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1. New roles for nuclear EGFR in regulating the stability and translation of mRNAs associated with VEGF signaling.

Author

Klaus Dittmann, Claus Mayer, Stefan Czemmel, Stephan M Huber, and H Peter Rodemann

Subjects
Medicine, Science
Abstract

Cell membrane-associated epidermal growth factor receptor (EGFR) translocates into a perinuclear/nuclear location upon stimulation, where it complexes with mRNAs. Treatment with radiation and cisplatin decreases the amounts of mRNAs present within this complex. Gene array analyses of mRNAs in complex with immunoprecipitated nEGFR revealed significant enrichment of different mRNA species compared to the control immunoprecipitation. Functional annotation with help of DAVID Gene Ontology Analysis identified under other terms the HIF-1A/VEGF signaling pathway as one of the top scoring KEGG pathways. RT-PCR and western blots revealed the radiation-induced expression of mRNAs and proteins involved in HIF-1A/VEGF signaling. Simultaneously, the levels of the corresponding validated miRNAs within the complex containing nEGFR and mRNAs were decreased. This finding argues that an mRNA/miRNA/nEGFR complex regulates protein expression. Indeed, we detected the GW182, AGO2, PABPC1 and cNOT1 proteins, which belong to the deadenylase complex, in a complex with nuclear EGFR. Erlotinib-mediated inhibition of EGFR kinase reduced the radiation-induced increase in mRNA expression. In this context, erlotinib reduced AGO2 phosphorylation by the EGFR kinase at residue Y393, which was associated with increased cNOT1 deadenylase activity and reduced mRNA stability. To prove the roles of miRNAs in this context, we transfected cells with an inhibitor of Hsa-mir-1180p5, which targets the NFATC4 mRNA, an mRNA associated with VEGF signaling, or pretreated cells with erlotinib. Indeed, Hsa-mir-1180p5 knockdown increased and the erlotinib treatment decreased the expression of the NFATC4 protein. The expression of the NFATC4 protein controlled the cloning efficiency and radiosensitivity of A549 and FaDu tumor cells. Thus, this study is the first to show that a membrane-located tyrosine kinase receptor, such as EGFR, is internalized to a nuclear/perinuclear location upon exposure to stress and modulates the stability and translation of miRNA-selected mRNAs. This mechanism enables cells to directly express proteins in response to EGFR activation and may contribute to treatment resistance in EGFR-overexpressing tumors.

Published
2017
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2. Low-dose total body irradiation facilitates antitumoral Th1 immune responses

Author

Manfred Kneilling, Dominik Sonanini, Philipp Knopf, Barbara F. Schörg, Christoph M. Griessinger, Klaus Dittmann, Martin Röcken, and Bernd J. Pichler

Subjects
medicine.drug_class, T cell, medicine.medical_treatment, Medicine (miscellaneous), Monoclonal antibody, cancer immunology, Immunotherapy, Adoptive, B7-H1 Antigen, Cell therapy, T helper cells, combined immunotherapy, Mice, Immune system, Antigens, CD, Antigens, Neoplasm, Total body irradiation, Positron Emission Tomography Computed Tomography, medicine, Animals, Tissue Distribution, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Cancer immunology, Mice, Inbred C3H, RIP1-Tag2, business.industry, Optical Imaging, Immunity, Antibodies, Monoclonal, Immunotherapy, Th1 Cells, Lymphocyte Activation Gene 3 Protein, Immune checkpoint, Pancreatic Neoplasms, medicine.anatomical_structure, Cancer research, Female, business, Whole-Body Irradiation, Research Paper
Abstract

CD4+ T helper cells are capable of mediating long-term antitumoral immune responses. We developed a combined immunotherapy (COMBO) using tumor antigen-specific T helper 1 cells (Tag-Th1), dual PD-L1/LAG-3 immune checkpoint blockade, and a low-dose total body irradiation (TBI) of 2 Gy, that was highly efficient in controlling the tumor burden of non-immunogenic RIP1-Tag2 mice with late-stage endogenous pancreatic islet carcinomas. In this study, we aimed to explore the impact of 2 Gy TBI on the treatment efficacy and the underlying mechanisms to boost CD4+ T cell-based immunotherapies. Methods: Heavily progressed RIP1-Tag2 mice underwent COMBO treatment and their survival was compared to a cohort without 2 Gy TBI. Positron emission tomography/computed tomography (PET/CT) with radiolabeled anti-CD3 monoclonal antibodies and flow cytometry were applied to investigate 2 Gy TBI-induced alterations in the biodistribution of endogenous T cells of healthy C3H mice. Migration and homing properties of Cy5-labeled adoptive Tag-Th1 cells were monitored by optical imaging and flow cytometric analyses in C3H and tumor-bearing RIP1-Tag2 mice. Splenectomy or sham-surgery of late-stage RIP1-Tag2 mice was performed before onset of COMBO treatment to elucidate the impact of the spleen on the therapy response. Results: First, we determined a significant longer survival of RIP1-Tag2 mice and an increased CD4+ T cell tumor infiltrate when 2 Gy TBI was applied in addition to Tag-Th1 cell PD-L1/LAG-3 treatment. In non-tumor-bearing C3H mice, TBI induced a moderate host lymphodepletion and a tumor antigen-independent accumulation of Tag-Th1 cells in lymphoid and non-lymphoid organs. In RIP1-Tag2, we found increased numbers of effector memory-like Tag-Th1 and endogenous CD4+ T cells in the pancreatic tumor tissue after TBI, accompanied by a tumor-specific Th1-driven immune response. Furthermore, the spleen negatively regulated T cell effector function by upregulation PD-1/LAG-3/TIM-3 immune checkpoints, providing a further rationale for this combined treatment approach. Conclusion: Low-dose TBI represents a powerful tool to foster CD4+ T cell-based cancer immunotherapies by favoring Th1-driven antitumoral immunity. As TBI is a clinically approved and well-established technique it might be an ideal addition for adoptive cell therapy with CD4+ T cells in the clinical setting.

Published
2021

3. 027 2Gy low-dose total body irradiation facilitates antitumoral Th1 immune responses in tumor antigen specific Th1 cell and immune checkpoint inhibitor-based cancer immunotherapy

Author

Christoph M. Griessinger, Bernd J. Pichler, S.F. Barbara, Klaus Dittmann, Manfred Kneilling, Dominik Sonanini, Martin Röcken, and P. Knopf

Subjects
business.industry, medicine.medical_treatment, Immune checkpoint inhibitors, Low dose, Cell, Cell Biology, Dermatology, Total body irradiation, Biochemistry, Tumor antigen, medicine.anatomical_structure, Immune system, Cancer immunotherapy, Cancer research, medicine, business, Molecular Biology
Published
2021

4. The radioprotector ortho-phospho- L -tyrosine (pTyr) attenuates the side effects of fractionated irradiation in retinoblastoma mouse models but also decreases the local tumour control

Author

Stephan M. Huber, Alexander Tschulakow, Sylvie Julien-Schraermeyer, H. Peter Rodemann, Dominik Klumpp, Klaus Dittmann, Ulrich Schraermeyer, and Benjamin Stegen

Subjects
0301 basic medicine, Retinal degeneration, Pathology, medicine.medical_specialty, Cell Survival, Retinal Neoplasms, Cell, Radiation-Protective Agents, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, medicine, Animals, Radiology, Nuclear Medicine and imaging, Tyrosine, Phosphotyrosine, Retinoblastoma, business.industry, Retinal, Hematology, medicine.disease, In vitro, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Oncology, chemistry, 030220 oncology & carcinogenesis, Toxicity, Cancer research, Dose Fractionation, Radiation, Tumor Suppressor Protein p53, business
Abstract

