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Biomedical subjects

A Johns

Publications and source records attributed to A Johns.

At least 55 records · Page 3Linked to original sources
PubMed1993

Cocaine in the UK--1991.

More than 100 years after Freud's original endorsement of the drug, the use of cocaine is a problem for both users and for society, which struggles to organise effective responses to the epidemic of the last decade. During the 1980s the rapid spread of smokeable cocaine (including 'crack') was seen in the Americas (particularly the US). The initial simple predictions of an identical European epidemic were mistaken. The available data on the extent of cocaine use and of cocaine problems in the UK are examined. New forms of cocaine have been developed by black-market entrepreneurs ('freebase' and 'crack'), and new technologies have emerged for their use; with these new technologies have come new effects and new problems. The general psychiatrist now needs a knowledge of directly and indirectly related psychopathology which has an increasing relevance to the diagnosis and management of the younger patient.

Cocaine↗
PubMed1991

The effects of lectins on the release of EDRF from rabbit aorta.

The effects of the lectins, wheat germ agglutinin (WGA) and concanavalin A (Con A) on endothelium intact pre-contracted rabbit aorta were investigated. WGA (8.3 microM) produced endothelium-dependent relaxations, while Con A (4.3 microM) produced a partially endothelium-dependent relaxation. The endothelium-dependent relaxations to WGA were completely reversed by N-acetylglucosamine, haemoglobin and methylene blue and were partially reversed by NG-monomethyl-L-arginine (L-NMMA). It is suggested that WGA works as an agonist in releasing endothelium-derived relaxing factor (EDRF) from the endothelium of rabbit aorta by interacting with a glycosylated receptor on endothelial cells.

Animals↗
PubMed1991

Phorbol dibutyrate stimulates the release of diffusible endothelium-derived vasoconstrictor factor(s) from canine femoral arteries.

The purpose of this study was to analyze the effect of the tumor-promoting phorbol ester 12,13-dibutyrate (PDBu) on the synthesis/release of nonprostanoid endothelium-derived vasoactive factors. In bioassay experiments (in the presence of 10(-5) M indomethacin), infusion of PDBu (10(-9)-10(-7) M) through a femoral artery (donor) segment with endothelium evoked further, concentration-dependent contraction of superfused canine coronary artery bioassay rings without endothelium (already contracted with 10(-7) M PDBu). Removal of the endothelium from the donor segment abolished further contractions of the bioassay ring to 10(-9) M PDBu and significantly depressed the contractile responses to 10(-9) and 10(-7) M PDBu infused through the donor segment. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate had no effect on vascular preparations mounted in the bioassay system. Selective exposure of the bioassay tissue to 10(-7) M PDBu completely inhibited its responsiveness to basally released endothelium-derived relaxing factor. These data indicate that PDBu stimulates the release of a diffusible and bioassayable vasoconstrictor mediator(s) from the endothelium of canine femoral arteries.

Acetylcholine↗
PubMed1990

Receptor kinetics differ for endothelin-1 and endothelin-2 binding to Swiss 3T3 fibroblasts.

The equilibrium binding, kinetics of ligand-receptor interactions, and biological activity of endothelin-1 and -2 have been studied in Swiss 3T3 fibroblasts. Scatchard analyses of saturation binding data for ET-1 and -2, performed at 4 degrees C to prevent internalization of the occupied receptor, revealed similar affinity constants and numbers of binding sites for endothelin-1 and -2. Experiments designed to determine ligand-induced effects on 45Ca efflux demonstrated no qualitative or quantitative differences between the two endothelin isoforms. In contrast, kinetic studies resulted in different rates of dissociation for the two isoforms and different extents of dissociation. Specifically, only 40% of the bound [125I]endothelin-1 was dissociated at 4 h following the addition of excess unlabeled ligand, whereas 85-90% of the bound [125I]endothelin-2 was dissociated under the same conditions. Endothelin-1 and -2 also differed in the percent of specific cell-associated ligand bound after a 2 h incubation at 37 degrees C following an initial equilibration at 4 degrees C. The differences in dissociation rates and association or internalization rates at 37 degrees C are the first data that differentiate between the two isoforms. It is suggested that isoform-specific differences in the rate of dissociation from cell surface endothelin receptors influence the level of cell-associated endothelin and may be important in determining physiologic responses in vivo.

