Search PubMed⌕ Search

Biomedical subjects

C B Smith

Publications and source records attributed to C B Smith.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of thiopental anesthesia on local rates of cerebral protein synthesis in rats.

We have examined the effects of a surgical level of thiopental anesthesia in adult male rats on local rates of cerebral protein synthesis with the quantitative autoradiographic L-[1-14C]leucine method. The relative contribution of leucine derived from protein breakdown to the intracellular precursor amino acid pool for protein synthesis was found to be statistically significantly decreased in the anesthetized rats compared with controls. In the brain as a whole and in 30 of the 35 brain regions examined, rates of protein synthesis were decreased (1-11%) in the anesthetized rats. Decreases were statistically significant (P < or = 0.05) in the brain as a whole and in six of the regions, and they approached statistical significance in an additional 13 regions, indicating a tendency for a generalized but small effect.

Amino Acids↗
PubMed1998

Glucose transporter expression in brain: relationship to cerebral glucose utilization.

Glucose is the principle energy source for mammalian brain. Delivery of glucose from the blood to the brain requires its transport across the endothelial cells of the blood-brain barrier and across the plasma membranes of neurons and glia, which is mediated by the facilitative glucose transporter proteins. The two primary glucose transporter isoforms which function in cerebral glucose metabolism are GLUT1 and GLUT3. GLUT1 is the primary transporter in the blood-brain barrier, choroid plexus, ependyma, and glia; GLUT3 is the neuronal glucose transporter. The levels of expression of both transporters are regulated in concert with metabolic demand and regional rates of cerebral glucose utilization. We present several experimental paradigms in which alterations in energetic demand and/or substrate supply affect glucose transporter expression. These include normal cerebral development in the rat, Alzheimer's disease, neuronal differentiation in vitro, and dehydration in the rat.

Aging↗
PubMed1997

Positive correlations between cerebral protein synthesis rates and deep sleep in Macaca mulatta.

Local rates of cerebral protein synthesis (ICPSleu) were determined with the autoradiographic L-[1-14C]leucine method in seven awake and seven asleep, adult rhesus monkeys conditioned to sleep in a restraining chair in a darkened, ventilated chamber while EEG, EOG, and EMG were monitored. Prior to the period of measurement all animals slept for 1-4 h. Controls were awakened after at least one period of rapid-eye-movement (REM) sleep. Experimental animals were allowed to remain asleep, and they exhibited non-REM sleep for 71-99% of the experimental period. Statistically significant differences in ICPSleu between control and experimental animals were found in four of the 57 regions of brain examined, but these effects may have occurred by chance. In the sleeping animals, however, correlations between ICPSleu and percent time in deep sleep were positive in all regions and were statistically significant (P < or = 0.05) in 35 of the regions. When time in deep sleep was weighted for the integrated specific activity of leucine in grey matter, positive correlations were statistically significant (P < or = 0.05) in 18 regions in the experimental animals. These results suggest that rates of protein synthesis are increased in many regions of the brain during deep sleep compared with light sleep.

Animals↗
PubMed1997

Rates of local cerebral protein synthesis in fetal and neonatal sheep.

During gestation there is likely to be a constantly changing rate of protein synthesis in the brain that may exhibit regional specificity. With the use of the quantitative autoradiographic L-[1-(14)C]leucine method for the determination of local rates of leucine incorporation into cerebral protein (lCPS(Leu)), we have sought to characterize this important process. lCPS(Leu) was measured in nine fetal sheep (118-139 days gestational age) and five newborn lambs (1-5 days of age). In other experiments, the fraction of leucine in the precursor pool for protein synthesis in the brain derived from the arterial plasma was determined to be 0.57 +/- 0.04 (mean +/- SE) in one fetus and two lambs. This value was used in the calculation of lCPS(Leu) in 35 regions of the central nervous system, pineal body, and whole brain. Regardless of age, lCPS(Leu) was highest in the pineal body, brain stem, and hypothalamic nuclei and lowest in white matter. In sensorimotor cortex, corona radiata, pyramidal tracts, and whole brain, lCPS(Leu) was positively correlated with prenatal age (P < or = 0.05). These increases in lCPS(Leu) probably reflect myelination in the cerebrum, which is known to occur in late gestation.

Aging↗
PubMed1997

Validity of utilization management criteria for psychiatry.

