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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMDS 2014; 59. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS); 20140907-20140910; Göttingen; DOCAbstr. 255 /20140904/
    Publication Date: 2014-09-05
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
    Keywords: brain ; RECEPTOR ; EXPRESSION ; IN-VITRO ; tumor ; Germany ; human ; LUNG ; VITRO ; SYSTEM ; DISEASE ; HYBRIDIZATION ; PROTEIN ; TUMORS ; MOLECULE ; TARGET ; IN-SITU ; immunohistochemistry ; MEMBRANE ; SURFACE ; CALCIUM ; MEMBRANES ; BINDS ; DMBT1 ; SALIVARY AGGLUTININ ; RESPIRATORY-DISTRESS-SYNDROME ; SCAVENGER RECEPTOR ; in situ hybridization ; ELISA ; RECOMBINANT ; RE ; BRAIN-TUMORS ; INCREASE ; SUPPLEMENTATION ; methods ; BOVINE ; function ; CANDIDATE ; CAPILLARIES ; lungs ; ENGLAND ; host ; INCREASES ; TENSION ; INFANT ; CALCIUM-IONS ; EXOGENOUS SURFACTANT ; POLYMORPHONUCLEAR LEUKOCYTES ; PRETERM INFANTS ; PROTEIN-D ; PULMONARY SURFACTANT
    Abstract: Background: Deleted in Malignant Brain Tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome in neonates by modulating surfactant function. Methods: DMBT1 expression was studied by immunohistochemistry and mRNA in situ hybridization in post-mortem lungs of preterm and full-term neonates with pulmonary hyaline membranes. The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer. DMBT1-levels in tracheal aspirates of ventilated preterm and term infants were determined by ELISA. Results: Pulmonary DMBT1 was localized in hyaline membranes during respiratory distress syndrome. In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner. The DMBT1- mediated effect was reverted by the addition of calcium depending on the surfactant preparation. Conclusion: Our data showed pulmonary DMBT1 expression in hyaline membranes during respiratory distress syndrome and demonstrated that DMBT1 increases lung surface tension in vitro. This raises the possibility that DMBT1 could antagonize surfactant supplementation in respiratory distress syndrome and could represent a candidate target molecule for therapeutic intervention in neonatal lung disease
    Type of Publication: Journal article published
    PubMed ID: 17908325
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  • 3
    ISSN: 1432-1076
    Keywords: Glucocorticoid receptors ; Asthma ; Prednisolone therapy ; Free serum and urine cortisol ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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°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 corticod-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. Short-term glucocorticoid administration resulted in suppression of endogenous corticoids to undetectable levels accompanied by down-regulation of glucocorticoid-receptor BS to about 55% of control levels.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1076
    Keywords: Human basophils ; Histamine release ; Pertussis toxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of childhood pertussis infection and of purified pertussis toxin on histamine relase from human basophil leucocytes was investigated. Three different stimuli, the peptide N-formyl-Met-Phe (NFMP), anti-IgE, and the calciuminnophore A23187 were used to challenge the cells. When NFMP was the stimulus, histamine release in the control group (age 0.5–17 years) increased in an age-dependent fashion, whereas anti-IgE and A23187 stimulated release did not vary with age. During the convulsive state of pertussis infection there was a significant reduction of histamine release in response to 10 μM NFMP (from 9.5±1.4 [n=21] to 6.7±1.5 [n=19],P〈0.05) and in response to 800 and 80 U/ml anti-IgE (from 28.5±5 [n=19] to 16.3±5 [n=13],P〈0.05, and from 6.9±1.7 [n=16] to 2±0.8 [n=13],P〈0.01), whereas histamine release stimulated by A23187 was unchanged compared to release in control children. In vitro pretreatment of basophils from healthy children and adults with pertussis toxin also inhibited histamine release. When NFMP was the stimulus, release was completely blocked by pertussis toxin with an IC50 of about 11 ng/ml whereas anti-IgE stimulated release was only inhibited by 20%–30% and release induced by A23187 was reduced to 40%–50% by toxin treatment. In conclusion we have demonstrated a functional impairment of histamine release during the convulsive state of pertussis and that this inhibition is likely to be mediated by pertussis toxin.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1076
