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Biomedical subjects

A Schuster

Publications and source records attributed to A Schuster.

At least 91 records · Page 5Linked to original sources

Influence of short- and long-term inhalation of salbutamol on lung function and beta 2-adrenoceptors of mononuclear blood cells in asthmatic children.

Clinical observations have shown that some asthma patients develop tachyphylaxis to beta-sympathomimetic drugs. As down-regulation of the number of beta-adrenoceptors in different human tissues after exposure to catecholamines and beta-adrenergic drugs is well known, we investigated whether a interrelation exists between beta-adrenoceptor down-regulation and clinically detectable beta-adrenergic subsensitivity during beta-sympathomimetic treatment. The following results were obtained: 1. beta 2-Sympathomimetic inhalation treatment with salbutamol in therapeutic doses led to a significant down-regulation of beta 2-adrenoceptors and consecutive cyclic adenosine monophosphate response to isoprenaline. This effect was already detectable after short-term treatment of 3-7 days in 9 asthmatic children. 2. In the long-term study over 6 months, salbutamol inhalation in 12 asthmatic children led to a significant down-regulation of beta-adrenoceptor binding sites on mononuclear blood cells (MNC) from 1539 +/- 91 to 1115 +/- 99 after 14 days, remaining in this range thereafter. 3. The mean airway resistance (Raw) of these 12 patients decreased significantly within 14 days from 8.1 +/- 0.8 to 5.7 +/- 0.5 cm H2O/l/s to remain stable throughout the 6 months of salbutamol treatment. The differences in Raw before and immediately after inhalation of 0.2 mg salbutamol (2 puffs) were unchanged during the study period. It is concluded, that long-term inhalative treatment with salbutamol over a period of 6 months does not result in refractoriness to beta-adrenergic drugs in the airways of asthmatic children, even though a significant down-regulation of beta 2-receptors on peripheral MNC occurs.

Administration, Inhalation↗

Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells.

In reticulocytes, the enzyme 15-lipoxygenase (15-LO) is believed to contribute to cellular differentiation, and in leukocytes and airway cells 15-LO generates inflammatory mediators. The recent availability of antibodies to 15-LO now allows us to determine which specific cells contain the enzyme, to characterize its subcellular localization, and to determine its expression at the translational level. A polyclonal antibody to recombinant human reticulocyte 15-LO was used with a standard immunofluorescent technique. In rabbit red blood cells, fluorescence appeared during the course of anemia. Early reticulocytes did not fluoresce, but more mature reticulocytes showed increased fluorescent intensity. Late reticulocytes contained little fluorescence. Among human leukocytes, only eosinophils fluoresced. In human trachea, 15-LO immunofluorescence was localized to epithelial cells, and both basal and ciliated cells fluoresced. In all cells studied, fluorescence was localized to the cytoplasm and was variable in degree among cells in each preparation. We conclude that the 15-LO of airway cells and eosinophils is immunologically related to the reticulocyte 15-LO. Furthermore, the variable fluorescence among cells (e.g., in epithelium) and during development (e.g., reticulocytes) suggests a role of 15-LO in cell growth and development.

Animals↗

[Diagnosis of lung sarcoidosis in the hospital].

To confirm the diagnosis of sarcoidosis a characteristic X-ray and a positive histologic pattern is essential. In most cases one can get the histology by a rather simple bronchoscopy. In cases of negative bronchoscopic findings one should perform a mediastinoscopy, which can be done by an expert thoracic surgeon almost on outpatient basis. In rare cases the final diagnostic step is the open lung biopsy, preferably done on the right thoracic side, as the lung transplanting surgeons recommend for a possible lung transplant the left side.

Adult↗

Solubilization of multilamellar liposomes of egg yolk lecithin by the bile salt sodiumtaurodeoxycholate and the effect of cholesterol--a rapid-ultrafiltration study.

