[Pharmacologic characterization of formoterol in comparison with isoprenaline, fenoterol and salbutamol in tracheal muscle strips and lung membranes of the guinea pig].

In severe asthma attacks, beta 2-sympathomimetics can lose part of their therapeutic potency possibly due to a predominance of contractile mediators. To elucidate this loss of potency, we chose tracheal smooth muscle strips as experimental model which were partially and maximally precontracted with 100 and 6,000 nmol/l carbachol, respectively, reflecting different contractile states of the smooth muscle strips. Both contractures were dose-dependently relaxed by fenoterol and salbutamol which are well established as beta 2-sympathomimetics, by a new compound (formoterol) and by isoprenaline as standard.

Does pertussis infection induce manifestation of allergy?

To evaluate whether pertussis induces the development of allergy, a prospective study was performed in 25 children aged 0.8-12.2 years.

Nidogen mediates the formation of ternary complexes of basement membrane components.

Using a recombinant nidogen we have probed the calcium binding potential of various nidogen domains, examined the binding of nidogen to various basement membrane proteins and assessed the ability of nidogen to mediate the formation of ternary complexes between laminin and heparan sulfate proteoglycan and collagen IV and laminin. The results of these experiments indicate that the Ca+2 binding is on the rod-like domain with additional binding observed on the N-terminal G1 domain. With regard to the role of nidogen in mediating complex formation among basement membrane components it was demonstrated that nidogen effectively promotes the formation of a ternary complex between laminin and collagen IV, with both of these components interacting independently with nidogen.

Dose-dependent effect of growth hormone therapy on glucose metabolism in subjects with Turner syndrome. The German Lilly Ullrich-Turner Syndrome Study Group.

Recombinant human growth hormone (GH) is effective in promoting growth velocity in subjects with Turner syndrome. As higher doses are used for this indication than for substitution therapy in GH deficiency, the long-term effects of GH therapy on carbohydrate metabolism represent a safety issue; this is particularly important in Turner syndrome, in which there is an increased prevalence of impaired glucose tolerance. So far, GH therapy has been given to patients with Turner syndrome for up to 7 years without any significant changes having been reported in glycosylated haemoglobin (HbA1c) values, unstimulated and stimulated oral glucose tolerance test (OGTT) blood glucose and serum insulin concentrations.

Glutathione homeostasis in rats chronically treated with ethanol. Evidence for an increased hepatic GSH export in vivo.

The influence of chronic ethanol feeding to rats on the hepatic glutathione (GSH and GSSG) system (synthesis, catabolism, export) and on the GSH and GSSG concentrations in extrahepatic tissues was investigated. Histological examination of livers from ethanol pretreated rats revealed a minor dilatation of the hepatic sinusoids. After ethanol administration the distribution pattern of gamma-glutamyltranspeptidase (enzymehistochemistry) was nearly unchanged, but the hepatic activity of this enzyme was increased.

Atrial natriuretic peptide is phosphorylated by intact cells through cAMP-dependent ecto-protein kinase.

Recently we demonstrated the presence of cell-surface-located cAMP-dependent protein kinase (ecto-PK A) activity in a number of different cell types [Kübler, D., Pyerin, W., Bill, O.

Formoterol, fenoterol, and salbutamol as partial agonists for relaxation of maximally contracted guinea pig tracheae: comparison of relaxation with receptor binding.

In severe asthma attacks beta 2-sympathomimetics lose part of their therapeutic efficiency. To elucidate this loss of efficiency in an experimental model we compared the relaxant potency of salbutamol (SAL), fenoterol (FEN), formoterol (FOR), and (-)-isoprenaline (ISO) in guinea pig tracheae partially and maximally precontracted by 0.1 and 60 mumol/L carbachol, respectively.

Beta-adrenoceptor density on mononuclear leukocytes and right atrial myocardium in infants and children with congenital heart disease.

