Preequilibrium Asymmetries in the

The physical properties of neutrons emitted from neutron-induced fission are fundamental to our understanding of nuclear fission. However, while state-of-the-art fission models still incorporate isotropic fission neutron spectra, it is believed that the preequilibrium prefission component of these spectra is strongly anisotropic. The lack of experimental guidance on this feature has not motivated incorporation of anisotropic neutron spectra in fission models, though any significant anisotropy would impact descriptions of a fissioning system. In the present work, an excess of counts at high energies in the fission neutron spectrum of ^{239}Pu is clearly observed and identified as an excess of the preequilibrium prefission distribution above the postfission neutron spectrum. This excess is separated from the underlying postfission neutron spectrum, and its angular distribution is determined as a function in incident neutron energy and outgoing neutron detection angle. Comparison with neutron scattering models provides the first experimental evidence that the preequilibrium angular distribution is uncorrelated with the fission axis. The results presented here also impact the interpretation of several influential prompt fission neutron spectrum measurements.

Skeletal outcomes by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in adolescent girls with anorexia nervosa.

We conducted the first comparison of dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) outcomes in adolescent girls with anorexia nervosa. We observed deficits in bone density by both tools. pQCT assessments were associated with many of the same clinical parameters as have been previously established for DXA. INTRODUCTION: Adolescents with anorexia nervosa (AN) commonly exhibit bone loss, but effects on bone geometry are less clear. We compared measures obtained by DXA and pQCT in girls with AN. METHODS: Seventy females (age 15.5 ± 1.9 years ) with AN and 132 normal-weighted controls underwent tibial measures by pQCT including trabecular volumetric bone mineral density (vBMD) at the 3 % site, cortical vBMD and dimensions at the 38 % site, and muscle cross-sectional area (CSA) at the 66 % site. Participants with AN also underwent standard DXA measures. Independent t tests compared the pQCT results, while Pearson coefficient assessed correlations among DXA and pQCT measures. RESULTS: Trabecular vBMD Z-scores were lower in AN compared to controls (AN -0.31 ± 1.42 vs +0.11 ± 1.01, p = 0.01) and cortical vBMD Z-scores were higher (AN +0.18 ± 0.92 vs -0.50 ± 0.88, p < 0.001). Trabecular vBMD and cortical CSA Z-scores positively correlated with DXA BMD Z-scores (r range 0.57-0.82, p < 0.001). Markers of nutritional status positively correlated with Z-scores for trabecular vBMD, cortical CSA, section modulus, and muscle CSA (p < 0.04 for all). CONCLUSIONS: This study is the first to compare DXA and pQCT measurements in adolescent girls with AN. We observed deficits in BMD by both DXA and pQCT. pQCT assessments correlated well with DXA bone and body composition measures and were associated with many of the same clinical parameters and disease severity markers as have been previously established for DXA. The differences in cortical vBMD merit further study.

The Effect of Caffeine Ingestion during Evening Exercise on Subsequent Sleep Quality in Females.

In a randomised, double-blind, placebo-controlled crossover design, 10 females taking monophasic oral contraceptives completed 90 min intermittent treadmill-running 45 min after ingestion of 6 mg∙kg(-1) body mass anhydrous caffeine or artificial sweetener (placebo). Water (3 mL∙kg(-1)) was provided every 15 min during exercise. Venous blood samples were taken before, during and after exercise, as well as after sleep (~15 h post-ingestion), and levels of caffeine, paraxanthine, theobromine and theophylline were measured using high-performance liquid chromatography. Sleep quality was assessed using the Leeds Sleep Evaluation Questionnaire. Plasma caffeine concentration peaked 100 min after ingestion. Caffeine clearance was 0.95±0.14 mL·min(-1)·kg(-1) while the elimination half-life of caffeine was 17.63±8.06 h. Paraxanthine and theophylline levels were significantly elevated at 15 h with no significant change in theobromine. Sleep latency and subsequent quality of sleep was impaired following caffeine supplementation (P<0.05); there were no differences between trials for how participants were feeling upon awakening. This is the first controlled study to examine caffeine supplementation on sleep quality in female athletes taking a low-dose monophasic oral contraceptive steroid following an intermittent-exercise running protocol. The data shows that female athletes using monophasic oral contraceptive steroids will have impaired sleep quality following evening caffeine ingestion.

