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Biomedical subjects

M Griese

Publications and source records attributed to M Griese.

At least 91 records · Page 5Linked to original sources
PubMed1991

A2 and P2 purine receptor interactions and surfactant secretion in primary cultures of type II cells.

Phosphatidylcholine secretion in type II pneumocytes can be stimulated by P1 (adenosine) and P2 (ATP) purinoceptor agonists. The effect of adenosine is mediated by the A2 subtype of the P1 receptor. The A1 subtype is inhibitory. We examined the influence of ATP and the A2 agonist 5'-(N-ethylcarboxyamido)adenosine (NECA) on phosphatidylcholine secretion in primary cultures of rat type II cells. The stimulatory effects of ATP and NECA were less than additive, suggesting a common mechanism of action. NECA and ATP both caused a rapid increase in cAMP, and the combination enhanced this even further. ATP promoted inositol trisphosphate (IP3) formation, whereas NECA did not. The effect of ATP on adenosine 3',5'-cyclic monophosphate (cAMP) but not on IP3 was abolished by a P1 antagonist, and such antagonists diminished its effect on secretion by as much as 75%. The potency orders of ATP analogues in increasing formation of cAMP and IP3 were different. The effects of the ATP analogues on phosphatidylcholine secretion were also inhibited by the P1 antagonists, with the greatest degree of inhibition being observed with the analogue that increased cAMP to the greatest extent. The effect of ATP on secretion was not diminished by either adenosine deaminase (previous data) or AMP deaminase showing that the effects of ATP were not mediated by its metabolism to the P1 agonists adenosine or AMP. These data show that ATP acts at both A2 and P2 receptors but that most of its effects on phosphatidylcholine secretion are mediated by the A2 receptor.

AMP Deaminase↗
PubMed1991

Surfactant lipid uptake and secretion in type II cells in response to lectins and secretagogues.

Secretion of surfactant phospholipids can be inhibited by the surfactant-associated protein SP-A. SP-A was reported to stimulate lipid uptake by type II cells, whereas surfactant secretagogues were reported to have the same effect in isolated perfused lungs. We examined the effect of such secretagogues on uptake of liposomes containing L-alpha-[2-palmitoyl-9,103H(N)]-dipalmitoyl phosphatidylcholine in primary cultures of type II cells. As SP-A contains a lectinlike domain and other lectins were reported to inhibit surfactant secretion, we also examined the effect of such lectins on lipid uptake. At concentrations at which they maximally stimulate phosphatidylcholine secretion in type II cells, several secretagogues had no effect on liposome uptake. Maclura pomifera agglutinin (MPA) stimulated uptake approximately 10-fold with a concentration eliciting 50% maximum stimulation (EC50) of 17 micrograms/ml. The effect of MPA on uptake was considerably greater than that of SP-A. However, although the stimulatory effect of ATP on phosphatidylcholine secretion was almost completely antagonized by SP-A, it was maximally inhibited only 75% by MPA. The concentration eliciting 50% maximum inhibition (IC50) for MPA inhibition of secretion was 0.5 micrograms/ml. Concanavalin A, another lectin, had no effect on lipid uptake but completely inhibited secretion. These data show that a lectin other than SP-A can stimulate phospholipid uptake by type II cells cultured on plastic and suggest that surfactant secretion and reuptake are independently regulated processes.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

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. In allergic asthmatics eicosapentaenoic acid (20:5n-3) was significantly elevated in both plasma and MNC. The relative amount of 20:5n-3 in MNC as well as in plasma correlated positively with increasing levels of total serum IgE (P less than 0.02). The pattern of the other FAs in plasma and of MNC phospholipids did not differ between allergic asthmatic and non-allergic control children. In children with an acute attack of asthma, who had been treated with glucocorticoids (2 mg prednisolone/kg body weight for 2-4 days), distinct changes of relative FA composition of phospholipids were restricted to plasma, where some very long chain FA (22:4n-6, 22:5n-6) were elevated. No significant changes in FA from MNC phospholipids could be observed after glucocorticoid treatment. These findings may indicate a possible role of 20:5n-3, the precursor of "group 3" eicosanoids, in allergic asthmatic children.

