Search PubMed⌕ Search

Biomedical subjects

B R Smith

Publications and source records attributed to B R Smith.

At least 163 records · Page 9Linked to original sources
PubMed1991

Differential effects of an early housing manipulation on cocaine-induced activity and self-administration in laboratory rats.

Several reports in the literature suggested that environmental influences which are reflected in the social housing conditions of the rat may play a role in the expression of individual differences in drug self-administration. The present experiments were performed in order to further examine the effects of early housing manipulations, as reflected by grouped or isolation housing, on cocaine-induced behavioral responding. The first study examined the effects of this manipulation on the locomotor stimulant properties of cocaine. The results suggested that grouped housing produced a significantly greater increase in cocaine-induced locomotion than was observed in animals housed in isolation. Experiment 2 examined the effects of housing manipulations on the self-administration of cocaine under a continuous reinforcement schedule. Differences in the rate of cocaine self-administration were only observed at the lowest dose tested. Responding at all other doses was equivalent, including the optimal dose for both groups, suggesting that the housing manipulations failed to affect the reinforcing efficacy of cocaine. The present investigation suggests that, while the early housing manipulation produced a differential sensitivity in rats to the stimulant properties of cocaine, the same manipulation failed to alter the sensitivity of rats to the reinforcing properties of cocaine as assessed through self-administration.

Analysis of Variance↗
PubMed1991

Mandibular ramus anatomy as it relates to the medial osteotomy of the sagittal split ramus osteotomy.

The sagittal split ramus osteotomy is probably the most frequently used procedure for correction of mandibular skeletal dentofacial deformities. Despite numerous improvements in the technique in the 30 years since the procedure was introduced, a number of troublesome complications still occur. These include unfavorable fracture during surgery, paresthesia, and relapse. The purpose of this study was to determine where fusion of the buccal and lingual cortical plates occurs in the upper mandibular ramus, as it is thought that placement of the horizontal medial osteotomy above the point of fusion (without any intervening medullary bone) may lead to unfavorable fracture during splitting. Forty-nine human mandibles were sectioned vertically at three locations perpendicular to the surface of the ramus and the occlusal plane. Measurements were made to locate vertically the point of fusion of the buccal and lingual cortical plates relative to the lingula and to the depth of the sigmoid notch. The point of fusion occurred between 7.5 and 13.3 mm above the lingula. Only 2% of mandibles had fusion at or below the level of the lingula in the anterior ramus, whereas in the posterior ramus, 6.1% of mandibles were fused at that level. At a level halfway from the lingula to the sigmoid notch, 20% of mandibles were fused in the anterior ramus, whereas in the mid- to posterior ramus, the incidence was as high as 39%. The location of the medial horizontal osteotomy should be at or just above the tip of the lingula. A higher level of cut may be associated with an increased difficulty in splitting or incidence of unfavorable fracture.

Humans↗
PubMed1991

Mandibular anatomy as it relates to rigid fixation of the sagittal ramus split osteotomy.

Rigid fixation of osteotomy segments is frequently used to reduce relapse and allow for early mobilization of the mandible following the sagittal ramus split osteotomy. This study evaluated cortical bone thickness in the retromolar area of 49 human mandibles to determine if there is an advantage (in terms of cortical thickness) to placement of screws for rigid fixation at the external oblique ridge versus placement at the inferior border. The mandibles were sectioned vertically at three sites in the retromolar area, corresponding to the bone available for rigid fixation of the sagittal osteotomy. Cortical bone thickness was measured at the external oblique ridge and 5 mm above the inferior border. The buccal and lingual cortices were found to be significantly (P less than .001) thicker at the external oblique ridge than at the inferior border. This suggests that there may be an advantage in terms of stability to placement of internal fixation screws at the superior border.

Bone Screws↗
PubMed1991

Effects of GABA antagonists and habituation to novelty on ethanol-induced locomotor activity in mice.