The solubilization of multilamellar egg yolk lecithin liposomes by sodiumtaurodeoxycholate in aqueous phase was studied by ultrafiltration as a function of time, bile salt and cholesterol concentration. The corresponding equilibrium states were analysed. Complete solubilization was achieved at total bile salt/lecithin molar mixing ratios of approximately 5. The minimum ratio to start solubilization was 0.1, corresponding to a free bile salt concentration of only 5% of the critical micelle concentration (CMC). Mean equilibrium constants for the partition of bile salts between non-filterable aggregates and filterable mixed micelles and also the free bile salt concentration were determined. Sodiumtaurodeoxycholate had a higher affinity for small mixed micelles than for lamellar mixed aggregates especially in the presence of cholesterol, which reduces the degree and rate of the solubilization process. A non-homogeneous distribution of bile salts in the lipid phase was detected at low bile salt concentrations.

Bile Acids and Salts↗

Pain in newborns and prematures: current practice and knowledge.

No unambiguous answer can be given as to whether newborns are able to feel pain similar to that experienced by older children and adults. However, there are several lines of evidence--anatomical, physiological and behavioral--which substantiate the possible presence of distressing nociceptive activity in the full-term and preterm neonate. Although the efficacy and safety of anesthesia in newborns and prematures has repeatedly been demonstrated, there are still numerous recommendations and current practices, based on antiquated theories, that withhold adequate medications from neonates during surgery. Even if the emotional and cognitive aspects of nociception in the newborn remain a subject of speculation giving rise to philosophical discussions as to the correct terminology, it is the mandate of newborns' physicians to provide the best possible therapy to their patients and to protect them from distress, unease and presumptive pain.

Humans↗

Evaluation of experimental combined toxicity by use of dose-frequency curves: comparison with theoretical additivity as well as independence.

Dose-frequency curves of toxic effects of a substance A were evaluated in the absence and in the presence of a fixed dose of a second substance B. Data were fitted by the curve-fitting program ALLFIT. Observed combined frequencies of A + B were compared statistically with the expected frequencies of additivity and (or) independence by the phi 2-square goodness-of-fit test. The theoretical dose-frequency curves expected for an additive response were obtained by a solely graphical procedure and the theoretical curves for independent effects were calculated from the effects of B and A at certain doses. In rotarod tests with trained mice, the combined deteriorating effect of ethanol and benzodiazepines were significantly over-additive. However, their lethal interaction appeared underadditive in mice. The lethal underadditive interaction of ethanol and phencyclidine (PCP) can be ascribed largely to independent actions of these compounds. Loss of righting reflex was additively enhanced by PCP, whereas PCP overadditively enhanced the effect of ethanol. The insecticidal action of the cholinesterase inhibitors malathion and parathion appeared additive and significantly different from independent interaction. A comparison of results from dose-response curves with isoboles showed good agreement. The method appears as an attractive alternative or as a complementary procedure to the isobolographic analysis. Combination experiments as described can be carried out and evaluated rather simply, with a minimum of expenditure and a maximum of information.

Animals↗

[Urological aspects of non-urological tumor in the lesser pelvis].

The surgical outcome in 30 patients with advanced pelvic malignancies of nonurological origin infiltrating the urinary tract was analyzed. The pelvic mass was totally removed by multivisceral resection in 15 patients, and incompletely removed in 11 patients; 4 patients underwent only palliative treatment in the form of urinary diversion, because of unresectable tumors. Mortality, morbidity, survival rates and quality of life were evaluated and showed significant differences. The best results were achieved in the group with complete excision of pelvic viscera. Patients treated with incomplete resection or palliative urinary diversion because of unresectable mass had a poor outcome.

Colorectal Neoplasms↗

The adrenergic system in lymphocytes from children with cystic fibrosis.

Several in vivo and in vitro studies have suggested that children suffering from cystic fibrosis (CF) might have a general defect of beta-adrenoceptors on the cell surface which might account for an unbalanced secretory process. In order to investigate if this view holds true, we determined the beta-adrenoceptor density and affinity on lymphocytes by means of radioligand studies using 125-iodo-cyano-pindolol (125-ICYP) in 20 children with CF. Cyclic AMP (cAMP) response was also investigated after specific beta-adrenoceptor stimulation with isoprenaline (IPN) and after direct stimulation of the adenylate cyclase with forskolin in lymphocytes. Children with CF and controls have identical numbers and affinities of beta-adrenoceptors on lymphocytes. The cyclic AMP response was identical in CF- and in age-matched control children regardless whether adenylate cyclase was stimulated directly or via beta-adrenoceptors. In conclusion, the data support the view that no general adrenoceptor or adenylate cyclase defect exists in CF. As several studies have found abnormal reactions to adrenergic stimuli in CF patients, we presume that there is a defect beyond the level of adrenergic receptors and cAMP which remains to be identified.

