[Therapeutic attitude in Cushing's disease associated with empty sella turcica].
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Adrenalectomy↗
Biomedical subjects
J Sastre
Publications and source records attributed to J Sastre.
Significance of gamma-glutamyltranspeptidase in exocrine pancreatic amino acid transport.
The exocrine pancreas is rich in gamma-glutamyltranspeptidase (GGT, EC 2.3.2.2) and exhibits high rates of amino acid transport and protein synthesis. The role of the gamma-glutamyl cycle in mediating neutral amino acid transport in the isolated perfused rat pancreas was investigated using acivicin, an inhibitor of GGT, and a rapid dual isotope dilution technique. When treatment in vivo with acivicin (50 mg/kg) was followed 1 h later by continuous perfusion of the isolated pancreas with 10 microM acivicin, GGT levels decreased from 53 +/- 3 IU/g to 4.9 +/- 1.5 IU/g. This marked inhibition of GGT activity was not associated with decreased uptake for either L-alanine or L-glutamine, suggesting that the gamma-glutamyl cycle plays a negligible role in amino acid transport across the basolateral membrane of the pancreatic epithelium.
Alanine↗
Physiological changes in glutathione metabolism in foetal and newborn rat liver.
Glutathione metabolism was studied in isolated hepatocytes from foetal, newborn and adult rats. The GSH/GSSG ratio decreased 15-20-fold through the foetal-neonatal-adult transition. This was mainly due to an increase in GSSG. All enzyme activities involved in the glutathione redox cycle tend to increase during that transition, but the relative increases in glutathione peroxidase and glutathione S-transferase were 3-5 times those of glutathione reductase or glucose-6-phosphate dehydrogenase. GSH synthesis from methionine as a sulphur source was 6 times lower in foetal than in adult hepatocytes. However, when N-acetylcysteine was used as a sulphur donor to by-pass the cystathionine pathway, the rates of GSH synthesis were similar in foetal and adult cells. This is due to the fact that cystathionase activity in foetal cells is very low. This low activity is reflected in the blood amino acid pattern, where the concentration of cysteine rises from 8 to 52 microM from foetuses to adult rats. This supports the idea that cysteine may be an essential amino acid for the premature animal.
Aging↗
Inhibition of gluconeogenesis by extracellular ATP in isolated rat hepatocytes.
The aim of this study was to determine the effect of externally added ATP on gluconeogenesis by isolated hepatocytes from starved rats. High concentrations of extracellular ATP inhibited gluconeogenesis from lactate and pyruvate but not from glycerol or fructose. This inhibition was associated with an increase in intracellular adenosine contents. ADP, AMP, or adenosine but not guanosine 5'triphosphate, inosine 5' triphosphate, or adenine also inhibited gluconeogenesis. alpha, beta-Methylene-ATP, a nonmetabolizable structural analogue of ATP, did not affect the rate of gluconeogenesis. Intracellular ATP levels were increased by externally added ATP or adenosine, but ATP-to-ADP ratios in the cytosolic and mitochondrial compartments were diminished. Malate and phosphoenolpyruvate contents were decreased by extracellular ATP or adenosine. Our results show that inhibition of gluconeogenesis by high levels of extracellular ATP may be mediated by adenosine derived from ATP catabolism at the plasma membrane.
Adenosine Diphosphate↗
Age-related changes in glutathione synthesis in the eye lens.
Eye lenses from young rats or mice synthesize GSH from methionine or N-acetylcysteine. However, lenses from old animals do not synthesize GSH from methionine. This is due to the absence of cystathionase activity in old lenses. GSH monoethyl ester, but not free GSH, increases GSH content and protects the lens against experimental oxidative stress. The importance of these results in the prevention of cataractogenesis is discussed.
Acetylcysteine↗
Neutrophil chemotactic activity in toluene diisocyanate (TDI)-induced asthma.
