51 results on '"Dieter Engelhardt"'
Search Results
2. Flansche und Werkstoffe : Normen und Tabellen
- Author
-
Hans-Dieter Engelhardt, DIN e.V, Hans-Dieter Engelhardt, and DIN e.V
- Abstract
Das Tabellenbuch fasst übersichtlich grundlegende Informationen und Zahlenwerte (Werkstoffe, Technische Lieferbedingungen, Abmessungen) zu gebräuchlichen Flanschen zusammen. Abgedruckt sind Auszüge (teilweise zweisprachig) aus den wichtigsten nationalen und internationalen Maß- und Werkstoffnormen (DIN-EN-ISO-Normen, ASME/ASTM, VdTÜV-Werkstoffblätter, AD-Merkblätter).
- Published
- 2019
3. Herausgeber- und Autorenverzeichnis
- Author
-
Kurt Possinger, Anne Regierer, Jan Eucker, Annette Dieing, Bernd Flath, Gunnar Folprecht, Michael Geißler, Erhard Hiller, Andreas Hochhaus, Christian Jehn, Ulrich Keilholz, Konrad Klinghammer, Wolfgang Knauf, Hans-Jochem Kolb, Diana Lüftner, Matthias Möhlig, Helmut Oettle, null Oettle, null Mayer, Ulrich-Frank Pape, Gabriele Pecher, Uwe Platzbecker, Andreas Rank, Peter Reichardt, Oliver Rick, Ebel Fachkliniken, Hanno Riess, Markus Ruhnke, Markus Schaich, Andreas Schalhorn, Alexander Schmittel, Christian Scholz, Hubert Schrezenmeier, Carsten-Oliver Schulz, Bertram Wiedenmann, Isrid Sturm, Dieter Engelhardt, Ralph Naumann, and Peter Schmid
- Published
- 2017
4. Malignome endokriner Organe
- Author
-
Ulrich-Frank Pape, Bertram Wiedenmann, and Dieter Engelhardt
- Subjects
business.industry ,Medicine ,business - Published
- 2017
5. Herausgeber- und Autorenverzeichnis
- Author
-
Kurt Possinger, Anne Constanze Regierer, Annette Dieing, Dieter Engelhardt, Jan Eucker, Bernd Flath, Gunnar Folprecht, Michael Geißler, Erhard Hiller, Andreas Hochhaus, Christian Jehn, Ulrich Keilholz, Wolfgang Knauf, Hans-Jochem Kolb, Diana Lüftner, Ralph Naumann, Helmut Oettle, Ulrich-Frank Pape, Gabriele Pecher, Uwe Platzbecker, Andreas Rank, Peter Reichardt, Oliver Rick, Hanno Riess, Markus Ruhnke, Markus Schaich, Andreas Schalhorn, Peter Schmid, Alexander Schmittel, Christian Scholz, Carsten-Oliver Schulz, Bertram Wiedenmann, and Isrid Sturm
- Published
- 2015
6. Endokrin-aktive maligne Tumoren
- Author
-
Dieter Engelhardt, Klaus Mann, Dieter Engelhardt, and Klaus Mann
- Subjects
- Endocrinology, Oncology
- Published
- 2013
7. Prim�rer Hyperparathyreoidismus, Tumoren der Nebenniere und neuroendokrine Tumoren des Pankreas
- Author
-
Burkhard Göke, Dieter Engelhardt, and Christoph J. Auernhammer
- Subjects
Gynecology ,medicine.medical_specialty ,Pathology ,business.industry ,Clinical diagnosis ,medicine ,Radiology, Nuclear Medicine and imaging ,Neuroendocrine tumors ,medicine.disease ,business ,Adrenal tumors ,Primary hyperparathyroidism - Abstract
Einleitung. Die Diagnostik von Erkrankungen der Nebenschilddruse, der Nebenniere und von neuroendokrinen Tumoren des Pankreas erfolgt primar klinisch-endokrinologisch.Die Anforderungen an die Bildgebung bei der nachfolgenden Lokalisationsdiagnostik sind komplex, und die verschiedenen bildgebenden Verfahren bei den jeweiligen Tumorentitaten von unterschiedlichem Stellenwert. Material und Methodik. Aktuelle Literaturrecherche mittels PubMed. Ergebnisse. Beim primaren Hyperparathyreoidismus sind die Bestimmung der Knochendichte mittels DXA und der Nachweis einer Nephrolithiasis mittels Sonographie oder nativem Niedrigdosis-CT indiziert. Eine uber die Sonographie von Schilddruse und Nebenschilddruse hinausgehende praoperative Lokalisationsdiagnostik (Sestamibiszintigraphie, MRT) ist nur beim geplanten Einsatz von minimalinvasiven Operationstechniken oder bei Zweiteingriffen notwendig. Bei Tumoren der Nebenniere ist die diagnostische Wertigkeit von CT und MRT in etwa gleich.Beim Phaochromozytom ist zusatzlich die MIBG-Szintigraphie indiziert.Jedes Inzidentalom der Nebenniere muss endokrinologisch abgeklart werden.Eine Feinnadelpunktion oder Stanzbiopsie der Nebenniere ist nur selten indiziert; vorher muss laborchemisch ein Phaochromozytom ausgeschlossen werden.Fur die Lokalisationsdiagnostik der neuroendokrinen Tumoren des Pankreas werden v. a.Somatostatinrezeptorszintigraphie, Endosonographie und spezielle Sequenzprotokolle der MRT erfolgreich eingesetzt. Diskussion. Spezifische Lokalisationsstrategien werden fur die einzelnen Tumorentitaten vorgeschlagen. Die kontinuierliche technische Weiterentwicklung der einzelnen bildgebenden Verfahren erfordert eine regelmasige Neubewertung.
- Published
- 2003
8. Novel Neurotrophin-1/B Cell-Stimulating Factor-3 (Cardiotrophin-Like Cytokine) Stimulates Corticotroph Function via a Signal Transducer and Activator of Transcription-Dependent Mechanism Negatively Regulated by Suppressor of Cytokine Signaling-3
- Author
-
Dieter Engelhardt, Neziha Cengic, Giorgio Senaldi, Matthias M. Weber, Christoph J. Auernhammer, Nicola B. Isele, Gerald Spoettl, and Florian Kopp
- Subjects
STAT3 Transcription Factor ,medicine.medical_specialty ,Pro-Opiomelanocortin ,Leukemia Inhibitory Factor Receptor alpha Subunit ,Receptors, OSM-LIF ,Neuroimmunomodulation ,Gene Expression ,Suppressor of Cytokine Signaling Proteins ,Leukemia inhibitory factor receptor ,Biology ,Endocrinology ,Adrenocorticotropic Hormone ,Antigens, CD ,Internal medicine ,Cytokine Receptor gp130 ,medicine ,Animals ,Humans ,RNA, Messenger ,Phosphorylation ,Receptors, Cytokine ,Receptor, Ciliary Neurotrophic Factor ,SOCS2 ,Cells, Cultured ,Membrane Glycoproteins ,Suppressor of cytokine signaling 1 ,Proteins ,Glycoprotein 130 ,DNA-Binding Proteins ,Repressor Proteins ,STAT1 Transcription Factor ,Suppressor of Cytokine Signaling 3 Protein ,Pituitary Gland ,Interleukin-21 receptor ,Interleukin-6 receptor ,Trans-Activators ,Cytokines ,Ciliary neurotrophic factor receptor ,CLCF1 ,Signal Transduction ,Transcription Factors - Abstract
Novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3) is a recently cloned gp130 cytokine, acting through the tripartite ciliary neurotrophic factor receptor (CNTFR) alpha/leukemia inhibitory factor receptor (LIFR)/gp130 receptor complex. The aim of the current study was to investigate the role of NNT-1/BSF-3 in corticotroph cell function and further characterize NNT-1/BSF-3 signaling pathways. Using RT-PCR, expression of ciliary neurotrophic factor receptor alpha, leukemia inhibitory factor receptor, and gp130 could be demonstrated in mRNA derived from murine corticotroph AtT-20 cells and murine pituitary tissue. Incubation of AtT-20 cells with 10 ng/ml recombinant human NNT-1/BSF-3 rapidly induced tyrosine-phosphorylation of signal transducer and activator of transcription (STAT)3 and STAT1 at 5 and 10 min. Proopiomelanocortin promoter activity and suppressor of cytokine signaling (SOCS)-3 promoter activity were significantly stimulated by NNT-1/BSF-3 4.0 +/- 0.3- and 5.9 +/- 0.2-fold, respectively. In comparison with untreated control, NNT-1/BSF-3 significantly stimulated ACTH secretion at 24 and 48 h 1.7 +/- 0.2-fold and 1.5 +/- 0.1-fold above baseline. In comparison with mock-transfected cells, stable overexpression of SOCS-3 in AtT-20 cells abolished NNT-1/BSF-3-induced STAT1 and STAT3 phosphorylation and almost completely inhibited STAT-dependent proopiomelanocortin promoter and SOCS-3 promoter activities. In addition, NNT-1/BSF-3-induced ACTH secretion at 48 h was significantly attenuated by SOCS-3 overexpression. In summary, we have shown that NNT-1/BSF-3 is a modulator of corticotroph cell function, which is negatively regulated by SOCS-3. Our data indicate that the activation of the Jak-STAT cascade is essential for corticotroph NNT-1/BSF-3 signaling. Further studies will have to investigate the possible in vivo role of NNT-1/BSF-3 as a neuroimmunoendocrine modulator of hypothalamus-pituitary-adrenal axis stress response.
