Search PubMed⌕ Search

Biomedical subjects

T Welte

Publications and source records attributed to T Welte.

At least 109 records · Page 6Linked to original sources
PubMed1999

Localization of TFF3, a new mucus-associated peptide of the human respiratory tract.

Trefoil factor family (TFF)-domain peptides (formerly P-domain peptides, trefoil factors) represent major mucin-associated peptides of the gastrointestinal tract. Here, the first localization studies on TFF3 in the lower respiratory tract of human material are presented. Immunohistochemistry revealed significant accumulation of TFF3 to mucous cells in the acini of submucosal glands and varying amounts in goblet cells at the ductular portions and the surface epithelium. TFF3 appears also as a component of the mucus, for example from patients with chronic bronchitis. Expression of TFF3 was also shown by use of the polymerase chain reaction. In contrast, TFF1 and TFF2 transcripts were hardly detectable in the human respiratory tract. Thus, a structural function of TFF3 for the airway mucus is discussed, possibly together with the mucins MUC5B and MUC5AC.

Blotting, Western↗
PubMed1999

Expression of cathepsin K in lung epithelial cells.

Alveolar and bronchial epithelial cells have been shown to have regulatory functions in the maintenance of lung structure and function. Recent evidence supports the premise that these cells can synthesize a variety of extracellular matrix components in vitro, suggesting an active participation in connective tissue remodeling. Their possible role in extracellular matrix degradation, however, is less clear. This study addresses the question of whether alveolar and bronchial epithelial cells express the highly collagenolytic and elastinolytic cysteine proteinase cathepsin K, which has recently been newly described. We provide evidence that the epithelial cell lines A549 and BEAS-2B are capable of expressing cathepsin K messenger RNA. Furthermore, we show that cathepsin K is expressed in normal bronchial epithelial cells. Western blot analyses of human lung-tissue lysates revealed specific immunoreactivity at molecular weights of 46 and 27 kD, corresponding to the procathepsin and the mature cathepsin K. Immunohistochemical analyses showed a pronounced staining of bronchial epithelial cells and in single alveolar epithelial cells. Using a specific fluorogenic cytochemical assay, the intracellular activity of the enzyme was localized. These findings demonstrate that bronchial and alveolar epithelial cells are capable of expressing cathepsin K, which could be of considerable importance for remodeling processes of the extracellular matrix in the lung.

Bronchi↗
PubMed1999

[Percutaneous dilatational tracheostomy].

BACKGROUND: Tracheostomy provides a method for long-term ventilation in intensive care, which reduces the risk of necrotizing lesions of the pharyngeal and laryngeal mucosa. Since the introduction of the percutaneous dilatational tracheostomy, experienced physicians are able to perform bedside tracheostomies. This presentation reviews the complication rate and long-term outcome of percutaneous dilatational tracheostomy. PATIENTS AND METHOD: The method was applied in 57 patients following previous orotracheal intubation averaging 7.8 days (3 to 15 days). Underlying diseases were sepsis/SIRS in 29, stroke in 7, cerebral hypoxemia after cardiopulmonary resuscitation in 10, trauma in 7, prolonged weaning in 2, primary neurological diseases in 2. RESULTS: The following complications occurred during the procedure: 1 major and 7 minor bleedings. 2 subcutaneous emphysemas, 1 mediastinal emphysema following tracheal injury. No complication required surgical intervention. In the follow-up 17 patients (30%) died from their underlying disease, none from complications of the tracheostomy. After removed of the tracheal tube, in 39 patients the stoma closed spontaneously within 7 to 14 days. In 8 patients the tracheostoma persisted for more than 3 months, but no clinically relevant tracheal stenosis was found. CONCLUSION: Percutaneous dilatational tracheostomy is a safe procedure easy to perform in intensive care units. Bronchoscopic control is necessary to avoid complications.

Dilatation↗
PubMed1999

[Non-invasive positive pressure ventilation in cardiogenic pulmonary edema].

PATIENTS AND METHOD: 30 patients being admitted to our intensive care unit with severe cardiogenic pulmonary edema received non-invasive positive pressure ventilation (NIPPV) via face mask. RESULT: 29 responded well, 1 patient had to be intubated. Within 30 minutes those who responded well showed a significant improvement of the following parameters: rise of peripheral saturation from 75.5 to 90.1% and of pH from 7.24 to 7.29, decrease of pCO2 from 60.7 to 48.8 mm Hg and of systolic blood pressure from 144 to 124 mm Hg. Mean duration of ventilation was 6 h 55 min. Mean stay in intensive care unit was 2 days. No patient required ventilator support within 24 hours after NIPPV. Four patients died during hospital stay as a result of their underlying disease but not due to pulmonary edema. Observed side effects were vomiting in 4 cases during NIPPV without aspiration and 3 cases of skin lesions which healed uneventfully. CONCLUSION: Key role for this highly effective method seems to be the rapid improvement of left ventricular function during NIPPV.