Adolescent↗
PubMed1990

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 0.01 to 1000 ng ml-1 to about 65% of control levels. Stimulation of PT-pretreated cells (100 ng ml-1, 90 min, 37 degrees C) showed significantly reduced IPN and PGE1-induced cAMP accumulation, indicated by a depression and shift of the dose-response curves to the right. In contrast, cAMP generation was unchanged by forskolin, a diterpene that is believed to directly stimulate adenylyl cyclase. The anti-allergic drug ketotifen had no direct effects on basal, IPN or PGE1-induced cAMP responses; however the inhibitory actions of PT pretreatment on cAMP levels were diminished (basal and isoprenaline-stimulated) or reversed (PGE1-stimulated). To further locate the site of impaired cAMP responses, beta-adrenoceptor binding, as well as displacement characteristics of the receptor, were estimated by 125I-cyanopindolol binding to a plasma membrane fraction pretreated with or without PT. No differences in beta-adrenoceptor number or in the affinities of the binding sites could be detected. These data are in close agreement with the findings on MN leucocytes from pertussis-infected children and support the notion of PT-induced impaired signal transduction in the cAMP generating system in human MN leucocytes.

Adenylate Cyclase Toxin↗
PubMed1990

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.

Adolescent↗
PubMed1990

[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. 11.5% of the children with frequent airway infections had IgG3 values below 2 SD below the mean for age compared to 2.8% in the control group (p less than 0.01). Likewise a low IgG4 level was observed more frequently in children prone to airway infections (9.8% versus 2.8% in control; p less than 0.05). IgG4 was undetectable (level less than 3.4 mg/dl) in 5 of the 175 control children. Despite an accumulation of low or undetectable IgG3 or IgG4 levels in children with frequent respiratory tract infections, no correlation between low IgG subclass-levels and the degree of the individual disease could be detected. Based on this lack of a simple causal relationship between frequent respiratory tract infections and the finding of low or undetectable IgG-subclass levels, an immunoglobulin replacement therapy has to be considered with reserve.

Adolescent↗
PubMed1989

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↗
PubMed1989

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. The density and affinity of beta-R, estimated by 125I-cyanopindolol-binding studies, were not significantly altered. The suggestion that PT might impair the coupling of the beta-R signals to the adenylyl cyclase was confirmed by parallel in vitro studies on MN leukocytes from adults. These cells, when incubated with purified PT, showed a significantly diminished cAMP response to isoprenaline, whereas that to forskolin remained unaffected. As cAMP accumulation in response to prostaglandin E1 and hydrocortisone was also reduced, it appears that PT may directly affect G-proteins serving as signal transducers for several stimulatory receptors. In contrast to the actual disease, in children treated with pertussis monovaccine, cAMP accumulation as well as the beta-R were unaffected. It is concluded that in MN leukocytes obtained from children during the natural course of pertussis, as well as after incubation of normal MN leukocytes with PT, the stimulatory signal-transducing system for cAMP generation is inhibited.

Adenylate Cyclase Toxin↗
PubMed1988

Glucocorticoid receptors in mononuclear blood cells and their correlation to endogenous and exogenous corticoids in healthy and asthmatic children.

The number and affinity of glucocorticoid binding sites in peripheral mononuclear cells (MNC) of asthmatic and healthy children were determined by a whole cell (3H)dexamethasone binding assay at 37 degrees C. Using HPLC determination, corresponding serum levels of non-protein-bound (free) cortisol, whole cortisol and cortisone as well as urine excretion of free cortisone and cortisol were assessed. The average number of binding sites (BS) per cell and the dissociation constant (KD) respectively, in atopic asthmatics (7768 +/- 666 BS/MNC resp. KD = 17.2 +/- 2 nM) did not differ from the values measured in our control group (8333 +/- 691 BS/MNC resp. 25.4 +/- 4.8 nM). Within the age range 1 month-15.8 years neither age-dependent changes nor sex-related differences in the number of binding sites or the KD values could be detected. Active or currently inactive asthmatics, and patients under different antiasthmatic drug regimes, had similar binding sites on MNC. No differences in serum levels of cortisol, cortisone and free cortisol or in free cortisol and free cortisone of 24-h urine samples were found between healthy children and asthmatics. After a short course of prednisolone therapy for an acute severe asthmatic attack the number of glucocorticoid binding sites in peripheral MNC decreased to an average of 4632 +/- 421 BS/MNC, whereas the dissociation constant did not change significantly (14.5 +/- 3.6 nM). The corticoid-hormone pattern in the serum, 24-h urine excretion, and the normal number and affinity of glucocorticoid receptors on peripheral MNC suggest that there is no primary, general impairment of glucocorticoid metabolism in asthmatic children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Beta-adrenoceptor density and resolution of high and low affinity state on B- and T-cells in asthmatic and non-asthmatic children.

