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1.
Langenbecks Arch Surg ; 406(4): 945-969, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33844077

RESUMEN

PURPOSE: Postoperative lymphorrhea can occur after different surgical procedures and may prolong the hospital stay due to the need for specific treatment. In this work, the therapeutic significance of the radiological management of postoperative lymphorrhea was assessed and illustrated. METHOD: A standardized search of the literature was performed in PubMed applying the Medical Subject Headings (MeSH) term "lymphangiography." For the review, the inclusion criterion was "studies with original data on Lipiodol-based Conventional Lymphangiography (CL) with subsequent Percutaneous Lymphatic Intervention (PLI)." Different exclusion criteria were defined (e.g., studies with <15 patients). The collected data comprised of clinical background and indications, procedural aspects and types of PLI, and outcomes. In the form of a pictorial essay, each author illustrated a clinical case with CL and/or PLI. RESULTS: Seven studies (corresponding to evidence level 4 [Oxford Centre for Evidence-Based Medicine]) accounting for 196 patients were included in the synthesis and analysis of data. Preceding surgery resulting in postoperative lymphorrhea included different surgical procedures such as extended oncologic surgery or vascular surgery. Central (e.g., chylothorax) and peripheral (e.g., lymphocele) types of postoperative lymphorrhea with a drainage volume of 100-4000 ml/day underwent CL with subsequent PLI. The intervals between "preceding surgery and CL" and between "CL and PLI" were 2-330 days and 0-5 days, respectively. CL was performed before PLI to visualize the lymphatic pathology (e.g., leakage point or inflow lymph ducts), applying fluoroscopy, radiography, and/or computed tomography (CT). In total, seven different types of PLI were identified: (1) thoracic duct (or thoracic inflow lymph duct) embolization, (2) thoracic duct (or thoracic inflow lymph duct) maceration, (3) leakage point direct embolization, (4) inflow lymph node interstitial embolization, (5) inflow lymph duct (other than thoracic) embolization, (6) inflow lymph duct (other than thoracic) maceration, and (7) transvenous retrograde lymph duct embolization. CL-associated and PLI-associated technical success rates were 97-100% and 89-100%, respectively. The clinical success rate of CL and PLI was 73-95%. CL-associated and PLI-associated major complication rates were 0-3% and 0-5%, respectively. The combined CL- and PLI-associated 30-day mortality rate was 0%, and the overall mortality rate was 3% (corresponding to six patients). In the pictorial essay, the spectrum of CL and/or PLI was illustrated. CONCLUSION: The radiological management of postoperative lymphorrhea is feasible, safe, and effective. Standardized radiological treatments embedded in an interdisciplinary concept are a step towards improving outcomes.


Asunto(s)
Quilotórax , Embolización Terapéutica , Linfocele , Quilotórax/diagnóstico por imagen , Quilotórax/etiología , Quilotórax/terapia , Aceite Etiodizado , Humanos , Linfografía , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/terapia , Conducto Torácico
2.
Br J Dermatol ; 178(2): 473-481, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28986976

RESUMEN

BACKGROUND: An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome. OBJECTIVES: To reach international consensus on a core outcome set (COS) for clinical research on peripheral vascular malformations: lymphatic (LM), venous (VM) and arteriovenous malformations (AVM). In this consensus study, we determined what domains should constitute the COS. METHODS: Thirty-six possibly relevant outcome domains were proposed to an international group of physicians, patients and the parents of patients. In a three-round e-Delphi process using online surveys, participants repeatedly rated the importance of these domains on a five-point Likert scale. Participants could also propose other relevant domains. This process was performed for LM, VM and AVM separately. Consensus was predefined as 80% agreement on the importance of a domain among both the physician group and the patient/parent group. Outcomes were then re-evaluated in an online consensus meeting. RESULTS: 167 physicians and 134 patients and parents of patients with LM (n = 50), VM (n = 71) and AVM (n = 29) participated in the study. After three rounds and a consensus meeting, consensus was reached for all three types of vascular malformations on the core domains of radiological assessment, physician-reported location-specific signs, patient-reported severity of symptoms, pain, quality of life, satisfaction and adverse events. Vascular malformation type-specific signs and symptoms were included for LM, VM and AVM, separately. CONCLUSIONS: Our recommendation is that therapeutic-efficacy studies on peripheral vascular malformations should measure at least these core outcome domains.