New precision measurements of the 235U(n,γ) cross section.

The neutron capture cross section of (235)U was measured for the neutron incident energy region between 4 eV and 1 MeV at the DANCE facility at the Los Alamos Neutron Science Center with an unprecedented accuracy of 2-3% at 1 keV. The new methodology combined three independent measurements. In the main experiment, a thick actinide sample was used to determine neutron capture and neutron-induced fission rates simultaneously. In the second measurement, a fission tagging detector was used with a thin actinide sample and detailed characteristics of the prompt-fission gamma rays were obtained. In the third measurement, the neutron scattering background was characterized using a sample of (208)Pb. The relative capture cross section was obtained from the experiment with the thick (235)U sample using a ratio method after the subtraction of the fission and neutron scattering backgrounds. Our result indicates errors that are as large as 30% in the 0.5-2.5 keV region, in the current knowledge of neutron capture as embodied in major nuclear data evaluations. Future modifications of these databases using the improved precision data given herein will have significant impacts in neutronics calculations for a variety of nuclear technologies.

Abrupt change in radiation-width distribution for 147Sm neutron resonances.

We obtained the total radiation widths of s-wave resonances through an R-matrix analysis of (147)Sm(n,γ) cross sections. Distributions of these widths differ markedly for resonances below and above E(n)=300 eV, which is in stark contrast to long-established theory. We show that this change, as well as a similar change in the neutron-width distribution reported previously, is reflected in abrupt increases in both the average (147)Sm(n,γ) cross section and fluctuations about the average near 300 eV. Such effects could have important consequences for applications such as nuclear astrophysics and nuclear criticality safety.

Corticosterone induced morphological changes of hippocampal and amygdaloid cell lines are dependent on 5-HT7 receptor related signal pathway.

Stress is an unavoidable life experience. It induces mood, cognitive dysfunction and plasticity changes in chronically stressed individuals. Among the various brain regions that have been studied, the hippocampus and amygdala have been observed to have different roles in controlling the limbic-hypothalamic-pituitary-adrenal axis (limbic-HPA axis). This study investigated how the stress hormone corticosterone (CORT) affects neuronal cells. The first aim is to test whether administration of CORT to hippocampal and amygdaloid cell lines induces different changes in the 5-HT receptor subtypes. The second goal is to determine whether stress induced morphological changes in these two cell lines were involved in the 5-HT receptor subtypes expression. We now show that 5-HT(7) receptor mRNA levels were significantly upregulated in HT-22 cells, but downregulated in AR-5 cells by exposure to a physiologically relevant level of CORT (50 µM) for 24 h, which was later confirmed by primary hippocampal and amygdaloid neuron cultures. Additionally, pretreatment of cells with 5-HT(7) antagonist SB-269970 or agonist LP-44 reversed CORT induced cell lesion in a dose-dependent manner. Moreover, CORT induced different changes in neurite length, number of neurites and soma size in HT-22 and AR-5 cells were also reversed by pretreatment with either SB-269970 or LP-44. The different effects of 5-HT(7) receptors on cell lines were observed in two members of the Rho family small GTPase expression: the Cdc-42 and RhoA. These observed results support the hypothesis that 5-HT may differentially modulate neuronal morphology in the hippocampus and amygdala depending on the expression levels of the 5-HT receptor subtypes during stress hormone insults.

Arthroscopic femoral osteochondroplasty for cam femoroacetabular impingement in patients over 60 years of age.