Beta-adrenoceptor binding in lymphocytes of asthmatic and non-asthmatic children and healthy adult volunteers was investigated with the radioligand 125-iodocyanopindolol (ICYP). Binding studies were performed with 4 to 5 different concentrations of ICYP. Receptor density and affinity were calculated by Scatchard plots. Resolution of beta-adrenoceptors into those of high and low affinity state was obtained from inhibition curves with salbutamol using Hofstee plots. Receptor density in B-cell enriched fractions was two to three-fold higher than in T-cells for all patients and volunteers studied (P less than 0.025). No difference in beta-adrenoceptor density on B and T-cells occurred neither in age-matched asthmatic and non-asthmatic children nor in adult volunteers. The affinity of beta-adrenoceptors did not differ for B and T-cells nor for the patients or volunteers studied. However, when two distinct binding states for beta-adrenoceptor agonists were obtained using salbutamol displacement curves it appeared that beta-adrenoceptors on T-cells were at a higher affinity state compared to those on B-cells in asthmatic and non-asthmatic children, as well as in adults. Since the ability of an agonist to activate adenylate cyclase correlates closely with the amount of high affinity receptor state formed in the presence of the agonist, increased intrinsic activity of the beta-adrenoceptor agonist on T-cells may be postulated. In conclusion, age-related control groups and determination of the B/T ratio are necessary for interpretation of beta-adrenoceptor changes in bronchial asthma.

Adolescent↗
PubMed1988

Myocardial performance and free energy of ATP-hydrolysis in isolated rat hearts during graded hypoxia, reoxygenation and high Ke+-perfusion.

The effects of graded hypoxia, graded reoxygenation after anoxic perfusion and of different extracellular K+-concentrations on cardiac energy metabolism and performance were studied in isolated, perfused, electrically paced rat hearts. Graded hypoxia was induced by different oxygen partial pressure (PO2: 736 to 43 mmHg, nine intermediate steps; O2 supply: (AVD*CF): 300 to 21 microliters/g*min) in perfusate for 3 min, thus leading to different levels of relative mechanical steady state. Evaluated free energy change of ATP-hydrolysis (dG/d zeta) decreased largely in parallel with peak systolic pressure (Psyst) and systolic dP/dtmax, whereas diastolic dP/dtmin declined already to lowest values with moderate hypoxia. For regular beats and beats potentiated by paired stimulation the same relationships were found. Complete reoxygenation of hearts perfused anoxically beforehand (10 or 30 min, PO2 less than 6 mmHg), restored Psyst and dG/d zeta completely. Graded reoxygenation from different levels of hypoxia resulted in restitution of dG/d zeta and Psyst to the same levels as in graded hypoxia. The inotropic effect of paired stimulation was moderately reduced. Cytosolic Pi-levels remained increased during partial reoxygenation and exhibited no distinct relationship with mechanical performance. High extracellular K+ (13.5 mM) resulted in increased Psyst and elevated dG/d zeta-levels. Cardiac failure during graded hypoxia and high K+ occurred at comparatively high dG/d zeta levels. Reoxygenation with high K+, led to recovery of dG/d zeta levels but not of Psyst values. According to the results obtained in early hypoxic failure free energy dependence of Na+/K+-ATPase is of minor relevance whereas free energy dependence of sarcoplasmic Ca2+ regulating processes appears to be important.

Adenosine Triphosphate↗
PubMed1988

Density and agonist-promoted high and low affinity states of the beta-adrenoceptor on human B- and T-cells.

beta-Adrenoceptor binding on peripheral blood mononuclear cells (PBMC) of healthy adult volunteers was investigated using the radioligand 125iodo-cyanopindolol (ICYP). Saturation binding studies were performed with nine different concentrations of ICYP. Receptor density and affinity were calculated by Scatchard plots. Resolution of beta-adrenoceptors into those with high and low affinity state of the beta-adrenoceptor was obtained from inhibition curves with salbutamol using Hofstee plots. Receptor density on enriched B-cells ('B-cells') was two-fold higher than on enriched T-cells ('T-cells') (P less than 0.025). Affinity (KD values) of beta-adrenoceptors did not differ for B- and T-cells. However, when two distinct binding states for beta-adrenoceptor agonists were identified using salbutamol displacement curves, beta-adrenoceptors on T-cells presented more receptors in a high affinity state than those on B-cells (P less than 0.01). Since the ability of an agonist to activate adenylate cyclase is closely correlated with the ratio of low to high affinity states formed in the presence of the agonist, increased intrinsic activity for the beta-adrenoceptor agonist on T-cells may be postulated. In conclusion, determination of the B/T ratio is a prerequisite for interpretation of beta-adrenoceptor changes on peripheral lymphocytes in various diseases.

Adolescent↗
PubMed1988

Effects of the antiallergic drug ketotifen on bronchial resistance and beta-adrenoceptor density of lymphocytes in children with exercise-induced asthma.

