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Biomedical subjects

D Cooper

Publications and source records attributed to D Cooper.

At least 235 records · Page 13Linked to original sources

Microbial flora of the mouse ileum mucous layer and epithelial surface.

We have developed new methods to minimize fluid shear during preparation of specimens for electron microscopy and to retain the mucous blanket that covers the tissue surface of the ileum in mice. We also used general stabilization by nonspecific antibodies to minimize the collapse of the mucous layer during dehydration for electron microscopy. These methods allowed us to visualize the gradual progression of the mucous blanket from a thin diaphanous layer in newborn animals to a very thick (ca. 50 micrometers), coherent structure in older animals that contained a mixed population of bacteria and protozoa. Some bacteria, notably filamentous forms, were patently anchored to the epithelial tissue but projected into the mucous blanket, whereas others clearly existed within the mucous blanket and were unattached to the epithelial surface. Similarly, some protozoa were firmly attached to the tissue surface, whereas others were suspended in the viscous mucous blanket. In an adult animal, the mucous blanket was a very thick layer which actually occluded most of the tissue surface and contained a rich variety of bacteria and protozoa.

Animals↗

Relationship between plasma levels of procainamide, suppression of premature ventricular complexes and prevention of recurrent ventricular tachycardia.

We compared the relationship between plasma levels of procainamide and suppression or prevention of various forms of ventricular arrhythmias in 18 patients, six of whom had premature ventricular complexes (PVCs) during acute myocardial infarction (AMI), six of whom had PVCs in the setting of stable chronic ischemic heart disease (CIHD), and six of whom had recurrent symptomatic ventricular tachycardia (VT) with chronic PVCs between episodes of VT. The mean plasma level of procainamide required for 85% suppression of PVCs in the AMI patients was 5.0 +/- 0.5 micrograms/ml, while that required for the CIHD patients was 9.3 +/- 0.7 micrograms/ml (p less than 0.05). The mean plasma level required for prevention of spontaneous episodes of symptomatic sustained tachycardia in the VT group was 9.1 +/- 3.4 micrograms/ml, while the mean level required for 85% suppression of PVCs in the same patients was 14.9 +/- 3.8 micrograms/ml (p less than 0.01). In the VT group, PVC frequency was decreased by a mean of only 36% (range 11-63%) at plasma levels of procainamide sufficient to prevent spontaneous VT. The relationship between plasma levels of procainamide and PVC suppression appears to be different in AMI and CIHD patients; furthermore, a high degree of PVC suppression is not a necessary endpoint of antiarrhythmic therapy when attempting to protect patients against recurrent symptomatic VT.

Acute Disease↗

Rearrangement of immunoglobulin heavy chain genes during B-lymphocyte development as revealed by studies of mouse plasmacytoma cells.

We have used Southern's blotting technique to determine the extent to which the genes encoding the constant (C) regions of mu, alpha, gamma(1), and gamma(2b) immunoglobulin heavy (H) chains are altered in number and context from their germline (embryo) state in a series of 14 plasmacytomas expressing various H chain classes. In the three mu chain-producing plasmacytomas studied there was no evidence of rearrangement of C(H) genes other than C(mu). In contrast, rearrangement and deletion of nonexpressed C(H) genes was frequent in plasmacytomas that produce gamma or alpha chains. The observed pattern of deletions is consistent with the idea that the ontogenetic switch in H chain class requires C(H) gene deletion. Frequently, though not always, such deletions as well as other types of rearrangement occur in both allelic loci. Particularly noteworthy are three gamma(2a)-expressing tumors in which C(alpha) gene rearrangement is evident in both alleles. We incorporate these observations into a probabilistic model of B cell development: in the first phase, deletions may occur between the C(mu) gene and the variable (V(H)) gene array, which result in the formation of a productive fused V(H)-C(mu) gene. The cell may then enter a second phase, which allows deletions within the C(H) gene arrays of both homologous chromosomes. Some deletions juxtapose the expressed V(H) gene with a second C(H) gene and result in a H chain class switch; others delete or alter the context of C(H) genes without changing the phenotype of the cell. We predict that switching can be both a single-step and a multi-step process, and that in the latter case those rearrangements that do not result in a switch may be physiologically significant in that they may limit the options of further switching.

Animals↗

Maternal perception of fetal motor activity.

