@article{HammHoeger2011, author = {Hamm, Henning and H{\"o}ger, Peter H}, title = {Skin Tumors in Childhood}, series = {Deutsches {\"A}rzteblatt International}, volume = {108}, journal = {Deutsches {\"A}rzteblatt International}, number = {20}, doi = {10.3238/arztebl.2011.0347}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142402}, pages = {347-353}, year = {2011}, abstract = {Background: Dermatologists, paediatricians, and general practitioners are often consulted by worried parents for the evaluation of a cutaneous tumor. Methods: Selective literature review. Results: Only 1-2\% of skin tumors excised in children turn out to be malignant when examined histologically. Warning signs of malignancy include rapid growth, firm consistency, diameter exceeding 3 cm, ulceration, a non-movable mass, and presence in the neonatal period. The more common malignant skin tumors in adults-basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma-are very rare in childhood. Congenital melanocytic nevi and sebaceous nevi bear a lower malignant potential than previously believed; nevertheless, their excision is often indicated. A Spitz nevus can mimic a melanoma both clinically and histologically. Some benign skin tumors of childhood tend to regress spontaneously within a few years but may cause complications at particular locations and when multiple. For infantile hemangiomas requiring systemic treatment because of imminent obstruction or ulceration, propranolol seems to have a far more favorable risk-benefit ratio than corticosteroids. Conclusion: Physicians need specialized knowledge in order to decide whether a skin tumor in a child should be excised, non-surgically treated, or further evaluated, or whether it can be safely left untreated because of the likelihood of spontaneous remission.}, language = {en} } @article{WilliamsMachannKuehleretal.2011, author = {Williams, Tatjana and Machann, Wolfram and K{\"u}hler, Leif and Hamm, Henning and M{\"u}ller-H{\"o}cker, Josef and Zimmer, Michael and Ertl, Georg and Ritter, Oliver and Beer, Meinrad and Sch{\"o}nberger, Jost}, title = {Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma}, series = {Clinical Research in Cardiology}, volume = {100}, journal = {Clinical Research in Cardiology}, number = {12}, doi = {10.1007/s00392-011-0345-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141198}, pages = {1087-1093}, year = {2011}, abstract = {Two sons of a consanguineous marriage developed biventricular cardiomyopathy. One boy died of severe heart failure at the age of 6 years, the other was transplanted because of severe heart failure at the age of 10 years. In addition, focal palmoplantar keratoderma and woolly hair were apparent in both boys. As similar phenotypes have been described in Naxos disease and Carvajal syndrome, respectively, the genes for plakoglobin (JUP) and desmoplakin (DSP) were screened for mutations using direct genomic sequencing. A novel homozygous 2 bp deletion was identified in an alternatively spliced region of DSP. The deletion 5208_5209delAG led to a frameshift downstream of amino acid 1,736 with a premature truncation of the predominant cardiac isoform DSP-1. This novel homozygous truncating mutation in the isoform-1 specific region of the DSP C-terminus caused Carvajal syndrome comprising severe early-onset heart failure with features of non-compaction cardiomyopathy, woolly hair and an acantholytic form of palmoplantar keratoderma in our patient. Congenital hair abnormality and manifestation of the cutaneous phenotype in toddler age can help to identify children at risk for cardiac death.}, language = {en} } @phdthesis{Storim2011, author = {Storim, Julian}, title = {Dynamic mapping of the immunological synapse in T cell homeostasis and activation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70114}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Polarity and migration are essential for T cell activation, homeostasis, recirculation and effector function. To address how T cells coordinate polarization and migration when interacting with dendritic cells (DC) during homeostatic and activating conditions, a low density collagen model was used for confocal live-cell imaging and high-resolution 3D reconstruction of fixed samples. During short-lived (5 to 15 min) and migratory homeostatic interactions, recently activated T cells simultaneously maintained their amoeboid polarization and polarized towards the DC. The resulting fully dynamic and asymmetrical interaction plane comprised all compartments of the migrating T cell: the actin-rich leading edge drove migration but displayed only moderate signaling activity; the mid-zone mediated TCR/MHC induced signals associated with homeostatic proliferation; and the rear uropod