The effects of the gamma-aminobutyric acid (GABA) antagonists picrotoxin and bicuculline on ethanol-induced motor excitation were assessed on habituated and non-habituated mice. Habituated mice were exposed to the testing apparatus for 30 min on 4 consecutive days before testing. Mice were treated with several doses of ethanol (0.8, 1.2 and 1.6 g/kg, intraperitoneally) and at each dose were pretreated with picrotoxin (0.25, 0.5 and 1.0 mg/kg, i.p.) or bicuculline (0.5, 1.0 and 2.0 mg/kg, i.p.). Habituated animals had consistently lower scores than non-habituated animals throughout the experiment. Ethanol alone produced a significant increase in motor activity. Picrotoxin and bicuculline alone decreased motor activity only at the two higher doses in both habituated and non-habituated mice. For the non-habituated mice, picrotoxin and bicuculline at the lowest doses decreased ethanol induced motor activity at the 0.8 and 1.2 g/kg ethanol doses, whereas in habituated mice, only bicuculline attenuated activity. At the highest dose of ethanol, picrotoxin increased ethanol-induced excitation for both non-habituated and habituated animals, whereas bicuculline only augmented the activity of the non-habituated animals at this ethanol dose. Neither antagonist affected blood-ethanol levels. These results suggest that habituation affects not only motor activity per se but also changes in activity due to the combination of GABA antagonists and ethanol.

Animals↗
PubMed1991

Modulation of platelet surface adhesion receptors during cardiopulmonary bypass.

Alterations in platelet receptors critical to adhesion may play a role in the pathogenesis of the qualitative platelet defect associated with cardiopulmonary bypass. Using flow cytometry, we measured changes in the following platelet surface adhesive proteins: the von Willebrand factor receptor, glycoprotein Ib; the fibrinogen receptor, glycoprotein IIb/IIIa; the thrombospondin receptor, glycoprotein IV; the adhesive glycoprotein granule membrane protein 140, whose expression also reflects platelet activation and alpha-granule release; and, as a control, the nonreceptor protein HLA, A,B,C. Glycoprotein Ib decreased during cardiopulmonary bypass (P less than 0.05) and reached a nadir at 72% (P less than 0.05) of its baseline value at 2-4 h after bypass. This decrease correlated (r = 0.76) with the magnitude of platelet activation (alpha-granule release) in any given patient, but even platelets that were not activated demonstrated a decrease in glycoprotein Ib expression. Glycoprotein IIb/IIIa also decreased in both the activated (47% of baseline, P less than 0.01) and unactivated (63% of baseline, P less than 0.01) subsets of platelets at the end of cardiopulmonary bypass. Glycoprotein IV and HLA A,B,C did not decrease, but instead increased 2-4 h after cardiopulmonary bypass (P less than 0.05). We conclude that cardiopulmonary bypass produces selective decreases in surface glycoproteins Ib and IIb/IIIa as well as in platelet activation; that these two alterations are temporally but not necessarily mechanistically linked; and that these changes have the potential to adversely affect platelet function.

CD36 Antigens↗
PubMed1991

Activity-dependent recruitment of silent synapses.

At the crayfish neuromuscular junction, a long-lasting enhancement of synaptic transmission can be induced by tetanic stimulation of 10-20 Hz for several minutes. The long-lasting enhancement is presynaptic in origin, because quantal content increases but not quantal size, and is not dependent upon broadening or enlargement of the presynaptic action potential. The enhancement can be selectively blocked by presynaptic injection of agents that inhibit adenylate cyclase or the cyclic AMP-dependent protein kinase. Entry of calcium may not be sufficient in itself to produce the enhancement. Analyses of quantal events using both a simple binomial statistical method, and a more refined method that takes into account the possibility of unequal probabilities of responding units, have shown that the number of responding units increases during the long-lasting enhancement. In addition, there is an increase in the probability of transmitter release at preexisting units. In contrast, during short-term facilitation accompanying repetitive stimulation, response probability increases greatly whereas the number of responding units increases only moderately with frequencies of activation up to 20 Hz, which increase quantal output severalfold. These results indicate that responding units, hypothesized to be transmitting synapses, can be recruited to active transmission from an unresponsive pool by tetanic activity, and that protein phosphorylation is required for long-lasting changes to occur. The existence of an excess of synapses on crustacean nerve terminals is indicated by ultrastructural studies, which invariably show many synapses on the terminals. The number of morphologically defined synapses is always greater than the number of responding units seen in statistical analyses of quantal release for the same recording location.

Animals↗
PubMed1991

The role of metabolism in chemical-induced pulmonary toxicity.