- Published
- 2003
9. Overexpression of the insulin-like growth factor I receptor in human colon carcinomas
- Author
-
Dieter Engelhardt, M. Christina Jung M.D., Christian Fottner, Gustavo Baretton, Matthias M. Weber, and Sun Bin Liu
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Gene Expression ,Adenocarcinoma ,Biology ,Receptor, IGF Type 1 ,Pathogenesis ,Paracrine signalling ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Autocrine signalling ,Receptor ,Reverse Transcriptase Polymerase Chain Reaction ,Growth factor ,Cancer ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Endocrinology ,Oncology ,Female ,Colorectal Neoplasms - Abstract
BACKGROUND High concentrations of insulin-like growth factor (IGF)-I and IGF-II have been demonstrated in human colonic adenocarcinomas and exert mitogenic effects through paracrine/autocrine interactions with the IGF-I receptor (IGF-IR). However, definitive studies of IGF-IR expression in these tissues have not been performed. METHODS To study changes in the levels of the IGF-IR in colorectal carcinoma, we analyzed the expression of IGF-IR in 40 paired samples of normal and carcinomatous colonic tissue by quantitative reverse-transcription–polymerase chain reaction (RT-PCR), immunohistochemistry, and ligand binding. RESULTS As measured by RT-PCR, the IGF-IR mRNA ratio in paired tumor and adjacent normal mucosa was higher than 2.0 in 32 of 40 (80%) samples. The overall mean IGF-IR mRNA level was five-fold higher in tumor versus adjacent normal mucosa (P < 0.0001). Overexpression of IGF-IR in colon carcinomas was confirmed at the protein level by immunohistochemistry and receptor-binding studies. Colon carcinoma cells exhibited a positive staining for IGF-IR in 91% of all tumors (30 of 33) whereas the adjacent normal colonic epithelial cells showed only a very faint or no significant IGF-IR immunoreactivity. Radioligand assays and Scatchard analysis in both tissue types revealed a single class of high-affinity IGF-IR–binding sites with a similar dissociation constant (Kd; 0.14 ± 0.02 nmol/L, n = 18). However, specific 125IGF-I–binding and receptor concentrations were elevated in tumor membranes compared with normal mucosa (33.6 ± 5.6 vs. 22.7 ± 3.4 fmol/mg protein, P < 0.05). IGF-I affinity crosslinking and sodium dodecyl sulfate–polyacrylamide gel electrophoresis displayed specific bands corresponding to the size of the normal α-subunit of the IGF-IR that were more intense in carcinomatous samples. IGF-II mRNA levels were significantly elevated in colorectal carcinomas (P < 0.0001). The IGF-II mRNA ratio in tumor versus normal tissue was elevated more than twofold in 28 of 40 paired samples and a positive correlation was observed between the overexpression of IGF-II and IGF-IR in the tumors. CONCLUSIONS Our results demonstrate that, in addition to IGF-II, a strong overexpression of IGF-IR is found in the majority of colorectal carcinomas, supporting the hypothesis of an important role of the IGF system in the pathogenesis of colorectal carcinoma. Cancer 2002;95:2086–95. © 2002 American Cancer Society. DOI 10.1002/cncr.10945
- Published
- 2002
10. Insulin-Like Growth Factors and Insulin-Like Growth Factor Binding Proteins in Adult Patients with Severe Liver Disease before and after Orthotopic Liver Transplantation
- Author
-
Matthias M. Weber, Dieter Engelhardt, Reinhart Zachoval, Christopher J Auernhammer, and Phillip D.K. Lee
- Subjects
Adult ,medicine.medical_specialty ,Time Factors ,Orthotopic liver transplantation ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Liver transplantation ,DNA-binding protein ,Insulin-like growth factor-binding protein ,Liver disease ,Endocrinology ,Insulin-Like Growth Factor II ,Internal medicine ,medicine ,Humans ,Insulin ,Insulin-Like Growth Factor I ,Retrospective Studies ,Adult patients ,biology ,business.industry ,medicine.disease ,Liver Transplantation ,Insulin-Like Growth Factor Binding Protein 1 ,Insulin-Like Growth Factor Binding Protein 2 ,Insulin-Like Growth Factor Binding Protein 3 ,Pediatrics, Perinatology and Child Health ,biology.protein ,Regression Analysis ,Liver function ,business ,Insulin-Like Growth Factor Binding Protein 6 ,Liver Failure ,Follow-Up Studies - Abstract
Introduction: The liver is the main source of serum insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) and the concentration of these proteins might reflect liver function. Methods: In a retrospective longitudinal study we examined serum levels of total and free IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-6 in 21 adult patients with end-stage liver disease before and after orthotopic liver transplantation (LTX) by sensitive and specific RIAs. In each patient, the mean value of at least three measurements before and after LTX was calculated. Results: Before LTX, serum levels of total and free IGF-I, IGF-II, IGFBP-3 were low and showed a rapid and significant increase in almost all patients after successful LTX (total IGF-I: 30 ± 7 vs. 256 ± 30 ng/ml, p < 0.001; free IGF-I: 1.3 ± 0.3 vs. 3.5 ± 0.6 ng/ml, p < 0.01; IGF-II: 177 ± 28 vs. 618 ± 30 ng/ml, p < 0.001; IGFBP-3: 1,230 ± 136 vs. 3,665 ± 264 ng/ml, p < 0.001). In contrast, IGFBP-1 was found to be high immediately before LTX, and declined to normal levels after LTX (210 ± 40 vs. 90 ± 15 ng/ml, p < 0.01), while IGFBP-2 did not show any significant changes (1,154 ± 296 vs. 1,303 ± 192 ng/ ml). Positive correlations were found between IGF-I, IGF-II or IGFBP-3, and serum pseudocholinesterase (R = 0.50, 0.72 and 0.61 respectively, p < 0.001). Negative correlations were found between IGF-I, IGF-II or IGFBP-3, and prothrombin time (R = 0.50, 0.59 and 0.51 respectively, p < 0.001). Conclusion: Patients with severe liver disease show decreased levels of total and free IGF-I, IGF-II and IGFBP-3, and increased levels of IGFBP-1. These abnormalities are promptly normalized after successful LTX. Thus, serum levels of IGF-I, IGF-II and IGFBP-3 might be useful parameters for the assessment of liver function.
- Published
- 2002
11. Differential Regulation of Insulin-Like Growth Factor-(IGF) I and IGF-Binding Protein (IGFBP) Secretion by Human Peripheral Blood Mononuclear Cells
- Author
-
Martin Bidlingmaier, Christoph J. Auernhammer, Matthias M. Weber, Dieter Engelhardt, C. Fottner, and Christian J. Strasburger
- Subjects
Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Blotting, Western ,Peripheral blood mononuclear cell ,Monocytes ,Insulin-like growth factor ,Endocrinology ,Internal medicine ,medicine ,Humans ,Growth factor receptor inhibitor ,Secretion ,Insulin-Like Growth Factor I ,Phytohemagglutinins ,Receptor ,Cells, Cultured ,Insulin-like growth factor 1 receptor ,Chemistry ,Binding protein ,Growth factor ,Middle Aged ,Insulin-Like Growth Factor Binding Proteins ,Insulin-Like Growth Factor Binding Protein 2 ,Insulin-Like Growth Factor Binding Protein 3 ,Insulin-Like Growth Factor Binding Protein 4 ,Pokeweed Mitogens ,Culture Media, Conditioned ,Pediatrics, Perinatology and Child Health ,Female ,Mitogens - Abstract
Background: Recent studies have shown that immunocompetent cells synthesize and express growth hormone (GH), growth hormone receptors (GH-R), insulin-like growth factor I (IGF-I), IGF-I receptors (IGF-I-R) and different insulin-like growth factor binding proteins (IGFBPs). The aim of the current study was to evaluate the regulation of IGFBP and IGF-I secretion from immunocompetent cells by different mitogens. Methods/Results: We studied the in vitro secretion pattern of IGFBPs and IGF-I from human peripheral blood mononuclear cells (PBMC), derived from 10 normal adults and 8 GH-deficient patients with adult onset. In serum-free conditioned medium of unstimulated PBMC, derived from normal adults, Western ligand blotting (1D-WLB) revealed a 24-kD, a 34-kD and a 39/43-kD doublet band to be most prominent. According to their molecular weight and two-dimensional Western ligand blot analysis (2D-WLB), these bands are deglycosylated IGFBP-4, IGFBP-2 and IGFBP-3, respectively. When the cells were treated with the T-cell mitogen phytohemagglutinin (PHA) (10 µg/ml), a differential stimulation of IGFBPs was found with a 2.57 ± 0.48-fold increase of IGFBP-4 (p < 0.01), a 1.55 ± 0.13-fold increase of IGFBP-2 (p < 0.01), and a 1.35 ± 0.19-fold increase of IGFBP-3 (n.s.). In contrast, treatment with the B-cell mitogen pokeweed mitogen (PWM) (10 µg/ml) caused only a modest 1.40 ± 0.07-fold increase of IGFBP-4 (p < 0.01). Treatment with rhGH (100 ng/ml) or rhIGF-I (200 ng/ml) caused no significant induction of any specific band, respectively. In contrast to the secretion pattern of IGFBPs, IGF-I secretion of the PBMC was not stimulated by either PHA or PWM, but showed a significant increase after GH incubation (p < 0.01). A similar differentiated secretion pattern of IGFBPs and IGF-I was also observed in the conditioned medium of PBMC, derived from GH-deficient patients. Conclusion: In summary, at least three different IGFBPs are secreted by human PBMC. Secretion of IGFBPs by PBMC is differentially regulated by different lymphocyte mitogens. Secretion of IGFBPs by PBMC is independent of GH or IGF-I, whereas the secretion of IGF-I is stimulated by GH. PBMC derived from normal adults and GH-deficient patients show similar patterns of IGF-I and IGFBPs secretion, thus indicating that the paracrine/autocrine IGF-I–IGFBPs interactions of the PBMC are not altered by pituitary GH deficiency.
- Published
- 2002
12. Identification and characterization of insulin-like growth factor (IGF)-binding protein expression and secretion by adult human adrenocortical cells: differential regulation by IGFs and adrenocorticotropin
- Author
-
Matthias M. Weber, Christian Fottner, MW Elmlinger, and Dieter Engelhardt
- Subjects
Adult ,Cortisol secretion ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Blotting, Western ,Cell Culture Techniques ,Adrenocorticotropic hormone ,Insulin-like growth factor-binding protein ,Insulin-like growth factor ,Endocrinology ,Adrenocorticotropic Hormone ,Somatomedins ,Internal medicine ,medicine ,Humans ,Secretion ,RNA, Messenger ,Receptor ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Adrenal cortex ,Recombinant Proteins ,Insulin-Like Growth Factor Binding Proteins ,medicine.anatomical_structure ,Gene Expression Regulation ,Cell culture ,Adrenal Cortex ,biology.protein ,hormones, hormone substitutes, and hormone antagonists - Abstract
In previous studies we have shown that IGF-II stimulates basal as well as ACTH-induced cortisol secretion from adult human adrenocortical cells more potently than IGF-I, and that both IGFs predominantly stimulate androgen biosynthesis. The steroidogenic effect of IGF-I and IGF-II is mediated through interaction with the IGF-I receptor, and modified by locally produced IGF-binding proteins (IGFBPs). In the present study, we identified and characterized IGFBP synthesis in normal adult human adrenocortical cells in primary culture, and investigated the effect of ACTH and recombinant human IGF-I and -II on the regulation of IGFBP expression and secretion. Using RT-PCR, we identified the mRNA of all six high-affinity IGFBPs, in both adrenocortical tissue and monolayer cell cultures of adrenocortical cells. Using Western ligand and immunoblotting and two-dimensional Western ligand blotting we confirmed the secretion of IGFBP-1, -2, -3, -4 and -5 by adrenocortical cells in primary culture. The quantification of IGFBPs indicated that IGFBP-3 accounts for almost half the binding activity in conditioned medium of unstimulated cells (47%), followed by IGFBP-4 (20%), IGFBP-5 (15%), IGFBP-2 (12%) and IGFBP-1 (6%). After treatment with ACTH, the abundance of IGFBP-1 was upregulated significantly 2.6-fold, while IGFBP-3 was induced only slightly (1.3-fold). IGFBP-2, -4 and -5 remained unchanged. In contrast, IGF-I and -II (6.5 nM) predominantly induced the abundance of IGFBP-5 (2- and 1.6-fold respectively) and IGFBP-3 (2- and 1.7-fold respectively), while IGFBP-1, -2 and -4 were unaltered. The induction of IGFBP-1 and -5 by ACTH and IGFs, respectively, was paralleled by an increase in the amount of IGFBP-1 and -5 mRNA in these cells. In conclusion, all six high-affinity IGFBPs are expressed in the adult human adrenal gland, and the presence of at least five high-affinity IGFBPs has been demonstrated in conditioned medium of adult human adrenocortical cells. Furthermore, the expression and secretion of IGFBP-1 is upregulated by ACTH, whereas IGFBP-5 is induced by IGF-I and -II. Together with earlier findings, these results suggest that IGFBPs play an important modulatory role in the regulation of the differentiated adrenocortical function.
