Osteossarcoma em maxila: relato de caso

ResumoO osteossarcoma é a neoplasia maligna mais comum do osso, ocorrendo com maior frequência nos ossos longos; nos maxilares é uma lesão rara. Os sintomas mais frequentes são o aumento de volume local, dor intensa e limitação funcional. O tratamento atual do osteossarcoma consiste em ressecção cirúrgica associada ou não à radioterapia e/ou quimioterapia. O objetivo deste trabalho é apresentar um caso de osteossarcoma no maxilar de um paciente de 24 anos do género masculino, abrangendo o palato duro, estendendo-se até o palato mole, com evolução de 6 meses. O diagnóstico foi estabelecido por achados clínicos, imagiológicos e histopatológicos. O paciente foi submetido a quimioterapia, mas faleceu passados 6 meses com o aparecimento de metástases.AbstractOsteosarcoma is the most common malignancy of bone, occurring more frequently in long bones, being rare in jaws. The most common symptoms are swelling, local pain and functional limitation; current treatment of osteosarcoma consists of surgical resection and additional chemotherapy. The objective of this work is to present a case of osteosarcoma of the maxilla of a patient 24 years old with a tumor involving the hard palate, extending to the soft palate, with an evolution of six months. The diagnosis was established by clinical, imaging and histopathology. The patient was subject to chemoterapy but died after 6 months with metastases

Molecular allergen profiling in horses by microarray reveals Fag e 2 from buckwheat as a frequent sensitizer.

BACKGROUND Companion animals are also affected by IgE-mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles. METHODS Custom-designed allergen microarray was produced on the basis of the ImmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction and urticaria or were clinically asymptomatic. RESULTS Horses showed individual IgE-binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S-albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet. CONCLUSION In line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen-specific preventive and therapeutic concepts

Allergenicity of type I allergens : examination on different levels of complexity

