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Biomedical subjects

J B Chapman

Publications and source records attributed to J B Chapman.

At least 19 recordsLinked to original sources
PubMed1995

Steady-state rate analysis: application to biological transport.

A novel method for defining the steady-state unidirectional rates of complex reactions has previously been developed (Wagg, 1988 Ph.D. Thesis, Monash University, Australia). This methodology is based upon the method of Wagg (1987, J. theor. Biol. 128, 375-385) for defining the steady-state unidirectional fluxes of chemical species through branched chemical, osmotic and chemiosmotic reactions. It offers a number of distinct advantages over existing approaches to steady-state rate analysis: it is relatively simple to apply to complex reactions and is readily amenable to computer-based application. The method is demonstrated by direct application to a number of hypothetical models for biological transport phenomena.

Animals↗
PubMed1995

A flux ratio analysis of the Post-Albers mechanism of the sodium pump.

A thermodynamically constrained method of flux ratio analysis has been applied to the Post-Albers mechanism of the sodium pump to establish a relationship between the thermodynamic "boundary conditions" for the overall pump reaction and the unidirectional flux ratios for the pump-mediated fluxes of sodium and potassium. This relationship provides an experimental criterion for assessing whether or not the reactions associated with ion binding and dissociation to and from the pump, respectively, are close to equilibrium. Examination of experimental data from the current body of literature indicates that the above criterion is not satisfied for the sodium pump of human red blood cells under normal physiological conditions. On the basis of this result, it is concluded that within the context of a Post-Albers mechanism one or more of the ion binding and dissociation steps are not in rapid equilibrium with other such steps, at least not for the sodium pump of human red blood cells under normal physiological conditions.

Animals↗
PubMed1995

Steady-state flux ratio analysis: application to biological transport.

A thermodynamically constrained method of flux ratio analysis, based upon a previously developed thermodynamic rate ratio equation has been developed. In this paper it is demonstrated that, for a complex reaction, application of the thermodynamic rate ratio equation may provide a useful tool for the interpretation of unidirectional flux data thought to be mediated by the reaction, provided that: (i) a clearly defined mechanism for the reaction has been proposed; (ii) a set of partial reaction components may be defined for the reaction from the proposed mechanism, with the rate ratio of at least one of these components being amenable to experimental measurement. This paper defines the conditions for which the rate ratio of a component reaction may be measured, and illustrates the basic principles underlying this approach to flux ratio analysis by direct application to a number of hypothetical mechanisms for biological transport phenomena.

Animals↗
PubMed1995

Clinical correlates of gallstone composition: distinguishing pigment from cholesterol stones.

OBJECTIVES: The prevalence of cholelithiasis has been established in population-based surveys employing ultrasonography, and major risk factors have been identified. However, the clinical and epidemiological features that distinguish patients with pigment gallstones from those with cholesterol stones have received little attention. METHODS: We prospectively surveyed 551 patients undergoing cholecystectomy for gallstones at two teaching hospitals. Clinical and epidemiological data were collected during patient interviews and by chart review. Gallstones were collected at surgery; physical measurements were recorded, and stone composition was determined by visual inspection and infrared spectroscopy. RESULTS: Patients with pigment stones were older than patients with cholesterol stones (p < 0.00001). Almost all patients under age 40 yr old had cholesterol stones, but most patients over 70 had pigment stones. Cirrhosis was strongly associated with pigment gallstones (p < 0.00001), although alcohol consumption was unrelated. Univariate analyses suggested associations of stone composition with male sex, diabetes mellitus, educational attainment, and use of thiazides or oral contraceptives, but these were not significant in a logistic regression that adjusted for age, cirrhosis, and other variables. Patients with pigment cholelithiasis had stones that were generally smaller in diameter and fewer in number than those with cholesterol stones. CONCLUSIONS: Compared to patients with cholesterol gallstones, those with pigment stones are older and more likely to have a diagnosis of cirrhosis. In addition, their stones are smaller in size and fewer in number than those from patients with cholesterol cholelithiasis.

