcriptase, and virus particles. No transformation occurred with T cell donor lines that do not express HTLV. Low virus expressor DCs could only, with rare exception, transform preactivated TMCs. High-titer virus-producing DCs could transform activated and nonactivated cord blood cells and activated adult TMCs. Only MT-2 could routinely transform nonactivated normal adult and activated AIDS TMCs. HUT 102 B2 could transform only one activated AIDS sample, the cells of which initially expressed HTLV-like proteins and virions. Transformed cell lines contained subsets of mature T lymphocytes with variable HTLV expression. Prior activation and culture of the T lymphocytes increases the probability and rate of transformation by HTLV, allowing for biologic detection of low HTLV-producing cells and for in vitro expansion of T lymphocyte subsets from selected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Factors affecting the entry of antibiotics into Escherichia coli.

Factors affecting the entry into Escherichia coli of diverse antibacterial agents, especially beta-lactams were investigated. Agents of greater than a critical molecular weight (approximately 600 Daltons) penetrated extremely poorly. However, there was little correlation between penetrative ability and molecular weight for substances below the critical size. Within classes of related antibiotics (e.g. cephalosporins) penetrative ability was highly dependent on hydrophobicity. The relationship was parabolic rather than linear in nature. The proposal that the envelope of E. coli preferentially excludes hydrophobic molecules is to some extent an artefact arising from pre-selection of the agents used. For unrelated antibiotics hydrophobic nature was a poor guide to penetrative ability. A rather empirical property, diffusion ability through agar, was found to show good inverse correlation with penetrative ability for many unrelated antibiotics.

Anti-Bacterial Agents↗
PubMed1983

Central dopamine receptor agonist and antagonist actions of the enantiomers of 3-PPP.

The two enantiomers of the putative centrally acting dopamine (DA) autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP (Hjorth et al. 1981), were pharmacologically evaluated. An extensive series of biochemical and behavioural experiments unexpectedly revealed that both (+)- and (-)-3-PPP showed clear, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA agonist with autoreceptor as well as postsynaptic receptor stimulatory properties. In contrast, although (-)-3-PPP similarly activates DA autoreceptors it acts concomitantly as an antagonist at postsynaptic DA receptors. Moreover, both behavioural and biochemical data on motor activity and DA synthesis and turnover suggest a preferential limbic action for the (-)-enantiomer. These results are discussed in terms of the dual antidopaminergic action of (-)-3-PPP coupled with anatomical differences in the feedback organisation in central (viz, limbic vs striatal) DA systems. It is suggested that compounds like (-)-3-PPP may be of potential clinical utility in the treatment of psychotic disorders, whilst lacking the seriously incapacitating motor dysfunctions produced by current neuroleptic therapy.

Animals↗