74 results on '"Gudrun Ratzinger"'
Search Results
52. Inflammation and lipid accumulation in xanthoma disseminatum: Therapeutic considerations
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Peter O. Fritsch, B Zelger, Hildegunde Piza, Dennis Linder, W. Philipp, Gudrun Ratzinger, Klaus Eisendle, and Matthias Schmuth
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Lipid accumulation ,business.industry ,Simvastatin ,Medicine ,Xanthoma disseminatum ,Lipid metabolism ,Inflammation ,Dermatology ,Pharmacology ,medicine.symptom ,business ,medicine.disease ,medicine.drug - Published
- 2008
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53. Österreichische Gesellschaft für Dermatologie und Venerologie (ÖGDV)
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Gudrun Ratzinger
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030228 respiratory system ,business.industry ,Medicine ,Dermatology ,business - Published
- 2015
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54. Das kutane Larva migrans Syndrom: Schwierigkeiten bei Diagnose und Behandlung anhand von drei Fallbeispielen
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Matthias Schmuth, Maria Kitchen, Reinhard Höpfl, Sabine Moser-Oberthaler, Manuel Wilhelm, Gudrun Ratzinger, and Ahn Van Nguyen
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Gynecology ,medicine.medical_specialty ,business.industry ,Treatment outcome ,medicine ,General Medicine ,business ,Skin pathology ,Larva migrans - Abstract
Die kutane Larva migrans ist eine haufige Dermatose nach Urlaubsaufenthalten an tropischen Stranden. Die Hautlasionen entstehen durch die intradermale Migration von Hakenwurmlarven von Hunden und Katzen, die sich im menschlichen Fehlwirt nicht weiterentwickeln konnen und letztlich in der Haut absterben. Obwohl die typischen gewundenen Larvengange meist sehr einfach zu diagnostizieren und mit Albendazol oder Ivermectin zu behandeln sind, kommt es bei ungewohnlichen klinischen Prasentationen auch zu Fehldiagnosen und langen Krankheitsverlaufen. Wir stellen drei klinische Falle vor, bei denen die Diagnose erst verzogert gestellt wurde bzw. die Behandlung erschwert war.
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- 2013
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55. [Pitfalls in diagnosis and treatment of cutaneous larva migrans: three unusual cases from a dermatology clinic]
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Maria, Kitchen, Manuel, Wilhelm, Sabine, Moser-Oberthaler, Reinhard, Höpfl, Gudrun, Ratzinger, Van Ahn, Nguyen, and Matthias, Schmuth
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Adult ,Anthelmintics ,Diagnosis, Differential ,Male ,Ivermectin ,Treatment Outcome ,Humans ,Larva Migrans ,Middle Aged ,Albendazole ,Skin - Abstract
Cutaneous larva migrans (CLM, creeping eruption) is a skin disease commonly seen in travelers returning from the tropics. The lesions are caused by intradermal migration of animal hookworm larvae which cannot mature in humans. While the typical serpiginous skin lesions are easily diagnosed and treated with albendazole or ivermectin, unusual presentations can be misdiagnosed and cause prolonged morbidity. We present 3 cases of CLM, which were difficult to diagnose and/or treat.Case 1 is a 34-year old Caucasian male who presented with itchy papular lesions on the soles of both feet and was initially treated for plantar psoriasis.Case 2 is a 54-year old Caucasian male who suffered from extensive follicular larva migrans on the buttocks for several months and was only cured after repeated courses of albendazole and ivermectin.Case 3 is a 29-year old Caucasian male with pruritic inflammatory papules on the trunk. Despite extensive diagnostic procedures including skin biopsies and tissue cultures the correct diagnosis was only made later during the course of the illness. After treatment for CLM with albendazole (800 mg/d for 3 days) and after resolution of perifocal edema and inflammation the typical serpiginous tracks became more obvious. They responded rapidly to anthelminthic treatment.These cases highlight the importance of careful history taking and work-up in individuals presenting with atypical skin lesions. In case of exposure to CLM empiric anthelminthic treatment might be considered.