- Published
- 2001
13. Characterization of Human Insulin-Like Growth Factor-Binding Proteins by Two-Dimensional Polyacrylamide Gel Electrophoresis and Western Ligand Blot Analysis1
- Author
-
Matthias M. Weber, Gerald Spöttl, Dieter Engelhardt, and Christoph Gössl
- Subjects
Gel electrophoresis ,Molecular mass ,Isoelectric focusing ,Endocrinology, Diabetes and Metabolism ,Biochemistry (medical) ,Clinical Biochemistry ,Biology ,Ligand (biochemistry) ,Biochemistry ,Molecular biology ,Blot ,Endocrinology ,Isoelectric point ,Immobilized pH gradient ,Polyacrylamide gel electrophoresis - Abstract
The insulin-like growth factor (IGF)-binding proteins (IGFBPs) from adult human serum, amniotic fluid, and cerebrospinal fluid were analyzed by a modified two-dimensional gel electrophoresis followed by Western ligand blotting. The samples were subjected to immobilized pH gradient isoelectric focusing in the first dimension, followed by nondenaturing SDS-PAGE in the second dimension and autoradiography after ligand blotting with [125I]IGF-I or[ 125I]IGF-II. The identity of the binding proteins was confirmed by immunoblotting and immunoprecipitation with specific antibodies. Using this method, all six human high affinity IGFBPs could be clearly separated from each other according to their molecular mass and isoelectric points (pI). All IGFBPs exhibited a variety of specific pI isoforms, which presumably represent posttranslational modifications. In adult human serum, glycosylated IGFBP-3 is found as a broad band of spots with molecular masses of 41 and 45 kDa and a pI in the range of 4.8–8.2. The two IGFBP...
- Published
- 1999
14. Postnatal Overexpression of Insulin-Like Growth Factor II in Transgenic Mice Is Associated with Adrenocortical Hyperplasia and Enhanced Steroidogenesis1
- Author
-
Eckhard Wolf, Dieter Engelhardt, Harald Lahm, Peter J. Schmidt, Matthias M. Weber, Christian Fottner, Katinka Gittner, and Kathrin M. H. Brodowski
- Subjects
Genetically modified mouse ,medicine.medical_specialty ,Growth factor ,medicine.medical_treatment ,Transgene ,Biology ,Hyperplasia ,medicine.disease ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,Zona fasciculata ,chemistry ,Corticosterone ,Internal medicine ,medicine ,Secretion ,Phosphoenolpyruvate carboxykinase - Abstract
The influence of postnatal insulin-like growth factor II (IGF-II) overexpression on adrenal growth and function was investigated in 3-month-old male phosphoenolpyruvate carboxykinase (PEPCK) promoter human IGF-II transgenic mice, which are characterized by 4-to 6-fold elevated postnatal IGF-II serum levels. Plasma corticosterone levels of PEPCK-IGF-II transgenic mice were 2-fold higher than in age- and sex-matched controls, both in the morning (7.4 +/- 1.5 vs. 17.8 +/- 3.9 ng/ml, P < 0.01) and in the evening (33.3 +/- 6.5 vs. 65.3 +/- 12 ng/ml, P < 0.01). When PEPCK-IGF-II transgenic mice were subjected to an ACTH challenge, corticosterone levels were stimulated 6-fold, to 396 +/- 17 ng/ml after 60 min, compared with 230 +/- 24 ng/ml in the control group. In contrast to corticosterone, plasma ACTH levels were similar in transgenic and control mice, excluding an indirect effect of IGF-II at the hypothalamic or pituitary level. In vitro, the basal and ACTH-induced corticosterone production of adrenal glands from transgenic mice was higher (2-fold and 1.8-fold, respectively) than that of control organs. However, when normalized for adrenal weight, the in vitro corticosterone secretion was similar in both groups. At autopsy, adrenal weights of transgenic mice were significantly greater than those of control adrenal glands (3.3 +/- 0.2 vs. 2.0 +/- 0.2 mg, P < 0.01, n = 10). Furthermore, a local expression of human IGF-II could be demonstrated in transgenic adrenal glands by RT-PCR, whereas in normal adult mice, no adrenal expression of IGF-II was detected. Stereological investigation of adrenal glands from another set of PEPCK-IGF-II transgenic mice and controls (6-month-old males) demonstrated that the increase in adrenal weight in transgenic mice is mainly caused by a 50% increase in the number of zona fasciculata cells, whereas cell volume and zonation of transgenic adrenal glands remained unchanged. In conclusion, our data indicate that postnatal overexpression of IGF-II induces an increased adrenal weight and elevated corticosterone serum levels, presumably by a direct mitogenic effect of IGF-II on adrenocortical fasciculata cells.
- Published
- 1999
15. Growth Hormone has no Direct Effect on Human Adrenal Steroid and Insulin-Like Growth Factor-Binding Protein Secretion
- Author
-
Matthias M. Weber, Dieter Engelhardt, R. Oberneder, and P. Michl
- Subjects
Cortisol secretion ,endocrine system ,medicine.medical_specialty ,Hydrocortisone ,medicine.medical_treatment ,Blotting, Western ,Culture Media, Serum-Free ,Insulin-like growth factor-binding protein ,chemistry.chemical_compound ,Endocrinology ,Adrenocorticotropic Hormone ,In vivo ,Corticosterone ,Internal medicine ,medicine ,Humans ,Secretion ,Cells, Cultured ,biology ,Human Growth Hormone ,Chemistry ,Growth factor ,General Medicine ,Insulin-Like Growth Factor Binding Proteins ,Blot ,Kinetics ,Cell culture ,Adrenal Cortex ,biology.protein ,hormones, hormone substitutes, and hormone antagonists - Abstract
Although it is known that growth hormone (GH) exerts its growth-promoting effects mainly via Insulin-like growth factor-I (IGF-I), an increasing number of direct effects of GH has been described in many tissues. In vivo, mice transgenic for human growth hormone (hGH) show significantly elevated levels of corticosterone, enlarged adrenal glands, and altered levels of insulin-like growth factor binding proteins (IGF-BPs). Recently, we have shown that IGF's induce the secretion of cortisol and IGF-BP's in adult human adrenocortical cells. However, since human adrenal glands express the intact GH-receptor, the objective of this study was to investigate whether GH exerts a direct effect on the steroidogenesis and IGF-BP synthesis in adult human adrenocortical cells. Primary cell cultures in monolayer were incubated under serum-free conditions with human growth hormone and/or ACTH for up to 72 hours. Cortisol was measured by specific RIA and the secretion of insulin-like growth factor binding proteins was analyzed by Western ligand blotting. hGH alone was unable to stimulate basal or ACTH-induced cortisol secretion. Additionally, neither hGH alone or in combination with ACTH did significantly alter the secretion of IGF-BP's. Therefore we conclude that hGH is unable to directly stimulate cortisol secretion and IGF-BP secretion in cultured human adrenocortical cells.
- Published
- 1999
16. Sporadic Pheochromocytomas Are Rarely Associated with Germline Mutations in thevhlTumor Suppressor Gene or theretProtooncogene1
- Author
-
Wolfgang Hoeppner, Dieter Engelhardt, Hendrik Jähnig, Michael M. Ritter, Fritz Spelsberg, Hiltrud Brauch, and Thorsten Wöhl
- Subjects
medicine.medical_specialty ,Mutation ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Biochemistry (medical) ,Clinical Biochemistry ,Single-strand conformation polymorphism ,Biology ,urologic and male genital diseases ,medicine.disease ,medicine.disease_cause ,Biochemistry ,female genital diseases and pregnancy complications ,Germline ,Pheochromocytoma ,Endocrinology ,Germline mutation ,Internal medicine ,medicine ,Von Hippel–Lindau disease ,Multiple endocrine neoplasia ,neoplasms ,Index case - Abstract
Pheochromocytoma is a tumor that may occur sporadically or may be a manifestation of a hereditary disease, such as von Hippel-Lindau disease (VHL) and multiple endocrine neoplasia (MEN) type 2. As patients with VHL or MEN type 2 are at risk to develop multiple tumors, they must be distinguished from sporadic cases. We determined the incidence of VHL and MEN type 2 among 62 German patients diagnosed with pheochromocytoma without a history of a hereditary disease. Germline analyses of the vhl gene and exons 10, 11, and 13 of the ret protooncogene were performed by PCR, single strand conformation polymorphism, enzyme digestion, or sequencing. Two patients (3%) showed vhl mutations (95% confidence interval, 1-11%). One patient showed loss of the MspI restriction site at nucleotides 712/713. Another patient had a C/T change at an intronic site that was also detected in 2 of his offspring. No mutations were detected in the ret protooncogene (97.5% confidence interval, 0-6%). In Germany, most sporadic pheochromocytomas are not due to VHL or MEN type 2. Therefore, clinical work-up in patients with pheochromocytoma without signs of hereditary disease is not recommended. However, because the costs of genetic screening are relatively low, and each index case allows optimal care for family members, molecular testing might be cost-effective.
- Published
- 1997
17. Interleukin-3 and Interleukin-6 Stimulate Cortisol Secretion from Adult Human Adrenocortical Cells
- Author
-
P. Michl, Dieter Engelhardt, Matthias M. Weber, and Christoph J. Auernhammer
- Subjects
Adult ,Cortisol secretion ,medicine.medical_specialty ,Hydrocortisone ,Indomethacin ,Cyclooxygenase pathway ,chemistry.chemical_compound ,Lipoxygenase ,Endocrinology ,Adrenocorticotropic Hormone ,Internal medicine ,Cyclic AMP ,medicine ,Humans ,Masoprocol ,Cyclooxygenase Inhibitors ,Lipoxygenase Inhibitors ,Interleukin 6 ,Cells, Cultured ,Interleukin 3 ,biology ,Interleukin-6 ,Interleukin ,Recombinant Proteins ,Nordihydroguaiaretic acid ,Kinetics ,chemistry ,Adrenal Cortex ,biology.protein ,Interleukin-3 ,medicine.drug - Abstract
Accumulating data indicate that interleukins can activate the hypothalamic-pituitary-adrenal (HPA) axis. We evaluated the effect of human recombinant interleukin-3 (IL-3) and interleukin-6 (IL-6) on cortisol secretion from adult human adrenocortical cells in primary culture. IL-3 and IL-6 (100 μg/L) equipotently stimulated basal cortisol secretion approximately 5-fold. The stimulatory effect was significant after 12 h (p < 0.01) and maximum cortisol levels were induced after 48 h. In contrast to ACTH, which significantly induced cAMP levels in parallel to its steroidogenic effect, IL-3 or IL-6 had no significant effect on cAMP. Furthermore, we showed that specific inhibition of the cyclooxygenase pathway by indomethacin completely blocked the steroidogenic effect of IL-6 while the effect of IL-3 was not affected. In contrast, coincubation with nordihydroguaiaretic acid—a specific inhibitor of the lipoxygenase system—abolished IL-3 stimulated steroidogenesis but had no effect on IL-6 stimulated cortisol secretion. These findings indicate that IL-3 and Il-6 directly stimulate the steroidogenesis at the adrenal level through activation of different, cAMP-independent pathways. While the stimulatory effect of IL-6 on cortisol secretion from adult human adrenocortical cells seems to be mediated through the cyclooxygenase pathway, the effect of IL-3 on adrenocortical cortisol secretion is dependent on the lipoxygenase pathway.
