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Biomedical subjects

R H Cox

Publications and source records attributed to R H Cox.

At least 109 records · Page 6Linked to original sources
PubMed1981

Mouse liver glutathione S-transferases. Biochemical and immunological characterization.

Three major forms of cytosolic glutathione S-transferase (designated F1, F2, and F3 transferases according to increasing isoelectric points) were purified to homogeneity from liver of DBA/2J mice, primarily by CM-cellulose and hydroxylapatite chromatography. The purified enzymes were shown to have specific activities of 104, 281, and 143 units/mg, respectively, when assayed with 1 mM each of 1-chloro-2,4-dinitrobenzene and reduced glutathione. Antisera against these three forms of mouse transferase were raised separately in rabbits. F1 and F2 transferases showed complete immunological identity either by double immunodiffusion or enzyme immunoinactivation tests. No cross-reactivity was observed between the antisera to F1 (or F2) transferase an F3 transferase or between the antisera to F3 transferase and F1 (or F2) transferase. F1 and F2 transferases were shown to be homodimers with an identical molecular weight of 44,000 +/- 1,000, whereas F3 transferase has a dimeric molecular weight of 51,000 +/- 2,000. The amino acid composition and tryptic peptide map of F1 transferase are similar to those of F2 transferase, but are distinct from those of F3 transferase. In addition to these major forms, a minor form of mouse transferase (F4) with a high isoelectric point (greater than 9.5) was shown to be a mixture of interconvertible isomers of F2 and F3 transferase. Different forms of mouse transferase were studied extensively with respect to their biochemical properties, including Michaelis constants, substrate specificity, thermal stability, and fluorometric ligand binding. The results of this study suggest great species variations regarding the multiple forms as well as the substrate specificity of this family of enzymes.

Amino Acids↗
PubMed1981

Synthesis and relative stereochemistry of the four mercapturic acids derived from styrene oxide and N-acetylcysteine.

The chemical reaction between (+/-)-styrene oxide and N-acetylcysteine produces both positional isomers (1 and 2) as a mixture of diastereoisomers with a preference for the benzylic thioether isomer 1 (2 : 1). Synthesis of the mercapturic acid conjugates from either (+)- or (-)-styrene oxide produces only two of the four possible stereoisomers. The single diastereoisomers of 1 and 2 were separated by high pressure liquid chromatography (HPLC) and identified by 1H- and 13C-nuclear magnetic resonance (NMR). The relative stereochemistry at the benzylic carbon center of the mercapturic acid conjugates was assigned on the basis of the established chemical correlation between optically pure styrene oxide and its precursor mandelic acid, and considerations on the mechanism of ring opening of epoxides by sulfur nucleophiles. The stereochemical definition of the isomers 3-6 should prove useful in investigations of the biotransformation of the glutathione (GSH) conjugates of styrene oxide.

Acetylcysteine↗
PubMed1981

Effects of incremental halothane levels on the reflex responses to carotid hypotension in the dog.

Arterial baroreceptor function was assessed in trained, chronically instrumented dogs by measuring the systemic haemodynamic responses to brachiocephalic artery occlusion (BCO). BCO was carried out in awake dogs and repeated at end-tidal halothane levels of 0.75 +/- 0.01% (H1), 0.94 +/- 0.02% (H2) and 1.13 +/- 0.02% (H3). Before BCO, at H1 only the increased heart rate and decreased stroke volume were significantly different from awake controls (P less than 0.01). Mean atrial pressure and cardiac output at H2 and H3 were significantly lower than in the awake controls (P less than 0.05). The pressor response to BCO fell progressively with increasing halothane levels, the decrease being significant at the H2 and H3 levels (P less than 0.001). There was a good linear correlation between the pressor response to BCO as a percentage of the response in awake animals, and the end-tidal halothane levels (r = -0.816, P less than 0.001). This indicated a sensitive dose-dependent modification of the haemodynamic response to BCO by halothane. However, halothane levels existed between about 0.7-0.8%, at which levels the average pressor response to BCO was not significantly different from awake values.

