Biomedical subjects

S B Jones

Publications and source records attributed to S B Jones.

At least 109 records · Page 6Linked to original sources

PubMed1987

Regulation of aflatoxin biosynthesis: assessment of the role of cellular energy status as a regulator of the induction of aflatoxin production.

Possible relationships among cellular energy status and the induction and initiation of aflatoxin synthesis were studied by using replacement culture techniques in conjunction with aflatoxin-supporting and-nonsupporting media. Transcription and translation processes associated with the induction of aflatoxin synthesis occurred 3 to 6 and 6 to 10 h, respectively, after mycelia were transferred to glucose-containing media. From adenylate energy charge determinations and in situ 31P nuclear magnetic resonance analyses, a relationship between overall energy status and the induction or initiation of aflatoxin synthesis could not be identified; however, electron microscopic evaluations indicated that aflatoxin synthesis occurred in association with a glucose-mediated inactivation of mitochondria. The results suggest that aflatoxin synthesis is not regulated by the overall energy status of the fungal cell but may be controlled by the energy status of specific subcellular compartments.

Aflatoxins↗

PubMed1987

Alpha-1 adrenergic receptor binding in aortas from rat and dog: comparison of [3H]prazosin and beta-iodo-[125I]-4-hydroxyphenyl-ethyl-aminomethyl-tetralone.

We have identified and characterized pharmacologically alpha-1 adrenergic receptors in aorta from dog and rat utilizing two alpha-1 antagonists, [3H]prazosin and beta-3-iodo[125I]-4-hydroxyphenyl-ethyl-aminoethyl-tetralone [125I]HEAT, to determine receptor number and affinity. The rat and dog alpha-1 receptors were found to be very similar. In the dog, KD values were 27 and 11 pM for [3H]prazosin and [125I]HEAT, respectively, whereas maximum binding values were 89 and 65 fmol/mg of protein. KD values in rat aorta were 22 and 15 pM for [3H]prazosin and [125I]HEAT, respectively, whereas maximum binding values were 62 and 47 fmol/mg of protein. Both tissues demonstrated a rank order potency of antagonist inhibition of the two radioligands consistent with an alpha-1 adrenergic receptor with prazosin greater than phentolamine greater than yohimbine. A comparison between IC50 values for both the ligands and the tissues shows strong correlations suggesting the two radioligands are identifying a similar receptor population and that the receptor labeled by the ligands has similar pharmacologic characteristics in the two tissues.

Adrenergic alpha-Antagonists↗

PubMed1987

Competition or conscience? Mixed-mission dilemmas of the voluntary hospital.

Voluntary hospitals must develop increasingly businesslike strategies to survive in today's market-driven health care system. While challenging and necessary, this behavior is stirring fears that the time-honored mission of these hospitals will be seriously undermined. Noting that the voluntary tradition leavens the competitive marketplace, the authors suggest that we have much to lose if voluntary not-for-profit hospitals no longer play a leading role in the health care system, including: needed services to all classes of patients, paying and nonpaying; an important locus of community expressions of compassion and charity; and the settings that have inspired the vision of what medicine and health care can accomplish for mankind.

Attitude↗

PubMed1987

Characterization of the alpha-1 adrenergic receptors in the thoracic aorta of control and aldosterone hypertensive rats: correlation of radioligand binding with potassium efflux and contraction.

Pharmacologic analysis of functional and radioligand binding studies were used to determine whether alterations in adrenergic receptors contribute to the catecholamine supersensitivity observed in the thoracic aorta of aldosterone hypertensive rats (AHR). Adrenergic function was evaluated using receptor-mediated contraction and rate of 42K efflux. The pA2 for phentolamine was the same in AHR (7.9 +/- 0.1 and 8.0 +/- 0.1) and control (7.9 +/- 0.2 and 8.1 +/- 0.1) rats whether measured by contraction or 42K efflux. The pA2 value for the selective alpha-1 antagonist prazosin (9.8 +/- 0.1 to 10.7 +/- 0.2) and the alpha-2 antagonist yohimbine (6.6 +/- 0.2 to 7.4 +/- 0.2) was similar in AHR and control groups using both norepinephrine and phenylephrine as agonists. The rank order of potency was prazosin greater than phentolamine greater than yohimbine in both groups. The KD for [3H]prazosin binding to AHR (26 +/- 3 pM) and control tissue (34 +/- 6 pM) agreed with the prazosin KB obtained by measurements of contraction and 42K efflux. The alpha-1 receptor density was also unaltered: 39 +/- 1 fmol/mg in AHR and 44 +/- 3 fmol/mg in control. Assessment of the NE dissociation constant (Ka) by method of fractional receptor inactivation indicated that the Ka was 4.8 X 10(-7) M in both AHR and control tissues. However, at the same receptor occupancy, the NE-induced increase in 42K efflux was elevated markedly in aorta from AHR. We conclude that alteration in adrenergic receptor density, affinity or type is not the cause of catecholamine supersensitivity in the aorta from AHR and that postreceptor events mediate this phenomenon.