Aged↗
PubMed1999

[Noninvasive pressure support ventilation (NIPSV) as therapy for severe respiratory insufficiency due to pulmonary edema].

OBJECTIVE: Experimental use of noninvasive pressure support ventilation (NIPSV) in patients with severe pulmonary oedema who would have been intubated if noninvasive ventilation were not available. DESIGN: Open, prospective, within patients non comparative study. SETTING: Internal intensive care unit (11 beds) at a university hospital. PATIENTS: 29 patients with severe respiratory distress and confirmed pulmonary oedema. INTERVENTIONS: NIPSV was applied via a tight fitting face mask delivering between 13 and 24 cm H2O inspiratory airway pressure and between 2 and 8 cm H2O expiratory airway pressure. MEASUREMENTS AND RESULTS: One patient required endotracheal intubation. Mean plethysmographic oxygen saturation rose significantly within 30 min from 73.8 +/- 11 to 90.3 +/- 5% while the oxygen supply was reduced from 7.3 +/- 3.7 to 5.1 +/- 3 l/min. Mean pH increased significantly (p < 0.01) from 7.22 +/- 0.1 before NIPSV to 7.31 +/- 0.01 after 60 min of NIPSV. Partial pressure of carbon dioxide was 62 +/- 18.5 mmHg, but decreased significantly within 60 min to 48.4 +/- 11.5 mm Hg. Heart rate and blood pressure established continuously during observation time. Mean duration of NIPSV was 6 h 9 min (range 120 min to 24 h). There were no serious side effects. Four patients died from underlying diseases between 1 and 28 days after NIPSV. CONCLUSION: NIPSV is a highly effective technique with which to treat patients with severe cardiogenic pulmonary oedema.

Aged↗
PubMed1999

[Cathepsin cysteine proteinases in the lung].

Proteolytic enzymes play an important role during remodeling and digestion of extracellular matrix proteins. An overproduction of extracellular matrix or insufficient extracellular matrix digestion may result in fibrosis. Enhanced proteolytic activity or an insufficient inhibitory potential could be followed by emphysema development. Since the first reports showed an emphysema induction in rats after intratracheal application of the cysteine protease papain, a number of proteolytic enzymes involved in the remodeling of the extracellular matrix of the lung were discovered. Most of them are cysteine-, metallo-, serine- or aspartic proteases. In this paper some new findings concerning the expression, function and regulation of the activity of papain-like cysteine proteases in the process of tissue destruction and remodeling in the lung are reviewed. The functional relationship between cathepsins and other proteolytic enzymes are discussed.

Animals↗
PubMed1999

[Our first experiences with intermittent assisted ventilation in patients with amyotrophic lateral sclerosis].

Amyotrophic lateral sclerosis is one of the most frequent neuromuscular diseases in adults. Chronic respiratory failures is an almost compulsory symptom in the progression of this disease, and in association with pulmonary infections, responsible for the majority of deaths. We report on a series of 43 patients. An advanced stage of clinical disease was seen in half of them. After detection of respiratory failure corresponding to the guidelines of muscle centres of the DGM (Deutsche Gesellschaft für Muskelerkrankungen), seven patients (16.3%) were willing to be provided with a system for intermittent non-invasive ventilation. All patients achieved stabilisation of respiratory function, both with respect to the normalisation of arterial gases and subjective improvement of well-being. During the course of treatment four patients deliberately underwent permanent invasive ventilation. In our opinion home ventilation is a valid additional tool in the palliative treatment of amyotrophic lateral sclerosis. The treatment, however, must be supported by an interdisciplinary team.

Adult↗
PubMed1998

Selective coupling of STAT factors to the mouse prolactin receptor.

Prolactin has been reported to induce distinct sets of signal transducers and activators of transcription (STAT) in a cell-type-specific fashion. In the mammary epithelium, although STAT1, STAT3, STAT5A, STAT5B and STAT6 are present in a latent form, only STAT5A and STAT5B are activated. This selective activation of STAT5 by prolactin was also observed in COS-7 cells cotransfected with the long form of the mouse prolactin receptor (PRL-R) and expression vectors for STAT1, STAT3, STAT5 and STAT6. Mutated PRL-Rs and chimeric erythropoietin/gp130 (EPO/gp130) receptors with a tyrosine-containing motif attached at the carboxy terminus were employed to determine the sites in the PRL-R required for the specific activation of STAT5. The experiments revealed the importance of two motifs containing Y477 and Y578 in the PRL-R. When linked to the EPO/gp130 receptor, these sequences were sufficient to specifically induce DNA binding of STAT5 and to activate transcription from the beta-casein gene promoter. By contrast, only weakly they induced DNA binding of STAT6 and STAT3 and did not induce STAT1. A synthetic nonapeptide with phosphorylated Y477 was able to disrupt STAT5 DNA binding in vitro. Our results define structural domains within the carboxy terminus of the PRL-R which recruit STAT5 for signalling and which are capable of distinguishing STAT5 from other STAT proteins. The activity of STAT5 forms with deletions of the carboxy terminus was induced more strongly than that of their full-length counterparts 2 min after activation of the PRL-R. This effect was not dependent on the presence of Y477 and Y578 in the PRL-R, indicating that facilitated activation of short STAT5 isoforms relies on mechanisms other than increased coupling to specific regions of the PRL-R.

