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Biomedical subjects

S P Brooks

Publications and source records attributed to S P Brooks.

At least 19 recordsLinked to original sources
PubMed2002

Nimodipine prevents the effects of ethanol in tests of memory.

The effects of acute administration of the dihydropyridine calcium channel antagonist, nimodipine, were studied on the actions of ethanol in the radial arm maze and the object recognition test. In the former test, the effects of the drugs were examined on the performance in finding the four baited arms, after previous training in this task. Ethanol, at 1 g/kg, increased both the number of re-entries into baited arms (counted as errors of working memory) and the total number of arm choices required to complete the task. Administration of nimodipine, 10 mg/kg, with the ethanol, completely prevented the deleterious effects on memory in this task, but had no effects on the performance when given in the absence of ethanol. In the object recognition task, ethanol, 1 g/kg, significantly decreased the differences in the time spent exploring novel and familiar objects. Nimodipine, 10 mg/kg, given with the ethanol, completely prevented this effect, but nimodipine alone had no effects. The lack of changes in total exploration times indicated that the effects of ethanol in these tests were not due to loss of motor co-ordination or of alertness. The results are discussed in the light of the known actions of the drugs on brain function.

Animals↗
PubMed2002

Low alcohol preference among the "high alcohol preference" C57/BL10 mice; factors affecting such preference.

The effects of age, ethanol concentration and minor stress on the variation in alcohol preference of C57 strain mice were determined. In two bottle choice tests, an older population of mice contained slightly more low-preference mice than a younger population. A wide range of ethanol preference was consistently seen in young mice for 8% and 6% ethanol, but the previously reported biphasic pattern of distribution was revealed only with 8% ethanol. Very few animals showed high preference for concentrations of 10% or 12% ethanol. Moving low alcohol preference mice to a new location (but not repeated cage changing or ultrasonic noise) significantly increased the alcohol preference. Exploratory locomotor activity did not correlate with the subsequent alcohol consumption. Blood and brain alcohol concentrations showed that the differences in alcohol preference were not due to differences in metabolism of ethanol. The C57 strain mice with low preference for alcohol provides a valuable model for the study of the effects of minor stress on alcohol consumption.

Acoustic Stimulation↗
PubMed2001

Chronic infusion of nicotine can increase operant self-administration of alcohol.

Effects of nicotine, administered by continuous infusion via osmotic minipumps, were studied on the operant self-administration of alcohol by rats, using a variable interval (15 s) schedule, and measuring the acquisition, maintenance, extinction and reinstatement of responding for alcohol. Doses of nicotine of 0.25, 1.25 and 7.5 mg/kg/24 h had no significant effects on the maintenance of responding for alcohol, but 5 mg/kg/24 h nicotine resulted in a significant increase in responding on the lever delivering the reward when water was substituted for the alcohol, indicating delayed extinction of responding. During infusion of 2.5 mg/kg/24 h nicotine, responding was significantly greater over the "sucrose-fading" training sessions, during acquisition of responding, when mixtures of alcohol and sucrose were provided as reward. When minipumps infusing 2.5 mg/kg/24 h nicotine were implanted after the alcohol responding had been acquired, the responding for alcohol increase during the first week of nicotine infusion, but corresponding nicotine infusion doses of 0.25, 1.25 and 7.5 had no significant effects. The results indicate that nicotine can increase operant responding for alcohol and this is crucially dependent on the dose of nicotine and the time of testing. The results have implications for the frequently encountered dependence on the combination of alcohol and nicotine.

Alcohol Drinking↗
PubMed2001

Problems associated with measuring phytate in infant cereals.

The inositol hexaphosphate (IP6) content of commercially available dried infant cereals was measured by ion pair high-pressure liquid chromatography (ion pair HPLC) and ion exchange high-pressure liquid chromatography (ion exchange HPLC). Large differences between methods were apparent: ion pair HPLC gave values 14 to 190-fold lower than the values from ion exchange HPLC. Poor recoveries of added IP6 (25 to 60%) by ion pair HPLC suggested that some component of the infant cereal was responsible for the difference. Further experimentation suggested that an excess of minerals (approximately 11 mg/g calcium and 0.3 mg/g iron) in these samples sequestered the endogenously low phytate content. This problem may be unique to samples with low IP6 and high mineral content as wheat bran was not problematic. These results suggest that ion exchange HPLC is the method of choice for measuring inositol phosphates in infant cereals.