OBJECTIVE: This study examined the validity of four psychiatric utilization management criteria sets: the 1992 and 1993 InterQual Intensity, Severity, and Discharge (ISD) criteria, the Managed Care Appropriateness Protocol, and an instrument developed by the Department of Veterans Affairs (VA). METHOD: The appropriateness of acute care admission and continued stay for 70 randomly selected VA psychiatric inpatients was retrospectively assessed with each criteria set. The sensitivity and specificity of each instrument were evaluated by comparing its assessments to the consensus of judgments of a panel of expert psychiatrists who reviewed the same cases. Sensitivity was defined as the proportion of admissions or continued-stay days the panel found appropriate for acute care that the criteria judged to be appropriate for acute care; specificity was the proportion the panel found inappropriate for acute care that the criteria judged to be inappropriate for acute care. RESULTS: For admissions, there were only minor differences in the validity of the four criteria sets as assessed by agreement with the panel's judgments. For each of 4 continued-stay days studied, either the sensitivity or specificity of the 1993 InterQual ISD criteria was below 0.30. The specificity of the 1992 InterQual ISD criteria was below 0.60 for 2 days. In contrast, for the Managed Care Appropriateness Protocol, sensitivity was 0.73-0.93 and specificity was 0.78-0.88 over the 4 days. CONCLUSIONS: The findings raise major concerns about the validity of the widely used InterQual ISD psychiatry criteria, suggest that the Managed Care Appropriateness Protocol may be a useful tool for psychiatric utilization management, strongly underline the need to validate all criteria used to assess medical care, and support the appropriateness of the procedures used to perform these assessments.

Adult↗
PubMed1997

The future of Veterans Affairs Medical Centers.

In the past four years, the Department of Veterans Affairs (VA) has experienced unprecedented changes in the ways it provides medical care, trains medical residents, and supports its clinical research program. For the most part, these changes have improved the quality and efficiency of care provided to veterans, and they have improved the chances that the VA will survive in an increasingly competitive medical market place. While the changes in priorities for training medical residents and funding clinical research have been designed to be more consistent with the overall mission of the VA, these changes have been stressful for many of the VA/medical school affiliations. Our challenge is to understand and manage these changes so that the many benefits that have derived from more than fifty years of VA/medical school affiliations can be retained.

Forecasting↗
PubMed1996

Simultaneous independent measurement of endocytosis and exocytosis.

Studies of membrane traffic between the cytoplasm and surface of a cell suggest that membrane internalization is tightly coupled to secretion. Studies using the capacitance technique show that endocytosis can follow evoked exocytosis within a second or less. The capacitance technique, however, measures only the net change in cell surface area, and thus separating exocytosis from endocytosis requires that the two events do not overlap in time. This condition is probably met with small, brief stimuli, but during prolonged stimulation it is more likely that exocytosis and endocytosis occur simultaneously, We used FM1-43 fluorescence, which provides a cumulative measure of exocytosis, independent of endocytosis, in combination with capacitance monitoring to track unidirectional movements of membrane simultaneously and in real time in bovine adrenal chromaffin cells. We confirm that, with relatively small stimuli, exocytosis ceases before endocytosis begins (no overlap). In contrast, during prolonged stimulation, the onset of endocytosis is delayed by 2-3 min, but then the rate of endocytosis quickly grows to equal that of exocytosis. The delayed onset of endocytosis may be an emergency defence against catastrophic cell swelling.

Adrenal Cortex↗
PubMed1996

Zipeprol: preclinical assessment of abuse potential.

Zipeprol was evaluated in a number of in vitro and in vivo assays predictive of stimulant, depressant, or opioid abuse potential. Zipeprol had affinity for mu and kappa opioid binding sites as well as sigma binding sites. However, it failed to exert opioid-like agonist actions in rodents, and did not attenuate withdrawal signs in morphine- or pentobarbital-dependent rats. Zipeprol did not substitute for either amphetamine or pentobarbital in drug discrimination assays in rhesus monkeys. On the other hand, it suppressed morphine withdrawal signs in rhesus monkeys in two assays, and it acted as a quadazocine-sensitive reinforcer in monkeys trained to self-inject alfentanil. Zipeprol also acted as a reinforcer in monkeys trained to self-inject methohexital. In a dose range of 10-18 mg/kg, zipeprol induced convulsions in monkeys. Zipeprol appears to have abuse potential and a novel spectrum of action involving both opioid and non-opioid effects.

Animals↗
PubMed1996

Imaging exocytosis and endocytosis.