Sympathetic regulation of myocardial performance has been shown to be altered in congestive heart failure. Right atrial tissue of children with severe acyanotic and cyanotic congenital heart disease (CHD) showed a significantly lower beta-receptor density than that of children with less severe defects. Since mononuclear leukocytes (MNL) contain a homogeneous population of beta 2-adrenoceptors which have similar properties to those of cardiac beta 2-adrenoceptors, they are frequently used for studying the beta-adrenergic system.

[Pharmacokinetics and pharmacodynamics of twice-daily unequal administration of theophylline retard pellets in children of various age groups].

To assess the pharmacokinetic parameters of theophylline (Euphylong as retard pellets) children were studied belonging to age groups between 9 to 13 and 5 to 9 years in twice-daily dosage with unequal distribution of the daily doses. For the older children the dose was 400 + 200 mg and for the younger ones 300 + 150 mg theophylline (these quantities represent the evening and morning doses). 16 and 14 children, respectively, completed the studies regularly.

Recombinant nidogen consists of three globular domains and mediates binding of laminin to collagen type IV.

Recombinant mouse nidogen and two fragments were produced in mammalian cells and purified from culture medium without resorting to denaturing conditions. The truncated products were fragments Nd-I (positions 1-905) comprising the N-terminal globule and rod-like domain and Nd-II corresponding mainly to the C-terminal globule (position 906-1217). Recombinant nidogen was indistinguishable from authentic nidogen obtained by guanidine dissociation from tumor tissue with respect to size, N-terminal sequence, CD spectra and immunochemical properties.

Analysis and cloning of the ethylene-forming enzyme from tomato by functional expression of its mRNA in Xenopus laevis oocytes.

The last step in biosynthesis of the plant hormone ethylene, oxidation of 1-aminocyclopropane-1-carboxylic acid (ACC), is catalysed by the elusive ethylene-forming enzyme (EFE). EFE is induced by fungal elicitors in suspension-cultured tomato cells. We demonstrate that Xenopus laevis oocytes injected with RNA from elicitor-treated tomato cells gain the ability to convert ACC to ethylene.

Myocardial beta-adrenoceptor density and the distribution of beta 1- and beta 2-adrenoceptor subpopulations in children with congenital heart disease.

Twenty-six infants and children with congenital heart disease (CHD) undergoing cardiac surgery were investigated for alterations in myocardial beta-adrenoceptor density. The patients were divided into three groups according to type and severity of CHD: group I consisted of 6 patients with acyanotic shunt lesions of moderate severity; group II comprised 13 children with severe acyanotic shunt and valve lesions and group III included 7 children with cyanotic CHD. The myocardial beta-adrenoceptor density was determined using (-)3-[125I]Iodocyanopindolol [( 125I]ICYP) and was reduced by approximately 50% in severe acyanotic CHD (33.

Inhibition of in vitro differentiation of human monocytes to macrophages by lipopolysaccharides (LPS): phenotypic and functional analysis.

Blood monocytes (MO) undergo maturation into macrophages (MAC) upon migration from the capillary bed to tissue sites of inflammation where they are exposed to environmental signals. Functional competence and phenotype heterogeneity is the result of both differentiation-inducing and -activating events. In vitro, MO to MAC maturation is induced by serum factors, can be followed by the expression of specific maturation-associated antigens and is accompanied by a characteristic change in the secretory repertoire of MAC in comparison to MO.

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.

Polysaccharides from Peptostreptococcus anaerobius and structure of the species-specific antigen.

The cell-envelope antigens of Peptostreptococcus anaerobius were extracted from intact cells by autoclave or alkaline treatment. The purified species-specific antigen (G) was identified among several polysaccharides obtained from the extracts by successive treatments with ribonuclease and pronase followed by ion-exchange and gel-filtration chromatography. G was investigated by 13C- and 31P-n.

[IgG subclasses in healthy children and in children with frequent respiratory tract infections].