Adult↗
PubMed1994

Gallstone characteristics in Mexican Americans and non-Hispanic whites.

Mexican Americans have an elevated risk of gallstones. Their increased rates may be due to genetic admixture with Native Americans, who have extremely high prevalences of cholelithiasis. Native Americans are believed to have almost exclusively cholesterol stones, whereas only 73% of non-Hispanics are reported to have such stones. Hence we hypothesized that Mexican Americans would have a higher proportion of cholesterol stones than would non-Hispanic whites. We interviewed 398 Mexican Americans and 93 non-Hispanic whites undergoing cholecystectomy and analyzed the composition of their gallstones. Mexican Americans were younger than non-Hispanic whites (P < 0.05). However, the age-sex standardized proportion of cholesterol stones was 89.7% in Mexican Americans and 87.2% in non-Hispanic whites. We conclude that Mexican Americans and non-Hispanic whites have gallstones of similar composition. The higher stone prevalence of Mexican Americans may be due to factors that predispose to both cholesterol and pigment stones.

Adult↗
PubMed1988

Phenobarbitone: adverse effects on reproductive performance and offspring development in the Mongolian gerbil, (Meriones unguiculatus).

Phenobarbitone at a concentration of 500 mg/l in drinking fluid of gerbils during pregnancy (60 mg/kg) and lactation (136 mg/kg) markedly reduced the proportion of animals bearing litters, decreased pup weights at birth and during later life and delayed development of the self-righting reflex, auditory startle reaction, eye opening and full fur coverage. It also prolonged the period of suckling. Scars of implantation were evident in uterine horns of 60% of treated and in none of control females that had failed to give birth. Treated offspring after weaning were given phenobarbitone (500 mg/l; 42-124 mg/kg) as their drinking fluid throughout life and a further group of gerbils received this concentration of the drug from the time of weaning. Seizure susceptibility was unaltered by the drug treatment, and the only evidence of behavioural change was seen in offspring gerbils at 6 weeks when the bout length of social investigation during encounters was increased. Drug-treated offspring showed no abnormality in brain weight relative to body weight. Weight gain and brain weight remained normal among the gerbils given phenobarbitone after weaning. The drug treatment reduced scent gland size in breeding males, though not in the offspring, and had no effect on weights of the testes or ovaries and uterus. no effect on weights of the testes or ovaries and uterus. Plasma concentrations of phenobarbitone in females of the postweaning group amounted on average to 4.4 mg/kg. Most of the adverse effects of this dose of phenobarbitone in the gerbil can thus be seen to be associated either with reproductive impairment or with exposure during sensitive periods of early development.

Animals↗
PubMed1987

Sodium valproate: effects on maternal behaviour in the mouse.

The behaviour of lactating mice in their home cages was examined by ethological procedures at 1, 7, 14 and 21 days postpartum. Early in lactation, maternal behaviour was more frequent in the light phase of the 24 hr cycle, whereas non-social activity occupied a greater amount of time during the dark phase. As the pups became older, maternal behaviour declined, and at 21 days the dams showed a marked increase of solitary immobility. Behavioural alterations produced by the administration of sodium valproate at 600 mg/l as drinking fluid during pregnancy and lactation (group SVP), and during lactation only, (group PN) were assessed. (Intake of drug amounted to 153 mg/kg during gestation and 186 mg/kg in lactation). Dams of group PN showed behavioural differences from controls in late lactation, pup nursing being prolonged at day 14 postpartum and the frequency of all categories of active behaviour, other than nursing and nestbuilding, was increased at day 21 postpartum in the dark phase of their daily cycle. There was not significant effect on categories of behaviour in dams of the SVP group. Overall, sodium valproate, at this dose, did not reduce maternal care.

