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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
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↗
PubMed1991

Effect of loading doses of L-valine on relative contributions of valine derived from protein degradation and plasma to the precursor pool for protein synthesis in rat brain.

"Flooding" amino acid pools with high doses of labeled amino acids of low specific activity has been proposed to minimize the effects of recycling of amino acids derived from protein degradation on the specific activity of the amino acid precursor pool for protein synthesis. We have examined the influence of recycling on the precursor pool for protein synthesis under conditions in which plasma valine concentrations were normal (0.19 mM) and "flooded" (10-28 mM) by comparing the steady-state specific activity of the tRNA-bound valine with that of the plasma valine. Under normal and "flooding" conditions, the relative contributions of valine from protein degradation to the precursor pool were 63 and 26%, respectively; "flooding" with a plasma level of 28 mM raised the brain acid-soluble pool level to 3.1 mM but was no more effective in decreasing the relative contribution of valine from protein degradation to the precursor pool than "flooding" with a plasma level of 17 mM valine, which raised the brain acid-soluble level only to 2.3 mM. The results of these studies show that "flooding" amino acid pools does indeed reduce the effect of recycling on the precursor amino acid pool for protein synthesis, but it does not totally eliminate it.

Animals↗
PubMed1991

Changes in alpha 2-adrenoceptors on vascular smooth muscle and neural membranes following hypertension induced by renal ischemia.

alpha 2-Adrenoceptors were characterized on neural and vascular membranes from 2-kidney-1-clip renal hypertensive (RHT) and normotensive (NT) rats. Rats were sacrificed 6 weeks after induction of renal ischemia, and the specific binding of 3H-clonidine to smooth muscle membranes form tail arteries and neural membranes from various brain regions was examined. Additionally, isometric contractions of helically cut tail artery strips produced by various alpha-adrenoceptor agonists were measured. Scatchard analysis indicated an increased number of high-affinity binding sites on the smooth muscle membranes from RHT rats (Bmax = 43.5 +/- 1.4 fmol/mg protein) compared to that from the NT rats (25.4 +/- 3.8 fmol/mg protein). An increased contractile sensitivity to clonidine was also observed in tail artery strips from RHT rats (EC50 for RHT = 3.04 x 10(-8) M; NT = 1.52 x 10(-7) M). In neural tissue, the number of alpha 2-adrenoceptor-binding sites was significantly increased in the locus coeruleus from RHT rats, but not in the amygdala, hypothalamus, parietal cortex, hippocampus or lower brain stem. These results demonstrate that renal ischemia produces changes in both peripheral and neural alpha 2-adrenoceptor density. The increase in smooth muscle alpha 2-adrenoceptors might also provide a partial explanation for the supersensitivity to adrenergic agonists in this model of hypertension.

Adrenergic alpha-Agonists↗
PubMed1991

Assessing quality of ambulatory care. A comparative analysis in rural versus tertiary general medical clinics.

The purpose of this study is to report the results and feasibility of a "multi-methods" assessment of ambulatory health care in both rural and tertiary care settings. Our method used an expert panel's assessment of patient health and satisfaction outcomes (measured by follow-up telephone interviews) and care processes (measured by chart review) for assessing complete episodes of care. Subjects consisted of a matched cohort of ambulatory adult patients from the above two settings. We identified and analyzed specific clinical errors to confirm the expert panel's judgment of inadequacy. Results indicate that in both settings unacceptable health outcomes were found, at least partially explained by serious care deficiencies for 1 out of 2 to 3 patients seen. The problems, which involved mostly laboratory and pharmaceutic management, are probably preventable using newer education and computer technologies. Our method, though dependent on adequate medical records, proved feasible in both the rural and tertiary ambulatory care settings studied.

Ambulatory Care↗
PubMed1991

Effects of rat cytomegalovirus infection on immune functions in rats with collagen induced arthritis.

The effect of rat cytomegalovirus (CMV) infection on immune function was studied in rats with collagen induced arthritis, an experimental model of autoimmunity targeted to cartilage and previously shown to be greatly augmented in severity by rat CMV. Rat CMV infection induced an early (7 to 14 day), 2.5-fold increase in circulating B cells (SIgG+) which was associated with moderate increases in the titers of serum IgG antirat type II collagen antibody. A significantly increased skin test reactivity (p less than 0.025) to rat type II collagen was detected at Day 14 and followed a small increase in numbers of W3/25+ T-helper cells in peripheral blood noted at Day 8. A 3-fold expansion of OX8+ peripheral lymphocytes, occurring maximally at Day 8, was tentatively identified as a natural killer cell population by functional 51Cr-release assays. Our data indicate that rat CMV augmentation of collagen induced arthritis is associated with a generalized but modest increase in immune reactivity towards rat type II collagen and with significant alterations of peripheral lymphocyte subsets.

Animals↗