- Published
- 1997
18. Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe
- Author
-
Hiltrud Brauch, Karl H. Plate, Dieter Engelhardt, Otakar Masek, Teodor Streicher, F. Pausch, Berton Zbar, Hartmut P. H. Neumann, Damjan Glavac, F. Chen, Claudia Wittke, Heinz Höfler, and Hendrik Jaenig
- Subjects
Male ,von Hippel-Lindau Disease ,Genotype ,endocrine system diseases ,DNA Mutational Analysis ,Molecular Sequence Data ,Population ,Biology ,urologic and male genital diseases ,medicine.disease_cause ,Pheochromocytoma ,Cancer syndrome ,Germline mutation ,Genetics ,medicine ,Humans ,Missense mutation ,Genes, Tumor Suppressor ,Von Hippel–Lindau disease ,education ,neoplasms ,Germ-Line Mutation ,Genetics (clinical) ,DNA Primers ,education.field_of_study ,Mutation ,Base Sequence ,Genetic Carrier Screening ,medicine.disease ,Phenotype ,female genital diseases and pregnancy complications ,Pedigree ,Europe ,Female - Abstract
von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome predisposing to retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma and pancreatic tumors. Clinically two types of the disease can be distinguished: VHL type 1 (without pheochromocytoma) and VHL type 2 (with pheochromocytoma). We report VHL germline mutations and trends in phenotypic variation in families from central Europe. We identified 28 mutations in 53/65 (81.5%) families with 18 (64%) mutations being unique to this population. Whereas types and distribution of mutations as well as a strong correlation of missense mutations with the VHL 2 phenotype were similar to those identified in other populations, these families have provided new insights into the molecular basis for variability in the VHL 2 phenotype. Seven different missense mutations in exons 1 and 3 varied in their biological consequences from a minimal VHL 2 phenotype with pheochromocytoma only to a full VHL 2 phenotype with RCC and pancreatic lesion. These findings contribute to a better understanding of the fundamental mechanisms of VHL disease and its phenotypic variability. Further, we have provided rapid VHL screening for the families in central Europe, which has resulted in improved diagnosis and clinical management.
- Published
- 1996
19. Insulin-like growth factor II (IGF-II) is more potent than IGF-I in stimulating cortisol secretion from cultured bovine adrenocortical cells: interaction with the IGF-I receptor and IGF-binding proteins
- Author
-
Dieter Engelhardt, Christian Fottner, Pia Simmler, and Matthias M. Weber
- Subjects
Cortisol secretion ,medicine.medical_specialty ,Hydrocortisone ,medicine.medical_treatment ,Blotting, Western ,Stimulation ,Insulin-Like Growth Factor Receptor ,Insulin-like growth factor-binding protein ,Receptor, IGF Type 1 ,Endocrinology ,Adrenocorticotropic Hormone ,Insulin-Like Growth Factor II ,Internal medicine ,medicine ,Animals ,Insulin-Like Growth Factor I ,Receptor ,Cells, Cultured ,Dose-Response Relationship, Drug ,biology ,Adrenal gland ,Growth factor ,Drug Synergism ,Recombinant Proteins ,Up-Regulation ,Insulin-Like Growth Factor Binding Proteins ,medicine.anatomical_structure ,Adrenal Cortex ,biology.protein ,Cattle ,Carrier Proteins ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Although the stimulating effect of insulin-like growth factor I (IGF-I) on adrenal steroidogenesis has been well established, the role of IGF-II in the adult adrenal gland remains unknown. We, therefore, investigated the effect of recombinant human IGF-II on cortisol and cAMP synthesis from adult bovine adrenocortical cells. IGF-II, time and dose dependently, stimulated basal cortisol secretion maximally 3-fold. In combination with ACTH, IGF-II (13 nM) synergistically increased cortisol secretion from 1-fold (10(-8) M ACTH) to 28-fold of untreated control levels. In contrast, IGF-I at equimolar concentrations did not show an effect on basal cortisol secretion, and in combination with ACTH elicited a significant weaker stimulatory effect than IGF-II (22-fold increase). The synergistic effect of IGF-II on ACTH-promoted cortisol secretion was paralleled by accumulation of cAMP in the culture medium. Although both IGF receptors are present in adult bovine adrenocortical cells, the effect of IGF-II seems to be mediated through interaction with the IGF-I receptor, as [Arg54,55]IGF-II, which only binds to the IGF-I receptor, was equipotent to native IGF-II, whereas [Leu27]IGF-II, which preferentially binds to the type II IGF receptor, did not show any effect. By Western ligand blotting, four different molecular forms of IGF-binding proteins (IGFBPs) were identified in conditioned medium of bovine adrenocortical cells with apparent molecular masses of 39-44, 34, 29, and 24 kilodaltons. ACTH treatment increased the abundance of all binding proteins, on the average, 2.3-fold, except for the 29-kDa band, which was predominantly induced 6.8-fold. Additionally, [des1-3]IGF-I, a truncated IGF variant that exhibits only minimal binding to IGFBPs, was significant more potent than IGF-I and elicited the same maximum stimulatory effect on cortisol secretion as IGF-II and [des1-6]IGF-II. In conclusion, these results demonstrate that 1) IGF-II stimulates basal as well as ACTH-induced cortisol secretion from bovine adrenocortical cells more potently than IGF-I; 2) this effect is mediated through interaction of IGF-II with the IGF-I receptor; 3) bovine adrenocortical cells synthesize various IGFBPs that are induced differentially by ACTH; and 4) IGFBPs apparently play a modulatory role in IGF-induced stimulation of adrenal steroidogenesis. Therefore, bovine adult adrenocortical cells provide a useful tissue culture model in which the interactions among locally produced IGFs, IGFBPs, and the IGF-I receptor can be evaluated.
- Published
- 1995
20. Autosomal dominant malignant and catecholamine-producing paraganglioma caused by a splice donor site mutation in SDHC
- Author
-
Peter Lohse, Dieter Engelhardt, Stephan Niemann, and Ulrich Müller
- Subjects
Adult ,Biology ,Carotid Body Tumor ,Exon ,Catecholamines ,Splice Donor Site ,Paraganglioma ,Genetics ,medicine ,Humans ,Transversion ,Genetics (clinical) ,Genes, Dominant ,Intron ,Membrane Proteins ,Exons ,medicine.disease ,Magnetic Resonance Imaging ,Molecular biology ,Introns ,Human genetics ,Succinate Dehydrogenase ,Mutation ,Mutation (genetic algorithm) ,Catecholamine ,Female ,RNA Splice Sites ,medicine.drug - Abstract
Mutations in SDHC cause autosomal dominant paraganglioma, type 3 (PGL3), and have to date been demonstrated in only one family. Here, we report on a novel mutation in a patient with a malignant, catecholamine-producing paraganglioma at the carotid bifurcation. The mutation is a G--T transversion at position +1 of intron 5 of the SDHC gene, leading to the deletion of exon 5 and a shift in the reading frame.
- Published
- 2003
21. Herausgeber- und Autorenverzeichnis
- Author
-
Kurt Possinger, Anne Constanze Regierer, Annette Dieing, Dieter Engelhardt, Jan Eucker, Bernd Flath, Gunnar Folprecht, Michael Geißler, Erhard Hiller, Andreas Hochhaus, Christian Jehn, Ulrich Keilholz, Wolfgang Knauf, Hans-Jochem Kolb, Diana Lüftner, Ralph Naumann, Helmut Oettle, Ulrich-Frank Pape, Gabriele Pecher, Uwe Platzbecker, Andreas Rank, Peter Reichardt, Oliver Rick, Markus Ruhnke, Markus Schaich, Andreas Schalhorn, Peter Schmid, Alexander Schmittel, Christian Scholz, Carsten-Oliver Schulz, Isrid Sturm, and Bertram Wiedenmann
- Published
- 2012
22. Enhancement of Magnetic Fields in High-Gravity Stars Due to an Intrinsic Dynamo Effect
- Author
-
Dieter Engelhardt and Irmela Bues
- Subjects
Astrophysics::Solar and Stellar Astrophysics - Abstract
A model of a local magnetic field within a white dwarf is constructed by the use of quantum statistics. The polarized Fermi, Bose and Maxwell statistics is calculated within a Heisenberg magnetism model by the use of Jones calculus. With a mesoscopic description the quantum mechanical dynamo can be discussed. The result is an efficient excitation mechanism, based on Lorentz time transformations and magnetic interactions. An Ap star as progenitor of a polarized white dwarf may loose its field and can generate a stronger one due to an intrinsic dynamo on a time scale of 107 years.
- Published
- 1993
23. Resection of a branchiomeric paraganglioma at a rare extrapulmonary location
- Author
-
Horst-Guenter Rau, Michael M. Ritter, Dieter Engelhardt, and Borika Szukics
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Scintigraphy ,Resection ,Iodine Radioisotopes ,Paraganglioma ,Norepinephrine ,medicine.artery ,medicine ,Humans ,Posterolateral thoracotomy ,medicine.diagnostic_test ,Vascular disease ,business.industry ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Right pulmonary artery ,Surgery ,3-Iodobenzylguanidine ,Branchial Region ,Pulmonary artery ,Radiopharmaceuticals ,Cardiology and Cardiovascular Medicine ,business - Abstract
Thoracic paragangliomas are a rare cause of hypertension. We report the occurrence of a sporadic benign norepinephrine-producing branchiomeric paraganglioma in a 32-year-old man with paroxysms of hypertension. After localization by iodine 123–metaiodobenzylguanidine scintigraphy and magnetic resonance imaging, the paraganglioma was resected successfully below the right pulmonary artery through a right-sided posterolateral thoracotomy. The particular location was consistent with a branchiomeric paraganglioma in an extremely rare extrapulmonary location.
- Published
- 2000
24. Treatment Of strong magnetic fields in very hot stellar atmospheres
- Author
-
Irmela Bues and Dieter Engelhardt
- Subjects
Physics ,symbols.namesake ,Zeeman effect ,Magnetic energy ,Quantum electrodynamics ,Dirac equation ,Radiative transfer ,symbols ,Rate equation ,Electron ,Electron magnetic dipole moment ,Magnetic field - Abstract
Polarized radiative transfer in a hydrogen-rich model atmosphere of an effective temperature of 50000 K and a magnetic field strength of B=1000 Tesla must be investigated in the NLTE scheme. The four transfer equations for each Zeeman transition Δm = 0, + 1, -1 coupled by the interaction of the polarized beam and the electron, are connected to the rate equations in terms of energy. Within the framework of the Dirac equation as a transfer equation the four equations decouple including magnetooptical parameters. Application of the Greens's function method leads to a formal solution, which is inverted numerically.
