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Biomedical subjects

D Y Cooper

Publications and source records attributed to D Y Cooper.

At least 19 recordsLinked to original sources
PubMed2000

The evolution of orthopaedic surgeons from bone and joint surgery at the University of Pennsylvania.

When the first medical school in the North American colonies was founded in 1765 at the Philadelphia College (University of Pennsylvania) there were only two branches of medicine physic (medicine) and surgery. Surgeons such as Philip Syng Physick, and his successors William Gibson, Henry Hollingsworth Smith, and D. Hayes Agnew, in addition to performing general surgery, treated patients with orthopaedic, ophthalmologic, and nuerosurgical problems. Treatment of patients with orthopaedic problems by surgeons continued at the University of Pennsylvania until DeForest Willard founded the Department of Orthopaedics in 1889. In the interval between 1805, when Physick was appointed the first professor of surgery at the University of Pennsylvania, and 1889 many ingenious instruments, splints, and operative procedures for treating patients with orthopaedic problems were developed. The author will describe some of the accomplishments of these pioneers.

Education, Medical, Graduate↗
PubMed1988

Alteration by perfluorodecalin of hepatic metabolism and excretion of phenobarbital.

The bile duct was cannulated in rats that had been infused intravenously with an emulsion of perfluorodecalin at intervals from 2 to 34 weeks earlier. After injection of [14C]phenobarbital, urine and bile were collected during the next 24 hr and were analyzed for phenobarbital and its metabolites. There was a decrease in the biliary excretion of phenobarbital and its metabolites for several weeks after infusion of perfluorodecalin, but conjugation of the metabolites was not decreased. The reduced excretion returned to normal after about 20 weeks.

Animals↗
PubMed1988

Biophysical and catalytic properties of the phenobarbital p-hydroxylase--a cytochrome P-450 dependent mixed function oxidase.

1. A sensitive method to detect and quantify the products of phenobarbital (PB) hydroxylation by model chemical systems and by biological systems has been developed. 2. Chemical model systems hydroxylate PB in the p-position of the phenyl ring and form one or two additional oxidation products, while in vitro and in vivo (bile fistula rats) biological systems hydroxylate PB only in the p-position. 3. Phenobarbital hydroxylation rates in vitro are of the order of 0.007 nmol/nmol cytochrome P-450 per min. These values are decreased by pretreatment of the rats with inducing doses of phenobarbital. 4. Enzymes catalysing the p-hydroxylation reaction of phenobarbital are localized in the microsomes and have the biophysical and chemical properties that are usually associated with cytochrome P-450-dependent mixed function oxidases.

Animals↗
PubMed1988

Reduced availability of energy initiates pulmonary vasoconstriction.

The mechanism responsible for initiating hypoxic pulmonary vasoconstriction (HPV) remains controversial. In this study, reversible constriction of the pulmonary artery was produced when the ratio of carbon monoxide to oxygen was increased, demonstrating that HPV could be imitated even in the presence of a constant oxygen tension. Isolated rat lungs from 14 adult rats were perfused with a 5% albumin-physiological salt solution and ventilated with 21% O2, 5% CO2, balance N2. At the end of a 30-min stabilization period, the lungs were injected with a bolus of angiotensin II (0.2 micrograms). They were then challenged three times for 5 min with an hypoxic gas mixture alternating with 5 min of normoxia. The ventilatory circuit was then changed to one in which 10% O2, 5% CO2 and varying concentrations of CO (balance N2) could be administered. The concentration ratios of CO:O2 were 0.5:1, 1:1, 2:1, 4:1, and 8:1. These were randomly administered for 6 min interspersed with 6 min of normoxia; a final angiotensin II challenge was given. The results show a slight but significant vasodilation with CO:O2 of 0.5:1, 1:1 with mean depressor responses of 0.7 +/- 0.1, -0.7 +/- 0.1 cm H2O and progressive vasoconstriction with CO:O2 of 2:1, 4:1, 8.5:1 with mean pressor responses of 0.11 +/- 0.3, 4.0 +/- 0.4 and 6.2 +/- 0.5 cm H2O. The pressor response to angiotensin II remained unchanged from beginning to end (9.5 +/- 0.5, 8.1 +/- 0.7 cm H2O. The pressor responses, therefore, are consistent with reduced function of the cytochromes of the electron transport chain. These results suggest that HPV may be initiated by a reduction of energy state of the vascular smooth muscle and that postulation of a specific oxygen receptor is not necessary.

Animals↗
PubMed1987

Effects of intravenous emulsified perfluorochemicals on hepatic cytochrome P-450.

Intravenous infusion of emulsified perfluorodecalin in rats caused a large increase in hepatic cytochrome P-450 concentration which persisted for many weeks. In contrast, hepatic cytochrome P-450 concentration was not changed significantly after infusion of perfluorotributylamine, but subsequent administration of phenobarbital caused the usual increase of cytochrome P-450. The cytochrome P-450 activity for demethylation of benzphetamine was decreased slightly after perfluorodecalin but was unchanged after perfluorotributylamine. The difference in the effects of these perfluorochemicals on hepatic cytochrome P-450 may be related to the difference in the time these compounds are retained in the liver.

Animals↗
PubMed1986

The metabolism and excretion of enzyme-inducing doses of phenobarbital by rats with bile fistulas.