Artifacts↗
PubMed2001

Comparison of dietary fiber contents of selected baby foods from two major brands in Canada using three methods.

Of the two major brands of baby foods in Canada, one reports lower dietary fiber values than the other, although the products appear to be similar. To investigate the reasons for this discrepancy, seven selected samples of baby foods from both brands were analyzed for total dietary fiber (TDF) according to the Mongeau (rapid Health Protection Branch; HPB) method. Two cereals were also analyzed by using the Prosky and the Englyst (nonstarch polysaccharide; NSP) methods as an internal check on the methodology as well as a means of investigating the reasons for the discrepancies. The sampling included at least four different lots of each product (cereals, fruits, vegetables, and legumes). Each lot was analyzed individually. The TDF values determined using the rapid HPB method were in agreement with those obtained by other dietary fiber methods. Comparison between manufacturer-reported and measured values showed that the low values reported in brand A products were due, in part, to under-reporting of TDF content: measured TDF values were significantly higher than manufacturer-reported values. For brand B products, the manufacturer-reported and measured TDF values were in general agreement. This shows that a large part of the discrepancy between the two brands was due to methodological problems associated with measuring TDF in brand A. Differences in TDF content were also apparent as shown by the fact that brand A TDF values were consistently lower than those of brand B when both were measured by the same method. The differences in TDF content were not explained by differences in the polysaccharide composition of the fiber residues or by differences in water content. Although the limited number of samples does not allow any general conclusion about the TDF content of specific brands, the results show that formulation and/or manufacturing differences may influence TDF values in processed baby foods.

Canada↗
PubMed2000

On the Bayesian analysis of ring-recovery data.

Vounatsou and Smith (1995, Biometrics 51, 687-708) describe the modern Bayesian analysis of ring-recovery data. Here we discuss and extend their work. We draw different conclusions from two major data analyses. We emphasize the extreme sensitivity of certain parameter estimates to the choice of prior distribution and conclude that naive use of Bayesian methods in this area can be misleading. Additionally, we explain the discrepancy between the Bayesian and classical analyses when the likelihood surface has a flat ridge. In this case, when there is no unique maximum likelihood estimate, the Bayesian estimators are remarkably precise.

Animals↗
PubMed1999

Temperature regulation of glucose metabolism in red blood cells of the freeze-tolerant wood frog.

The low-temperature metabolism of erythrocytes from the freeze-tolerant frog Rana sylvatica was investigated by (13)C and (31)P NMR spectroscopy. Erythrocytes readily took up high concentrations of the natural cryoprotectant, glucose, at both high (12 and 17 degrees C) and low (4 degrees C) temperatures but glucose was apparently not metabolized at 4 degrees C. Strong inhibition of glucose catabolism at low temperature would facilitate the maintenance of the very high concentrations of glucose (approximately 200 mM) that are accumulated to provide cryoprotection during freezing in wood frogs. Analysis of (13)C labeling of glycolytic intermediates at 4 degrees C showed mixing of label primarily in hexose (fructose) and hexose phosphate (glucose 6-phosphate, fructose 6-phosphate) pools but little label incorporation into triose phosphate intermediates. These data are consistent with a profound low-temperature-induced inhibition of phosphofructokinase (PFK). Investigations into potential PFK control mechanisms were undertaken. (31)P NMR analysis showed that the intracellular pH of erythrocytes increased from 7.0 to 7.3 as temperature decreased from 17 to 4 degrees C in a manner consistent with alphastat regulation. This change is exactly opposite to that expected if overall PFK activity was regulated by changes in cellular pH since PFK is less active at lower pH values in vitro. Other factors must, therefore, operate to regulate PFK at lower temperatures.

Animals↗
PubMed1999

Metabolic adjustments during daily torpor in the Djungarian hamster.

Djungarian hamsters (Phodopus sungorus) acclimated to a short photoperiod (8:16-h light-dark cycle) display spontaneous daily torpor with ad libitum food availability. The time course of body temperature (Tb), metabolic rate, respiratory quotient (RQ), and substrate and enzyme changes was measured during entrance into torpor and in deep torpor. RQ, blood glucose, and serum lipids are high during the first hours of torpor but then gradually decline, suggesting that glucose is the primary fuel during the first hours of torpor, with a gradual change to lipid utilization. No major changes in enzyme activities were observed during torpor except for inactivation of the pyruvate dehydrogenase (PDH) complex in liver, brown adipose tissue, and heart muscle. PDH inactivation closely correlates with the reduction of total metabolic rate, whereas in brain, kidney, diaphragm, and skeletal muscle, PDH activity was maintained at the initial level. These findings suggest inhibition of carbohydrate oxidation in heart, brown adipose tissue, and liver during entrance into daily torpor.

