88 results on '"Wolfgang A. Schmidt"'
Search Results
2. OMERACT definition and reliability assessment of chronic ultrasound lesions of the axillary artery in giant cell arteritis
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Alojzija Hočevar, Pierluigi Macchioni, Chetan Mukhtyar, Lene Terslev, Greta Carrara, Tove Lorenzen, Carlo Alberto Scirè, Helen Keen, Cristina Ponte, Aaron Juche, Valentin S. Schäfer, Annamaria Iagnocco, Uffe Møller Døhn, Stavros Chrysidis, Luca Seitz, Christina Duftner, Eugenio de Miguel, Ulrich Fredberg, Wolfgang A. Schmidt, Andreas P. Diamantopoulos, Carlos Pineda, George A W Bruyn, Sara Monti, Petra Hanova, Wolfgang Hartung, Christian Dejaco, Berit Dalsgaard Nielsen, Ib Tønder Hansen, Marcin Milchert, Bhaskar Dasgupta, Tanaz A. Kermani, Schafer, V, Chrysidis, S, Schmidt, W, Duftner, C, Iagnocco, A, Bruyn, G, Carrara, G, De Miguel, E, Diamantopoulos, A, Nielsen, B, Fredberg, U, Hartung, W, Hanova, P, Hansen, I, Hocevar, A, Juche, A, Kermani, T, Lorenzen, T, Macchioni, P, Milchert, M, Dohn, U, Mukhtyar, C, Monti, S, Ponte, C, Seitz, L, Scire, C, Terslev, L, Dasgupta, B, Keen, H, Pineda, C, and Dejaco, C
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medicine.medical_specialty ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Axillary artery ,Giant cell arteriti ,Internal medicine ,medicine.artery ,Large vessel vasculitis ,Ultrasound ,medicine ,Humans ,030212 general & internal medicine ,Chronic ,610 Medicine & health ,Reliability (statistics) ,Ultrasonography ,Giant cell arteritis ,030203 arthritis & rheumatology ,business.industry ,Definition ,OMERACT ,Reproducibility of Results ,medicine.disease ,Anesthesiology and Pain Medicine ,Radiology ,business ,Vasculitis ,Kappa - Abstract
Objectives To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. Methods A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. Results The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. Conclusion The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.
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- 2021
3. Corrigendum to 'Tentative study on radial endobronchial ultrasonography evaluating airway wall thickness before and after bronchial thermoplasty' [Respir. Med. Case Rep. 36 (2022) 101571]
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Shang Yan, Haidong Huang, Zhu Chengjie, Wang Qin, Wolfgang Hohenforst-Schmidt, Lutz Freitag, Kosmas Tsakiridis, Paul Zarogoulidis, Christos Arnaoutoglou, Aris Ioannidis, and Bai Chong
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Pulmonary and Respiratory Medicine - Published
- 2022
4. Cryobiopsy for pneumonitis diagnosis in NSCLC immunotherapy
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Paul Zarogoulidis, Christoforos Kosmidis, Eleni-Isidora Perdikouri, Wolfgang Hohemforst-Schmidt, and Chrisanthi Sardeli
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Pulmonary and Respiratory Medicine - Published
- 2022
5. Investigations in systemic vasculitis – The role of imaging
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Daniel Engelbert Blockmans and Wolfgang A. Schmidt
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030203 arthritis & rheumatology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Systemic Vasculitis ,Ultrasound ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Giant cell arteritis ,0302 clinical medicine ,Rheumatology ,Positron emission tomography ,Positron-Emission Tomography ,Biopsy ,medicine ,Humans ,Radiology ,Tomography, X-Ray Computed ,Vasculitis ,business ,Microscopic polyangiitis ,Systemic vasculitis - Abstract
Imaging plays an increasing role for confirming a suspected diagnosis of giant cell arteritis (GCA) or Takayasu arteritis (TAK). Ultrasound, magnetic resonance imaging (MRI), and computed tomography demonstrate a homogeneous, most commonly concentric, arterial wall thickening. 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) displays increased FDG uptake of inflamed artery walls delineating increased metabolism. Ultrasound and MRI are recommended to be the initial imaging modalities in cranial GCA and TAK, respectively. Extracranial disease can be confirmed by all four modalities, particularly by PET in case of inflammation of unknown origin. If the diagnosis remains uncertain, additional investigations including biopsy and/or additional imaging are recommended. Imaging should be performed by a trained specialist using appropriate operational procedures and settings with appropriate equipment. Further research is necessary on the role of imaging for disease monitoring. This review will discuss advantages and disadvantages of imaging modalities in the diagnosis of vasculitis.
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- 2018
6. A new mode of ventilation for interventional pulmonology. A case with EBUS-TBNA and debulking
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Haidong Huang, Paul Zarogoulidis, Anastasios Kallianos, Georgia Trakada, Christoforos Kosmidis, Wolfgang Hohenforst-Schmidt, Lemonia Veletza, Naim Benhassen, Chong Bai, and Konstantinos Porpodis
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Pulmonary and Respiratory Medicine ,Ebus tbna ,medicine.medical_specialty ,Interventional pulmonology ,Case Report ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,030202 anesthesiology ,law ,medicine ,Intensive care medicine ,Lung cancer ,lcsh:RC705-779 ,Modalities ,business.industry ,Late stage ,lcsh:Diseases of the respiratory system ,medicine.disease ,Debulking ,Ventilation ,030220 oncology & carcinogenesis ,EBUS ,Ventilation (architecture) ,Radiology ,business - Abstract
Lung cancer is still underdiagnosed mainly due to lack of symptoms. Most patients are diagnosed in a late stage where unfortunately only systematic therapy can be applied. Fortunately in the last five years several novel therapies and combinations have emerged. However; in certain situations local therapeutics modalities have to be applied in order to solve emergency problems as in the case that we will present. Convex-EBUS probe was used along with a novel method of ventilation which keeps PCO2 concentration satisfyingly low. Keywords: Lung cancer, Interventional pulmonology, Ventilation, EBUS
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- 2018
7. A prospective controlled randomized multicenter study to evaluate the severity of compensatory sweating after one-stage bilateral thoracic sympathectomy versus unilateral thoracic sympathectomy in the dominant side
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Hamilton, Niura Noro, primary, Tedde, Miguel Lia, additional, Wolosker, Nelson, additional, Aguiar, Wolfgang William Schmidt, additional, Ferreira, Hylas Paiva da Costa, additional, Oliveira, Humberto Alves de, additional, Lima, Alexandre Marcelo Rodrigues, additional, Westphal, Fernando Luiz, additional, Oliveira, Marina Varela Braga de, additional, Riuto, Fabio de Oliveira, additional, Pereira, Sergio Tadeu Lima F, additional, Rezende, Guilherme Cançado, additional, Valero, Caroline Elizabeth Brero, additional, and Pego-Fernandes, Paulo M., additional
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- 2020
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8. Solitary fibrous tumor: A center's experience and an overview of the symptomatology, the diagnostic and therapeutic procedures of this rare tumor
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Periclis Tomos, Christoforos Kosmidis, Bora Kosan, Vasileios Leivaditis, Zoi Tsilogianni, Christophoros Kotoulas, Manfred Dahm, Naim Benhassen, Konstantinos Grapatsas, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Haidong Huang, and Efstratios Koletsis
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Pulmonary and Respiratory Medicine ,Solitary fibrous tumor ,medicine.medical_specialty ,medicine.medical_treatment ,Case Report ,Disease ,Video-assisted thoracoscopic surgery (VATS) ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Thoracotomy ,lcsh:RC705-779 ,Solitary Fibrous Tumor of the Pleura (SFTP) ,business.industry ,lcsh:Diseases of the respiratory system ,medicine.disease ,Surgery ,Rare tumor ,030228 respiratory system ,030220 oncology & carcinogenesis ,Needle biopsy ,Lobectomy ,medicine.symptom ,business ,Rare disease - Abstract
Solitary Fibrous Tumor of the Pleura (SFTP) is a rare tumor of the pleura. Worldwide about 800 patients diagnosed with this oncological entity have been described in the existing literature. We report our center's 13 year experience. During this time three patients suffering from this rare disease have been treated in our department. All patients were asymptomatic and their diagnosis was initially triggered by a random finding in a routine chest x-ray. The diagnosis was set preoperatively through a needle biopsy under computer tomography (CT) guidance. The tumors were resected surgically though video-assisted thoracoscopic surgery (VATS) or thoracotomy. Because of the lack of specific guidelines due to the rarity of the disease a long-term, systematic follow-up was recommended and performed. Parallel an overview of the diagnostic and therapeutic procedures of the rare tumor is made.
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- 2017
9. Immunotherapy 'Shock' with vitiligo due to nivolumab administration as third line therapy in lung adenocarcinoma
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Aggeliki Rapti, Dimitrios Drougas, Chong Bai, Chrysa Sardeli, Haidong Huang, Liana Papaemmanouil, Christoforos Kosmidis, Dimitrios Hatzibougias, Paul Zarogoulidis, Wolfgang Hohenforst-Schmidt, Lemonia Veletza, Georgia Trakada, Anastasios Kallianos, and Theodora Tsiouda
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Case Report ,Vitiligo ,Adenocarcinoma ,NSCLC ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Adverse effect ,lcsh:RC705-779 ,Lung ,business.industry ,lcsh:Diseases of the respiratory system ,Immunotherapy ,medicine.disease ,Nivolumab ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Shock (circulatory) ,EBUS ,medicine.symptom ,business ,Tyrosine kinase - Abstract
Non-small cell lung cancer is still diagnosed at late stage due to the lack of early symptoms and methods of diagnostic prevention. In the past ten years several targeted therapies have been introduced or explored. Tyrosine kinase inhibitors and immunotherapy are currently considered the most effective and safe therapies in comparison to the non-specific cytotoxic agents. Regarding tyrosine kinase inhibitors the adverse effects have been fully explored, however; on the other hand for immunotherapy there are still several issues to be clarified. We report a rare case of a patient with lung cancer adenocarcinoma who developed vitiligo throughout his body after nivolumab administration.
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- 2017
10. Bronchogenic cyst or lung cancer. Only biopsy can tell
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Dimitris Paliouras, Haidong Huang, Chong Bai, Dimitrios Hatzibougias, Electra Michalopoulou-Manoloutsiou, Wolfgang Hohenforst-Schmidt, Maria Saroglou, Paul Zarogoulidis, Anastasios Vagionas, Konstantinos Drevelegas, Nikolaos Barbetakis, Bojan Zaric, Stavros Tryfon, and Kosmas Tsakiridis
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Pulmonary and Respiratory Medicine ,Thorax ,medicine.medical_specialty ,Bronchogenic cyst ,Case Report ,19G needle ,Chest pain ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Biopsy ,medicine ,Esophagus ,Lung cancer ,lcsh:RC705-779 ,Bronchus ,medicine.diagnostic_test ,business.industry ,lcsh:Diseases of the respiratory system ,medicine.disease ,medicine.anatomical_structure ,030228 respiratory system ,030220 oncology & carcinogenesis ,EBUS ,Radiology ,medicine.symptom ,business - Abstract
Bronchogenic cysts are rare congenital malformations which derive from primitive ventral foregut. They are usually observed in intrathoracically. A fifty year old male was admitted for the investigation of a three month chest pain. Computed tomography scan of the thorax revealed a lesion around the esophagus and left stem bronchus. Endobronchial ultrasound with convex probe and a 19G needle biopsy revealed a bronchogenic cystic which was removed with video assisted thoracic surgery. Initial radiologic assessment although was thought to be lung cancer because of the smoking habit it turned out to be benignancy. EBUS-TBNAB with 10G needle is safe and absolutely necessary for these lesions, as they take large samples.