Aldosterone↗

PubMed1987

Plasma catecholamines following cecal ligation and puncture in the rat.

Peripheral sympathetic responses to septic peritonitis and developing septic shock were studied in conscious rats by measuring plasma catecholamines. Adult male Holtzman rats in the fasted state were subjected to anesthesia for implantation of carotid artery cannulae and were divided into three groups: (1) controls with cannulation only, (2) abdominal laparotomy control, and (3) cecal ligation and puncture (CLP) following cannulation. Arterial plasma levels of epinephrine were significantly (P less than .05) elevated at 5 h post-CLP whereas elevations at 16, 20, 24 and 41 h post-CLP were not significant. Plasma NE levels were significantly (P less than .05) elevated at 5, 16, 20, 24 and 41 h post-CLP. Adrenal medullary content of E was not different from control at 20 h following CLP, suggesting that adrenomedullary depletion could not account for low levels of plasma E during developing septic shock. Heart rate was significantly elevated (P less than .05) at 20 h post-CLP and was attenuated by (cardioselective) beta blockade. Mean blood pressure was not altered by CLP treatment. These findings are consistent with the interpretation that there are elevations in local nerve-stimulated release of NE in peripheral tissues during septic peritonitis.

Adrenal Medulla↗

PubMed1986

Ascorbic acid inhibition of alpha-adrenergic receptor binding.

Relatively low concentrations of ascorbic acid inhibited the binding of the alpha-1 adrenergic antagonist [125I]HEAT [DL-[beta(3-iodo-4-hydroxyphenyl)-ethyl-aminomethyl]-tetralone) in rat submandibular gland and rat aorta. However, no inhibition was observed with this ligand in several other tissues, nor with several other ligands in these tissues. The inhibition observed was dependent on the concentration of both the ascorbic acid and the tissue. Maximal inhibition of [125I]HEAT occurred in submandibular gland at 10 microM ascorbic acid with Bmax values reduced 65% and no change in affinity. Ascorbic acid had a greater effect in assays in which less tissue was used, causing a 22% decrease in binding at 46 micrograms/ml, but a 48% decrease in binding at a tissue concentration of 12 micrograms/ml. EDTA prevented the loss of binding normally seen with ascorbic acid at a tissue concentration of 17 micrograms/ml. We suggest that, if an antioxidant is thought to be necessary in an assay system, its effects be carefully examined before routine use.

Adrenergic alpha-Antagonists↗

PubMed1986

Platelet MAO and measures of attention and impulsivity in boys with attention deficit disorder and hyperactivity.

Platelet monoamine oxidase (MAO) activity was studied in 22 boys diagnosed as having attention deficit disorder with hyperactivity and 12 healthy control boys admitted to a clinical research center and placed on a diet low in monoamines. The hyperactive boys had lower platelet MAO activity than controls, and MAO activity was related to performance on the Matching Familiar Figures Test (MFF) and the Continuous Performance Test (CPT), which yield scores sensitive to impulsivity and inattention. Furthermore, it was negatively related, in hyperactive boys only, to two tests of reading and spelling achievement. Administration of d-amphetamine and placebo in a double-blind crossover design did not significantly raise MAO levels above baseline and was minimally related to improved performance on the MFF and CPT.

Achievement↗

PubMed1986

Alterations in beta-adrenergic stimulation of myocardial adenylate cyclase in endotoxic rats.

