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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 19 recordsLinked to original sources

Effect of electroconvulsive shock on 5-HT2 and alpha 1-adrenoceptors and phosphoinositide signalling system in rat brain.

We studied the effect of repeated administration of electroconvulsive shock (ECS) on alpha 1-adrenoceptor subtype (alpha 1A and alpha 1B) and 5-HT2 (serotonin-2) receptors and receptor-mediated phosphoinositide (PI) hydrolysis in rat cerebral cortex. We observed that repeated administration with ECS significantly increased the density of 5-HT2 receptors, as labeled by [3H]ketanserin, as well as 5-HT-stimulated [3H]inositol-1-phosphate ([3H]IP1) in rat cerebral cortex. We also observed that repeated ECS administration caused a significant increase in the number of alpha 1-adrenoceptors and the alpha 1B-adrenoceptor subtype as measured by (+/-)-beta-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone binding. However, it had no significant effects on norepinephrine (NE)-stimulated [3H]IP1 formation or alpha 1A-adrenoceptor subtype. These results thus suggest that up-regulation of 5-HT2 receptors after administration with ECS is associated with increased 5-HT-stimulated [3H]IP1 formation. The lack of effects on NE-stimulated PI turnover in ECS treated rats may be due to its lack of effect on the alpha 1A-adrenoceptor subtype.

Animals

Structural and functional characterization of Escherichia coli peptidyl-prolyl cis-trans isomerases.

Peptidyl-prolyl cis-trans isomerases (PPIases), enzymes that catalyze the cis-trans isomerization of peptide bonds to which proline contributes the nitrogen, were purified from Escherichia coli. In this organism, at least two PPIases are present. Both the cationic (periplasmic) and anionic (cytoplasmic) PPIases are inhibited by cyclosporin A with a Ki of 25-50 microM, a concentration 1000-fold higher than that required for eukaryotic PPIases. Although isoelectric focusing indicates that the two enzymes differ in isoelectric point by at least 4.0 pH units, the specific activities of the enzymes toward the tetrapeptide substrate succinyl-Ala-Ala-Pro-Phe-methyl-coumarylamide are equivalent. The activity of both enzymes for a series of substituted succinyl-Ala-Xaa-Pro-Phe-para-nitroanilide tetrapeptides suggests that the structure and function of the active site of the prokaryotic proteins is similar to that of eukaryotic cyclophilins. Both enzymes are capable of catalyzing the refolding of thermally denatured type III collagen. Antibodies against the periplasmic PPIase do not recognize the cytoplasmic enzyme, indicating significant differences in epitopes between the two forms. Circular dichroism spectroscopy indicates that the secondary structure of the cationic protein consists of 17% alpha-helix, 34% beta-sheet, 17% turns, 33% random coil and is very similar to human cytosolic PPIase.

Amino Acid Isomerases

The Surgical Infection Society's policy on human immunodeficiency virus and hepatitis B and C infection. The Ad Hoc Committee on Acquired Immunodeficiency Syndrome and Hepatitis.

The Ad Hoc Committee on Acquired Immunodeficiency Syndrome and Hepatitis of The Surgical Infection Society has outlined its policy regarding three deadly blood-borne viral infections. The risk of transmission of these microbes, the role of preoperative testing, the problem of the human immunodeficiency virus-infected surgeon, and conduct in the operating room are discussed.

General Surgery

High-frequency jet ventilation and surfactant treatment of newborns with severe respiratory failure.

Twenty-eight newborn infants (birthweight, 2.4 +/- 1.1 kg; gestational age, 34.6 +/- 6.1 weeks) with respiratory distress syndrome (RDS), meconium aspiration syndrome, or pneumonia who deteriorated in spite of optimal conventional mechanical ventilation (CMV) and exogenous surfactant therapy were treated with high-frequency jet ventilation (HFJV) and continued surfactant therapy. For enrollment, infants had to have a limited response to surfactant therapy and conventional ventilation, and meet clinical criteria that confirmed clinical deterioration and severity of illness. Study infants had received exogenous calf lung surfactant extract (CLSE) and conventional ventilation prior to the start of HFJV at 46.3 +/- 8.2 hours of age. Patients initially responded to HFJV alone with significant improvement in several respiratory variables, but deteriorated subsequently and receive additional doses of exogenous surfactant on HFJV. Exogenous surfactant and HFJV resulted in significant and sustained improvement in several respiratory variables. Only ten patients deteriorated to meet criteria for a second surfactant dose on HFJV, and two patients received a third dose. Twenty-five of the 28 patients studied survived (89%). No patients received extracorporeal membrane oxygenation or were discharged home on oxygen. The results of this pilot study suggest that the combination of HFJV and exogenous surfactant replacement may be effective in treating infants with more severe respiratory failure, and indicate the need for more extensive controlled investigations.