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- 2021
11. Treg-dependent immunosuppression triggers effector T cell dysfunction via the STING/ILC2 axis
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Haidong Huang, Savvas Petanidis, Konstantinos Porpodis, Wolfgang Hohenforst-Schmidt, Doxakis Anestakis, Drosos Tsavlis, Paul Zarogoulidis, Kalliopi Domvri, Lutz Freitag, Theodora Katopodi, and Chong Bai
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Male ,0301 basic medicine ,Lung Neoplasms ,LAG3 ,medicine.medical_treatment ,Transplantation, Heterologous ,Immunology ,Nitric Oxide Synthase Type II ,GATA3 Transcription Factor ,CD8-Positive T-Lymphocytes ,T-Lymphocytes, Regulatory ,Proto-Oncogene Proteins p21(ras) ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cell Line, Tumor ,Immune Tolerance ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Lung cancer ,Tumor microenvironment ,business.industry ,GATA3 ,Membrane Proteins ,Immunosuppression ,medicine.disease ,Immunity, Innate ,Mitochondria ,Mice, Inbred C57BL ,030104 developmental biology ,A549 Cells ,Cancer research ,Reactive Oxygen Species ,business ,Neoplasm Transplantation ,CD8 ,030215 immunology - Abstract
Lung cancer remains the leading cause of cancer-related deaths and despite extensive research, the survival rate of lung cancer patients remains significantly low. Recent data reveal that aberrant Kras signaling drives regulatory T cells (Tregs) present in lung tumor microenvironment to establish immune deregulation and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras in Treg-related immunosuppression and its involvement in tumor-associated metabolic reprogramming. Findings reveal Tregs to prompt GATA3/NOS2-related immunosuppression via STING inhibition which triggers a decline in CD4+ T infiltration, and a subsequent increase in lung metastatic burden. Enhanced Treg expression was also associated with low T/MDSC ratio through restriction of CD8+CD44+CD62L- T effector cells, contributing to a tumor-promoting status. Specifically, TIM3+/LAG3+ Tregs prompted Kras-related immunosuppressive chemoresistance and were associated with T cell dysfunction. This Treg-dependent immunosuppression correlated with CD8 T cell exhaustion phenotype and ILC2 augmentation in mice. Moreover, enhanced Treg expression promoted activation-induced cell death (AICD) of T lymphocytes and guided lymph node metastasis in vivo. Overall, these findings demonstrate the multifaceted roles of Tregs in sustaining lung immunosuppressive neoplasia through tumor microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
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- 2021
12. Imaging of vasculitis: State of the art
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Francesco Muratore, Carlo Salvarani, Nicolò Pipitone, and Wolfgang A. Schmidt
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Vasculitis ,Positron emission tomography ,medicine.medical_specialty ,Vascular complication ,030204 cardiovascular system & hematology ,Imaging ,Disease course ,03 medical and health sciences ,Magnetic resonance imaging ,0302 clinical medicine ,Rheumatology ,Large vessel vasculitis ,Ultrasound ,medicine ,Medical imaging ,Humans ,Color duplex ultrasonography ,Computed tomography ,Ultrasonography ,030203 arthritis & rheumatology ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,Positron-Emission Tomography ,cardiovascular system ,Radiology ,Tomography, X-Ray Computed ,business ,Preclinical imaging - Abstract
The increasing availability and improvement of imaging techniques are making a profound impact in the evaluation and management of patients with vasculitis, particularly for those with large vessel vasculitis, and will most likely play an ever more important role in the future. Deep, large vessels can be examined by CT or MRI, while ultrasound is the method of choice for the evaluation of superficial vessels (such as temporal, carotid, and axillary arteries). PET is very sensitive in detecting large vessel inflammation, but it does not delineate the vessel wall. Imaging studies can also be used to monitor the disease course and the development of late vascular complication. This review will focus on the role of imaging studies in diagnosing and monitoring LVV, but will also mention their principal applications in medium and small-sized vessel vasculitis. Indications and limitations of the available imaging modalities will be discussed as well.
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- 2016
13. An approximation of small-time probability density functions in a general jump diffusion model
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Le Zhang and Wolfgang M. Schmidt
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Mathematical optimization ,050208 finance ,Characteristic function (probability theory) ,Stochastic volatility ,Applied Mathematics ,05 social sciences ,Jump diffusion ,Probability density function ,Moment-generating function ,01 natural sciences ,Heston model ,010104 statistics & probability ,Computational Mathematics ,0502 economics and business ,Jump ,Statistical physics ,0101 mathematics ,Diffusion (business) ,Mathematics - Abstract
We propose a method for approximating probability density functions related to multidimensional jump diffusion processes. For small-time horizons, a closed-form approximation of the characteristic function is derived based on the Ito-Taylor expansion. The probability density function is then approximated numerically by inverting the characteristic function using fast Fourier transform. As application we consider a general stochastic volatility model, which involves time-/state-dependent drift and diffusion functions as well as jump components. We test our approach under the Heston model and the Bates model and show that our method provides accurate approximations.
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- 2016
14. Long-Term Outcomes After Treatment With a Paclitaxel-Coated Balloon Versus Balloon Angioplasty
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Wolfgang Hohenforst-Schmidt, Volkhard Kurowski, Marc Ohlow, Holger Thiele, Sinisa Markovic, Ralf Birkemeyer, Stephan Achenbach, Stefan Zimmermann, Moritz von Cranach, Jochen Wöhrle, Matthias Waliszewski, Sandra Lonke, Andreas Brugger, Harald Rittger, Johannes Brachmann, Werner G. Daniel, and Christian Schlundt
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Stent ,medicine.disease ,Balloon ,Surgery ,Coronary artery disease ,Restenosis ,Drug-eluting stent ,Internal medicine ,Angioplasty ,Cardiovascular agent ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Mace - Abstract
Objectives The intention this PEPCAD-DES (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter) study update was to demonstrate the safety and efficacy of paclitaxel-coated balloon (PCB) angioplasty in patients with DES-ISR at 3 years. Background In the PEPCAD-DES trial late lumen loss and the need for repeat target lesion revascularization (TLR) was significantly reduced with PCB angioplasty compared with plain old balloon angioplasty (POBA) in patients with drug-eluting stent in-stent restenosis (DES-ISR) at 6 months. We evaluated whether the clinical benefit of reduced TLR and major adverse cardiac events (MACE) was maintained up to 3 years. Methods A total of 110 patients with DES-ISR in native coronary arteries with reference diameters ranging from 2.5 mm to 3.5 mm and lesion lengths ≤22 mm were randomized to treatment with either PCB or POBA in a multicenter, randomized, single-blind clinical study. With a 2:1 randomization, 72 patients were randomized to the PCB group and 38 patients to the POBA group. At baseline, there were lesions with at least 2 stent layers in PCB (52.8%, 38 of 72) and POBA (55.3%, 21 of 38) patients. Results At 36 months, the TLR rates were significantly lower in the PCB group compared with the POBA control group (19.4% vs. 36.8%; p = 0.046). Multiple TLRs in individual patients were more frequent in the POBA group compared with the PCB group (more than 1 TLR: POBA, 13.2%; PCB, 1.4%; p = 0.021). The 36-month MACE rate was significantly reduced in the PCB group compared with the POBA group (20.8% vs. 52.6%, log-rank p = 0.001). Conclusions PCB angioplasty was superior to POBA for the treatment of DES-ISR patients in terms of MACE and TLR for up to 36 months. There was no late catch-up phenomenon. (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter [PEPCAD-DES]; NCT00998439 )
- Published
- 2015
15. 'Liquid elbows' due to afatinib administration
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Aggeliki Rapti, Konstantinos Porpodis, Panos Chinelis, Haidong Huang, Anastasios Kallianos, Lemonia Velentza, Paul Zarogoulidis, Georgia Trakada, Wolfgang Hohenforst-Schmidt, Anastasia Athanasiadou, and Theodora Tsiouda
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,medicine.drug_class ,Afatinib ,Case Report ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Gefitinib ,medicine ,Epidermal growth factor receptor ,lcsh:RC705-779 ,Tyrosine kinase inhibitors ,Olecranon bursitis ,biology ,business.industry ,lcsh:Diseases of the respiratory system ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Elbow bursitis ,Adenocarcinoma ,Erlotinib ,business ,Tyrosine kinase ,medicine.drug - Abstract
Non-small cell lung cancer adenocarcinoma in the past decade has targeted therapies as the cornerstone for therapy. In specific patients with epidermal growth factor receptor mutation have three different therapy approaches with the tyrosine kinase inhibitors: erlotinib, gefitinib and afatinib. Nowadays we can use tyrosine kinase inhibitors as second line treatment for squamous cell carcinoma. We present a case with a patient with squamous cell carcinoma receiving afatinib tyrosine kinase inhibitor who presented elbow bursitis or olecranon bursitis in both elbows.
- Published
- 2017
16. Innovative use of a Montgomery cannula in the bronchoscopic management of tracheal stenosis and failed tracheostomy decannulation
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Qiang Li, Paul Zarogoulidis, Haidong Huang, Wolfgang Hohenforst-Schmidt, Changming Chen, Harmeet Bedi, and Chong Bai
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Interventional pulmonology ,Therapeutic Bronchoscopy ,medicine.medical_treatment ,Tracheal stenosis ,Case Report ,Case presentation ,030204 cardiovascular system & hematology ,Montgomery cannula ,03 medical and health sciences ,Therapeutic bronchoscopy ,0302 clinical medicine ,Tracheotomy ,medicine ,030223 otorhinolaryngology ,Tracheostomy tube ,lcsh:RC705-779 ,business.industry ,lcsh:Diseases of the respiratory system ,Cannula ,Silicone stent ,Difficult decannulation ,Tracheal Stenosis ,Surgery ,Clinical Practice ,business - Abstract
Background Endoprosthesis are being used in the everyday clinical practice either as a permanent solution or transient. They can be used in both benign and malignant situations. Case presentation We report a case in which a temporary Montgomery cannula is used in conjunction with therapeutic bronchoscopy to manage a patient with failed tracheostomy decannulation secondary to a distal complex tracheal stenosis. Conclusions This innovative use of the Montgomery cannula allowed for successful management of the patient's tracheal stenosis and subsequent tracheostomy tube decannulation.
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- 2017
17. Bronchial HPV; the good the bad and the unknown
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Maria Saroglou, Wolfgang Hohenforst-Schmidt, Chong Bai, Haidong Huang, Kosmas Tsakiridis, Evaggelia Athanasiou, Stavros Tryfon, Paul Zarogoulidis, Konstantinos Sapalidis, Christoforos Kosmidis, Anastasios Vagionas, Dimitris Hatzibougias, and Sofia Baka
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Case Report ,Cruotherapy ,Benign tumor ,03 medical and health sciences ,0302 clinical medicine ,Bronchial structure ,Bronchoscopy ,Atypia ,medicine ,Carcinoma ,Nuclear atypia ,Solitary tracheobronchial papilloma ,YAG-Laser ,hpv ,lcsh:RC705-779 ,medicine.diagnostic_test ,business.industry ,lcsh:Diseases of the respiratory system ,medicine.disease ,Jet-ventilation ,Argon plasma ,030228 respiratory system ,Dysplasia ,030220 oncology & carcinogenesis ,EBUS ,Surgery ,business - Abstract
Background Solitary tracheobronchial papilloma (STBP) is a rare benign tumor. Human papilloma virus (HPV) infection is associated with dysplasia and a high risk of carcinoma. Case 1 Sixty five year old male with hemoptysis and with coilocytic atypia, indicating the presence of HPV. Case 2 Thirty two year old female with a polypoid villoglandular bronchial structure and no cytoplasmic or nuclear atypia but prominent microvilli. Discussion Tissue sample is the best sample in order to determine and distinguish the two entities, local treatment should be considered as first option when possible.