We reviewed the clinical outcome of arthroscopic femoral osteochondroplasty for cam femoroacetabular impingement performed between August 2005 and March 2009 in a series of 40 patients over 60 years of age. The group comprised 26 men and 14 women with a mean age of 65 years (60 to 82). The mean follow-up was 30 months (12 to 54). The mean modified Harris hip score improved by 19.2 points (95% confidence interval 13.6 to 24.9; p < 0.001) while the mean non-arthritic hip score improved by 15.0 points (95% confidence interval 10.9 to 19.1, p < 0.001). Seven patients underwent total hip replacement after a mean interval of 12 months (6 to 24 months) at a mean age of 63 years (60 to 70). The overall level of satisfaction was high with most patients indicating that they would undergo similar surgery in the future to the contralateral hip, if indicated. No serious complications occurred. Arthroscopic femoral osteochondroplasty performed in selected patients over 60 years of age, who have hip pain and mechanical symptoms resulting from cam femoroacetabular impingement, is beneficial with a minimal risk of complications at a mean follow-up of 30 months.

Neutron multiplicity in the fission of 238U and 235U with neutrons up to 200 MeV.

Prompt-fission-neutron multiplicities were measured for 238U(n,f) and 235U(n,f) from 0.4 to 200 MeV. The data are of great importance in connection with accelerator-coupled nuclear reactor systems incinerating actinides. We report that fission induced by 200 MeV neutrons produces approximately 10 more prompt neutrons than fission induced by reactor neutrons. Most neutrons are evaporated from the fission fragments and the prefission compound nucleus, as the preequilibrium emission of energetic neutrons accounts for a maximum of 15% of the prompt neutrons at 200 MeV.

Measurement of Neutron Decay Parameters-The abBA Experiment.

We are developing an experiment to measure the correlations a, A, and B, and the Fierz interference term b in neutron decay, with a precision of approximately 10(-4). The experiment uses an electromagnetic spectrometer in combination with two large-area segmented silicon detectors to detect the proton and electron from the decay in coincidence, with 4π acceptance for both particles. For the neutron-polarization-dependent observables A and B, precision neutron polarimetry is achieved through the combination of a pulsed neutron beam, under construction at the SNS, and a polarized (3)He neutron polarizer. Measuring a and A in the same apparatus provides a redundant determination of λ = gA/gV . Uncertainty in λ dominates the uncertainty of CKM unitarity tests.

Outbreak of Vero cytotoxin-producing Escherichia coli O157 in a child day care facility.

In December 1998, an outbreak of Vero cytotoxin-producing Escherichia coli (VTEC) O157 in a crèche affected ten out of 45 children and one out of five staff members. Eight cases were symptomatic and three were asymptomatic. There were two asymptomatic adult family contacts of child cases. All specimens were identified as VTEC O157:H7, phage type 32. None of the cases were seriously ill and none developed haemolytic uraemic syndrome (HUS). One child continued to excrete the organism for 14 weeks. The origin of the outbreak was not found but epidemiological investigation was suggestive of person-to-person spread. All children and staff were screened and excluded from the crèche until microbiological clearance was obtained. An inspection of the crèche revealed overcrowding and inadequacies in cleaning and in the food preparation facilities. These problems were remedied before children were re-admitted to the crèche. This outbreak demonstrates the ease with which VTEC O157 can be transmitted between small children. Two specific features of this outbreak were notable: (1) the mild self-limiting nature of the illness and (2) the prolonged shedding of the bacterium by one child.

Discriminative stimulus effects of the type-4 phosphodiesterase inhibitor rolipram in rats.