Adenylyl Cyclases↗

Status of plasma and erythrocyte fatty acids and vitamin A and E in young children with cystic fibrosis.

The fatty acid (FA) status in young children with cystic fibrosis (CF) was investigated. The FA composition of the plasma cholesterol esters (CE) and phospholipids (PL) and of the erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was estimated in 11 patients with CF and pancreatic insufficiency (median age, 3.0 years; range, 3 months to 7 years) and in 10 age-matched controls. Linoleic acid values ranged widely but were not significantly reduced in the patients. However, arachidonic acid (20:4w6) and docosahexaenoic acid were decreased in all lipid classes. The ratio of dihomo-gamma-linoleic acid to arachidonic acid (20:3w6/20:4w6) was significantly increased in the patients, indicating an impairment of FA metabolism (delta 5-desaturation). Plasma retinol concentrations were normal and did not differ between the supplemented patients and controls. Plasma total tocopherols and alpha-tocopherol and their ratios to total lipids were significantly reduced in the CF patients, but all values were within the normal ranges for the pediatric age group, and no child met the criterion for vitamin E deficiency.

Child↗

[Plasma cell granuloma of the lung and mediastinum in a ten year old girl].

A ten-year-old girl presented with an asymptomatic tumor of the lung. X-ray morphology suggested malignancy. Laboratory investigations revealed hypochromic anaemia, strong signs of inflammation, and hypergammaglobulinaemia. By means of surgery the tumor was completely removed. Histologic analysis established the diagnosis of a plasma cell granuloma. Postoperatively, laboratory parameters normalized. During the follow-up period of now 30 months there has been no relapse.

Child↗

Structure and thermodynamics of the dihexadecylphosphatidylcholine-water system.

X-ray small- and wide-angle diffraction, differential scanning calorimetry (DSC), temperature scanning densitometry (TSD) and electron microscopy were used to study the lyotropic and thermotropic properties of the system 1,2-O-dihexadecyl-sn-glycero-3-phosphocholine-water over a wide range of compositions from the dry lipids to a large excess of water, and in the temperature range between 0 degrees C and 150 degrees C. The results were used to construct a temperature-composition phase diagram. The phases have been characterized with respect to their molecular arrangements and hydrocarbon chain packing subcells. In the fully hydrated state (greater than 45 wt% H2O) four thermotropic phases were found, with readily reversible transitions at 5 degrees C, 32.5 degrees C and 43.6 degrees C, respectively. The two lower temperature phases deviate from all others in consisting of bilayers with fully interdigitated hydrocarbon chains, while above 32.5 degrees C the structures resemble closely those of the analog diester lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). At hydrations between 30 and 45 wt% H2O, and below 32 degrees C, interdigitated and non-interdigitated multilayers coexist in one coherent phase. A bilayer tilting mechanism is proposed for the formation of this coexistence of two regular structures. Below 30 wt% H2O, hydrated 1,2-O-dihexadecyl-sn-glycero-3-phosphocholine (DHPC) exists in lamellar, non-interdigitated bilayers, showing very weak interbilayer swelling. There, the water molecules appear to occupy voids between the polar headgroups.

Calorimetry, Differential Scanning↗

Thermal phase behaviour and structure of hydrated mixtures between dipalmitoyl- and dihexadecylphosphatidylcholine.