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- 2013
56. Wells syndrome and its relationship to Churg-Strauss syndrome
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Gudrun, Ratzinger, Julia, Zankl, and Bernhard, Zelger
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Adult ,Male ,Urticaria ,Erythema ,Biopsy ,Eosinophilia ,Humans ,Cellulitis ,Female ,Churg-Strauss Syndrome ,Middle Aged ,Child ,Skin - Abstract
Wells syndrome has been described as an inflammatory disorder based on typical clinical appearance combined with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Churg-Strauss syndrome, on the other hand, is primarily a diffuse, necrotizing vasculitis but is also typically displaying eosinophils and flame figures. Despite several parallels, the present understanding of these two diseases excludes any pathogenetic relationship. We describe the clinical course and histopathological appearance of three patients who had initially been diagnosed with Wells syndrome that developed into Churg-Strauss syndrome during the course of their disease. The clinical presentation of all three patients led to the diagnosis of Wells syndrome by independent specialists. Histopathology showed an eosinophilic infiltrate and flame figures next to features of leukocytoclastic vasculitis. Detailed examination revealed asthma bronchiale and additional symptoms indicating Churg-Strauss syndrome. The initial diagnosis of Wells syndrome had to be revised to Churg-Strauss syndrome. We conclude that Wells syndrome could be the starting point of a pathogenetic process that might reach its maximum in Churg-Strauss syndrome. As a clinical consequence, patients with Wells syndrome should be evaluated and followed for Churg-Strauss syndrome.
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- 2013
57. UVB-Induced Senescence of Human Dermal Fibroblasts Involves Impairment of Proteasome and Enhanced Autophagic Activity
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Maria Cavinato, Pidder Jansen-Dürr, Rafal Koziel, Regina Weinmüllner, Gudrun Ratzinger, Nikolaus Romani, Sandrine Dubrac, Martin Hermann, Johannes Grillari, Matthias Schmuth, and Brigitte Jenewein
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0301 basic medicine ,Senescence ,Proteasome Endopeptidase Complex ,Radioimmunoprecipitation Assay ,Aging ,Programmed cell death ,Ultraviolet Rays ,Photoaging ,Blotting, Western ,Biology ,Real-Time Polymerase Chain Reaction ,Skin Aging ,03 medical and health sciences ,Autophagy ,medicine ,Humans ,skin and connective tissue diseases ,Cells, Cultured ,Cellular Senescence ,Cell Proliferation ,chemistry.chemical_classification ,Reactive oxygen species ,integumentary system ,Dose-Response Relationship, Radiation ,Fibroblasts ,medicine.disease ,Cell biology ,030104 developmental biology ,Proteasome ,chemistry ,Apoptosis ,Geriatrics and Gerontology ,Reactive Oxygen Species - Abstract
In the current study, we have extended previous findings aiming at a better understanding of molecular mechanisms underlying UVB-induced senescence of diploid human dermal fibroblasts (HDFs), an experimental model to study the process of photoaging in the skin. We provide evidence that the inhibition of proteasomal degradation of damaged proteins and the activation of autophagosome formation are early events in UVB-induced senescence of HDFs, dependent on UVB-induced accumulation of reactive oxygen species. Our data suggest that autophagy is required for the establishment of the senescent phenotype in UVB-treated HDFs and that inhibition of autophagy is sufficient to change the cell fate from senescence to cell death by apoptosis. Studies in reconstructed skin equivalents revealed that UVB irradiation triggers hallmarks of autophagy induction in the dermal layer. These findings have potential implications for fundamental as well as translational research into skin aging, in particular photoaging.