- Published
- 2020
18. How past market movements affect correlation and volatility
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Wolfgang M. Schmidt and Christoph Becker
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Driving factors ,Correlation ,Economics and Econometrics ,Financial contagion ,Financial economics ,Autoregressive conditional heteroskedasticity ,Financial market ,Economics ,Diversification (finance) ,Volatility (finance) ,Finance ,Stock (geology) - Abstract
The influence of past stock price movements on correlations and volatilities is essential for understanding diversification and contagion in financial markets. We develop a model that makes the influence of past returns, aggregated into driving factors for correlations and volatilities, explicit. Employing information about recent market movements leads to a more realistic model for the behavior of stock returns in a downturn than conventional models. Our approach offers a fresh perspective on the behavior of stock markets, and provides an alternative to the concept of exceedance correlation. For a US investor we find that international diversification in China or the UK remains beneficial in a crisis.
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- 2015
19. Internal mouthpiece designs as a future perspective for enhanced aerosol deposition. Comparative results for aerosol chemotherapy and aerosol antibiotics
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Qiang Li, Dimitris Petridis, Wolfgang Hohenforst-Schmidt, Lutz Freitag, Lonny Yarmus, Ioannis Kioumis, Dionysios Spyratos, Kaid Darwiche, Paul Zarogoulidis, Konstantinos Zarogoulidis, Konstantinos Porpodis, Christos Ritzoulis, and Haidong Huang
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Aerosols ,Future perspective ,Chemistry ,Medizin ,Analytical chemistry ,Mist ,Pharmaceutical Science ,Antineoplastic Agents ,Equipment Design ,Anti-Bacterial Agents ,Aerosol ,Toxicology ,Drug Delivery Systems ,Aerosol deposition ,Delayed-Action Preparations ,Aerodynamic diameter ,Mouthpiece ,Forecasting - Abstract
Background In an effort to identify factors producing a finest mist from Jet-Nebulizers we designed 2 mouthpieces with 4 different internal designs and 1–3 compartments. Materials and methods Ten different drugs previous used with their “ideal” combination of jet-nebulizer, residual-cup and loading were used. For each drug the mass median aerodynamic diameter size had been established along with their “ideal” combination. Results For both mouthpiece, drug was the most important factor due the high F -values ( F large = 251.7, p F small = 60.1, p F large = 5.99, p = 0.001, F small = 1.72, p = 0.178). Cross designs create the smallest droplets (2.271) so differing from the other designs whose mean droplets were greater and equal ranging between 2.39 and 2.447. The number of compartments in the two devices regarding the 10 drugs was found not statistically significant ( p -values 0.768 and 0.532 respectively). Interaction effects between drugs and design were statistically significant for both devices ( F large = 8.87, p F small = 5.33, p Conclusion Based on our experiment we conclude that further improvement of the drugs intended for aerosol production is needed. In addition, the mouthpiece design and size play an important role in further enhancing the fine mist production and therefore further experimentation is needed.
- Published
- 2013
20. Interest rate term structure modelling
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Wolfgang M. Schmidt
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Information Systems and Management ,Actuarial science ,General Computer Science ,business.industry ,media_common.quotation_subject ,Risk-free interest rate ,Management Science and Operations Research ,Industrial and Manufacturing Engineering ,Interest rate ,Investment theory ,Risk analysis (engineering) ,Modeling and Simulation ,Covered interest arbitrage ,Economics ,Yield curve ,Rational pricing ,business ,Rendleman–Bartter model ,Risk management ,media_common - Abstract
This article surveys approaches to modelling the term structure of interest rates. Over the last few decades several frameworks have been developed, which are actively used in banks for the pricing and risk management of interest rate related products. There seems to be a need for an introductory overview of modelling approaches aimed at the yet unfamiliar reader with a quantitative background.
- Published
- 2011
21. SNP-array based whole genome homozygosity mapping: A quick and powerful tool to achieve an accurate diagnosis in LGMD2 patients
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Reginald E. Bittner, Karin Gruber, Maria Schabhüttl, Lea Papić, Romana Höftberger, Michaela Auer-Grumbach, Wolfgang M. Schmidt, Thomas R. Pieber, Dirk Fischer, Carina Fischer, Andreas R. Janecke, Thomas Ströbel, and Slave Trajanoski
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Male ,Caveolin 3 ,DNA Mutational Analysis ,Muscle Proteins ,Genome-wide association study ,Consanguinity ,0302 clinical medicine ,CAPN3 ,Genetics(clinical) ,Child ,Genetics (clinical) ,Genetics ,0303 health sciences ,Calpain ,Homozygote ,Chromosome Mapping ,General Medicine ,Disease gene identification ,3. Good health ,Pedigree ,Female ,Original Article ,SNP array ,FKRP ,Adult ,Adolescent ,Genotype ,Blotting, Western ,Single-nucleotide polymorphism ,Locus (genetics) ,LGMD2 ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Chromosome 15 ,Homozygosity mapping ,SNP ,Humans ,Pentosyltransferases ,030304 developmental biology ,Family Health ,Base Sequence ,Genome, Human ,Proteins ,Muscular Dystrophies, Limb-Girdle ,CAV3 ,Mutation ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
A large number of novel disease genes have been identified by homozygosity mapping and the positional candidate approach. In this study we used single nucleotide polymorphism (SNP) array-based, whole genome homozygosity mapping as the first step to a molecular diagnosis in the highly heterogeneous muscle disease, limb girdle muscular dystrophy (LGMD). In a consanguineous family, both affected siblings showed homozygous blocks on chromosome 15 corresponding to the LGMD2A locus. Direct sequencing of CAPN3, encoding calpain-3, identified a homozygous deletion c.483delG (p.Ile162SerfsX17). In a sporadic LGMD patient complete absence of caveolin-3 on Western blot was observed. However, a mutation in CAV3 could not be detected. Homozygosity mapping revealed a large homozygous block at the LGMD2I locus, and direct sequencing of FKRP encoding fukutin-related-protein detected the common homozygous c.826 C>A (p.Leu276Ile) mutation. Subsequent re-examination of this patient's muscle biopsy showed aberrant α-dystroglycan glycosylation. In summary, we show that whole-genome homozygosity mapping using low cost SNP arrays provides a fast and non-invasive method to identify disease-causing mutations in sporadic patients or sibs from consanguineous families in LGMD2. Furthermore, this is the first study describing that in addition to PTRF, encoding polymerase I and transcript release factor, FKRP mutations may cause secondary caveolin-3 deficiency.
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- 2011
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22. Endogenous hyperinsulinaemia in insulinoma patients is not associated with changes in beta-cell area and turnover in the tumor-adjacent pancreas
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Enzo Bonora, Wolfgang E. Schmidt, Chiara Montemurro, Juris J. Meier, Christina U. Köhler, Waldemar Uhl, and Andrea Tannapfel
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Pancreatic disease ,Physiology ,medicine.medical_treatment ,Hyperinsulinemia ,beta-cell ,insulinoma ,Clinical Biochemistry ,Apoptosis ,In Vitro Techniques ,Biology ,Biochemistry ,Cellular and Molecular Neuroscience ,Endocrinology ,Hyperinsulinism ,Insulin-Secreting Cells ,Internal medicine ,In Situ Nick-End Labeling ,medicine ,Humans ,Insulin ,Insulinoma ,Aged ,Aged, 80 and over ,geography ,geography.geographical_feature_category ,Middle Aged ,medicine.disease ,Islet ,Immunohistochemistry ,Ki-67 Antigen ,medicine.anatomical_structure ,Female ,Beta cell ,Pancreas - Abstract
Introduction Insulin therapy has been suggested to preserve beta-cell mass in patients with diabetes through the mechanisms of beta-cell rest as well as direct effects on beta-cell proliferation. However, data about the effects of hyperinsulinism on beta-cell mass and turnover in humans are sparse. Patients and methods Pancreatic tissue specimens from five patients with pancreatic insulinomas and ten non-diabetic control subjects were examined. Pancreatic sections were stained for insulin, Ki67 (replication) and TUNEL (apoptosis), and quantitative morphometric analyses were performed. Results Fractional beta-cell area was 1.11% ± 0.67% in the tumor-free pancreatic tissue of the insulinoma patients and 0.78% ± 0.26% in the control group (p = 0.19). There also were no differences in islet size (p = 0.62) or beta-cell nuclear diameter (p = 0.20). Beta-cell replication and apoptosis were infrequently detected, without any measurable differences between the groups. There were also no differences in percentage of duct cells expressing insulin (p = 0.47), a surrogate marker for islet neogenesis. Conclusions Beta-cell area and turnover are not significantly altered in the proximity of intra-pancreatic insulinomas. Future in vivo studies, ideally employing larger animal models, are warranted to further evaluate the impact of exogenous insulin on beta-cell turnover.
- Published
- 2010
23. Pituitary Adenylate Cyclase Activating Polypeptide
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Carine Rosignoli, Martin Steinhoff, Martin Schmelz, Ralf Paus, Victoria M. Shpacovitch, Stephan Seeliger, Dieter Metze, Roman Rukwied, Wolfgang E. Schmidt, Ulrike von Arnim, Johannes Voegel, Anjona Schmidt-Choudhury, and Jörg Buddenkotte
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CD31 ,endocrine system ,0303 health sciences ,medicine.medical_specialty ,Neurogenic inflammation ,integumentary system ,Vasoactive intestinal peptide ,Human skin ,Biology ,3. Good health ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,medicine.anatomical_structure ,In vivo ,Internal medicine ,medicine ,Receptor ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,030304 developmental biology ,Endocrine gland ,Blood vessel - Abstract
Pituitary adenylate cyclase-activating peptide (PACAP) is an important neuropeptide and immunomodulator in various tissues. Although this peptide and its receptors (ie, VPAC1R, VPAC2R, and PAC1R) are expressed in human skin, their biological roles are unknown. Therefore, we tested whether PACAP regulates vascular responses in human skin in vivo. When injected intravenously, PACAP induced a significant, concentration-dependent vascular response (ie, flush, erythema, edema) and mediated a significant and concentration-dependent increase in intrarectal body temperature that peaked at 2.7°C. Topical application of PACAP induced marked concentration-dependent edema. Immunohistochemistry revealed a close association of PACAP-immunoreactive nerve fibers with mast cells and dermal blood vessels. VPAC1R was expressed by dermal endothelial cells, CD4+ and CD8+ T cells, mast cells, and keratinocytes, whereas VPAC2R was expressed only in keratinocytes. VPAC1R protein and mRNA were also detected in human dermal microvascular endothelial cells. The PACAP-induced change in cAMP production in these cells demonstrated VPAC1R to be functional. PACAP treatment of organ-cultured human skin strongly increased the number of CD31+ vessel cross-sections. Taken together, these results suggest that PACAP directly induces vascular responses that may be associated with neurogenic inflammation, indicating for the first time that PACAP may be a crucial vascular regulator in human skin in vivo. Antagonists to PACAP function may be beneficial for the treatment of inflammatory skin diseases with a neurogenic component.
