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Biomedical subjects

D G Taylor

Publications and source records attributed to D G Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1989

Anaphylactoid reactions mediated by autoantibodies to cholesterol in miniature pigs.

Antoantibodies to cholesterol were detected and purified from normal (nonimmunized) pig serum. The antibodies were assayed by ELISA with crystalline cholesterol as an Ag and by C-dependent damage to cholesterol-laden liposomes. Intravenous injection of liposomes containing cholesterol into anesthetized animals caused decreased hemolytic complement titers, and induced a reaction consisting of transient neutropenia, thrombocytopenia, respiratory distress, cyanosis, pulmonary and systemic hypertension, and decreased cardiac output. Plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha increased 1300 and 200%, respectively, and leukocyte and platelet counts decreased by 36 and 38%, respectively. Injection of cholesterol-free liposomes did not induce the reaction. These results show that naturally occurring autoantibodies to cholesterol can initiate C activation and can be associated with anaphylactoid reaction to exogenously administered cholesterol in pigs.

Anaphylaxis↗
PubMed1989

Two phases of contractile response in rat isolated vas deferens and their regulation by adenosine and alpha-receptors.

Contractions to transmural electrical stimulation and exogenous norepinephrine were recorded in isolated longitudinal segments of rat vas deferens. Electrical stimulation for 30 s produced a biphasic contraction in the vas deferens consisting of a rapid, transient response (Phase I), followed by a slowly developing, sustained contraction (Phase II). N6-Cyclohexyladenosine (CHA), a selective adenosine1 (A1)-receptor agonist, attenuated in a concentration-dependent manner the Phase I contractile response, while having little effect on the Phase II response. In contrast, 2-(phenylamino)adenosine (CV-1808), a selective adenosine2 (A2)-receptor agonist had little effect on either contractile phase. CHA did not inhibit the contraction to exogenous norepinephrine, suggesting that A1-receptors were located at a presynaptic site. The relatively selective alpha 2-receptor agonist clonidine produced the same pattern of contractile inhibition as CHA. The inhibitory effect of CHA on the Phase I contractile response in the vas deferens could be antagonized by the selective A1-receptor antagonist 8-cyclopentyltheophylline, while the selective alpha 2-receptor antagonist idazoxan preferentially antagonized the inhibitory effect of clonidine on the Phase I response. Both the Phase I and Phase II contractile responses were reduced by the selective alpha 1-adrenoceptor antagonist prazosin and the ATP analog alpha, beta-methylene adenosine triphosphate (alpha, beta-methylene ATP), suggesting that norepinephrine and ATP are coreleased as neurotransmitters for both responses. The results of the present study demonstrate that in the rat vas deferens the presynaptic inhibitory effects of adenosine is mediated by the A1-receptor subtype, and that both A1- and alpha 2-receptor agonists exert a selective inhibitory effect on the Phase I contractile response to electrical stimulation.

Adenosine↗
PubMed1989

Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314.

Following documented evidence of the synergism of 5-fluorouracil (5-FU) and radiation therapy and an additive effect with mitomycin and irradiation, pilot studies have demonstrated the potential for definitive radiation therapy in the management of squamous cell and basaloid carcinomas of the anal canal, allowing sphincter preservation. Our study explored the long-term effectiveness of combined therapy at this disease site and examined the feasibility of a Radiation Therapy Oncology Group study involving concomitant radiation therapy and chemotherapy. Between 1983 and 1987, 79 assessable patients with any primary tumor stage of anal canal carcinoma were treated by external-beam irradiation combined with mitomycin given by bolus iv injection and 5-FU given by continuous infusion. Radiation was delivered to the perineum and pelvis to a total dose of 4,080 cGy in 4.5-5 weeks. The inguinal nodal areas received 4,080 cGy, calculated at a 3-cm depth in the center of the nodal area. A 96-hour infusion of 5-FU was started on days 2 and 28 of the irradiation at a dose of 1,000 mg/m2 over 24 hours, and a bolus injection of mitomycin was administered on day 2 at a dose of 10 mg/m2. The overall survival rates are 97% at 1 year and 73% at 3 years. Patients with lesions less than 3 cm in diameter and those treated strictly according to the protocol did significantly better than those with larger lesions and those whose treatment did not comply with the protocol. The interim outcome of the study demonstrates that this combined therapy is effective for patients with anal cancer and allows preservation of the sphincter and of sexual function.

Anal Canal↗
PubMed1989

Quinapril--a preclinical review of the pharmacology, pharmacokinetics, and toxicology.