Asunto(s)
Malformaciones Vasculares/terapia , Malformaciones Arteriovenosas/terapia , Consenso , Técnica Delphi , Humanos , Sistema Linfático/anomalías , Resultado del Tratamiento
3.
Radiologe ; 57(2): 80-89, 2017 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-28130580

RESUMEN

CLINICAL/METHODICAL ISSUE: In the treatment of localized renal cell carcinoma, the lack of randomization in controlled trials on thermal ablation is a major limitation. The latter leads to significant study bias and it ultimately remains unclear whether the improved overall survival in favor of partial nephrectomy can actually be attributed to the treatment method. STANDARD RADIOLOGICAL METHODS: For T1a (≤4 cm) renal cell carcinoma without lymph node and distant metastases, excellent technical and clinical results have been described after imaging-guided radiofrequency ablation and cryoablation. METHODICAL INNOVATIONS: Low major complication rates, preservation of renal function and three-dimensional confirmation of negative ablation margins (A0 ablation) are the advantages of computed tomography (CT)-guided thermal ablation. PERFORMANCE: According to the results of controlled (non-randomized) trials on T1a renal cell cancer, the cancer-specific survival rates are comparable between ablative and surgical techniques. ACHIEVEMENTS: It is high time for prospective randomized controlled trials to define the actual value of percutaneous thermal ablation and partial nephrectomy in the treatment of T1a renal cell carcinoma. PRACTICAL RECOMMENDATIONS: Apart from localized renal cell carcinoma, angiomyolipoma and oncocytoma can be treated by thermal ablation. Transarterial embolization extends the radiological spectrum for the treatment of renal tumors, either as complementary embolization (e. g. before thermal ablation of T1a and T1b renal cell carcinoma), prophylactic embolization (e. g. angiomyolipoma >6 cm), preoperative embolization (e. g. before laparoscopic partial nephrectomy) or palliative embolization (e. g. in patients with symptomatic macrohematuria due to renal cell carcinoma).


Asunto(s)
Técnicas de Ablación/estadística & datos numéricos , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/cirugía , Neoplasias Renales/epidemiología , Neoplasias Renales/cirugía , Nefrectomía/estadística & datos numéricos , Sesgo , Carcinoma de Células Renales/diagnóstico por imagen , Medicina Basada en la Evidencia , Humanos , Neoplasias Renales/diagnóstico por imagen , Selección de Paciente , Prevalencia , Pronóstico , Factores de Riesgo , Resultado del Tratamiento
4.
J Synchrotron Radiat ; 23(Pt 6): 1395-1400, 2016 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-27787245

RESUMEN

A mapping technique has been developed where a sub-micrometer focused polychromatic X-ray beam is scanned across a stationary sample instead of scanning the sample in front of the X-ray microbeam. This method is applied to a gold nanowire during its mechanical loading using the tip of an atomic force microscope. During the loading process, such a sample is `accelero-phobic', i.e. the sample scanning stages must not to be moved to avoid parasitic additional load. Without beam scanning, only one single position within the sample can be probed during the test. The probed material point may even change because of drifts or movements induced by the test itself. The new scanning approach facilitates the in situ mapping of the entire wire giving access to the evolution of the wire shape as well as to the boundary conditions. This novel scanning technique opens promising perspectives for studies where sample motion is forbidden because of the sample environment.