The metabolism of enzyme-inducing doses of 14C-phenobarbital injected i. p. into bile duct-cannulated rats has been studied using improved chromatographic separation and quantification techniques. In animals with bile fistulas most of the 14C-phenobarbital was excreted in bile as p-hydroxyphenobarbital conjugated with glucuronic acid. In urine the main substance found was phenobarbital, with significant amounts of p-hydroxyphenobarbital and varying amounts of its glucuronide conjugate. Animals without bile fistulas excreted 80% dose of phenobarbital in the urine; metabolites were free phenobarbital, p-hydroxyphenobarbital and conjugated material. Approx 90% of the conjugated material was the glucuronide. Only free phenobarbital and p-hydroxyphenobarbital were found in the faeces. Animals drinking plain water excreted 50-65% dose of phenobarbital (80 mg/kg) in bile and the remainder mainly in the urine, whereas superhydrated animals (drinking 5% glucose and 0.9% NaCl) excreted 90% of the dose as free phenobarbital in the urine. Phenobarbital is the only labelled material detectable in hepatic tissue and portal, vena caval or aortic blood, which indicates that phenobarbital is the enzyme-inducing substance and that liver and kidney rapidly eliminate all metabolites. Metabolism of phenobarbital in vivo is a complex process involving interaction of hepatic and intestinal metabolism, partial readsorption from the intestinal tract and renal elimination.

Animals↗
PubMed1983

Comparative kinetic studies of the dealkylation reaction and steroid hydroxylations in various oxygen and carbon monoxide:oxygen atmospheres.

The time-course kinetics of the cytochrome P-450-catalyzed dealkylations of the exogenous compounds benzphetamine, ethylmorphine, codeine, and 7-ethoxycoumarin were compared to the hydroxylation of the endogenous compound testosterone. Using liver microsomes from phenobarbital-induced rats, the time course of the demethylations of ethylmorphine, codeine, and especially benzphetamine was characterized by a fast initial phase of enzymatic activity and then a steady decline in the rate throughout the remainder of the reaction. In contrast, under the same experimental conditions, both the dealkylation of 7-ethoxycoumarin and the hydroxylation of testosterone showed no initial fast phase of activity and a constant rate of product formation for most of the remainder of the time course. The difference also held for the carbon monoxide inhibition studies in which the degree inhibition of the demethylation reactions by a variety of CO:O2 mixtures was time dependent, in contrast to the constant, time-independent degree of CO inhibition of the other two reactions. The kinetics of the demethylation reactions could not be explained by enzyme destruction, back reaction, or product adduct formation and were further confirmed by measurements of the rate of O2 utilization and NADPH oxidation. The complexity of the demethylation reaction should be taken into consideration in any detailed studies of the monooxygenation reaction system.

Animals↗
PubMed1983

A kinetic study comparing the light-reversal properties of carbon monoxide inhibition of ethylmorphine, benzphetamine, and 7-ethoxycoumarin dealkylation with those of hydroxylation of 17-hydroxyprogesterone and testosterone.

The light-reversal properties of carbon monoxide (CO) inhibition of the dealkylation of benzphetamine, ethylmorphine, and 7-ethoxycoumarin by microsomes from phenobarbital (PB)-induced rat livers were compared with those of the 6 beta-, 7 alpha-, and 16 alpha-hydroxylations of testosterone by the same rat hepatic microsomes and C-21 hydroxylation of 17-OH progesterone by steer adrenal microsomes. CO inhibited all reactions studied to essentially the same degree. The significant finding was that the dealkylations were reversed most effectively by light of wavelengths between 440 and 445 nm, rather than around 450 nm, the optimal wavelength for steroid hydroxylations. Moreover, the dealkylations required several-fold higher light intensities for equivalent light reversal. These studies suggest that the heme protein-CO complex responsible for dealkylations has a spectrum corresponding to the shape of the pass band of the 445-nm filter, whereas that of the steroid hydroxylations has its light-reversal maximum at 450 nm and appears to be broader. The measurable differences in the light-reversal properties between the monooxygenations of two groups of substrates, (i) dealkylations and (ii) hydroxylations of lipid substrates, furnish biophysical properties that allow a better characterization of microsomal monooxygenases which should be of value in forwarding progress in the study of these systems.

17-alpha-Hydroxyprogesterone↗
PubMed1979

Ecdysone 20-monooxygenase: characterization of an insect cytochrome p-450 dependent steroid hydroxylase.

Ecdysone 20-monooxygenase, the enzyme system that hydroxylates ecdysone at C-20 of the side-chain to form ecdysterone, has been characterized in the fat body of early last instar larvae of the tobacco hornworm, Manduca sexta, using a radioenzymological assay. Ecdysterone was demonstrated to be the product of the enzyme system by high-pressure liquid chromatography, gas-liquid chromatography and mass spectrometry. Differential centrifugation, sucrose-gradient centrifugation, electron microscopy and organelle-marker enzyme analysis revealed that ecdysone 20-monooxygenase activity is associated with the mitochondria. The enzymatic properties of ecdysone 20-monooxygenase are that it is most active in a 0.05 M phosphate buffer, is inhibited by Mg2+ and exhibits pH and temperature optima at 7.5 and 30 degrees C, respectively. The enzyme complex has an apparent Km for ecdysone of 1.60 x 10(-7) M and is competitively inhibited by its product, ecdysterone, with an apparent Ki of 2.72 x 10(-5) M. The cytochrome P-450 nature of this insect steroid hydroxylase was initially suggested by its obligate requirement for NADPH and its inhibition by carbon monoxide, p-chloromercuribenzoate, metyrapone and p-aminoglutethimide but not by cyanide. Difference spectroscopy revealed the presence of cytochrome P-450 in the fat-body mitochondrial fraction. A photochemical action spectrum of ecdysone 20-monooxygenase activity confirmed the involvement of cytochrome P-450 in this monooxygenase system.

Animals↗