Animals↗
PubMed1998

A distal enhancer region in the human beta-casein gene mediates the response to prolactin and glucocorticoid hormones.

The 5' flanking region of the human beta-casein gene was investigated for the presence of regulatory sequences mediating the action of the lactogenic hormones prolactin and dexamethasone. DNA encompassing 9389 base pairs of the flanking region was isolated and a sequence comparison performed with regulatory regions previously identified in the beta-casein gene of rodents and ruminants. The analysis revealed the presence of a distal region between -4700 and -4550 with a high percentage of identity to the bovine beta-casein enhancer region, and a proximal region between -1 and -200 similar to the proximal promoter regions found in rodents and ruminants. Reporter gene constructs under the control of the distal or the proximal region of the human beta-casein gene were tested for their responsiveness to prolactin and dexamethasone. In transfection experiments, the distal region functioned as a lactogenic hormone inducible enhancer, whereas the proximal region exhibited low activity. In electromobility shift assays, multiple binding sites for Stat5, CCAAT/enhancer-binding proteins, and Ets domain proteins were identified in the distal human enhancer. These transcription factors have already been demonstrated as important regulators of the transcription of milk protein genes in rodents. Thus, a common set of transcription factors appears to be required for the expression of the human beta-casein gene and of milk protein genes in other species.

Animals↗
PubMed1998

[Acute dyspnea].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1998

Comparison of three-dimensional virtual endoscopy with bronchoscopy in patients with oesophageal carcinoma infiltrating the tracheobronchial tree.

Virtual endoscopy (VE) is a technique for performing simulated bronchoscopy using helical CT data of the tracheobronchial tree. In order to evaluate a virtual three-dimensional (3D) endoluminal procedure for the tracheobronchial tree, comparison was made between bronchoscopy, axial CT images and minimal intensity projections (MIP). 21 patients were referred for helical CT because of oesophageal carcinoma shown by bronchoscopy to infiltrate into the trachea or bronchi. Axial CT images obtained on a helical scanner were transferred to a Sparc20 workstation. VE was compared with the axial CT images and the MIP concerning additional information on the location and degree of stenosis gained after 3D reconstruction of the inner surface of the tracheobronchial tree. The accuracy of this VE system was compared with bronchoscopy. Follow-up was performed in two patients to evaluate the tracheobronchial system after stent implantation. All stenoses were identified by VE with no statistically significant difference in detection of location or grading of the stenosis to real time bronchoscopy. Passage of subtotal stenosis was only possible with VE. VE is suitable for following up stent implantation. Submucosal lesions of the tracheobronchial tree could not be detected by VE. There was no statistically significant difference regarding the location of the stenoses between VE, axial CT slices, MIP and bronchoscopy. The VE showed only a statistically significant difference with regard to the degree of stenosis which was underrated on axial CT slices and MIPs. Pitfalls including mucus plugs and wall defects due to the wrong threshold value were a limitation of VE. VE is presently too time-consuming to use in every patient with an infiltrating tumour into the tracheobronchial tree. In conclusion, while VE cannot replace endoscopy of the tracheobronchial tree or the oesophagus, it is an accurate and non-invasive method for identifying endoluminal tumours, grading stenoses and visualizing the tracheobronchial tree beyond stenoses in a small number of patients who are not amenable to endoscopy.

Aged↗
PubMed1998

[Unilateral pulmonary vein atresia in early adulthood].

Unilateral pulmonary vein atresia is a rare condition in adults that may cause serious diagnostic problems because of unspecific clinical findings. A 28-year old female patient is described who presented with signs of recurrent pulmonary embolism with shortness of breathing, unilateral thoracic pain and several episodes of haemoptysis. Ventilation and perfusion scans showed a total lack of perfusion in the right lung with only slight disturbance of ventilation. However, no marked increase of pulmonary artery pressure and no signs of a recent thrombosis of peripheral veins were found. Transoesophageal echocardiography and pulmonary angiography in combination with aortography revealed the diagnosis of unilateral pulmonary vein atresia with abnormal branches of bronchial arteries. There is a considerably left-to-right shunt with return of flow from the bronchial arteries to the right and afterwards to the left pulmonary artery. Clinical, radiological and nuclear medical findings as well as therapeutical options are described.

