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Biomedical subjects

C B Smith

Publications and source records attributed to C B Smith.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Differential regulation by anti-tumor-promoting 12-deoxyphorbol-13-phenylacetate reveals distinct roles of the classical and novel protein kinase C isozymes in biological responses of primary mouse keratinocytes.

12-Deoxyphorbol-13-phenylacetate (dPP) is the prototype for a new class of phorbol derivatives that function as protein kinase C (PKC) activators with potent anti-tumor-promoting activity. To explore the mechanism of action of dPP, we have conducted detailed analyses of the translocation and down-regulation patterns of individual PKC isozymes in mouse primary keratinocytes upon dPP treatment. PKC-alpha, -delta, and -epsilon were very quickly (within 2-5 min) translocated from the soluble fraction to the Triton X-100-soluble particulate fraction. PKC-delta and -epsilon were translocated with 2 orders of magnitude higher potency than was PKC-alpha. After translocation, PKC-alpha, -delta, -eta, and -epsilon were down-regulated; the down-regulation of PKC-epsilon contrasts with its retention after phorbol-12-myristate-13-acetate or bryostatin treatment. As was the case with translocation, dPP down-regulated the novel PKC isozymes (delta, epsilon, and eta) with 2 orders of magnitude higher potency (ED50, about 1-2 nM), compared with PKC-alpha (ED50, about 100 nM). dPP induced transglutaminase activity, ornithine decarboxylase activity, and cornification with potencies similar to that for PKC-alpha translocation. On the other hand, dPP caused inhibition of EGF binding with a potency similar to that for the translocation of the novel PKC isozymes. Although the generality of its selectivity in different cell types remains to be determined, at least in keratinocytes dPP is a powerful tool for dissecting the involvement of the classical and novel PKC isozymes in biological responses. The unique regulatory pattern of PKC-epsilon could contribute to the anti-tumor-promoting activity of dPP.

Animals↗
PubMed1992

Residual effects of tracer in sequential double label deoxyglucose studies.

The validity of sequential double label deoxyglucose (DG) determinations of local metabolic rate for glucose (IMRglc) was examined by quantifying the degree of trapping of residual first DG tracer during the second experimental period. One sciatic nerve was repetitively stimulated for 25 min, beginning either at the time of the DG injection or 25 min later. IMRglc in the ipsilateral dorsal horn of the lumbar spinal cord was found to be 105% and 56%, respectively, greater than that of the contralateral unstimulated side. Attempts to lower the body burden of radioactive DG by exchange blood transfusion failed to reduce this delayed effect. These data indicate that residual effects of the first tracer could obscure possible differences in IMRglc between two sequential experimental states.

Animals↗
PubMed1992

Alpha 2-adrenoceptor modulation of 5-HT biosynthesis in the rat brain.

The purpose of the present study is to clarify the modulation of the biosynthesis of serotonin (5-HT) via the alpha 2-adrenoceptors in the brain. For this purpose, 5-hydroxytryptophan (5-HTP) accumulation was determined using an HPLC-ECD system in the presence of the inhibition of aromatic L-amino acid decarboxylase. Administration of alpha 2-adrenoceptor agonist, clonidine, produced a reduction of the in vivo 5-HTP accumulation in both the rat hippocampus and dorsal raphe nucleus. In addition, alpha 2-adrenoceptor antagonist, idazoxan, increased the 5-HTP accumulation in both the hippocampus and the dorsal raphe nucleus. In rats with catecholaminergic neurons denervated by pretreatment with 6-hydroxydopamine, clonidine failed to produce a reduction of 5-HTP accumulation in the dorsal raphe nucleus. On the other hand, hippocampal 5-HTP accumulation was decreased significantly. Brain tryptophan levels were unaffected by either clonidine or idazoxan. These results suggest that alpha 2-adrenoceptors might modulate serotonin biosynthesis and this modulation might be related to the neuroanatomical differences in the rat brain.

5-Hydroxytryptophan↗
PubMed1992

Effect of clonidine on the release of serotonin from the rat hippocampus as measured by microdialysis.

The purpose of the present study is to clarify the effect of clonidine on the release of serotonin from the rat hippocampus in vivo. For this purpose, endogenous serotonin release was measured by brain microdialysis. Potassium-evoked serotonin release from the hippocampus of freely moving rats was significantly inhibited when clonidine (10(-5) M) was added to the perfusion solution, while the 5-hydroxyindoleacetic acid output remained unchanged. In catecholaminergically denervated rats, clonidine (10(-5) M) also inhibited the potassium-evoked serotonin release from the hippocampus and the 5-hydroxyindoleacetic acid output was unaffected by clonidine. These results suggest that the inhibitory effect of clonidine on serotonin release from the hippocampus might reflect the activation of alpha 2-adrenoceptors which are localized on the serotonergic nerve terminals.

Animals↗
PubMed1992

Additivity of protein deficiency and carbon monoxide on placental carboxyhemoglobin in mice.

OBJECTIVES: The purpose of the study was to estimate maternal and placental carboxyhemoglobin in protein-deficient and carbon monoxide-exposed mice. STUDY DESIGN: Pregnant CD-1 mice were placed on diets containing 27% (control), 16%, 8%, or 4% protein on gestation day 1. The dams were exposed to carbon monoxide concentrations of 0 (control), 65, 125, 250, or 500 ppm from gestation days 8 to 18. The dams were killed on gestation day 18, and blood samples were collected from the maternal hearts and placentas for carboxyhemoglobin determination. RESULTS: Maternal carboxyhemoglobin levels were related to the carbon monoxide exposure levels and were not affected by protein deficiency. Placental carboxyhemoglobin levels were higher than maternal carboxyhemoglobin levels, were related to carbon monoxide exposure levels, and were inversely related to dietary protein levels. CONCLUSION: The data suggest that maternal protein deficiency enhances the placental carboxyhemoglobin levels resulting from carbon monoxide exposure and exacerbates hypoxic conditions for the developing fetus. Special groups at risk may include drug abusers and cigarette or marijuana smokers.