Quinapril is an orally active, non-peptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor that acts potently and specifically to interrupt the conversion of angiotensin I to angiotensin II in both plasma and tissue. Quinapril is enzymatically hydrolyzed to a pharmacologically active diacid form quinaprilat. Quinapril is efficacious in hypertensive models exhibiting both high (renal hypertensive rats, diuretic-treated dogs) and normal (spontaneously hypertensive rats) plasma renin activity. Quinapril does not prevent the development of hypertension when plasma renin activity (PRA) is markedly suppressed as in the deoxycorticosterone-saline treated rat. Hemodynamic studies in dogs indicate that quinapril decreases total peripheral and renal vascular resistance. Quinaprilat produces natriuresis and mild diuresis at doses that do not alter mean arterial blood pressure. Quinapril has the potential to affect plasma lipids beneficially or at least be "lipid neutral." Oral absorption of quinapril is rapid in rats, dogs, and monkeys. There is rapid and extensive distribution of radiolabel to most tissues except brain. Plasma radiolabel concentration-time profiles exhibit polyexponential decay with a prolonged terminal phase at low concentrations in all species. Metabolism to compounds other than quinaprilat is not extensive. Quinapril is excreted primarily as quinaprilat and to a lesser degree as quinapril. Quinapril is well tolerated in a variety of pharmacologic safety screens and its toxicity profile is similar to that of other ACE inhibitors. Quinapril does not adversely affect reproduction; it is not teratogenic, carcinogenic, or mutagenic.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Immunoassay detection of drugs in racing horses. XI. ELISA and RIA detection of fentanyl, alfentanil, sufentanil and carfentanil in equine blood and urine.

We have developed and evaluated a one step enzyme-linked immunosorbent assay (ELISA) test for sufentanil and a 125I radioimmunoassay test for alfentanil as part of a panel of pre- and post-race tests for narcotic analgesics in racing horses. Our sufentanil ELISA test detects sufentanil with an I-50 of about 0.5 ng/ml. The test is rapid and economical in that it can be read with an inexpensive spectrophotometer, or even by eye. The test readily detects the presence of sufentanil or its metabolites in equine blood and urine from 1 to 24 hours respectively after administration of therapeutic or sub-therapeutic doses of this drug. Our sufentanil assay also cross-reacts with fentanyl, the methylated analogs of fentanyl (designer fentanyls), and carfentanil and detected these drugs in urine for several hours after their administration to horses. It does not, however, cross-react significantly with alfentanil. We have also developed an 125I radioimmunoassay for alfentanil. This test allows detection of alfentanil in blood and urine of horses for up to 4 hours after administration of this drug. As such, these tests are capable of improving the quality and reducing the cost of pre-race and post-race testing for fentanyl, sufentanil, carfentanil and alfentanil and a number of their congeners in racing horses. Similarly, these tests are capable of screening for these drugs in human drug abuse monitoring.

Alfentanil↗
PubMed1989

Immunoassay detection of drugs in racing horses. IX. Detection of detomidine in equine blood and urine by radioimmunoassay.

Detomidine is a potent non-narcotic sedative agent which is currently in the process of being approved for veterinary clinical use in the United States. Since no effective screening method in horses is available for detomidine, we have developed an 125I radioimmunoassay for detomidine in equine blood and urine as part of a panel of tests for illegal drugs in performance horses. Our 125I radioimmunoassay has an I-50 for detomidine of approximately 2 ng/ml. Our assay shows limited cross-reactivity with the pharmacodynamically similar xylazine, but does not cross-react with acepromazine, epinephrine, haloperidol or promazine. The plasma kinetic data from clinical (greater than or equal to 5 mg/horse) as well as sub-clinical doses indicate first-order elimination in a dose-dependent manner. Within the first 30 minutes after intravenous (IV) administration of 30 mg/horse, plasma levels peak at approximately 20 ng/ml and then decline with an apparent plasma half-life of 25 minutes. Diuresis can occur with administration of clinical doses of detomidine and this effect was accounted for in the analysis of urine samples. Using this method, administration of 30 mg/horse can be readily detected in equine urine for up to 8 hours after IV injection. Additionally, doses as low as 0.5 mg/horse can be detected for short periods of time in blood and urine with use of this assay. Utilization of this assay by research scientists and forensic analysts will allow for the establishment of proper guidelines and controls regarding detomidine administration to performance horses and assurance of compliance with these guidelines.

Analgesics↗
PubMed1988

Interaction between propranolol and calcium channel blockers in cardiac and vascular smooth muscle.