Animals↗
PubMed1990

Membrane potential and Na(+)-K+ pump activity modulate resting and bradykinin-stimulated changes in cytosolic free calcium in cultured endothelial cells from bovine atria.

The effects of membrane potential on resting and bradykinin-stimulated changes in [Ca2+]i were measured in fura-2 loaded cultured endothelial cells from bovine atria by spectrofluorimetry. The basal and bradykinin-stimulated release of endothelium-derived relaxing factor, monitored by bioassay methods, were dependent on extracellular Ca2+. Similarly, the plateau phase of the biphasic [Ca2+]i response to bradykinin stimulation exhibited a dependence on extracellular Ca2+, whereas the initial transient [Ca2+]i peak was refractory to the removal of extracellular Ca2+. The effect of membrane depolarization on the plateau phase of the bradykinin-induced change in [Ca2+]i was determined by varying [K+]o. The resting membrane potential measured under current clamp conditions was positively correlated with the extracellular [K+] (52 mV change/10-fold change in [K+]o). The observed decrease in resting and bradykinin-stimulated changes in [Ca2+]i upon depolarization is consistent with an ion transport mechanism where the influx is linearly related to the electrochemical gradient for Ca2+ entry (Em - ECa). The inhibition of bradykinin-stimulated Ca2+ entry by isotonic K+ was not due to the absence of extracellular Na+ since Li+ substitution did not inhibit the agonist-induced Ca2+ entry. In K(+)-free solutions and in the presence of ouabain, bradykinin evoked synchronized oscillations in [Ca2+]i in confluent endothelial cell monolayers. These [Ca2+]i oscillations between the plateau and resting [Ca2+]i levels were dependent on extracellular Ca2+ and K+ concentrations. Although the mechanism(s) underlying [Ca2+]i oscillations in vascular endothelial cells is unclear, these results suggest a role of the membrane conductance.

Animals↗
PubMed1990

Social and drug-taking behaviour of 'maintained' opiate addicts.

The roles of the prescribing of maintenance methadone and prescribing injectable drugs in the management of opiate addicts have become subjects of active debate since the advent of HIV. Data are presented on the social circumstances and drug-taking behaviour of 26 opiate addicts who had been receiving maintenance methadone (24 of whom had been receiving at least part of the prescription as injectible methadone ampoules.

Adult↗
PubMed1990

Mechanoreception by the endothelium: mediators and mechanisms of pressure- and flow-induced vascular responses.

Mechanoreception, a widely distributed sensory modality, has been shown to be present in certain blood vessels. Changes in physical forces, like sudden increase of transmural pressure or flow velocity (shear stress), trigger changes in blood vessel diameter; the former reduces it while the latter increases vessel caliber. These changes in diameter, which are the result of contraction and relaxation of vascular smooth muscle in the blood vessel media, can serve the purpose of physiological regulation of blood flow (autoregulation) and protection of the intima against damages from high shear forces. The precise location of mechanosensor(s) and the mechanism of mechanoreception and signal transduction are poorly understood. Accumulating evidence suggests that the endothelium may be a site of mechanoreception and that changes in the synthesis/release of endothelium-derived relaxing (EDRF, EDHF, PGI2) and contracting factors (EDCF) result in altered vascular smooth muscle tone and vessel caliber. Increased shear stress stimulates the release of EDRF and PGI2 probably via activation of a K+ channel (inward rectifier) in endothelial cell membrane. Endothelium-dependent vascular contraction evoked by increased transmural pressure may be the result of (1) reduced release of EDRF (canine carotid artery) and (2) stimulation of the release of a still unidentified EDCF(s) (feline cerebral artery). Thus the endothelium can serve as pressure and flow sensor and is capable of transducing changes in mechanical forces into changes of vascular smooth muscle tone by modulating the release of endothelium-derived vasoactive factors. The physiological importance of the mechanoreception by endothelial cells in the intact circulation remains to be determined.

Animals↗
PubMed1990

Drug use, crime and the attitudes of magistrates.

