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Biomedical subjects

D A Thompson

Publications and source records attributed to D A Thompson.

At least 145 records · Page 8Linked to original sources
PubMed1985

Failure of autotransplantation of the spleen in dogs: an anatomic, radionuclide imaging, and pathologic study.

Although splenic autotransplantation is successful in mice and rats, with regeneration occurring in any location, no extensive study had been performed on dogs. We transplanted the spleen into subcutaneous and intraperitoneal locations on 40 dogs. Four to six months later, splenic scanning and reexploration was carried out. Spleens were removed, weighed, and microscopic sections were made. Months later, no uptake was present on scanning, weight was less than 6% of original weight, and little identifiable splenic tissue was present on microscopic sections. When 15 small sections were transplanted to the omentum in a "necklace" fashion, good uptake and preservation were seen after six months. The small amount of spleen transplanted by this method, however, makes this an unsatisfactory option. We conclude, therefore that our large-animal experiments do not provide a basis on which to recommend autotransplantation of the spleen in humans. Preservation of splenic tissue by splenorrhaphy is still the treatment of choice.

Animals↗
PubMed1985

The significance of scapular fractures.

Scapular fractures in the multiply injured patient have received little attention. Fifty-six patients with 58 scapular fractures secondary to blunt trauma were reviewed. The patients averaged 3.9 major injuries excluding their scapular fractures. The injury pattern associated with blunt scapular fracture is unique. Patients with scapular fracture have a high incidence of injury to the ipsilateral lung and chest wall and to the ipsilateral shoulder girdle and its contained structures: rib fractures, 53.6%; pulmonary contusions, 53.6%; clavicular fracture, 26.8%; brachial plexus injury, 12.5%; subclavian, brachial, or axillary artery injury, 10.7%. Eight patients died (14.3%). Although no patient died from the scapular fracture, half of the deaths in this series were the result of pulmonary sepsis arising in an associated ipsilateral pulmonary contusion. Scapular fractures provide the trauma surgeon with a reliable clinical clue that the patient is at inordinate risk to have associated injuries of major consequence to the ipsilateral lung and chest wall, the ipsilateral shoulder girdle, and the ipsilateral subclavian, axillary, or brachial artery.

Adolescent↗
PubMed1984

Effects of systemic or intracerebroventricular naloxone injection on basal and 2-deoxy-D-glucose-induced ingestive behavior.

In order to examine the role and site of action of opiates on both hunger and thirst and food and water intake in rats after short term (3 hr.) food deprivation alone or in combination with 2DG-induced glucoprivic stress, naloxone was given to rats in either the jugular vein or the lateral ventricle. Both basal and 2DG-induced food and water intake were reduced by naloxone injected either peripherally or centrally. Latencies to eat and drink were used as measures of hunger and thirst respectively. Only central injection of naloxone significantly reduced 2DG-induced but not basal hunger. These results suggest a central site of action of naloxone on both food and water intake even if some peripheral effects cannot be totally ruled out. Our findings indicate central nervous system opiate receptor involvement in the hunger response to 2DG-induced glucoprivation. In all other treatment conditions, decreases in food intake cannot be related to reduction of hunger but may be due to potentiation of satiation during opiate receptor blockade.

Animals↗
PubMed1984

The functional and physical form of mammalian cytochrome c oxidase determined by gel filtration, radiation inactivation, and sedimentation equilibrium analysis.

When solubilized in laurylmaltoside, cytochrome oxidases from beef heart and rat liver mitochondria exist as monodisperse populations that are stable, highly active, and have apparent molecular weights of 300,000 to 350,000, as measured by gel filtration. To determine whether these are monomeric (2 heme A, 2 Cu) or dimeric forms of the enzyme, we performed radiation inactivation and sedimentation equilibrium analyses. From radiation inactivation experiments under two different sets of conditions, we obtained estimates for the functional molecular weight of beef heart cytochrome oxidase of 114,000 and 99,000, much less than a dimer and significantly smaller than a 200,000 molecular weight monomer containing one copy of each of the 12 subunits normally present in the complex. The same functional size is obtained for a rat liver oxidase preparation depleted of subunit III. The physical molecular weight of cytochrome oxidase was determined by sedimentation equilibrium measurements in solvents of different densities using mixtures of H2O and D218O. Estimates of Mr = 194,000 +/- 9,000 for the beef heart oxidase and Mr = 152,000 +/- 6,000 for the rat liver enzyme were obtained, consistent with the size predicted for monomers of their subunit composition. From these results we conclude that mammalian cytochrome oxidases from beef heart and rat liver exist in laurylmaltoside as monomers capable of high rates of electron transfer and normal substrate binding. Further, these functions appear to be associated with a subset of the peptides present in the monomer, mainly composed of subunits I and II.