- Published
- 2010
24. Substance P and calcitonin gene related peptide induce TGF-alpha expression in epithelial cells via mast cells and fibroblasts
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I Werner-Martini, Wolfgang E. Schmidt, Peter R. Hoffmann, Karoline Hoeck, and Susanne Deters
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Nervous system ,TGF alpha ,medicine.medical_specialty ,Neuroeffector ,Physiology ,Calcitonin Gene-Related Peptide ,Blotting, Western ,Clinical Biochemistry ,Substance P ,Calcitonin gene-related peptide ,Biology ,Biochemistry ,Cell Line ,Mice ,Cellular and Molecular Neuroscience ,Endocrinology ,Transforming Growth Factor beta ,Internal medicine ,medicine ,Animals ,Mast Cells ,Intestinal Mucosa ,Fibroblast ,Cell Proliferation ,Reverse Transcriptase Polymerase Chain Reaction ,Epithelial Cells ,Fibroblasts ,Transforming Growth Factor alpha ,Mast cell ,Epithelium ,Rats ,Cell biology ,ErbB Receptors ,medicine.anatomical_structure ,Transforming growth factor - Abstract
Objective/background Signals for the expression of EGF, TGFα and related proteins are largely unknown. Having shown earlier, that activation of the afferent sensory nervous system by capsaicin induced epithelial cell proliferation and TGFα expression in vivo the aim of this study was to demonstrate, that neurotransmitters of the afferent sensory nervous system induce TGFα expression via mast cells and fibroblasts. Results A significant increase in TGFα-mRNA and protein expression was detected in epithelial cells exposed to supernatants of CGRP-stimulated mast cells and SP-stimulated fibroblasts. Epithelial cell proliferation was only detected in epithelial cells exposed to supernatants of CGRP-stimulated mast cells but not in epithelial cells exposed to supernatants of SP-stimulated fibroblasts. TGFβ mRNA expression was increased in epithelial cells exposed to fibroblasts but not to mast cells. No increase in EGF-receptor expression was detected in epithelial cells exposed to either fibroblast or mast cell supernatants. Conclusion Neurotransmitters of the afferent sensory nervous system induce TGFα expression in epithelial cells mediated by mast cells and fibroblasts. Release of CGRP and SP from neuroeffector junctions is an important signal for the TGFα expression after mucosal injury. Mucosal expression of TGFα may contribute to the protective effects of the sensory nervous system after mucosal injury.
- Published
- 2010
25. Selective amino acid deficiency in patients with impaired glucose tolerance and type 2 diabetes
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Juris J. Meier, Peter R. Ritter, Bjoern A. Menge, Mark Ellrichmann, Henning Schrader, Waldemar Uhl, and Wolfgang E. Schmidt
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Male ,medicine.medical_specialty ,Arginine ,Physiology ,Clinical Biochemistry ,Protein metabolism ,Type 2 diabetes ,Biology ,Biochemistry ,Impaired glucose tolerance ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,Glucose Intolerance ,medicine ,Humans ,Amino Acids ,chemistry.chemical_classification ,Middle Aged ,Reference Standards ,medicine.disease ,Amino acid ,Glutamine ,Diabetes Mellitus, Type 2 ,chemistry ,Female - Abstract
Amino acids are important modulators of glucose metabolism, insulin secretion and insulin sensitivity. However, little is known about the changes in amino acid metabolism in patients with diabetes.The circulating amino acid levels were determined in 17 patients with type 2 diabetes, 17 individuals with impaired glucose tolerance (IGT), and 14 control subjects.Total amino acid concentrations were 2850+/-57micromol/l in patients with type 2 diabetes, 2980+/-77micromol/l in individuals with IGT, and 2886+/-74micromol/l in control subjects (p=0.38). Patients with type 2 diabetes exhibited significant reductions in the concentrations of gamma-aminobutyric acid (GABA), arginine, glutamine and phosphoethanolamine (p0.05), whereas valine levels were higher than in controls (p=0.008). In IGT subjects, GABA levels were reduced, while tyrosine concentrations were increased (p0.05). The plasma levels of essential amino acids were positively related to fasting and post-challenge glucose levels, fasting C-peptide, HOMA insulin resistance and fasting glucagon levels (p0.05).Total amino acid levels are similar in patients with diabetes, IGT subjects and controls, but the individual levels of several amino acids differ significantly between these groups. These alterations may contribute to the disturbances in insulin secretion and action in diabetic patients and may provide a rationale for offering specific amino acid supplementations to diabetic patients.
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- 2010
26. Effects of the cathelicidin LL-37 on intestinal epithelial barrier integrity
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Jan-Michel Otte, Sarah Strauss, Wolfgang E. Schmidt, Frank Schmitz, Ansgar M. Chromik, Lars Steinstraesser, Stephan Brand, and Anna-Elisabeth Zdebik
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MAPK/ERK pathway ,Cell Survival ,Physiology ,Angiogenesis ,medicine.medical_treatment ,Blotting, Western ,Clinical Biochemistry ,Apoptosis ,Polymerase Chain Reaction ,Biochemistry ,Cell Line ,Cathelicidin ,Necrosis ,Cellular and Molecular Neuroscience ,HT29 Cells ,Endocrinology ,Cathelicidins ,medicine ,Humans ,Epidermal growth factor receptor ,Fibroblast ,Cell Proliferation ,biology ,Epithelial Cells ,Intestinal epithelium ,Peptide Fragments ,Cell biology ,Intestines ,medicine.anatomical_structure ,Immunology ,biology.protein ,Caco-2 Cells ,Wound healing - Abstract
The human cathelicidin LL-37 is involved in innate immune responses, angiogenesis and wound healing. Functions in maintenance and re-establishment of intestinal barrier integrity have not been characterized yet. Following direct and indirect stimulation of human colonic HT-29 and Caco-2 cells with LL-37 the cellular viability, rate of apoptosis, proliferation and wound healing were determined. Expression of mucins and growth factors was quantified by real-time PCR and Western blotting. Direct application of LL-37 stimulated migration in Caco-2 cells expressing the proposed LL-37 receptor P2X7. Intestinal epithelial cell (IEC) proliferation was not altered. Indirectly, LL-37 significantly enhanced IEC migration via release of growth factors from subepithelial fibroblasts and IEC. Furthermore, LL-37 induced the expression of protective mucins in IEC and abated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis in IEC. LL-37 induced signaling is mediated in part by the P2X7 receptor, the epidermal growth factor receptor and the p38 mitogen-activated protein kinase (MAPK). LL-37 contributes to maintenance and re-establishment of the intestinal barrier integrity via direct and indirect pathways. These features, in addition to its known antimicrobial properties, suggest an important role for this peptide in intestinal homeostasis.
- Published
- 2009
27. Powers of roots in linear spaces
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Wolfgang M. Schmidt and Andrzej Schinzel
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Combinatorics ,Algebra and Number Theory ,Property (philosophy) ,Linear form ,Mathematical analysis ,Radicals in a vector space ,Field (mathematics) ,Natural number ,Powers of radicals ,Space (mathematics) ,Mathematics - Abstract
Suppose K is a field, αn∈K∗, and n is the least natural number with this property. We study the question on how many powers αj, 0⩽j
- Published
- 2009
28. Reduced Pancreatic Volume and β-Cell Area in Patients With Chronic Pancreatitis
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Henning Schrader, Waldemar Uhl, Wolfgang E. Schmidt, Simone Schneider, Bjoern A. Menge, Andrea Tannapfel, Juris J. Meier, and Orlin Belyaev
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Adult ,Male ,medicine.medical_specialty ,Cell ,Apoptosis ,Islets of Langerhans ,Insulin-Secreting Cells ,Pancreatitis, Chronic ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Endocrine system ,Pancreas ,Aged ,geography ,geography.geographical_feature_category ,Hepatology ,business.industry ,Gastroenterology ,Organ Size ,Middle Aged ,medicine.disease ,Islet ,medicine.anatomical_structure ,Endocrinology ,Case-Control Studies ,Pancreatitis ,Immunohistochemistry ,Female ,Tomography, X-Ray Computed ,business ,Follow-Up Studies - Abstract
Chronic pancreatitis (CP) often leads to the development of diabetes. To understand better this pathogenic mechanism, we investigated whether islet cell area and pancreatic volume are reduced in CP patients, islet cell turnover increases in CP patients, and islet cells are less vulnerable to apoptosis than acinar cells.Pancreatic tissues from 43 patients with CP and 27 controls were examined by immunohistochemistry and quantitative morphometry. Pancreas volume was determined using abdominal computed tomography data.The pancreatic volumes were 64.9 +/- 4.3 cm(3) in CP patients and 82.3 +/- 6.7 cm(3) in controls (P = .035). beta-cell areas were 0.69% +/- 0.08% in CP patients and 0.97% +/- 0.08% in controls (P = .017), whereas alpha-cell areas did not differ between the groups (P = .47). There were no differences in the frequencies of replication among groups of alpha-cells, beta-cells, duct cells, or acinar cells nor were there differences in numbers of apoptotic alpha-cells or beta-cells between CP patients and controls. However, CP patients had an approximately 10-fold increase in numbers of apoptotic acinar cells compared with controls (P.0001).Pancreatic volume was reduced by 21%, and the area comprising beta-cells was reduced by 29% in patients with CP. The lack of increased beta-cells turnover in CP patients, despite an approximately 10-fold increase in the number of apoptotic acinar cells, suggests that the damage to the pancreas is highly specific for the exocrine compartment and affects the endocrine islets to a lesser extent.