Animals↗
PubMed1992

Determination of regional rates of cerebral protein synthesis adjusted for regional differences in recycling of leucine derived from protein degradation into the precursor pool in conscious adult rats.

The quantitative autoradiographic L-[1-14C]leucine method for the determination of regional rates of cerebral protein synthesis in vivo takes into account recycling of unlabeled leucine derived from protein degradation into the precursor pool for protein synthesis. We have evaluated the degree of recycling by measuring the ratio of the apparent steady-state leucine specific activity in the precursor amino acid pool (tRNA-bound leucine) to that in the arterial plasma. In the whole brain of the conscious rat this ratio (lambda WB) equals 0.58. The equivalent ratio for leucine in the acid-soluble pool in whole brain (psi WB) is 0.49. A first-degree polynomial equation for lambda WB as a function of psi WB was fitted from paired determinations. To determine the degree of recycling in local regions of the brain, we have measured in individual brain regions (i) psi i and calculated lambda i assuming that the fitted equation also applies to these localized regions. Our results indicate that the degree of recycling into the precursor pool does vary regionally; lambda i in the individual regions varies from 0.62 in the hypoglossal nucleus to 0.50 in the globus pallidus. Local rates of protein synthesis were then determined by the autoradiographic technique with regional corrections for recycling of unlabeled leucine. Rates of leucine incorporation into protein averaged 6.1 nmol/g of tissue/min in the brain as a whole, with the rates in gray matter about twice those in white matter.

Amino Acids↗
PubMed1992

Opioid and non-opioid effects of novel butyrophenone analogues.

Haloperidol, haloperidol propionate, and a haloperidol analogue N-3-(p-fluorobenzoyl) propyl-4-phenyl-4-propionyl-oxypiperidine (NIH 10495) were evaluated in several in vitro and in vivo tests of opioid effects. Haloperidol bound to opioid receptors with very low affinity and had no opioid agonist effects in the other test systems. Haloperidol propionate was 10 times less potent than NIH 10495 in the binding assay and in the smooth-muscle assay. Both of these haloperidol analogues decreased the rate and volume of respiration in air and in 5% CO2 with NIH 10495 being approximately 50 times more potent than haloperidol propionate. The NIH 10495, but not the haloperidol propionate, attenuated naltrexone-like discriminative stimulus effects in morphine-dependent withdrawn rhesus monkeys. Intravenously delivered NIH 10495 maintained higher rates of responding than did haloperidol propionate when evaluated for reinforcing effects. These drugs appear to have novel spectra of action that suggest possible value for this synthetic approach to the development of clinically useful analgesics and to the development of novel neuroleptics.

Animals↗
PubMed1991

Quantification of training in obstetrical ultrasound: a study of family practice residents.

This study was done to determine how rapidly physicians in training could become competent in performing obstetrical ultrasound for the purposes of routine evaluations (i.e., the standard examination as defined by AIUM). The scan measurements and results of organ surveys of 12 family medicine residents were compared with the results obtained by faculty members experienced in obstetrical ultrasound. Residents rapidly became proficient in biometry. The mean menstrual age calculated from BPD, AC, HC, and FL differed from faculty values by 0.381 weeks after residents had performed 40 supervised scans. Organ survey success rates demonstrated similar high concordance between resident and faculty scans.

Faculty, Medical↗
PubMed1991

Control of hypertensive emergencies.

Although uncommon, hypertensive emergencies require prompt recognition and treatment to reduce very high morbidity and mortality rates. Admission to an intensive care unit for treatment and monitoring is essential for optimal care. A Swan-Ganz catheter is often helpful in management. Intravenous nitroprusside sodium (Nipride, Nitropress) is probably the drug of choice for hypertensive emergencies other than those due to eclampsia or pheochromocytoma.

Antihypertensive Agents↗
PubMed1991

Opioid receptor affinity and selectivity effects of second residue and carboxy terminal residue variation in a cyclic disulfide-containing opioid tetrapeptide.

The previously described cyclic, delta opioid receptor-selective tetrapeptide H-Tyr-D-Cys-Phe-D-Pen-OH, where Pen, penicillamine, is beta-beta-dimethylcysteine, was modified at residues 2 and 4 by varying combinations of D- and L-Cys and D- and L-Pen, and effects on mu and delta opioid receptor binding affinities and on potency in the mouse vas deferens (MVD) smooth muscle assay were evaluated. A comparison was drawn between consequences of alterations in this series of analogs and those of analogous modifications in the related cyclic pentapeptide series which includes the highly delta receptor-selective [D-Pen2,D-Pen5]enkephalin, DPDPE. Unlike effects observed in the cyclic pentapeptide series, the mu receptor binding affinities of the cyclic tetrapeptides are not dramatically influenced by substitution of Pen for Cys at residue 2. Conversely, while binding of the pentapeptides is only slightly affected by alteration of the chirality of the carboxy-terminal residue, modification of stereochemistry at the carboxy terminus in the tetrapeptides critically alters binding behavior at both mu and delta sites. In contrast with the pentapeptide series, the tetrapeptides appear to be highly dependent upon primary sequence for binding and activity, as only the lead compound binds with high affinity to the delta site. Results suggest that the less flexible cyclic tetrapeptides, lacking the Gly3 residue, display more stringent structural requirements for binding and activity than do the corresponding cyclic pentapeptides.

Amino Acid Sequence↗