Anesthesia, Inhalation↗
PubMed1981

Baroreceptor control of systemic haemodynamic at incremental halothane levels in the dog.

The open-loop carotid sinus reflex control of systemic haemodynamics was studied in an acute dog preparation with isolated perfused carotid sinuses at three end-tidal halothane levels of 0.66 +/- 0.02% (HI); 0.88 +/- 0.02% (H2); and 1.17 +/- 0.02% (H3), in order to investigate the dose dependency of the carotid sinus reflex operating characteristics for halothane. Corresponding to the above halothane levels were reflex operating point pressures (set point pressures) of 104.9 +/- 2.9, 103.3 +/- 4.1 and 76.0 +/- 3.8 mmHg, respectively. Carotid sinus reflex gain decreased significantly with progressively increasing halothane levels (1.4. +/- 0.18; 0.84 +/- 0.12; 0.48 +/- 0.09), as did the range of reflex changes in systemic arterial pressure for equal overall changes in carotid sinus pressure (87.1 +/- 7.9; 64.1 +/- 7.4; 33.6 +/- 5.1 mmHg; P less than 0.01). For halothane levels below approximately 0.9%, this depression was not dependent upon changes in mean systemic arterial pressure. The relationship between reflex gain and halothane concentration could be described by a first-order exponential which suggested virtual ablation of the carotid sinus reflex control of mean arterial pressure at an end-tidal halothane concentration exceeding about 1.6%.

Animals↗
PubMed1981

Isolation of Citreoviridin from Penicillium charlesii Cultures and Molded Pecan Fragments.

The extraction and systematic fractionation of Penicillium charlesii Smith cultures and contaminated pecan fragments yielded the yellow mycotoxin citreoviridin. Citreoviridin proved acutely toxic to 1-day-old chickens, with an oral 50% lethal dose of 37.5 mg/kg, and showed plant growth inhibition in wheat coleoptiles even at concentrations as low as 10 M. It was toxic to corn seedlings but did not affect young tobacco seedlings.

Journal Article↗
PubMed1981

Arterial baroreceptor reflexes in young and old racing greyhounds.

The characteristics of the carotid sinus baroreceptor (CSB) reflex control of arterial pressure-flow relations were studied in young (18 mo) and old (10.5 yr) racing greyhounds anesthetized with chloralose. Pressure and flow were simultaneously measured in the ascending aorta, the celiac, superior mesenteric, renal, and iliac arteries under steady-state conditions of pulsatile perfusion of the isolated carotid sinuses before and after bilateral cervical vagotomy. Operating-point (OP) values of mean pressure were not significantly different between the young or old greyhounds, but OP values of cardiac output were lower and of peripheral resistance were higher in the older animals. OP values of regional resistances were higher in the older animals, but only those of the celiac and mesenteric beds were significantly different. Values of OP sensitivity of central hemodynamic variables were not decreased in the older animals. OP values of renal and iliac resistance sensitivity tended to be lower in the older animals. The overall range of control of the various hemodynamic variables by the CSB was lower in the older group only in the case of iliac resistance. The characteristics of the CSB were not uniformly depressed in the older animals but were relatively well maintained compared with those of the younger group.

Aging↗
PubMed1981

Reflex control of canine hindlimb resistance under different modes of perfusion.

The carotid sinus control of hindlimb hemodynamics was determined in halothane-anesthetized vagotomized dogs. The carotid sinuses were bilaterally isolated and perfused under controlled conditions. The hindlimb was perfused under conditions of 1) physiological inflow, 2) constant pressure, and 3) constant flow. The variation of hindlimb resistance with mean carotid sinus perfusion pressure was largest under conditions of constant-pressure perfusion and smallest with physiological inflow. Values for constant-flow perfusion were intermediate. The effects of different values of constant-flow perfusion on the carotid sinus control of hindlimb hemodynamics was also determined. Values of hindlimb resistance increased with decreasing flow rate as did the variation with carotid sinus perfusion pressure. No evidence of a contribution of local control mechanisms related to changes in perfusion pressure or bed inflow could be demonstrated. The differences in the variation of hindlimb resistance with carotid sinus pressure under the various perfusion conditions can be explained on the basis of the mechanics of vascular smooth muscle. The amount of lumen constriction associated with changes in degree of activation depends on the conditions under which shortening occurs as well as upon the initial muscle length. It appears that local factors do not contribute to the control of hindlimb hemodynamics under the conditions in which these studies were performed.

