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Biomedical subjects

P Duffy

Publications and source records attributed to P Duffy.

At least 109 records · Page 6Linked to original sources
PubMed1988

Behavioral and neurochemical effects of acute and daily cocaine administration in rats.

Daily cocaine injection into rodents produces a progressive increase in the motor stimulant effect of acute cocaine administration. In this study it was found that daily cocaine injection (15 mg/kg i.p. x 3 days) produced an enhanced motor stimulant response to acute cocaine injection. The behavioral augmentation was linear with regards to dose in horizontal activity and behavioral intensity rating, but was biphasic in vertical activity. Augmented vertical, but not horizontal, activity in response to acute cocaine was found to persist for 2 weeks after the last daily injection of cocaine. Acute injection of cocaine was found to significantly decrease the level of dopamine (DA) metabolites in the nucleus accumbens, striatum and A10 DA region. In rats pretreated with daily injections of cocaine (15 mg/kg i.p. x 3 days), an acute challenge of cocaine 14 days after the last daily injection produced a more consistent decrease in DA metabolites in the nucleus accumbens, striatum and prefrontal cortex compared to daily saline-pretreated rats. In contrast, daily cocaine treatment abolished the decrease in DA metabolites produced in the A10 region by an acute cocaine challenge. Acute injection with cocaine was found to significantly depress dopa accumulation in the A10 region, nucleus accumbens and striatum. This effect was abolished in the A10 region in rats pretreated 14 days previously with daily injections of cocaine (7.5, 15.0 or 30 mg/kg i.p. x 3 days), but remained intact in the nucleus accumbens and striatum, except after daily pretreatment with the highest dose of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The viable cryopreserved allograft aortic valve.

One hundred and twenty-four patients underwent aortic valve replacement with a nonviable 4 degrees C refrigerated aortic allograft valve. One hundred and eighty-four patients underwent aortic valve replacement with a viable cryopreserved aortic allograft valve in a later era. The longest follow-up was 16 years for the group with the nonviable valve and 11 years for the group with the viable valves. Within this time frame, reoperation was required in 23 patients with nonviable valves for leaflet perforation or rupture whereas no patients in the group with viable valves developed this complication (p less than 0.0001). The prevalence of endocarditis and thromboembolism was very low in both groups. Viability of leaflet tissue is associated with an important improvement in durability over nonviable allograft valves. Consequently, long-term follow-up results of allograft valves might be best expressed in terms of viability. The current evidence suggests that the viable cells are donor in origin. The viable cryopreserved aortic allograft valve offers significant advantages over current nonviable allograft valves, mechanical valves, and bioprostheses.

Actuarial Analysis↗
PubMed1987

Mu opioid receptor involvement in enkephalin activation of dopamine neurons in the ventral tegmental area.

Many lines of evidence suggest that opioids act in the A10 dopamine (DA) region to activate DA neurons projecting to limbic terminal areas. Thus, injection of morphine and enkephalin analogs into the ventral tegmental area (a major subnucleus of the A10 DA region) produces an increase in spontaneous motor activity that is blocked by DA receptor antagonists and increases DA metabolism in the nucleus accumbens. The present study utilized enkephalin analogs specific for either the mu or delta opioid receptor to evaluate which receptor subtype(s) is activating the A10 DA neurons. It was found that the specific mu agonist, Try-D-Ala-Gly-NMe-Phe-Gly-ol, was significantly more potent than the specific delta agonist, [D-Pen2,5]-enkephalin, at increasing spontaneous motor activity or DA metabolism in the nucleus accumbens, septum, striatum and prefrontal cortex. Further, naloxonazine, a putative antagonist of the mu-1 isoreceptor, significantly attenuated the motor-stimulant effect and increase in DA metabolism produced by intra-ventral tegmental area injection of Tyr-D-Ala-Gly-NMe-Phe-Gly-ol. It was found that the disposition of microinjected Tyr-D-Ala-Gly-NMe-Phe-Gly-ol or [D-Pen2,5]-enkephalin was not responsible for the difference in their potency. It is concluded that the mu receptor and, perhaps, the mu-1 isoreceptor mediate a major portion of the activation of A10 DA neurons previously demonstrated with mixed mu and delta opioid agonists.

Animals↗
PubMed1987

Neurochemical and behavioral effects of corticotropin-releasing factor in the ventral tegmental area of the rat.

Corticotropin-releasing factor (CRF) is thought to have a neurotransmitter function in the mammalian central nervous system. The release of CRF into the hypothalamic-hypophyseal portal system in response to stress is known, and it has been suggested that CRF may function elsewhere in the central nervous system to promote stress-induced physiological and behavioral changes. Acute stress has been shown to activate dopamine (DA) neurons in the ventral tegmental area (VTA) that project to the prefrontal cortex. To determine whether CRF may act in the VTA to activate the mesocortical or mesolimbic DA systems, it was injected into the VTA of rats, and changes in spontaneous motor behavior and DA metabolism were measured. Intra-VTA injection of CRF produced a dose-dependent increase in horizontal and vertical photocell counts with a minimal effective dose of 0.01 and 0.1 nmol, respectively. In contrast, the minimal effective dose for CRF-stimulated motor behavior after injection into the lateral ventricles was 0.3 nmol for horizontal activity. Furthermore, in the open field, the behavioral profile of CRF (0.3 nmol) given intra-VTA differed from that observed after intraventricular injection. The motor stimulant effect of intra-VTA CRF was not blocked by pretreatment with the DA receptor antagonist haloperidol. After intra-VTA injection, CRF produced a dose-dependent decrease in DA metabolism in the prefrontal cortex. The decrease in DA metabolism in the prefrontal cortex was present at 30 and 60 min but not at 120 min after injection, and in the nucleus accumbens DA metabolism was increased only at 60 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Sensitization to repeated morphine injection in the rat: possible involvement of A10 dopamine neurons.

