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Biomedical subjects

R L Coulson

Publications and source records attributed to R L Coulson.

At least 19 recordsLinked to original sources
PubMed1997

Rapid development of synaptic connections and plasticity between sensory neurons and motor neurons of Aplysia in cell culture: implications for learning and regulation of synaptic strength.

We describe here the time course of functional synapse formation and of the development of short-term synaptic plasticity at Aplysia sensorimotor synapses in cell culture, as well as the effects of blocking protein synthesis or postsynaptic receptors on the development of synaptic transmission and plasticity. We find that synaptic responses can be elicited in 50% of sensory neuron-motor neuron pairs by 1 h after cell contact and that short-term homosynaptic depression and synaptic augmentation and restoration by the endogenous facilitatory transmitter serotonin are present at the earliest stages of synapse formation. Neither block of protein synthesis with anisomycin nor block of two types of postsynaptic glutamate receptor has any effect on the development of synaptic transmission or synaptic plasticity. The rapidity of synapse formation and maturation and their independence of protein synthesis suggest that changes in the number of functional synapses could contribute to short- and intermediate-term forms of synaptic plasticity and learning.

Animals↗
PubMed1993

Neuroanatomical differentiation in the brain of the spontaneously hypertensive rat (SHR). I. Volumetric comparisons with WKY control.

A series of measurements was made to assess the morphology of the brain of the spontaneously hypertensive rat (SHR). The SHR brain was smaller than that of age-matched normotensive Wistar-Kyoto (WKY) controls in a majority of measures of external surface landmarks. This reduction in size was evident in the youngest age group examined (94 days) and persisted in older groups (170, 240 and 350 days). The brain of the SHR was also smaller in terms of brain weight and brain weight:body weight ratios. Section-by-section digitized analyses of coronal histologic sections from 94-day-old rats revealed significant reductions in mean cross-sectional area and volume of midbrain/pons (10%) and hindbrain (11%) regions, but not of forebrain, in the SHR. Alterations in the mediolateral dimension, particularly within the pontomedullary brainstem, accounted for more of these volumetric changes than those in the dorsoventral dimension. Using the same coronal sections, it was found that surface areas and volumes of five individual nuclei/fiber tracts, selected for their involvement in central cardiovascular regulation, were significantly decreased in the SHR. The largest reduction in volume (30%) was found in the nucleus tractus solitarius, the primary site of termination of afferent baroreceptor fibers. No differences in surface area or volume were found in that portion of the cerebroventricular system (aqueduct of Sylvius) associated with the periventricular grey region, or in the inferior colliculus, which is not thought to be involved in cardiovascular control. These observations not only have practical implications, but suggest that the pathophysiological condition expressed as spontaneous hypertension in this widely-used model may be related to morphological alterations in the central nervous system.

Animals↗
PubMed1993

Problem-based student-directed learning in medicine.

Since World War II, there has been an explosion of medical facts and knowledge. It is almost impossible for a medical student to memorize and retain all there is to know. Even if he or she could, the data base is constantly changing, and new knowledge is being discovered. It is the responsibility of the physician to remain current, even though there are no daily lectures. Problem-based student-directed learning offers the student a different context within which to learn and lays the foundation for becoming a lifelong independent learner.

Curriculum↗
PubMed1990

A survey of medical school teachers to identify basic biomedical concepts medical students should understand.

Insights from the cognitive sciences indicate a continuing need for physicians to understand conceptual knowledge from the basic sciences, despite recent concerns regarding the increasing amount of information in medicine and the growing emphasis on performance skills. A 1987 survey of selected basic science and clinical teachers in North American medical schools was undertaken to identify basic biomedical concepts that are important in the practice of medicine and to specify how difficult these are for students to learn, apply, or both. Responses from faculty (nominated by their deans to answer the survey) from 82% of the medical schools indicated considerable agreement between the basic science teachers and clinical teachers on the relative importance of a set of biomedical concepts, and showed relatively minor levels of disagreement on how difficult these concepts are. The judgments of these teachers could prove extremely useful in (1) determining concepts that--because of their importance--should receive special attention in curriculum efforts, and (2) determining concepts that--because of their difficulty--need "special handling."