Background Radiotherapy (RT) is used to treat retinoblastoma (Rb), the most frequent ocular tumour in children. Besides eradicating the tumour, RT can cause severe side effects including secondary malignancies. This study aimed to define whether the radioprotector ortho-phospho- L -tyrosine (pTyr) prevents RT-induced side effects and affects local tumour control in a xeno graft and a genetic orthotopic Rb mouse model. Methods B6;129-Rb1tm3Tyj/J (Rb +/− ) and Y79-Rb cell- xeno grafted nude mice were fractionated external beam irradiated (15 fractions of 5 Gy 6 MV photons during 3 weeks) with or without pTyr pre-treatment (100 mg/kg BW, 16 h prior to each irradiation). One, three, six and nine months after RT, tumour control and RT toxicity were evaluated using in vivo imaging and histology. We also analysed pTyr dependant post irradiation cell survival and p53 activity in vitro . Results In vitro pTyr pre-treatment showed no radioprotection on Y79 cells, but led to p53 stabilisation in unirradiated Y79 cells and to a facilitation of radiation-induced p21 up-regulation, confirming a modulation of p53 activity by pTyr. In both mouse models, secondary tumours were undetectable. In Rb +/− mice, pTyr significantly lowered RT-induced greying of the fur, retinal thickness reduction and photoreceptor loss. However, in the xeno grafted Rb model, pTyr considerably decreased RT-mediated tumour control, which was observed in 16 out of 22 control eyes but in none of the 24 pTyr treated eyes. Conclusions In Rb +/− mice pTyr significantly prevents RT-induced greying of the fur as well as retinal degeneration. However, since non-irradiated control mice were not used in our study, a formal possibility exists that the effect shown in the retina of Rb +/− mice may be due to ageing of the animals and/or actions of pTyr alone. Unfortunately, as tested in a xeno graft model, pTyr treatment reduced the control of Rb tumours.

Published
2017

5. Reduced exosomal L-Plastin is responsible for radiation-induced bystander effect

Author

Lena Katharina Freudenmann, Claus Mayer, Klaus Dittmann, and H. Peter Rodemann

Subjects
0301 basic medicine, Male, Lung Neoplasms, Cell Survival, Biology, Exosomes, 03 medical and health sciences, 0302 clinical medicine, Radiation, Ionizing, Bystander effect, Humans, Secretion, Clonogenic assay, Exosomal secretion, Cells, Cultured, Cell Proliferation, Tumor microenvironment, Cell growth, Microfilament Proteins, Prostatic Neoplasms, Cell Biology, Bystander Effect, Fibroblasts, Microvesicles, 030104 developmental biology, 030220 oncology & carcinogenesis, Culture Media, Conditioned, Cancer cell, Cancer research
Abstract

Radiation-induced bystander effects (RIBE) are discussed as relevant processes during radiotherapy. Irradiated cells are suggested to release growth-inhibitory/DNA-damaging factors transported to non-irradiated cells. However, the molecular nature of this phenomenon has not yet been resolved. We aimed at identifying the growth-inhibitory factor(s) transmitted to non-irradiated cells. RIBE-competent PC3 cells were used to produce conditioned medium (CM) after exposure to ionizing radiation. Indicator cells were incubated with CM and clonogenic survival as well as cell proliferation were determined as endpoints. A549 indicator cells exhibited a bystander effect upon incubation with CM from irradiated PC3 cells. This bystander effect was not due to DNA-damaging factors, but a radiation-triggered reduction of mitogenic/clonogenic activity present in CM. Several tumor cells, but not normal fibroblasts secrete this factor, whose release is reduced by irradiation. We identified L-Plastin to be responsible for the mitogenic/clonogenic activity. Removal of L-Plastin from CM by immunoprecipitation or siRNA-mediated knockdown of L-Plastin expression resulted in loss or reduction of mitogenic/clonogenic activity transmitted via CM, respectively. Exosome-transported L-Plastin was constitutively Ser5-phosphorylated, indicative of its bioactive conformation. In summary, we observed production and exosomal secretion of L-Plastin by cancer cells. Via exosome-transmitted L-Plastin, tumors induce clonogenic and mitogenic activity in cancer and normal cells of the tumor microenvironment. Irradiation inhibits L-Plastin production targeting both cancer cells and the tumor niche and may explain the high impact of radiotherapy in tumor control.

Published
2019

6. The nuclear aryl hydocarbon receptor is involved in regulation of DNA repair and cell survival following treatment with ionizing radiation

Author

Klaus Dittmann, Thomas Haarmann-Stemmann, A. Paasch, Martin Schaller, Ellen Fritsche, K. Frauenstein, Claus Mayer, Albert Braeuning, M.C. Rothmund, Birgit Fehrenbacher, and H. P. Rodemann

Subjects
Transcriptional Activation, 0301 basic medicine, Aryl hydrocarbon receptor nuclear translocator, DNA Repair, Cell Survival, DNA repair, Receptors, Cytoplasmic and Nuclear, CHO Cells, DNA-Activated Protein Kinase, Toxicology, Histones, 03 medical and health sciences, Cricetulus, Cell Line, Tumor, Animals, Humans, Transcription factor, Microscopy, Confocal, biology, Acetylation, Hep G2 Cells, General Medicine, respiratory system, Lamin Type A, Aryl hydrocarbon receptor, Molecular biology, respiratory tract diseases, Chromatin, Cell biology, 030104 developmental biology, Histone, Gene Expression Regulation, Receptors, Aryl Hydrocarbon, Gamma Rays, biology.protein, Lipid Peroxidation, Protein stabilization, Lamin
Abstract

In the present study, we explored the role of the aryl hydrocarbon receptor (AhR) for γ-H2AX associated DNA repair in response to treatment with ionizing radiation. Ionizing radiation was able to stabilize AhR protein and to induce a nuclear translocation in a similar way as described for exposure to aromatic hydrocarbons. A comparable AhR protein stabilization was obtained by treatment with hydroxyl-nonenal-generated by radiation-induced lipid peroxidation. AhR knockdown resulted in significant radio-sensitization of both A549- and HaCaT cells. Under these conditions an increased amount of residual γ-H2AX foci and a delayed decline of γ-H2AX foci was observed. Knockdown of the co-activator ARNT, which is essential for transcriptional activation of AhR target genes, reduced AhR-dependent CYP1A expression in response to irradiation, but was without effect on the amount of residual γ-H2AX foci. Nuclear AhR was found in complex with γ-H2AX, DNA-PK, ATM and Lamin A. AhR and γ-H2AX form together nuclear foci, which disappear during DNA repair. Presence of nuclear AhR protein is associated with ATM activation and chromatin relaxation indicated by acetylation of histone H3. Taken together, we could show, that beyond the function as a transcription factor the nuclear AhR is involved in the regulation of DNA repair. Reduction of nuclear AhR inhibits DNA-double stand repair and radiosensitizes cells. First hints for its molecular mechanism suggest a role during ATM activation and chromatin relaxation, both essential for DNA repair.

Published
2016

7. EGFR-mediated stimulation of sodium/glucose cotransport promotes survival of irradiated human A549 lung adenocarcinoma cells

Author

Klaus Dittmann, Stephan M. Huber, H. P. Rodemann, Milan Misovic, and Claus Mayer

Subjects
medicine.medical_specialty, Lung Neoplasms, Patch-Clamp Techniques, Cell Survival, Phlorizin, Glucose uptake, Adenocarcinoma of Lung, Adenocarcinoma, Radiation Dosage, Sodium-Glucose Transport Proteins, Membrane Potentials, Erlotinib Hydrochloride, chemistry.chemical_compound, Cell Line, Tumor, Internal medicine, Tumor Cells, Cultured, medicine, Extracellular, Humans, Radiology, Nuclear Medicine and imaging, Patch clamp, A549 cell, Hematology, Protein-Tyrosine Kinases, ErbB Receptors, Glucose, Phlorhizin, Endocrinology, Oncology, chemistry, Head and Neck Neoplasms, Cell culture, Carcinoma, Squamous Cell, Quinazolines, Cancer research, Erlotinib, medicine.drug
Abstract

Background and purpose Solid tumor cells may adapt to an ischemic microenvironment by upregulation of sodium/glucose cotransport (SGLT) in the plasma membrane which supplies the tumor cell with glucose even at very low extracellular glucose concentration. Since SGLT activity has been shown to depend on the epithelial growth factor receptor (EGFR) and EGFR reportedly is activated by ionizing radiation, we tested for irradiation-induced SGLT activity. Materials and methods A549 lung adenocarcinoma and FaDu head and neck squamous cancer cells were irradiated with 0 and 4 Gy X-ray and electrogenic SGLT transport activity was recorded by patch clamp current clamp in the presence and absence of extracellular glucose (5 mM), the SGLT inhibitor phlorizin (500 μM), and the inhibitor of the EGFR tyrosine kinase activity erlotinib (1 μM). In addition, the effect of phlorizin and erlotinib on glucose uptake and clonogenic survival was tested in irradiated and control cells by tracer flux and colony formation assays, respectively. Results Irradiated A549 cells exhibited a significantly lower membrane potential 3 h after irradiation than the control cells. Phlorizin, erlotinib or removal of extracellular glucose, hyperpolarized the irradiated A549 cells to a significantly higher extent than the control cells. Similarly, but less pronounced, glucose removal hyperpolarized irradiated FaDu cells. In addition, irradiated A549 cells exhibited a highly increased 3H-glucose uptake which was sensitive to phlorizin. Finally, phlorizin radiosensitized the A549 and FaDu cells as evident from the colony formation assays. Conclusions Taken together, these data suggest an irradiation-stimulated and EGFR-mediated increase in SGLT-generated glucose uptake which is required for the survival of the genotoxically stressed tumor cells.