Mixtures of 1,2-dipalmitoyl- and 1,2-O-dihexadecyl-sn-glycero-3-phosphocholine (DPPC and DHPC) in dispersion with excess water were studied by differential scanning calorimetry (DSC) and X-ray diffraction techniques. The transition parameters of the main gel-to-liquid crystalline transition show a monotonous dependence on the composition, indicating ideal miscibility of the two lipids, in keeping with the closely similar structures of the pure, hydrated lipids in the P beta' and L alpha states. The pre-transition shows a depression to a minimum temperature of 23 degrees C occurring around equimolar mixtures. Below the pre-transition temperatures, the L beta' gel phase of DPPC maintains bimolecular structure up to DHPC admixtures of 50 mol%, with adaptations in hydrocarbon chain packing and multilayer periodicity. On the side of DHPC, the interdigitated gel structure shows full solubility for DPPC up to equimolarity without major structural changes. The crystalline Lc-phase of DPPC exhibits immiscibility with DHPC, demonstrated by the fact that the subtransition is abolished already at less than 15 mol% DHPC. DHPC, below its subtransition, can accommodate up to 50 mol% DPPC within an interdigitated layer structure with unperturbed, crystalline hydrocarbon chain packing.

1,2-Dipalmitoylphosphatidylcholine↗

Role of lipid peroxidation in the toxicity of T-2 toxin.

Recent reports suggest that lipid peroxidation may be involved in the toxicity of T-2 toxin. In the present study the influence of T-2 toxin on two parameters of lipid peroxidation was examined: the formation of thiobarbituric acid reactive material in isolated hepatocytes and liver homogenates from rats and ethane exhalation in vivo. In isolated hepatocytes there was no significant increase in thiobarbituric acid reactive material, neither after addition of T-2 toxin in vitro nor when the toxin had been applied to the rats 15 hr before preparation of hepatocytes. In liver homogenates the amount of thiobarbituric acid reactive material was increased up to 50% over the controls, depending on the dose of T-2 toxin. The increased values are difficult to interpret, because the extent of the increase depends on the method used for determination of thiobarbituric acid reactive material. Measuring another parameter of lipid peroxidation, i.e. ethane exhalation, there was no difference between the T-2 toxin treated rats and the controls whereas carbon tetrachloride treated rats exhaled high amounts of ethane. These results suggest that lipid peroxidation does not play a major role in T-2 toxin toxicity.

Animals↗

A Low Molecular Weight Polypeptide Which Accumulates upon Inhibition of Porphyrin Biosynthesis in Maize.

Levulinic acid, an inhibitor of porphyrin biosynthesis, causes marked accumulation of a low molecular weight polypeptide in greening maize (Zea mays L.) leaves. Additional compounds which interfere with porphyrin synthesis (e.g. aminooxyacetate, iron-chelators, 4,6-dioxoheptanoic acid) had a similar effect. The polypeptide accumulated in the cytosol and could not be detected in the plastid stroma. Its molecular weight was estimated as 4800 daltons by electrophoresis in sodium dodecyl sulfate-acrylamide gels containing urea and glycerol. The accumulation of the polypeptide did not result from inhibition of chlorophyll or protoheme syntheses. Compounds which caused its accumulation markedly reduced the activity of nitrite reductase. It is suggested that the accumulation is caused by inhibition of siroheme synthesis which interferes with the formation of nitrite or sulfite reductase.

Journal Article↗

Affinity of various ligands for benzodiazepine receptors in rat cerebellum and hippocampus.

The structure-affinity relationship of benzodiazepine receptor ligands for binding to their receptors was investigated by measuring the potency of 41 benzodiazepines or benzodiazepine analogues and of 9 non-benzodiazepines for inhibition of [3H]flunitrazepam binding to cerebellar or hippocampal membranes. It was found that a chloro or a fluoro substitutent in position 2' enhanced whereas substituents in position 3 and substituents larger than a methyl group in position 1 of the benzodiazepine ring system reduced the potency of benzodiazepines for inhibition of [3H]flunitrazepam binding in cerebellum or hippocampus. In addition, several benzodiazepines could be identified which have a higher affinity for benzodiazepine receptors in cerebellum than for those in hippocampus. A selectivity of benzodiazepines for their receptors in cerebellum seems to be caused not only by certain substituents in position 1 but also by a chloro group in position 2' and together with this substituent by a hydroxy group in position 3.

Animals↗