5.
J Exp Bot ; 67(3): 961-77, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26663471

RESUMEN

Identifying key performance traits is essential for elucidating crop growth processes and breeding. In Salix spp., genotypic diversity is being exploited to tailor new varieties to overcome environmental yield constraints. Process-based models can assist these efforts by identifying key parameters of yield formation for different genotype×environment (G×E) combinations. Here, four commercial willow varieties grown in contrasting environments (west and south-east UK) were intensively sampled for growth traits over two 2-year rotations. A sink-source interaction model was developed to parameterize the balance of source (carbon capture/mobilization) and sink formation (morphogenesis, carbon allocation) during growth. Global sensitivity analysis consistently identified day length for the onset of stem elongation as most important factor for yield formation, followed by various 'sink>source' controlling parameters. In coastal climates, the chilling control of budburst ranked higher compared with the more eastern climate. Sensitivity to drought, including canopy size and rooting depth, was potentially growth limiting in the south-east and west of the UK. Potential yields increased from the first to the second rotation, but less so for broad- than for narrow-leaved varieties (20 and 47%, respectively), which had established less well initially (-19%). The establishment was confounded by drought during the first rotation, affecting broad- more than narrow-leaved canopy phenotypes (-29%). The analysis emphasized quantum efficiency at low light intensity as key to assimilation; however, on average, sink parameters were more important than source parameters. The G×E pairings described with this new process model will help to identify parameters of sink-source control for future willow breeding.


Asunto(s)
Agricultura , Simulación por Computador , Ambiente , Modelos Biológicos , Salix/crecimiento & desarrollo , Biomasa , Calibración , Genotipo , Luz , Conceptos Meteorológicos , Tallos de la Planta/anatomía & histología , Tallos de la Planta/efectos de la radiación , Reproducibilidad de los Resultados , Salix/efectos de la radiación
6.
Clin Oral Investig ; 20(4): 831-40, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26280753

RESUMEN

OBJECTIVES: The present study aimed to evaluate the suitability of self-etch adhesives for restoration of deciduous teeth compared with etch and rinse approaches. MATERIALS AND METHODS: One hundred twenty primary teeth were divided into five groups, each being assigned to an adhesive system. Self-etch adhesives XenoV (XV) and Clearfil S(3) Bond (CB), Prime&Bond NT with (PBE)/without preliminary etching (PBN), and Optibond FL (OBFL) as an etch and rinse system were included. Enamel and dentin specimens were prepared (n = 36/group), adhesives applied, and compomer cylinders polymerized. After 24-h storage in 37 °C distilled water and thermo-cycling (1440 cycles, 5/55 °C, 27 s), shear bond tests and fracture mode classification based on SEM investigation were performed. Statistical analysis involved ANOVA and Scheffé procedure with Bonferroni-Holm correction (p ≤ 0.005). RESULTS: High shear bond strengths to primary enamel were determined for PBE (mean [M] = 22.48 ± 7.7 MPa) > OBFL (M = 19.06 ± 5.62 MPa) > CB (M = 17.6 ± 6.55 MPa), and XV (M = 16.85 ± 5.38 MPa) and PBN (M = 8.26 ± 4.46 MPa) formed significantly less reliable enamel-resin interfaces (p ≤ 0.005). PBE generated the highest bond strength on primary dentin (M = 21.97 ± 8.02 MPa); significantly lower values were measured for XV (M = 13.44 ± 5.43 MPa) and OBFL (M = 12.92 ± 4.31 MPa) (p ≤ 0.005). CONCLUSIONS: Adhesives requiring preliminary etching ensure optimal bond strength to primary enamel. If separate etching is to be avoided, selected self-etch adhesives obtain acceptable shear bond values on primary enamel and dentin. CLINICAL RELEVANCE: The treatment of pediatric patients presents a great challenge in dental practice, and optimization of treatment processes is important.


Asunto(s)
Grabado Ácido Dental , Adhesivos , Recubrimientos Dentinarios , Recubrimiento Dental Adhesivo , Esmalte Dental , Dentina , Humanos , Ensayo de Materiales , Cementos de Resina , Resistencia al Corte , Diente Primario
7.
ScientificWorldJournal ; 2016: 7959273, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27430013