Published
2012

8. Ionizing radiation induces migration of glioblastoma cells by activating BK K+ channels

Author

Daniela Palme, Marc Steinle, Klaus Dittmann, Stephan M. Huber, Peter Ruth, Justine Rudner, Milan Misovic, and Robert Lukowski

Subjects
Benzylamines, BK channel, Patch-Clamp Techniques, Potassium Channels, Calcium-Activated, chemistry.chemical_compound, Cell Movement, Radiation, Ionizing, Ca2+/calmodulin-dependent protein kinase, Tumor Cells, Cultured, Humans, Radiology, Nuclear Medicine and imaging, Large-Conductance Calcium-Activated Potassium Channels, Patch clamp, Paxilline, Sulfonamides, Migration Assay, biology, Brain Neoplasms, Chemistry, Cell migration, Hematology, Potassium channel, Cell biology, Oncology, Immunology, biology.protein, Signal transduction, Glioblastoma, Signal Transduction
Abstract

Background and purpose Glioblastoma cells express high levels of Ca 2+ -activated BK K + channels which have been proposed to be indispensable for glioblastoma proliferation and migration. Since migration of glioblastoma cells is reportedly stimulated by ionizing radiation (IR), we tested for an IR-induced increase in BK channel activity and its effect on cell migration. Materials and Methods T98G and U87MG cells were X-ray-irradiated with 0–2Gy, BK channel activity was assessed by patch-clamp recording, migration by trans-well migration assay, and activation of the Ca 2+ /calmodulin-dependent kinase II (CaMKII) by immunoblotting. Results IR dose-dependently stimulated migration of glioblastoma cells which was sensitive to the BK channel inhibitor paxilline. Ca 2+ -permeabilization of T98G cells activated up to 350 BK channels per cells. Importantly, IR stimulated an increase in BK channel open probability but did not modify the total number of channels. Moreover, IR activated CaMKII in a paxilline-sensitive manner. Finally, inhibition of CaMKII by KN-93 abolished the IR-stimulated migration. Conclusions We conclude that IR stimulates BK channel activity which results in activation of CaMKII leading to enhanced glioblastoma cell migration.

Published
2011

9. Radiation-Induced Survivin Nuclear Accumulation is Linked to DNA Damage Repair

Author

Eva Hausmann, Christian Weiss, Franz Rödel, Claus Rödel, Sebastian Reichert, Gianni Capalbo, and Klaus Dittmann

Subjects
Cytoplasm, Cancer Research, DNA Repair, DNA repair, DNA damage, Survivin, Cell Cycle Proteins, DNA-Activated Protein Kinase, Inhibitor of Apoptosis Proteins, Histones, Tumor Cells, Cultured, Humans, Medicine, DNA Breaks, Double-Stranded, Radiology, Nuclear Medicine and imaging, Phosphorylation, RNA, Small Interfering, Nuclear protein, DNA-PKcs, Adaptor Proteins, Signal Transducing, Cell Nucleus, Ku70, Radiation, business.industry, Nuclear Proteins, Double Strand Break Repair, MDC1, enzymes and coenzymes (carbohydrates), Oncology, Trans-Activators, Cancer research, business, Microtubule-Associated Proteins, DNA Damage
Abstract

Purpose Increased expression of survivin has been identified as a negative prognostic marker in a variety of human cancers. We have previously shown that survivin is a radiation-resistance factor and that the therapeutic effect of survivin knock-down might result from an impaired DNA repair capacity. In this study, we aimed to elucidate an interrelationship between survivin's cellular localization and DNA double-strand break repair. Methods and Materials Survivin's cellular distribution and nuclear complex formation were assayed by Western blotting of subcellular fractions, by immunofluorescence staining, and co-immunoprecipitation in SW480 colorectal cancer cells. DNA repair capacity was analyzed by kinetics of γ-H2AX foci formation, and by DNA-dependent protein kinase (DNA-PKcs) assays in the presence of survivin-specific or nonspecific control siRNA. Results Following irradiation, we observed a rapid nuclear accumulation of survivin and subsequent phosphorylation of the protein in the nucleus. Co-immunoprecipitation analyses from nuclear extracts revealed an interaction among survivin, Ku70, γ-H2AX, MDC1, and DNA-PKcs that was confirmed by immunofluorescence co-localization in nuclear foci. Survivin knock down by siRNA resulted in an impaired DNA double strand break repair, as demonstrated by an increased detection of γ-H2AX foci/nucleus at 60 min and a higher amount of residual γ-H2AX foci at 24 hr postirradiation. Furthermore, we detected in survivin-depleted cells a hampered S2056 autophosphorylation of DNA-PKcs and a significantly decreased DNA-PKcs kinase activity. Conclusion These data indicate that nuclear survivin is linked to DNA double-strand break repair by interaction with members of the DNA double-strand breaks repair machinery, thus regulating DNA-PKcs activity.

Published
2010

10. Nuclear EGFR as Novel Therapeutic Target

Author

Claus Mayer, Klaus Dittmann, and H. Peter Rodemann

Subjects
biology, business.industry, Cell cycle, Cell nucleus, medicine.anatomical_structure, Oncology, medicine, biology.protein, Cancer research, Radiology, Nuclear Medicine and imaging, ERBB3, Epidermal growth factor receptor, Kinase activity, Signal transduction, business, Tyrosine kinase, Platelet-derived growth factor receptor
Abstract

Emerging evidence suggests the existence of a new mode of epidermal growth factor receptor (EGFR) signaling in which activated EGFR undergoes nuclear translocation following treatment with ionizing radiation. The authors provide evidence that the nuclear EGFR transport is a stress-specific cellular reaction, which is linked to src-dependent EGFR internalization into caveolae. These flask-shaped pits can fuse with endoplasmic reticulum and the EGFR is sorted into a perinuclear localization. This compartment may serve as a reservoir for nuclear EGFR transport which is regulated by PKCepsilon (protein kinase Cepsilon). Nuclear EGFR is able to induce transcription of genes essential for cell proliferation and cell-cycle regulation. Moreover, nuclear EGFR has physical contact with compounds of the DNA repair machinery and is involved in removal of DNA damage. Anti-EGFR strategies target radiation-associated EGFR nuclear translocation in different manners. EGFR-inhibitory antibodies, i.e., cetuximab (Erbitux((R))), can block nuclear translocation by EGFR immobilization within the cytosol in responder cell lines, whereas tyrosine kinase inhibitors rather target nuclear kinase activity of EGFR linked with cytosolic or nuclear functions. However, both strategies can inhibit DNA repair following irradiation.