Canada↗
PubMed1990

Endocrine regulation of tissue glucose-6-phosphatase activity in the fetal sheep during late gestation.

Endocrine regulation of tissue glucose-6-phosphatase activity in utero was examined by measuring enzyme levels in liver and kidneys of fetal sheep during the second half of gestation and after experimental manipulation of fetal plasma cortisol and insulin levels. Tissue glucose-6-phosphatase activities increased toward term in parallel with the rise in fetal plasma cortisol. At birth, the activities were significantly higher than in utero, but significantly less than in adult nonpregnant sheep. Fetal hypophysectomy lowered fetal plasma cortisol and reduced hepatic and renal glucose-6-phosphatase activities compared with those in intact fetuses near term. Conversely, intrafetal cortisol infusion raised fetal plasma cortisol and significantly increased tissue glucose-6-phosphatase activity to values similar to those in older fetuses. When the data from these groups of fetuses and the newborn lambs were combined, there was a significant positive correlation between the plasma cortisol level and the glucose-6-phosphatase activity in both liver and kidney. Fetal hypoinsulinemia was induced by fasting the ewe for 48 h and by fetal pancreatectomy. Fetal hepatic and renal glucose-6-phosphatase activities were higher in fasted than in fed animals, while pancreatectomy had little apparent effect on enzyme activity in either tissue. However, when differences in plasma cortisol were taken into account, hepatic, but not renal, glucose-6-phosphatase activities were higher in both groups of hypoinsulinemic fetuses than would have been observed in normoinsulinemic animals with a similar plasma cortisol level. Partial correlation analysis of the data showed that plasma insulin and cortisol were both significant influences on hepatic glucose-6-phosphatase activity in utero, but plasma cortisol had the more pronounced effect. Cortisol, therefore, appears to be a physiological regulator of tissue glucose-6-phosphatase activity in utero and enhances the glucogenic capacity of the sheep fetus during late gestation.

Animals↗
PubMed1989

Foundations of a misunderstanding of the ultrastructural basis of myocardial failure: a reciprocation network of oversimplifications.

A misconception regarding the ultrastructural basis of myocardial failure has been observed in laboratory studies involving medical students and practicing physicians, in medical textbooks, and in clinical instruction of students. This misconception attributes heart failure to overextension of individual cardiac muscle fibres and their sarcomeres, resulting in a mechanically based decline in contractile force production. The basis of the misconception is a set of component misconceptions which interact in reciprocally supportive ways. The interlocking nature of the component misunderstandings strengthens the overall misconception, making it difficult to undermine. A contributor to many aspects of the faulty account of heart failure is a tendency toward oversimplification of complex phenomena in learning, instruction, and scientific research. Implications for medical education are considered.

Cognitive Dissonance↗
PubMed1987

Discrepancy in stoichiometry of steady-state muscle [Pi] and [PCr] induced by exercise.

Phosphorus nuclear magnetic resonance was used to quantify the relations between metabolic phosphates, intracellular pH, and work rate in forearm muscle of six adult men over a range of work rates from 1.0 to 3.5 W. Three work rates were studied in each of four sessions (either 1.0, 2.0, and 3.0 or 1.5, 2.5, and 3.5 W), with measurements made before and during each bout, thereby permitting the partition of the variance attributable to rest, work-dependent, and time-dependent metabolic functions by regression analysis. There were no time-dependent changes in either [ATP] or intracellular [H+] as assessed during the rest intervals between bouts of exercise. In contrast, the total nuclear magnetic resonance (NMR)-visible phosphorus pool (TVPP) decreased with time, with both phosphocreatine (PCr) and inorganic phosphate (Pi) contributing significantly to TVPP reduction. Muscle [ATP] was unchanged by work at all intensities. Intracellular [H+] increased moderately and proportionately to work rate. [PCr] decreased and [Pi] increased in proportion to work rate, with the work-dependent coefficient for PCr consumption approximately 1.5 times that of Pi production. Neither Pi line width nor motion artifact accounted for the decrease in TVPP, so the reduced Pi accumulation in exercise may represent its sequestering in some NMR-invisible muscle pool and/or loss to the blood. Whatever the process involved, it is proportional to work rate and persists for at least 10-15 min after exercise.