A group of 130 children presenting with frequent respiratory tract infections was examined for serum levels of IgG-subclasses IgG1, IgG2, IgG3 and IgG4 using radial immunodiffusion according to Mancini. Additionally a control group of 175 children not prone to infections was investigated. Both, low and high levels compared to controls were observed for IgG3 and IgG4.

Histamine release test in comparison to standard tests in diagnosis of childhood allergic asthma.

An allergen-specific histamine release test (HR) was investigated in 93 children with a history of extrinsic asthma and suspected allergy to house dust mite or fungi. For both allergy groups the correlations between HR and the bronchial provocation test were better than those between the inhalation test and prick test or RAST. It is concluded that, especially in childhood where performance of a bronchial provocation should be avoided because of its potential risk and required hospitalization, the HR test can represent a significant diagnostic aid.

Inhibitory effects of pertussis toxin on the cAMP generating system in human mononuclear leucocytes.

In a previous investigation of children infected with pertussis during the first week of paroxysmal stage, we found a 50-75% reduction of the isoprenaline (IPN)-induced cAMP response in peripheral MN leucocytes. In order to characterize these findings further, intact human MN leucocytes from healthy adults were treated with PT in vitro. Basal, as well as prostaglandin E1-stimulated cAMP levels were decreased by PT in a dose-dependent fashion over a range of 0.

Fatty acid composition of phospholipids of plasma and of mononuclear blood cells in children with allergic asthma and the influence of glucocorticoids.

Fatty acid (FA) composition of plasma phospholipids and phospholipids extracted from peripheral mononuclear white blood cells (MNC) was investigated in 11 allergic asthmatic children (age 8.9 +/- 4.6 years), in 10 age-matched non-allergic healthy controls and in 14 allergic and non-allergic children with an acute attack of asthma, who had received prednisolone medication for 2-4 days.

[The beta adrenergic system of lymphocytes in children with atopic dermatitis].

A defect in the beta-adrenergic system is considered to be one of the basal causes of atopic dermatitis (AD). The number and affinity (KD) of beta-receptors was determined in lymphocytes of 19 children with AD and of 17 controls using the radioligand 125JCYP to find out whether this hypothesis is relevant. In addition, the basal cAMP level was measured as well as the cAMP-accumulation after stimulation of the adenylcyclase (AC) via the beta-receptor with 10(-4) M isoprenaline (IPN) and after direct stimulation of AC with 10(-4) M forskolin.

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.

[Surgical correction of bronchial stenosis: increased somatic development following elimination of the stenosis].

A 5 year old girl suffered from nearly total stenosis of the bronchus intermedius and exspiratory collaps of both main bronchi. Because of preterm birth she was postnatally intubated and mechanically ventilated for 6 weeks. Her somatic development was significantly retarded in comparison with the monozygotic twin, and pulmonary impairment increased again in the last preoperative year.

Impaired formation of the second messenger cAMP in mononuclear blood cells of children with pertussis.

To determine the pathophysiologic significance of pertussis toxin (PT) on the human beta-adrenergic system, beta-adrenoceptor (beta-R)-density and cyclic AMP response of peripheral mononuclear blood cells (MN leukocytes) were studied in children during the paroxysmal stage of natural pertussis infection, after vaccination with pertussis monovaccine, and in controls. Isoprenaline-induced cAMP accumulation, measured in a protein-binding assay, was significantly reduced to about 25-50% in children during the first week of paroxysmal pertussis, compared with controls. In contrast, cAMP accumulation after stimulation of the adenylyl cyclase by forskolin was unaffected.

Adrenoceptors and the lung: their role in health and disease.

alpha- and beta-Adrenoceptors have each been divided into two subgroups (alpha 1, alpha 2, beta 1 and beta 2). The basic mechanisms underlying the adrenoceptor/effector coupling are complex and vary for the alpha-, but not for the beta-subpopulations. Adrenoceptors of the bronchi and the lung show a special pattern of distribution and response, ensuring that the airway system works as a functionary unit.