Animals↗
PubMed1985

Cardiac mechanics and energetics: chemomechanical transduction in cardiac muscle.

When a heart is in a stable inotropic state, the end-systolic pressure-volume points of each work cycle fall on a straight line regardless of the magnitude of the afterload or the initial end-diastolic volume: cardiac O2 consumption (MVO2) per beat is linearly correlated with ventricular systolic pressure-volume area (PVA), defined in terms of stroke work and potential energy components. Moreover, if the basal and activation components of the cardiac energy cycle are subtracted, hearts operate at a constant PVA/MVO2 efficiency. The present review examines the energetic implications of these results for current muscle models, discussing the energetic background of earlier skeletal muscle viscoelastic models and examining differences between the vectorial outputs of ion transport ATPases and myofibrillar ATPases. The PVA data point to a unique stoichiometric relationship between myocardial energy flux and vectorial output, and it is shown that most existing myocardial O2 consumption data can be reconciled with the PVA concept. However, most muscle models would not predict a linear stoichiometric relation between energy flux and pressure-volume potential energy. We pose the question as to whether there is an undiscovered autoregulatory process at work in muscle.

Adenosine Triphosphate↗
PubMed1984

Sodium valproate: effects on social behaviour and physical development in the mouse.

Sodium valproate given in drinking fluid at 600 mg/l (160-180 mg/kg daily) to breeding mice did not affect fertility, birth weights or physical development of pups. Postnatal and postweaning administration of this dose also had no effects upon development or weight gain. The offspring ingested 103-158 mg/kg valproate daily after weaning. Behaviour was examined in a neutral enclosure by ethological methods. Offspring exposed to valproate in utero and throughout postnatal life showed no behavioural changes at 5 weeks, although at 15 weeks Immobility was reduced in females and Social Investigation increased. At 25 weeks when encountering mice of the opposite sex, treated males showed increase in Social Investigation and treated females increases in Other Non-social Activity. Postnatal and postweaning treatment with valproate caused behavioural changes both in juveniles and adults. After postnatal exposure, reduced Immobility with increased Social Investigation and Explore and Scan occurred at 5 and 15 weeks, at 25 weeks valproate increased Social Investigation in males encountering females and at 30 weeks enhanced Aggression in pair-housed males. Stimulation of Social Investigation was the only significant behavioural effect after postweaning exposure. Overall valproate appears to enhance behaviour stimulated by the test situation; urinary pheromones do not appear to play a part in this behavioural action.

Animals↗
PubMed1983

Behavioral effects of phenobarbitone II. Effects in nursing female mice.

Phenobarbitone supplied at concentrations of 187.5 mg/l and 500 mg/l (50--60 mg/kg and 120--190 mg/kg daily) in the drinking fluid of mice throughout pregnancy and lactation did not affect gestation period, numbers born or resorbed or pup weights at birth and weaning. The higher dose caused significant retardation in eye-opening, development of forelimb extension, negative geotaxis, in appearance of washing and self-grooming behaviours and in cessation of suckling. The lower dose had no detectable effects. Ethological methods were used to examine spontaneous behaviour of nursing dams within home cages on days 1, 7, 14 and 21 postpartum. Treated dams showed differences in behaviour from controls, the most marked of which were increased levels of Maternal Behaviour and decreases in Non-Social Activity in the high-dose group at day 1, and continuance of pup Nursing in both treated groups and Nest Building in the high-dose group at day 21 when controls were ceasing these behaviours. At 21 days all treated dams also showed less Immobility than controls and high-dose dams a smaller amount of pup Social Investigation. Many behavioural differences at 21 days were related to developmental delay of treated pups. Overall, phenobarbitone did not impair maternal care.

Animals↗
PubMed1983

Behavioural effects of phenobarbitone. 1. Effects in the offspring of laboratory mice.