Published
2009

11. Activation of protein kinase Cε stimulates DNA-repair via epidermal growth factor receptor nuclear accumulation

Author

H. Peter Rodemann, Rainer Kehlbach, Claus Mayer, Gabriele Wanner, and Klaus Dittmann

Subjects
DNA Repair, Blotting, Western, Protein Kinase C-epsilon, Radiation-Protective Agents, Cell Line, Tumor, medicine, Humans, DNA Breaks, Double-Stranded, Radiology, Nuclear Medicine and imaging, ERBB3, Epidermal growth factor receptor, Phosphotyrosine, Protein kinase A, Protein kinase C, Cell Nucleus, Gene knockdown, Microscopy, Confocal, biology, Chemistry, Hematology, Cell biology, ErbB Receptors, Cell nucleus, medicine.anatomical_structure, Oncology, biology.protein, Phosphorylation
Abstract

Purpose To elucidate the interaction between radioprotector O -phospho-l-tyrosine (P-Tyr) with epidermal growth factor receptor (EGFR). Methods Molecular effects of P-Tyr at the level of EGFR responses were investigated in vitro with TP53-wildtype bronchial carcinoma cell line A549, which is radio-protected by P-Tyr treatment. Nuclear EGFR accumulation was followed by confocal microscopy and Western blotting. PKC e protein expression was impaired by specific siRNA. Residual DNA-damage was quantified with γH 2 AX foci analysis. Results P-Tyr mediated radio-protection was associated with nuclear EGFR accumulation. Radiation-induced nuclear EGFR presented increased phosphorylation at residue No. T654. We identified PKC e as responsible for T654-phosphorylation. Knockdown of PKC e by siRNA blocked both radiation- and P-Tyr-triggered nuclear EGFR accumulation. Furthermore, nuclear accumulation of EGFR was associated with increased phosphorylation of DNA-dependent protein kinase (DNA-PK) at residue No. T2609, essential for DNA-repair. Consequently P-Tyr mediated effects upon DNA-PK resulted in a significant reduction of radiation-induced residual γH 2 AX-foci. Knockdown of PKC e increased radiation-induced residual damage and abolished the P-Tyr associated radioprotection. In addition, P-Tyr mediated radioprotection was completely absent in colony formation assay. Conclusion The data presented herein suggest that P-Tyr-treatment mediates activation of PKC e , which triggers nuclear EGFR accumulation. Nuclear EGFR is involved in phosphorylation of DNA-PK at Thr2609, which has a significant impact upon DNA–DSB repair.

Published
2008

12. Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism

Author

Petra Ohneseit, Nickolaus H. Andratschke, Uma Raju, Claus Mayer, H. Peter Rodemann, Luka Milas, and Klaus Dittmann

Subjects
Radiation-Sensitizing Agents, Cancer Research, Pathology, medicine.medical_specialty, DNA Repair, Cell Survival, DNA damage, DNA repair, Blotting, Western, Active Transport, Cell Nucleus, DNA-Activated Protein Kinase, Radiation Tolerance, Dinoprostone, Cell Line, Tumor, Radioresistance, medicine, Humans, Radiology, Nuclear Medicine and imaging, Epidermal growth factor receptor, Radiosensitivity, neoplasms, Cell Nucleus, Sulfonamides, Radiation, biology, business.industry, Fibroblasts, HCT116 Cells, ErbB Receptors, Oncology, Celecoxib, Cyclooxygenase 2, Cell culture, Cancer research, biology.protein, Pyrazoles, Cyclooxygenase, business, medicine.drug
Abstract

Purpose The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib. Methods and Materials Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by γH 2 AX foci assay. Results Celecoxib treatment resulted in a pronounced radiosensitization of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not radiosensitized. The observed radiosensitization could neither be correlated with basal COX-2 expression pattern nor with basal production of prostaglandin E2, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-2–deficient HCT116 cells, which were radiosensitized, but not in FaDu and HH4dd cells, which resisted celecoxib-induced radiosensitization. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual γH2AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions Celecoxib enhanced radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-2 activity. This novel observation may have therapeutic implications such that COX-2 inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-2.

Published
2008

13. The radioprotector O-phospho-tyrosine stimulates DNA-repair via epidermal growth factor receptor- and DNA-dependent kinase phosphorylation

Author

Rainer Kehlbach, H. Peter Rodemann, Claus Mayer, Klaus Dittmann, and Gabriele Wanner

Subjects
Lung Neoplasms, DNA Repair, DNA repair, Blotting, Western, Cetuximab, Radiation-Protective Agents, DNA-Activated Protein Kinase, Antibodies, Monoclonal, Humanized, chemistry.chemical_compound, Cell Line, Tumor, Humans, Radiology, Nuclear Medicine and imaging, Epidermal growth factor receptor, Phosphorylation, Tyrosine, Phosphotyrosine, biology, Kinase, Chemistry, Antibodies, Monoclonal, Hematology, ErbB Receptors, Blot, Carcinoma, Bronchogenic, Oncology, Cell culture, Cancer research, biology.protein, DNA
Abstract

Background and purpose Purpose of the study was to elucidate the underlying molecular mechanism of the radioprotector O -phospho-tyrosine (P-Tyr). Methods Molecular effects of P-Tyr at the level of EGFR responses were investigated in vitro with bronchial carcinoma cell line A549. Nuclear EGFR transport and DNA-PK activation were quantified after Western blotting. Residual DNA-damages were quantified by help of γH 2 AX focus assay. Results As determined by dose–response curves, treatment of cells with P-Tyr for 16h before irradiation results in radioprotection. Simultaneous treatment with EGFR blocking antibody Cetuximab abolished P-Tyr associated radioprotection. At the molecular level P-Tyr mediated a general phosphorylation of EGFR and a pronounced phosphorylation of nuclear EGFR at residue Thr No. 654, also observed after treatment with ionizing radiation. This phosphorylation was associated with nuclear EGFR accumulation. Moreover, P-Tyr-triggered EGFR nuclear accumulation was associated with phosphorylation of DNA-PK at Thr 2609. This activated form of DNA-PK was not DNA associated, but after radiation, DNA binding increased, particularly after P-Tyr pre-treatment. These molecular effects of P-Tyr resulted in a reduction of residual DNA-damage after irradiation. Conclusions Radioprotection by P-Tyr is mediated through its stimulation of nuclear EGFR transport and concurrent, but DNA-damage independent, activation of DNA-PK. Thus, subsequent irradiation results in increased binding of DNA-PK to DNA, improved DNA-repair and increased cell survival.

Published
2007

14. EGFR-targeted anti-cancer drugs in radiotherapy: Preclinical evaluation of mechanisms

Author

Wolfgang Dörr, Ulla Kasten-Pisula, Mechthild Krause, H. Peter Rodemann, Klaus Dittmann, Michael Baumann, and Ekkehard Dikomey

Subjects
Chemotherapy, Pathology, medicine.medical_specialty, DNA repair, business.industry, medicine.medical_treatment, Drug Evaluation, Preclinical, Antineoplastic Agents, Hematology, ErbB Receptors, Radiation therapy, Oncology, Cancer stem cell, In vivo, Neoplasms, Radioresistance, Antineoplastic Combined Chemotherapy Protocols, Cancer research, medicine, Humans, Radiology, Nuclear Medicine and imaging, Animal studies, business, Signal Transduction, EGFR inhibitors
Abstract

Preclinical and clinical results indicate that the EGFR can mediate radioresistance in different solid human tumours. Combination of radiotherapy and EGFR inhibitors can improve local tumour control compared to irradiation alone and has been introduced into clinical radiotherapy practice. So far several mechanisms have been identified in preclinical studies to contribute to improved local tumour control after radiation combined with EGFR inhibitors. These include direct kill of cancer stem cells by EGFR inhibitors, cellular radiosensitization through modified signal transduction, inhibition of repair of DNA damage, reduced repopulation and improved reoxygenation during fractionated radiotherapy. Effects and mechanisms may differ for different classes of EGFR inhibitors, for different tumours and for normal tissues. The mechanisms underlying this heterogeneity are currently poorly understood, and predictive assays are not available yet. Importantly, mechanisms and predictors for the combined effects of radiation with EGFR inhibitors appear to be considerably different to those for application of EGFR inhibitors alone or in combination with chemotherapy. Therefore to further evaluate the efficacy and mechanisms of EGFR-inhibition in combined treatments, radiotherapy-specific preclinical research strategies, which include in vivo experiments using local tumour control as an endpoint, as well as animal studies on normal tissue toxicity are needed.