We quantitated serum neutrophil chemotactic activity (NCA), which is associated with mast cell or basophil activation, to determine if mast cell or basophil mediators are released during bronchoprovocation-inhalation challenge with subirritant levels of toluene diisocyanate (TDI). Four subjects with suspected TDI-induced asthma and four mite-sensitive subjects with asthma who served as a comparison group were studied. NCA was measured in a multiwell, microchemotaxis chamber. Blood samples were collected, and FEV1 measurements were performed before challenge and at regular intervals during the subsequent 24 hours. Three of four workers clinically sensitive to TDI reacted to a subirritant TDI exposure. There was no increase in NCA during placebo challenges. NCA increased in the three TDI-sensitive workers during early and late asthmatic reactions in quantities proportional to the FEV1 decline. No increase in NCA was found during TDI exposures in the TDI-negative worker. Gel filtration analysis demonstrated the main NCA fraction eluted with macromolecules of an estimated molecular weight greater than 440,000 daltons. This characteristic is compatible with neutrophil chemotactic factor of basophil or mast cell origin. The kinetics of NCA release were similar in mite- and TDI-induced asthmatic reactions. A high correlation (r = 0.97; p = 0.0006) was obtained between the percent decrease in FEV1 during early asthmatic reactions and percent increase in NCA. These observations support the hypothesis that activation of mast cells or basophils is associated with TDI-induced early and late asthmatic reaction.
Animals↗
Respiratory and immunological reactions among Shiitake (Lentinus edodes) mushroom workers.
Four workers, the total work force employed at a Shiitake farm, developed cough and sputum production following a variable period of exposure to Shiitake mushrooms. All four had abnormal diffusing capacity and three had abnormal spirometry values. Chest roentgenograms demonstrated an interstitial pattern in one worker. Pulmonary function tests performed before and during several days of work demonstrated a significant decrease (greater than 20%) in forced vital capacity (FVC) and/or maximal mid-expiratory flow (MMEF) in three workers. Although specific antibodies to an extract of Shiitake spores were detected in sera from three workers none were IgE. High levels of Shiitake spores were detected in growing rooms (greater than 10(6)/m3) as well as other locations at the farm. Shiitake spore airborne antigen, detected by an immunochemical assay, was present in dust collected with a volumetric sampler from different locations at the farm. Antigenic determinants of Shiitake spore antigens, in common with antigens from other cultivated mushrooms (Agaricus and Pleurotus) were demonstrated by ELISA inhibition assay. This study demonstrates that workers exposed to high levels of Shiitake spores develop symptoms and laboratory findings suggestive of hypersensitivity pneumonitis (HP). Strict environmental control and the wearing of a face mask is probably needed to reduce the high risk of sensitization and possible development of immunological lung disease. Shiitake spores must be considered as an aetiological agent of mushroom workers' lung.
Agricultural Workers' Diseases↗
Glutathione depletion by hyperphagia-induced obesity.
Reduced glutathione (GSH) levels in freeze-clamped livers of rats and mice in which hyperphagia is induced by cafeteria diet are 45% lower than in controls. Freshly isolated hepatocytes from mice fed cafeteria diet show a 45% decrease in GSH concentration and a 54% decrease in oxidized glutathione (GSSG) concentration when compared with controls. The rate of GSH synthesis in isolated hepatocytes from control mice is significantly higher than in those from mice fed cafeteria diet. Oral GSH is effective to prevent the decrease in hepatic GSH levels found in cafeteria fed mice.
Animals↗
Role of inhalation challenge testing in the diagnosis of isocyanate-induced asthma.