Adenosine Triphosphate↗
PubMed1986

Measurement of solute proton spin-lattice relaxation times in water using the 1,3,3,1 sequence.

1H NMR spin-lattice relaxation times (T1) of the N-CH3 proton resonances of phosphocreatine (PCr) and creatine (Cr) in water solutions were obtained using the 1,3,3,1 pulse sequence. These T1 values were equivalent to those obtained in D2O and water using either the conventional inversion-recovery experiment or the 1,3,3,1 pulse sequence. Thus, the 1,3,3,1 sequence of proton NMR can provide an independent means along with phosphorous NMR for assess PCr and for the study of the creatine kinase reaction (PCr + ADP in equilibrium ATP + Cr) in aqueous solutions and perhaps in biological preparations.

Adenosine Diphosphate↗
PubMed1985

In vivo 31P-NMR in human muscle: transient patterns with exercise.

Evaluation of dynamic changes in pH and concentrations of adenosine 5'-triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) during the transition from rest to steady-state exercise in the human has been methodologically limited. Previous work has relied on muscle biopsy of exercising subjects at different times in different exercise bouts. Chemical evaluation of metabolites has been hampered by continuing change in metabolic concentration during the biopsy procedure. Recently, Fourier-transformed 31P nuclear magnetic resonance (31P-NMR), employing surface coils, has made evaluation of phosphorus metabolites possible by noninvasive atraumatic means in human muscle. Relative concentrations of PCr, Pi, and ATP, together with pH, have been obtained with 31P-NMR from the flexor digitorum superficialis muscle on two occasions in four adult men during the transition from rest to exercise. [PCr] rapidly fell and was mirrored by a rise in [Pi]. The former temporarily exceeded the latter with the discrepancy apparently being absorbed by a transient rise in [ATP], which was itself mirrored by alteration in [H+].

Adenosine Triphosphate↗
PubMed1985

Energetics of myocardial function.

The question of whether the heart in humans is resistant to deterioration during prolonged exercise is addressed in this review. An evaluation of the available data in the literature shows: 1) whole body VO2 increases during vigorous prolonged exercise, primarily due to an increase in O2 consumption of working muscles; 2) heat exacerbates the rise in VO2; 3) these factors, hard exercise and heat, induce cardiovascular drift which involves progressive decreases in mean arterial pressure and stroke volume, with heart rate increasing to maintain cardiac output; 4) the fall in stroke volume appears to occur, at least in part, because ventricular filling pressure is lowered with a fall in central venous volume as cutaneous venous volume increases; 5) there is some limited indirect evidence that the inotropic state of the heart may also decrease with prolonged exhaustive exercise; and (6) neither estimates of heart work nor myocardial energetics appear to change in healthy men after 1 h of exercise under temperate conditions.

Energy Metabolism↗
PubMed1982

Isolated while heart calorimetry: energetics of length-dependent activation.

Myocardial energy expenditure measured by whole heart calorimetry has in the past been used to demonstrate that the thermal accompaniment of contractile activity is indicative of both force-related and force-independent activities. A mechanical technique for demonstrating the length dependence of activation in the right ventricular papillary muscle has been extended to the intact but isolated whole left ventricle of the heart. A functional relationship between the degree of length-dependent activation and force-independent energy expenditure has been observed. Potentiation of isovolumic cardiac mechanical activity by inotropic stimulation with extracellular calcium is thermally more economic than similar potentiation by length-dependent activation, particularly at large ventricular volumes (long muscle fiber lengths). A hypothesis is formulated that explains both the current myothermic observations and the aequorin calcium transients observed by Allen and Kurihara. Important analytic limitations of whole heart calorimetry are acknowledged.

Animals↗
PubMed1981

Resting potential changes associated with Na-K pump in failing heart muscle.