Published
2007

15. Inhibition of cyclooxygenase-2 activity by celecoxib does not lead to radiosensitization of human prostate cancer cells in vitro

Author

Klaus Dittmann, Guido Krebiehl, Rainer Kehlbach, Petra Ohneseit, and Hans Peter Rodemann

Subjects
Male, Oncology, medicine.medical_specialty, Apoptosis, Radiation Tolerance, Dinoprostone, Prostate cancer, DU145, Prostate, Cell Line, Tumor, Internal medicine, LNCaP, medicine, Humans, Radiology, Nuclear Medicine and imaging, Sulfonamides, Cyclooxygenase 2 Inhibitors, biology, business.industry, Cell Cycle, Prostatic Neoplasms, Dose-Response Relationship, Radiation, Hematology, Cell cycle, medicine.disease, medicine.anatomical_structure, Celecoxib, Cyclooxygenase 2, Cancer cell, biology.protein, Cancer research, Pyrazoles, lipids (amino acids, peptides, and proteins), Cyclooxygenase, business, medicine.drug
Abstract

Purpose To evaluate the potential radiosensitizing effect of the specific COX-2 inhibitor celecoxib (Celebrex ® ) on prostate carcinoma cells in vitro . Materials and methods The influence of celecoxib (concentration range 5 to 75μM) on radiation-induced cellular and clonogenic survival was investigated in prostate carcinoma cell lines PC-3, DU145, LNCaP and normal prostate epithelial cells (PrEC). Western blot analysis and ELISA were used to determine the impact of radiation alone or radiation combined with celecoxib treatment on COX-2 expression and prostaglandin E2 synthesis. To evaluate induction of celecoxib-induced apoptosis cell cycle analysis has been performed. Results Celecoxib (5, 10 and 25μM) in combination with single-dose irradiation of 2Gy induced a significant radiosensitization in normal prostate epithelial cells which could not be observed for any of the prostate carcinoma cell lines investigated. Increased COX-2 protein expression in PC-3 cells was obvious only after IR with 15Gy, while PGE 2 production was elevated following irradiation (2–15Gy) in a dose-dependent manner. Treatment with celecoxib alone or in combination with IR led to a dose-dependent increase in COX-2 protein expression. Nevertheless pre-treatment with celecoxib caused a marked reduction of radiation-induced enzyme activity as tested at the level of PGE 2 production, both in PC-3 and DU145 cells. Following fractionated irradiation with single doses of 2Gy, elevated COX-2 protein expression as well as enhanced PGE 2 production was observed already after the second fraction in PC-3 cells. Pre-treatment with celecoxib reduced the amount of PGE 2 significantly, but not of COX-2 protein. Conclusions Our data obtained for the human prostate cancer cell lines do not indicate that a marked inhibition of prostaglandin E2 synthesis by celecoxib leads to enhanced radiosensitization. Thus, in terms of radiosensitization the analysed prostate cancer cells can be classified as non-responders to celecoxib treatment.

Published
2007

16. Nuclear EGFR renders cells radio-resistant by binding mRNA species and triggering a metabolic switch to increase lactate production

Author

H. Peter Rodemann, Stephan M. Huber, Martin Schaller, Angela Paasch, Claus Mayer, Klaus Dittmann, and Birgit Fehrenbacher

Subjects
Blotting, Western, Dasatinib, Gene Expression, Heterogeneous ribonucleoprotein particle, Radiation Tolerance, Erlotinib Hydrochloride, Cell Line, Tumor, Gene expression, medicine, Humans, Radiology, Nuclear Medicine and imaging, Lactic Acid, RNA, Messenger, Nuclear protein, Protein Kinase Inhibitors, Cell Nucleus, Oxadiazoles, Chemistry, Bronchial Neoplasms, Colocalization, Nuclear Proteins, Hematology, Hypoxia-Inducible Factor 1, alpha Subunit, Warburg effect, Cell biology, Blot, ErbB Receptors, Cell nucleus, medicine.anatomical_structure, Oncology, Head and Neck Neoplasms, Pyrazoles, Lamin
Abstract

Background and purpose EGFR is translocated into the cell nucleus in response to irradiation, where it is involved in regulation of radio-sensitivity. The aim of this study is to elucidate the functional role of nuclear EGFR. Material and methods To identify EGFR-bound nuclear proteins and mRNAs, Maldi-TOF analysis and mRNA gene arrays were used. Complex formation of proteins was shown by confocal microscopy, immunoprecipitation and Western blotting. The effect of EGFR binding to mRNAs was exhibited by quantitative RT-PCR. Cellular endpoints were shown by Western blotting, mitochondrial mass quantification, lactate quantification and clonogenic survival assays. Results Maldi-TOF analysis of proteins bound to nuclear EGFR in response to irradiation showed colocalization with Lamin A and heterogeneous nuclear ribonucleoproteins. Confocal microscopy and Western blotting confirmed this colocalization. Both Lamin A and heterogeneous nuclear ribonucleoproteins are involved in mRNA processing. To support a role of nEGFR in this context after irradiation, we isolated EGFR-bound mRNA and observed an EGFR kinase-dependent mRNA stabilizing effect. With the help of DNA microarrays, we identified mRNAs associated with the Warburg effect that were bound to nuclear EGFR. In this context, we observed radiation-induced HIF1α expression, which triggers inhibition of pyruvate dehydrogenase and blocks the tricarboxylic acid cycle. Consequently, we detected mitophagy and increased lactate production, which is associated with increased treatment resistance. Reduction of nEGFR decreased radiation-induced expression of Hif1α and lactate production. Conclusions We showed that nuclear EGFR selectively binds and stabilizes mRNA involved in the Warburg effect in response to irradiation. As a consequence, cells switch from aerobic to anaerobic glucose metabolism, which can be prevented by HIF1α inhibitor BAY87-2243, Dasatinib, Erlotinib or EGFR siRNA.

Published
2015

17. Inhibition of DNA repair as a mechanism of enhanced radioresponse of head and neck carcinoma cells by a selective cyclooxygenase-2 inhibitor, celecoxib

Author

Luka Milas, Hisanori Ariga, Eiko Nakata, Uma Raju, Klaus Dittmann, and Kian K. Ang

Subjects
Radiation-Sensitizing Agents, Cancer Research, DNA Repair, DNA repair, Blotting, Western, Down-Regulation, DNA-Activated Protein Kinase, Protein Serine-Threonine Kinases, chemistry.chemical_compound, Cell Line, Tumor, medicine, Humans, Cyclooxygenase Inhibitors, Radiology, Nuclear Medicine and imaging, Kinase activity, Protein kinase A, Sulfonamides, Ku70, Radiation, biology, Cell growth, business.industry, NF-kappa B, Nuclear Proteins, DNA, DNA-Binding Proteins, Oncology, chemistry, Celecoxib, Head and Neck Neoplasms, Cancer research, biology.protein, Pyrazoles, Cyclooxygenase, Growth inhibition, business, medicine.drug
Abstract

Purpose: Previously, we reported that inhibitors of cyclooxygenase-2 (COX-2) enzyme enhanced murine and human tumor cell response to radiation in vitro and in vivo . However, the molecular mechanisms mediating the effects of COX-2 inhibitors are not clear. The present study was designed to investigate the ability of celecoxib, a selective COX-2 inhibitor, to sensitize human head-and-neck cancer cell line, HN5, to radiation, and examine its effects on DNA repair, which may be a potential mechanism of radiosensitization. Methods and Materials: Cells were assessed for the effect of celecoxib (5–50 μM), by 3-[4,5-dimethylthiozol-2-yl]-2,5-diphenyltetrazolium bromide assay for growth inhibition and by clonogenic cell survival assay for the radiosensitizing effect. Kinase assay and Western analysis were conducted to assess the effect of celecoxib on DNA-dependent protein kinase catalytic subunit (PKcs) and Ku proteins. Electrophoretic mobility shift assays (EMSA) were performed to determine the DNA-binding activity of Ku/DNA-PKcs protein complex and nuclear factor kappa B (NFκB). Results: Celecoxib (10 and 50 μM, for 2 days) inhibited the HN5 cell growth and significantly enhanced the cell radiosensitivity in a dose-dependent manner. It also reduced the shoulder region on the radiation-survival curve, suggesting that inhibition of DNA repair processes may have occurred. Western blot analysis demonstrated that celecoxib downregulated the expression of Ku70 protein and inhibited the kinase activity of DNA-PKcs, which are involved in the double-stranded DNA-break repair machinery. By EMSA, it was further shown that celecoxib reduced DNA-binding activity of Ku/DNA-PKcs protein complex. In addition, celecoxib inhibited the constitutively active NFκB and the radiation-induced NFκB in HN5 cells, suggesting that NFκB may play a role in mediating the effects of celecoxib. Conclusions: Celecoxib strongly enhanced the sensitivity of HN5 carcinoma cells to radiation, which, mechanistically, can be attributed to the inhibition of DNA repair processes in radiation-damaged cells.