Results of isocyanate challenge tests performed on 63 workers referred with a diagnosis of probable isocyanate asthma between 1974 and 1988 were reviewed. Thirty (48 percent) had an acute episode of asthma with a greater than 20 percent decline in FEV1 following subirritant exposure to isocyanates. No difference in the frequency or type of respiratory complaints between isocyanate reactors and nonreactors was found. No differences in lung function results were present when comparing smoking and ex-smoking reactors and nonreactors. In never-smokers with complaints consistent with isocyanate-induced asthma, the presence of obstructive lung disease increased the likelihood that isocyanate-induced asthma was present. Bronchial responsiveness to methacholine occurred in nearly all isocyanate reactors but predicted isocyanate-induced asthma in only 68 percent of the workers. In nearly all cases of challenge-confirmed toluene diisocyanate (TDI)-induced asthma, a 15-min exposure to 20 ppb of the commercial TDI mixture (80:20 2,4:2,6) provoked asthma. Conversely, in the absence of an asthmatic response following exposure to this dose for this duration, a second exposure at this concentration for a longer time would be reasonable to confirm the absence of isocyanate-induced asthma. Among workers employed in the production of polyurethane foam and confirmed to have TDI-induced asthma by inhalation challenge to the different TDI isomers, there appeared to be increased airway reactivity to the 2,6 isomer. This may have relevance to the frequency and intensity of respiratory symptoms that workers with TDI-induced asthma develop in differing industrial settings.
Adult↗
Identification and analysis of basidiospore allergens from puffballs.
Spore extracts from four common puffballs (Calvatia cyathiformis, Geaster saccatum, Pisolithus tinctorius, and Scleroderma areolatum) were fractionated by Sephadex G-75 gel filtration. Pooled fractions, analyzed by skin test or direct RAST, contained allergenic components over a molecular weight range of 10,500 to 20,000 daltons for all puffball spores studied except for S. areolatum (greater than 70,000 daltons). The Sephadex G-75 allergenic pool of C. cyathiformis was further fractionated by hydrophobic interaction chromatography. Fractions were successively eluted with 4 and 1 mol/L buffered saline solutions and water. The 1 mol/L fraction contained maximal allergenic activity as determined by RAST-inhibition studies. At least 15 Coomassie blue staining bands were identified after isoelectrofocusing, of which 7 were shown by immunoprinting to bind IgE from a serum pool of five patients with allergy. Our results demonstrate that a combination of gel filtration, hydrophobic interaction chromatography, RAST-inhibition, and immunoprinting studies can be used to fractionate, characterize, and standardize spore allergen extracts of puffballs for diagnostic and therapeutic purpose.
Allergens↗
Pulmonary ceroidosis.
We describe a patient with pulmonary ceroid histiocytosis. Skin pigmentation, chest x-ray film and laboratory findings were normal. Only pulmonary function tests were abnormal (TLC = 63 percent, DLco = 52 percent). Based on these functional data, the patient was submitted to a lung biopsy by thoracotomy. Brown pigmented histiocytes were shown occupying alveolar spaces. Similar brown pigmented hepatocytes were seen in the liver biopsy.
Adult↗
Use of 11C-triphenylmethylphosphonium for the evaluation of membrane potential in the heart by positron-emission tomography.
The membrane potential in cells can be estimated by electrophysiological techniques and biomedical methods using lipophilic cations labelled with 14C. However, these techniques cannot be applied to the human heart. In this study a lipophilic cation, triphenylmethylphosphonium (TPMP), was labelled with carbon-11 with the purpose of investigating its suitability for the estimation of membrane potential in vivo. A biodistribution study in mice and rats showed significant uptake of the cation in the heart a few minutes after IV injection which remained constant for 60 min. In vivo study by positron-emission tomography showed that after IV injection of 11C-TPMP in the dog, activity rose almost immediately in the myocardium and then remained constant for 60 min. A rapid injection of KCl (greater than 40 mg/kg) 20 min after injection of 11C-TPMP led to an instantaneous fall in myocardial 11C-TPMP concentration. Membrane potential (delta psi), calculated from the TPMP distribution ratio between intracellular and plasma water space by the Nernst equation, was estimated at -148.1 +/- 6.0 mV for the dog heart. This value reflected both cell membrane potential and mitochondrial membrane potential and, thus, the energy state of the myocardial cells.
Animals↗
Visualization by positron emission tomography of the apparent regional heterogeneity of central type benzodiazepine receptors in the brain of living baboons.