Adaptation, Physiological↗
PubMed1998

Role of transforming growth factor-beta1 in the suppressed allostimulatory function of AIDS patients.

BACKGROUND: The T-cell stimulatory function of accessory cells isolated from peripheral blood lymphocytes of AIDS patients has been reported to be suppressed. These patients also have elevated levels of the immunosuppressive factor transforming growth factor (TGF)-beta1 in their serum and plasma. OBJECTIVE: To explore the role of TGF-beta1 in the loss of accessory cell function of peripheral blood lymphocytes from AIDS patients. METHODS: Fluorescent labeled anti-TGF-beta1 and confocal microscopy were used to detect the presence of TGF-beta1 on the cell membrane of dendritic cells. To assess the role of TGF-beta1 in the inhibition of accessory cell function in AIDS, antibodies against TGF-beta1 or the TGF-beta1 type III receptor, beta-glycan, were added to a mixed lymphocyte reaction. RESULTS: TGF-beta1 was detected on the cell membrane of dendritic cells isolated from AIDS patients. The addition of blocking antibodies against either TGF-beta1 or beta-glycan restored the T-cell stimulatory function to accessory cells from these patients. CONCLUSIONS: T-cell stimulatory function was not irreversibly lost in AIDS patients. Our data suggested that beta-glycan-TGF-beta1 immunosuppressive complexes may contribute to the suppression of accessory cell function in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Protein kinase C from rainbow trout brain: identification and characterization of three isozymes.

Free and membrane-associated fractions of protein kinase C (PKC) from rainbow trout (Onchorynchus mykiss) brain tissue were separated by hydroxylapatite chromatography and characterized kinetically. In both resting fish and in fish swum to exhaustion, approximately 40% of the total PKC activity was bound to membranes. Quantification of the three distinct hydroxylapatite chromatography peaks (PKC types gamma, beta and alpha) in cytosolic and membrane fractions revealed different isozyme distributions. The cytosolic fraction contained 21% PKC type gamma, 52% PKC type beta and 27% PKC type alpha. The membrane-associated fraction contained 23% PKC type gamma, 28% PKC type beta and 49% PKC type alpha. Kinetic characterization of the three isozymes showed that PKC type gamma was almost completely activated by Ca2+ alone whereas PKC type beta and PKC type alpha were 40% and 60% activated by Ca2+. Full activity for all enzymes was observed only in the presence of phosphatidylserine and diacylglycerol. Differences in the kinetic constants for the three isozymes were also apparent. PKC type gamma had a much lower affinity for Histone III-S when compared with PKC types beta and alpha (100 micrograms/ml as compared with 1.7 and 5.7 micrograms/ml). PKC type gamma also had a lower affinity for calcium (0.22 microM) when compared with PKC type beta (0.08 microM) and PKC type alpha (0.05 microM). PKC type alpha had a lower affinity for phosphatidylserine (8.6 micrograms/ml) when compared with PKC type gamma (0.37 microgram/ml) and PKC type beta (0.89 microgram/ml).

Animals↗
PubMed1997

Glycolytic controls in estivation and anoxia: a comparison of metabolic arrest in land and marine molluscs.

Facultative metabolic rate depression is the common adaptive strategy underlying various animal mechanisms for surviving harsh environmental conditions. This strategy is common among molluscs, enabling animals to survive over days or even months in the absence of oxygen or under extremely dry conditions. The large reductions in metabolic rate during estivation and anoxia can translate into considerable energy savings when dormant animals are compared to active animals. A complex metabolic coordination is required during the transition into the dormant state to maintain cellular homeostasis and involves both energy-consuming and energy-producing pathways. With regard to energy-producing pathways, several different mechanisms have been identified that participate in controlling flux. One such mechanism, enzyme phosphorylation, can have a wide-ranging effect. For example, phosphorylated enzymes exhibit altered substrate, activator, and inhibitor affinities. This effect may be magnified by changes in the concentrations of allosteric effectors, such as fructose 2,6-bisphosphate, that occur during hypometabolic states. Changes in fructose 2,6-bisphosphate are related to changes in enzyme phosphorylation through changes in the relative activity of phosphofructokinase-2. Alterations in glycolytic enzyme binding can also be brought about through changes in enzyme phosphorylation. The present review focuses on identifying hypometabolism-related changes in enzyme phosphorylation as well as characterizing the mechanisms involved in mediating these phosphorylation events.

