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Biomedical subjects

D B Friedman

Publications and source records attributed to D B Friedman.

At least 55 records · Page 3Linked to original sources
PubMed1988

Three mutants that extend both mean and maximum life span of the nematode, Caenorhabditis elegans, define the age-1 gene.

Long-lived mutants in the nematode Caenorhabditis elegans have been studied to determine if the mutations responsible for extended life were allelic. Three of four mutant strains studied (MK31, MK542, MK546) contain recessive mutations that significantly lengthen life; MK542 and MK546 consistently fail to complement the long life phenotype of age-1 and are therefore allelic. MK31, although longer lived than wild type, is equivocal, in some cases failing to complement age-1 but not in others. All three long-lived strains have reduced hermaphrodite self-fertility and also fail to complement for this presumed pleiotropic effect of the age-1 mutation. Each of these three strains also contains an independent mutation at unc-31 IV. Since the mutants were isolated in the same mutant hunt (Klass, 1983) using protocols that did not guarantee independence, the mutations cannot be assumed to be independently isolated.

Aging↗
PubMed1987

Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta 2 adrenoceptors in the sinoatrial node.

To test the hypothesis that beta 2 adrenergic receptors mediate the chronotropic more than the inotropic response to endogenous catecholamines the effects on the haemodynamic responses to exercise in dogs of the beta 1 specific antagonist atenolol were compared with those of the non-selective beta antagonist propranolol. Heart rate, left ventricular dP/dt at 40 mmHg developed pressure (dP/dt40), and oxygen consumption (VO2) were determined at seven to eight exercise levels in 16 chronically instrumented adult mongrel dogs with and without beta blockade. In doses that produced equivalent suppression of resting heart rate, propranolol and atenolol affected dP/dt40 similarly at all exercise levels. In contrast to atenolol, which affected heart rate equally at all workloads, propranolol inhibited heart rate more as the workload increased, resulting in a 1.55-fold greater percentage inhibition of chronotropy at a VO2 of 60 ml.Kg-1.min-1 a than at a VO2 of 30 ml.kg-1.min-1. These results are compatible with the hypothesis that, although beta 2 receptors appear to have little influence over cardiac inotropy during exercise, sinoatrial beta 2 receptors may be stimulated by circulating catecholamines and contribute greatly to sympathetic modulation of heart rate during heavy exercise in dogs.

Animals↗
PubMed1987

Exercise-induced functional desensitization of canine cardiac beta-adrenergic receptors.

To test the hypothesis that the high levels of endogenous catecholamines associated with strenuous exercise produce functional desensitization of cardiac beta-adrenergic receptors, we measured the bolus chronotropic dose of isoproterenol necessary to produce a 25-beats/min increase in heart rate (CD25) in the resting state and after the return of heart rate to resting levels after 60 min of treadmill running in 13 normal dogs. Immediately after exercise, 12 of 13 dogs were less sensitive to the chronotropic effects of beta-adrenergic receptor stimulation: mean CD25 increased from 1.16 +/- 0.17 to 3.50 +/- 0.98 micrograms (P less than 0.02). A similar reduction in isoproterenol sensitivity was evident regardless of whether testing was performed in the presence or absence of vagal blockade with atropine. By 3 h after exercise, CD25 had returned to the preexercise level, with no further change noted 24 h after exercise. There was no change in the CD25 when measured serially in three unexercised dogs. We conclude that a single bout of dynamic exercise is sufficient to produce a significantly decreased chronotropic responsiveness to isoproterenol. This phenomenon may represent an acute but transient desensitization of cardiac beta-adrenergic receptors.

Animals↗
PubMed1987

Regional distribution of blood flow of dogs during graded dynamic exercise.