The effect of in vivo endotoxin administration on adenylate cyclase in rat ventricular membranes was studied. Basal, fluoride-, and 5'-guanylylimidodiphosphate-stimulated adenylate cyclase activities were not affected throughout the period of endotoxicosis. Isoproterenol-stimulated adenylate cyclase activity was not different at 0.5 or 3 h after endotoxin. At the agonal stage, the isoproterenol dose-response curve was shifted significantly to the right in myocardial membranes from endotoxic rats, but there was no significant decrease in maximum stimulated activity. These data indicate that endotoxicosis does not inhibit the adenylate cyclase enzyme system but does decrease stimulation of adenylate cyclase via beta-adrenergic receptors when the animal is approaching death.

Adenylyl Cyclases↗

PubMed1986

Cardiac and splenic norepinephrine turnover during septic peritonitis.

Postganglionic sympathetic activity was assessed in heart and spleen tissue in conscious rats under conditions of developing septic shock by quantitating norepinephrine (NE) turnover. Fasted male rats were subjected to cecal ligation and puncture and allowed to recover for 12-14 h. NE turnovers were measured by following the rate of [3H]NE decay, and measurements were made between 12 and 24 h after surgery. Plasma glucose and lactate were determined at times throughout the turnover protocol. NE turnover in cardiac tissue of septic animals was increased (0.134 micrograms X g-1 X h-1) in comparison with both surgical sham (0.052 micrograms X g-1 X h-1) and unoperated controls (0.051 micrograms X g-1 X h-1). NE turnover rates were also elevated in spleen tissue of septic rats (0.152 micrograms X g-1 X h-1) in comparison with both surgical sham (0.094 micrograms X g-1 X h-1) and unoperated controls (0.087 micrograms X g-1 X h-1). Plasma glucose levels suggest that septic rats are in the hyperglycemic phase of sepsis. These experiments support the concept of increased peripheral sympathetic outflow during the development of septic shock that would support hypermetabolic and subsequent hyperdynamic alterations which are well-recognized characteristics of the early stages of sepsis leading to septic shock.

Animals↗

PubMed1986

Characteristics of myocardial beta-adrenergic receptors during endotoxicosis in the rat.

The effects of in vivo endotoxin administration on beta-adrenergic receptors in rat ventricle membranes were studied using [3H]dihydroalprenolol as a radioligand. Nonlinear regression analysis of saturation binding indicated one-site binding of antagonist in both control and endotoxic tissues. There was no change in maximum binding or dissociation constant of [3H]dihydroalprenolol at 0.5 or 3 h after endotoxin administration or when the rats were in the agonal stage of shock. Isoproterenol competition studies revealed that there was an increase in the slope of the curve from endotoxic tissues at the agonal stages (0.6 +/- 0.06 vs. 0.91 +/- 0.12, control and endotoxic, respectively, P less than 0.05) and that there was a decrease in affinity for isoproterenol binding. Control binding modeled to a two-state fit, whereas binding to endotoxin-exposed membranes modeled to one state of lower affinity. These data suggest that there is an alteration in receptor-adenylate cyclase coupling, which may account for an attenuation of agonist-stimulated cyclase activity. A modification in the beta-adrenergic receptor may contribute to the decrease in myocardial performance during shock.

Animals↗

PubMed1986

Spirometry as a preoperative screening test in morbidly obese patients.

We performed spirometry on 114 morbidly obese patients considered for gastric bypass surgery to assess its efficacy as a preoperative screening test. One hundred eight subjects underwent surgery, and 61 patients returned for repeat spirometry 1 year later. The average preoperative forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and mid flow (FEF25-75%) were 100% of predicted. Spirometry identified no more of our obese subjects as abnormal than would have been identified in a group of healthy, nonobese individuals. Each surgical case was reviewed. An abnormal preoperative spirogram did not identify the patients who experienced postoperative complications. Weight loss was associated with very small increases in FVC (300 ml) and FEV1 (245 ml). Preoperative spirometric testing is not indicated in morbidly obese patients with no other identifiable risk factors for postoperative respiratory complications.

Adult↗

PubMed1986

Changes in serum lipids after gastric bypass surgery. Lack of a relationship to weight loss.