In a study concerned with the views of magistrates' on crime related to drug use, a 27-item attitudinal questionnaire was sent to a random sample of 154 subjects drawn from all magistrates in the London area. The response rate was 72%. There was broad agreement on the seriousness of crime related to drug use but there were also interesting differences of opinion. A principal components analysis revealed three factors which accounted for 67% of the variance. Factor 1, labelled 'seriousness' relates to the attitude that the extent of drug use and drug-related crimes such as possession, are serious offences. Factor 2, labelled 'intervention', reflects the view that sentencing and treatment are valuable in dealing with drug-related crime. Factor 3, labelled 'responsibility' describes the attitude that drug users are responsible for their offences and for the contents of statements made when withdrawing from drugs. There were differences between the magistrates on items concerning cannabis, personal responsibility for drug-related crime and the value of sentencing options. Magistrates tended to value psychiatric court-reports but some found them unclearly worded and partial to the defendant. Implications for the legal and medical response to drug use and crime are discussed.

Attitude↗
PubMed1989

Bradykinin and inositol 1,4,5-trisphosphate-stimulated calcium release from intracellular stores in cultured bovine endothelial cells.

The relative importance of intracellular and extracellular Ca2+ in the release of endothelium-derived relaxing factor (EDRF) and the mechanisms involved in the release of intracellular Ca2+ were investigated in cultured bovine endothelial cells. The release of EDRF by bradykinin, determined by bioassay, was dose-dependent showing an EC50 of 4 x 10(-10) M. The bradykinin-induced EDRF release from endothelial cells was maintained in the presence of extracellular Ca2+. However, in the absence of external Ca2+, bradykinin-induced EDRF release was both attenuated and transient. In cells loaded to isotopic equilibrium with 45Ca, bradykinin increased the 45Ca efflux into both calcium-containing and calcium-free solutions, with an EC50 for the increase in 45Ca efflux induced by bradykinin of 1.3 x 10(-9) M. The involvement of an intracellular Ca2+ store and the participation of a second messenger in its release were investigated in saponin-permeabilized endothelial cells. In saponin-permeabilized cells, ATP-sensitive calcium uptake was Ca2+,Mg2+ -ATPase-dependent. The ATP-sensitive uptake of calcium at different free Ca2+ concentrations showed at least two compartments involved in the uptake of Ca2+. The 45Ca uptake into the compartment with the lowest affinity and highest capacity could be inhibited by sodium azide, suggesting that this uptake was into mitochondria. The majority of the 45Ca uptake into the azide-insensitive store could be released by inositol-1,4,5-trisphosphate (IP3). The IP3-induced release was not affected by apyrase or exogenous GTP. The EC50 for the release of Ca2+ by IP3 was 1.0 microM and was unaffected by an inhibitor of IP3 breakdown (2,3-diphosphoglyceric acid).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1989

Durability of immunity to diphtheria, tetanus and poliomyelitis after a three dose immunization schedule completed in the first eight months of life.

Blood samples were obtained from school entrants whose primary immunization schedule had consisted of three doses of DT or DTP vaccine and three doses of OPV all given before the age of 8 months. The sera were separated and assayed for diphtheria antitoxin, tetanus antitoxin and antibodies to the three serotypes of poliovirus. The results of the assays showed that the abbreviated three dose schedule induced satisfactory immunity to all five infections until school entry and that a reinforcing dose at 18 months was unnecessary.

Antibodies, Viral↗
PubMed1989

Endothelin-1 stimulates phosphatidylinositol hydrolysis and calcium uptake in isolated canine coronary arteries.

The effects of synthetic endothelin-1 (ET-1) (10(-10)-3 x 10(-7) M) on isometric force, 45Ca2+ uptake, and phosphatidylinositol (PI) hydrolysis were determined in isolated canine coronary artery rings. ET-1 caused contraction and stimulated 45Ca2+ uptake and PI hydrolysis (determined as inositol monophosphate accumulation) in a concentration-dependent manner with EC50 values of 6.3 x 10(-9), 2 x 10(-9), and 3 x 10(-9) M, respectively. Maximal responses were obtained with 3 x 10(-8) M ET-1 for all three parameters. At the maximally effective concentration, ET-1 caused a 1.8-fold increase in the rate of 45Ca2+ uptake following a 1-min exposure (the shortest time point tested) while the contractile response reached maximum only after 6 min. ET-1 (3 x 10(-8) M) stimulated a biphasic accumulation of inositol monophosphate with an initial rapid 1.4-fold increase detectable between 30 and 60 s followed by a secondary 11.9-fold increase at 30 min. These data show that PI hydrolysis and Ca2+ uptake are early events in the action of ET-1 on coronary artery vascular smooth muscle that precede the maximal contractile response. It is suggested that all of these responses are triggered by the interaction of ET-1 with a cell-surface receptor.

Animals↗