RESUMEN

For the purpose of erosion prevention the present study aimed to compare the efficacy of two biomimetic products and a fluoride solution to optimize the protective properties of the pellicle. After 1 min of in situ pellicle formation on bovine enamel slabs, 8 subjects adopted CPP-ACP (GC Tooth Mousse), a mouthwash with hydroxyapatite microclusters (Biorepair), or a fluoride based mouthwash (elmex Kariesschutz) for 1 min each. Afterwards, samples were exposed in the oral cavity for 28 min. Native enamel slabs and slabs exposed to the oral cavity for 30 min without any rinse served as controls. After oral exposure, slabs were incubated in HCl (pH values 2, 2.3, and 3) for 120 s and kinetics of calcium and phosphate release were measured photometrically; representative samples were evaluated by SEM and TEM. The physiological pellicle reduced demineralization at all pH values; the protective effect was enhanced by fluoride. The biomimetic materials also reduced ion release but their effect was less pronounced. SEM indicated no layer formation after use of the different products. However, TEM confirmed the potential accumulation of mineral components at the pellicle surface. The tested products improve the protective properties of the in situ pellicle but not as effectively as fluorides.


Asunto(s)
Fosfatos de Calcio/farmacología , Caseínas/farmacología , Durapatita/farmacología , Fluoruros/farmacología , Erosión de los Dientes/tratamiento farmacológico , Animales , Materiales Biomiméticos/farmacología , Bovinos , Esmalte Dental , Técnicas In Vitro , Antisépticos Bucales/farmacología
8.
Herz ; 39(5): 567-75, 2014 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-24902533

RESUMEN

Although ethics committees are well established in the medical sciences for human clinical trials, animal research and scientific integrity, the development of clinical ethics in German hospitals started much later during the first decade of the twenty-first century. Clinical ethics consultation should be pragmatic and problem-centered and can be defined as an ethically qualified and informed conflict management within a given legal framework to deal with and resolve value-driven, normative problems in the care of patients. Clinical ethics consultations enable shared clinical decision-making of all parties (e.g. clinicians, patients, family and surrogates) involved in a particular patient's care. The clinical ethicist does not act as an ethics expert by making independent recommendations or decisions; therefore, the focus is different from other medical consultants. Ethics consultation was first established by healthcare ethics committees (HEC) or clinical ethics consultation (CEC) groups which were called in to respond to an ethically problematic situation. To avoid ethical dilemmas or crises and to act preventively with regard to ethical issues in individual patients, an ethics liaison service is an additional option to ethics case consultations which take place on a regular basis by scheduled ethics rounds during the normal ward rounds. The presence of the ethicist offers some unique advantages: it allows early recognition of even minor ethical problems and accommodates the dynamics of ethical and clinical goal-setting in the course of patient care. Most importantly, regular and non-authoritative participation of the ethicist in normal ward rounds allows continuous ethical education of the staff within the everyday clinical routine. By facilitating clinical ethical decision-making, the ethicist seeks to empower physicians and medical staff to deal appropriately with ethical problems by themselves. Because of this proactive approach, the ethics liaison service can make a significant contribution to preventative ethics in reducing the number of emerging ethical problems to the satisfaction of all parties involved.


Asunto(s)
Centros Médicos Académicos/ética , Centros Médicos Académicos/tendencias , Comités de Ética Clínica/tendencias , Ética Institucional , Ética Médica , Derivación y Consulta/ética , Derivación y Consulta/tendencias , Toma de Decisiones/ética , Atención a la Salud/ética , Alemania , Humanos , Programas Nacionales de Salud/ética , Poder Psicológico , Solución de Problemas
9.
Unfallchirurg ; 117(1): 72-4, 2014 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-23483252

RESUMEN

The occurrence of aortic dissections after deceleration trauma is commonplace but aortic injuries after blunt trauma are extremely rare complications. We report a case of an acute aortic rupture accompanied by a type B dissection after a skiing accident with blunt thoracic trauma and renal contusion. The leading symptom was the onset of hematuria 12 h later. The computed tomography (CT) angiography permitted the exact diagnosis and the patient was transferred for acute thoracic endovascular aortic repair. This regimen resulted in the patient achieving a stable condition and potentially harmful complications could be avoided.