Gestational Age

Effects of carbohydrate feedings on plasma free tryptophan and branched-chain amino acids during prolonged cycling.

Brain serotonin (5-hydroxytryptamine, 5-HT) has been suggested to be involved in central fatigue during prolonged exercise. Changes in the ratio of plasma free tryptophan (free Trp) to branched-chain amino acids (BCAA) are associated with altered brain 5-HT synthesis. The purposes of this study were to describe systematically the effects of prolonged exercise on changes in plasma free Trp and BCAA and to examine the effects of carbohydrate (CHO) feedings on these same variables. Eight well-trained men [VO2max = 57.8 (SE 4.1) ml kg-1 min-1] cycled for up to 255 min at a power output corresponding to VO2 at lactate threshold (approximately 68% VO2max) on three occasions separated by at least 1 week. Subjects drank 5 ml kg-1 body wt-1 of either a water placebo, or a liquid beverage containing a moderate (6% CHO) or high (12% CHO) concentration of carbohydrate beginning at min 14 of exercise and every 30 min thereafter. Exercise time to fatigue was shorter in subjects receiving placebo [190 (SE 4) min] as compared to 6% CHO [235 (SE 10) min] and 12% CHO [234 (SE 9) min] (P < 0.05). Glucose and insulin decreased in the placebo group, and free Trp, free-Trp/BCAA, and free fatty acids increased approximately five- to sevenfold (P < 0.05). These changes were attenuated in a dose-related manner by the carbohydrate drinks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Monoamine oxidase and cortisol response in depression and schizophrenia.

The relationship between hypothalamic-pituitary-adrenal (HPA) axis function and platelet monoamine oxidase (MAO) activity was examined in drug-free depressed (n = 32) and schizophrenic (n = 36) inpatients. HPA function was measured by determining plasma cortisol levels at 8:30 a.m. and 11 p.m. before, and 8:30 a.m., 4 p.m., and 11 p.m. after administration of 1 mg of dexamethasone (DEX). There was a significant correlation between platelet MAO activity and all post-DEX cortisol levels (8:30 a.m., 4 a.m., and 11 p.m.) in depressed patients, and MAO activity and pre-DEX cortisol levels (11 p.m.) in schizophrenic patients. MAO activity was significantly higher in depressed DST nonsuppressors than in suppressors, and there were more DST nonsuppressors in high-MAO groups as compared with low-MAO groups. Our results thus suggest a strong relationship between platelet MAO activity and HPA function in depressed patients. These biochemical markers are potentially useful in the identification of biochemically and clinically homogeneous subgroups of depressed patients.

Adult

Thermogenic effects of pre-prandial and post-prandial exercise in obese females.

The thermogenic effects of pre- and postprandial exercise was examined in six obese premenopausal females. Using open circuit calorimetry, energy expenditure was measured for 3 hours following five separate treatments: Resting Control, Exercise Only (25 min cycle at 60% VO2 max), Meal Only (902 kcal mixed meal), Exercise-Meal, and Meal-Exercise. Meal Only, Exercise-Meal, and Meal-Exercise were significantly higher than Rest Only and Exercise Only treatments. However, Meal-Exercise resulted in the greatest energy expenditure. These results suggest that in obese female subjects exercise following a meal will produce the greatest thermogenic response and could possibly influence weight maintenance or weight loss if implemented in food and exercise patterns of behavior.

Adult

The effect of a support group on grieving individuals' levels of perceived support and stress.

This study examined the effects of support group participation on bereaved individuals' levels of perceived support and stress. Using a single group pretest/posttest design, data were collected from a convenience sample of 21 grieving individuals who participated in 10 weekly support group sessions. Perceived stress decreased significantly (P less than .002) following support group participation. However, although perceived support increased, the change was not statistically significant. These findings indicate that a support group can be an effective intervention to decrease feelings of stress in bereaved individuals.