From the secretion of neurotransmitters via synaptic vesicles to the expulsion of cellular waste via contractile vacuoles, exocytosis and its sequel, endocytosis, are being explored with a variety of new optical tools. Fluorescent markers, especially styryl dyes such as FM1-43 (which reversibly labels endosomal membranes), have been used to follow exo- and endocytic events in many cell types. Even though the development of new dyes is still largely empirical, some theoretical principles have emerged to guide future dye chemistry. Moreover, advances in optical imaging technology that augment conventional fluorescence microscopy are appearing. For example, interference reflection microscopy (which requires no flurophore) and total internal reflection microscopy have recently been used to observe single exocytic events at the contact point between a glass coverslip and the plasma membrane.

Animals↗
PubMed1996

Overutilization of acute-care beds in Veterans Affairs hospitals.

The authors tested the hypothesis that the Department of Veterans Affairs (VA) hospitals would have substantial overutilization of acute care beds and services because of policies that emphasize inpatient care over ambulatory care. Reviewers from 24 randomly selected VA hospitals applied the InterQual ISD* (Intensity, Severity, Discharge) criteria for appropriateness concurrently to a random sample of 2,432 admissions to acute medical, surgical, and psychiatry services. Reliability of hospital reviewers in applying the ISD* criteria was tested by comparing their reviews with those of a small group of expert reviewers. Validity of the ISD* criteria was tested by comparing the assessments of master reviewers with the implicit judgments of panels of nine physicians. The physician panels validated the ISD* admission criteria for medicine and surgery (74% agreement with master reviewers, kappa > 0.4), whereas the psychiatry criteria were not validated (66% agreement, kappa 0.29). Hospital reviewers reliably used all three criteria sets (> 83% agreement with master reviewers, kappa > 0.6). Rates of nonacute admissions to acute medical and surgical services were > 38% as determined by the hospital and master reviewers and by the physician panels. Nonacute rates of continued stay were > 32% for both medicine and surgery services. Similar rates of nonacute admissions and continued stay were found for all 24 hospitals. Reasons for nonacute admissions and continued stay included lack of an ambulatory care alternative, conservative physician practices, delays in discharge planning, and social factors such as homelessness and long travel distances to the hospital. Using criteria that the authors showed to be reliable and valid, substantial overutilization of acute medicine and surgical beds was found in a representative sample of VA hospitals. Correcting this situation will require changes in physician practice patterns, development of ambulatory care alternatives to inpatient care, and modification of current VA policies determining eligibility for care.

Acute Disease↗
PubMed1996

Plasticity of metabolic whisker maps in somatosensory brainstem and thalamus of mice with neonatal lesions of whisker follicles.

We employed the autoradiographic deoxyglucose method to study metabolic whisker maps of the adult mouse somatosensory brainstem and thalamus after the neonatal removal of left whisker follicles C1, C2 and C3. Left whiskers B1-3 and D1-3 were deflected to metabolically activate the somatosensory pathway. Unoperated mice that were stimulated in the same fashion served as controls. Whisker stimulation resulted in an ipsilateral increase in metabolic activity in the three trigeminal brainstem structures in which the whiskers are represented topologically by segments of high cytochrome oxidase activity, i.e. subnucleus caudalis, subnucleus interpolaris and nucleus principalis. In the two subnuclei of mice with lesions and of controls, there was an increase in metabolic activity of the representations of the deflected whiskers, whereas the metabolic activity of representations A1-3 and E1-3 was low. Apart from these similarities, the metabolic activation of the representations originally representing whiskers C1-3 was remarkably greater in mice with lesions than in controls. This increase reached statistical significance in subnucleus caudalis and approached statistical significance in subnucleus interpolaris. In nucleus principalis the deprived territory was only partially activated and the degree of metabolic activation was less than in the subnuclei. In the thalamic ventrobasal complex of mice with lesions metabolic activity was unpatterned whereas two areas of metabolic activation were distinct in controls. Hence, the removal of whisker follicles in newborn mice resulted in the suppression of localized metabolic responses to whisker stimulation in the thalamus, whereas in the brainstem stimulus-related activity was prominent and the deprived territory became responsive to the stimulation of whisker follicles adjacent to the lesion. Apparently, the modification of the whisker representation at the first synapse of the pathway induces a diminution of localized responsivity in the thalamus.

Animals↗
PubMed1995

Changes in the regulation of 5-hydroxytryptamine release by alpha2-adrenoceptors in the rat hippocampus after long-term desipramine treatment.

