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21 results on '"Seydewitz, Hans H"'

5. CFTR Cl− channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis

Author

Gonska, Tanja, Lopes, Ana Isabel, Seydewitz, Hans H., Kuehr, Joachim, Mall, Marcus, Ramalho, Anabela, Eichler, Irmgard, Hirtz, Stephanie, Thomas, Jörg, Greiner, Peter, Barreto, Celeste, Rocha, Herculano, Amaral, Margarida D., Kunzelmann, Karl, and Brandis, Matthias

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, respiratory system, digestive system diseases, respiratory tract diseases
Abstract

BACKGROUND & AIMS: Cystic fibrosis (CF) is caused by over 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and presents with a widely variable phenotype. Genotype-phenotype studies identified CFTR mutations that were associated with pancreatic sufficiency (PS). Residual Cl- channel function was shown for selected PS mutations in heterologous cells. However, the functional consequences of most CFTR mutations in native epithelia are not well established. METHODS: To elucidate the relationships between epithelial CFTR function, CFTR genotype, and patient phenotype, we measured cyclic adenosine monophosphate (cAMP)-mediated Cl- secretion in rectal biopsy specimens from 45 CF patients who had at least 1 non-DeltaF508 mutation carrying a wide spectrum of CFTR mutations. We compared CFTR genotypes and clinical manifestations of CF patients who expressed residual CFTR-mediated Cl- secretion with patients in whom Cl- secretion was absent. RESULTS: Residual anion secretion was detected in 40% of CF patients, and was associated with later disease onset (P < 0.0001), higher frequency of PS (P < 0.0001), and less severe lung disease (P < 0.05). Clinical outcomes correlated with the magnitude of residual CFTR activity, which was in the range of approximately 12%-54% of controls. CONCLUSIONS: Specific CFTR mutations confer residual CFTR function to rectal epithelia, which is related closely to a mild disease phenotype. Quantification of rectal CFTR-mediated Cl- secretion may be a sensitive test to predict the prognosis of CF disease and identify CF patients who would benefit from therapeutic strategies that would increase residual CFTR activity.

Published
2004
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7. CFTR Cl− channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis

Author

Hirtz, Stephanie, primary, Gonska, Tanja, additional, Seydewitz, Hans H., additional, Thomas, Jörg, additional, Greiner, Peter, additional, Kuehr, Joachim, additional, Brandis, Matthias, additional, Eichler, Irmgard, additional, Rocha, Herculano, additional, Lopes, Ana—Isabel, additional, Barreto, Celeste, additional, Ramalho, Anabela, additional, Amaral, Margarida D., additional, Kunzelmann, Karl, additional, and Mall, Marcus, additional

Published
2004
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15. Isolation and complete amino-acid sequence of the small polypeptide from light-harvesting pigment-protein complex I (B870) of <em>Rhodopseudomonas capsulata</em>.

Author

Tadros, Monier H., Suter, Franz, Seydewitz, Hans H., Witt, Irene, Zuber, Herbert, and Drews, Gerhart

Subjects
AMINO acid sequence, PROTEIN analysis, AMINO acid analysis, CELL membranes, AMINO acids, BIOCHEMISTRY
Abstract

The small bacteriochlorophyll-binding polypeptide of the light-harvesting complex B 870 was extracted from the intracytoplasmic membrane of the strain A1a+ of Rhodopseudomonas capsulata With chloroform/methanol/ammonium acetate and separated by chromatography on Sephadex LH60 using the same solvent. The potypeptide obtained from the peak fraction III was found to be homogeneous and identical with the small polypeptide isolated from the B870 complex as shown by dodecyl sulfate/polyacrylamide gel electrophoresis, amino acid composition and N-terminal sequence. The complete amino acid sequence is given. The relative molecular mass based on the amino acid sequence is 5341. The polarity of amino acids is 35.42 %. The C-terminal part of the peptide chain from residue 29 to 48 is hydrophobic and includes one His residue. [ABSTRACT FROM AUTHOR]

Published
1984
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16. Modulation of Ca2-Activated Cl−Secretion by Basolateral KChannels in Human Normal and Cystic Fibrosis Airway Epithelia

Author

MALL, MARCUS, GONSKA, TANJA, THOMAS, JÖRG, SCHREIBER, RAINER, SEYDEWITZ, HANS H., KUEHR, JOACHIM, BRANDIS, MATTHIAS, and KUNZELMANN, KARL