Adaptation, Psychological

Platelet monoamine oxidase in schizophrenia: a meta-analysis.

We did a meta-analysis on all publications (English and other languages) concerned with platelet monoamine oxidase (MAO) in schizophrenia. Essentially, when patients were medicated with a neuroleptic, most studies found that schizophrenics had lower platelet MAO levels than controls. Administration of neuroleptic lowers MAO levels. MAO levels in drug-free schizophrenics were similar to controls. Only a minority of studies found drug-free schizophrenics had decreased platelet MAO levels.

Antipsychotic Agents

Proton magnetic resonance spectroscopy of the brain in schizophrenic and affective patients.

Water-suppressed 1H magnetic resonance spectra were recorded from two brain regions of psychiatric patients and normal volunteers. The two regions studied were (a) the basal ganglia structures surrounding the anterior horn of the lateral ventricle and (b) the occipital cortex. N-Acetylaspartate (NAA), phosphocreatine-creatine (PCr-Cr), choline and inositol resonances were seen in both regions. Ratios of metabolite peak integrals to PCr-Cr peak integral were calculated for each spectrum. To control for partial volume effects, comparisons between patients and controls were made only from identical regions i.e. basal ganglia vs basal ganglia, and likewise for occipital cortex. Metabolite ratios from the occipital region of patients were similar to those from the occipital region of normal subjects. Bipolar patients being treated with lithium had elevated NAA/PCr-Cr in the basal ganglia region when compared to normals. These patients also demonstrated elevated choline/PCr-Cr and inositol/PCr-Cr ratios in the basal ganglia region.

Adult

Altered cellular distribution of hexokinase in skeletal muscle after exercise.

The purpose of this study was to determine the effects of a single period of swim exercise to exhaustion on the cellular distribution of hexokinase in rat skeletal muscle. The gastrocnemius muscle from male rats exercised (n = 16) to exhaustion or allowed to remain inactive (n = 14) was analyzed for hexokinase activity (HK) in the whole muscle homogenate and the mitochondrial-rich fraction. Although exercise produced a slight, non-significant, increase in HK activity in the whole muscle homogenate (p less than 0.09), HK activity in the mitochondrial-rich fraction was significantly increased in the exercised muscle (p less than 0.02). This shift in the cellular distribution of HK is towards the more active mitochondrial bound form and indicates an enhanced regulation of HK activity during physical exercise.

Animals

Effect of ethanol administration and withdrawal on serotonin receptor subtypes and receptor-mediated phosphoinositide hydrolysis in rat brain.

The effect of short-term (15 days) and long-term (60 days) ethanol treatment and withdrawal on agonist-stimulated phosphoinositide (Pl) hydrolysis, serotonin receptor subtypes (5HT1A and 5HT2), and alpha 1-adrenergic receptors were studied in rat cerebral cortex. Short-term ethanol treatment had no significant effect on serotonin (5HT), norepinephrine (NE), and calcium ionophore (A23187)-stimulated [3H]-inositol-1-phosphate ([3H]-IP1) formation and 5-HT2 receptors as measured by 125I-lysergic acid diethylamide (125I-LSD) binding, in rat cerebral cortex. However, 15 days of ethanol treatment, followed by 24 hr of withdrawal resulted in a decrease in Bmax of 125I-LSD binding without significant change in KD, as well as a decrease in 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. 5HT1A and alpha 1-adrenergic receptors were determined by using [3H]-8-hydroxy-2-(di-N-propylamino)tetralin and [3H]-prazosin as radioligand, respectively. We also observed that long-term ethanol treatment had no significant effect on Bmax and KD of 5HT2, 5HT1A, and alpha 1-adrenergic receptors, as well as NE and A23187-stimulated [3H]-IP1 formation, but significantly decreased the 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. It is possible that a decrease in 5HT-induced PI turnover after long-term ethanol exposure may be due to a decrease in coupling of 5HT2 receptors to G protein or PLC enzyme, whereas the decrease in 5HT-induced PI turnover after withdrawal may be due to a decrease in functional 5HT2 receptor number.

8-Hydroxy-2-(di-n-propylamino)tetralin

Prophylactic effects of dexamethasone in lung injury caused by hyperoxia and hyperventilation.