In vivo microdialysis was used to measure the effects of long-term treatment of rats with desipramine upon the regulation by alpha2-adrenoceptors of serotonin (5-hydroxytryptamine, 5-HT) release from the serotonergic neurons in the hippocampus. Rats were injected with saline or desipramine, 10 mg/kg, i.p., every 12 h for 14 days. When added to the perfusion solution, brimonidine, an alpha2-adrenoceptor agonist, significantly inhibited the K+-evoked release of 5-HT in the hippocampi of saline-treated, control rats. This action of brimonidine was prevented by pretreating the rats with idazoxan, an alpha2-adrenoceptor antagonist. Long-term desipramine treatment significantly reduced the inhibitory effect of brimonidine upon the K+-evoked 5-HT release. With long-term administration of desipramine, noradrenaline content in the hippocampi was significantly decreased as compared with that of the control rats, whereas the basal noradrenaline concentration in the dialysate was significantly increased. On the other hand, both the 5-HT content of the hippocampus and the basal 5-HT concentration in the dialysate were significantly increased. The present study suggests that long-term administration of desipramine causes a functional subsensitivity of the presynaptic alpha2-adrenoceptors that regulate serotonergic neuronal function in the rat hippocampus. It also supports the concept that changes in the sensitivity of alpha2-adrenoceptors that regulate neurotransmitter release play an important role in the mechanism of antidepressant drug action.

Animals↗
PubMed1995

Influence of valine flooding on channeling of valine into tissue pools and on protein synthesis.

Rates of valine incorporation into protein were measured under control and valine-"flooding" conditions and included correction for the degree of recycling of unlabeled valine derived from the steady-state breakdown of tissue protein into the precursor pool (tRNA bound). The correction factor lambda, which is the ratio of the steady-state specific activity of valine in the tissue tRNA-bound pool to that in the arterial plasma, was determined for each of the tissues. In controls, values of lambda ranged from 0.31 in adrenals to 0.54 in heart; in flooded animals, values were higher, but only in liver was the value of lambda close to 1.0. In control and flooded rats, rates of protein synthesis were highest in liver and adrenals and lowest in skeletal muscle, with intermediate values in brain and heart. Flooding resulted in increased rates of protein synthesis in liver and decreased rates in adrenals. Rates of protein synthesis in brain, heart, and skeletal muscle were not statistically significantly affected by flooding.

Animals↗
PubMed1995

Rates of local cerebral protein synthesis in the rat during normal postnatal development.

The degree of recycling of leucine derived from protein breakdown into the precursor pool for protein synthesis was measured in rat brain at different postnatal ages, and age-specific values were used in the calculation of regional (local) rates of cerebral leucine incorporation into protein (lCPSleu) in 44 brain regions and the brain as a whole. Early in development, a greater fraction of the precursor leucine pool is derived from protein breakdown, indicating that protein degradation is higher in young rats compared with adults. In whole brain and in most regions, values for lCPSleu were highest at 10 days and gradually decreased with age. By 60 days of age, values in cortex were approximately 60% of those at 10 days of age. In the paraventricular and supraoptic nuclei of the hypothalamus, however, lCPSleu increased during development, reaching peak values in adults. In white matter of the cerebellum and the cerebrum, peaks of lCPSleu were reached at 14 and 21 days, respectively, approximately at the times of maximum rates of myelination.

Aging↗
PubMed1995

Effects of acute and delayed effects of prior chronic cocaine administration on regional rates of cerebral protein synthesis in rats.

Single or repeated treatments with cocaine (15 mg/kg, i.p.) in rats modify rates of local cerebral protein synthesis (ICPSleu) measured with the [1-14C]leucine method. A single dose of cocaine to naive rats reduced ICPSleu by about 10% throughout the brain; the most statistically significant reduction was in the nucleus accumbens, shell portion (P = .0003). A comparable dose of cocaine administered acutely after 1 wk of daily cocaine injections had no effects on ICPSleu. Delayed effects of prior chronic cocaine treatment were studied in experiments in which one rat of each pair received injections with saline for 8 days and the other cocaine, and on the 15th day ICPSleu was measured. In these experiments delayed effects of the chronic cocaine treatment were observed; in the cocaine-treated rats ICPSleu was significantly increased in selective brain regions, i.e., prefrontal and primary olfactory cortex (P < .006). These results suggest that acute effects of a single dose of cocaine and residual effects of chronic cocaine treatment on ICPSleu are distinctly different and occur in different regions of the brain.

Animals↗