Abstract

Human airway epithelia express Ca2-activated Cl−channels (CaCC) that are activated by extracellular nucleotides (ATP and UTP). CaCC is preserved and seems to be up-regulated in the airways of cystic fibrosis (CF) patients. In the present study, we examined the role of basolateral Kchannels in CaCC-mediated Cl−secretion in native nasal tissues from normal individuals and CF patients by measuring ion transport in perfused micro Ussing chambers. In the presence of amiloride, UTP-mediated peak secretory responses were increased in CF compared with normal nasal tissues. Activation of the cAMP pathway further increased CaCC-mediated secretion in CF but not in normal nasal mucosa. CaCC-dependent ion transport was inhibited by the chromanol 293B, an inhibitor of cAMP-activated hKvLQT1 Kchannels, and by clotrimazole, an inhibitor of Ca2-activated hSK4 Kchannels. The Kchannel opener 1-ethyl-2-benzimidazolinone further increased CaCC-mediated Cl−secretion in normal and CF tissues. Expression of hSK4 as well as hCACC-2 and hCACC-3 but not hCACC-1 was demonstrated by reverse transcriptase PCR on native nasal tissues. We conclude that Ca2-activated Cl−secretion in native human airway epithelia requires activation of Ca2-dependent basolateral Kchannels (hSK4). Co-activation of hKvLQT1 improves CaCC-mediated Cl−secretion in native CF airway epithelia, and may have a therapeutic effect in the treatment of CF lung disease.

Published
2003
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17. Modulation of Ca2+-Activated Cl-Secretion by Basolateral K+Channels in Human Normal and Cystic Fibrosis Airway Epithelia

Author

Mall, Marcus, Gonska, Tanja, Thomas, Jörg, Schreiber, Rainer, Seydewitz, Hans H, Kuehr, Joachim, Brandis, Matthias, and Kunzelmann, Karl

Abstract

Human airway epithelia express Ca2+-activated Cl-channels (CaCC) that are activated by extracellular nucleotides (ATP and UTP). CaCC is preserved and seems to be up-regulated in the airways of cystic fibrosis (CF) patients. In the present study, we examined the role of basolateral K+channels in CaCC-mediated Cl-secretion in native nasal tissues from normal individuals and CF patients by measuring ion transport in perfused micro Ussing chambers. In the presence of amiloride, UTP-mediated peak secretory responses were increased in CF compared with normal nasal tissues. Activation of the cAMP pathway further increased CaCC-mediated secretion in CF but not in normal nasal mucosa. CaCC-dependent ion transport was inhibited by the chromanol 293B, an inhibitor of cAMP-activated hKvLQT1 K+channels, and by clotrimazole, an inhibitor of Ca2+-activated hSK4 K+channels. The K+channel opener 1-ethyl-2-benzimidazolinone further increased CaCC-mediated Cl-secretion in normal and CF tissues. Expression of hSK4 as well as hCACC-2 and hCACC-3 but not hCACC-1 was demonstrated by reverse transcriptase PCR on native nasal tissues. We conclude that Ca2+-activated Cl-secretion in native human airway epithelia requires activation of Ca2+-dependent basolateral K+channels (hSK4). Co-activation of hKvLQT1 improves CaCC-mediated Cl-secretion in native CF airway epithelia, and may have a therapeutic effect in the treatment of CF lung disease.

Published
2003
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21. The DeltaF508 mutation results in loss of CFTR function and mature protein in native human colon.

Author

Mall M, Kreda SM, Mengos A, Jensen TJ, Hirtz S, Seydewitz HH, Yankaskas J, Kunzelmann K, Riordan JR, and Boucher RC

Subjects
Adolescent, Adult, Case-Control Studies, Child, Child, Preschool, Chlorides metabolism, Cholinergic Agonists pharmacology, Cyclic AMP metabolism, Female, Homozygote, Humans, Immunologic Techniques, Infant, Infant, Newborn, Intestinal Mucosa metabolism, Male, Rectum metabolism, Rectum pathology, Tissue Distribution, Colon metabolism, Cystic Fibrosis genetics, Cystic Fibrosis metabolism, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Mutation physiology
Abstract

Background and Aims: Deletion of the codon for phenylalanine at position 508 (DeltaF508) is the most frequent disease-causing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In heterologous cells, defective processing of the DeltaF508 protein results in endoplasmic reticulum retention, proteolytic degradation, and absence of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent plasma membrane Cl(-) conductance. However, data with respect to the processing block of DeltaF508 protein in native epithelia are limited and conflicting., Methods: To characterize both the fate and function of DeltaF508 protein in a native epithelium, we measured CFTR-mediated Cl(-) secretion, localization of the CFTR protein, and CFTR maturation in rectal biopsy specimens from normal individuals and DeltaF508 homozygous patients with cystic fibrosis (CF)., Results: Ussing chamber studies showed that cAMP-dependent and cholinergic Cl(-) secretion was absent from rectal tissues freshly excised from DeltaF508 homozygous patients with CF. By immunohistochemistry, we detected wild-type but not DeltaF508 CFTR at the luminal membrane of crypt colonocytes. By sequential immunoprecipitation and immunoblotting analyses, mature CFTR protein was detected in normal but not in DeltaF508 homozygous tissues., Conclusions: Collectively, these data show that there is insufficient maturation and transport of DeltaF508 CFTR from the endoplasmic reticulum to the apical membrane to support CFTR-mediated Cl(-) secretion in the CF colon.

Published
2004
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