- Published
- 2008
25. Pure hydrogen in the spectrum of GD229
- Author
-
Irmela Bues and Dieter Engelhardt
- Subjects
Physics ,symbols.namesake ,Hydrogen ,chemistry ,Dirac equation ,Spectrum (functional analysis) ,symbols ,chemistry.chemical_element ,Atomic physics - Published
- 2008
26. Malignome endokriner Organe
- Author
-
Ursula Plöckinger, Ulrich-Frank Pape, Dieter Engelhardt, and Bertram Wiedenmann
- Subjects
business.industry ,Medicine ,business - Published
- 2007
27. Role of the intracellular receptor domain of gp130 (exon 17) in human inflammatory bowel disease
- Author
-
Peter Lohse, Julia Seiderer, George Vlotides, Dieter Engelhardt, Fabian Schnitzler, Burkhard Göke, Michael Sackmann, Christoph J. Auernhammer, Thomas Ochsenkühn, and Kathrin Zitzmann
- Subjects
Adult ,Male ,Cytokine Receptor gp130 ,Biology ,Inflammatory bowel disease ,digestive system ,Exon ,Antigen ,Crohn Disease ,Antigens, CD ,Intracellular receptor ,medicine ,Humans ,Colitis ,Aged ,Membrane Glycoproteins ,digestive, oral, and skin physiology ,Gastroenterology ,General Medicine ,Exons ,Middle Aged ,medicine.disease ,Glycoprotein 130 ,biological factors ,digestive system diseases ,Protein Structure, Tertiary ,Immunology ,Colitis, Ulcerative ,Female ,Brief Reports ,biological phenomena, cell phenomena, and immunity - Abstract
To study the role of the intracellular receptor domain of gp130 in human inflammatory bowel disease (IBD).We amplified and sequenced the complete exon 17 of the human gp130 gene in 146 patients with IBD. According to clinical and histopathological signs, the 146 patients with IBD were classified as having Crohn's disease (n = 73) or ulcerative colitis (n = 63), or as indeterminate status (n = 10).No mutations in exon 17 of the gp130 gene could be detected in any of the 146 patients with IBD examined.There is no evidence that mutations in exon 17 of the gp130 gene are involved in the pathogenesis of human IBD.
- Published
- 2005
28. Isolated familial pheochromocytoma as a variant of von Hippel-Lindau disease
- Author
-
W. Höppner, Dieter Engelhardt, B.A.J. Ponder, Eamonn R. Maher, L. Mulligan, A. Frilling, P A Crossey, and Michael M. Ritter
- Subjects
Male ,medicine.medical_specialty ,Pathology ,von Hippel-Lindau Disease ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Adrenal Gland Neoplasms ,Multiple Endocrine Neoplasia Type 2a ,Multiple endocrine neoplasia type 2 ,Pheochromocytoma ,urologic and male genital diseases ,Biochemistry ,Endocrinology ,Pregnancy ,Internal medicine ,medicine ,Humans ,Missense mutation ,Neurofibromatosis ,Von Hippel–Lindau disease ,neoplasms ,Gene Rearrangement ,Vascular disease ,business.industry ,Point mutation ,Biochemistry (medical) ,Genetic Variation ,Gene rearrangement ,medicine.disease ,female genital diseases and pregnancy complications ,Pedigree ,Female ,business - Abstract
Inherited pheochromocytomas are often part of familial syndromes, especially multiple endocrine neoplasia type 2 (MEN 2), retinal cerebellar hemangioblastomatosis [von Hippel-Lindau (vHL) disease] or neurofibromatosis type 1. It is not clear whether isolated familial pheochromocytoma exists as a separate clinical entity. In a family with pheochromocytomas in three generations and with at least seven affected members, we investigated by clinical and genetic analyses the presence or absence of associated conditions. The clinical investigations included ophthalmological and radiological studies for von Hippel-Lindau disease (magnetic resonance imaging of the brain, computed tomography of the abdomen, and direct ophthalmoscopy after mydriasis) and annual calcitonin stimulation tests for C cell disease in five members who agreed to regular follow-up. Besides the pheochromocytomas (so far, these have been multiple in five of seven individuals) no definite second associated condition was found. Genetic analysis did not identify any MEN 2-specific RET protooncogene point mutations (which are present in 97% of MEN 2a families). However, despite the complete absence of other clinical manifestations of the vHL disease (besides pheochromocytomas), a previously undescribed germline missense mutation in the vHL tumor suppressor gene was found (C775G transversion with a predicted substitution of a leucine by a valine at codon 259 in the putative vHL protein). We conclude that in this family the sole occurrence of pheochromocytoma is a variant of vHL disease.
- Published
- 1996
29. The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells
- Author
-
Florian Kopp, Christoph J. Auernhammer, Franziska Dorn, Neziha Cengic, Gerald Spoettl, Dieter Engelhardt, Sabine Hengge, George Vlotides, and Matthias M. Weber
- Subjects
medicine.medical_specialty ,Receptor complex ,Programmed cell death ,Endocrinology, Diabetes and Metabolism ,Poly ADP ribose polymerase ,Apoptosis ,Oncostatin M ,Cleavage (embryo) ,Amino Acid Chloromethyl Ketones ,Mice ,Endocrinology ,Antigens, CD ,Internal medicine ,Cell Line, Tumor ,Proto-Oncogene Proteins ,medicine ,Cytokine Receptor gp130 ,Animals ,Membrane Glycoproteins ,biology ,Oncostatin M receptor ,Janus Kinase 2 ,Protein-Tyrosine Kinases ,Tyrphostins ,Glycoprotein 130 ,Molecular biology ,Caspase Inhibitors ,Adrenal Cortex Neoplasms ,Caspases ,biology.protein ,Peptides ,Signal Transduction - Abstract
The effects of murine oncostatin M (mOSM) are specifically mediated by the heterodimeric oncostatin M receptor (OSMR)/gp130 receptor complex. In the current study we demonstrate that murine adrenocortical Y-1 tumor cells express the OSMR/gp130 complex. Incubation of Y-1 cells with 1 and 10 ng/ml mOSM induces cell death due to specific induction of apoptosis. Western blot analysis of Y-1 cells incubated with mOSM for 24 h revealed caspase-3 cleavage and poly(ADP-ribase) polymerase (PARP) cleavage. In a proliferation assay system, incubation of Y-1 cells with 0.01, 0.1, 1 and 10 ng/ml mOSM for 24 h resulted in a decrease in cell numbers to 99+/-2%, 84+/-9%, 50+/-7% and 43+/-5% respectively of untreated control (defined as 100%). Pretreatment of Y-1 cells with the Jak2 inhibitor AG490 (100 microM) rescued Y-1 cells from OSM-induced (10 ng/ml) cell death. Similarly, pretreatment of Y-1 cells with the general caspase inhibitor Z-VAD-FMK (42 microM) rescued Y-1 cells from OSM-induced (10 ng/ml) cell death. In summary, we show that adrenocortical Y-1 tumor cells express the OSMR/gp130 complex and that mOSM induces the Jak-STAT signaling cascade in these cells. Murine OSM in a dose-dependent manner induces apoptosis in adrenocortical Y-1 tumor cells. Apoptosis was demonstrated by caspase-3 cleavage and PARP cleavage. Rescue of Y-1 cells from mOSM-induced apoptosis by the Jak2 inhibitor, AG490, and the general caspase inhibitor, Z-VAD-FMK, demonstrates Jak activation and subsequent caspase activation to be essential for mOSM-induced apoptosis in adrenocortical Y-1 tumor cells. The putative role of OSM as an immunotherapeutic agent in human adrenocortical cancer remains to be elucidated.
- Published
- 2004
30. Expression of novel neurotrophin-1/B-cell stimulating factor-3 (NNT-1/BSF-3) in murine pituitary folliculostellate TtT/GF cells: pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide-induced stimulation of NNT-1/BSF-3 is mediated by protein kinase A, protein kinase C, and extracellular-signal-regulated kinase1/2 pathways
- Author
-
Dieter Engelhardt, Kathrin Zitzmann, Günter K. Stalla, Christoph J. Auernhammer, George Vlotides, and Sabine Hengge
- Subjects
medicine.medical_specialty ,Vasoactive intestinal peptide ,Adenylate kinase ,Cell Line ,Mice ,Endocrinology ,Proopiomelanocortin ,Internal medicine ,medicine ,Animals ,Northern blot ,RNA, Messenger ,Enzyme Inhibitors ,Protein kinase A ,Protein kinase C ,Protein Kinase C ,Mitogen-Activated Protein Kinase 1 ,Mitogen-Activated Protein Kinase 3 ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Neuropeptides ,Glycoprotein 130 ,Blotting, Northern ,Cyclic AMP-Dependent Protein Kinases ,Pituitary adenylate cyclase-activating peptide ,Bucladesine ,Gene Expression Regulation ,Pituitary Gland ,biology.protein ,Cytokines ,Pituitary Adenylate Cyclase-Activating Polypeptide ,Tetradecanoylphorbol Acetate ,Mitogen-Activated Protein Kinases ,Protein Kinases ,hormones, hormone substitutes, and hormone antagonists ,Vasoactive Intestinal Peptide - Abstract
Novel neurotrophin-1/B cell stimulating factor-3 (NNT-1/BSF-3) is a gp130 cytokine potently stimulating corticotroph proopiomelanocortin gene expression and ACTH secretion by a Janus kinase-signal transducer and activator of transcription (JAK-STAT)-dependent mechanism. In the current study, we examined the regulation of NNT-1/BSF-3 mRNA expression in murine pituitary folliculostellate TtT/GF cells using Northern blot technique. A 5- to 9-fold and a 4- to 7-fold induction in NNT-1/BSF-3 mRNA expression was observed between 2 and 6 h stimulation with the protein kinase C (PKC) stimulus phorbol-12-myristate-13-acetate (100 nm) and the protein kinase A (PKA) stimulus Bu2cAMP (5 mm), respectively. Pituitary adenylate cyclase-activating polypeptide (PACAP-38, 50 nm) and vasoactive intestinal peptide (VIP, 50 nm) also stimulated NNT-1/BSF-3 mRNA expression 5- to 9-fold between 2 and 6 h. Preincubation with PKC and PKA inhibitors such as H-7 (20 μm), GF109203X (50 μm), and H-89 (50 μm) decreased the stimulatory effects of PACAP and VIP. Both PACAP-38 and VIP also rapidly induced ERK1/2 phosphorylation and their stimulatory effect on NNT-1/BSF-3 mRNA expression was reduced by the MAPK kinase/ERK kinase (MEK) inhibitor U0126 (10 μm). Dexamethasone (10−7m) was a potent inhibitor of phorbol-12-myristate-13-acetate-induced NNT-1/BSF-3 expression. RT-PCR analysis demonstrated TtT/GF cells to express the short and the hop variant but not the hip variant of the PACAP-1 receptor (PAC1-R). In addition, TtT/GF cells express the VIP/PACAP-2 receptor (VPAC2-R). In summary, NNT-1/BSF-3 is expressed in pituitary folliculostellate TtT/GF cells and induced by PKC-, PKA-, and ERK1/2-dependent mechanisms. The novel gp130 cytokine NNT-1/BSF-3 derived from folliculostellate cells might act as a paracrine neuroimmunoendocrine modulator of pituitary corticotroph function.
- Published
- 2003
31. Comparative study of gp130 cytokine effects on corticotroph AtT-20 cells--redundancy or specificity of neuroimmunoendocrine modulators?