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- 2016
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58. Chondrodermatitis nodularis chronica helicis - a conservative therapeutic approach by decompression
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Marlene, Kuen-Spiegl, Gudrun, Ratzinger, Norbert, Sepp, and Peter, Fritsch
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Male ,Treatment Outcome ,Humans ,Dermatitis ,Female ,Syndrome ,Middle Aged ,Decompression, Surgical ,Ear Diseases ,Cartilage Diseases ,Aged - Abstract
Chondrodermatitis nodularis chronica helicis is a rather common condition which substantially affects quality of life causing pain and sleeping disturbances. Surgical treatment is connected with a tendency to recurrence. Mechanical pressure is probably the main etiological factor.A prospective study was performed with 18 patients that were offered a non-surgical treatment using a self-made bandage of foam plastic which they applied during the night. Of these, 12 performed the treatment including follow-up; 6 patients initially also consented, but they did not return after the initial visit.11 patients reported substantial reduction of pain within the first month; after an average of 1.75 months they were free of pain. All 8 patients with initial sleeping problems caused by pain reported undisturbed sleep after only one month. In 11 patients the lesions receded satisfactorily, in 9 patients completely, in 2 patients leaving small asymptomatic residual lesions. Recurrences appeared in 3 patients with 2 of them having been surgically pretreated at the same location.We recommend conservative treatment using protective padding as first line treatment for chondrodermatitis nodularis chronica helicis. The successful outcome achieved only by relief of pressure supports pressure as the main etiological factor in the development of the disease.
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- 2010
59. Conditioning of the injection site with CpG enhances the migration of adoptively transferred dendritic cells and endogenous CD8+ T-cell responses
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Christoph H. Tripp, Patrizia Stoitzner, Susanne Ebner, Nikolaus Romani, and Gudrun Ratzinger
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Lipopolysaccharides ,Cancer Research ,Adoptive cell transfer ,Receptors, CCR7 ,Injections, Intradermal ,medicine.medical_treatment ,Immunology ,C-C chemokine receptor type 7 ,Peptidoglycan ,Biology ,Cancer Vaccines ,Mice ,Antigens, Neoplasm ,Cell Movement ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Antigen-presenting cell ,Dendritic cell migration ,Cells, Cultured ,Skin ,Pharmacology ,Toll-Like Receptors ,Imidazoles ,Cell migration ,Dendritic cell ,DNA ,Dendritic Cells ,Adoptive Transfer ,Cell biology ,Mice, Inbred C57BL ,Cytokine ,Oligodeoxyribonucleotides ,Lymph Nodes - Abstract
The efficiency of immunotherapy using tumor-antigen-loaded dendritic cells (DCs) is severely limited by the impaired migration of injected cells from the application site to the draining lymph nodes. As described earlier, pretreatment of the injection site with inflammatory cytokines enhances DC migration. We wanted to test whether toll-like receptor (TLR) ligands can improve migration of murine bone marrow-derived DC (BMDC) and the subsequent T-cell responses. For this purpose, we established an experimental setup closely resembling human vaccination protocols that served to investigate DC migration from the skin to the draining lymph nodes. We observed that BMDC, matured with a cytokine cocktail (tumor necrosis factor-alpha, interleukin-beta, interleukin-6, prostaglandin E2), strongly expressed CCR7. The migration efficiency of adoptively transferred mature BMDCs was determined by the number of cells injected and the application site. We decided to inject DC intradermally into the ear skin and investigated the effects of pretreatment of the injection site with various TLR ligands. Conditioning of the skin site with the TLR ligands CpG and Peptidoglycan increased the number of DCs arriving in the lymph node. Mechanical stress applied to the skin, such as tape stripping of the skin was equally effective. Importantly, only pretreatment with CpG enhanced responses of endogenous CD8 T cells. Thus, conditioning of the injection site with the TLR ligand CpG could be a new promising way to improve the outcome of DC immunotherapy.
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- 2010
60. Epidermal Langerhans Cells
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Gudrun Ratzinger, Nikolaus Romani, Franz Koch, Sem Saeland, Christoph H. Tripp, Christine Heufler, and Patrizia Stoitzner
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Epidermis (zoology) ,Morphology (linguistics) ,Ontogeny ,Biology ,Cell biology - Published
- 2008
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61. Matrix
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Gudrun Ratzinger and Sabine Mostegl
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media_common.quotation_subject ,Art ,media_common - Published
- 2008
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62. [Cholesterol embolism after renal transplantation]
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Gudrun, Ratzinger, Peter, Fritsch, and Bernhard, Zelger
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Treatment Outcome ,Buttocks ,Humans ,Female ,Skin Diseases, Vascular ,Kidney Transplantation ,Aged ,Embolism, Cholesterol - Abstract
A 70-year-old woman developed localized livedo racemosa on the right buttock 2 months after renal transplantation. The suspected diagnosis of cholesterol embolism was confirmed by histopathological demonstration of cholesterol crystals in the wall of a small artery. The gluteal region is supplied by blood vessels that branch off the internal iliac artery distal to the usual anastomosing site of the donor kidney. Cholesterol emboli dislocated in the course of a kidney transplantation can reach the gluteal region. Cholesterol embolism after renal transplantation as well as the observation of cholesterol crystals in the histological preparation are rare findings.