The regional blood flow response to progressive treadmill exercise was measured with radioactive microspheres in 25 untrained mongrel dogs. Incremental increases in work intensity resulted in corresponding increases in blood flows to the gracilis, gastrocnemius, semimembranosus, and semitendinosus muscles of the hindlimb and to the heart. During maximal exercise, blood flow was greatest in the semimembranosus muscle and lowest in the semitendinosus muscle (342 and 134 ml-1.100 g tissue-1.min-1, respectively). Exercise produced a decrease in blood flow to the temporalis muscle, which was classified as nonlocomotive in function. Blood flows to the stomach, pancreas, and large intestine decreased at the lowest exercise work load and remained diminished throughout the continuum to maximal exercise. Blood flows to the small intestine and spleen were maintained during submaximal exercise but were reduced by 50% at maximal O2 consumption (VO2max). No changes in blood flows to the kidneys, adrenal glands, liver, and brain were found. These results demonstrate that 1) renal blood flow is maintained at resting levels during exercise in untrained dogs; 2) blood flow changes in the various organs of the splanchnic region of dogs during exercise are heterogeneous; and 3) blood flows to the working skeletal muscles of dogs progressively increase with increasing work loads up to VO2max.

Animals↗
PubMed1986

Arterial blood gases and acid-base status of dogs during graded dynamic exercise.

The objective of this study was to determine whether arterial PCO2 (PaCO2) decreases or remains unchanged from resting levels during mild to moderate steady-state exercise in the dog. To accomplish this, O2 consumption (VO2) arterial blood gases and acid-base status, arterial lactate concentration ([LA-]a), and rectal temperature (Tr) were measured in 27 chronically instrumented dogs at rest, during different levels of submaximal exercise, and during maximal exercise on a motor-driven treadmill. During mild exercise [35% of maximal O2 consumption (VO2 max)], PaCO2 decreased 5.3 +/- 0.4 Torr and resulted in a respiratory alkalosis (delta pHa = +0.029 +/- 0.005). Arterial PO2 (PaO2) increased 5.9 +/- 1.5 Torr and Tr increased 0.5 +/- 0.1 degree C. As the exercise levels progressed from mild to moderate exercise (64% of VO2 max) the magnitude of the hypocapnia and the resultant respiratory alkalosis remained unchanged as PaCO2 remained 5.9 +/- 0.7 Torr below and delta pHa remained 0.029 +/- 0.008 above resting values. When the exercise work rate was increased to elicit VO2 max (96 +/- 2 ml X kg-1 X min-1) the amount of hypocapnia again remained unchanged from submaximal exercise levels and PaCO2 remained 6.0 +/- 0.6 Torr below resting values; however, this response occurred despite continued increases in Tr (delta Tr = 1.7 +/- 0.1 degree C), significant increases in [LA-]a (delta [LA-]a = 2.5 +/- 0.4), and a resultant metabolic acidosis (delta pHa = -0.031 +/- 0.011). The dog, like other nonhuman vertebrates, responded to mild and moderate steady-state exercise with a significant hyperventilation and respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1982

Changes in proteolytic activities of human leukemic promyelocytes (HL-60 cells) during maturation.

Proteolytic activity was measured in human leukemic promyelocytic cell line (HL-60) grown in culture, before and after the addition of agents which promote differentiation. The 36000 X g soluble fraction of the cells degraded [14C]globin with maximal activity at pH 3.6, while the insoluble fraction had a pH optimum at 8.0. This pattern did not change upon differentiation. The acid protease activity of the soluble fraction increased following differentiation. After 4 days in the presence of dimethyl sulfoxide, the differentiated cells exhibited 4-fold higher specific activity as compared with 4 day-old control cells. In contrast, the alkaline activity of the insoluble fraction of the differentiated cells was 4-fold lower than that of the undifferentiated cells. It is suggested that the changes in enzyme activities may serve the new functions acquired by the mature granulocytes.

Aspartic Acid Endopeptidases↗
PubMed1969

Immunization for children. Motivating families to complete a series.

A communication gap in transmission of information from health professionals to indigent parents is demonstrated by the incomplete immunization of children attending pediatric health facilities. To bridge this gap, young women of similar ethnic and social backgrounds were recruited and trained briefly in counseling parents concerning adequate immunization. The effectiveness of these Health Aides in motivating parents to complete an immunization series was less than that of Public Health Nurses. Even so, the Aides were able to motivate two-thirds of the families that they counseled. Conclusions were that a significant number of children appearing in a large public emergency room facility are unimmunized. Many of these children are not seriously ill and an immunization series can be initiated "on the spot." Motivation to complete the series can be done almost as satisfactorily by young rapidly trained indigenous Health Aides as by professionals.

Adolescent↗