The ability of the beta-receptor antagonist propranolol to influence the response of isolated cardiac and vascular smooth muscle to several classes of calcium channel blockers was examined. For comparison, the interactions between propranolol and other classes of negative inotropic and vasorelaxant agents was also evaluated. The results of these studies demonstrate that propranolol pre-treatment significantly enhances the in vitro response to the dihydropyridine calcium channel blocker nifedipine, but not the thiazapine calcium channel blocker diltiazem. This enhancement was unrelated to the negative inotropic or vasorelaxant properties of these agents. In addition, propranolol pre-treatment of rat cortical membranes also enhanced the affinity of nifedipine for the 3H-nitrendipine binding site, but did not alter the effect of diltiazem on 3H-nitrendipine binding. These observations suggest that a direct interaction may exist between beta-receptor antagonists and dihydropyrine-type calcium channel blockers. This interaction may be an important factor in selecting drug therapy for conditions such as hypertension and angina.

Animals↗
PubMed1986

NMR characterisation of healthy rat tissues in vivo.

This study using healthy rats has shown that the prospects for quantitative tissue characterisation using NMR parameters are very encouraging. Imaging allowed the relaxation rates of six rat tissues to be obtained in vivo. On the same imaging system and using identical experimental conditions the variation in T**1 (T1 evaluated assuming a monoexponential decay) of a tissue across up to 20 rats of the same age, sex and species was less than 7%. When individuals of different ages, sex and strain were used a similar small variation was observed. Further, we believe that any inherent biological variation in T**1 and T**2 values has not yet been detected in our studies.

Age Factors↗
PubMed1986

Camphor revisited: studies of 2,5-diketocamphane 1,2-monooxygenase from Pseudomonas putida ATCC 17453.

The oxygenating component of 2,5-diketocamphane 1,2-monooxygenase from Pseudomonas putida ATCC 17453 was purified to homogeneity by a combination of ammonium sulfate fractionation and chromatography on DEAE-cellulose and polyanion SI-17 columns. It had an Mr of 78,000, bound one molecule of nonautooxidizable flavin mononucleotide (FMN), consisted of two subunits of equal molecular weight, and existed in two electrophoretically distinguishable active forms. The oxygenating complex was constructed from equimolecular amounts of an NADH oxidase, which could be purified separately (Mr, 36,000), and the oxygenating component. Most of the NADH oxidase dissociated from the oxygenating component during purification, although traces remained, to give the final preparation of the oxygenating component significant oxygenase activity. FMN did not dissociate significantly from the oxygenating component during purification, but it was not covalently bound and could be removed under a variety of conditions. Binding between the two proteins that made up the active complex was fairly weak and freely reversible. It probably occurred through the FMN which was strongly bound to the oxygenating component and for which the NADH had a weak binding site. Iron was not present at a significant level in the oxygenating component, and in common with other characterized Baeyer Villiger monooxygenases, 2,5-diketocamphane 1,2-monooxygenase was found to be a simple flavoprotein.

Apoenzymes↗
PubMed1984

Identification and counting of asbestos fibers.

A combined analytical electron microscopic/optical count method for the determination of airborne asbestos fibers was tested for precision and bias. A modified phase contrast microscopic count method (NIOSH Method 7400) was used to determine total fiber content. The analytical electron microscope (AEM) procedure was added to identify the fraction of amosite asbestos fibers in airborne, laboratory-generated samples containing amosite and wollastonite fibers. Then this fraction was applied to the routine optical counts of all the samples in the set to estimate the asbestos fiber concentration. The effects of sample to sample, wedge to wedge, within wedge and between and counter variability were examined. In addition, the variabilities of the elemental ratio within a fiber and between fibers was also determined to find their possible influence on the ability to identify the fiber as amosite in the presence of other silicate fibers. A precision of 20.1% relative standard deviation (RSD) and a bias of -9.1% for the AEM count method compared with the optical count procedure were found for these mixed fiber samples.

Air Pollutants↗
PubMed1984

Discrimination of time: comparison of foveal and peripheral sensitivity.

Temporal processing is different in the periphery than in the fovea. Two measures of temporal sensitivity, increment thresholds for onset asynchrony and temporal modulation thresholds (flicker), were studied in the fovea and at 20 deg in the lower visual field. The ability to detect incremental changes in the time between the onsets of two vertical lines was generally more precise in the fovea than at the peripheral locus, at least for asynchronies ranging from 10 to 80 msec. Flicker thresholds were measured from 1 to 40 Hz with a vertical-line target used for the asynchrony thresholds. The peripheral flicker function peaks at a higher temporal frequency (15-20 Hz) than the foveal function (8-10 Hz); this suggests that the peripheral temporal impulse response follows a faster time course than the foveal impulse response. Asynchrony discrimination would potentially provide a simple estimate of the temporal sensitivity underlying velocity discrimination. We find that asynchrony discrimination is not a good predictor of velocity thresholds; it fails at the high velocities at which velocity discrimination is most precise.