Ob ein Protein als Allergen wirken kann oder nicht hängt von vielerlei Faktoren ab. Diese reichen von der Struktur und enzymatischen Aktivität des Allergens selbst über Effekte von anderen Proteinen die gemeinsam mit dem Allergen aufgenommen werden bis zu kurzfristigen Einflüssen im Patienten selbst wie Medikation oder Erkrankungen. Um der komplexen Frage der Allergenität gerecht zu werden verwendeten wir daher einen mehrgleisigen Ansatz um verschiedene Aspekte zu untersuchen. Auf der kleinsten Größenebene, dem Epitop, konnten wir durch Selektion von anti-idiotypischen Spezifitäten aus einer Phagenbibliothek, welche das IgG Repertoir eines Graspollenallergikers repräsentiert eine Antikörperbindungsregion an der Interfaceregion der beiden Proteinketten des dimeren Graspollenallergens Phl p 1 charakterisieren. Die Rolle von individuellen Allergenen, welche jeweils auch über ihr allergenes Potential hinausgehen Eigenschaften besitzen welche potentiell das angeborene Immunsystem aktivieren könnten, in der Sensibilisierungsphase wurde in einem murinen Modell der atopischen Dermatitis (AD) untersucht. Dazu wurden die Hauptallergene der Hausstaubmilbe Der p 1 und Der p 2 in recombinanter Form epikutan appliziert. Dabei zeigte sich, dass diese starke Symptome auf der Haut auslösen obwohl nur modereate Mengen an spezischen Antikörpern produziert wurden. Um zu untersuchen welchen Impakt die Verdauung auf die Sensibilisierungsfähigkeit von Nahrungsmittelallergenen hat BALB/c Mäuse unter Einfluss von nicht verschreibungspflichtigen Medikamenten zur Behandlung von Sodbrennen wie Rennie®-Antazid, Rennie-Digestiv® oder Basenpulver mit Kabeljau gefüttert. Diese Magensäure neutralisierenden Substanzen führten zu einem erhöhten Risiko der Sensibilisierung durch den Fischextrakts. Zusammenfassend konnten wir in dieser Arbeit expemplarisch verschiedene Aspekte beschreiben, welche die Allergenität beinflussen. Diese reichen von der Proteinstruktur bis zum Einfluss von Medikation. Dies stellt die Komplexität der Frage, was ein Protein zum Allergen macht, exemplarisch dar und unterstreicht die Notwendigkeit einer systemischen Betrachtung dieses Problems.Until today no definite answer has been found as to the reason why a given protein can act as an allergen or is non-allergenic. Allergenicity is dependent on many diverse factors, ranging from protein structure to enzymatic activity, to interaction both with other allergens and non-allergenic matrix proteins. Transient influences present in the patient at the time of first allergen contact may also play a role. To tackle the high complexity of the problem of protein allergenicity, we used a multi-pronged approach to examine some of these aspects. On the lowest level of complexity, the epitope structure, we aimed to characterize the antibody binding site on the major grass pollen allergen Phl p 1. For this purpose we selected anti-idiotypic specificities from a Fab-display phage library presenting the IgG repertoire of a grass pollen allergic patient uncovering an epitope patch located at the interface region of the two peptide chains comprising the homo-dimeric allergen. The next level of complexity, the role of protein functions beside allergenicity was examined in a murine model of atopic dermatitis. For this purpose we used house dust mite allergens Der p 1 and Der p 2 as models, as these proteins possess characteristics potentially able to activate the innate immune systeme. Der p 1 is a cystein protease and Der p 2 has been implicated to be a functional mimic of MD-2, a part of the TLR 4 signaling complex. In this model, skin lesions and eosinophil infiltrates into the dermis were observed despite only moderate levels of specific antibodies. To examine the impact of digestion on allergenicity, the effects of common over-the-counter remedies for heartburn on the allergenic potential of codfish were investigated. We fed BALB/c with extract from this source under concomitant treatment with either Rennie®-Antazid, Rennie-Digestiv® or base powder. This study allowed us to show that indeed these acid-neutralizing compounds were able to heighten the allergenicity of the fish extract. Taken together, in this work we could show some examples of aspects influencing allergenicity, from protein structure and function to medical treatment having influence on the ability of proteins to sensitize patients. This underscores the complexity of the question of allergenicity and highlights the necessity of a multi-facetted approach to the problem.submitted by Anna LukschalAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. Spracheteilweise erschienen in: Clin Exp Allergy. 2010 Jul;40(7):1091-8 und The Open Allergy Journal 2011 p 16-23; teilweise submitted an: Experimental DermatologyWien, Med. Univ., Diss., 2011OeBB(VLID)171652

AllergoOncology:High innate IgE levels are decisive for the survival of cancer-bearing mice

Background Atopics have a lower risk for malignancies, and IgE targeted to tumors is superior to IgG in fighting cancer. Whether IgE-mediated innate or adaptive immune surveillance can confer protection against tumors remains unclear. Objective We aimed to investigate the effects of active and passive immunotherapy to the tumor-associated antigen HER-2 in three murine models differing in Epsilon-B-cell-receptor expression affecting the levels of expressed IgE. Methods We compared the levels of several serum specific anti-HER-2 antibodies (IgE, IgG1, IgG2a, IgG2b, IgA) and the survival rates in low-IgE M1M2 mice lacking the transmembrane/cytoplasmic domain of Epsilon-B-cell-receptors expressing reduced IgE levels, high-IgE KN1 mice expressing chimeric Epsilon-Gamma1-B-cell receptors with 4-6-fold elevated serum IgE levels, and wild type (WT) BALB/c. Prior engrafting mice with D2F2/E2 mammary tumors overexpressing HER-2, mice were vaccinated with HER-2 or vehicle control PBS using the Th2-adjuvant Al(OH) (active immunotherapy), or treated with the murine anti-HER-2 IgG1 antibody 4D5 (passive immunotherapy). Results Overall, among the three strains of mice, HER-2 vaccination induced significantly higher levels of HER-2 specific IgE and IgG1 in high-IgE KN1, while low-IgE M1M2 mice had higher IgG2a levels. HER-2 vaccination and passive immunotherapy prolonged the survival in tumor-grafted WT and low-IgE M1M2 strains compared with treatment controls; active vaccination provided the highest benefit. Notably, untreated high-IgE KN1 mice displayed the longest survival of all strains, which could not be further extended by active or passive immunotherapy. Conclusion Active and passive immunotherapies prolong survival in wild type and low-IgE M1M2 mice engrafted with mammary tumors. High-IgE KN1 mice have an innate survival benefit following tumor challenge.(VLID)490427