Asunto(s)
Disección Aórtica/cirugía , Rotura de la Aorta/cirugía , Traumatismos en Atletas/cirugía , Traumatismo Múltiple/cirugía , Esquí/lesiones , Heridas no Penetrantes/cirugía , Accidentes , Anciano , Disección Aórtica/diagnóstico , Rotura de la Aorta/diagnóstico , Traumatismos en Atletas/diagnóstico , Humanos , Masculino , Traumatismo Múltiple/diagnóstico , Resultado del Tratamiento , Heridas no Penetrantes/diagnóstico
10.
J Bacteriol ; 195(5): 977-89, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23243307

RESUMEN

The envelope of Bacillus anthracis encompasses a proteinaceous S-layer with two S-layer proteins (Sap and EA1). Protein assembly in the envelope of B. anthracis requires S-layer homology domains (SLH) within S-layer proteins and S-layer-associated proteins (BSLs), which associate with the secondary cell wall polysaccharide (SCWP), an acetylated carbohydrate that is tethered to peptidoglycan. Here, we investigated the contributions of two putative acetyltransferases, PatA1 and PatA2, on SCWP acetylation and S-layer assembly. We show that mutations in patA1 and patA2 affect the chain lengths of B. anthracis vegetative forms and perturb the deposition of the BslO murein hydrolase at cell division septa. The patA1 and patA2 mutants are defective for the assembly of EA1 in the envelope but retain the ability of S-layer formation with Sap. SCWP isolated from the patA1 patA2 mutant lacked acetyl moieties identified in wild-type polysaccharide and failed to associate with the SLH domains of EA1. A model is discussed whereby patA1- and patA2-mediated acetylation of SCWP enables the deposition of EA1 as well as BslO near the septal region of the B. anthracis envelope.


Asunto(s)
Acetiltransferasas/metabolismo , Bacillus anthracis/enzimología , Pared Celular/metabolismo , Glicoproteínas de Membrana/biosíntesis , Polisacáridos Bacterianos/metabolismo , Acetilación , Acetiltransferasas/genética , Bacillus anthracis/genética , Bacillus anthracis/metabolismo , Bacillus subtilis/enzimología , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Mutación , N-Acetil Muramoil-L-Alanina Amidasa/metabolismo
11.
Infect Immun ; 81(3): 1008-17, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23319564

RESUMEN

Bacillus cereus strains harboring a pXO1-like virulence plasmid cause respiratory anthrax-like disease in humans, particularly in welders. We developed mouse models for intraperitoneal as well as aerosol challenge with spores of B. cereus G9241, harboring pBCXO1 and pBC218 virulence plasmids. Compared to wild-type B. cereus G9241, spores with a deletion of the pBCXO1-carried protective antigen gene (pagA1) were severely attenuated, whereas spores with a deletion of the pBC218-carried protective antigen homologue (pagA2) were not. Anthrax vaccine adsorbed (AVA) immunization raised antibodies that bound and neutralized the pagA1-encoded protective antigen (PA1) but not the PA2 orthologue encoded by pagA2. AVA immunization protected mice against a lethal challenge with spores from B. cereus G9241 or B. cereus Elc4, a strain that had been isolated from a fatal case of anthrax-like disease. As the pathogenesis of B. cereus anthrax-like disease in mice is dependent on pagA1 and PA-neutralizing antibodies provide protection, AVA immunization may also protect humans from respiratory anthrax-like death.


Asunto(s)
Bacillus cereus/inmunología , Vacunas Bacterianas/inmunología , Infecciones por Bacterias Grampositivas/prevención & control , Infecciones del Sistema Respiratorio/prevención & control , Animales , Femenino , Infecciones por Bacterias Grampositivas/microbiología , Ratones , Ratones Endogámicos C57BL , Mutación , Infecciones del Sistema Respiratorio/microbiología
12.
Caries Res ; 47(2): 150-61, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23207875