Animals↗
PubMed1984

"Pink urine" in morbidly obese patients following gastric partitioning.

A pink coating on the inner surface of plastic urinary tubing, which gave the impression that the urine was pink, had frequently been noted 4 to 24 hours following gastric partitioning by means of a stapler in morbidly obese patients. A study was therefore done in 187 such patients as well as in 14 patients of normal weight who had undergone abdominal surgery of comparable magnitude. Postoperatively "pink urine" was observed in 32% of the obese patients but in none of the nonobese patients; however, a pink sediment remained following centrifugation of urine collected postoperatively from all the obese patients. Microscopy of this sediment showed crystals of uric acid dihydrate; these were infrequent in the preoperative specimens but present in high concentration in the postoperative specimens, particularly those of "pink urine". X-ray diffraction analysis confirmed the nature of the crystals. Preoperatively the obese patients had high-normal serum levels of uric acid. Postoperatively in all the groups of patients the serum levels of uric acid decreased while the urine levels and the urinary clearance of uric acid increased; the last two values, however, were significantly greater, both preoperatively and postoperatively, in those who were morbidly obese. Compared with the patients who did not have "pink urine" the patients with "pink urine" were significantly more obese and had a significantly lower postoperative urine pH. The latter also had a marked postoperative increase in urine osmolality and were the only patients to have a significant postoperative decrease in urine output. Thus, the pink colour of this group's urine was attributed to precipitation of uric acid crystals, fostered by a decrease in pH and an increase in concentration of the urine.

Adult↗
PubMed1984

Alpha 2-adrenoreceptor stimulation inhibits thermogenesis and food intake during glucoprivation in humans.

Noradrenergic central and peripheral nervous system mechanisms for the control of food intake and thermogenesis, respectively, have been described in rats and, to a lesser extent, in humans. To examine further the role of the sympathetic nervous system in energy balance modulation during glucoprivation, the alpha 2-adrenoreceptor agonist clonidine was given to subjects receiving 2-deoxy-D-glucose, a competitive inhibitor of glucose utilization, which induces sympathetic discharge, ingestive behavior, and thermogenesis by initial actions in the central nervous system. Increases in food intake and thermogenesis in association with activation of descending sympathetic outflow during 2-deoxy-D-glucose-induced glucoprivation were totally abolished by clonidine administration. Neither increases in hunger ratings after 2-deoxy-D-glucose infusions nor basal hunger and food intake after sham infusions were decreased by clonidine treatment, which nevertheless reduced thermogenesis under basal conditions. These results clearly indicate that catecholamine-mediated thermogenesis under both stimulated and basal conditions is inhibited by central or peripheral actions of clonidine, presumably at the level of alpha 2-adrenoreceptors. The reduction in food intake brought about by clonidine treatment in subjects undergoing glucoprivic stress may be the result of potentiation of satiation or reduction of hunger during a test meal rather than decreased hunger before a test meal.

Adrenergic alpha-Agonists↗
PubMed1984

Ultrastructural morphometric of gap junctions during differentiation of stratified squamous epithelium.

The presence of gap junctions in stratified epithelia has now been extensively documented, but there have been few attempts to quantify them. In the present report, samples of hamster cheek pouch mucosa were processed for electron microscopy and electron micrographs from defined basal, spinous and granular layers were obtained. Using a combination of direct measurement and stereological intersection counting techniques, the relative surface areas of peripheral gap junctions (i.e. those in direct contact with the epithelial plasma membrane) and annular gap junctions (i.e. those present as complete, approximately circular profiles within the epithelial cell cytoplasm) were determined. Following estimation of the plasma membrane surface area of 'average' epithelial cells from each of the defined strata, relative values were transformed into absolute data. Data from peripheral and annular junctions were pooled to provide an estimate of total gap junctions area. Relative surface area estimates were similar for peripheral, annular and total gap junctions, in that values were invariably highest in the spinous layer and lowest in the granular layer. Absolute data indicate that there is more than a threefold increase in the area of membrane differentiated into gap junctions in the average spinous cell when compared with the average basal cell. Values for total gap-junctional areas in the average granular cell are reduced somewhat with respect to the average spinous cell and this is effected by a decrease in the area of peripheral gap junctions. We conclude that there is synthesis of gap junctions between basal and spinous cells, which is followed by evidence of degradation between spinous and granular cells. The magnitude of the estimates of area is comparable to those obtained from other stratified and non-stratified epithelia and it would thus appear that gap junctions may play a significant role in cellular control processes in all viable epithelial strata.

