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Biomedical subjects

J Patton

Publications and source records attributed to J Patton.

17 recordsLinked to original sources

Alpha-adrenergic and angiotensin II pressor sensitivity in hypertensive patients treated with an angiotensin-converting enzyme inhibitor.

We investigated pressor sensitivity to infused phenylephrine (PE), 0.05 to 0.4 micrograms/kg/min, and angiotensin II (Ang II), 2.5 to 10 ng/kg/min, in 35 patients with mild-to-moderate hypertension, before and at the end of a 4-week treatment period with the angiotensin-converting enzyme (ACE) inhibitor, cilazapril, 2.5 or 5.0 mg/day. Cilazapril lowered the mean systolic and diastolic blood pressure by 10.6/3.5 mm Hg, but had no effect on the dose-response curves of dose of PE or Ang II vs. the increase in systolic, diastolic, or mean blood pressure, or heart rate. There were also no significant effects of cilazapril on PD20 values, i.e., the dose of PE or Ang II required to increase mean arterial blood pressure (MAP) by 20 mm Hg, or on delta R-R/delta MAP (ratio of the increase of the ECG R-R interval to the increase in mean arterial blood pressure) as a measure of baroreflex sensitivity. Plasma renin activity was significantly increased by cilazapril therapy, but there were no changes in plasma concentrations of Ang II or atrial natriuretic factor. We conclude that cilazapril, an ACE inhibitor, does not alter alpha 1-adrenoceptor and Ang II receptor sensitivity to selective agonists, nor does it affect baroreflex sensitivity.

Adolescent

Photoaffinity labeling of rotavirus VP1 with 8-azido-ATP: identification of the viral RNA polymerase.

Rotavirus single-shelled particles have several enzymatic activities that are involved with the synthesis of capped mRNAs both in vivo and in vitro. Because single-shelled particles must be structurally intact to carry out transcription, it has proven to be difficult to identify the protein within such particles that possesses associated RNA polymerase activity. One approach for characterizing the function of the individual proteins within single-shelled particles is to use nucleotide analogs to specifically label those proteins, such as the viral RNA polymerase, that have affinity for nucleotides. In this study, 8-azido-ATP (azido-ATP), a photoreactable nucleotide analog, was used to identify the viral RNA polymerase on the basis of the ability of the analog to inhibit transcription activity associated with rotavirus particles on exposure to UV light. When single-shelled particles were treated with UV light in the presence of [alpha-32P]azido-ATP, the structural protein VP1 became radiolabeled because of cross-linking of the nucleotide analog, and there was a corresponding decrease in the ability of the particles to synthesize mRNA. In parallel experiments in which single-shelled particles were not exposed to UV light, VP1 was not radiolabeled and the particles successfully used azido-ATP as a substrate for the synthesis of viral mRNAs. Taken together, these results are consistent only with the conclusion that VP1 is the rotavirus RNA-dependent RNA polymerase.

Adenosine Triphosphate

Metabolic and cardiorespiratory parameters during three consecutive days of exhaustive running.

The purpose of this study was to examine serum metabolites, cardiorespiratory parameters and creatine kinase during running on 3 consecutive days. Thirteen trained marathon runners exercised to exhaustion on a treadmill at 85 +/- 3% VO2max on each day. Expired gases and blood samples were obtained at rest, after 10 and 30 min of exercise and at exhaustion. There were no significant differences over days for glucose, insulin, lactate, free fatty acids, creatine kinase, oxygen uptake, minute ventilation, heart rate, rating of perceived exertion, respiratory exchange ratio or run times. Serum glycerol was elevated (p less than 0.05) both at rest and during exercise on each successive day. The findings suggested that, except for serum glycerol, acute metabolic and cardiorespiratory responses to exhaustive aerobic exercise are not altered by 3 days daily repetition by endurance trained individuals.

Cardiovascular System

Liposome-associated tumor necrosis factor retains bioactivity in the presence of neutralizing anti-tumor necrosis factor antibodies.