A technique using real-time ultrasound for comprehensive recording of fetal motor activity was used in 20 subjects in the third trimester of pregnancy. Maternal awareness of fetal movement correlated with the number of fetal parts contributing to the movement but not with maternal parity or obesity, gestational age, placental site, or duration of the fetal movement. Some subjects recorded fetal breathing, passive fetal displacement, and Braxton Hicks's contractions as fetal movement. Most of our subjects were consistent and accurate in their perception of major fetal movements, but a few were inconsistent and one was completely unaware of major fetal movements. These results suggest that kick counts kept by most mothers will be accurate. Low counts of fetal movement should be an indication for fetal monitoring by other means and not, unconfirmed, for intervention.

Female↗

Comparative bioavailability of a microcrystalline theophylline tablet and uncoated aminophylline tablets.

The bioavailability of a rapidly dissolving tablet of theophylline and three brands of standard aminophylline tablets was estimated in a four way cross-over study involving 8 healthy adult volunteers. The relative extent of bioavailability as assessed by the measurement of the total area under the plasma concentration time curves showed no difference between the products (P greater than 0.05). Computed estimates of the rate of drug absorption were similar for all 4 products tested. The results indicate that the rapidly dissolving tablet offers no advantage in respect to rate and extent of absorption over conventional aminophylline tablets.

Aminophylline↗

Normal patterns of fetal activity in the third trimester.

The incidence and frequency of fetal respiratory movements (FRM) and fetal trunk movements (FTM) were measured in 21 normal pregnancies between 28 and 39 weeks gestation. Fetal activity was assessed with a real-time ultrasound scanner and all observed movements were punched directly onto computer tape. Recordings were made for one hour in three over a 24 hour period, providing a total of 168 hours for analysis. The overall mean percentage incidence of FRM was 31 per cent at a mean breathing rate of 43 breaths/minute. The mean percentage incidence of FRM during the day (0800-1759 hours) was 37 per cent. The overall mean percentage incidence of FTM was 18 per cent with a mean of 29 moves per 30 minute observation period. The mean percentage incidence of FTM during the day (0800-1759 hours) was 16 per cent. There was a well-defined circadian variation in fetal activity with FRM peaking between 1900 and 2200 hours, and FTM between 2200 and 0100 hours. There was considerable variation in the amount of FRM and FTM recorded from hour to hour. Total fetal activity rarely fell below 10 per cent in any one recording period and this measurement may be a more useful clinical test of fetal well-being than FRM or FTM alone.

Adolescent↗

Cardiac arrhythmias.

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Arrhythmias, Cardiac↗

Identity of proline dehydrogenase and delta1-pyrroline-5-carboxylic acid reductase in Clostridium sporogenes.

Proline dehydrogenase and delta1-pyrroline-5-carboxylic acid (PCA) reductase activities were copurified 60- and 130-fold, respectively, from extracts of Clostridium sporogenes. The primary change in the ratio of activites was the result of a loss of proline dehydrogenase activity during dialysis. Both activities were eluted in single peaks from diethylaminoethyl-cellulose, hydroxylapatite, and Sephadex G-200 columns. They had identical sedimentation coefficients (10.3S), as determined in linear sucrose gradients, and identical isoelectric points (4.95 to 5.12) based on isoelectric focusing. The proline dehydrogenase activity was dependent on nicotinamide adenine dinucleotide and L-proline, and the PCA reductase required L-PCA and reduced nicotinamide adenine dinucleotide. The optimum pH for the assay of proline dehydrogenase was approximately 10.2, whereas that for PCA reductase was 6.5 to 7.5. An increase in pH from 8.0 to 10.2 greatly decreased the apparent Michaelis constant observed for L-proline, and an increase from pH 8.3 to 8.6 resulted in a large shift in the reaction equilibrium toward PCA. Both the dehydrogenase and reductase activities were stabilized to heating at 65 degrees C for 5 min by solutes of high ionic strength and were inactivated in a similar fashion when dissolved in low-ionic-strength buffer. The specific activities for both were reduced by about 50% when glucose was added to the growth medium. The data support the conclusion that L-proline and L-PCA are interconverted by either a single enzyme or an enzyme complex in extracts of C. sporogenes cells.

Amino Acid Oxidoreductases↗

Increased cellular responsiveness to epinephrine in primary open-angle glaucoma.

The concentration of I-epinephrine hydrochloride necessary to inhibit lymphocyte transformation by 50% (I50 value) was determined in vitro for nine patients with primary open-angle glaucoma (POAG) and in seven controls. The lymphocytes of the patients with POAG were significantly (P less than .05) more responsive. This result is consistent with the hypothesis that patients with POAG have an increased responsiveness to agents that elevate intracellular cyclic adenosine monophosphate levels.