Published
2005

18. Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity

Author

H. P. Rodemann, Claus Mayer, and Klaus Dittmann

Subjects
Cytoplasm, DNA Repair, DNA repair, Cetuximab, Antineoplastic Agents, DNA-Activated Protein Kinase, Antibodies, Monoclonal, Humanized, Radiation Tolerance, chemistry.chemical_compound, Cell Line, Tumor, Tumor Cells, Cultured, medicine, Humans, Radiology, Nuclear Medicine and imaging, Protein kinase A, Cell Nucleus, Chemistry, Kinase, Antibodies, Monoclonal, Hematology, Enzyme Activation, ErbB Receptors, Blot, Oncology, Immunology, Cancer research, Nuclear transport, DNA, medicine.drug
Abstract

Background and purpose Inhibition of EGFR-function can induce radiosensitization in tumor cells. Purpose of our investigation was to identify the possible molecular mechanism of radiosensitization following treatment with anti-EGFR-antibody C225 (Cetuximab). Materials and methods The effect of C225 on radiation response was determined in human cell lines of bronchial carcinoma (A549) and breast adenoma cells (MDA MB 231). The molecular effects of C225 on EGFR-function after irradiation were analyzed applying western blotting, immune-precipitation and kinase assays. Effects on DNA-repair were detected by quantification of γ-H2AX positive foci 24 h after irradiation. Results The EGFR specific antibody C225 induced radiosensitization in A549 and also in MDA MB 231 cells. Radiosensitization in A549 was associated with blockage of radiation-induced EGFR transport into the nucleus, and immobilized the complex of EGFR with DNA-dependent protein kinase (DNA-PK) in the cytoplasm. As a consequence radiation-induced DNA-PK activation was abolished, a process that is essential for DNA-repair after radiation exposure. Likewise C225 treatment increased the residual amount of γ-H2AX-positive foci 24 h after irradiation in A549 and in MDA MB 231 cells. Conclusions Our results suggest that irradiation induced DNA-PK activation—essential for DNA repair—may be hampered specifically by use of the anti-EGFR-antibody C225. This process is associated with radiosensitization.

Published
2005

19. Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway

Author

Mahmoud Toulany, H. Peter Rodemann, Michael H. Baumann, Maren Krüger, and Klaus Dittmann

Subjects
EGF Family of Proteins, Ligands, Amphiregulin, Radiation Tolerance, Phosphatidylinositol 3-Kinases, Paracrine signalling, Cell Line, Tumor, Radioresistance, Anti-apoptotic Ras signalling cascade, Tumor Cells, Cultured, Humans, Radiology, Nuclear Medicine and imaging, Phosphorylation, Autocrine signalling, PI3K/AKT/mTOR pathway, Glycoproteins, A549 cell, Chemistry, Hematology, Transfection, Enzyme Activation, ErbB Receptors, Genes, ras, Oncology, Culture Media, Conditioned, Immunology, Cancer research, Intercellular Signaling Peptides and Proteins, Signal transduction, Signal Transduction
Abstract

Background and purpose In the context of EGFR-targeting strategies we investigated autocrine/paracrine factors leading to in vitro radioresistance of K-Ras mutated tumor cells through activation of EGFR mediated signal transduction. Patients and methods Ras mutated (Ras mt ) and normal Ras (Ras wt ) presenting human tumor cell lines were used to analyze the potential of conditioned media (CM) of both cell types to mediate radioresistance and to activate EGFR-signaling cascades. Therefore, clonogenic assays as well as SDS-PAGE combined with immunoblotting was performed. Additionally, Ras-mutated cells were transfected with K-Ras-siRNA to investigate, how downregulation of mutated K-Ras affects secretion of EGFR-ligands, stimulation of EGFR-signaling and modulation of radiation response. Results TGFα, Amphiregulin (ARG) and CM from Ras mt cells (Ras mt -CM) resulted in an increased clonogenic survival of irradiated Ras wt cells. Both, EGFR ligands as well as Ras mt -CM led to a strong phosphorylation of EGFR and activation of downstream pathways, i.e. PI3K-AKT. However, neutralization of TGFα or ARG in Ras mt -CM led to a marked reduction of P-AKT. Furthermore, Ras mt -CM from K-Ras-siRNA transfected Ras mt -cells markedly inhibited phosphorylation of AKT in Ras wt cells and enhanced radiation sensitivity of A549 cells transfected with the siRNA. Conclusion The data suggest that constitutively upregulated autocrine/paracrine secretion of EGF receptor ligands, especially ARG from K-Ras mutated cells, mediates radioresistance in Ras mt -cells through stimulation of EGFR-PI3K-AKT pathway.

Published
2005

20. Selective Radioprotection of Normal Tissues by Bowman-Birk Proteinase Inhibitor (BBI) in Mice

Author

Johannes Classen, Mahmoud Toulany, Klaus Dittmann, Vanessa Heinrich, Luka Milas, and H. Peter Rodemann

Subjects
Male, Pathology, medicine.medical_specialty, Bowman birk, Proteinase inhibitor, medicine.medical_treatment, Normal tissue, Pharmacology, Mice, Radiation Protection, In vivo, medicine, Animals, Radiology, Nuclear Medicine and imaging, Tumor growth, Trypsin Inhibitor, Bowman-Birk Soybean, Mice, Inbred C3H, Radiotherapy, business.industry, Neoplasms, Experimental, In vitro, Hindlimb, Radiation therapy, Oncology, Models, Animal, Female, Contracture, medicine.symptom, business, Cell Division, Muscle Contraction
Abstract

The efficacy of radiotherapy is limited by the response of normal tissues within the radiation field. The application of normal-tissue-specific radioprotectors may improve the therapeutic benefit of radiotherapy. The purpose of the present study was to explore the in vivo normal-tissue radioprotective potential of Bowman-Birk proteinase inhibitor (BBI), which acts as a normal-cell-specific radioprotector in vitro.The leg contracture assay in mice, a model system assessing radiation-induced fibrotic processes, was used. To determine whether BBI acts also as a radioprotector of tumors (i. e., FSA and FSAII), the tumor growth delay assay was used.Radiation induced leg contracture in mice with a maximum of about 8 mm at day 150 after irradiation. Treatment of mice with 100 mg/kg BBI before irradiation reduced leg contracture by4 mm, by about 50% (p0.05, t-test). Doses100 mg/kg were ineffective, and doses100 mg/kg did not further increase the degree of radioprotection. By contrast, BBI did not induce radioprotection of either TP53-mutated FSA or TP53-normal FSAII tumor xenografts in mice, which argues for normal-tissue-specific effect.BBI acts as a potent selective normal-tissue radioprotector in vitro and in vivo, apparently without protecting tumors, and thus has the potential to improve clinical radiotherapy.