RATIONALE: Rolipram, an inhibitor of cyclic AMP phosphodiesterase (PDE4) produces discriminative stimulus effects in rats. These effects may be related to a wide range of central nervous system effects described previously. OBJECTIVE: The purposes of the present study were to: (i) assess the specificity of the discriminative stimulus effects of rolipram; (ii) examine the role of beta adrenergic receptors; (iii) assess the effects of imipramine and nisoxetine; and (iv) determine whether SKF 38393, a compound which also increases cAMP levels, substitutes for rolipram. METHODS: Rats were trained to discriminate 0.1 mg/kg rolipram from its vehicle in a two-lever task. Following discrimination training, substitution and antagonism tests were carried out. RESULTS: In generalization tests, the PDE4 inhibitors ICI 63,197 and Ro 20-1724 substituted for rolipram in a dose-dependent manner (substitution at 0.3 mg/kg and 3 mg/kg, respectively). The selective inhibitors of PDE1, PDE2, and PDE5/6 did not substitute for rolipram; however, a dose of 10 mg/kg of the PDE3 inhibitor milrinone did substitute. The beta adrenergic agonists clenbuterol and dobutamine at least partially substituted for rolipram (0.1 mg/kg and 18 mg/kg, respectively). By contrast, the D1 dopaminergic agonist SKF 38393 and the monoamine uptake inhibitors imipramine and nisoxetine were ineffective (at doses up to 3, 10, and 10 mg/kg, respectively). CONCLUSIONS: The present results indicate that the discriminative stimulus effects of rolipram are related to the inhibition of the hydrolytic activity of PDE4. Generalized increases in cyclic nucleotides do not appear to be sufficient for producing rolipram-like effects. It appears that a mechanism involving beta adrenergic receptors may contribute to the effects of rolipram, consistent with previous neuropharmacological data. Finally, the discriminative stimulus effects of rolipram appear to be unrelated to its antidepressant-like effect, but may provide a surrogate marker for central nervous system-related side effects of PDE4 inhibitors.

Development of rolipram-sensitive, cyclic AMP phosphodiesterase (PDE4) in rat primary neuronal cultures.

The development of PDE4 was examined in primary neuronal cultures of rat cerebral cortex. Three days after culturing, neurons exhibited relatively low PDE4 activity (i.e., rolipram-sensitive PDE activity). It gradually increased over time, approximately doubling by day 12. The increase in activity was accompanied by an increase in the expression of the PDE4A variants, PDE4A5 and PDE4A1, as well as of the synaptic marker protein synapsin I. There was a strong correlation between the expression of the PDE4A variants with that of synapsin I, which suggests that as neurons develop and signal transduction increases there is a regulated increase in PDE4 expression and activity. Consistent with this interpretation, it was found that treatment with the sodium channel blocker tetrodotoxin, which inhibits depolarization-induced neurotransmitter release, reduced the expression of the PDE4A variants. These data demonstrate the developmental regulation of PDE4 in neurons and offer a manner by which the association of PDE4 variants with particular signal transduction pathways may be studied in vitro.

Paternal involvement in kinship foster care services in one father and multiple father families.

Using data from case records and from questionnaires completed by caseworkers, this article describes contact between 132 fathers of children in kinship foster care and their caseworkers over a period of 12 months, and the fathers' involvement in permanency planning for their children. The data indicate that most fathers had no contact with the caseworkers during the period under study and had never participated in planning. Analysis revealed that paternal involvement varied significantly by the child's family composition. Fathers of two or more children from a one-father family were most involved, while fathers of one child from a multiple-father family were least involved. Possible explanations for the findings are identified, and implications for practice and research are presented.

Surgically induced cryptorchidism-related degenerative changes in spermatogonia are associated with loss of cyclic adenosine monophosphate-dependent phosphodiesterases type 4 in abdominal testes of rats.