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- 2005
63. CADASIL-an unusual manifestation with prominent cutaneous involvement
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Nikolaus Romani, G Ransmayr, Bernhard Zelger, and Gudrun Ratzinger
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Male ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,Central nervous system ,CADASIL ,Hemorrhage ,Dermatology ,Transient ischaemic attacks ,Middle Aged ,Skin Diseases, Vascular ,medicine.disease ,Fibrin ,medicine.anatomical_structure ,Vascular Disorder ,biology.protein ,Medicine ,Dementia ,Humans ,Histopathology ,Basal lamina ,business ,Skin - Abstract
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucencephalopathy (CADASIL) is a rare vascular disorder affecting mainly the central nervous system with transient ischaemic attacks, strokes, psychiatric symptoms and dementia. It is a progressive familial disease owing to mutations in the Notch3 gene. Clinically apparent skin involvement is usually absent. Electron microscopy of seemingly uninvolved skin reveals characteristic granular deposits in the basal lamina of vessels and adnexals. We report on a case of CADASIL with generalized haemorrhagic macules and patches. Typical neurological symptoms as well as classical findings in histopathology and electron microscopy confirmed the diagnosis. Immunofluorescence showed an increased number of vessels with walls markedly thickened by deposits of fibrin, complement and immunoglobulins. This method could serve as an additional method for accurate diagnosis of CADASIL.
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- 2005
64. Sinus histiocytosis with massive lymphadenopathy Rosai-Dorfman: three unusual manifestations
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Bettina G. Zelger, Walter Höbling, Bernhard Zelger, Gregor Mikuz, and Gudrun Ratzinger
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Eye disease ,Mucocutaneous zone ,Pathology and Forensic Medicine ,Extranodal Disease ,medicine ,Humans ,Lung cancer ,Molecular Biology ,Lymphatic Diseases ,Nose ,Rosai–Dorfman disease ,Skin ,business.industry ,Sinus Histiocytosis with Massive Lymphadenopathy ,Anatomical pathology ,Cell Biology ,General Medicine ,Middle Aged ,medicine.disease ,Dermatology ,Immunohistochemistry ,medicine.anatomical_structure ,Female ,Lymph Nodes ,Histiocytosis, Sinus ,business - Abstract
We report on three exceptional courses of sinus histiocytosis Rosai-Dorfman. Patient one developed regional lymph-node disease subsequent to two independent malignancies in the right head and neck region. Patient two suffered from extensive extranodal disease with more than 100 mucocutaneous lesions over 17 years, which spontaneously resolved. Patient three showed exclusively extranodal disease, including bilateral conjunctival/scleral lesions, before he developed lung cancer. Our cases are unique for three reasons: the association of the disease with solid malignancies in two cases, the extent and persistence of exclusively extranodal disease in one patient and the appearance of thus far undescribed conjunctival/scleral lesions.