- Author
-
Giorgio Senaldi, Matthias M. Weber, Dieter Engelhardt, Franziska Dorn, George Vlotides, Neziha Cengic, Nicola B. Isele, Christoph J. Auernhammer, Gerald Spöttl, and Florian Kopp
- Subjects
Pro-Opiomelanocortin ,Leukemia Inhibitory Factor Receptor alpha Subunit ,medicine.medical_treatment ,Gene Expression ,Suppressor of Cytokine Signaling Proteins ,Ligands ,Mice ,Endocrinology ,Cytokine Receptor gp130 ,Phosphorylation ,Receptor ,Promoter Regions, Genetic ,Receptor, Ciliary Neurotrophic Factor ,Membrane Glycoproteins ,DNA-Binding Proteins ,Cytokine ,STAT1 Transcription Factor ,Neurology ,Cytokines ,hormones, hormone substitutes, and hormone antagonists ,STAT3 Transcription Factor ,endocrine system ,Hypothalamo-Hypophyseal System ,Receptors, OSM-LIF ,Neuroimmunomodulation ,Immunology ,Biology ,stat ,Cell Line ,Antigen ,Adrenocorticotropic Hormone ,Antigens, CD ,Pituitary Gland, Anterior ,medicine ,Animals ,RNA, Messenger ,Receptors, Cytokine ,Dose-Response Relationship, Drug ,Endocrine and Autonomic Systems ,Glycoprotein 130 ,Repressor Proteins ,Cell culture ,Suppressor of Cytokine Signaling 3 Protein ,Cancer research ,Trans-Activators ,Tyrosine ,Corticotropic cell ,Transcription Factors - Abstract
Objective: This comparative in vitro study examined the effects of all known gp130 cytokines on murine corticotroph AtT-20 cell function. Methods: Cytokines were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine phosphorylation of the signal transducer and activator of transcription (STAT)3 and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and adrenocorticotropic hormone (ACTH) secretion were determined. Results: Leukemia inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1 (LIFR/gp130 ligands), as well as ciliary neurotrophic factor (CNTF) and novel neurotrophin-1/B-cell stimulating factor-3 (CNTFRα/LIFR/gp130 ligands) are potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6 (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect. Conclusion: (i) CNTFR complex ligands are potent stimuli of corticotroph function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively weak direct stimuli of corticotroph function; (iii) differential effects of human and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto unknown ability to stimulate corticotroph function, and (v) despite redundant immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells are preferably activated through the LIFR and CNTFR complexes.
- Published
- 2003
32. VHL2C phenotype in a German von Hippel-Lindau family with concurrent VHL germline mutations P81S and L188V
- Author
-
Hiltrud Brauch, Bettina Klein, Thorsten Wöhl, Dieter Engelhardt, and Gregor Weirich
- Subjects
Male ,medicine.medical_specialty ,von Hippel-Lindau Disease ,endocrine system diseases ,Tumor suppressor gene ,Endocrinology, Diabetes and Metabolism ,Ubiquitin-Protein Ligases ,Clinical Biochemistry ,DNA Mutational Analysis ,Molecular Sequence Data ,Disease ,Biology ,urologic and male genital diseases ,medicine.disease_cause ,Nucleic Acid Denaturation ,Biochemistry ,Polymerase Chain Reaction ,Protein Structure, Secondary ,Pheochromocytoma ,Ligases ,Structure-Activity Relationship ,Endocrinology ,Germline mutation ,Internal medicine ,Germany ,medicine ,Humans ,Amino Acid Sequence ,neoplasms ,Chromatography, High Pressure Liquid ,Germ-Line Mutation ,Denaturing hplc ,Genetics ,Mutation ,Base Sequence ,Tumor Suppressor Proteins ,Biochemistry (medical) ,Sequence Analysis, DNA ,Von hippel lindau ,medicine.disease ,Phenotype ,female genital diseases and pregnancy complications ,Pedigree ,Von Hippel-Lindau Tumor Suppressor Protein ,Female - Abstract
Von Hippel-Lindau disease (VHL) is a multitumor syndrome that develops on the basis of germline mutations in the VHL tumor suppressor gene. Genotype-phenotype correlations have helped to stratify the disease into VHL type 1 (without pheochromocytoma) and VHL type 2A, 2B, and 2C (with pheochromocytoma). VHL2C is characterized by a pheochromocytoma-only phenotype. We report on the P81S germline mutation in a German VHL2C family with the previously identified L188V mutation. The concurrent P81S mutation was identified by novel screening approaches including denaturing HPLC and sequencing. We show the co-segregation of these two mutations with the disease and discuss their possible impact on pVHL function and phenotype.
- Published
- 2002
33. Alterations of the insulin-like growth factor system in patients with polycythemia vera
- Author
-
Dieter Engelhardt, Matthias M. Weber, Gerald Spoettl, and P. Michl
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Blotting, Western ,Radioimmunoassay ,Biology ,Biochemistry ,Peripheral blood mononuclear cell ,Polymerase Chain Reaction ,Receptor, IGF Type 1 ,Pathogenesis ,chemistry.chemical_compound ,Insulin-like growth factor ,Endocrinology ,Polycythemia vera ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Phosphorylation ,Phosphotyrosine ,Molecular Biology ,Polycythemia Vera ,Polymorphism, Single-Stranded Conformational ,Aged ,Growth factor ,Tyrosine phosphorylation ,Exons ,Middle Aged ,medicine.disease ,Blot ,Insulin-Like Growth Factor Binding Proteins ,chemistry ,Leukocytes, Mononuclear ,Female ,Tyrosine kinase - Abstract
The molecular etiology of Polycythemia vera (PV) is still undetermined. Recently, enhanced tyrosine phosphorylation of the insulin-like growth factor-I receptor (IGF-IR) has been shown in PV bone marrow progenitors and peripheral blood mononuclear cells (PBMNC), and elevated levels of IGF binding protein-1 (IGFBP-1) in the serum of PV patients have been reported. To identify further alterations of circulating IGFBPs, the IGFBP profile in the serum of 12 PV patients was compared with age- and sex-matched controls by Western ligand blot (WLB), two-dimensional WLB, IGFBP-3 immunoblot and specific RIA for IGFBP-1, -2, -3 and IGFBP-4. To elucidate a role for the IGF-IR in the pathogenesis of PV, basal and IGF-I stimulated tyrosine phosphorylation of the IGF-IR β-subunit in PBMNC of PV patients or controls was determined by WLB. Furthermore, exons 2, 3 and 15-21 of the IGF-IR were screened for mutations by PCR-single strand conformation polymorphism analysis (PCR-SSCP). We found alterations of the IGFBP profile in the serum of eight out of 12 examined patients including elevated levels of IGFBP-1, -2 and -4, decreased levels of IGFBP-3 and an increase in IGFBP-3 fragment. However, no differences in tyrosine phosphorylation of the IGF-IR in PV patients, neither basal nor IGF-I induced, were detected. Furthermore, no mutations within the screened exons of the IGF-IR could be identified by PCR-SSCP. We conclude that there is no direct impairment of IGF-IR structure or function, but an altered IGFBP profile in a significant portion of PV patients which might contribute to the pathogenesis of PV in these patients.
- Published
- 2001
34. Comparison of two automated adrenocorticotropic hormone assays
- Author
-
Michael Vogeser, Dieter Engelhardt, and Karl Jacob
- Subjects
Adult ,medicine.medical_specialty ,Calibration curve ,Clinical Biochemistry ,Adrenocorticotropic hormone ,Peptide hormone ,law.invention ,Adrenocorticotropic Hormone ,law ,Reference Values ,Internal medicine ,medicine ,Humans ,Chemiluminescence ,Immunoassay ,Chromatography ,Autoanalysis ,biology ,Chemistry ,Biochemistry (medical) ,Reproducibility of Results ,Middle Aged ,Endocrinology ,Polyclonal antibodies ,Reagent ,Luminescent Measurements ,biology.protein ,Light emission ,Female ,Antibody - Abstract
The measurement of adrenocorticotropic hormone (ACTH 1-39; M r 4500) plays a key role in the evaluation of hyper- and hypocortisolism (1)(2)(3), but low ACTH concentrations make accurate measurement challenging. Two automated, nonisotopic ACTH assays have become available in recent years. Because it is usual for rather small series to be assayed for ACTH in a clinical setting and because nonisotopic methods with stable calibration are of great practical interest, we compared these assays. Both assays investigated were solid-phase, sandwich immunoassays that use chemiluminescence for signal generation and are implemented on benchtop, multichannel, random-access analyzers with ready-to-use reagents. The Nichols Advantage ACTH assay (Nichols Institute Diagnostics) uses one acridinium ester-labeled mouse monoclonal antibody that specifically binds to the C-terminal region of ACTH and one biotin-labeled goat polyclonal antibody that binds to the N-terminal region. The sample is incubated for 21 min at 37 °C with both antibodies simultaneously, leading to the formation of a soluble sandwich complex in the presence of ACTH molecules. Streptavidin-coated magnetic particles are then added, and the reaction mixture is incubated for 10 min, during which the sandwich complex binds to the particles by biotin-avidin interaction. The particles are fixed to the wall of the single-use reaction cell magnetically, and unbound, labeled antibody is separated by aspiration and subsequent washing. Finally, two trigger solutions are injected into the reaction cells to initiate the chemiluminescent reaction, and the light emission is quantified over 2 s by a luminometer. A lot-specific master calibration curve is loaded by barcode and adjusted weekly with two calibrators by the user. The reported measuring range extends to 1500 ng/L. Barcode-labeled sample tubes are processed directly. The sample throughput is ∼90/h, and the time to first result is 37 min with a start-up time of ∼15 min. In the …
- Published
- 2000
35. Regulation of steroidogenesis by insulin-like growth factors (IGFs) in adult human adrenocortical cells: IGF-I and, more potently, IGF-II preferentially enhance androgen biosynthesis through interaction with the IGF-I receptor and IGF-binding proteins
- Author
-
Christian Fottner, Dieter Engelhardt, and Matthias M. Weber
- Subjects
Cortisol secretion ,Adult ,medicine.medical_specialty ,Hydrocortisone ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Blotting, Western ,Dehydroepiandrosterone ,Stimulation ,Biology ,Insulin-like growth factor ,Endocrinology ,Adrenocorticotropic Hormone ,Insulin-Like Growth Factor II ,Somatomedins ,Internal medicine ,medicine ,Cyclic AMP ,Humans ,Insulin-Like Growth Factor I ,Cells, Cultured ,Dose-Response Relationship, Drug ,Adrenal cortex ,Adrenal gland ,Dehydroepiandrosterone Sulfate ,Androgen ,Recombinant Proteins ,Insulin-Like Growth Factor Binding Proteins ,medicine.anatomical_structure ,Adrenal Cortex ,Androgens ,hormones, hormone substitutes, and hormone antagonists ,Glucocorticoid ,medicine.drug - Abstract
Although the effect of insulin-like growth factors (IGFs) in fetal adrenocortical cells has been investigated extensively, the role of the IGF system in the adult human adrenal gland remains unclear. In the present study we investigated the effect of recombinant human IGF-I and IGF-II on cortisol, dehydroepiandrosterone sulfate (DHEA-S) and cAMP synthesis in adult human adrenocortical cells in primary culture. Both IGFs stimulate basal as well as adrenocorticotropin (ACTH)-induced steroid secretion in a time- and dose-dependent fashion. While both IGFs (6.5 nM) induced only a moderate 2-fold increase in basal cortisol output after 48 h, the effect on basal DHEA-S secretion was significantly stronger, with a 2.7- and 3.7-fold stimulation by IGF-I and IGF-II respectively. Similarly, IGF-II enhanced ACTH-induced cortisol and DHEA-S secretion more potently than IGF-I. In dose-response experiments, the maximum stimulation of ACTH-induced DHEA-S secretion was induced by 1.6 nM IGF-I (2-fold increase) or IGF-II (2.9-fold increase), while the maximum response of cortisol secretion was elicited only at 13 nM IGF-I (2-fold increase) or IGF-II (2.5-fold increase). This resulted in a significant shift of the DHEA-S dose-response curves to the left, indicating a relative selective stimulation of androgen biosynthesis by physiologically low concentrations (0.4-3.2 nM) of IGF-II, and less potently by IGF-I. At all doses tested, the steroidogenic effect of IGF-II was significantly stronger than the effect of IGF-I. Although both IGF receptors are present in adult human adrenocortical cells, the steroidogenic effect of IGF-II is mediated through the IGF-I receptor, since [Arg54,55]IGF-II, which only binds to the IGF-I receptor, was equipotent with native IGF-II, whereas [Leu27]IGF-II, which preferentially binds to the type II IGF receptor, did not show any effect. In addition, [des1-3]IGF-I, which exhibits only minimal binding to IGFBPs, was significantly more potent than native IGF-I in stimulating adrenal steroid biosynthesis, and elicited almost the same maximum stimulatory effect as IGF-II and [des1-6]IGF-II. By Western ligand blotting of conditioned medium it was shown that adult human adrenocortical cells secrete various IGF-binding proteins (IGFBPs), which are induced differentially by treatment with ACTH. In conclusion, these results demonstrate that: (1)IGF-II stimulates basal as well as ACTH-induced DHEA-S and cortisol secretion from adult human adrenocortical cells more potently than IGF-I; (2) both IGFs predominantly stimulate androgen biosynthesis; (3) the steroidogenic effect of IGF-I and IGF-II is mediated through interaction with the IGF-I receptor; (4) the different steroidogenic potency of IGF-I and IGF-II might be explained by interaction of these ligands with locally produced IGFBPs. These data indicate that the IGF system plays an important role in the regulation of the differentiated function of adult human adrenocortical cells.