- Published
- 2009
29. Glucagon like peptide-2 induces intestinal restitution through VEGF release from subepithelial myofibroblasts
- Author
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Daniel Bulut, P. Felderbauer, Kerem Bulut, Frank Schmitz, Wolfgang E. Schmidt, Juris J. Meier, Matthias Banasch, Peter R. Hoffmann, and C Pennartz
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Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Fibroblast Growth Factor 7 ,Cell Survival ,Colon ,Receptor expression ,Transforming Growth Factor beta1 ,chemistry.chemical_compound ,Cell Movement ,Ileum ,Internal medicine ,Paracrine Communication ,Glucagon-Like Peptide 2 ,Receptors, Glucagon ,medicine ,Animals ,Humans ,RNA, Messenger ,Cell Proliferation ,Pharmacology ,Wound Healing ,Dose-Response Relationship, Drug ,biology ,Cell growth ,Antibodies, Monoclonal ,Epithelial Cells ,Cell migration ,Transforming growth factor beta ,Fibroblasts ,Rats ,Cell biology ,Vascular endothelial growth factor ,Endocrinology ,chemistry ,Culture Media, Conditioned ,Glucagon-Like Peptide-2 Receptor ,biology.protein ,Keratinocyte growth factor ,Caco-2 Cells ,Wound healing - Abstract
Glucagon like peptide-2 (GLP-2) exerts intestinotrophic actions, but the underlying mechanisms are still a matter of debate. Recent studies demonstrated the expression of the GLP-2 receptor on fibroblasts located in the subepithelial tissue, where it might induce the release of growth factors such as keratinocyte growth factor (KGF) or vascular endothelial growth factor (VEGF). Therefore, in the present studies we sought to elucidate the downstream mechanisms involved in improved intestinal adaptation by GLP-2. Human colonic fibroblasts (CCD-18Co), human colonic cancer cells (Caco-2 cells) and rat ileum IEC-18 cells were used. GLP-2 receptor mRNA expression was determined using real time RT-PCR. Conditioned media from CCD-18Co cells were obtained following incubation with GLP-2 (50-250 nM) for 24 h. Cell viability was assessed by a 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT)-assay, and wound healing was determined with an established migration-assay. Transforming Growth Factor beta (TGF-beta), VEGF and KGF mRNA levels were determined by RT-PCR. Protein levels of VEGF and TGF-beta in CCD-18Co cells following GLP-2 stimulation were determined using ELISA. Neutralizing TGF-beta and VEGF-A antibodies were utilized to assess the role of TGF-beta and VEGF-A in the process of wound healing. GLP-2 receptor expression was detected in CCD-18Co cells. Conditioned media from CCD-18Co cells dose-dependently induced proliferation in Caco-2 cells, but not in IEC-18 cells. Conditioned media also enhanced cell migration in IEC-18 cells (P
- Published
- 2008
30. Differential regulated expression of keratinocyte growth factor and its receptor in experimental and human liver fibrosis
- Author
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Wolfgang E. Schmidt, S. Kloehn, Heiner Mönig, Karl-Heinz Herzig, Karlheinz Kiehne, Jan-Michel Otte, Martin Schwenger, Gabriele Brunke, Claudia Otte, and Frank Schmitz
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Fibroblast Growth Factor 7 ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Biology ,Liver Cirrhosis, Experimental ,Fibroblast growth factor ,Biochemistry ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Growth factor receptor ,Fibrosis ,Internal medicine ,medicine ,Animals ,Humans ,RNA, Messenger ,Rats, Wistar ,Receptor, Fibroblast Growth Factor, Type 2 ,Growth factor ,medicine.disease ,Immunohistochemistry ,Rats ,Transplantation ,Gene Expression Regulation ,chemistry ,Keratinocyte growth factor ,Hepatic fibrosis - Abstract
Background and aim Immunomodulatory and protective properties have been identified for the keratinocyte growth factor (KGF). For hepatocytes, pro-proliferative and anti-apoptotic effects of this growth factor have been reported in vitro. This study was designed to characterize a putative role of KGF in observed histomorphological changes in both, human and experimental liver fibrosis. Methods Liver fibrosis and cirrhosis was induced in rats by repetitive exposure to phenobarbitone and increasing doses of carbon tetrachloride. Human samples were obtained from patients undergoing surgery for partial hepatectomy or transplantation. Organ samples were scored for inflammation and morphological changes. Expression of KGF and its receptor (KGFR) mRNA was quantified by real-time RT-PCR. Protein expression and receptor phosphorylation was determined by Western blot analysis. In-situ hybridization and immunohistochemistry were utilized to determine distribution of KGF and KGFR in the liver. Results Expression of KGF was significantly increased in damaged liver tissue in correlation to the degree of fibrosis, whereas expression of the receptor was up-regulated in early stages of liver fibrosis and down-regulated in cirrhotic organs. Protein expression of this growth factor and its receptor correlated with the alterations in mRNA. KGF expression was restricted to mesenchymal cells, whereas expression of KGFR was detected on hepatocytes only. Conclusion The expression of KGF and KGFR is differentially and significantly regulated in damaged liver tissue. This growth factor might therefore not only contribute to morphological alterations but also regeneration of liver parenchyma most likely mediated by indirect mechanisms of action.
- Published
- 2007
31. An upstream CRE-E-box element is essential for gastrin-dependent activation of the cyclooxygenase-2 gene in human colon cancer cells
- Author
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Wolfgang E. Schmidt, Stefan Jüttner, Thorsten Cramer, N Ansorge, Frank Schmitz, and Michael Höcker
- Subjects
Transcriptional Activation ,medicine.medical_specialty ,Physiology ,Clinical Biochemistry ,E-box ,Biology ,Response Elements ,Transfection ,Biochemistry ,Dinoprostone ,Cellular and Molecular Neuroscience ,Endocrinology ,Internal medicine ,Gastrins ,Tumor Cells, Cultured ,medicine ,Humans ,RNA, Messenger ,Cyclic AMP Response Element-Binding Protein ,Promoter Regions, Genetic ,Gene ,Transcription factor ,Gastrin ,Reporter gene ,Messenger RNA ,Binding Sites ,Cancer ,medicine.disease ,Molecular biology ,Cyclooxygenase 2 ,Colonic Neoplasms ,Upstream Stimulatory Factors - Abstract
Cyclooxygenase-2, the inducible enzyme of arachidonic acid metabolism and prostaglandin synthesis, is over expressed in colorectal cancer. Inhibition of COX-1/-2 by non-steroidal anti-inflammatory drugs is associated with a decreased risk for these malignancies, whereas high serum gastrin levels elevate this risk. As gastrin exhibits trophical effects on colonic epithelium we sought to explore whether it is capable to induce COX-2 expression in a human colon cancer cell line. The aim of this study is the description of the gastrin evoked effects on the transcriptional activity of the COX-2 gene in colorectal cancer cells and the identification of regulatory promoter elements. Reporter gene assays were performed with the gastrin-stimulated human colorectal cancer cell-line Colo-320, which was stable transfected with the human cholecystokinin-B/gastrin receptor cDNA and COX-2-promoter-luciferase constructs containing different segments of the 5'-region of the COX-2 gene or with mutated promoter constructs. Transcription factors were characterized with electrophoretic mobility shift assays. Gastrin-dependent induction of COX-2 mRNA was shown using "real-time" PCR. Resulting elevated Prostaglandin E2-levels were measured using ELISA. Gastrin stimulated the PGE2-generation and COX-2-mRNA expression in human Colo-320-B cells potently, obviously by transactivating the COX-2-promoter using a region between - 68 bp and + 70 bp. Further examinations identified a CRE-E-box element between - 56 bp and - 48 bp mediating the gastrin-effects on the COX-2 gene. Transcription factors binding to this promoter element were USF-1 und -2. These results show the necessity to perform succeeding studies, which could describe possible mechanisms in which gastrin and COX-2 contribute to the induction of colorectal carcinomas.
- Published
- 2007
32. Value, Size, Momentum and the Average Correlation of Stock Returns
- Author
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Christoph Becker and Wolfgang M. Schmidt
- Subjects
Correlation ,Financial economics ,Moving average ,Autoregressive conditional heteroskedasticity ,Sharpe ratio ,Economics ,Econometrics ,Portfolio ,Volatility (finance) ,Stock (geology) ,Minimum variance portfolio - Abstract
Dynamic average correlations of stock returns are predicted by the volatility of the market excess return and moving average returns of value, size and momentum portfolios. While the influence of market volatility on average correlation is well-known, the role of value, size and momentum appears to be underappreciated. Correlations of stock returns and stock returns share sources of risk like the market volatility, but there are other sources that are distinct. In particular, correlations are increased when value or momentum returns are roughly zero, while strongly negative returns of value or momentum are associated with lower correlations. Using the market volatility and a moving average return of the value portfolio as predictors of average correlation, we obtain a global minimum variance portfolio with a Sharpe ratio that is 1.5% higher relative to the one based on a Dynamic Equicorrelation Garch model, and the difference in portfolio volatility is statistically significant.
- Published
- 2015
33. Evidence for an association between mannose-binding lectin 2 (MBL2) gene polymorphisms and pre-term birth
- Author
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Manfred W. Mueller, Wolfgang M. Schmidt, Olaf Bodamer, Wolfgang Maurer, Arnold Pollak, and Georg Mitterer
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Male ,Genotype ,Microarray ,Biology ,Mannose-Binding Lectin ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Gene Frequency ,Pregnancy ,Risk Factors ,Genetic predisposition ,medicine ,Humans ,Codon ,Promoter Regions, Genetic ,Allele frequency ,Genetics (clinical) ,Oligonucleotide Array Sequence Analysis ,Mannan-binding lectin ,Fetus ,Polymorphism, Genetic ,Infant, Newborn ,Fetal Blood ,medicine.disease ,Premature birth ,Austria ,Immunology ,Premature Birth ,Female - Abstract
Purpose: Human mannose-binding lectin, encoded by the MBL2 gene, is an important component of innate immunity and an important regulator of inflammatory processes. MBL2 gene polymorphisms are associated with an increased risk of neonatal infections and some data suggest a relation between the maternal MBL2 genotype and the risk of premature delivery. In this study, we evaluated whether there is an association between the fetal MBL2 genotype and prematurity. Methods: A microarray-based on-chip PCR method was used to simultaneously detect five common MBL2 polymorphisms (codon 52, 54, 57; promoter -550, -221) in 204 DNA samples isolated from archival blood cards. MBL2 genotypes of infants born before the 36th week of pregnancy (N = 102) were compared to a control group of infants born at term after the 37th week (N = 102). Results: The frequency of the codon 52 polymorphism was significantly higher in the pre-term group compared to the term group (10.8% versus 4.9%, P = 0.04), while the frequency of the codon 54 polymorphism was equal in both groups (11.3% versus 11.8%). Interestingly, carriers of genotypes (O/O) likely conferring deficient MBL plasma levels were more common in the group of premature birth (9.8% versus 2.9%, P = 0.05), while the promoter -550 C/C genotype was underrepresented in the pre-term birth group (24.5% versus 39.2%, P = 0.03). Conclusion: Our data add to the knowledge about genetic predisposition to prematurity and suggest that the fetal MBL2 genotype might be an additional genetic factor contributing to the risk of premature delivery.
- Published
- 2006
34. Valine-286 residue in the third intracellular loop of the cholecystokinin 2 receptor exerts a pivotal role in cholecystokinin 2 receptor mediated intracellular signal transduction in human colon cancer cells
- Author
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Torsten Cramer, H Schäfer, Wolfgang E. Schmidt, Susanne Müerköster, Frank Schmitz, Michael Höcker, Hong-Gang Yu, Stefan Mergler, and Karl-Heinz Herzig
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MAPK/ERK pathway ,Apoptosis ,Inositol 1,4,5-Trisphosphate ,Biology ,Transfection ,Protein Structure, Secondary ,Calcium in biology ,chemistry.chemical_compound ,Cell Line, Tumor ,Gastrins ,Cyclic AMP ,Humans ,Point Mutation ,RNA, Messenger ,Phosphorylation ,Genes, Immediate-Early ,Cell Proliferation ,Gastrin ,G protein-coupled receptor ,Valine ,Tyrosine phosphorylation ,Cell Biology ,Molecular biology ,Receptor, Cholecystokinin B ,Up-Regulation ,Intracellular signal transduction ,chemistry ,Focal Adhesion Kinase 1 ,Colonic Neoplasms ,Tyrosine ,Paxillin ,Intracellular ,Signal Transduction - Abstract
Although expression of the gastrin/cholecystokinin-2 receptor (CCK2R) is widely reported in human colorectal cancer, little is known on its role in mediating mature amidated gastrin (gastrin-17 amide, G-17) induced intracellular signal transduction in colon cancer cells. The purpose of this study was to explore the intracellular events of colorectal cancer cells after gastrin binding to CCK2R. Meanwhile, the influence of a natural point mutation 286V→F in the third intracellular loop of CCK2R on gastrin-envoked intracellular signal transduction was also investigated. Firstly, Colo320 cells were stably transfected with wild type (Colo320 WT) and mutant CCK2R (Colo320 M), respectively. The intracellular signal transduction events in response to gastrin were investigated in both Colo320 WT and Colo320 M cells. In Colo320 WT cells, G-17 induced formation of intracellular cyclic AMP and inositol 1,4,5-trisphosphate, and stimulated intracellular calcium mobilization. G-17 also stimulated tyrosine phosphorylation of ERKl/2, p38, FAK, and paxillin, and up-regulated the mRNA expression of early response gene c-Jun and c-Fos. However, G-17 inhibited proliferation and induced apoptosis in Colo320 WT cells. Mutation 286V→F in the third intracellular loop of CCK2R blocked G-17 induced biological without affecting binding affinity of CCK2R to G-17. Our results suggest that activation of CCK2R by gastrin stimulates heterotrimeric G-protein Gq and G12/13 mediated intracellular signal transduction pathway in colon cancer cells. The valine-287 residue in third intracellular loop of CCK2R plays a pivotal role in CCK2R mediated intracellular signal transduction.