Daily administration of morphine in rats produces an increase in the motor stimulant effect of subsequent morphine injections. This study was designed to characterize the behavioral sensitization produced by daily morphine and to evaluate the involvement of the mesolimbic and/or mesocortical dopamine (DA) neurons. Daily injection of morphine for 7 days produced an increase in both horizontal and vertical photocell counts. There was no difference in morphine levels in the blood or brain between daily morphine- and daily saline-treated rats at 30 or 90 min after acute injection of morphine. The increase was present for 60 days after initiating treatment and was associated with increases in locomotion, rearing, sniffing, grooming and bursting. Sensitization to morphine was prevented by pretreatment with naloxone i.p. or naltrexone methobromide injection into the ventral tegmental area (VTA; location of A10 DA perikarya projecting to limbic and cortical areas). In contrast, pretreatment with the same dose of naltrexone methobromide injected into the nucleus accumbens (limbic DA terminal field) or lateral ventricles did not significantly attenuate behavioral sensitization to morphine. Daily intra-VTA injections of the mu opioid agonist Tyr-D-Ala-Gly-NMe-Phe-Gly-ol enhanced the behavioral stimulant effect of acute morphine. The effects of daily morphine treatment on DA systems were evaluated by measuring DA metabolism, dopa accumulation and DA depletion in the VTA and various DA terminal fields including the prefrontal cortex, nucleus accumbens and striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

A theoretical model simulating the anomalous concentration dependence of the equilibrium thermal unfolding curve of noncrosslinked tropomyosin.

Thermal unfolding curves of tropomyosin have so far been fit only semi-quantitatively by the statistical-mechanical theory of the helix-coil transition. The calculated values of helix content are a bit too small for the most dilute solutions and a bit too large for the most concentrated ones. The theory, as hitherto used, assumes a uniform helix-helix interaction, whereas evidence from studies on molecular segments suggests otherwise. A theoretical model incorporating such non-uniformity in helix-helix interaction is used to produce simulated thermal unfolding curves. These simulated curves, when fit to the theory using the assumption of uniformity, reveal precisely the same discrepancies seen with the experimental data. We conclude that non-uniformity in helix-helix interaction along the tropomyosin molecule is responsible for the small discrepancy between experimental data and the uniform-model theory previously employed.

Models, Theoretical↗
PubMed1986

Naturally occurring cardiac glycosides.

Cardiac glycoside poisoning from the ingestion of plants, particularly of oleanders, occurs with reasonable frequency in tropical and subtropical areas. We have assessed a variety of plant specimens for their cardiac glycoside content by means of radioimmunoassays with antibodies that differ in their specificity for cardiac glycosides. Significant amounts of immunoreactive cardiac glycoside were found to be present in the ornamental shrubs: yellow oleander (Thevetia peruviana); oleander (Nerium oleander); wintersweet (Carissa spectabilis); bushman's poison (Carissa acokanthera); sea-mango (Cerbera manghas); and frangipani (Plumeria rubra); and in the milkweeds: redheaded cotton-bush (Asclepias curassavica); balloon cotton (Asclepias fruiticosa); king's crown (Calotropis procera); and rubber vine (Cryptostegia grandifolia). The venom gland of the cane toad (Bufo marinus) also contained large quantities of cardiac glycosides. The competitive immunoassay method permits the rapid screening of specimens that are suspected to contain cardiac glycosides. Awareness of the existence of these plant and animal toxins and their dangers allows them to be avoided and poisoning prevented. The method is also useful for the confirmation of the presence of cardiac glycosides in serum in cases of poisoning.

Amphibian Venoms↗
PubMed1986

Competitive solid-phase enzyme immunoassay for measuring digoxin in serum.

In this clinically useful enzyme immunoassay of digoxin in serum, we mix sample, beta-galactosidase-labeled digoxin, and anti-digoxin Fab fragments for 30 min at room temperature, then use Sepharose-bound second antibody for phase separation, and measure the unbound enzyme activity directly in the supernate of the equilibrium reaction mixture. The immunoassay buffer--phosphate-buffered isotonic saline with added rabbit globulin (4 g/L), hydrolyzed gelatin (2 g/L), Brij 96 detergent (5 g/L), glycerol (0.25 mol/L), and N-acetyl-8-anilinonaphthalene-1-sulfonic acid (2 mmol/L)--minimizes serum matrix effects for convenient measuring of unbound enzyme--digoxin conjugate. The immunoassay developed with Fab fragments has better displacement characteristics than that with intact antibody. Performance of the assay compares favorably with that of other manual digoxin immunoassays; in comparison studies with EMIT involving 110 clinical specimens, the coefficient of correlation was 0.97.