The lung is a target organ for the toxic effects of several chemical agents, including natural products, industrial chemicals, pesticides, environmental agents, and occasionally, drugs. Factors that establish the lung as a target organ include selective tissue exposure, high tissue oxygenation, and the presence of bioactivating systems that can generate toxic products from initially innocuous substances. Selective pulmonary exposure most often results from the fact that the lung serves as the major portal of entry for most airborne substances, but in some cases, selective exposure is the consequence of accumulation of agents, such as certain basic amines, from the circulation. Lung tumor development following long-term exposure to cigarette smoke or diesel engine exhaust is an example of pulmonary toxicity resulting from selective external exposure. Selective internal exposure, on the other hand, is exemplified by the pulmonary uptake of the herbicide paraquat from the circulation which is in part responsible for its lung-toxic effects. Although the lung contains drug metabolizing enzymes similar to those found in the liver, the enzymatic systems in the lung are sometimes highly concentrated in specific cell types. In the rabbit, for example, the lung-selective toxicity of the natural product ipomeanol is the consequence of relatively large amounts of cytochromes P450 2B1 and 4B1 in nonciliated bronchiolar epithelial cells (Clara cells) of the terminal airways. These P450 enzymes are highly proficient in vitro at converting ipomeanol to reactive products. Lung tissue contains other enzymic systems which are capable of catalyzing phase I biostransformation pathways (e.g., flavin-containing amine monooxygenase, amine oxidase, and prostaglandin synthase). Examples, however, where pulmonary metabolism by these pathways results in lung toxicity are less numerous than with P450 mediated reactions. Pulmonary prostaglandin H-synthase mediated cooxygenation has been shown to activate procarcinogens such as benzo(a)pyrene 7,8-dihydrodiol, aflatoxin B1, and monosubstituted hydrazines. The activities of pulmonary phase II (conjugation) pathways may also contribute to lung toxicity. Low glutathione transferase activity (relative to P450 mediated aryl hydrocarbon hydroxylase activity) in lung tissue has been suggested to correlate with elevated risk of lung cancer in smokers. Other examples of lung-specific toxic agents and possible causative roles of biotransformation are also discussed.

Animals↗
PubMed1991

Autosomal dominant inheritance of autoantibodies to thyroid peroxidase and thyroglobulin--studies in families not selected for autoimmune thyroid disease.

Recently the tendency to produce autoantibodies to thyroid peroxidase (TPO Ab) and thyroglobulin (Tg Ab) was shown to be inherited as an autosomal dominant characteristic in women but not in men. Because of potential bias in this study which was carried out in families with autoimmune thyroid disease (AITD), the inheritance of thyroid autoantibodies has been evaluated in 49 families unselected for autoimmune thyroid disease. Among these families (24 with facioscapulohumeral disease, 10 with Friedreich's ataxia, and 15 with schizophrenia) the prevalences of TPO Ab and Tg Ab were 27.8% and 26.7%, respectively, in women and 9.2% and 11.7%, respectively, in men. In 40 families where one or more individual had TPO Ab and/or Tg Ab, segregation analysis showed that the tendency to make antibodies was consistent with a Mendelian dominant trait in women but not in men. In young women, however, the prevalence of both TPO Ab and Tg Ab increased with age, rising from 14% and 10%, respectively, at age 15-24 to 35% and 40% at age 35-44. As this is inconsistent with a simple dominant hypothesis, a further segregation analysis by age was carried out in the families unselected for thyroid disease together with 16 pedigrees with AITD previously studied and two additional large AITD families. The results of the combined analysis provided strong support for the hypothesis of dominant inheritance but also showed significant reduction in gene expression among women aged 15-24 yr.

Adolescent↗
PubMed1991

Reevaluation of the periodic acid-Schiff stain in acute leukemia with immunophenotypic analyses.

To determine the sensitivity and specificity of the periodic acid-Schiff (PAS) stain in the diagnosis of acute leukemia in light of the finer characterization of this disorder now available through immunophenotyping, we examined the blasts from 51 patients with newly diagnosed acute leukemia by morphological, cytochemical, and immunophenotypic analyses. The 51 patients represented every new case of acute leukemia subjected to cytochemical stains and flow cytometry between July 1987 and February 1989. By cell-surface marker analysis, 29 exhibited lymphocytic lineage, while 21 were myelocytic. One was mixed lineage. The PAS positivity, defined by the presence of blocks or coarse granules in 5% or more of the blasts, was found in 15 of 29 lymphoblastic leukemias and in four of the myeloblastic leukemias. However, PAS-positive lymphoblastic leukemias were negative with the other cytochemical stains: myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase. The PAS-positive myeloblastic leukemias were positive with at least one other stain. Three cases of myeloblastic leukemia exhibited greater than 10% PAS-positive blasts, with all three being acute monoblastic leukemia. Thus, the sensitivity and specificity of the PAS stain alone for lymphoblastic leukemia was 52% (15 true positives of 29) and 81% (four false positives), respectively. The sensitivity of a cytochemical-staining combination of PAS positivity and myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase negativity in defining cases of lymphoblastic leukemia remained at 52%; however, the specificity of this combination for lymphoblastic leukemia was 100% (no false positives). Thus, a positive PAS stain, in combination with negative myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase stains, continues to have a diagnostic role in the distinction between lymphoblastic and myeloblastic leukemia, and greater immunologic sophistication serves to support this position.