mediated predominantly MHC independent signals possibly connected to contact-dependent T cell survival. This "dynamic immunological synapse" with distinct signaling sectors enables moving T cells to serially sample antigen-presenting cells and resident tissue cells and thus to collect information along the way. In contrast to homeostatic contacts, recognition of the cognate antigen led to long-lasting T cell/DC interaction with T cell rounding, disintegration of the uropod, T cell polarization towards the DC, and the formation of a symmetrical contact plane. However, the polarity of the continuously migrating DC remained intact and T cells aggregated within the DC uropod, an interesting cellular compartment potentially involved in T cell activation and regulation of the immune response. Taken together, 3D collagen facilitates high resolution morphological studies of T cell function under realistic, in vivo-like conditions.}, subject = {T-Lymphozyt}, language = {en} } @phdthesis{Erdem2011, author = {Erdem, Chris Jakob}, title = {Immunhistochemische Analyse von P16 in obligaten und potentiellen Pr{\"a}kanzerosen und Tumoren der Mundh{\"o}hle}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71062}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Die Expression des p16-Tumorsuppressorgens spielt in der Fr{\"u}herkennung von Geb{\"a}rmutterhalskrebs eine außerordentlich wichtige Rolle. Hier dient p16INK4a als immunhistochemisch evaluierter Biomarker f{\"u}r pr{\"a}kanzer{\"o}se L{\"a}sionen der Zervix. In der vorliegenden Arbeit wurde die Expression des p16-Proteins immunhistologisch anhand obligaten Pr{\"a}kanzerosen, potentiell pr{\"a}kanzer{\"o}ser Entz{\"u}ndungen und Karzinomen der Mundh{\"o}hle untersucht. Hierzu wurden 80 F{\"a}lle aus dem histologischen Archiv der Klinik und Poliklinik f{\"u}r Dermatologie, Venerologie und Allergologie des Universit{\"a}ts-Klinikums W{\"u}rzburg sowie aus dem Institut f{\"u}r Pathologie der Universit{\"a}t W{\"u}rzburg verwendet. Die F{\"a}lle stammen aus dem Zeitraum von 2000 bis 2011. Ziel der vorliegenden Arbeit war zu untersuchen, inwiefern das p16INK4a-Protein als Biomarker f{\"u}r pr{\"a}maligne und maligne L{\"a}sionen fungieren kann. Die untersuchten Pr{\"a}parate beinhalteten orale Leukoplakien mit geringen und hoch dysplastischen Ver{\"a}nderungen sowie orale als auch extraorale Lichen planus und orale Plattenepithelkarzinome. Als Ergebnis l{\"a}sst sich festhalten, dass die p16-Expression der oralen Leukoplakien nicht mit dem vorliegenden Dysplasiegrad korrelierte und ausgesprochen schwach ausfiel. Die Plattenepithelkarzinome der Mundh{\"o}hle zeigten gr{\"o}ßtenteils (75\%) keine p16-Expression im invasiven Anteil des Tumors. Hier geht man davon aus, dass durch homozygote Deletionen, inaktivierende Mutationen sowie durch eine nicht korrekt ausgef{\"u}hrte Promotormethylierung die p16-Expression ausgeschaltet wird. Dar{\"u}ber hinaus wiesen die F{\"a}lle des Lichen planus eine zumeist stark positive Expression von p16INK4a auf, da 93,3 \% der oralen und 95\% der extraoralen Lichen planus positiv ausfielen. Verglichen mit oralen Leukoplakien weisen der orale und kutane Lichen planus ein sehr viel geringeres Risiko der malignen Transformation auf. Zusammenfassend l{\"a}sst sich sagen, dass die hier demonstrierten Ergebnisse die Hypothese zulassen, dass eine {\"U}berexpression des p16-Proteins das Risiko einer malignen Entartung niedrig h{\"a}lt. Ein Herunterfahren des p16-Tumorsuppressorgens kann somit ein erster Schritt der Genese eines malignen Tumors sein. Die Diskussion dieser Hypothesen sollte jedoch durch weiterf{\"u}hrende Untersuchungen best{\"a}tigt werden.}, subject = {p16 immunhistochemie}, language = {de} } @article{WobserGaiglTrautmann2011, author = {Wobser, Marion and Gaigl, Zeno and Trautmann, Axel}, title = {The concept of "compartment allergy": prilocaine injected into different skin layers}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68679}, year = {2011}, abstract = {We herein present a patient with delayed-type allergic hypersensitivity against prilocaine leading to spreading eczematous dermatitis after subcutaneous injections for local anesthesia with prilocaine. Prilocaine allergy was proven by positive skin testing and subcutaneous provocation, whereas the evaluation of other local anesthetics - among them lidocaine, articaine and mepivacaine - did not exhibit any evidence for cross-reactivity. Interestingly, our patient repeatedly tolerated strictly deep subcutaneous injection of prilocaine in provocation testing while patch and superficial subcutaneous application mounted strong allergic responses. We hypothesize, that lower DC density in deeper cutaneous compartments and/or different DC subsets exhibiting distinct functional immunomodulatory properties in the various layers of the skin may confer to the observed absence of clinical reactivity against prilocaine after deep subcutaneous injection. The term compartment allergy indicates that the route of allergen administration together with the targeted immunologic environment orchestrates on the immunologic outcome: overt T-cell mediated allergy or clinical tolerance.