Anti-idiotypic Fab Fragments Image a Conserved N-terminal Epitope Patch of Grass Pollen Allergen Phl p 1

BACKGROUND AND AIMS: Naturally occurring anti-idiotypic antibodies structurally mimic the original antibody epitope. Anti-idiotypes, therefore, are interesting tools for the portrayal of conformational B-cell epitopes of allergens. In this study we used this strategy particularly for major timothy grass pollen (Phleum pratense) allergen Phl p 1. METHODS AND RESULTS: We used a combinatorial phage display library constructed from the peripheral IgG repertoire of a grass pollen allergic patient which was supposed to contain anti-idiotypic Fab specificities. Using purified anti-Phl p 1 IgG for biopanning, several Fab displaying phage clones could be isolated. 100 amplified colonies were screened for their binding capacity to anti-Phl p 1-specific antibodies, finally resulting in four distinct Fab clones according to sequence analysis. Interestingly, heavy chains of all clones derived from the same germ line sequence and showed high homology in their CDRs. Projecting their sequence information on the surface of the natural allergen Phl p 1 (PDB ID: 1N10) indicated matches on the N-terminal domain of the homo-dimeric allergen, including the bridging region between the two monomers. The resulting epitope patches were formed by spatially distant sections of the primary allergen sequence. CONCLUSION: In this study we report that anti-idiotypic specificities towards anti-Phl p 1 IgG, selected from a Fab library of a grass pollen allergic patient, mimic a conformational epitope patch being distinct from a previously reported IgE epitope area

Interleukin-10: An Anti-Inflammatory Marker To Target Atherosclerotic Lesions via PEGylated Liposomes

Atherosclerosis (AS) causes cardiovascular disease, which leads to fatal clinical end points like myocardial infarction or stroke, the most prevalent causes of death in developed countries. An early, noninvasive method of detection and diagnosis of atherosclerotic lesions is necessary to prevent and treat these clinical end points. Working toward this goal, we examined recombinant interleukin-10 (IL-10), stealth liposomes with nanocargo potency for NMRI relevant contrast agents, and IL-10 coupled to stealth liposomes in an ApoE-deficient mouse model using confocal laser-scanning microscopy (CLSM). Through <i>ex vivo</i> incubation and imaging with CLSM, we showed that fluorescently labeled IL-10 is internalized by AS plaques, and a low signal is detected in both the less injured aortic surfaces and the arteries of wild-type mice. <i>In vivo</i> experiments included intravenous injections of (i) fluorescent IL-10, (ii) IL-10 targeted carboxyfluorescin (CF−) labeled stealth liposomes, and (iii) untargeted CF-labeled stealth liposomes. Twenty-four hours after injection the arteries were dissected and imaged <i>ex vivo</i>. Compared to free IL-10, we observed a markedly stronger fluorescence intensity with IL-10 targeted liposomes at AS plaque regions. Moreover, untargeted CF-labeled liposomes showed only weak, unspecific binding. Neither free IL-10 nor IL-10 targeted liposomes showed significant immune reaction when injected into wild-type mice. Thus, the combined use of specific anti-inflammatory proteins, high payloads of contrast agents, and liposome particles should enable current imaging techniques to better recognize and visualize AS plaques for research and prospective therapeutic strategies