- Published
- 2004
65. Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation
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Gudrun Ratzinger, John L. Reagan, Klaus J. Busam, Glenn Heller, and James W. Young
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Guanine ,CD52 ,Antibodies, Neoplasm ,T-Lymphocytes ,Immunology ,Antigen presentation ,Graft vs Host Disease ,Major histocompatibility complex ,Antibodies, Monoclonal, Humanized ,Biochemistry ,Graft vs Host Reaction ,Immune system ,Antigen ,Antigens, CD ,Antigens, Neoplasm ,Cell Adhesion ,Humans ,Transplantation, Homologous ,Antigen-presenting cell ,Alemtuzumab ,Glycoproteins ,Antigen Presentation ,biology ,Antibody-Dependent Cell Cytotoxicity ,Antibodies, Monoclonal ,Cell Biology ,Hematology ,Dendritic cell ,Dendritic Cells ,Coculture Techniques ,Transplantation ,Intestines ,CD52 Antigen ,biology.protein ,Lymphocyte Culture Test, Mixed ,Cell Division ,Granulocytes - Abstract
Alemtuzumab (anti-CD52; Campath 1-H) depletes both host and donor T cells when used in preparative regimens for allogeneic transplantation. This promotes engraftment even after nonmyeloablative conditioning and limits graft-versus-host disease (GVHD) even after unrelated or major histocompatibility complex (MHC) disparate allografts. We asked whether anti-CD52 differentially targets antigen-presenting cells (APCs), in addition to depleting T cells. Monocyte-derived dendritic cells (moDCs) expressed abundant CD52 as expected. Langerhans cells (LCs) and dermal-interstitial DCs (DDC-IDCs), however, never expressed CD52. Immunostaining of skin and gut confirmed the absence of CD52 on these resident DC populations under both steady-state and inflammatory conditions. Although anti-CD52 functions primarily by antibody-dependent cellular cytotoxicity (ADCC) in vivo, assessment of its activity in vitro included complement-dependent lysis of CD52+ cells. Anti-CD52 did not impair DC–T–cell adhesion, diminish DC-stimulated T-cell proliferation, or alter moDC development in vitro. We propose that anti-CD52 abrogates GVHD not only by T-cell depletion, but also by removing moDCs and their precursors. This would mitigate moDC phagocytosis and presentation of host-derived antigens to donor T cells in the inflammatory peritransplantation environment, thereby limiting GVHD. The sparing of LCs and DDC-IDCs by anti-CD52, as well as the recovery of donor-derived moDCs in a less inflammatory environment later after transplantation, may allow all these DCs to exert formative roles in graft-versus-tumor (GVT) reactions and immune reconstitution. Whether these results support a separation of deleterious from beneficial graft-host interactions at the level of antigen presentation, rather than solely at the level of T cells, will require further evaluation.
- Published
- 2002
66. Migration of dendritic cells into lymphatics—The langerhans cell example: Routes, regulation, and relevance
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Gudrun Ratzinger, Willi Salvenmoser, Hella Stössel, Nikolaus Romani, Patrizia Stoitzner, Kristian Pfaller, and Franz Koch
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Langerhans cell ,medicine.anatomical_structure ,Follicular dendritic cells ,Antigen presentation ,CD1 ,Myeloid-derived Suppressor Cell ,medicine ,Cytotoxic T cell ,Dendritic cell ,Biology ,Antigen-presenting cell ,Cell biology - Abstract
Dendritic cells are leukocytes of bone marrow origin. They are central to the control of the immune response. Dendritic cells are highly specialized in processing and presenting antigens (microbes, proteins) to helper T lymphocytes. Thereby, they critically regulate further downstream processes such as the development of cytotoxic T lymphocytes, the production of antibodies by B lymphocytes, or the activation of macrophages. A new field of dendritic cell biology is the study of their potential role in inducing peripheral tolerance. The immunogenic/tolerogenic potential of dendritic cells is increasingly being utilized in immunotherapy, particularly for the elicitation of antitumor responses. One very important specialization of dendritic cells is their outstanding capacity to migrate from sites of antigen uptake to lymphoid organs. Much has been learned about this process from studying one particular type of dendritic cell, namely, the Langerhans cell of the epidermis. Therefore, the migratory properties of Langerhans cells are reviewed. Knowledge about this “prototype dendritic cell” may help researchers to understand migration of other types of dendritic cells.
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- 2001
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67. Successful treatment of recalcitrant relapsing polychondritis with monoclonal antibodies
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Marlene Kuen-Spiegl, N Sepp, and Gudrun Ratzinger
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Pathology ,medicine.medical_specialty ,Infectious Diseases ,medicine.drug_class ,business.industry ,Immunology ,medicine ,Dermatology ,Monoclonal antibody ,business ,medicine.disease ,Relapsing polychondritis - Published
- 2009
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68. Dapsone in combination with topical triamcinolone as a therapeutic option for cheilitis granulomatosa and MelkerssonRosenthal disease?