Animals↗
PubMed1997

Time course of enzyme changes after a switch from a high-fat to a low-fat diet.

This study was conducted to determine the time course of metabolic changes associated with a switch from a high-fat to a low-fat diet in rats. Adult rats, maintained on a high-fat diet (42% of energy from fat) for 4-5 weeks were switched to a low-fat diet (11% of energy from fat), and the activities of several liver enzymes were followed. Three different phases could be distinguished. The early phase, complete by 2 days after the switch in diets, included an increase in the activity of glucose 6-phosphate dehydrogenase (pentose phosphate pathway), an increase in pyruvate kinase and pyruvate dehydrogenase activities (terminal end of the glycolytic pathway) and an increase in ATP-citrate lyase and fatty acid synthetase (fatty acid synthesis pathway). The early phase also included a decrease in the activity of phosphoenolpyruvate carboxykinase (PEPCK, gluconeogenesis) and a lower branched-chain amino acid dehydrogenase activity (BCAADH, branched-chain amino acid degradation). The concentration of the allosteric phosphofructokinase regulator, fructose 2,6-bisphosphate (Fru-2,6-P2, glycolysis), decreased during the early phase. An intermediate phase could also be discerned between 3 and 10 days after the switch in diets. In this phase, the decreased Fru-2,6-P2 concentration and the decreased PEPCK and BCAADH activities observed in the early phase were reversed. The late phase occurred 10 days after the dietary switch and was characterized by an increase in the activities of glucokinase (glycolytic pathway) and glycogen phosphorylase (associated with glycogenolysis) and by a decrease in glutamate dehydrogenase, PEPCK and BCAADH activities. These measurements indicate that at least 20 days are required before metabolic changes associated with a switch in diet are complete.

Alanine Transaminase↗
PubMed1997

Glycolytic enzyme binding in Otala lactea hepatopancreas: effect of taxol, colchicine and cytochalasin B and D on the in vivo enzyme distribution.

The effect of cytoskeleton modulators on glycolytic enzyme binding was examined in the hepatopancreas of Otala lactea in an attempt to identify potential cellular binding sites. Binding was followed by measuring phosphofructokinase (PFK), aldolase (ALD), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and pyruvate kinase (PK) distribution between low speed pellets (12,000 xg), high speed pellets (100,000 xg) and high speed supernatants. Taxol (which stabilizes microtubules), colchicine (which destabilizes microtubules) and cytochalasin B and D (which destabilize F-actin filaments) were added to the homogenate prior to centrifugation. Addition of taxol increased the amount of PFK associated with the high speed pellet. Cytochalasin B and D reduced the binding of PFK and PK to the low speed pellet. ALD and GAPDH binding were unaffected by any treatment. Lowering the pH of the crude homogenate increased PFK binding to the low speed pellet by 33%. This effect could be reversed by addition of cytochalasin B and D suggesting that pH influences the PFK-F-actin interaction in vivo. The differential binding response of PFK, PK, ALD and GAPDH to added effectors suggests that, in the cell, PFK and PK are bound to different subcellular structural elements than are ALD and GAPDH.

Alkaloids↗
PubMed1997

Finite mixture models for proportions.

Six data sets recording fetal control mortality in mouse litters are presented. The data are clearly overdispersed, and a standard approach would be to describe the data by means of a beta-binomial model or to use quasi-likelihood methods. For five of the examples, we show that beta-binomial model provides a reasonable description but that the fit can be significantly improved by using a mixture of a beta-binomial model with a binomial distribution. This mixture provides two alternative solutions, in one of which the binomial component indicates a high probability of death but is selected infrequently; this accounts for outlying litters with high mortality. The influence of the outliers on the beta-binomial fits is also demonstrated. The location and nature of the two main maxima to the likelihood are investigated through profile log-likelihoods. Comparisons are made with the performance of finite mixtures of binomial distributions.

Animals↗
PubMed1996

Enzymes of carbohydrate metabolism in young and adult rats fed diets differing in fat and carbohydrate.