- Published
- 2005
35. Glucagon-like peptide 2 improves intestinal wound healing through induction of epithelial cell migration in vitro—evidence for a TGF-β-mediated effect
- Author
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P. Felderbauer, Wolfgang E. Schmidt, Kerem Bulut, N Ansorge, Frank Schmitz, P Hoffmann, Baptist Gallwitz, and Juris J. Meier
- Subjects
Pathology ,medicine.medical_specialty ,Physiology ,Clinical Biochemistry ,Glucagon-Like Peptides ,Apoptosis ,Enteroendocrine cell ,Biology ,Epithelial cell migration ,Biochemistry ,Cell Line ,Transforming Growth Factor beta1 ,Cellular and Molecular Neuroscience ,Endocrinology ,Intestinal mucosa ,Cell Movement ,Glucagon-Like Peptide 1 ,Transforming Growth Factor beta ,Cell Line, Tumor ,Glucagon-Like Peptide 2 ,medicine ,Animals ,Humans ,Protein Precursors ,Cell Proliferation ,Wound Healing ,Antibodies, Monoclonal ,Epithelial Cells ,Cell migration ,Flow Cytometry ,Glucagon ,Glucagon-like peptide-2 ,Peptide Fragments ,Epithelium ,Rats ,Intestines ,medicine.anatomical_structure ,Cancer research ,Intestinal Disorder ,Peptides ,Wound healing - Abstract
Background/aims: In vitro studies suggest that glucagon-like peptide 2 (GLP-2), secreted from enteroendocrine cells in the gastrointestinal tract after food intake, is able to ameliorate mucosal injury in settings of human disease characterized by injury and dysfunction of the intestinal mucosal epithelium. We evaluated this potential of GLP-2 after epithelial trauma by using two in vitro models measuring intestinal epithelial cell proliferation and cell migration. Materials and methods: Injuries were induced in confluent monolayers of the small intestinal cells lines IEC-6 and IEC-18, as well as in the colonic cell lines Caco-2 and Colo 320. GLP-2 (50–500 nM) or other peptides were added to the media. Wound healing was investigated after 24 h by quantification of the number of cells migrating across the wound edge. Proliferation of cells was assessed by using photometric mitochondrial incorporation measurement of MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide). Monoclonal TGF-β antibodies were added to wounded monolayers to examine whether the GLP-2-induced wound healing was TGF-β-mediated. Results: Migration assessments revealed a significant stimulation of GLP-2-induced migration in IEC-6 and IEC-18 monolayers compared to the placebo group. No effect was observed in the colon cancer cell lines Caco-2 and Colo 320. Results of the proliferation assays show a significant inhibition of proliferation by GLP-2 in small intestinal cell lines whereas a dose-dependent stimulation of proliferation in colonic epithelial cells was observed. Addition of neutralizing TGF-β1 antibodies to wounded IEC-6 and IEC-18 monolayers incubated with GLP-2 significantly reduced the number of migrating cells to the level of the placebo group. Conclusions: In our in vitro model, it was shown that the GLP-2-induced improvement of intestinal wound healing is TGF-β-mediated. These effects were predominant in the epithelium of the small intestine compared to colonic epithelium. Our findings provide further insight into mechanisms leading to GLP-2-induced mucosal wound healing. These results suggest that GLP-2 or analogues of this peptide may potentially be useful for the treatment of intestinal disorders characterized by injury and ineffective repair of the intestinal mucosa.
- Published
- 2004
36. Blood glucose control in healthy subject and patients receiving intravenous glucose infusion or total parenteral nutrition using glucagon-like peptide 1
- Author
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Michael A, Nauck, Jörg, Walberg, Arndt, Vethacke, Andrea, El-Ouaghlidi, Metin, Senkal, Jens J, Holst, Baptist, Gallwitz, J Baptist, Gallwitz, Wolfgang E, Schmidt, and W, Schmiegel
- Subjects
Adult ,Blood Glucose ,Male ,endocrine system ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Glucagon-Like Peptides ,Type 2 diabetes ,Placebo ,Biochemistry ,Glucagon ,Placebos ,Cellular and Molecular Neuroscience ,Endocrinology ,Glucagon-Like Peptide 1 ,Internal medicine ,Humans ,Insulin ,Medicine ,Infusions, Intravenous ,Dose-Response Relationship, Drug ,business.industry ,Fatty Acids ,digestive, oral, and skin physiology ,Glucagon secretion ,Middle Aged ,medicine.disease ,Glucagon-like peptide-1 ,Peptide Fragments ,Glucose ,Parenteral nutrition ,Diabetes Mellitus, Type 2 ,Gastrointestinal hormone ,Hyperglycemia ,Female ,Parenteral Nutrition, Total ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Aims: It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition. Patients and methods: Eight healthy subjects and nine patients were examined. The volunteers received, in six separate experiments in randomised order, intravenous glucose at doses of 0, 2 and 5mg kg−1 min−1, each with intravenous GLP-1 or placebo for 6 h. Patients were selected on the basis of hyperglycaemia (>150 mg/dl) during complete parenteral nutrition with glucose (3.2±1.4 mg kg−1 min−1), amino acids (n=8; 0.9±0.2 mg kg−1 min−1), with or without lipid emulsions. Four hours (8 a.m. to 12 a.m. on parenteral nutrition plus NaCl as placebo) were compared to 4 h (12 a.m. to 4 p.m.) with additional GLP-1 administered intravenously. The dose of GLP-1 was 1.2 pmol kg−1 min−1. Blood was drawn for the determination of glucose, insulin, C-peptide, GLP-1, glucagon, and free fatty acids. Results: Glycaemia was raised dose-dependently by glucose infusions in healthy volunteers (p
- Published
- 2004
37. Galanin in pituitary adenomas
- Author
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Katarina Åman, Wolfgang E. Schmidt, Eva Grenbäck, Marc Landry, Anders Änggård, Ella Wallerman, Tomas Hökfelt, Per Bjellerup, Lars Lundblad, Kaj Ericson, and Anna-Lena Hulting
- Subjects
Adenoma ,Adult ,Male ,endocrine system ,medicine.medical_specialty ,Pituitary gland ,Physiology ,Clinical Biochemistry ,Population ,Radioimmunoassay ,Neuropeptide ,Galanin ,Adrenocorticotropic hormone ,Biochemistry ,Cellular and Molecular Neuroscience ,Endocrinology ,Adrenocorticotropic Hormone ,Internal medicine ,medicine ,Humans ,Pituitary Neoplasms ,education ,Chromatography, High Pressure Liquid ,In Situ Hybridization, Fluorescence ,Aged ,education.field_of_study ,Chemistry ,digestive, oral, and skin physiology ,Pituitary tumors ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,nervous system ,Female ,Corticotropic cell ,Oligonucleotide Probes ,hormones, hormone substitutes, and hormone antagonists - Abstract
Tumor galanin content was measured in extracts from human pituitary adenomas using a specific RIA method for monitoring human galanin. Twenty-two out of twenty-four tumors contained galanin with notably high levels in corticotroph adenomas, varying levels in clinically inactive tumors, and low levels in GH secreting adenomas. Tumor galanin and ACTH contents were closely correlated in all tumors. In four young patients with microadenomas and highly active Mb Cushing tumor galanin was inversely related to tumor volume. The molecular form of tumor galanin, studied with reverse-phase HPLC, was homogeneous with the majority of tumor galanin coeluting with standard human galanin. In the tumors analysed with in situ hybridization there was a good correlation between galanin peptide levels and galanin mRNA expression. In some tumors galanin mRNA and POMC levels coexisted, in others they were essentially in different cell populations. Levels of plasma galanin-LI were not related to tumor galanin concentration, and galanin levels were in the same range in sinus petrosus close to the pituitary venous drainage as in peripheral blood. Corticotrophin releasing hormone injections in two patients caused ACTH, but no detectable galanin release into sinus petrosus. Our results demonstrate that corticotroph, but not GH adenomas, express high levels of galanin, in addition to ACTH, and that in some tumors both polypeptides are synthesised in the same cell population. However, galanin levels in plasma were not influenced by the tumor galanin content.
- Published
- 2004
38. Rapid tyrosine phosphorylation of focal adhesion kinase, paxillin, and p130Cas by gastrin in human colon cancer cells
- Author
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Wolfgang E. Schmidt, Jan-Michel Otte, Henning Schrader, Hong-Gang Yu, and Frank Schmitz
- Subjects
PTK2 ,macromolecular substances ,Biochemistry ,Focal adhesion ,chemistry.chemical_compound ,Gastrins ,Tumor Cells, Cultured ,Humans ,Phosphorylation ,Tyrosine ,Paxillin ,Gastrin ,Pharmacology ,Retinoblastoma-Like Protein p130 ,biology ,digestive, oral, and skin physiology ,Proteins ,Tyrosine phosphorylation ,Protein-Tyrosine Kinases ,Phosphoproteins ,Receptor, Cholecystokinin B ,Cytoskeletal Proteins ,Crk-Associated Substrate Protein ,chemistry ,Focal Adhesion Kinase 1 ,Focal Adhesion Protein-Tyrosine Kinases ,Colonic Neoplasms ,embryonic structures ,biology.protein ,Cancer research ,biological phenomena, cell phenomena, and immunity ,Signal transduction ,hormones, hormone substitutes, and hormone antagonists ,Densitometry - Abstract
Although the expression of CCK(2) receptors is widely reported in human colorectal cancers, little is known on its role in mediating the proliferative effects of mature amidated gastrin (G17 amide) on colorectal cancers. The purpose of the present study was to determine the effects of G17 amide on tyrosine phosphorylation of focal adhesion kinase (FAK), paxillin, and p130 Crk-associated substrate (p130(Cas)) in Colo 320 cells, a human colorectal cancer cell line which expresses CCK(2) receptors. By immunoprecipitation and immunoblotting, an increase in tyrosine phosphorylation of FAK (tyrosine-397), paxillin (tyrosine-31), and p130(Cas) was detected in a time- and dose-dependent manner. Overexpression of CCK(2) receptors in Colo 320 cells (Colo 320 WT) by stable transfection with the human CCK(2) receptor cDNA resulted in an increased tyrosine phosphorylation of FAK, paxillin, and p130(Cas). After incubation with 1 microM L-365,260, a specific CCK(2) receptor antagonist, this increase was completely inhibited. Our results demonstrate that in human colon cancer cells, gastrin caused a rapid tyrosine phosphorylation of FAK, paxillin, and p130(Cas) by activation of CCK(2) receptor. The phosphorylation of these proteins might be important in mediating gastrin effects on proliferation, apoptosis, and metastasis.