Animals↗
PubMed1983

Lipid and subunit III depleted cytochrome c oxidase purified by horse cytochrome c affinity chromatography in lauryl maltoside.

Cytochrome oxidase is purified from rat liver and beef heart by affinity chromatography on a matrix of horse cytochrome c-Sepharose 4B. The success of this procedure, which employs a matrix previously found ineffective with beef or yeast oxidase, is attributed to thorough dispersion of the enzyme with nonionic detergent and a low density of cross-linking between the lysine residues of cytochrome c and the cyanogen bromide activated Sepharose. Beef heart oxidase is purified in one step from mitochondrial membranes solubilized with lauryl maltoside, yielding an enzyme of purity comparable to that obtained on a yeast cytochrome c matrix [Azzi, A., Bill, K., & Broger, C. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 2447-2450]. Rat liver oxidase is prepared by hydroxyapatite and horse cytochrome c affinity chromatography in lauryl maltoside, yielding enzyme of high purity (12.5-13.5 nmol of heme a/mg of protein), high activity (TN = 270-400 s-1), and very low lipid content (1 mol of DPG and 1 mol of PI per mol of aa3). The activity of the enzyme is characterized by two kinetic phases, and electron transfer can be stimulated to maximal rates as high as 650 s-1 when supplemented with asolectin vesicles. The rat liver oxidase purified by this method does not contain the polypeptide designated as subunit III. Comparisons of the kinetic behavior of the enzyme in intact membranes, solubilized membranes, and the purified delipidated form reveal complex changes in kinetic parameters accompanying the changes in state and assay conditions, but do not support previous suggestions that subunit III is a critical factor in the binding of cytochrome c at the high-affinity site on oxidase or that cardiolipin is essential for the low-affinity interaction of cytochrome c. The purified rat liver oxidase retains the ability to exhibit respiratory control when reconstituted into phospholipid vesicles, providing definitive evidence that subunit III is not solely responsible for the ability of cytochrome oxidase to produce or respond to a membrane potential or proton gradient.

Animals↗
PubMed1983

Experimental immunisation of lambs against pneumonic pasteurellosis.

Methods of immunising lambs against pneumonic pasteurellosis, caused by several serotypes of Pasteurella haemolytica, were assessed in specific pathogen free lambs. Lambs were vaccinated intramuscularly with sodium salicylate extract (SSE) of P haemolytica, either alone or in combination with heat-killed organisms (HKO). SSE of P haemolytica type A1 protected vaccinated lambs against pneumonia resulting from challenge with the homologous serotype. SSE of type A2 also provided some protection but this was improved by vaccination with a combination of SSE and HKO.

Animals↗
PubMed1982

Opiate receptor blockade in man reduces 2-deoxy-D-glucose-induced food intake but not hunger, thirst, and hypothermia.

Opioid peptides may act as neuromodulators in the central nervous system to conserve energy stores and water in mammals. To examine this hypothesis in man, the effect of opiate receptor blockade with naloxone on the hunger, thirst, and hypothermic response to 2-deoxy-D-glucose-induced glucoprivic stress was assessed. Opiate receptor blockade decreased stress-induced food intake but did not reduce marked increases in hunger produced by glucoprivation. Naloxone infusions did not change the hypercortisolemic, polydipsic, hypothermic, and thermogenic response to 2-deoxy-D-glucose. While these results do not suggest a major role for a beta-endorphin modulation of stress-induced hunger, hypothermia and water conservation, the reduction of food intake could be due to augmented satiety, perhaps associated with retardation of gastric emptying during opiate receptor blockade.

Blood Glucose↗
PubMed1982

The active form of cytochrome c oxidase: effects of detergent, the intact membrane, and radiation inactivation.