The present study was undertaken to investigate the role of phosphodiesterase type 4 (PDE4) enzymes in cryptorchidism-induced apoptosis of the germ cells. Regulation of expression of PDE4 enzymes was studied in the abdominal and scrotal testes of surgically induced cryptorchid rats for 10, 20, and 30 days. In some cases orchidopexy was performed after 30 days of cryptorchidism, and rats were allowed to recover for an additional 50 days. Upon histological examination, marked degenerative changes in the epithelial lining of the seminiferous tubules within abdominal testes were observed compared with contralateral control or age-matched sham-operated rats. These changes included degeneration of some spermatogonia, apoptosis of the secondary spermatocytes, incomplete spermatogenesis, and lack of spermatozoa in the lumen. In contrast, contralateral scrotal testes exhibited normal histology. Significant improvement in the regeneration of spermatogonia was observed in rats after 50 days of recovery following orchidopexy. Immunocytochemical examination suggested the presence of PDE4A in germ cells while PDE4B was predominantly expressed on somatic cells. Western blotting using PDE4 subtype-selective antibodies showed the presence of two PDE4A variants (a 109-kDa PDE4A8 and a previously uncharacterized 88-kDa PDE4A variant) and two PDE4B (78-kDa PDE4B2 and 66-kDa PDE4B variant) bands. In unilaterally cryptorchid animals, the abdominal testis showed a time-dependent decrease in both PDE4A8 and 88-kDa PDE4A variants. In contrast, the expression of 66-kDa PDE4B was markedly increased in a time-dependent fashion in abdominal testes of cryptorchid rats. Animals surgically corrected for cryptorchidism and allowed to recover for 50 days exhibited normal expression of both PDE4A and PDE4B variants compared with aged-matched, sham-operated controls. In conclusion, this study suggests that down-regulation of PDE4A variants in cryptorchid testes may play an important role in the degeneration of spermatogonia and increased apoptotic activity in the germ cells.

Discriminative stimulus effects of centrally administered isoproterenol in rats: mediation by beta-1 adrenergic receptors.

RATIONALE: Centrally active beta-1 and beta-2 adrenergic agonists produce antidepressant-like effects in several behavioral tests, suggesting that these receptors may be involved in the mediation of the effects of antidepressant drugs. OBJECTIVES: This study aimed to evaluate the ability of intra-cerebral ventricular (ICV) isoproterenol to produce discriminative stimulus effects mediated by beta adrenergic receptors, establishing a reliable model of in vivo activation of central beta adrenergic receptors. METHODS: Rats were trained to discriminate the non-selective beta adrenergic agonist isoproterenol (10 microg ICV) from artificial cerebral spinal fluid (aCSF) using a water-reinforced two-lever operant task [fixed ratio-10 schedule of reinforcement (FR10)]. For substitution and antagonism tests, drugs were administered IP. RESULTS: Following acquisition of the discrimination, ICV isoproterenol produced dose-related increases in drug-appropriate responding (ED50 = 1.14 microg). The beta-1 selective adrenergic agonist dobutamine fully substituted for isoproterenol at a dose of 0.3 mg/kg (ED50 = 0.15 mg/kg). By contrast, the beta-2 selective adrenergic agonist clenbuterol produced 20% isoproterenol-appropriate responding when administered at doses up to 0.1 mg/kg. The beta adrenergic antagonist propranolol fully antagonized the isoproterenol cue at a dose of 0.03 mg/kg (ID50 = 0.013 mg/kg). The beta-1 selective antagonist betaxolol (ID50 = 0.03 mg/kg) more potently antagonized isoproterenol's cue than did the beta-2 selective antagonist ICI 118,551 (ID50 = 0.41 mg/kg). The antidepressant desipramine (1.0 mg/kg) substituted for isoproterenol. CONCLUSIONS: These results demonstrate that the discriminative stimulus effects of isoproterenol are mediated primarily via beta-1 adrenergic receptors. This provides a functional model for activation of central beta-1 adrenergic receptors, permitting further characterization of the role of this receptor subtype in the mechanism of action of antidepressant drugs.

Modulation of MK-801-induced behaviour by noradrenergic agents in mice.