Animals↗
PubMed1981

Functional consequences of expanded aortic bulb: a model study.

An investigation of the mechanical effects and physiological functions of the dilated ascending aorta of diving mammals was undertaken with mathematic modeling methods. A mathematical model of a prototype (canine) arterial system was constructed and was evaluated by comparing model-predicted pressure and flow wave forms at four vascular locations with published accounts of experimental measurements. The prototype model was modified to serve as a model of the diving mammal arterial system by changing peripheral vascular parameters and by changing the dimensions of the ascending aorta section of the model. This modified model gave a very good simulation of pressure and flow behavior in diving mammal arteries during a dive. Various distribution patterns of compliance addition to the prototype aortic pattern were evaluated as to the effect of these patterns on aortic input properties. It was concluded that the geometric distribution pattern found in diving mammal arteries was optimal with respect to reducing aortic impedance and peak systolic pressure development and thus favored the function of the left ventricle. This mechanical function could represent an important part of the total picture of adaptation to prolonged ischemia.

Animals↗
PubMed1981

Efficiency of trained subjects differing in maximal oxygen uptake and type of training.

This study was undertaken to examine the relationship between energy expenditure and work rate on a bicycle ergometer in five sprinters and five distance runners who differed in maximal oxygen uptake (VO2max) and type of training. Each subject performed at work rates of 30, 60, 90, 120, and 150 watts (W). The relationship between energy expenditure and work rates was most accurately described by a quadratic curve for both groups: for sprinters, energy expenditure (kJ) = 11.57 + 0.1812 (W) + 0.00046 (W)2; for distance runners, energy expenditure (kJ) = 11.74 + 0.1386 (W) + 0.00060 (W)2. Delta efficiency (delta work accomplished divided by delta energy expended X 100%) decreased as work rate increased. Statistical analyses revealed no significant differences between groups in delta efficiency at the same work rate (P greater than 0.25) or at the same relative work rate (P greater than 0.75). These results suggest that differences in VO2max and/or type of training have little or no causal effect on the decrease in delta efficiency with increasing work rate. The observed decrease in delta efficiency may be due to increases in metabolism not directly related to the performance of the external work or to an increasing amount of unmeasured work as work rate increases on a bicycle ergometer.

Adult↗
PubMed1981

Baroreceptor reflexes and pulmonary hemodynamics during halothane and halothane-nitrous oxide anesthesia in the dog.

The effects of reflexly induced changes in sympathetic nerve activity on pulmonary hemodynamics during halothane and halothane-nitrous oxide anesthesia were investigated. Perfusion pressure was changed in the isolated carotid sinuses (60 to 180 mm Hg) of vagotomized, open-chested dogs, anesthesized at three end-tidal halothane concentrations of 0.66% +/- 0.02% (H1), 0.88% +/- 0.02% (H2), and 1.16% +/- 0.03% (H3) with and without 67% nitrous oxide. At no levels of carotid sinus pressure were pulmonary vascular resistance or pulmonary input resistance affected by halothane or nitrous oxide. With increasing carotid sinus stimulation, pulmonary vascular resistance increased at high levels of carotid sinus pressure at the H3 halothane level and with nitrous oxide at the H1 level. Changes in pulmonary input resistance were opposite in direction to baroreceptor stimulation and were greatest at the H3 level with nitrous oxide. Thus for a wide range of baroreceptor stimulation, pulmonary vascular resistance and pulmonary input resistance remained constant at end-tidal halothane concentrations of approximately 0.9%, with or without nitrous oxide. Only when halothane concentrations were significantly above or below 0.9% did reflex changes become significant, particularly with respect to the pulmonary component of the resistive load upon the right ventricle.