Cytochrome oxidase is a multisubunit, intrinsic membrane protein with a complex function that includes oxidation of cytochrome c, reduction of oxygen and generation of a membrane potential. To clarify the relationship of its normal function to protein and membrane structure, we have examined the kinetic behavior of rat liver cytochrome oxidase in the intact inner mitochondrial membrane and in detergent solubilized states. Dissolution of rat liver mitochondrial membranes alters the kinetic parameters of the oxidase in a manner dependent in part on the dispersing agent, and characterized by a large increase in maximal activity which is not attributable to exposure of more oxidase or diminished affinity for cytochrome c. The most profound effect of solubilization of the membrane is seen on the low affinity reaction of cytochrome c, suggesting that the electron transfer pathway from this site to oxygen is sensitive to alterations in hydrophobic interactions within the oxidase. Purified rat liver and beef heart oxidase exists predominantly in a monodisperse, 300 kilodalton form in laurylmaltoside (Rosevear et al., 1980). However, a smaller, 130 kd species that exhibits high turnover rates equal to the 300 kd form is detected in some beef heart preparations, implying that the dimer may not be essential for high activity. Radiation inactivation studies on purified oxidase reveal a molecular weight for the functional unit of approximately 70 kd. It is concluded that less than a complete set of subunits may be sufficient for both normal binding of cytochrome c and rapid electron transfer to oxygen.

Animals↗
PubMed1982

Beta-adrenergic blockade inhibits thermogenesis and lipolysis during glucoprivation in humans.

Glucoprivic stress induced by 2-DG (2-deoxy-D-glucose) is associated with increased oxygen consumption (thermogenesis) and sympathetic nervous system activity, as well as elevations of circulating levels of various hormones and metabolic substrates. To examine the role of beta-adrenergic stimulation in the thermogenic, hyperglycemic, and lipolytic responses to glucoprivation, we administered intravenous infusions of propranolol or normal saline (placebo) during 2-DG challenges in seven healthy males. 2-DG alone produced large increments in plasma catecholamine levels, hyperglycemia, a 3.5-fold increase in plasma free fatty acid (FFA) levels, a 15 beat/min increase in pulse rate, and hypothermia in spite of a 20% increase in oxygen consumption. When propranolol was given, 2-DG produced only a 50% increase in FFA levels, no change in oxygen consumption, and a 17 beat/min fall in pulse rate associated with a 25% increase in mean arterial blood pressure. Propranolol only slightly attenuated the hyperglycemia and hypothermia associated with 2-DG but potentiated the elevations of plasma epinephrine levels. It is concluded that 2-DG-induced thermogenesis and lipolysis are primarily dependent on beta-adrenergic stimulation.

Adolescent↗
PubMed1982

Abdominal surgery in patients undergoing long-term peritoneal dialysis.

Nineteen patients undergoing long-term peritoneal dialysis (LTPD) required abdominal operations--11 elective and 8 emergency. The preoperative hemoglobin level was 9.0 +/- 2.6 gm/dl, and the serum albumin was 28.8 +/- 4.9 gm/L. There was one death in the elective group (an inguinal herniorrhaphy) and four deaths in the emergency group (three spontaneous colonic perforations and one strangulated ventral hernia). Wound complications occurred in five patients. To obtain an indication of nutritional status of patients on intermittent LTPD and high-protein diets, 17 in-center patients underwent nutritional assessment, and deficiencies in delayed hypersensitivity skin testing and total lymphocyte counts were prevalent. Wounds require secure, watertight closure to prevent dialysis leakage. In elective abdominal surgery, LTPD should be carried out shortly preoperatively to delay dialysis for a few days after operation and to decrease defective platelet function. Preoperative transfusion for anemia is generally unnecessary. Drains should be avoided or removed before resumption of LTPD. Abdominal wall hernias should be repaired electively. Constipation should be avoided. Marked protein loss accompanies peritonitis. In certain instances, transfer to hemodialysis is indicated.

Abdomen↗
PubMed1981

Suppression of prolactin and growth hormone responses to 2-deoxy-D-glucose-induced glucoprivation by mazindol in humans.