- Published
- 2004
39. Modafinil as Adjunct Therapy for Daytime Sleepiness in Obstructive Sleep Apnea
- Author
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Milton K. Erman, Max Hirshkowitz, Wolfgang W. Schmidt-Nowara, and Jonathan R L Schwartz
- Subjects
Pulmonary and Respiratory Medicine ,business.industry ,medicine.medical_treatment ,Epworth Sleepiness Scale ,Modafinil ,Sleep apnea ,Critical Care and Intensive Care Medicine ,medicine.disease ,Obstructive sleep apnea ,Anesthesia ,Respiratory disturbance index ,medicine ,Clinical Global Impression ,Continuous positive airway pressure ,Cardiology and Cardiovascular Medicine ,business ,Adverse effect ,medicine.drug - Abstract
Study objectives The purpose of this 12-week study was to evaluate the efficacy and safety of adjunct modafinil to treat excessive sleepiness in patients with obstructive sleep apnea (OSA) who experience residual sleepiness despite regular nasal continuous positive airway pressure (nCPAP) use. Design Twelve-week, open-label trial. Setting Twenty-two centers in the United States. Patients We studied 125 patients with moderate-to-severe OSA ( ie , respiratory disturbance index ≥ 15) before nCPAP therapy and residual daytime sleepiness (Epworth sleepiness scale [ESS] score ≥ 10) despite effective and regular nCPAP therapy. Patients were studied after completing a 4-week, double-blind, placebo-controlled trial of nCPAP plus modafinil for the treatment of residual daytime sleepiness. Interventions and measurements Patients received individually titrated doses of modafinil (200 to 400 mg qd). Sleepiness was assessed using the ESS, quality of life was evaluated using the Functional Outcomes of Sleep Questionnaire (FOSQ), and the overall clinical effect was indexed using the clinical global impression of change scale. Adverse events, nCPAP use, and vital sign measurements were also recorded. Results The significant improvements in daytime wakefulness and sleep-related functional status observed with modafinil treatment during the 4-week, double-blind study were maintained throughout 12 weeks of open-label treatment: week 12 ESS, 7.8 (4.7) vs 14.4 (3.1) at double-blind baseline; week 12 FOSQ, 3.3 (0.6) vs 14.4 (2.7) at double-blind baseline (mean [SD]). The percentage of patients rated as clinically improved increased from 83% after 1 week to ≥ 93% after 2 to 12 weeks of open-label treatment. Mean (SD) nCPAP use decreased from 6.3 (1.3) h/night at baseline to 5.9 (1.4) h/night (p = 0.004) during open-label treatment. The most common adverse events were headache (28%), anxiety (16%), and nervousness (14%). Conclusions Modafinil remained effective and well tolerated as an adjunct therapy for residual daytime sleepiness even after 12 weeks of daily dosing in patients with OSA receiving nCPAP therapy.
- Published
- 2003
40. Increased abundance of cyclooxygenase-2 correlates with vascular endothelial growth factor-A abundance and tumor angiogenesis in gastric cancer
- Author
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Jie-Ping Yu, Andreas Bastian, Wolfgang E. Schmidt, Frank Schmitz, Henning Schrader, Yanning Yang, Honggang Yu, Jian-ying Li, He-Sheng Luo, and Juris J. Meier
- Subjects
Adult ,Male ,Vascular Endothelial Growth Factor A ,Cancer Research ,Pathology ,medicine.medical_specialty ,CD34 ,Antigens, CD34 ,Endothelial Growth Factors ,Metastasis ,Neovascularization ,Stomach Neoplasms ,medicine ,Humans ,RNA, Messenger ,RNA, Neoplasm ,Aged ,Aged, 80 and over ,Messenger RNA ,Neovascularization, Pathologic ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Carcinoma ,Membrane Proteins ,Cancer ,Middle Aged ,medicine.disease ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Isoenzymes ,Vascular endothelial growth factor A ,Oncology ,Cyclooxygenase 2 ,Gastric Mucosa ,Prostaglandin-Endoperoxide Synthases ,Enzyme Induction ,Lymphatic Metastasis ,biology.protein ,Immunohistochemistry ,Female ,Cyclooxygenase ,medicine.symptom - Abstract
To understand the role of cyclooxygenase-2 (COX-2) in gastric cancer, we examined the abundance of COX-2, vascular endothelial growth factor-A (VEGF-A), and CD34 in 45 surgically resected human gastric cancers and paired normal gastric mucosa by immunohistochemical analysis. In addition, the message RNA (mRNA) expression of COX-2 and VEGF-A was evaluated in ten fresh surgically resected human gastric cancers and paired normal gastric mucosas using semi-quantitative reverse transcriptional polymerase chain reaction analysis. Our results confirmed an increased abundance of COX-2 and VEGF-A, and the microvessel density, which was assessed by CD34 abundance, in gastric cancer tissues compared with normal paired mucosa. Abundance of COX-2 and VEGF-A was significantly associated with tumor-node-metastasis (TNM) stage (P
- Published
- 2003
41. Transient agonist-induced regulation of the cholecystokinin-A and cholecystokinin-B receptor mRNA levels in rat pancreatic acinar AR42J cells
- Author
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Ulrich R. Fölsch, Wolfgang E. Schmidt, Ove C. Carstens, and Rainer Günther
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Receptor expression ,Down-Regulation ,Biology ,digestive system ,Tropomyosin receptor kinase C ,Sincalide ,Cell Line ,Internal medicine ,Gastrins ,medicine ,Animals ,5-HT5A receptor ,RNA, Messenger ,Pancreas ,Protease-activated receptor 2 ,Benzodiazepinones ,Hepatology ,Testicular receptor 4 ,Phenylurea Compounds ,Colforsin ,digestive, oral, and skin physiology ,Gastroenterology ,Molecular biology ,Receptor, Cholecystokinin B ,Rats ,Receptor, Cholecystokinin A ,Up-Regulation ,Endocrinology ,Bucladesine ,Interleukin-21 receptor ,Cholecystokinin B receptor ,Dactinomycin ,Tetradecanoylphorbol Acetate ,Receptors, Cholecystokinin ,Estrogen-related receptor gamma ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background: CCK-8 and gastrin exert multiple effects in the gastrointestinal tract and the nervous system. Their actions are mediated via the G-protein coupled CCK-A and CCK-B receptors. Methods: Rat pancreatic acinar tumor AR42J cells express both CCK receptor subtypes. This cell line was used to characterize the agonist-dependent regulation of CCK-A and CCK-B receptor gene expression. Results: CCK-8 (10 nM) or gastrin (10 nM) reduced CCK-A receptor mRNA expression to 56% and 53%, respectively 2 h after hormonal exposure. In contrast, the level of CCK-B receptor gene expression was upregulated to 157% and 153%, respectively. These effects are most probably linked to the CCK-B receptor in AR42J cells. The phorbolester PMA (100 nM), a protein kinase C activator, downregulated CCK-A receptor expression but did not affect CCK-B receptor gene transcription. Activation of protein kinase A by forskolin (10 µM) or Bt2cAMP (100 µM) is not involved in the transient regulation of CCK receptor mRNA expression. Both elevated CCK-B and decreased CCK-A receptor mRNA expression returned to basal levels 6 h after continuous stimulation. Conclusion: These results demonstrate that CCK-A and CCK-B receptor mRNA levels are differentially regulated by their agonists via distinct signal transduction mechanisms in AR42J cells.
- Published
- 2003
42. Gastric Inhibitory Polypeptide: the neglected incretin revisited
- Author
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Michael A. Nauck, Wolfgang E. Schmidt, Juris J. Meier, and Baptist Gallwitz
- Subjects
Blood Glucose ,endocrine system ,medicine.medical_specialty ,Physiology ,Molecular Sequence Data ,Clinical Biochemistry ,Adipose tissue ,Incretin ,Gastric Inhibitory Polypeptide ,Type 2 diabetes ,Models, Biological ,Biochemistry ,Cellular and Molecular Neuroscience ,Endocrinology ,Gastric inhibitory polypeptide ,Secretin ,Glucagon-Like Peptide 1 ,Internal medicine ,Diabetes mellitus ,Animals ,Humans ,Insulin ,Medicine ,Amino Acid Sequence ,Protein Precursors ,C-Peptide ,Sequence Homology, Amino Acid ,business.industry ,Stomach ,digestive, oral, and skin physiology ,Type 2 Diabetes Mellitus ,Glucagon ,Pancreatic Hormones ,Postprandial Period ,medicine.disease ,Lipids ,Glucagon-like peptide-1 ,Peptide Fragments ,Glucose ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,Gastrointestinal hormone ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
After the ingestion of fat- and glucose-rich meals, gut hormones are secreted into the circulation in order to stimulate insulin secretion. This so-called "incretin effect" is primarily conferred by Glucagon-like peptide 1 (GLP-1) and Gastric Inhibitory Polypeptide (GIP). In contrast to GLP-1, GIP has lost most of its insulinotropic effect in type 2 diabetic patients. In addition to its main physiological role in the regulation of endocrine pancreatic secretion, GIP exerts various peripheral effects on adipose tissue and lipid metabolism, thereby leading to increased lipid deposition in the postprandial state. In some animal models, an influence on gastrointestinal functions has been described. However, such effects do not seem to play an important role in humans. During the last years, the major line of research has focussed on GLP-1, due to its promising potential for the treatment of type 2 diabetes mellitus. However, the physiological importance of GIP in the regulation of insulin secretion has been shown to even exceed that of GLP-1. Furthermore, work from various groups has provided evidence that GIP contributes to the pathogenesis of type 2 diabetes to a considerable degree. Recent data with modified GIP analogues further suggested a possibility of therapeutic use in the treatment of type 2 diabetes. Thus, it seems worthwhile to refocus on this important and-sometimes-neglected incretin hormone. The present work aims to review the physiological functions of GIP, to characterize its role in the pathogenesis of type 2 diabetes, and to discuss possible clinical applications and future perspectives in the light of new findings.
- Published
- 2002
43. Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives
- Author
-
Michael A. Nauck, Wolfgang E. Schmidt, Baptist Gallwitz, and Juris J. Meier
- Subjects
endocrine system ,medicine.medical_specialty ,Stimulation ,Glucagon ,Neogenesis ,Eating ,Glucagon-Like Peptide 1 ,Internal medicine ,medicine ,Animals ,Humans ,Obesity ,Protein Precursors ,Proinsulin ,Pharmacology ,Gastric emptying ,biology ,business.industry ,Body Weight ,digestive, oral, and skin physiology ,Glucagon secretion ,biology.organism_classification ,Glucagon-like peptide-1 ,Peptide Fragments ,Endocrinology ,Anorectic ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
After ingestion of carbohydrate- and fat-rich meals, the incretin hormone glucagon-like peptide 1 (GLP-1) is secreted from the L-cells in the distal put into the circulation. Its major physiological effect lies in a strongly glucose-dependent stimulation of insulin secretion from pancreatic B-cells. Furthermore, GLP-1 suppresses glucagon secretion, stimulates B-cell neogenesis as well as proinsulin biosynthesis and inhibits gastric emptying and acid secretion. Recently, GLP-1 could be shown to reduce caloric intake and to enhance satiety, most likely via specific receptors within the central nervous system, resulting in reduced weight gain in experimental animals. In nondiabetic and Type 2 diabetic human subjects, exogenous GLP-1 reduces hunger, caloric intake and body weight. Therefore, in addition to its well-characterized antidiabetogenic effect, the anorectic effect may offer GLP-1 a potential in the pharmacotherapy of obesity. It is still unknown whether the GLP-1 effect on caloric intake is sustained after long-term treatment. Furthermore, the exact mechanisms by which the peptide exerts its biological effects have not yet been clarified. Due to the rapid degradation of native GLP-1, its therapeutic application is limited by the short half-life. Therefore, suitable modes of administration are needed in order to reach stable plasma concentrations. The present review aims to describe the role of GLP-1 in the central regulation of feeding and to discuss its possible application in the pharmacotherapy of obesity.