Cell-associated TNF-alpha, either bound to its receptor on monocyte membranes or expressed as an integral membrane protein, can exert potent tumor cytolytic activity. We assessed the interaction of TNF with the lipid bilayer membrane system, liposomes, and the effects of membrane association on TNF bioactivity. High levels of TNF can be encapsulated within liposomes. At neutral pH, TNF binds to the surface of preformed liposomes (liposome-associated TNF), but does not partition into the lipid bilayer. TNF appears to bind to negatively charged phospholipid head groups of the outer membrane leaflet. Free TNF, liposome-associated TNF, and liposome-encapsulated TNF display comparable abilities to activate human peripheral blood monocytes and to lyse tumor cells. However, liposome-encapsulated TNF, as well as TNF bound to the outer surface of preformed liposomes, retains bioactivity in the presence of anti-TNF antibodies that neutralize free TNF. The interaction of liposomal TNF with cell surface TNF receptors thus appears to be preserved in the presence of neutralizing antibodies.

Adult

Essential fatty acids modulate apomorphine activity at dopamine receptors in cat caudate slices.

We have used a classical neurotransmitter release model to investigate the effect of dietary polyenoic fatty acids on the sensitivity of the presynaptic dopamine autoreceptor in slices of cat caudate nucleus. Maximum inhibition of [3H]dopamine release was seen only in animals fed a diet containing post delta-6-desaturation fatty acids of both the w3 and w6 series. The removal of either or both groups of fatty acids resulted in attenuation of sensitivity of the autoreceptor to apomorphine. We propose that a balance of w3 and w6 fatty acids is required to maintain normal dopaminergic function in the cat caudate nucleus.

Animals

Age dependence of the pressor sensitivity to noradrenaline and angiotensin II during calcium channel blockade in hypertensive patients.

We investigated the hypothesis that at least part of the vasopressor activity of noradrenaline (NA) and angiotensin II (Ang II) in humans is due to the activation of receptor-dependent calcium channels. Thirty patients (15 aged 50-65 years and 15 aged 66-80 years) with diastolic blood pressure of 95-120 mm Hg were given placebo (P) for 4 weeks, and then nitrendipine (N) 20-40 mg/day for 12 weeks. After 4 weeks on placebo, and again after 12 weeks on nitrendipine, NA 40, 80, 160, and 320 ng/kg/min, followed by Ang II 2.5, 5, and 10 ng/kg/min, was infused intravenously, and steady state systolic, diastolic, and mean arterial blood pressure and heart rate were measured. Older patients were found to be significantly less sensitive than younger patients to the pressor effects of NA. N decreased NA sensitivity, more in younger than older patients. Older patients were significantly more sensitive than younger patients to the pressor effects of Ang II. N also decreased Ang II sensitivity, more in older than younger patients. We conclude that at least some of the vasopressor activity of NA and Ang II is due to activation of calcium channels, and that these effects are age dependent.

Aged

Changes of plasma levels of apolipoproteins A-I, A-II, and B and their isoforms in patients with intestinal failure receiving long-term parenteral nutrition.

We have studied the plasma lipid and apolipoprotein profiles of 19 patients with intestinal failure who are receiving long-term total parenteral nutrition (TPN). These patients had significantly reduced levels of total and HDL cholesterol and normal levels of triglycerides. Radioimmunoassay determination of apolipoproteins showed a 30% and 50% reduction in apo A-I and A-II levels, respectively. Apolipoprotein B was normal in all but three patients. Isoelectric focusing showed two major isoforms of apo A-I in patients as compared with four isoforms observed in normal subjects and one major isoform of apo A-II compared with multiple isoforms. Recent epidemiologic studies indicate that an increased apo B:apo A-I ratio may be an important factor in atherogenesis. We suggest that patients with small-bowel syndrome who are currently on TPN may be at greater risk for atherosclerosis. Since TPN has restored a reasonably normal life expectancy for these patients, long-term follow-up will likely provide answers.