Animals↗
PubMed1981

The metabolism and excretion of styrene oxide-glutathione conjugates in the rat and by isolated perfused liver, lung and kidney preparations.

The metabolism and excretion of styrene oxide-glutathione conjugates were studied in the intact rat and by isolated perfusion techniques in rat lung, liver and kidney. The intact animals converted the styrene oxide-glutathione conjugates almost entirely to styrene oxide-n-acetylcysteine derivatives mercapturic acids), with much smaller amounts of cysteine, cysteinylglycine and (unchanged) glutathione conjugates. Only small amounts of biliary excretion (approximately 5%) and less than 1% of fecal excretion of radioactivity were found. The isolated perfused kidney retains the capacity to transform virtually all of the glutathione conjugates at the dose level studied (25-30 mumol/kidney) and the principal component in urine from the isolated kidney was the cysteine conjugate. Isolated perfused lung experiments demonstrated that this organ has a minor role in styrene oxide-thioether conjugate. Isolated perfused lung experiments demonstrated that this organ has a minor role in styrene oxide-thioether conjugate metabolism. The isolated perfused liver experiments showed that phenobarbital pretreatment has little effect on biliary excretion but barbital pretreatment has little effect on biliary excretion but that it causes profound qualitative and quantitative effects on metabolism of styrene oxide-glutathione conjugates in the perfusion medium. The high level of styrene oxide-cysteine conjugates in the perfusion medium of an isolated perfused liver, especially after phenobarbital treatment, is consistent with the theory that gamma-glutamyltransferase activity is extracellular. The high-pressure liquid chromatography system of analysis described offers the ability to simultaneously separate and quantitate the major thioether conjugates of styrene oxide and other electrophilic epoxides.

Animals↗
PubMed1980

The effects of vasoconstriction on experimental coronary artery stenosis.

In summary, we have examined the response to arterial vasoconstriction in an in vitro coronary artery preparation. Without a preexisting stenosis, arterial vasoconstriction had minimal hemodynamic effects. Similarly, with a stenosis created by a circumferential snare, arterial vasoconstriction had minimal hemodynamic effects. In striking contrast, with a stenosis created by intraluminal obstruction, arterial vasoconstriction dramatically increased the hemodyamic severity of the stenosis. The use of an intraluminal obstruction provides a useful animal model for examining hemodynamics in coronary artery disease and had provided some insight into the effects of vasoconstriction on coronary artery hemodynamics. Obviously, this is an experimental study, and care must be taken in extrapolating these results to diseased human coronary arteries.

Angina Pectoris↗
PubMed1980

Effects of pulsations on carotid sinus control of regional arterial hemodynamics.

Studies were conducted in halothane-anesthetized dogs to evaluate the interaction of mean and pulsatile components of carotid sinus perfusion pressure on the control of regional pressure-flow relations. Pressure and flow were measured simultaneously in the ascending aorta, celiac, mesenteric, renal, and iliac arteries. The carotid sinuses were bilaterally isolated and perfused under controlled conditions. Mean (CSP) and pulsatile components (CSPP) of carotid sinus pressure were varied systemically. Values of mean aortic pressure (AP) at the operating point (AP = CSP) decreased with increasing CSPP (127 +/- 5 at CSPP = 0 to 103 +/- 5 at CSPP = 60). Reflex gains at the operating point also decreased with increasing CSPP (-1.35 +/- 0.16 for CSPP = 0 to -0.92 +/- 0.18 for CSPP = 60). Changes in cardiac output and peripheral resistance nonuniformly contributed to these responses, with the former predominating at low CSPP and the later at high CSPP. Operating-point values of regional resistance generally decreased with increasing CSPP but to different degrees in the various beds. With increasing CSPP amplitude, regional resistance sensitivity at the operating point (i.e., slope) increased in the celiac and decreased in the mesenteric, renal, and iliac vascular beds. Separate changes in mean and pulsatile components of carotid sinus pressure about the normal operating point produce quantitatively similar changes in systemic hemodynamic variables.

Animals↗