- Published
- 2002
44. A Functional Libor Market Model: Implementation and Application to Exposure Measurement
- Author
-
Wolfram Boenkost and Wolfgang M. Schmidt
- Subjects
Libor ,Actuarial science ,Interest rate derivative ,Econometrics ,Skew ,Economics ,Volatility smile ,LIBOR market model ,Volatility (finance) ,Potential future exposure ,SABR volatility model - Abstract
Evaluating interest rate derivatives stands and falls by a model properly capturing the volatility smile/skew. This does not only apply to pricing but also to evaluating counterparty default charges. We propose an arbitrage free model where forward Libor rates from the standard Libor Market Model (LMM) are transformed by an appropriate functional to reproduce the volatility structure in the cap market. Implementing the model is easy, efficient and stays as closely as possible to the standard LMM implementation. It combines both flexibility and factorness of the LMM and perfect consistency with the smile/skew. Calibration examples demonstrate the accuracy of the smile/skew calibration. Applications highlight the sensitivity of counterparty exposure measurement with respect to the volatility structure in the market.
- Published
- 2014
45. CVA/DVA Wrong Way Risk Put into Practice
- Author
-
Wolfgang M. Schmidt and Wolfram Boenkost
- Subjects
Actuarial science ,Default risk ,Credit derivative ,Counterparty ,Exposure at default ,Business ,Credit valuation adjustment ,Basel III ,Implementation ,Interest rate swap - Abstract
To account for counterparty default risk it is now common to require a credit valuation adjustment (CVA) charge, which is the price of a hypothetical credit derivative that would protect the dealer against counterparty default. The standard CVA approach, which is also advocated by the Basel III rules, ignores potential dependencies between the client's default probability and the exposure at default, which can either be in disadvantage or favor (wrong or right way risk) for the dealer. We propose a CVA formula that accounts for these dependencies and is easily put into practice since it stays closely to the standard simulation based CVA implementations and requires no additional simulation effort. The formula can be generalized to bilateral CVA thereby taking also into account default correlation between the dealer and client. Numerical examples for interest rate swaps, caps and swaptions illustrate the approach.
- Published
- 2014
46. Modeling Downturn LGD in a Basel Framework
- Author
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Nina Brumma, Wolfgang M. Schmidt, and Konrad Urlichs
- Subjects
Estimation ,Actuarial science ,Default rate ,media_common.quotation_subject ,Econometrics ,Economics ,Default ,Recession ,Loss given default ,media_common - Abstract
Under the Advanced Internal Rating-Based Approach of the Basel Accord banks are requested to calculate their Loss Given Default (LGD) aiming to reflect economic downturn conditions. We attempt to provide a methodology for the estimation of downturn effects on LGD with strict focus on the Basel requirements. The methodology is applied to historical default loss data from the PECDC database. It is essential to properly take into account time related effects like workout periods (time to resolution) and the Basel default definition. We find that for the class of large corporates the effect of downturn in a basic model with crisis indicator is statistically significant. Dependency of LGD and default rate is significant if a cash-flow weighted timestamp was applied to the LGD. A significant impact of macroeconomic factors like GDP growth rate could not be shown. Given spare data of resolved defaults under Basel default definition, also due to still pending workout periods, it is too early to conclude with certainty if and how much the LGD is affected by macroeconomic variables.
- Published
- 2014
47. Detection of Single Base Alterations in Genomic DNA by Solid Phase Polymerase Chain Reaction on Oligonucleotide Microarrays
- Author
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Wolfgang M. Schmidt, Manfred W. Mueller, Reinhard Hiller, Martin Huber, Doris Losert, and Christian Harwanegg
- Subjects
Mutation, Missense ,Biophysics ,Computational biology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Biochemistry ,Tumor Cells, Cultured ,Humans ,Point Mutation ,Molecular Biology ,Polymerase ,Oligonucleotide Array Sequence Analysis ,Base Composition ,Genome ,Tiling array ,biology ,Oligonucleotide ,Multiple displacement amplification ,DNA, Neoplasm ,Cell Biology ,Genes, p53 ,Molecular biology ,genomic DNA ,Colonic Neoplasms ,biology.protein ,Primer (molecular biology) ,DNA microarray ,Applications of PCR - Abstract
DNA microarray technology holds significant promise for human DNA diagnostics. A number of technical approaches directed at the parallel identification of mutations or single nucleotide polymorphisms make use of polymerase-based specificity, like minisequencing or allele-specific primer elongation. These techniques, however, require separate laborious sample amplification, preparation, and purification steps, making large-scale analyses time and cost consuming. Here, we address this challenge by applying an experimental setup using simultaneous solid and liquid phase PCR on polyethyleneimine-coated glass slides, a novel microarray support allowing on-chip amplification reactions with exquisite specificity. A gene-specific oligonucleotide tiling array contains covalently attached allele-specific primers which interrogate single nucleotide positions within a genomic region of interest. During a thermal cycling reaction amplification products remain covalently bound to the solid support and can be visualized and analyzed by the incorporation of fluorescent dyes. Using the described procedure we unequivocally defined the presence of point mutations in the human tumor suppressor gene p53 directly from a natural DNA source. This semi-multiplex solid phase amplification format allowed the rapid and correct identification of 20 nucleotide positions from minute amounts of human genomic DNA. Our results suggest that this approach might constitute a vital component of future integrated DNA chip devices used in gene analysis.
- Published
- 2001
48. Pericardial effusion as primary manifestation of Takayasu arteritis
- Author
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Sonja Huehns, Wolfgang A. Schmidt, Wolfgang Bocksch, Suzanne Fateh-Moghadam, and Rainer Dietz
- Subjects
medicine.medical_specialty ,Pericarditis ,business.industry ,Takayasu arteritis ,medicine ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Vasculitis ,Dermatology ,Pericardial effusion - Abstract
Takayasu arteritis (TA) is a chronic vasculitis, affecting young women in 80-90% of cases with greatest prevalence in Asians. As exudative pericarditis is an extremely rare, but a possible manifestation of TA, we report on a young women who presented with recurrent febrile pericardial effusion as primary manifestation of TA.
- Published
- 2010
49. GLP-1-analogues resistant to degradation by dipeptidyl-peptidase IV in vitro
- Author
-
Wolfgang E. Schmidt, Corinna Morys-Wortmann, Rolf Mentlein, E G Siegel, Baptist Gallwitz, and Torsten Ropeter
- Subjects
endocrine system ,Physiology ,Dipeptidyl Peptidase 4 ,Clinical Biochemistry ,Incretin ,Peptide ,Biology ,Binding, Competitive ,Biochemistry ,Dipeptidyl peptidase ,Receptors, G-Protein-Coupled ,Receptors, Gastrointestinal Hormone ,Cellular and Molecular Neuroscience ,Endocrinology ,Glucagon-Like Peptide 1 ,Cyclic AMP ,Tumor Cells, Cultured ,Animals ,Protein Precursors ,Receptor ,Chromatography, High Pressure Liquid ,Glucagon-like peptide 1 receptor ,chemistry.chemical_classification ,Molecular Structure ,digestive, oral, and skin physiology ,Biological activity ,Glucagon ,Glucagon-like peptide-1 ,Peptide Fragments ,In vitro ,Rats ,chemistry ,Insulinoma ,hormones, hormone substitutes, and hormone antagonists - Abstract
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion and improves glycemic control in type 2 diabetes. In serum the peptide is degraded by dipeptidyl peptidase IV (DPP IV). The resulting short biological half-time limits the therapeutic use of GLP-1. DPP IV requires an intact alpha-amino-group of the N-terminal histidine of GLP-1 in order to perform its enzymatic activity. Therefore, the following GLP- analogues with alterations in the N-terminal position 1 were synthesized: N-methylated- (N-me-GLP-1), alpha-methylated (alpha-me-GLP-1), desamidated- (desamino-GLP-1) and imidazole-lactic-acid substituted GLP-1 (imi-GLP-1). All GLP-1 analogues except alpha-me-GLP-1 were hardly degraded by DPP IV in vitro. The GLP-1 analogues showed receptor affinity and in vitro biological activity comparable to native GLP-1 in RINm5F cells. GLP-1 receptor affinity was highest for imi-GLP-1, followed by alpha-me-GLP-1 and N-me-GLP-1. Only desamino-GLP-1 showed a 15-fold loss of receptor affinity compared to native GLP-1. All analogues stimulated intracellular cAMP production in RINm5F cells in concentrations comparable to GLP-1. N-terminal modifications might therefore be useful in the development of long-acting GLP-1 analogues for type 2 diabetes therapy.
- Published
- 2000
50. Stem cell factor influences neuro-immune interactions: The response of mast cells to pituitary adenylate cyclase activating polypeptide is altered by stem cell factor
- Author
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E. J. Goetzl, Jörg Seebeck, Barry K. Wershil, Wolfgang E. Schmidt, J. Meissner, S. J. Galli, Menghang Xia, J. Schaub, and Anjona Schmidt-Choudhury
- Subjects
medicine.medical_specialty ,Physiology ,Clinical Biochemistry ,Vasoactive intestinal peptide ,Bone Marrow Cells ,Stem cell factor ,CHO Cells ,Biology ,Pertussis toxin ,Biochemistry ,Cell Degranulation ,Mice ,Cellular and Molecular Neuroscience ,Endocrinology ,Cricetinae ,Internal medicine ,medicine ,Animals ,Humans ,Mast Cells ,Receptor ,Peritoneal Cavity ,Mice, Inbred BALB C ,Stem Cell Factor ,Dose-Response Relationship, Drug ,Neuropeptides ,Degranulation ,Mast cell ,Cell biology ,Pituitary adenylate cyclase-activating peptide ,medicine.anatomical_structure ,Culture Media, Conditioned ,Pituitary Adenylate Cyclase-Activating Polypeptide ,Stem cell ,HT29 Cells ,hormones, hormone substitutes, and hormone antagonists ,Vasoactive Intestinal Peptide - Abstract
Mast cells degranulation can be elicited by a number of biologically important neuropeptides, but the mechanisms involved in mast cell–neuropeptide interactions have not been fully elucidated. Stem cell factor (SCF), also known as c-kit or kit ligand, induces multiple effects on mast cells, including proliferation, differentiation, maturation, and prevents apoptosis. We investigated the ability of SCF to affect mast cell responsiveness to the neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). PACAP 1-27, PACAP1-38, or VIP failed to induced preformed mediator release from mouse bone-marrow-cultured mast cells (BMCMC) derived in concanavalin A-stimulated spleen conditioned medium (CM). By contrast, BMCMC grown in SCF-containing medium or freshly isolated peritoneal mast cells exhibited significant 3H-hydroxytrypamine (5-HT) release in response to PACAP peptides or VIP. Deoxyglucose and the mitochondrial inhibitor antimycin significantly inhibited PACAP-induced 5-HT release indicating that the central event induced by PACAP peptides was exocytosis. The Gαi inhibitor, pertussis toxin, significantly diminished PACAP-induced 5-HT release from BMCMCs in SCF suggesting the involvement of heterotrimeric G-proteins. Western blot analysis using antibodies directed against the human VIP type I/PACAP type II receptor demonstrated a 70–72 kD immunoreactive protein expressed in greater amounts in BMCMC grown in SCF compared with BMCMC in CM. We conclude that SCF induces a mast cell population that is responsive to PACAPs and VIP involving a heterotrimeric G-protein-dependent mechanism.
- Published
- 1999
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