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Gudrun Ratzinger and N Sepp
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medicine.medical_specialty ,Infectious Diseases ,Triamcinolone acetonide ,business.industry ,medicine ,Dermatology ,Disease ,Dapsone ,business ,medicine.drug - Published
- 2008
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69. Is there a true association between Rosai-Dorfman disease and malignancy?
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Bernhard Zelger, Gudrun Ratzinger, and Bettina G. Zelger
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Pediatrics ,medicine.medical_specialty ,Histiocytosis ,business.industry ,medicine ,MEDLINE ,Dermatology ,Malignancy ,medicine.disease ,business ,Rosai–Dorfman disease - Published
- 2003
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70. [Untitled]
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Nikolaus Romani, Patrizia Stoitzner, Gudrun Ratzinger, Peter Fritsch, Hella Stössel, Susanne Ebner, and Sandra Holzmann
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Langerhans cell ,CD40 ,biology ,Follicular dendritic cells ,business.industry ,Antigen presentation ,CD1 ,medicine.anatomical_structure ,Rheumatology ,Immunology ,medicine ,Lymph node stromal cell ,biology.protein ,business ,Dendritic cell migration ,Antigen-presenting cell - Abstract
Dendritic cells, including Langerhans cells of the epidermis and the mucous membranes, are key leukocytes for the initiation of adaptive immune responses as well as for the maintenance of peripheral tolerance. In the former regard they may well play an important, but as yet unrecognized role in the pathogenesis of Behcet's disease. Epidermal Langerhans cells may serve as a paradigm for their counterparts in the mucosae. These cells efficiently take up (microbial) antigens, they process them into immunogenic MHC–peptide complexes, and they transport this form of antigen to the lymph nodes via lymphatic vessels. Depending on the milieu where Langerhans cells have encountered antigen (inflammatory versus non-inflammatory/steady-state), they make T cells proliferate and acquire effector functions (immunity) or render them unresponsive or even delete them (tolerance), respectively. In addition, plasmacytoid dendritic cells, a recently characterized type of dendritic cells, may also directly trigger innate responses (e.g. by secretion of type I interferons in response to virus). Studying the pathways and the regulation of dendritic cell migration might help to unravel a possible involvement of dendritic cells in Behcet's disease. We present observations on the physical obstacles that dendritic cells migrating in the skin have to overcome until they reach dermal lymphatic vessels. Furthermore, we show that migration is critically dependent on the function of matrix metalloproteinases, in particular MMP-2 and MMP-9. It becomes evident that Langerhans cells indeed carry antigens (including self antigens such as melanosomes or apoptotoic bodies or tumor antigens such as particular cytokeratins) through the lymphatics. Given these observations it may be worth studying Langerhans cells and dermal dendritic cells in Behcet's disease.
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- 2003
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71. Sinus histiocytosis with massive lymphadenopathy Rosai-Dorfman: three unusual manifestations.