Acute Disease↗
PubMed1991

Serotonin uptake inhibitors: effects on motivated consummatory behaviors.

Within the context of the role of serotonin (5-HT) in motivated behavior, the authors examine the effects of 5-HT uptake inhibitors on the regulation of motivated consummatory behavior. Emphasis in this field has for the most part focused on the consistent observation that treatment with these agents attenuates voluntary ethanol drinking behavior in both rats and humans. There has been extensive speculation that the underlying mechanism of the decrease in ethanol intake induced by 5-HT uptake inhibition may involve a modulation of ethanol's reinforcing properties. However, increasing evidence indicates that food consumption and fluid intake are also attenuated by these compounds. In addition, it has been shown that morphine, amphetamine, cocaine, and nicotine self-administration, as well as intracranial self-stimulation, are all decreased following 5-HT uptake inhibition. These observations support strongly the notion that the effects of these agents are global in nature and not specific to any single consummatory behavior. They also suggest that 5-HT uptake inhibition may result in nonspecific modification of motivated behavior in general.

Alcohol Drinking↗
PubMed1990

Retroviral mediated transfer and expression of exogenous genes in primary lymphoid cells: assaying for a viral transactivator activity in normal and malignant cells.

In this report we describe the use of recombinant retroviruses to characterize the activity of an exogenous promoter in primary cells obtained from patients with lymphoproliferative disorders. The infection of a variety of cultured and primary lymphoid cells with a recombinant retrovirus containing a histone promoter-driven beta-galactosidase gene is shown to result in the expression of beta-galactosidase in 50% to 100% of the cells. A similar infection with a recombinant retrovirus containing the beta-galactosidase gene with an adenovirus E2 promoter, results in beta-galactosidase activity in a limited number of cultured and primary cells. Since the adenovirus E2 promoter has been well characterized and is known to be regulated by transactivators encoded by many viruses, the activity of this promoter in specific cell types is discussed in reference to both the biology of the cell and the possible presence of as yet undetected viral gene products.

Adenovirus Early Proteins↗
PubMed1990

Retroviral mediated gene transfer into bone marrow progenitor cells: use of beta-galactosidase as a selectable marker.

Recombinant retroviruses have been utilized as vectors for gene transfer in model systems of gene therapy. Since many of these model systems require the transplantation of genetically modified primary cells it is important to devise methods which will allow the rapid and efficient selection for transplantation of only the cells which are capable of expressing high levels of the transferred gene. This report describes the use of beta-galactosidase as such a selectable marker. Bone marrow progenitors are infected with a recombinant retrovirus encoding beta-galactosidase. Using a fluorescence assay for beta-galactosidase we demonstrate that it is possible to use cell sorting to enrich for cells which will form bone marrow colonies that express high levels of beta-galactosidase. This rapid and non-toxic selection of bone marrow cells may facilitate attempts to achieve gene therapy in a variety of model systems.

Animals↗
PubMed1990

Differential effects of catecholamine antagonists on ethanol-induced excitation in mice.

Catecholamine antagonists were assessed for their effects on ethanol-induced motor excitation. Motor excitation was measured in male Swiss-Webster mice using an open-field apparatus. Mice were treated with several doses of ethanol and at each dose, mice were pretreated with pimozide, a dopamine D2 antagonist, Schering 23390, a dopamine D1 antagonist, phenoxybenzamine, a noradrenergic alpha-1 antagonist, or yohimbine, a noradrenergic alpha-2 antagonist. Each mouse was subjected to only one dose regimen, and all injections were given IP. Ethanol produced an increase in locomotor activity. The degree to which pimozide attenuated ethanol excitation decreased with increasing ethanol dosage. At the highest dose of ethanol, pimozide increased ethanol excitation. Schering 23390 attenuated ethanol-induced excitation only at doses which affected motor activity per se. Phenoxybenzamine produced a dose-dependent reduction in ethanol excitation. Yohimbine had its greatest effects at the medium dose (4.0 mg/kg). These observations seem to indicate a role for both the dopamine D2 receptor and the noradrenergic alpha-1 receptor in ethanol-induced motor excitation.