- Published
- 1998
36. New IUE-Spectra of the Magnetic White Dwarf GRW +70°8247 and Their Interpretation
- Author
-
Dieter Engelhardt and Irmela Bues
- Subjects
Physics ,White dwarf ,Astrophysics ,Physics::History of Physics ,Spectral line ,Magnetic field ,Interpretation (model theory) - Abstract
The hydrogen model of quasi-Landau-resonances in a very strong magnetic field (≈104 Tesla) is applied to Fourier-transformed IUE spectra of Grw +70°8247.
- Published
- 1997
37. Variations of steroid hormone metabolites in serum and urine in polycystic ovary syndrome after nafarelin stimulation: evidence for an altered corticoid excretion
- Author
-
Karl Jacob, Cornelia Höss, Peter B. Luppa, Dieter Engelhardt, Michael M. Weber, Burkhardt Müller, Rainer Kimmig, Thomas Strowitzki, and Rogerio A. Lobo
- Subjects
Adult ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Urinary system ,Clinical Biochemistry ,Urine ,Biology ,Biochemistry ,Excretion ,chemistry.chemical_compound ,Nafarelin ,Endocrinology ,Internal medicine ,medicine ,Humans ,Glucocorticoids ,Administration, Intranasal ,Creatinine ,Biochemistry (medical) ,Androgen ,Polycystic ovary ,Hormones ,Circadian Rhythm ,chemistry ,Female ,Steroids ,Glucocorticoid ,Gonadotropins ,medicine.drug ,Polycystic Ovary Syndrome - Abstract
To evaluate the clinical relevance of testing pituitary-ovarian responses in patients suffering from polycystic ovary syndrome (PCOS) with the GnRH agonist nafarelin, a 1.2-mg dose of nafarelin was given intranasally to 19 women with PCOS and 15 healthy premenopausal women. The subsequent analysis of steroids in both serum and urine during the test was carried out at several time points for up to 24 h. Serum levels of 17 alpha-hydroxyprogesterone were elevated at all time points of the test in PCOS patients vs. controls [at baseline, 3.5 +/- 0.2 vs. 1.8 +/- 0.1 nmol/L (P < 0.001); at 24 h, 9.9 +/- 0.9 vs. 4.9 +/- 0.3 nmol/L (P < 0.001)]. Basal levels of androstenedione were higher in the patient group, but there was no significant change during the test in either group. Serum testosterone levels were also found to differ in PCOS patients compared with the control values at baseline (2.2 +/- 0.2 vs. 1.5 +/- 0.1 nmol/L; P < 0.05) and after nafarelin treatment (at 24 h, 3.2 +/- 0.4 vs. 1.8 +/- 0.2 nmol/L; P < 0.05). Serum estradiol levels rose significantly in both groups during the test; the posttest levels were significantly higher in PCOS than in controls. The PCOS patients displayed a significant increase in androgen and gestagen metabolites as well as in glucocorticoid metabolites excreted in the urine during the 24 h. In the control subjects, except for 17 alpha-hydroxypregnanolone, which rose significantly, none of the urinary steroids investigated showed relevant changes during the nafarelin test. The posttest excretion of allo-tetrahydrocortisol (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mumol/g creatinine; P < 0.001) and the increase in 17 alpha-hydroxypregnanolone excretion (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mumol/g creatinine; P < 0.001) were distinctly higher in PCOS patients than in the controls; the diagnostic sensitivity of the combination of both parameters was 89% at a 93% specificity. Thus, measurements of 17 alpha-hydroxyprogesterone levels in serum and of urinary allo-tetrahydrocortisol and 17 alpha-hydroxypregnanolone after nafarelin treatment make this stimulation test a valuable diagnostic tool for identifying PCOS patients. The significant changes in the excretion of urinary androgen and gestagen metabolites, unmasked by GnRH agonist stimulation, suggest a functional alteration of the pituitary-ovarian axis. The reason for the increased excretion of glucocorticoid metabolites after nafarelin stimulation remains to be clarified.
- Published
- 1995
38. Therapy of Cushing's syndrome with steroid biosynthesis inhibitors
- Author
-
Dieter Engelhardt and Matthias M. Weber
- Subjects
Cortisol secretion ,medicine.medical_specialty ,3-Hydroxysteroid Dehydrogenases ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Trilostane ,Steroid biosynthesis ,Biochemistry ,Cushing syndrome ,Endocrinology ,Internal medicine ,medicine ,Adrenocortical carcinoma ,Humans ,Etomidate ,Molecular Biology ,Cushing Syndrome ,Metyrapone ,business.industry ,Dihydrotestosterone ,Cell Biology ,medicine.disease ,Aminoglutethimide ,Ketoconazole ,Molecular Medicine ,Steroids ,business ,medicine.drug - Abstract
Several substances with different inhibitory effects on adrenal steroid biosynthesis were investigated in patients with Cushing's syndrome. It has been shown that trilostane, a 3 beta-hydroxysteroid-dehydrogenase inhibitor, is not potent enough to block cortisol biosynthesis in patients with hypercortisolism. Aminoglutethimide inhibits side chain cleavage of cortisol synthesis, but it has been demonstrated that the blocking effect on cortisol secretion is not strong enough to normalize urinary cortisol excretion in patients with Cushing's disease. For metyrapone, an inhibitor of adrenal 11 beta-hydroxylase, promising results were reported for the treatment of Cushing's syndrome. However, the drug has several side effects and depending on the definition of the desired reduction of cortisol secretion a true remission was only found in a minority of patients. The antifungal drug ketoconazole in vitro predominantly blocks 17,20-desmolase (IC50 1 microM) and to a lesser extent 17 alpha-hydroxylase (IC50 10 microM) and 11 beta-hydroxylase (IC50 15-40 microM). Therefore, ketoconazole in vivo most potently suppresses androgen secretion and only to a lesser extent cortisol biosynthesis. Several therapeutic trials with ketoconazole treatment in patients with pituitary Cushing's disease showed various remission rates between 30 and 90%. In contrast, in almost all patients with benign, primary adrenal Cushing's syndrome cortisol levels were normalized. In patients with ectopic ACTH syndrome ketoconazole was effective in about 50% of all reported cases, while cortisol hypersecretion due to adrenocortical carcinoma was only rarely inhibited by ketoconazole. The main side effect of ketoconazole treatment was liver toxicity which occurred in 12% of all treated patients. In contrast to ketoconazole, the narcotic drug etomidate shows a strong inhibitory effect on 11 beta-hydroxylase (IC50 0.03-0.15 microM) but only a weak inhibition of 17,20 desmolase (IC50 380 microM). This correlates with in vivo studies where even low, non-hypnotic doses of etomidate induced a pronounced fall in serum cortisol levels in normals and in patients with Cushing's syndrome. However, its clinical use is limited by its mandatory intravenous application and its sedative effects. In conclusion, ketoconazole remains the only available steroid-inhibitory drug for a therapeutic trial in patients with Cushing's syndrome who cannot be treated definitively by surgery.