Adolescent

Addicted nurses.

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Humans

Peritoneal lavage cooling in an anesthetized dog heatstroke model.

This study was undertaken to compare cooling in room air (27 degrees C, 20% RH), ice slush surface cooling, and peritoneal lavage cooling (6-10 degrees C) as methods for lowering body temperature in an anesthetized dog heatstroke model. We anesthetized 19 animals with sodium pentobarbital (25 mg/kg) intravenously, and maintained them in an ambient temperature of 42-46 degrees C with a water heating blanket approximately 2.0 h until rectal temperatures rose to 43.2 +/- 0.2 degrees C. At the maximum rectal temperature, the heating blankets were removed, and animals were cooled, observed until death occurred or 18 h elapsed, and then sacrificed. The data demonstrate that maximum cooling rates of rectal temperature were: peritoneal lavage, 0.56 degrees C/min; ice slush, 0.11 degrees C/min; and 27 degrees C air cooling, 0.06 degrees C/min. The incidence of 18-h survival for lavage-cooled dogs when supported with normothermic dialysis every 4 h was significantly greater than for either ice slush or air cooled dogs.

Animals

An anesthetized dog heatstroke model.

This study was undertaken to develop an anesthetized dog heatstroke model. Forty-six animals were anesthetized with pentobarbital sodium (25 mg/kg) intravenously, and maintained at an ambient temperature of (42-46 degrees C) with a water-heated blanket over 2.5-3.0 h until rectal temperatures rose to 43.0-44.5 degrees C. Animals then cooled passively until death occurred or until 18 h elapsed, and were prepared for autopsy. Liver, kidney, and brain temperature, mean weighted skin temperature, mean weighted surface heat loss, and metabolic rates were obtained. There were no significant differences between liver, kidney, brain, and rectal temperatures during the heating and cooling periods. Cardiac output rose to 127% of initial value, and dropped rapidly to zero at 43.4 degrees C rectal temperature. The rapid decline was accompanied by a doubling of heart rate and a rapid drop in blood pressure and respiratory rate. Cheyne-Stokes respiration and apnea preceded bradycardia followed by asystole or ventricular fibrillation. Certain serum constituents demonstrated modest elevations suggestive of widespread tissue damage. Autopsy did not reveal a clear pattern of heat injury, with the exception of consistent congestion of the major organs and karyorrhexis of lymphocytes. These data are in agreement with similar data from human heatstroke victims and other heatstroke modeling in dogs, and support the concept that the anesthetized dog can in many respects provide an adequate model for human heatstroke.

Anesthesia, Intravenous

Transoral, transsphenoidal microsurgical exposure of the pituitary gland and infundibulum in the rhesus monkey. Description of operative technique.

A transoral, transsphenoidal microsurgical technique for exposing the pituitary stalk and gland of the rhesus monkey is described and illustrated. The technique has proved to be a safe and practical method for performing a variety of pituitary operations in a total of 37 animals. The procedures have included complete hypophysectomy, posterior lobe resection, pituitary stalk section, collection of portal venous blood, collection of pituitary venous blood, and placement of lessions in the organum vasculosum of the lamina terminalis.

Animals

Polyenoic fatty acid deprivation of juvenile cats modulates 3H-dopamine release from presynaptic receptors in caudate slices.

A classical neurotransmitter release model was used to investigate the effect of the limitation of dietary polyenoic fatty acids on the function of presynaptic dopamine autoreceptors in slices from the caudate nucleus of kittens (juvenile domestic cats). Maximum inhibition of 3H-dopamine release was detected only in the brains of animals receiving post delta-6-desaturation fatty acids of both the omega 3 and omega 6 series. The removal of either, or both, groups of fatty acids resulted in attenuation of sensitivity of the autoreceptor to apomorphine. It would appear that omega 6 fatty acids are more important for a normal pattern of dopaminergic function to be established in the caudate nucleus of kittens.

Animals