The feasibility of visualizing the heterogeneity of benzodiazepine (BDZ) receptors in the brain of living baboons was investigated using Positron Emission Tomography. Ethyl 8-fluoro-5,6-dihydro-5-methyl 6-oxo-4H-imidazo (1,5-a) (1, 4) benzodiazepine-3-carboxylate (RO 15 1788) labelled by carbon 11 (11C-RO 15 1788) was I.V. injected for the "in vivo" labelling of the central type BDZ receptors. Displacement experiments were performed 20 minutes after the administration of the radioligand by two different cold drugs: RO 15 1788 which has an equal affinity for central type BDZ receptors, and propyl B-Carboline-3-carboxylate (B-CCP) which favours the sites located in the cerebellum. Different sensitivities to these two drugs displacement of 11C-RO 15 1788 binding "in vivo" were observed: on the one hand in the regional localization of the displacement, and on the other hand, in the amount of the radioactivity displaced. The apparent interregional heterogeneity of the displacement seen in the cerebellum and in the temporal cortex are discussed in terms of discrepancies observed "in vitro" at physiological temperature, between cerebellar and non-cerebellar BDZ central type binding sites.
Animals↗
Pheochromocytoma and asthma.
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Adrenal Gland Neoplasms↗
Central type benzodiazepine binding sites: a positron emission tomography study in the baboon's brain.
An in vivo characterization of specific central type benzodiazepine (BZD) binding sites, labelled with [11C]Ro 15-1788 was performed, using positron emission tomography. After i.v. injection of 10 mCi [11C]Ro 15-1788 (corresponding to 1 nmol/kg), sequential quantitative tomographic slices of the brain were obtained during 80 min. In some experiments various doses of different cold drugs (BZD agonist or antagonist) were injected i.v. subsequently in order to explore the specificity of the binding of the radioligand in brain structures. The main criteria usually utilized in vitro to demonstrate a specific binding to receptors, such as regional distribution, stereospecificity and saturability of the binding and pharmacological effect linked to the receptor's occupancy, were demonstrated in the brain of a living baboon.
Animals↗
llC labelling of a protein: concanavalin A.
A method is described for the 11C labelling of a phytoagglutinin, concanavalin A, involving reductive methylation by formaldehyde and sodium cyanoborohydride. The reaction mixture is then chromatographed by gel permeation. The quantities (20-80 mCi) and specific activities (20-170 mCi/mg) obtained are such that a practical application of the method is possible. No evidence was found, however, of any preferential uptake of concanavalin A by Krebs II ascite cells in Swiss mice.
Animals↗
Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine-3-carboxylate (RO 15.1788-11C): a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography.
A method of labelling ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate (RO 15.1788 11C), a benzodiazepine antagonist with carbon-11 has been developed. RO 15.1788-11C was prepared by methylation of the nor derivative by I11CH3. About 100 mCi (maximum 153 mCi, 5.66 GBq) of the chemically and radiochemically pure labelled product were obtained within 25 min with a specific activity on average of 1100 mCi/mumol (maximum 1740 mCi/mu mol--64.4 GBq/mu mol). Preliminary results obtained after i.v. administration in the baboon have shown RO 15.1788-11C to be of interest as a benzodiazepine radioligand for the in vivo study of benzodiazepine receptors by positron emission tomography.
Animals↗
Transmethylation reactions in human basophils induced by anti-IgE or specific antigen.
The activation of methyl transferases in the membrane of human basophilic leukocytes was measured by incorporation of 3H-methyl groups into phospholipids. Basophils of healthy individuals were activated by anti-IgE, those of pollen allergic patients by the specific antigen, Lolium perenne extract. Basophil-rich fraction was obtained from peripheral blood by centrifugation in a gradient of Ficoll/metrizamide (g = 1.085). After incubation with anti-IgE an increase in the 3H-methyl incorporation was detected during the first 30 s of the reaction. The maximal incorporation in basophils of the pollen allergic patients, activated by L. perenne extract, was enhanced at 15 s. Appropriate controls showed that the activation of methyl transferases occurred in basophils only.
Animals↗