RESUMEN

AIM: The study aimed to investigate the effect of a customary fluoride solution, containing sodium fluoride and amine fluoride, on initial biofilm formation on enamel and dentin in situ compared directly to chlorhexidine. METHODS: Bovine enamel and dentin specimens were mounted on maxillary splints carried by 9 subjects. After 1 min of pellicle formation, rinses with tap water (control), chlorhexidine (meridol med CHX 0.2%, GABA) and a fluoride mouthrinse (elmex, GABA) were performed for 1 min. Subsequently, the slabs were carried for another 8 h. The adherent bacteria were determined by DAPI staining, live-dead staining and determination of colony-forming units after desorption; glucan formation was visualized with concanavalin A. Additionally, energy-dispersive X-ray spectroscopy (EDX) analysis of the in situ biofilm layers was conducted, and contact angle measurements were performed. Statistical evaluation was performed by means of the Kruskal-Wallis test followed by the Mann-Whitney U test (p < 0.05). RESULTS: In the control group, significantly higher amounts of adherent bacteria were detected on dentin (4.8 × 10(6) ± 5.4 × 10(6) bacteria/cm(2)) than on enamel (1.2 × 10(6) ± 1.5 × 10(6) bacteria/cm(2), DAPI). Chlorhexidine significantly reduced the amount of adherent bacteria (dentin: 2.8 × 10(5) ± 3.4 × 10(5) bacteria/cm(2); enamel: 4.2 × 10(5) ± 8.7 × 10(5) bacteria/cm(2)). Rinses with the fluoride solution also significantly reduced bacterial adherence to dentin (8.1 × 10(5) ± 1.5 × 10(6) bacteria/cm(2)). Fluoride could not be detected by EDX analysis of the biofilms. Fluoride mouthrinsing did not influence the wettability of the pellicle-covered enamel surface. CONCLUSION: In addition to the reduction of demineralization and antibacterial effects, fluorides inhibit initial biofilm formation on dental hard tissues considerably, especially on dentin.


Asunto(s)
Biopelículas/efectos de los fármacos , Cariostáticos/uso terapéutico , Esmalte Dental/microbiología , Dentina/microbiología , Fluoruros/uso terapéutico , Antisépticos Bucales/uso terapéutico , Adulto , Aminas/uso terapéutico , Animales , Antiinfecciosos Locales/uso terapéutico , Adhesión Bacteriana/efectos de los fármacos , Carga Bacteriana/efectos de los fármacos , Bovinos , Clorhexidina/uso terapéutico , Colorantes , Película Dental/fisiología , Diaminas/uso terapéutico , Combinación de Medicamentos , Colorantes Fluorescentes , Humanos , Indoles , Compuestos Orgánicos , Propidio , Fluoruro de Sodio/uso terapéutico , Espectrometría por Rayos X , Fluoruros de Estaño/uso terapéutico , Agua/química , Humectabilidad , Adulto Joven
13.
Ann Oncol ; 23(8): 2185-2190, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22317770

RESUMEN

BACKGROUND: Ewing's sarcoma (ES) is the second most common bone or soft-tissue sarcoma in childhood and adolescence and features a high propensity to metastasize. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is a membrane-bound mesenchymal stem cell marker highly expressed in ES. Here, we investigated the role of STEAP1 as an immunohistological marker for outcome prediction in patients with ES. PATIENTS AND METHODS: Membranous STEAP1 immunoreactivity was analyzed using immunohistochemistry in 114 primary pre-chemotherapy ES of patients diagnosed from 1983 to 2010 and compared with clinical parameters and patient outcome. Median follow-up was 3.85 years (range 0.43-17.51). RESULTS: A total of 62.3% of the ES samples displayed detectable STEAP1 expression with predominant localization of the protein at the plasma membrane. High membranous STEAP1 immunoreactivity was found in 53.5%, which correlated with better overall survival (P=0.021). Accordingly, no or low membranous STEAP1 expression was identified as an independent risk factor in multivariate analysis (hazard ratio 2.65, P=0.036). CONCLUSION: High membranous STEAP1 expression predicts improved outcome and may help to define a specific subgroup of ES patients, who might benefit from adapted therapy regimens.