Microelectrode and single sucrose gap techniques were used to measure transmembrane potentials in normal and failing papillary muscles. Six muscles from control animals and 10 from banded animals were cooled (2-4 degrees C) and subsequently rewarmed to 37 degrees C. Normal muscles demonstrated significantly greater increases in maximum diastolic potential (--Emax) on rewarming than those from failing animals. In muscles subjected to transient periods of rapid stimulation, --Emax depolarized initially on stimulation but eventually plateaued at a depolarized level and then hyperpolarized beyond prestimulation levels. These changes in --Emax were altered in failing muscles. The initial rate of depolarization (delta -- Emax/delta t) on stimulation and the magnitude of this depolarization (delta -- Emax) was decreased at all rates studied. The time necessary to arrive at the plateau (time to delta -- Emax) was significantly lengthened in failing muscles. The hyperpolarization seen on rewarming cooled preparations and the changes in --Emax during stimulation have both been related to an activation of an electrogenic Na-K pump suggesting that this ion-transport system is altered in failing heart muscle. The decrease in delta -- Emax/delta t and delta -- Emax seen in failing muscles indicates that K efflux may be lower or that the volume of confined intercellular spaces is greater in failing heart muscle.

Animals↗
PubMed1981

The direct myocardial energetic response to nitroglycerin in the rabbit heart.

The coronary resistance, total heat production, oxygen consumption and isovolumic mechanical performance were measured simultaneously in the isolated beating rabbit heart. The direct effects of nitroglycerin (0.12 mg/l) were determined. The expected coronary dilatation occurred; coronary resistance fell by 21.5% independent of mechanical performance. There was a 14% fall in mechanical performance at the apex of the Frank-Starling curve and lesser reductions at less-than-apical diastolic volumes. Oxidative metabolism was not affected; there was no change in the calorific equivalent of oxygen (20.97 mJ/mul:O2) nor was there any significant anerobic metabolism. The ergonic cost of the force-independent metabolism which includes calcium activation energy was reduced by 17.7%. The unit metabolic cost of mechanical performance, or the performance-dependent metabolism, was unchanged resulting in a net increase in overall mechanical economy. It is concluded that it is against a background of a more metabolically efficient but less mechanically active myocardium that nitroglycerin exhibits its well known peripheral and reflex in the intact organism.

Animals↗
PubMed1979

Increased passive stiffness of short-term pressure-overload hypertrophied myocardium in cat.

The passive stress-strain relationship of right ventricular papillary muscles from 10 normal and 9 experimental cats with short-term pressure-overload right ventricular hypertrophy-failure was examined by plotting the logarithm of instantaneous stress (ln sigma) against the natural strain calculated as ln(l/l0) where l = instantaneous length and l0 = length at zero force. Such a stress-strain relationship was well approximated by a linear relationship. The slope K obtained from this linear relationship was higher in the hypertrophy-failure muscles (normal, 15.01 +/- 0.87 (SEM); hypertrophy-failure, 31.79 +/- 4.09; P less than 0.005). The value of the intercept, ln C was similar in the two groups (normal, -4.33 +/- 0.20; hypertrophy-failure, -4.71 +/- 0.10). This analysis indicates the the ln sigma-natural strain relationship is linear in the papillary muscle and the slope of this relationship, an index of stiffness, is increased in hypertrophy-failure muscles. Using a three-element muscle model, it is shown that increased diastolic stiffness may contribute to the decreased systolic performance.

Animals↗
PubMed1978

Normal cardiac myosin ATPase and mechanics in pressure overload with digitalis treatment.

Cardiac muscle myosin ATPase activity is depressed and contractile function impaired when the heart is subjected to a chronic pressure overload. Administering digitalis in the presence of chronic pressure overload significantly attenuates the decline in mechanical function. The current study sought to determine if the cardiac muscle myosin ATPase activity of cats treated with digitalis in the presence of pressure overload remains normal in parallel with the mechanical function. Four groups of cats were studied: normal controls (C), animals with pressure-overload hypertrophy with or without failure (HF), normal cats that received treatment with digitalis (D), and animals that received digitalis prior to and together with pressure overload (DHF). Compared to C, the maximum myosin ATPase activity of HF was significantly (P less than 0.05) depressed, but the maximum ATPase activity of D and DHF was not altered significantly (P greater than 0.05) from C. In parallel with the enzyme maximum activity, the papillary muscle isometric rate of force development was significantly (P less than 0.005) depressed in HF compared to C; D and DHF were not significantly (P greater than 0.05) different from C. It is concluded that the depression of myosin ATPase observed in HF is not present when digitalis is administered concomitant with the pressure overload.

Adenosine Triphosphatases↗