In a parallel, double-blind, placebo-controlled study we investigated the effect of the antiallergic drug Ketotifen on bronchial resistance (determined body plethysmographically) and beta 2-adrenoceptor density of lymphocytes (determined by 125-iodo-cyano-pindolol binding) in asthmatic children suffering from exercise-induced asthma (EIA). In order to provoke EIA a test which involved running for 7 min was performed with 22 asthmatic children. 13 age-matched children not suffering from asthma served as controls. Control children showed a 30% increase in the number but not in the affinity of beta-adrenoceptors in response to a 7-min run. Asthmatic children with EIA showed no difference in the number and affinity of beta-adrenoceptors under resting conditions when compared with the controls. In contrast to what has been observed with control children, however, no increase in the number of beta-adrenoceptors in response to exercise was observed. A 1-week treatment with placebo neither affected the bronchoconstriction nor the number of lymphocyte beta 2-adrenoceptors. Ketotifen (2 X 1 mg/day for 1 week) protected asthmatic children from EIA, at least in part, and restored the up-regulation of beta-adrenoceptors in response to exercise in 9 of 14 children with EIA. However, no correlation between the serum concentration of Ketotifen and the number of binding sites could be found. It is therefore concluded that the preventive effect of Ketotifen in EIA might also involve mechanisms other than a recovery of the beta-adrenergic system.

Adolescent↗
PubMed1988

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↗
PubMed1988

[Significance of basal TSH and free T3 as compared with an extended in vitro diagnosis in the understanding of functional disorders of the thyroid].

Data of 411 untreated patients undergoing thyroid investigations were stored in a data base system. Three combinations of thyroidal hormone parameters were compared with respect to their clinical value. In patients with concordant basal TSH (bTSH) and free T3 (fT3)-values (e.g. bTSH normal and fT3 normal, bTSH decreased and fT3 increased) it could be demonstrated that the predictive value of the combined evaluation of basal TSH (supersensitive) and free T3 alone (97% in normal thyroid function, 98% in thyrotoxicosis, and 97% in hypothyroidism) was sufficient. Additional determinations of T4 parameters did not increase predictive value (e.g. TT4: 95% in thyrotoxicosis). Thus, thyroid disorders may currently be diagnosed by the combined evaluation of basal TSH and free T3, saving costs without loss of diagnostic efficacy.

Clinical Laboratory Techniques↗
PubMed1987

[Chronic recurrent pneumonias in ossifying bronchial carcinoid tumor].

We describe the case history of a 13 year old boy with recurrent bronchitis and pneumonia over a period of 8 years. Because of the peculiar bronchoscopic finding of an osseous foreign body a chronical foreign body aspiration was considered likely, but not confirmed histologically. A bronchial carcinoid tumor with ossifications proved to be the cause of recurrent chest infections. Tumors arising from bronchial epithelia in childhood and adolescence are very uncommon, ossification in this age group is a rarity. In the eight years following the operation there has been no relapse.

Adolescent↗
PubMed1987

[Causative relations between infections and allergies in obstructive respiratory tract diseases in childhood].

Obstructive bronchitis of young babies and infants is most often caused by respiratory-syncytial (RS)- and parainfluenza viruses, to a certain extent by adenoviruses. In the school age-group rhinoviruses and to a smaller extent mycoplasma pneumoniae gain further importance. All the viruses may cause or deteriorate asthmatic attacks, as well as during common cold or on the basis of documented allergies. Proposed mechanisms of viral-infection-induced obstructive airway disease are distinct lesions of bronchial-epithelium, followed by enhanced allergen-resorption and sensitization of submucosal mast cells, establishing an allergy. Following epithelial discontinuation airway irritant receptors which are raised in sensitivity by viral toxins are exposed and stimulated. Via vago-vagal reflexes this leads to bronchoconstriction. Furthermore, in the development of bronchial hyperresponsiveness there may be participation of virus-induced blockage of adrenoceptors, basophilic and mast-cell release of mediators as well as induction of specific IgE antibodies against RS- and/or Para-influenza-viruses. Viral airway infections are supposed to influence the immunological response of T-lymphocytes and probably macrophages selectively, e.g. to regulate IgE-antibody production. Especially in children with an atopic family history the RS-viruses cause obstructive airway disease. During acute respiratory-virus infections using electron microscopy marked pathological changes of bronchial-epithelium can be demonstrated causing disturbance or even stopage of mucus-transport. These changes are fully reversible within weeks after airway infection. Although there is no doubt about a causative relation between respiratory-tract infection and allergy, hardly any prediction for development of asthma bronchiale in later life, after having suffered from virus-induced obstructive airway disease early in life, can be made.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