Glucoprivation induced by 2-deoxy-D-glucose (2DG) 20 min infusions (50 mg/kg) increases growth hormone (GH) and prolactin (PRL) levels in humans. To determine if mazindol, a potent dopamine (DA) and norepinephrine (NE) reuptake blocking agent, might affect basal and stimulated GH and PRL levels in healthy male and female volunteers, mazindol (1 mg, TID,po) or placebo were administered for one week before 2DG infusions. Plasma samples for glucose, epinephrine (E), NE, PRL, and GH were collected before and after 2DG infusions. During placebo and mazindol therapy, basal values (ng/ml) did not differ for either PRL (8.8 +/- 1.6 versus 8.9 +/- 1.5 in females and 8.3 +/- 0.9 versus 7.7 +/- 0.6 in males) or GH (1.6 versus 1.7 +/- 0.1 in males and 6.6 +/- 3.3 versus 7.0 +/- 2.6 in females). Peak stimulated PRL levels were greater in females than in males (97.1 +/- 26.2 versus 21.4 +/- 5.3 ng/ml, p less than 0.05) while peak stimulated GH levels were greater in males than in females (28.2 +/- 1.7 versus 7.0 +/- 2.0 ng/ml, p less than 0.05). Mazindol therapy reduced 2DG-stimulated PRL responses (ng/ml) from 97.1 +/- 26.2 to 44.4 +/- 25.3 (p less than 0.0125) and from 21.4 +/- 5.3 to 13.6 +/- 3.4 (p less than 0.025) in females and males respectively, and GH responses (ng/ml) from 28.2 +/- 1.7 to 13.1 +/- 3.8 (p less than 0.05) and from 10.2 +/- 2.0 to 3.4 +/- 0.1 (p less than 0.05) in males and females respectively, but baseline PRL and GH levels were unaffected. A 50%-60% overall suppression of stimulated GH and PRL levels by mazindol was not significantly different between sexes and not consistently related to elevations in plasma glucose or E although stimulated plasma NE levels were higher during mazindol therapy.

Blood Glucose↗
PubMed1981

Increased thirst and plasma arginine vasopressin levels during 2-deoxy-D-glucose-induced glucoprivation in humans.

Insulin-induced hypoglycemia by unknown mechanism(s) increases plasma arginine vasopressin (AVP) levels in humans. Mechanisms for increased AVP levels during central nervous system glucoprivation were investigated by administering 20-min i.v. infusions of 2-deoxy-d-glucose (50 mg/kg), a competitive inhibitor of glucose utilization, or normal saline (sham), to 24 normal volunteers. Some of the infusions were administered in combination with neuropharmacological blocking agents (placebo). The behavioral, physiological, metabolic, and hormonal correlates of 2-deoxy-d-glucose (2DG)-induced gluco-privation and AVP secretion were studied in a group (n = 5) pretreated for 1 wk with either mazindol (1 mg per os three times per day), a potent norepinephrine and dopamine-reuptake blocker, or placebo. A second group (n = 5) received either propranolol (3 mg/3 min followed by 80 mug/min) or normal saline infusion before and during 2DG administration. With 2DG alone, plasma AVP levels increased from 1.3+/-0.3 pg/ml at base line to a peak of 4.5+/-1.4 pg/ml at 60 min and remained elevated for 150 min. From 30 to 180 min after 2DG administration, the 2DG-infused volunteers increased their water intake in comparison with sham-infused volunteers. Marked increases in epinephrine and slight increases in norepinephrine were associated with increases in plasma glucose and renin activity and decreases in plasma potassium. Plasma sodium and osmolality increased transiently and mean arterial pressure (MAP) fell. These changes, however, were small and inconstant and could not account for the observed increases in thirst and AVP levels. Pretreatment with mazindol prevented the decrease in MAP and the increase in plasma renin activity (PRA) following 2DG infusions without modifying increased thirst, water intake, or AVP responses to glucoprivation. Pretreatment with propranolol effectively blocked beta-adrenoreceptors as evidenced by increased MAP and plasma epinephrine, and abolition of the RPA increases during 2DG-induced glycoprivation, but did not suppress AVP and thirst responses. A cervical cord-sectioned patient lacking descending sympathetic out-flow had a potentiated thirst response to 2DG-induced glucoprivation in the absence of increases in sodium, catecholamines, and PRA. Thus 2DG administration activates mechanisms for increased thirst and AVP which are unrelated to changes in peripheral catecholamines, MAP, PRA, and osmolality.

Arginine Vasopressin↗
PubMed1980

Thermoregulatory and related responses to 2-deoxy-D-glucose administration in humans.

Hypothermia in humans during insulin-induced glucopenia has been largely attributed to impaired heat production. To further study the mechanism for hypothermia during glucoprivation six normal males were given 20-min intravenous infusions of 2-deoxy-D-glucose (2-DG), 50 mg/kg, a competitive inhibitor of glucose utilization. Oxygen and carbon dioxide exchange was measured to determine heat production by indirect calorimetry. Decreases in core temperature were initially associated with activation of mechanisms for heat loss such as sweating and hyperpnea 30-120 min after 2-DG infusion. Hypothermia persisted in spite of markedly increased plasma catecholamine, glucose, and free fatty acid levels from 60 to 180 min and increased heat production from 120 to 180 min after 2-DG infusion. Thus in contrast to the proposed mechanism for insulin-induced hypothermia, the hypothermia of 2-DG-induced glucoprivation is a consequence of increased heat loss and not of decreased heat production.

Adult↗