Antibody Formation↗
PubMed1986

Neuromedin N mimics the actions of neurotensin in the ventral tegmental area but not in the nucleus accumbens.

Neuromedin N (NN) is a hexapeptide recently isolated from porcine spinal cord that shares a four-amino acid homology with the C-terminus of the biologically active tridecapeptide neurotensin (NT). Microinjection with NT into the ventral tegmental area or nucleus accumbens of rats has been shown to increase locomotor activity and dopamine (DA) metabolism in some limbic areas or to inhibit the motor stimulant effect of intra-accumbens administration of DA, respectively. In this study the effects of microinjected NN were compared with those of NT. After injection into the ventral tegmental area, NN was shown to be more potent than NT at increasing spontaneous motor activity and to produce an increase in DA metabolism in the nucleus accumbens, prefrontal cortex, diagonal band of Broca and septum. However, when injected into the nucleus accumbens, NN was markedly less potent than NT at inhibiting DA-induced behavioral hyperactivity. In addition to DA-related effects, i.c.v. injection with NT causes hypothermia, and i.c.v. administration with NN was without effect on colonic temperature. These data demonstrate that NN has a behavioral profile distinct from that of NT.

Animals↗
PubMed1986

Microconductimetric assay of butyrylcholinesterase activity.

A conductimetric method for the assay of butyrylcholinesterase is described. A new conductimetric cell has been used which allows increased sensitivity. The physicochemical parameters (pH, buffer concentration) have been optimized. With 1 mM butyrylcholine, butyrylcholinesterase activities down to 2 x 10(-4) U ml-1 may be measured. Serum volumes needed for this assay are in the microliter range (1-5 microliters).

Animals↗
PubMed1985

Ligand displacement immunoassay--demonstration of its use for the measurement of serum phenobarbital and phenytoin.

We describe a clinically useful ligand displacement immunoassay for the measurement of serum or plasma phenobarbital and phenytoin. A conjugate of drug-specific antiserum covalently bound to micro-crystalline cellulose and a beta-galactosidase-labelled drug derivative is prepared as a lyophilized reagent. Sample is added to the conjugate and, after 5-min incubation at room temperature, the bound and displaced enzyme-ligand are separated by brief centrifugation. The enzyme activity of the displaced enzyme-ligand is measured on a spectrophotometer or centrifugal analyser. Linear calibration curves are obtained with appropriate sample dilution, allowing generation of the standard curve with a saline zero reference and a single calibrator. The performance of the assay compared favourably with other immunoassays; comparison studies with clinical specimens gave a correlation with EMIT of 0.96 (n = 122) for phenobarbital and 0.95 (n = 96) for phenytoin.

Humans↗
PubMed1985

The use of a monosaccharide linkage group in a heterologous solid-phase enzyme immunoassay for phenytoin.

The preparation is described of monosaccharide-hapten derivatives containing a galactosyl linkage group which bears little structural resemblance to the straight-chain hydrocarbons commonly used for attaching haptens to proteins for use as immunogens. These derivatives are readily synthesised and are coupled to enzymes under mild conditions to produce bridge-heterologous enzyme immunoassays. The use of beta-galactosidase-monosaccharide-phenytoin derivatives in the development of sensitive phenytoin enzyme immunoassays is described and the assays are compared with hapten-heterologous, site-heterologous and homologous phenytoin enzyme immunoassays prepared using other phenytoin derivatives. This technique has application in the development of immunoassays for haptens which have only one functional group to which linkage groups can be attached for covalent coupling of the hapten to proteins.

Animals↗
PubMed1985

Ciliated craniopharyngioma.

A tumor of Rathke's cleft origin was studied, which showed some histologic features consistent with craniopharyngioma, but also had ciliated and mucin-containing cells more commonly observed in Rathke's cleft cysts. The combination of features provides further evidence that craniopharyngiomas and Rathke's cleft cysts have a common embryonic origin.

Craniopharyngioma↗
PubMed1984

Ligand displacement immunoassay: a novel enzyme immunoassay demonstrated for measuring theophylline in serum.

We describe a ligand displacement immunoassay for measurement of theophylline in serum or plasma and show it to be clinically useful. A conjugate of theophylline-specific antiserum covalently bound to micro-crystalline cellulose and a beta-galactosidase-labeled theophylline derivative is prepared as a lyophilized reagent. Sample is added to the conjugate and, after 5-min incubation at room temperature, the bound and displaced enzyme-ligand are separated by brief centrifugation. The enzyme activity of the displaced enzyme-ligand is measured on a spectrophotometer or centrifugal analyzer. Linear calibration curves are obtained with appropriate sample dilution, allowing generation of the standard curve with a saline zero reference and a single calibrator. Performance of the assay compares favorably with that of other theophylline assays; comparison studies with use of 145 clinical specimens gave a coefficient of correlation with EMIT of 0.97.

Anticoagulants↗