RATIONALE: Inhibition of glutamatergic N-methyl-D-aspartate (NMDA) receptors following the administration of NMDA receptor antagonists results in psychotic-like behaviour. Whereas it is known that pharmacological manipulation of dopaminergic and serotonergic pathways affect this drug-induced psychosis, a role for noradrenaline has not yet been clearly defined. OBJECTIVES: Thus, in the present study, we assessed a possible role for noradrenaline in the behavioural response to the non-competitive NMDA receptor anatgonist, MK-801, in male CD-I mice. RESULTS: MK-801 (0.02-1.28 mg/kg; ED50 0.2 mg/kg; s.c.) induced a dose-dependent increase in locomotor, stereotypic and ataxic behaviours. Pre-treatment with the noradrenaline re-uptake inhibitors, desipramine (10 mg/kg; i.p.) and reboxetine (20 mg/kg; i.p.), attenuated the locomotor, stereotypic and ataxic response to MK-801 (0.2 mg/kg; s.c.). The noradrenergic system was lesioned with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, 50 mg/kg; i.p., 7 and 4 days prior to challenge) to reduce noradrenaline concentrations in the cortex by 70%-80%. Whereas DSP-4 lesioning had little effect on the response to MK-801, it completely reversed the attenuating effects of reboxetine. Pre-treatment with the alpha2 adrenoceptor agonist, clonidine (0.2 mg/kg; i.p.), and the antagonist, yohimbine (2 mg/kg; i.p.), attenuated and potentiated the response to MK-801, respectively. Pre-treatment with the alpha1 adrenoceptor antagonist, prazosin (2 mg/kg; i.p.), reduced the MK-801-induced response. CONCLUSIONS: It therefore appears that presynaptic noradrenergic alpha2 and postsynaptic alpha1 adrenoceptor stimulation exert opposing effects on the behavioural expression of MK-801 in mice.

Tight control of exogenous SERCA expression is required to obtain acceleration of calcium transients with minimal cytotoxic effects in cardiac myocytes.

Collateral effects of exogenous sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) expression were characterized in neonatal rat and chicken embryo cardiac myocytes, and the conditions required to produce acceleration of Ca(2+) transients with minimal toxicity were established. Cultured myocytes were infected with adenovirus vector carrying the cDNA of wild-type SERCA1, an inactive SERCA1 mutant, or enhanced green fluorescence protein under control of the cytomegalovirus promoter. Controls were exposed to empty virus vector. Each group was tested with and without phenylephrine (PHE) treatment. Under conditions of limited calf-serum exposure, the infected rat myocytes manifested a more rapid increase in size, protein content, and rate of protein synthesis relative to noninfected controls. These changes were not accompanied by reversal to fetal transcriptional pattern (as observed in hypertrophy triggered by PHE) and may be attributable to facilitated exchange with serum factors. SERCA virus titers >5 to 6 plaque-forming units per cell produced overcrowding of ATPase molecules on intracellular membranes, followed by apoptotic death of a significant number of rat but not chicken myocytes. Enhanced green fluorescence protein virus and empty virus also produced cytotoxic effects but at higher titers than SERCA. Expression of exogenous SERCA and enhancement of Ca(2+) transient kinetics could be obtained with minimal cell damage in rat myocytes if the SERCA virus titer were maintained within 1 to 4 plaque-forming units per cell. Expression of endogenous SERCA was unchanged, but expression of exogenous SERCA was higher in myocytes rendered hypertrophic by treatment with PHE than in nontreated controls.

Comparison of the effects of isoproterenol administered into the hippocampus, frontal cortex, or amygdala on behavior of rats maintained by differential reinforcement of low response rate.

RATIONALE: Central administration of isoproterenol, a non-selective beta adrenergic agonist, produces behavioral changes in animal models sensitive to antidepressants. However, it is not clear which brain regions mediate these effects. OBJECTIVES: To investigate the antidepressant-like effects of site-specific administration of isoproterenol and the involvement of beta adrenergic receptor subtypes. METHODS: The effects of isoproterenol, which was administered into the lateral ventricle, hippocampus, frontal cortex, or amygdala, were determined in rats under a differential-reinforcement-of-low-rate (DRL) 72-s schedule. The effects of beta adrenergic antagonists on the actions of isoproterenol also were determined. RESULTS: When injected bilaterally into the hippocampus, isoproterenol (1-30 microg/side) decreased response rate and increased reinforcement rate in a dose-dependent manner. The minimum dose of isoproterenol required for changing DRL behavior was 6 microg (i.e., 3 microg bilaterally), compared to 10 microg for intracerebroventricular and 60 microg (30 microg bilaterally) for administration into the frontal cortex or amygdala. These effects of isoproterenol were blocked by the beta adrenergic antagonist propranolol. In addition, the effects of isoproterenol injected intrahippocampally also were antagonized dose-dependently by the beta-1 selective antagonist betaxolol and the beta-2 selective antagonist ICI 118,551. The relative potency of these antagonists for blocking the effects of isoproterenol suggested predominant mediation by beta-1 adrenergic receptors. CONCLUSIONS: The hippocampus is an important site involved in mediating the antidepressant-like effect of isoproterenol. This suggests a key, although not exclusive, role for this site in the pathophysiology of depression and its pharmacotherapy.