Glycogen content as well as glycolytic, gluconeogenic and fatty acid synthesis enzyme activities were monitored in young and adult male rats fed diets differing in fat content: 11% (low), 22% (medium) and 42% (high) of total energy from fat. The results showed significant differences in the responses of young and adult rats to changes in dietary fat and carbohydrate. In young animals, increasing dietary fat decreased total liver glycogen phosphorylase (GP), pyruvate kinase (PK), glycerol 3-phosphate dehydrogenase, glucose 6-phosphate dehydrogenase, malic enzyme (ME), ATP-citrate lyase (ATP-CL) and fatty acid synthase (FAS). Increasing dietary fat also affected enzyme levels in other tissues: hexokinase (HK) and pyruvate dehydrogenase (PDH) activities decreased whereas skeletal muscle PK activity increased. The pattern of enzyme changes was similar in livers of fed adults with the exception that liver GP was not affected by dietary manipulations. Overnight food deprivation decreased liver glucokinase (GK), ME, ATP-CL, and FAS activities and increased liver phosphoenolpyruvate carboxykinase (PEPCK) and phosphofructokinase in both young and adult animals. In young animals, food deprivation also: (i) reduced liver GK and PK, (ii) increased kidney PEPCK, (iii) decreased muscle PEPCK and (iv) decreased kidney PDH. Food-deprived adults had increased skeletal muscle PEPCK and kidney glycogen synthetase as well as decreased kidney PEPCK muscle GP activity. These differences suggest that young animals are somewhat more responsive to changes in dietary manipulations. They also show that overnight food restriction causes a more profound metabolic re-organization in younger than in older animals.

Age Factors↗
PubMed1996

Protein kinase involvement in land snail aestivation and anoxia: protein kinase A kinetic properties and changes in second messenger compounds during depressed metabolism.

In response to environmental stress (low water, low oxygen) snails sharply suppress their metabolic rate, a process that is coordinated at the molecular level by reversible protein phosphorylation of key enzymes and functional proteins. Factors affecting protein kinase activity are, therefore, critical to metabolic suppression. Changes in the concentration of protein kinase second messenger compounds were followed over the first 24 h of aestivation and anoxia exposure in the terrestrial snail Otala lactea (Muller) (Pulmonata, Helicidae). The results showed declining concentrations of cyclic AMP over the first 24 h of anoxia exposure and aestivation in foot. Cyclic AMP concentrations in hepatopancreas transiently decreased with the lowest concentration observed at 4 h in both anoxic and aestivating animals. A transient increase in foot muscle cyclic GMP concentrations was apparent 4 h after the start of aestivation whereas a slow, steady increase was seen in anoxic foot muscle. Foot muscle 1,4,5-inositol triphosphate (IP3) concentrations decreased transiently during anoxia exposure and aestivation. Hepatopancreas IP3 concentrations were significantly lower in 24 h anoxic snails and foot IP3 concentrations were significantly lower in 24 h aestivating snails. Kinetic characterization of purified PKA catalytic subunit was also performed. Snail PKA catalytic subunit had an absolute requirement for Mg2+ ion but was inhibited at Mg2+ concentrations above 0.5 mM. Increasing concentrations of neutral salts and phosphate also inhibited activity although the inhibition by phosphate appeared to be specific since the inhibition constant (I50 = 39 mM) was much lower than that of the neutral salts (I50 approximately 240 mM). The enzyme exhibited a broad pH optimum between pH 6.5-8.5. Arrhenius plots gave an activation energy of 13.3 kcal/mol corresponding to a Q10 value of 2.3. The relationship between these results and temporal control of enzyme phosphorylation is discussed.

Animals↗
PubMed1996

Equilibrium enzymes in metabolic pathways.

It is commonly believed that certain reactions in a metabolic sequence may be at or close to equilibrium because of the large excess of catalytic capacity compared to the flux through these enzyme loci. Simple algebraic manipulations can show that the equilibrium and steady state conditions are mutually exclusive. However, solution of the complete reaction schemes for model "equilibrium" reactions shows that they can remain far from equilibrium even though the ratio of enzyme flux to steady state flux through the overall pathway is high. These calculations show that a reaction's proximity to equilibrium depends on the overall flux through the enzyme locus as well as on the kinetic parameters of the other enzymes in the pathway. Thus, combinations of kinetic parameters may exist that allow certain reactions to approach equilibrium but these conditions are not universal.

Animals↗