- Author
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Gudrun Ratzinger, Bettina Zelger, Walter Höbling, Gregor Mikuz, and Bernhard W. Zelger
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HISTIOCYTOSIS ,LYMPH node diseases ,LUNG cancer ,PRECANCEROUS conditions - Abstract
We report on three exceptional courses of sinus histiocytosis Rosai-Dorfman. Patient one developed regional lymph-node disease subsequent to two independent malignancies in the right head and neck region. Patient two suffered from extensive extranodal disease with more than 100 mucocutaneous lesions over 17 years, which spontaneously resolved. Patient three showed exclusively extranodal disease, including bilateral conjunctival/scleral lesions, before he developed lung cancer. Our cases are unique for three reasons: the association of the disease with solid malignancies in two cases, the extent and persistence of exclusively extranodal disease in one patient and the appearance of thus far undescribed conjunctival/scleral lesions. [ABSTRACT FROM AUTHOR]
- Published
- 2003
72. Interleukin-16 Supports the Migration of Langerhans Cells, Partly in a CD4-Independent Way
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Thomas Schöller, Herbert Tilg, Katrin Janke, Gudrun Ratzinger, Patrizia Stoitzner, William W. Cruikshank, Peter Fritsch, Franz Koch, Nikolaus Romani, and Arthur Kaser
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skin ,Langerhans cell ,Injections, Intradermal ,medicine.medical_treatment ,Human skin ,Dermatology ,Biology ,Biochemistry ,Mice ,Immune system ,Organ Culture Techniques ,Antigen ,Cell Movement ,medicine ,Animals ,Humans ,dendritic cells ,chemotaxis ,Molecular Biology ,Interleukin-16 ,Mice, Inbred BALB C ,Epidermis (botany) ,integumentary system ,Tumor Necrosis Factor-alpha ,Cell Biology ,Dendritic cell ,Dermis ,cytokines ,Cell biology ,Cytokine ,medicine.anatomical_structure ,Langerhans Cells ,Immunology ,CD4 Antigens ,Tumor necrosis factor alpha - Abstract
Migration of cutaneous dendritic cells is essential for the induction of primary immune responses. Chemotaxis plays an important part in guiding migrating cells through the skin. Therefore, we investigated the influence of interleukin-16, a potent chemoattractant, on the migratory properties of cutaneous dendritic cells. Interleukin-16 added to murine and human skin explant cultures, enhanced emigration of Langerhans cells as well as dermal dendritic cells out of the skin. In contrast to tumor necrosis factor-alpha, intradermally injected interleukin-16 did not reduce the density of Langerhans cells suggesting a chemotactic rather than a mechanistic migration-inducing effect of interleukin-16. In support of these findings, the known migration-promoting effect of tumor necrosis factor-alpha in skin explant cultures could be neutralized by anti-interleukin-16 antibody and vice versa, indicating different but cooperative ways of action for both cytokines. In whole skin explant cultures blocking of the interleukin-16 effect was also achieved with a monoclonal antibody against CD4, the receptor for interleukin-16. In contrast, in cultures of murine epidermis alone no blocking by anti-CD4 became obvious and in CD4-deficient mice Langerhans cell migration in response to interleukin-16 was maintained. This suggests that another receptor for interleukin-16 might be operative for Langerhans cells in the mouse epidermis. Finally, we detected interleukin-16-positive cells in the dermis of skin explants, tumor necrosis factor-alpha-treated and contact allergen-treated skin. Taken together, it seems likely that locally secreted interleukin-16 might serve to enhance the migration of cutaneous dendritic cells and optimize the response to foreign antigen encountering the skin.
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73. Production of IL-12 by human monocyte-derived dendritic cells is optimal when the stimulus is given at the onset of maturation, and is further enhanced by IL-4
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Gudrun Ratzinger, Richard A. Kroczek, Peter Fritsch, Manfred Herold, Susanne Ebner, Beate Krösbacher, Nikolaus Romani, Matthias Schmuth, Christine Heufler, Angelika Weiss, and Daniela Reider
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Intracellular Fluid ,Staphylococcus aureus ,Transcription, Genetic ,medicine.medical_treatment ,CD40 Ligand ,Immunology ,Monocytes ,Interferon-gamma ,Mice ,Adjuvants, Immunologic ,medicine ,Animals ,Humans ,Immunology and Allergy ,CD40 Antigens ,CD154 ,Cells, Cultured ,Interleukin 4 ,Skin ,CD40 ,biology ,Follicular dendritic cells ,Cell Differentiation ,Dendritic Cells ,Immunotherapy ,Flow Cytometry ,Interleukin-12 ,Growth Inhibitors ,Interleukin-10 ,Cell biology ,Membrane glycoproteins ,Cell culture ,Culture Media, Conditioned ,biology.protein ,Interleukin 12 ,Interleukin-4 - Abstract