To determine if prophylactic corticosteroids would prevent acute lung injury caused by hyperoxia and barotrauma, 29 piglets (1.2 +/- 0.3 kg, 1-2 days of age) were studied. Ten piglets were hyperventilated [arterial PCO2 (PaCO2) 15-20 Torr] with 100% O2 for 48 h and compared with 10 piglets treated with the identical management but given 0.7 mg/kg of dexamethasone at time 0 and every 12 h for the 48-h study. Six piglets were normally ventilated (PaCO2 40-45 Torr) for 48 h with 21% O2 as an additional control group. Pulmonary function and tracheal aspirates were examined at time 0 and every 24 h. Bronchoalveolar lavage was performed for surfactant analyses at the conclusion of the study. In animals treated with hyperoxia and hyperventilation, lung compliance decreased 32% and tracheal aspirate polymorphonuclear leukocyte (PMN) chemotactic activity increased by 51%, cell counts by 204%, number of PMNs by 277%, elastase activity by 111%, and albumin concentration by 328% over 48 h (P less than 0.05). In contrast, dexamethasone-treated piglets had increases in only tracheal aspirate albumin concentration (206%) over the 48-h study. All cellular and biochemical variables were lower in dexamethasone-treated compared with hyperoxic hyperventilated piglets. Room air normal ventilation controls had only a 108% increase in tracheal aspirate albumin concentration noted. Despite quantitative differences in surfactant among the three groups, activity was unaffected. Results indicate that hyperoxia and hyperventilation for 48 h causes significant inflammatory changes and acute lung injury and that prophylactic high-dose dexamethasone significantly ameliorates this lung damage.

Animals

Short-term distribution kinetics of intratracheally administered exogenous lung surfactant.

The short-term distribution kinetics of exogenous surfactant distribution after intratracheal instillation was investigated in surfactant-deficient neonatal piglets during assisted conventional mechanical ventilation and by high-frequency jet ventilation using exogenous calf lung surfactant extract (CLSE) labeled with 99mTc. Surfactant deficiency was induced by repeated bronchoalveolar lavage in piglets (1.2 +/- 0.4 kg, 1.4 +/- 0.7 d of age), and the short-term distribution kinetics of instilled, labeled CLSE were followed by gamma radioscintigraphy. Animals ventilated by either conventional mechanical ventilation or high-frequency jet ventilation showed similar improvement in arterial/alveolar oxygen ratios after surfactant replacement therapy (0.47 +/- 0.03 prelavage, 0.09 +/- 0.01 postlavage, 0.36 +/- 0.06 postsurfactant). This correlated directly with dynamic radioscintigraphic results showing that instilled CLSE began to distribute to the lungs within 5 s, and was present in substantial amounts in standardized symmetrical lung fields (central, right, and left; upper and lower) within 20 s of tracheal instillation. Subsequent measurements over 30 min showed continued presence of radiolabeled CLSE in all five areas of the lung, with no significant difference between conventional mechanical ventilation and high-frequency jet ventilation animals. Static (5-min) analyses at the end of this period showed that surfactant had distributed relatively symmetrically with 30% of the CLSE located in central regions, 40% in the upper lobes, and 30% in the lower lobes. In contrast, piglets receiving 99mTc in saline showed nonuniform distribution with multiple filling defects noted throughout the lungs. The rapid kinetics and ventilation independence of CLSE distribution suggest that surfactant spreading phenomena after tracheal instillation may facilitate the delivery of exogenous surfactant into aerated lungs in therapeutic applications.

Animals

Physiologic and perceptual responses to exercise on a new cycle ergometer.

This study observed oxygen consumption (VO2), heart rate (HR), and rating of perceived exertion (RPE) during both maximal and submaximal exercise tests on a conventional Monark cycle ergometer and a new Velodyne ergometer. The Velodyne uses the subject's own bicycle attached to an electrically braked roller, which regulates power output. Trained male cyclists performed maximal exercise tests on both ergometers (N = 7) and two submaximal tests on each of three identical Velodynes and a Monark (N = 6). VO2, HR and RPE were measured during the submaximal and maximal tests. Data were analyzed via multiple repeated-measures ANOVA. No differences were found across cycles during the maximal or submaximal tests. The results indicate that the Monark and the Velodyne ergometers elicited similar physiologic and perceptual responses and that the Velodyne can be a viable alternative to the conventional Monark ergometer.

Adult