Asunto(s)
Antígenos de Neoplasias/biosíntesis , Oxidorreductasas/biosíntesis , Sarcoma de Ewing/inmunología , Adolescente , Adulto , Biomarcadores de Tumor/biosíntesis , Membrana Celular/enzimología , Membrana Celular/inmunología , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , Persona de Mediana Edad , Análisis Multivariante , Sarcoma de Ewing/enzimología , Adulto Joven
14.
Klin Padiatr ; 224(6): 353-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22821288

RESUMEN

BACKGROUND: Risk stratification criteria for patients with Ewing's sarcoma family of tumors (ESFT) are still limited. We hypothesized divergent human leukocyte antigen (HLA) patterns in ESFT patients and compared HLA-A, -B and -DR phenotype frequencies of patients with advanced ESFT with those of healthy controls. PATIENTS: HLA types of all German Caucasian patients with advanced ESFT and available HLA-A, -B and -DR data registered in the European Group for Blood and Marrow Transplantation, Paediatric Registry for Stem Cell Transplantation and the MetaEICESS data bases (study group, n=30) were retrospectively compared with HLA types of healthy German stem cell donors (control group, n=8 862 for single HLA frequencies and n=8 839 for allele combinations). Study group patients had been immuno-typed due to eligibility for allogeneic stem cell transplantation for high risk of treatment failure, and thus constituted a selected subgroup of ESFT patients. RESULTS: After Bonferroni correction for multiple testing (PC), phenotype frequencies of HLA-A24 remained significantly higher in the study group compared to controls (PC<0.05). Furthermore, several HLA combinations were significantly more frequent in the study group compared to controls (all PC<0.05). CONCLUSION: We report an increased incidence of circumscribed HLA patterns in German Caucasians with advanced ESFT. The possible clinical significance of this observation has to be re-assessed in prospective trials comprising larger ESFT patient numbers of all risk groups.


Asunto(s)
Donantes de Sangre , Trasplante de Médula Ósea , Neoplasias Óseas/genética , Neoplasias Óseas/terapia , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Trasplante de Células Madre Hematopoyéticas , Sarcoma de Ewing/genética , Sarcoma de Ewing/terapia , Donantes de Tejidos , Adolescente , Adulto , Neoplasias Óseas/patología , Niño , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Genética de Población , Alemania , Humanos , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Estudios Retrospectivos , Sarcoma de Ewing/patología , Adulto Joven
15.
J Dent Res ; 101(2): 151-157, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34515563

RESUMEN

Periodontitis is characterized by alveolar bone loss leading to tooth loss. A small proportion of patients develop severe periodontitis at the juvenile or adolescent age without exposure to the main risk factors of the disease. It is considered that these cases carry rare variants with large causal effects, but the specific variants are largely unknown. In this study, we performed exome sequencing of 5 families with children who developed stage IV, grade C, periodontitis between 3 and 18 y of age. In 1 family, we found compound heterozygous variants in the gene CTSC (p.R272H, p.G139R), 1 of which was previously identified in a family with prepubertal periodontitis. Subsequent targeted resequencing of the CTSC gene in 24 patients <25 y of age (stage IV, grade C) identified the known mutation p.I453V (odds ratio = 4.06, 95% CI = 1.6 to 10.3, P = 0.001), which was previously reported to increase the risk for adolescent periodontitis. An affected sibling of another family carried a homozygous deleterious mutation in the gene TUT7 (p.R560Q, CADD score >30 [Combined Annotation Dependent Depletion]), which is implicated in regulation of interleukin 6 expression. Two other affected siblings shared heterozygous deleterious mutations in the interacting genes PADI1 and FLG (both CADD = 36), which contribute to the integrity of the environment-tissue barrier interface. Additionally, we found predicted deleterious mutations in the periodontitis risk genes ABCA1, GLT6D1, and SIGLEC5. We conclude that the CTSC variants p.R272H and p.I453V have different expressivity and diagnostic relevance for prepubertal and adolescent periodontitis, respectively. We propose additional causal variants for early-onset periodontitis, which also locate within genes that carry known susceptibility variants for common forms. However, the genetic architecture of juvenile periodontitis is complex and differs among the affected siblings of the sequenced families.