Adult↗

Selective bronchial intubation for the treatment of severe localized pulmonary interstitial emphysema in newborn infants.

As an alternative to lobectomy and in order to preserve lung tissue which may be potentially functional we have selectively intubated the right main bronchus in four infants 12 to 25 days old with severe, pulmonary interstitial emphysema of the left lung. In each case the localized hyperinflation disappeared within 5 to 48 hours of contralateral selective bronchial intubation. The duration of SBI was 1.5 to 5 days. Three patients benefited from the procedure; there were no serious complications. We propose that SBI should be tried in infants with severe, localized PIE which has caused mediastinal shift, compressive atelectasis, and respiratory acidosis requiring mechanical ventilation despite vigorous pulmonary therapy and usual supportive measures.

Bronchi↗

Relationship of serum theophylline concentration to inhibition of exercise-induced bronchospasm and comparison with cromolyn.

Exercise-induced bronchospasm was induced by treadmill running in 12 children on two days preceding either inhaled cromolyn sodium (Intal) or oral theophylline (Slo-Phyllin tablets), 7.5 mg/kg, administered in a double-blind manner. A second exercise period identical to the first followed two hours later; the medication administration had been timed so that the second exercise stress followed two hours after theophylline administration and 15 minutes following cromolyn administration. The patients subsequently were exercised twice more at two-hour intervals on both days. Blood was drawn from serum theophylline measurement immediately after each of the exercise periods. There was little demonstrable exercise-induced bronchospasm resulting from the first postmedication exercise period following theophylline administration. The two subsequent exercise periods were associated with some return of postexercise bronchospasm. The degree of inhibition of exercise-induced bronchospasm correlated with serum theophylline levels that averaged 16, 13, and 10 microgram/ml at two, four and six hours after the theophylline dose (mean Spearman rank correlation coefficient = .71, P less than .01). The effect of cromolyn in suppression exercise-induced bronchospasm that matched or excelled that seen with theophylline.

Adolescent↗

Physiologic responses of men 49 to 65 years of age to endurance training.

A study was made of the effects of training for 30 minutes, three days a week for 20 weeks on certain physiologic measures of sedentary men between 49 and 65 years of age. Twenty-two subjects volunteered for the experimental group, and 8 others for the control group. Exercise sessions were conducted on a quarter-mile track and consisted of continuous bouts of walking and jogging. The average daily energy expenditures progressed from 228 to 365 kilocalories between weeks 4 and 20. For the same period, average exercise heart rates (HRs) progressed from 149 beats/minute (83 per cent maximum HR) to 155 beats/minute (91 per cent maximum HR). The experimental group showed significant increases in maximum oxygen intake (VO2 max) from 2.47 to 2.90 liters/minute (18 per cent) and in maximum pulmonary ventilation (VE max) from 105 to 121 liters/minute (BTPS), and decreases in resting HR, diastolic blood pressure, body weight, skinfold fat, and abdominal girth. Serum cholesterol and triglyceride levels and heart volume remained unchanged. The control subjects showed no significant changes. Regression analysis, with use of age as a covariate, showed a small but significant inverse relationship with changes in VO2 max. It was concluded that men of the 49-65 age group respond favorably to endurance exercise and show a magnitude of change similar to that found in previous investigations of similar design with younger subjects.

Age Factors↗

Renal and intrarenal blood flow distribution in swine during severe exercise.

It is known that a compensatory reduction and diversion of renal flow occurs in severe exercise in humans but not in dogs. We investigated this in miniature swine by measuring changes in total renal blood flow (TRF) and intra-renal blood flow (IRBF) distribution with tracer microspheres (15 +/- 5 mum) at rest and during steady-state exercise at 4.8-7.2 kph and 0% grade, and during severe exercise at 4.8-7.2 kph and 10% grade. We measured heart rate and cardiac output (Q) via implanted probes. TRF was determined as a percent of Q and as ml/100 g per min. IRBF was determined for the outer cortex, inner cortex, outer medulla, and inner medulla. Our results show that renal blood flow is significantly (P less than 0.05) reduced in pigs with exercise. Steady-state exercise reduced flow to about 66% of control and severe exercise reduced renal flow to 30% of control. IRBF was unchanged throughout. These results show that the exercising pig augments blood flow to skeletal muscle by reducing blood flow to kidneys, a response known to occur in man.

Animals↗