    Keywords: β-Adrenoceptor density ; β-Adrenoceptor affinity ; High and low receptor affinity state ; B and T-cells ; Asthmatic children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract β-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 β-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 β-adrenoceptor density on B and T-cells occurred neither in age-matched asthmatic and non-asthmatic children nor in adult volunteers. The affinity of β-adrenoceptors did not differ for B and T-cells nor for the patients or volunteers studied. However, when two distinct binding states for β-adrenoceptor agonists were obtained using salbutamol displacement curves it appeared that β-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 β-adrenoceptor agonist on T-cells may be postulated. In conclusion, age-related control groups and determination of the B/T ratio are neccessary for interpretation of β-adrenoceptor changes in bronchial asthma.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1076
    Keywords: Allergic asthma ; Children ; Phospholipids ; Fatty acids ; Glucocorticoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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〈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.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Aspergillus ; Candida ; Leishmaniose ; Pilzinfektionen ; Lunge ; Key words Aspergillus ; Candida ; Leishmaniosis ; Fungal infection ; Lung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Amphotericin B (AmB) continues to maintain an important role in the treatment of invasive fungal infections. The substance is almost insoluble in water. Therefore special pharmacological solutions are required to dissolve Am B – usually prepared with bile acid (Deoxycholat ((AmB/Doc)). The association of the lipophil substance with lipids leads to a clear increase in the patient's tolerance of the compound and makes possible the use of much higher doses. The liposomal formulation can however, at the same time change the typical distribution of AmB in the body. At the present time ambisone is the only liposomal AmB-formulation. AmB is also often administered in combination with Intralipid. AmB-Lipid complex (ABLC) and AmB-Colloidal (ABCD) are the other pharmaceutical preparations which could become available in the future. The importance of immune competence and of prophylactic measures to prevent invasive fungal infection are stressed.
    Notes: Zusammenfassung Amphotericin B hat in der Behandlung invasiver Pilzinfektionen nach wie vor einen hohen Stellenwert. Da die Substanz praktisch unlöslich in Wasser ist, werden besondere pharmakologische Formulierungen benötigt. Konventionell wird AmB mit Gallensäuren (Deoxycholat) dispergiert. Die Assoziation der lipophilen Substanz mit Lipiden führt zu einer deutlichen Steigerung der Verträglichkeit und ermöglicht die Verabreichung höherer Dosen. Gleichzeitig kann sich jedoch durch die liposomale Verpackung das Verteilungsmuster von AmB im Körper ändern. An liposomalen AmB-Formulierungen steht derzeit Ambisome zur Verfügung, manchmal wird AmB/Doc auch in Kombination mit Intralipid verabreicht. AmB-Lipidkomplex und AmB-Colloidal Dispersion sind weitere pharmazeutische Präparationen, die in naher Zukunft verfügbar sein können. Neuere, z. Z. untersuchte Formulierungen werden besprochen. Die Bedeutung der Immunkompetenz und prophylaktischer Maßnahmen zur Verhinderung invasiver Pilzinfektionen wird betont.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1433-0474
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die Compliance bei inhalativen Therapien stellt im Alltag ein großes Problem dar, das nicht immer in das Behandlungskalkül einbezogen wird. Diese Arbeit gibt eine kurze Übersicht über Studien zur Compliance bei der Behandlung von Atemwegserkrankungen, vor allem im Kindes- und Jugendalter, und die Möglichkeiten zu ihrer Kontrolle und Verbesserung.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0022-2828
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1440
    Keywords: Cystic Fibrosis ; Blood cells ; Beta-adrenoceptors ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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