Dendritic cells produce IL-12 both in response to microbial stimuli and to T cells, and can thus skew T cell reactivity toward a Th1 pattern. We investigated the capacity of dendritic cells to elaborate IL-12 with special regard to their state of maturation, different maturation stimuli, and its regulation by Th1/Th2-influencing cytokines. Monocyte-derived dendritic cells were generated with GM-CSF and IL-4 for 7 days, followed by another 3 days ± monocyte-conditioned media, yielding mature (CD83+/dendritic cell-lysosome-associated membrane glycoprotein+) and immature (CD83−/dendritic cell-lysosome-associated membrane glycoprotein−) dendritic cells. These dendritic cells were stimulated for another 48 h, and IL-12 p70 was measured by ELISA. We found the following: 1) Immature dendritic cells stimulated with CD154/CD40 ligand or bacteria (both of which concurrently also induced maturation) secreted always more IL-12 than already mature dendritic cells. Mature CD154-stimulated dendritic cells still made significant levels (up to 4 ng/ml). 2) Terminally mature skin-derived dendritic cells did not make any IL-12 in response to these stimuli. 3) Appropriate maturation stimuli are required for IL-12 production: CD40 ligation and bacteria are sufficient; monocyte-conditioned media are not. 4) Unexpectedly, IL-4 markedly increased the amount of IL-12 produced by both immature and mature dendritic cells, when present during stimulation. 5) IL-10 inhibited the production of IL-12. Our results, employing a cell culture system that is now being widely used in immunotherapy, extend prior data that IL-12 is produced most abundantly by dendritic cells that are beginning to respond to maturation stimuli. Surprisingly, IL-12 is only elicited by select maturation stimuli, but can be markedly enhanced by the addition of the Th2 cytokine, IL-4.
74. Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin
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Guy T. Layton, Susanne Ebner, Manfred B. Lutz, Patrizia Stoitzner, Nikolaus Romani, Robert M. Senior, Christian Rainer, Peter Fritsch, J. Michael Shipley, Gerold Schuler, and Gudrun Ratzinger
- Subjects
Pathology ,medicine.medical_specialty ,Langerhans cell ,Matrix metalloproteinase inhibitor ,Cellular differentiation ,T cell ,Immunology ,Human skin ,Biology ,Matrix Metalloproteinase Inhibitors ,Basement Membrane ,Mice ,Organ Culture Techniques ,Cell Movement ,medicine ,Immunology and Allergy ,Animals ,Humans ,Protease Inhibitors ,Dendritic cell migration ,Histiocyte ,Cells, Cultured ,Skin ,Mice, Knockout ,Mice, Inbred BALB C ,Follicular dendritic cells ,Dose-Response Relationship, Drug ,Cell Differentiation ,Dendritic Cells ,Dermis ,Matrix Metalloproteinases ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Epidermal Cells ,Matrix Metalloproteinase 9 ,Langerhans Cells ,Matrix Metalloproteinase 2 ,Epidermis - Abstract
Dendritic cells migrate from the skin to the draining lymph nodes. They transport immunogenic MHC-peptide complexes, present them to Ag-specific T cells in the T areas, and thus generate immunity. Migrating dendritic cells encounter physical obstacles, such as basement membranes and collagen meshwork. Prior work has revealed that matrix metalloproteinase-9 (MMP-9) contributes to mouse Langerhans cell migration. In this study, we use mouse and human skin explant culture models to further study the role of MMPs in the migration and maturation of skin dendritic cells. We found that MMP-2 and MMP-9 are expressed on the surface of dendritic cells from the skin, but not from other sources. They are also expressed in migrating Langerhans cells in situ. The migration of both Langerhans cells and dermal dendritic cells is inhibited by a broad spectrum inhibitor of MMPs (BB-3103), by Abs to MMP-9 and -2, and by the natural tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-2. Inhibition by anti-MMP-2 and TIMP-2 define a functional role for MMP-2 in addition to the previously described function of MMP-9. The importance of MMP-9 was emphasized using MMP-9-deficient mice in which Langerhans cell migration from skin explants was strikingly reduced. However, MMP-9 was only required for Langerhans cell migration and not maturation, since nonmigrating Langerhans cells isolated from the epidermis matured normally with regard to morphology, phenotype, and T cell stimulatory function. These data underscore the importance of MMPs, and they may be of relevance for therapeutically regulating dendritic cell migration in clinical vaccination approaches.
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