Published
2005

21. The Bowman-Birk protease inhibitor enhances clonogenic cell survival of ionizing radiation-treated nucleotide excision repair-competent cells but not of xeroderma pigmentosum cells

Author

Ekkehard Dikomey, Klaus Dittmann, H. P. Rodemann, and Mayer C

Subjects
Methylnitronitrosoguanidine, Xeroderma pigmentosum, DNA Repair, Cell Survival, Ultraviolet Rays, DNA repair, DNA damage, Radiation-Protective Agents, Pyrimidine dimer, Biology, Bleomycin, chemistry.chemical_compound, medicine, Humans, Protease Inhibitors, Radiology, Nuclear Medicine and imaging, Cells, Cultured, Cisplatin, Xeroderma Pigmentosum, Radiological and Ultrasound Technology, X-Rays, Base excision repair, medicine.disease, Molecular biology, Biochemistry, chemistry, DNA, Nucleotide excision repair, medicine.drug
Abstract

The radioprotective effect of the Bowman-Birk protease inhibitor (BBI) was previously shown to result from a TP53 dependent mechanism. Whether this effect involves specific DNA repair mechanisms is now tested.Normal human fibroblasts were pre-treated with BBI before exposure to X-rays, UVB or to chemical agents (bleomycin, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cisplatin). These agents were chosen because of their ability to induce different spectra of DNA damage. The radiometric agent bleomycin primarily induces double-strand breaks (dsb), which are repaired by recombination; MNNG results in alkylated bases which are repaired by base excision repair (BER); cisplatin results in DNA-crosslinks which are repaired mainly by nucleotide excision repair (NER); and finally UVB generates thymine dimers and thymine-cytosine-6-4 products which are also repaired by NER. Cell survival was analysed by colony formation assay and DNA dsb by constant field gel electrophoresis. The combined effect of BBI and X-rays was also tested for XP-fibroblasts, which are defective in NER.For normal human fibroblasts the radioprotective effect of BBI was clearly found by using a delayed plating procedure. The radioprotective effect was found to be unrelated to an altered induction or repair of radiation-induced DNA dsb. Pretreatment with BBI did not affect cell killing after exposure to bleomycin or MNNG, but resulted in a significant protection of cells exposed to cisplatin or UVB. These results indicate that pre-treatment with BBI did not alter recombination repair or BER, but was able to modify NER. The latter finding was supported by the observation made for XP-cells, where pretreatment with BBI failed to result in radioprotection after exposure to ionizing radiation.On the basis of these data it is proposed that the radioprotective effect of BBI is the result of an improved nucleotide excision repair mechanism.

Published
2000

23. Nuclear epidermal growth factor receptor modulates cellular radio-sensitivity by regulation of chromatin access

Author

Klaus Dittmann, Martin Schaller, Claus Mayer, Rainer Kehlbach, Birgit Fehrenbacher, and H. Peter Rodemann

Subjects
DNA repair, Cell Survival, Blotting, Western, Radiation Tolerance, Histones, Histone H3, Promyelocytic leukemia protein, Cell Line, Tumor, Humans, Immunoprecipitation, Radiology, Nuclear Medicine and imaging, Epidermal growth factor receptor, Histone H3 acetylation, Cell Nucleus, Microscopy, Confocal, biology, Chemistry, Bronchial Neoplasms, Hematology, Immunohistochemistry, Chromatin, Cell biology, Up-Regulation, ErbB Receptors, Oncology, biology.protein, Phosphorylation, Heterochromatin protein 1, DNA Damage
Abstract

Purpose Nuclear EGFR is involved in cellular stress management and regulation of cellular radio-sensitivity. The aim of this study was to elucidate the molecular mode of nuclear EGFR action. Methods Radiation induced nuclear EGFR-shuttling and EGFR-foci formation was analyzed with immunohistochemistry and confocal microscopy. Composition of γH 2 AX–protein complexes was analyzed by western-blotting after immuno-precipitation. Functional relevance of nuclear EGFR was analyzed after siRNA mediated depletion of EGFR with respect to activation of ATM, histone H3 acetylation, residual DNA-damage and cell survival after irradiation. Results Following radiation nuclear EGFR was localized in foci similar to γH 2 AX. EGFR co-localized in a sub-fraction of γH 2 AX-foci. Analysis of composition of γH 2 AX-complexes revealed presence of EGFR, ATM, promyelocytic leukemia protein (PML), histone H3 and hetero-chromatin binding protein (HP1) in response to radiation. Depletion of EGFR protein inhibited ATM activation due to inhibition of acetylase TIP60 activity following irradiation. Consequently, histone H3 acetylation and phosphorylation was blocked and chromatin could not be opened for repair. Thus, residual DNA-damage was increased 24h after irradiation and cells were radio-sensitized. Comparable results were obtained when cells were treated with EGFR-NLS-peptide, which blocks EGFR nuclear shuttling specifically. Conclusions Nuclear EGFR is part of DNA-damage repair complex and is involved in regulation of TIP60-acetylase activity. TIP60 is essential for ATM activation and chromatin relaxation which is a prerequisite for DNA-repair in heterochromatic DNA. Thus interventional EGFR strategies during tumor treatment may also interact with DNA-repair by blocking access to damaged DNA.

Published
2011

24. Nuclear EGFR shuttling induced by ionizing radiation is regulated by phosphorylation at residue Thr654

Author

Martin Schaller, Rainer Kehlbach, Birgit Fehrenbacher, Claus Mayer, H. Peter Rodemann, and Klaus Dittmann

Subjects
Threonine, DNA repair, DNA damage, Nuclear Localization Signals, Biophysics, Active Transport, Cell Nucleus, Biology, Biochemistry, Cell survival, Cytosol, Structural Biology, Cell Line, Tumor, Radiation, Ionizing, Genetics, medicine, NLS, Humans, Phosphorylation, Molecular Biology, Cell Nucleus, DNA-repair, Cell Biology, Nuclear EGFR, ErbB Receptors, Cell nucleus, medicine.anatomical_structure, Cell culture, Cancer research, Nuclear transport
Abstract

Nuclear localisation of EGFR is associated with treatment resistance of tumor cells. The aim of this study was to identify molecular targets to block nuclear shuttling of EGFR. Mutation of Thr654, located within the putative EGFR NLS demonstrated that phosphorylation of this residue is essential for nuclear EGFR shuttling following irradiation. Deletion of Thr654 blocked nuclear transport of EGFR, whereas mutation to Glu increased shuttling. Treatment with a peptide, corresponding to the phosphorylated NLS, abolished nuclear EGFR transport and reduced radiation-induced activation of DNA-PK, essential for DNA-repair. In accordance with that, lack of nuclear EGFR increased residual DNA damage in tumor cells and reduced cellular survival following irradiation. Blockage of nuclear EGFR shuttling may be a new strategy to fight treatment resistance.Structured summaryMINT-7987956: Karyopherin alpha (uniprotkb:P52294) physically interacts (MI:0915) with EGFR (uniprotkb:P00533) by anti bait coimmunoprecipitation (MI:0006)

Published
2010

25. Radiation-induced lipid peroxidation activates src kinase and triggers nuclear EGFR transport

Author

Klaus Dittmann, H. Peter Rodemann, Rainer Kehlbach, Marie-Christine Rothmund, and Claus Mayer

Subjects
DNA Repair, media_common.quotation_subject, Blotting, Western, Caveolin 1, Active Transport, Cell Nucleus, Sensitivity and Specificity, Lipid peroxidation, chemistry.chemical_compound, Cell Line, Tumor, Radiation, Ionizing, medicine, Tumor Cells, Cultured, Humans, Radiology, Nuclear Medicine and imaging, DNA Breaks, Double-Stranded, Phosphorylation, Internalization, media_common, Chemistry, Hematology, Cell biology, Blot, ErbB Receptors, Cell nucleus, medicine.anatomical_structure, Carcinoma, Bronchogenic, src-Family Kinases, Oncology, Lipid Peroxidation, Nuclear transport, Proto-oncogene tyrosine-protein kinase Src
Abstract

Purpose Elucidation of the molecular mechanism of radiation-induced activation of src kinase, which initiates EGFR internalization and nuclear transport. Material and methods Radiation-induced src activation was investigated in the bronchial carcinoma cell line A549. Proteins were Western blotted and quantified by the help of specific antibodies. Residual DNA-damage was quantified with γH 2 AX-foci analysis. Radiation-induced lipid peroxidation was prevented by acetyl-cysteine. Results The radiation-induced src activation and EGFR stabilization could be mimicked by addition of hydroxy-nonenal (HNE), one of the major lipid peroxidation products. Radiation-generated HNE is bound to EGFR and src and correlated with complex formation between both following radiation. Treatment with HNE activated src and stimulated radiation-associated EGFR and caveolin 1 phosphorylations resulting in increased nuclear transport of EGFR. Consequently, radiation-induced phosphorylation and activation of DNA-PK were increased. This phosphorylation was associated with improved removal of residual damage 24h after irradiation. Inhibition of radiation-induced HNE generation by acetyl-cysteine blocked radiation-induced src activation and EGFR phosphorylation. Conclusions HNE generated in response to radiation exposure activates src kinase and is involved in regulation of radiation-stimulated DNA-repair processes.