- Published
- 1994
39. Identification and characterization of insulin-like growth factor I (IGF-I) and IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in bovine adrenal cells
- Author
-
Martin Reichel, Wieland Kiess, Pia Simmler, Ulrike Kessler, Barbara Adelmann, Thomas Beikler, Matthias M. Weber, and Dieter Engelhardt
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Blotting, Western ,Mannose 6-phosphate ,Biology ,Receptor, IGF Type 2 ,Receptor, IGF Type 1 ,chemistry.chemical_compound ,Insulin-like growth factor ,Endocrinology ,Internal medicine ,medicine ,Animals ,Binding site ,Receptor ,Cells, Cultured ,Binding Sites ,Adrenal cortex ,Cell Membrane ,General Medicine ,Receptor–ligand kinetics ,medicine.anatomical_structure ,chemistry ,Cell culture ,Insulin-like growth factor 2 ,biology.protein ,Adrenal Cortex ,Cattle ,Protein Binding - Abstract
Weber MM, Kiess W, Beikler T, Simmler P, Reichel M, Adelmann B, Kessler U, Engelhardt D. Identification and characterization of insulin-like growth factor I (IGF-I) and IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in bovine adrenal cells. Eur J Endocrinol 1994;130:265–70. ISSN 0804–4643 We have identified and characterized insulin-like growth factor I (IGF-I) and IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in bovine adrenal cells. Iodine-125-labeled IGF-I ([125I]IGF-I) binding was characteristic of the IGF-I receptor, and binding kinetics as well as receptor densities were similar in cortical and medullary membranes. Scatchard analysis of [125I]IGF-I binding to cultured adrenocortical cells showed a single class of high-affinity binding sites with a Kd of 1.4 nmol/l and an average of 150 000 binding sites/cell. Affinity cross-linking experiments displayed a band at an apparent molecular weight of 135 kD, corresponding to the size of the α-subunit of the IGF-I receptor. In analogy, the binding of [125I]IGF-II to bovine adrenal membranes was characteristic of the IGF-II/ M6P receptor and no differences between cortical and medullary membrane fractions were found. Scatchard analysis revealed a single class of high-affinity binding sites in adrenocortical cells with a Kd of 1.1 nmol/l and an average of 280 000 binding sites/cell. The identity of the IGF-II/M6P receptor was confirmed by western blotting of adrenocortical membranes with an anti-IGF-II/M6P receptor antibody and by affinity cross-linking of adrenocortical cells with labeled IGF-II. In conclusion, we have identified and characterized IGF-I and IGF-II/M6P receptors in bovine adrenocortical as well as medullary cells. In both regions of the bovine adrenal gland the IGF-II/M6P receptor is much more abundant than the IGF-I receptor. Matthias M Weber, Medizinische Klinik II, Klinikum Groβhadern, Marchioninistraβe 15, 81377 München, Germany
- Published
- 1994
40. Different inhibitory effect of etomidate and ketoconazole on the human adrenal steroid biosynthesis
- Author
-
J. Lang, B. C. Adelmann, Matthias M. Weber, Dieter Engelhardt, F. Abedinpour, and K. Zeilberger
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,In Vitro Techniques ,Pharmacology ,Steroid biosynthesis ,chemistry.chemical_compound ,Corticosterone ,Etomidate ,Internal medicine ,Adrenal Glands ,Drug Discovery ,medicine ,Cytochrome P-450 Enzyme Inhibitors ,Humans ,IC50 ,Genetics (clinical) ,Aldehyde-Lyases ,biology ,Adrenal gland ,Steroid 17-alpha-Hydroxylase ,General Medicine ,Steroid hormone ,Ketoconazole ,Endocrinology ,medicine.anatomical_structure ,Steroid 16-alpha-Hydroxylase ,chemistry ,Enzyme inhibitor ,Steroid Hydroxylases ,Androgens ,biology.protein ,Steroid 11-beta-Hydroxylase ,Molecular Medicine ,Aryl Hydrocarbon Hydroxylases ,Steroid 21-Hydroxylase ,medicine.drug - Abstract
The narcotic agent etomidate and the antimycotic drug ketoconazole are known to block steroid biosynthesis in man. To study the different effects of these imidazole derivatives on human adrenal steroid biosynthesis we incubated slices of human adrenal glands with 3H-labeled precursors and increasing concentrations of etomidate or ketoconazole (0-2000 microM). After extraction the labeled metabolites were separated by thin-layer chromatography and quantified by scintillation counting. Etomidate inhibited most potently 11 beta-hydroxylase activity by suppressing the formation of corticosterone from 11-deoxycorticosterone to 1% of control [50% inhibitory concentration (IC50) 0.03 microM] while ketoconazole suppressed 11 beta-hydroxylase to only 39% of control activity (IC50 15 microM). Ketoconazole however, most potently blocked the conversion of 17 alpha-hydroxy-progesterone to androstenedione by C17,20-desmolase to about 15% of control activity (IC50 1 microM) while etomidate showed a much weaker effect on this enzyme with a suppression to 50% of C17,20-desmolase control activity at a concentration of 380 microM. Both imidazole drugs showed a similar strong inhibitory effect on the activity of 17 alpha-hydroxylase (IC50 6-18 microM) and 16 alpha-hydroxylase (IC50 4-8 microM) and did not affect 21-hydroxylase. These in vitro data indicate a predominant inhibitory effect of etomidate on corticosteroid biosynthesis by relative selective inhibition of 11 beta-hydroxylase and of ketoconazole on the adrenal androgen biosynthesis by a predominant inhibition of C17,20-desmolase. This differential inhibitory effect of etomidate and ketoconazole on human steroid biosynthesis may be of clinical importance for a possible therapeutic use of these imidazole derivatives in endocrine disorders.
- Published
- 1993
41. Enhancement of Magnetic Fields in High-Gravity Stars due to an Intrinsic Dynamo Effect
- Author
-
Irmela Bues and Dieter Engelhardt
- Subjects
Physics ,Nuclear magnetic resonance ,Field (physics) ,Magnetism ,Quantum electrodynamics ,Dynamo theory ,Astrophysics::Solar and Stellar Astrophysics ,White dwarf ,Mercury's magnetic field ,Jones calculus ,Dynamo ,Magnetic field - Abstract
A model of a local magnetic field within a white dwarf is constructed by the use of quantum statistics. The polarized Fermi, Bose and Maxwell statistics is calculated within a Heisenberg magnetism model by the use of Jones calculus. With a mesoscopic description the quantum mechanical dynamo can be discussed. The result is an efficient excitation mechanism, based on Lorentz time transformations and magnetic interactions. An Ap star as progenitor of a polarized white dwarf may loose its field and can generate a stronger one due to an intrinsic dynamo on a time scale of 107 years.
- Published
- 1993
42. Macroscopic Flux of Spinning Photons in Hot Layers of High Gravity Stars
- Author
-
Irmela Bues and Dieter Engelhardt
- Subjects
Physics ,Density matrix ,Photon ,Condensed matter physics ,Magnetism ,Expectation value ,Elliptical polarization ,Spin (physics) ,Degenerate matter ,Magnetic field - Abstract
Photon flux models for lower layers of magnetic white dwarfs are computed with a proper treatment of quantum mechanics of the light and the partially degenerate plasma. The concept of a polarized Planck function is introduced and a microscopic density matrix of one photon is constructed by the use of a spin=l wave function of elliptical polarization. The thermal expectation value of the many photon density matrix is calculated within Heisenberg’s model of magnetism. The application to the cooling sequence of magnetic white dwarfs suggests an increase of the cooling time in terms of a magnetic field, independent of the chemical composition.
- Published
- 1993
43. Effect of ketoconazole on human ovarian C17,20-desmolase and aromatase
- Author
-
Dieter Engelhardt, B. Adelmann, A. Will, and Matthias M. Weber
- Subjects
endocrine system ,medicine.medical_specialty ,Estrone ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Ovary ,Steroid biosynthesis ,Biochemistry ,chemistry.chemical_compound ,Endocrinology ,Aromatase ,Cytochrome P-450 Enzyme System ,Internal medicine ,medicine ,Hydroxyprogesterones ,Humans ,Androstenedione ,Molecular Biology ,Aldehyde-Lyases ,Granulosa Cells ,biology ,Estradiol ,17-alpha-Hydroxyprogesterone ,Steroid 17-alpha-Hydroxylase ,Cell Biology ,medicine.anatomical_structure ,Ketoconazole ,chemistry ,Theca ,biology.protein ,Molecular Medicine ,Female ,medicine.drug - Abstract
Ketoconazole, an imidazole antimycotic drug, inhibits steroid biosynthesis in adrenal and testicular tissue by blocking cytochrome P-450 dependent enzymes. To study the effect of ketoconazole on steroid biosynthesis in the human ovary we incubated human ovarian tissue (mainly theca cells) or granulosa cells with radiolabeled precursors and increasing concentrations of ketoconazole. After incubation, steroids were extracted and separated by thin layer chromatography (TLC). Activity of C17,20-desmolase and aromatase was estimated by measuring the amount of their radioactive products with liquid scintillation counting. After incubation of ovarian tissue with [3H]17-hydroxyprogesterone the production of [3H]androstenedione was reduced by increasing concentrations of ketoconazole (0-200 microM) to a minimum of 31% of basal production. This indicates a strong inhibition of ovarian C17,20-desmolase by ketoconazole with a 50% inhibiting concentration (IC50) of 23 microM. After incubation of human granulosa cells with ketoconazole (0-2000 microM) and [3H]androstenedione the production of [3H]estrone and [3H]estradiol was suppressed to minimally 37 and 35% of basal values, indicating a significant inhibition of ovarian aromatase. IC50-values were 105 microM ketoconazole for estradiol and 130 microM for estrone. In conclusion, ketoconazole was shown to inhibit human ovarian C17,20-desmolase and aromatase in vitro. As in human adrenals and testes ovarian C17,20-desmolase seems to be most sensitive to the inhibitory effect of ketoconazole.
- Published
- 1991
44. The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells.
- Author
-
Christoph J Auernhammer, Franziska Dorn, George Vlotides, Sabine Hengge, Florian B Kopp, Gerald Spoettl, Neziha Cengic, Dieter Engelhardt, and Matthias M Weber
- Published
- 2004
45. Sézary-Syndrom
- Author
-
Dieter Engelhardt, Hendrik Dobbelstein, and Dieter Huhn
- Subjects
Gynecology ,medicine.medical_specialty ,Sézary's syndrome ,business.industry ,Medicine ,Hematology ,General Medicine ,business - Abstract
Klinische, zytologische, zytogenetische und histologische Befunde von 3 Patienten mit Sezary-Syndrom werden beschrieben und mit den Berichten aus der Literatur verglichen. Die Sezary-Zelle last sich durch ihre charakteristische elektronenmikroskopische Struktur von anderen normalen oder malignen Blut-und Knochenmarkzellen unterscheiden, weist aber grose Ahnlichkeit auf mit der Mycosis-fungoides-Zelle. Die Zugehorigkeit der Sezary-Zelle zur lymphozytaren Zellreihe ist auf Grund zytochemischer Befunde und der Stimulierbarkeit durch PHA wahrscheinlich. Die nosologische Stellung des Sezary-Syndroms wird diskutiert.
- Published
- 1972
46. Endokrin-aktive maligne Tumoren
- Author
-
Dieter Engelhardt and Klaus Mann
- Published
- 1987
47. Natur- und Landschaftsschutz
- Author
-
Dieter Engelhardt
- Abstract
Der Bereich des Natur- und Landschaftsschutzes steht in enger Beziehung zu anderen in diesem Werk gesondert behandelten Aufgabenbereichen, insbesondere zu den Fragen der kommunalen Planung, zum Umweltschutz, zur Landschaftspflege und zur Erholungsvorsorge (Freizeiteinrichtungen). Um eine zweckmasige Abgrenzung zu finden sollen im folgenden schwerpunktmasig die kommunalen Aufgaben dargestellt werden, die sich auf das Bundesnaturschutzgesetz und die Naturschutzgesetze der Lander stautzen.1
- Published
- 1983
48. Longterm treatment of Cushing's disease by ketoconazole
- Author
-
H. G. Dörr, Dieter Engelhardt, M. Ritter, and K. Jacob
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,medicine ,Ketoconazole ,General Medicine ,Cushing's disease ,medicine.disease ,business ,medicine.drug - Published
- 1987
49. Inhibition of adrenal androgen biosynthesis by ketoconazole in vivo and in vitro
- Author
-
Peter B. Luppa, F. Abedinpour, Matthias M. Weber, and Dieter Engelhardt
- Subjects
Androgen biosynthesis ,medicine.medical_specialty ,Endocrinology ,In vivo ,Chemistry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,medicine ,Ketoconazole ,General Medicine ,In vitro ,medicine.drug - Published
- 1989
50. Bergrecht : Kommentar zu den Landesberggesetzen und den sonstigen für den Bergbau einschlägigen bundes- und landesrechtlichen Vorschriften
- Author
-
Hermann Miesbach, Dieter Engelhardt, Hermann Miesbach, and Dieter Engelhardt
- Published
- 1962
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.