Postnatal expression and activity of the mitochondrial 2-oxoglutarate-malate carrier in intact hearts.

This study examines the functional implications of postnatal changes in the expression of the mitochondrial transporter protein, 2-oxoglutarate-malate carrier (OMC). Online (13)C nuclear magnetic resonance ((13)C NMR) measurements of isotope kinetics in hearts from neonate (3-4 days) and adult rabbits provided tricarboxylic acid cycle flux rates and flux rates through OMC. Neonate and adult hearts oxidizing 2.5 mM [2,4-(13)C(2)]butyrate were subjected to either normal or high cytosolic redox state (2.5 mM lactate) conditions to evaluate the recruitment of malate-aspartate activity and the resulting OMC flux. During development from neonate (3-4 days) to adult, mitochondrial protein density in the heart increased from 19 +/- 3% to 31 +/- 2%, whereas OMC expression decreased by 65% per mitochondrial protein content (P < 0.05). Correspondingly, OMC flux was lower in adults hearts than in neonates by 73% (neonate = 7. 4 +/- 0.4, adult = 2.0 +/- 0.1 micromol/min per 100 mg mitochondrial protein; P < 0.05). Despite clear changes in OMC content and flux, the responsiveness of the malate-aspartate shuttle to increased cytosolic NADH was similar in both adults and neonates with an approximate threefold increase in OMC flux (in densitometric units/100 mg mitochondrial protein: neonate = 25.8 +/- 2.5, adult = 6.0 +/- 0.2; P < 0.05). The (13)C NMR data demonstrate that OMC activity is a principal component of the rate of labeling of glutamate.

Exogenous Ca2+-ATPase isoform effects on Ca2+ transients of embryonic chicken and neonatal rat cardiac myocytes.

1. Sarco-endoplasmic reticulum Ca2+-ATPase from fast skeletal (SERCA1) or cardiac muscle (SERCA2a) was expressed in embryonic chicken and neonatal rat cardiac myocytes by adenovirus vectors, with c-myc tags on both constructs to compare expression and distinguish exogenous from endogenous SERCA2a in myocytes. 2. Expression of the two isoforms was similar (approximately 3-fold higher than endogenous SERCA). However, SERCA1 activity was 2-fold greater than SERCA2a activity, due to intrinsic differences in turnover rates. Activation of both exogenous SERCA isoforms by Ca2+ was displaced to slightly lower [Ca2+], suggesting that the overexpressed isoforms were independent of phospholamban. In fact, phospholamban and calsequestrin expression were unchanged. 3. Decay time constants of cytosolic Ca2+ transients from cells overexpressing SERCA1 were reduced by 30-40 % and half-widths by 10-15 % compared to controls. SERCA2a overexpression produced much less acceleration of transients in chick than in rat, and less acceleration than SERCA1 overexpression in either species. There was no significant change in resting [Ca2+], peak amplitudes, or in the amount of Ca2+ releasable by caffeine from overexpression of either SERCA isoform. However, the amplitudes of the transients increased with SERCA1 overexpression when pacing frequency limited refilling of the sarcoplasmic reticulum. 4. It is concluded that total SERCA transport velocity has a primary effect on the decay phase of transients. Transport velocity is affected by SERCA isoform turnover rate, temperature, and/or SERCA copy number.