Serum lipid levels were measured in 65 obese patients before and a mean of 13.4 +/- 0.2 months after gastric bypass surgery performed to facilitate weight reduction. The 58 women studied lost an average of 39.8 +/- 1.2 kg thereby reducing their mean body mass index from 41.9 +/- 0.7 to 26.8 +/- 0.6. Postoperatively, total cholesterol, LDL cholesterol, and triglyceride levels were significantly lower and HDL cholesterol levels significantly higher than preoperative values (for each of the four comparisons P less than 0.0001). Whereas before surgery 83 percent of the women had levels of total, LDL, or HDL cholesterol indicative of an increased risk of coronary heart disease, after surgery only 24 percent did so. Preoperative cholesterol abnormalities in the seven men were not as severe as were those in the women, and the men's postoperative cholesterol changes were not as marked. Correlations of the difference between pre- and post-operative weight and the difference between pre- and post-operative lipid levels showed that weight loss accounted at most for just 8 percent of the simultaneous lipid change. The data indicate that gastric bypass surgery for morbid obesity produces a favorable change in serum lipid profiles and suggest that the change is due primarily to factors other than the associated weight reduction.

Adult↗

PubMed1985

Effects of dihydropyridine derivatives and anticonvulsant drugs on [3H]nitrendipine binding and calcium and sodium fluxes in brain.

The binding of [3H]nitrendipine to rat cortical membranes was reduced by phenytoin, phenobarbital, and pentobarbital. The IC50 values were 0.09, 0.40, and 0.76 mM respectively. The drugs reduced the apparent binding affinity of [3H]nitrendipine with little effect on the maximum number of binding sites. The inhibitory effects of the drugs were similar in the absence and presence of calcium (4.5 mM). Neither nimodipine (10(-8) to 10(-5) M) nor nifedipine (10(-8) to 10(-7) M) altered the voltage-dependent uptake of 45Ca2+ by synaptosomes from rat cortex. Phenytoin inhibited 45Ca2+ influx, and this inhibition was not altered by nifedipine. Nimodipine and nifedipine (10(-6) M) produced a small inhibition of the voltage-dependent uptake of 24Na+ by synaptosomes. Ethanol, phenytoin or pentobarbital reduced 24Na+ influx, and this action was not altered by nimodipine. Thus, sedative-anticonvulsant drugs reduced the binding of dihydropyridines to brain membranes, but these interactions did not appear to involve either calcium or sodium channels.

Animals↗

PubMed1985

Hypoxemia after gastric bypass surgery for morbid obesity.

Fifty-six patients who underwent Roux-en-Y gastrojejunostomy for morbid obesity had arterial blood gas analysis before surgery and during the first five postoperative days. Preoperatively, seven subjects were hypoxemic and three were hypercapneic. Twenty-four hours after gastric bypass, 75% of the patients had an arterial oxygen pressure (Pao2) less than 60 mm Hg. Compared with preoperative measurements, blood gas values on the first postoperative day showed a 13.7-mm Hg decrease in the mean arterial Pao2 and a 5.0-mm Hg increase in the mean arterial carbon dioxide pressure. Arterial Pao2 determinations on the third, fourth, and fifth postoperative days returned toward, but remained significantly less than, paired values obtained before surgery. Patients with hypoxemia after gastrojejunostomy were significantly older and had significantly lower preoperative arterial Pao2 measurements than patients who were not hypoxemic after surgery. Weight, body mass index, and preoperative spirometric measurements did not distinguish between those patients who did and did not become hypoxemic postoperatively. We conclude that hypoxemia commonly follows gastric bypass for morbid obesity, and thus we recommend that all patients undergoing this procedure be treated with supplemental oxygen for at least the first three postoperative days.

Adolescent↗

PubMed1985

Medullary osteogenesis with platinum cathodes.

Studies of electrical stimulation of osteogenesis with stainless steel electrodes have previously established a dose-response relationship between current and bone growth. Examination of the effect of differing geometric current densities resulted in the conclusion that very little electrode surface area was involved in stimulation and led to the design of a multiport "distributive" cathode. A series of experiments were performed to extend these results to wire and multiport platinum electrodes. As before, a current-bone growth dose-response relationship was found. Peak bone growth was greater than for stainless steel. However, peak bone growth occurred at 2.0 microA (versus 20 microA for stainless steel). Correlation studies suggest that small changes in cathodic potential affect bone growth more than similar size changes in current. Finally, the generally benign local host response to platinum suggests that platinum may be a suitable material for chronic indwelling anodes for stimulation of osteogenesis.