Adult↗
PubMed1984

Comparison of calcium channel inhibitors on vagal heart rate responses elicited by arterial baroreceptor reflexes in anesthetized dogs.

Actions of the calcium channel inhibitors, nimodipine, nifedipine, verapamil and diltiazem, and the direct-acting vasodilator, sodium nitroprusside, were compared on baroreceptor reflex-induced bradycardia elicited by pressor responses produced by norepinephrine and on reflex-induced tachycardia elicited by the hypotensive responses to acetylcholine in alpha-chloralose anesthetized dogs. Beta adrenoceptor blockade with propranolol was maintained throughout the experiments to assure that the cardiac reflexes were vagal in origin. The reflex vagal bradycardic ratio (-delta heart rate/+delta blood pressure) elicited by norepinephrine-induced pressor responses was reduced dose-dependently by nimodipine (0.1-1.0 micrograms/kg/min i.v.) and diltiazem (3.0-30 micrograms/kg/min i.v.) at 20 min after starting each dose and by verapamil (100 micrograms/kg i.v. loading dose plus 1.0-30 micrograms/kg/min i.v.) at 10 min after each dose. In contrast, nifedipine (0.1-3.0 micrograms/kg/min i.v. at 20 min) and sodium nitroprusside (3.0-20 micrograms/kg/min i.v. at 20 min) did not inhibit the bradycardic ratio. Resting mean arterial blood pressure was reduced similarly by all of the agents and tonic heart rate was essentially unchanged. Studies on the site of action revealed that nimodipine (0.3 and 1.0 micrograms/kg/min i.v. at 20 min) attenuated the reflex vagal bradycardia evoked by pressure elevations in the isolated carotid sinus, but did not change the reflex responses elicited by electrical stimulation of afferent fibers in the carotid sinus nerve. The reflex tachycardic ratio (+ delta heart rate/-delta blood pressure) evoked by acetylcholine-induced hypotensive responses was reduced in a dose-related fashion by all of the agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1984

The Pennsylvania Infant and Family Development Project, II: The development of reciprocal interaction in the mother-infant dyad.

In order to assess stability and change in mother-infant interaction, 74 mother-infant dyads were observed at home under naturalistic conditions when infants were 1, 3, and 9 months. Both conceptually and empirically guided data-reduction procedures indicated that 4 summary constructs underlie 15 behavioral categories coded: reciprocal interaction, noninvolvement, distress, and basic care. Mean levels of reciprocal interaction remained unchanged over time, with individual differences being stable. Mean levels of noninvolvement increased from 1 to 3 months only, and remained stable across all time periods, while mean levels of distress and basic care declined linearly across the 9-month periods, with individual dyads displaying little stability. A final analysis assessed stability and change in the 9 component variables comprising the reciprocal interaction construct. Significant change was discerned with respect to several of these components, as well as a good deal of instability. These findings led to the conclusion that, in the face of sameness in mother-infant interaction across the first 9 months, there is also much change.

Adult↗
PubMed1984

The Pennsylvania Infant and Family Development Project, III: The origins of individual differences in infant-mother attachment: maternal and infant contributions.

In order to test 4 specific hypotheses regarding the interactional histories associated with variation in quality of infant-mother attachment, data gathered during naturalistic home observations at 1, 3, and 9 months on 60 babies seen in the Ainsworth and Wittig strange situation were examined. Planned comparisons revealed, as predicted, that securely attached infants had experienced intermediate levels of reciprocal interaction and maternal stimulation, considered to be reflective of sensitive care, and that resistant babies had experienced less responsive care than securely attached infants. No support was provided for the hypothesis that avoidant babies had experienced less physical contact with mothers than securely attached infants. Insecurely attached infants were observed to cry significantly more than securely attached infants at 3 and 9 months. A cross-lag panel analysis, designed to assess longitudinal processes of influence, revealed that fussiness was caused by mothering and did not serve to influence mothering. These results are discussed in terms of mothers' relatively greater influence in determining individual differences in attachment, with overstimulation leading to avoidance, understimulation leading to resistance, and intermediate levels of stimulation leading to security.

Child Behavior↗