Adult↗
PubMed1998

[Acute dyspnea].

Explore the source record for details and available documents.

Acute Disease↗
PubMed1998

[Bronchoscopically controlled percutaneous puncture tracheotomy].

With extending duration of translaryngeal intubation the rate of lesions in the oral cavity, pharynx and trachea caused by the orotracheal tube increase. To prevent these complications ventilated patients receive early tracheostomy. PDT is an alternative procedure to the conventional, surgically performed tracheostomy. We performed 60 dilatational tracheostomies using the Ciaglia percutaneous tracheostomy set (W. Cook-Critical Care, Bjaeverskov). Complication rate was 17% due to minor bleeding (n = 7), subcutaneous emphysema (n = 2) and fracture of one tracheal cartilage ring (n = 1). This rate is equivalent to that of surgical procedure. Advantage of PDT is that it can be performed by intensive care doctors without a specific surgical background. Further follow up after removal of the tracheal cannula was uneventful. Tracheal stenosis requiring intervention are rare. The remaining scar after PDT is significantly smaller than after conventional tracheostomy.

Adult↗
PubMed1997

Promoter-dependent synergy between glucocorticoid receptor and Stat5 in the activation of beta-casein gene transcription.

Steroid hormone receptors and Stat factors comprise two distinct families of inducible transcription factors. Activation of a member of each family, namely the glucocorticoid receptor by glucocorticoids and Stat5 by prolactin, is required for the efficient induction of the expression of milk protein genes in the mammary epithelium. We have studied the mode of interaction between Stat5 and the glucocorticoid receptor in the activation of beta-casein gene transcription. The functional role of potential half-palindromic glucocorticoid receptor-binding sites mapped previously in the promoter region was investigated. beta-Casein gene promoter chloramphenicol acetyltransferase constructs containing mutations and deletions in these sites were tested for their responsiveness to the synergistic effect of prolactin and dexamethasone employing COS-7 cells or HC11 mammary epithelial cells. Synergism depended on promoter regions containing intact binding sites for the glucocorticoid receptor and Stat5. The carboxyl-terminal transactivation domains of Stat5a and Stat5b were not required for this synergism. Our results suggest that in lactogenic hormone response elements glucocorticoid receptor molecules bound to nonclassical half-palindromic sites gain competence as transcriptional activators by the interaction with Stat5 molecules binding to vicinal sites.

Animals↗
PubMed1997

Granulocyte-macrophage colony-stimulating factor induces a unique set of STAT factors in murine dendritic cells.

Cytokine-mediated signaling pathways were studied in mouse dendritic cells (DC) by analysis of the activation pattern of STAT factors. Electrophoretic mobility shift assays were performed to detect STAT isoform-specific complexes. Granulocyte-macrophage colony-stimulating factor (GM-CSF) simultaneously induced complexes containing STAT1, STAT3, STAT5A, STAT5B and STAT6. In non-DC, a similar broad activation pattern of STAT factors by GM-CSF or other cytokines has not been observed so far. By comparison, in peritoneal macrophages, GM-CSF induced a complex with the properties of a truncated form of STAT5. Other cytokines tested on DC either failed to induce STAT factors [interleukin (IL)-1 beta, IL-2, IL-15], or activated the same STAT factors as observed in peritoneal macrophages (IL-4, IFN-gamma). Our results implicate a specific effect of GM-CSF on STAT signaling in DC which might account for the cell type-specific effect of this cytokine on development and function.

Animals↗
PubMed1997

Mechanism of interaction between the glucocorticoid receptor and Stat5: role of DNA-binding.

The functional interaction between the glucocorticoid receptor (GR) and the signal transducer and activator of transcription-5 (Stat5) was investigated by studying the synergistic activation of beta-cascin gene transcription by prolactin and glucocorticoids. The synergism was shown to be mediated by a complex hormone response region with multiple binding sites for Stat5, the glucocorticoid receptor, and CCAAT/enhancer binding proteins (C/EBP). HC11 mammary epithelial cells, which contain physiological levels of GR and Stat5, and COS-7 cells overexpressing GR and Stat5 were employed. In both cell types intact binding sites for Stat5 and the GR were a prerequisite for the synergism, whereas C/EBP sites were only required in HC11 cells. Interestingly, the GR sites employed for the synergism were nonclassical, half palindromic sites, which did not function in the absence of activated Stat5 to mediate the action of the GR on transcription. The interaction of GR and Stat5 triggered by the unusual configuration of binding sites appears to represent a novel mechanism by which these two distinct types of transcription factors cooperate. The mode of interaction provides an efficient means to restrict gene expression to conditions where both Stat5 and the GR are activated.

Animals↗