Animals↗

PubMed1985

Germination of spores from Clostridium botulinum B-aphis and Ba410.

The germination of spores from Clostridium botulinum B-aphis and Ba410 was examined. In a complex medium, heat activation of spores from both strains doubled the germination rates and was required for germination in the presence of 2% NaCl. In a defined medium (CTB [D. B. Rowley and F. Feeherry, J. Bacteriol. 104:1151-1157, 1970]), the parent strain B-aphis germinated at a rate of 0.77% min-1 in the absence of NaCl and was not affected by 2% NaCl. A salt-tolerant derivative, strain Ba410, germinated at rates of 0.16% min-1 in CTB and 0.04% min-1 in CTB containing 2% NaCl. L-Alanine-triggered spores germinated faster than did L-cysteine-triggered spores from both strains. When both amino acids were present, B-aphis germinated rapidly in the absence of NaCl and had biphasic kinetics in the presence of NaCl. Strain Ba410 had biphasic kinetics in the absence of NaCl and germinated slowly with single-phase kinetics in the presence of NaCl. L-Alanine- and L-cysteine-triggered germinations were each inhibited by both D-alanine and D-cysteine, indicating a common germinant-binding site for both alanine and cysteine. Attempts to select for variants with amino acid-specific germinant-binding sites were unsuccessful. Differences in the germination kinetics of both strains could not be explained by ultrastructural differences. Transmission electron micrographs revealed striking similarities between the strains.

Clostridium botulinum↗

PubMed1985

Beta-adrenergic stimulation of myocardial cyclic AMP in endotoxic rats.

Sympathetic nervous system activity and myocardial response to adrenergic stimulation were studied in the rat during endotoxicosis. Plasma glucose concentration, adrenal norepinephrine (NE) and epinephrine (E) content, spleen NE content, and myocardial NE and cAMP content were analyzed in fed rats given saline or endotoxin (ETOX, 16.7 mg/kg). Values were determined at various times during a 6-hour period or at the agonal stage of shock. Myocardial cAMP content was reduced by 1 hour, recovered at 4 hours, and was again depressed at the agonal stage. In addition, isoproterenol-stimulated cAMP production in ventricular slices from ETOX rats was attenuated by 3 hours after administration. These data suggest that myocardial beta-adrenergic receptor mechanisms are altered during endotoxicosis, which may account for reports of decreased functional responsiveness to catecholamines under similar conditions. At 1 hour after ETOX, adrenal NE did not change, but E was depleted and remained low throughout the period. By 2 hours, spleen NE was also found depleted. Myocardial NE did not change until the agonal stage, when it was severely depressed. This implies that there may be nonuniform activation (duration and/or intensity) of sympathetic pathways during endotoxicosis.

Adrenal Glands↗

PubMed1984

Functional characteristics and responses to adrenergic stimulation of isolated heart preparations from hypothermic and hibernating subjects.

Contemporary studies of isolated hearts from hibernators and nonhibernators are presented. Original experiments with isolated perfused hamster hearts are reported. Such hearts can maintain left ventricular function at temperatures as low as 7 degrees C. Generated left ventricular pressure was 40 +/- 9 mm Hg and heart rate was 7 +/- 1 beats/min. During cooling heart rate dropped dramatically, coronary flow increased, and ventricular pressure decreased initially, plateaued, and then fell as 7 degrees C was approached. Norepinephrine can cause increased heart rate and left ventricular pressure at 22 and 7 degrees C. This positive inotropic and chronotropic response was associated with increased cAMP at 30 sec after stimulation at 22 degrees C but not at 7 degrees C. Furthermore, cAMP was also not changed at peak response at 7 degrees C. Isoproterenol increased cAMP content in 37 degrees C ventricular slices but not at hypothermic temperatures. Possible mechanisms of nonadenylate cyclase mediation of inotropic and chronotropic responses at 7 degrees C are discussed.

Animals↗