Animals↗
PubMed1990

An improved technique for development of the pectoralis major myocutaneous flap.

The pectoralis major myocutaneous flap is the most commonly employed muscle skin transfer used in soft-tissue reconstruction of defects of the upper neck and jaw region. This article presents conceptual and technical changes in the development of the pectoralis major myocutaneous flap that preserve a greater vascular pedicle and enhance the flap's arc of rotation. Data from 54 consecutive cases using this modified approach show a reduction in complications, a greater range of use, and consistent healing in radiated and nonradiated tissues without requiring sectioning or removing the clavicle or causing significant chest deformities. These modifications have produced a more predictable transfer compared with other reported techniques.

Adolescent↗
PubMed1990

Equilibrium kinetics of the new experimental anti-tumour compound SK&F 104864-A in aqueous solution.

The equilibrium kinetics of lactone ring hydrolysis in the new experimental anti-tumour compound SK&F 104864-A. (S)-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride, have been studied. Only one product is formed, SK&F 105992. A stability-indicating HPLC method has been optimized to perform the analysis. The pH is the main factor influencing equilibrium; at pH greater than or equal to 10 the lactone ring is quantitatively opened while at pH values less than or equal to 4 the lactone form is exclusively present. Other parameters, such as buffer ions and ionic strength, do not influence equilibrium. Complexation with dimethyl-beta-cyclodextrin stabilizes the lactone form. Other cyclodextrins do not show this stabilization.

Camptothecin↗
PubMed1990

High-performance liquid chromatographic analysis of the new antitumour drug SK&F 104864-A (NSC 609699) in plasma.

A high-performance liquid chromatographic (HPLC) assay is described for the determination of the new, investigational antitumour drug SK&F 104864-A and its lactone ring opened form (SK&F 105992). The analytical methodology reported here involves a protein precipitation step with methanol as sample pretreatment procedure. The instability of the drug necessitates that the plasma fraction is obtained within 5 min after blood sampling by centrifugation, immediately followed by protein precipitation with cold methanol (-30 degrees C). The methanolic extract can be stored at -30 degrees C for several days without deterioration of the analyses. Stability data of the drug and its lactone ring opened metabolite in plasma and after methanolic extraction are discussed. The parent drug and the metabolite are separated by reversed-phase ion-pair liquid chromatography on a LiChrosorb RP-18 column, using methanol-water eluent (pH 6.0) with sodium dioctylsulphosuccinate (DOSS) as ion-pairing agent and fluorescence detection. The proposed method has been validated and, subsequently, implemented in a phase I clinical trial for pharmacokinetic evaluation of the new cytotoxic agent.

Aged↗
PubMed1990

Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study.

Cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) is a widely used conditioning regimen in autologous bone marrow transplantation (ABMT) of patients with refractory and relapsed lymphoma. However, the maximum-tolerated dose (MTD) of these agents when used in combination has not been systematically explored. We treated 58 patients (28 with non-Hodgkin's lymphoma [NHL], 30 with Hodgkin's disease [HD]) at seven dose levels of CBV. Doses were cyclophosphamide 4,500 to 7,200 mg/m2, BCNU 450 to 600 g/m2, and VP-16 1,200 to 2,000 mg/m2. The MTD was cyclophosphamide 7,200 mg/m2, BCNU 450 mg/m2, and VP-16 2,000 mg/m2. Six hundred milligrams per square meter of BCNU was associated with five of 18 cases of interstitial pneumonitis versus two of 40 at 450 mg/m2 (P = .02). Treatment-related mortality was 5% at dose levels less than or equal to the MTD and 22% at the highest dose. In this heavily pretreated patient population, most of whom had high volume residual disease, complete responses (CRs) to CBV and ABMT occurred in 25% of assessable patients with NHL and 43% of patients with HD. Thirteen of 28 patients with NHL and 14 of 30 with HD remain free from disease progression with median follow-up of 212 and 215 days, respectively. CBV can be administered with acceptable toxicity over a wide range of doses to patients with refractory and relapsed lymphoma.

Adolescent↗