Phenobarbitone at a concentration of 187.5 mg/l in drinking fluid of breeding mice and their offspring after weaning did not affect gestation period, litter size, litter weight or pup development before weaning, although a slight retardation of weight gain after weaning occurred. This level of phenobarbitone given to mice after weaning did not affect weight gain. The average daily intake of phenobarbitone ranged from 30 to 52 mg/kg body weight depending on age and sex. Behaviour of offspring and mice treated after weaning was examined by ethological analysis of encounters between unfamiliar mice of the same sex and treatment group in a neutral enclosure. After lifelong exposure to phenobarbitone mice at 5 and 15 weeks of age showed an increased amount of scanning and exploration of the unfamiliar cage coupled with a decrease of time spent in immobility. Difference from control levels was more pronounced at 15 than at 5 weeks of age, in part because controls showed more immobility and explored less as they matured. No behavioural changes were detected in mice treated with this level of phenobarbitone after weaning. Lifelong exposure to phenobarbitone did not affect agonistic behaviour in pair-housed males at 30 weeks of age, and under these circumstances no longer stimulated exploration to a significant extent.

Aging↗
PubMed1983

Electrical and biochemical properties of an enzyme model of the sodium pump.

The electrochemical properties of a widely accepted six-step reaction scheme for the Na+, K+-ATPase have been studied by computer simulation. Rate coefficients were chosen to fit the nonvectorial biochemical data for the isolated enzyme and a current-voltage (I-V) relation consistent with physiological observations was obtained with voltage dependence restricted to one (but not both) of the two translocational steps. The vectorial properties resulting from these choices were consistent with physiological activation of the electrogenic sodium pump by intracellular and extracellular sodium (Na+) and potassium (K+) ions. The model exhibited K+/K+ exchange but little Na+/Na+ exchange unless the energy available from the splitting of adenosine triphosphate (ATP) was reduced, mimicking the behavior seen in squid giant axon. The vectorial ionic activation curves were voltage dependent, resulting in large shifts in apparent Km's with depolarization. At potentials more negative than the equilibrium or reversal potential transport was greatly diminished unless the free energy of ATP splitting was reduced. While the pump reversal potential is at least 100 mV hyperpolarized relative to the resting potential of most cells, the voltage-dependent distribution of intermediate forms of the enzyme allows the possibility of considerable slope conductance of the pump I-V relation in the physiological range of membrane potentials. Some of the vectorial properties of an electrogenic sodium pump appear to be inescapable consequences of the nonvectorial properties of the isolated enzyme. Future application of this approach should allow rigorous quantitative testing of interpretative ideas concerning the mechanism and stoichiometry of the sodium pump.

Animals↗
PubMed1982

Myothermic, polarographic, and fluorometric data from mammalian muscles: correlations and an approach to a biochemical synthesis.

Energy output of mammalian cardiac, smooth, and skeletal muscles has been studied by recording oxygen consumption, heat production, the fluorescence of reduced nicotinamide adenine dinucleotide (NADH), and lactate production. Active oxygen consumption and heat production of all muscle types correlate well if one assumes a calorific equivalent of 20.2 kJ/liter of oxygen. At 27 C aerobic lactate production is low in all muscle types and is not appreciably increased after mechanical activity. Early oxidation of NADH within the time course of the mechanical event suggests that no temporal basis exists for distinguishing between initial and recovery heat production in mammalian muscles. For muscles consuming energy at low rates, the time course of fluorescence recovery to baseline correlates well with the time course of late heat production, and the area enclosed by a fluorescence waveform (fluorescence-time integral) correlates well with total energy consumption. At high energy rates these correlations disappear as the fluorescence waveforms display complex kinetics. A digital computer simulation of oxidative phosphorylation and intermediary metabolism predicts failure of correlation between mitochondrial NADH levels and other metabolic indices under such conditions. This lends indirect support to the assumption that cytoplasmic NADH does not complicate the fluorescence signals recorded from aerobic unpoisoned muscles.

Adenosine Diphosphate↗