Published
2009

26. Nuclear EGFR as novel therapeutic target: insights into nuclear translocation and function

Author

Klaus, Dittmann, Claus, Mayer, and H Peter, Rodemann

Subjects
Cell Nucleus, DNA Repair, Transcription, Genetic, Cell Survival, Cell Cycle, Antibodies, Monoclonal, Cetuximab, Antineoplastic Agents, Protein Kinase C-epsilon, Protein-Tyrosine Kinases, Antibodies, Monoclonal, Humanized, Caveolae, Translocation, Genetic, Cell Line, ErbB Receptors, Gene Expression Regulation, Neoplastic, Genes, src, Tumor Cells, Cultured, Humans, Cell Division, DNA Damage, Signal Transduction
Abstract

Emerging evidence suggests the existence of a new mode of epidermal growth factor receptor (EGFR) signaling in which activated EGFR undergoes nuclear translocation following treatment with ionizing radiation. The authors provide evidence that the nuclear EGFR transport is a stress-specific cellular reaction, which is linked to src-dependent EGFR internalization into caveolae. These flask-shaped pits can fuse with endoplasmic reticulum and the EGFR is sorted into a perinuclear localization. This compartment may serve as a reservoir for nuclear EGFR transport which is regulated by PKCepsilon (protein kinase Cepsilon). Nuclear EGFR is able to induce transcription of genes essential for cell proliferation and cell-cycle regulation. Moreover, nuclear EGFR has physical contact with compounds of the DNA repair machinery and is involved in removal of DNA damage. Anti-EGFR strategies target radiation-associated EGFR nuclear translocation in different manners. EGFR-inhibitory antibodies, i.e., cetuximab (Erbitux((R))), can block nuclear translocation by EGFR immobilization within the cytosol in responder cell lines, whereas tyrosine kinase inhibitors rather target nuclear kinase activity of EGFR linked with cytosolic or nuclear functions. However, both strategies can inhibit DNA repair following irradiation.

Published
2009

27. Cachexia-Anorexia Syndrome

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

28. Chorioretinitis

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

29. Churg Strauss Syndrome

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

30. Congenital Sucrose Intolerance

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

31. Congenital Generalized Fibromatosis

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

32. Common Variable Immunodeficiency

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

33. Clefts of the Lip, Alveolus and Palate

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

34. Carnitine Deficiency (without Transport and Uptake)

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

35. Cirrhose Cardiaque

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

36. Cobalamine Deficiency

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

37. Choledochal Cyst Type V

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

38. Congenital Hypothyroidism

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

39. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

40. Cold Thyroid Nodules

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

41. Coal Workers' Pneumoconiosis

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

42. Cholesterol Embolism

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

43. Corneal Dystrophy, Endothelial Fuchs

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

44. Corneal Dystrophy, X-linked Endothelial

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

45. Central Core Disease

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

46. Chondrodysplasia Punctata Rhizomelic Form

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

47. Chronic Obstructive Lung Disease

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

48. Cushing’s Syndrome

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

49. Congenital Nonautoimmune Hyperthyroidism

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

50. Cellular Nevus

Author

Nils Peters, Martin Dichgans, Sankar Surendran, Josep M. Argilés, Francisco J. López-Soriano, Sílvia Busquets, Klaus Dittmann, H. Peter Rodemann, Anca Sindrilaru, Cord Sunderkötter, Hiroshi Watanabe, Dan M. Roden, Giora Feuerstein, Robert Ruffolo, Ralph Knöll, Srijita Sen-Chowdhry, Deirdre Ward, William J. McKenna, Jens Mogensen, Mangala A. Nadkarni, F. Elizabeth Martin, Nicholas A. Jacques, Neil Hunter, Markus Böhm, Thomas A. Luger, Tilman Grune, Nicola Longo, Cristina Amat Di San Filippo, Elisabeth L. Schwarz, Marzia Pasquali, Elardus Erasmus, Lodewyk J. Mienie, Marcus Deschauer, Stephan Zierz, Du Toit Loots, Lee A. Denson, Helen C. Su, Michael J. Lenardo, Heather E. McDermid, Graeme Eisenhofer, Oscar De La Calle-Martin, Natalia Casamitjana, Cristina Woellner, Bodo Grimbacher, Detlef Schuppan, Walter Lisch, Berthold Seitz, Andreas Janecke, Tommie V. McCarthy, Carina Wallgren-Pettersson, Joost Haan, Michael T. Wunderlich, Nicole Revencu, Miikka Vikkula, Akira Honda, Seema R. Lalani, John W. Belmont, Julian Ilcheff Borissoff, Hugo Ten Cate, Takatoshi Kasai, Daniel Markovich, Michael Trauner, Carlo Selmi, M. Eric Gershwin, Malcolm A. Lyons, Kirk J. Maurer, Martin C. Carey, Frank Lammert, Tilman Sauerbruch, Peter L. M. Jansen, Holger Sudhoff, Stephan Vom Dahl, Detlev Ameis, Muhammad Faiyaz-Ul-Haque, Syed Hassan Ejaz Zaidi, Caroline Silve, Piero Pavone, Rosario Rich Trifiletti, Friedrich Asmus, Petra Weckerle, Gesa Schwanitz, Barbara Busert, Tanya Thiagarajah, Walter Muir, Ben Pickard, Anthony J. Cleare, Hubert Scharnagl, Winfried März, Ralf Kubitz, Dieter Häussinger, Norbert Schwenzer, Alexander K. C. Leung, William Lane M. Robson, Andrew L. Wong, Yener Güzelcan, Francesco Trotta, Andrea Lo Monaco, Reginald S. Sauve, Todd D. Rozen, Gloria L. David, Darryl C. Zeldin, P. Syamasundar Rao, Anne M. Molloy, John M. Scott, Göksel Somay, Sultan Ayoub Meo, Joshua Fierer, Mark Berneburg, Thomas Schwarz, Jürgen Schölmerich, Anne Katrin Lampe, Kate Bushby, William J. Speake, John Simpson, Hope E. Uronis, Gerard C. Blobe, Diego Franco, Amelia Aránega, Eggert Stockfleth, Ingo Nindl, Christian Hamel, Felix G. Riepe, Erich C. Strauss, Vinzenz Oji, Heiko Traupe, Thomas Frieling, Andrea Cavani, Giampiero Girolomoni, Randolf Brehler, Ortrud K. Steinlein, Janet Y. Uriu-Adams, Jean-Charles Deybach, Hervé Puy, Michael L. S. Ma, Patrick T. S. Ma, Alexander A. C. Leung, Jolanta Wierzba, Angelo Selicorni, Yskert Von Kodolitsch, Wulf Ito, Nilanjana Maulik, Rainer Voisard, Hiroki Teragawa, Kazuaki Chayama, Renzo Guerrini, Carla Marini, Elena Parrini, Alexander Storch, Johannes Schwarz, Sonja Ständer, Kam-Lun Ellis Hon, Chiu-Wing Winnie Chu, Olaf A. Bodamer, Sylvia Stöckler-Ipsiroglu, Tatsuro Kondoh, Osamu Shimokawa, Naoki Harada, Hiroyuki Moriuchi, Karsten Schulmann, Christian Pox, Wolff Schmiegel, James E. Crowe, Nan Hatch, Mark Bothwell, Holger S. Willenberg, Stefan R. Bornstein, Zsolt Urban, Francesco Borgia, Fabrizio Guarneri, Mario Vaccaro, Dieter Metze, Karl Kunzelmann, Marcus Mall, Paul Cheung-Lung Choi, William A. Gahl, Thomas Knoll, Albrecht Hesse, and Michaela Jaksch

Published
2009

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