}, subject = {Medizin}, language = {en} } @article{HoubenHesbacherSchmidetal.2011, author = {Houben, Roland and Hesbacher, Sonja and Schmid, Corinna P. and Kauczok, Claudia S. and Flohr, Ulrike and Haferkamp, Sebastian and M{\"u}ller, Cornelia S. L. and Schrama, David and Wischhusen, J{\"o}rg and Becker, J{\"u}rgen C.}, title = {High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69012}, year = {2011}, abstract = {Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5-8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.}, subject = {Krebs }, language = {en} } @phdthesis{Hofmann2011, author = {Hofmann, Bernd}, title = {Bienen-/Wespengiftallergie: Wirksamkeit und Sicherheit einer Immuntherapie mit 100 µg Gift {\"u}ber 3 bis 5 Jahre}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57500}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Die Bienen-/Wespengiftallergie ist auf der einen Seite eine potentiell lebensbedrohliche IgE-vermittelte Allergiekrankheit, in Deutschland neben den Nahrungsmittelallergien die h{\"a}ufigste Ursache f{\"u}r eine t{\"o}dlich verlaufende Anaphylaxie. Auf der anderen Seite steht mit der Bienen-/Wespengift-spezifischen Immuntherapie (SIT) gerade f{\"u}r diese Allergie seit Jahrzehnten eine hochwirksame kausale Therapie zur Verf{\"u}gung. Placebokontrollierte Studien mit unbehandelten Patienten sind daher aus ethischen Gr{\"u}nden nicht vertretbar. Neue Erkenntnisse zur Sicherheit dieser Therapieform k{\"o}nnen nur aus der Verlaufsbeobachtung standardisiert behandelter Patientenkollektive gewonnen werden. Der besondere Wert der hier analysierten großen Patientenserie liegt vor allem darin, dass alle Patienten in einer Allergieambulanz (der Klinik und Poliklinik f{\"u}r Dermatologie, Venerologie und Allergologie) betreut wurden. Im gesamten Behandlungszeitraum aller 679 Patienten wurde die Diagnostik und Therapie der Bienen-/Wespengiftallergie hoch standardisiert durchgef{\"u}hrt und nicht ver{\"a}ndert. Die dadurch gleichbleibende Betreuung garantierten Qualit{\"a}t, Umfang und Homogenit{\"a}t der Dokumentation und damit die Vergleichbarkeit der retrospektiv erfassten Daten {\"u}ber den gesamten Zeitraum 1988 bis 2008. F{\"u}r die besonders wichtige Verlaufsbeobachtung nach Ende der spezifischen Immuntherapie (SIT) wurden zus{\"a}tzlich 616 der 679 Patienten aus Unterfranken und Umgebung direkt telefonisch befragt. Die bekannten charakteristischen Merkmale von Patienten mit Bienen-/Wespengiftallergie zeigten sich auch in dem untersuchten Kollektiv. Imkert{\"a}tigkeit ist die wahrscheinlichste Erkl{\"a}rung warum Bienengiftallergiker j{\"u}nger und h{\"a}ufiger m{\"a}nnlich sind. Die prognostisch bedeutsamen Schweregrade der allergischen Indikatorstichreaktion (das Stichereignis mit der schwersten anaphylaktischen Reaktion vor SIT) unterscheiden sich zwischen Bienen- und Wespengiftallergikern dagegen nicht. In den diagnostischen Untersuchungen vor und auch am Ende der SIT waren die Schwellenwertkonzentrationen des Intrakutan- und Pricktests bei Bienengiftallergikern im Vergleich zu den Wespengiftallergikern signifikant niedriger, die spezifischen IgE-Serumspiegel h{\"o}her. Die Wirksamkeit der SIT mit Bienengift betrug 89,0 \%. Nur 11,0 \% der Patienten (8 von 73 Patienten mit erneutem Bienenstich) hatten nach Beginn der SIT erneut eine}, subject = {Bienengiftallergie}, language = {de} } @article{BaptistellaFlorenceMassudaBroeckeretal.2011, author = {Baptistella Florence, Michelle Etienne and Massuda, Juliana Yumi and Br{\"o}cker, Eva-Bettina and Metze, Konradin and Cintra, Maria Leticia and de Souza, Elemir Macedo}, title = {Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers}, series = {CLINICS}, volume = {66}, journal = {CLINICS}, number = {3}, doi = {10.1590/S1807-59322011000300018}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133650}, pages = {465-468}, year = {2011}, abstract = {OBJECTIVE: To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma. INTRODUCTION: Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established. METHODS: We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas. RESULTS: The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. DISCUSSION: The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis. CONCLUSION: This study demonstrated the dependence of skin carcinogenesis on angiogenesis.}, language = {en} }