Asunto(s)
Periodontitis Agresiva , Adolescente , Periodontitis Agresiva/genética , Catepsina C/genética , Exoma/genética , Humanos , Mutación , Linaje , Análisis de Secuencia de ADN , Secuenciación del Exoma
16.
Br J Cancer ; 104(6): 948-56, 2011 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-21407224

RESUMEN

BACKGROUND: The development of a successful immunotherapy is hampered by an ineffective T-cell repertoire against tumour antigens and the inability of the patient's immune system to overcome tolerance-inducing mechanisms. Here, we test the specific recognition and lytical potential of allo-restricted CD8(+) T cells against Ewing tumour (ET) associated antigens Enhancer of Zeste, Drosophila Homolog 2 (EZH2), and Chondromodulin-I (CHM1) identified through previous microarray analysis. METHODS: Following repetitive CHM1(319) (VIMPCSWWV) and EZH2(666) (YMCSFLFNL) peptide-driven stimulations with HLA-A 0201(+) dendritic cells (DC), allo-restricted HLA-A 0201(-) CD8(+) T cells were stained with HLA-A 0201/peptide multimers, sorted and expanded by limiting dilution. RESULTS: Expanded T cells specifically recognised peptide-pulsed target cells or antigen-transfected cells in the context of HLA-A 0201 and killed HLA-A 0201(+) ET lines expressing the antigen while HLA-A 0201(-) ET lines were not affected. Furthermore, adoptively transferred T cells caused significant ET growth delay in Rag2(-/-)γ(C)(-/-) mice. Within this context, we identified the CHM1(319) peptide as a new candidate target antigen for ET immunotherapy. CONCLUSION: These results clearly identify the ET-derived antigens, EZH2(666) and CHM1(319), as suitable targets for protective allo-restricted human CD8(+) T-cell responses against non-immunogenic ET and may benefit new therapeutic strategies in ET patients treated with allogeneic stem cell transplantation.


Asunto(s)
Antígenos de Neoplasias/inmunología , Neoplasias Óseas/patología , Isoantígenos/inmunología , Sarcoma de Ewing/patología , Linfocitos T Citotóxicos/inmunología , Animales , Antígenos de Neoplasias/metabolismo , Neoplasias Óseas/inmunología , Línea Celular Tumoral , Proliferación Celular , Células Cultivadas , Citotoxicidad Inmunológica/inmunología , Proteínas de Unión al ADN/genética , Regulación hacia Abajo , Humanos , Inmunoterapia Adoptiva , Isoantígenos/metabolismo , Células K562 , Ratones , Ratones Noqueados , Sarcoma de Ewing/inmunología , Especificidad del Receptor de Antígeno de Linfocitos T/inmunología , Linfocitos T Citotóxicos/metabolismo
17.
Nat Med ; 4(5): 627-30, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9585241

RESUMEN

Cytotoxic T lymphocyte (CTL) mediated tumor immunity against major histocompatibility antigen (MHC) class I-positive but class II-negative tumors often requires help from CD4+ T cells. These CD4 cells are activated by MHC class II-positive cells that present tumor derived antigens. Considering that different antigen presenting cells, such as B cells, macrophages and dendritic cells compete for antigen and influence the outcome of an immune response, we analyzed tumor immunity in B cell-deficient mice. These mice appear normal with regard to T cell immunity and tolerance to some pure foreign antigens. We show here that the low immunogenicity of tumors is caused by B cells whose presence in the priming phase results in disabled CD4+ T cell help for CTL mediated tumor immunity. Instead, in the presence of B cells, a non-protective humoral immune response is induced. Our results may explain the enigmatic observation that tumor-reactive antibodies occur frequently in cancer patients.


Asunto(s)
Adenocarcinoma/inmunología , Linfocitos B/inmunología , Neoplasias Mamarias Experimentales/inmunología , Linfocitos T/inmunología , Animales , Anticuerpos Antineoplásicos/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Ratones , Ratones Mutantes
18.
ACS Appl Mater Interfaces ; 13(3): 4750-4760, 2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33443407

RESUMEN

Near the interface of two contacting metallic bodies in relative motion, the microstructure changes. This modified microstructure leads to changes in material properties and thereby influences the tribological behavior of the entire contact. Tribological properties such as the friction coefficient and wear rate are controlled by the microstructure, while the elementary mechanisms for microstructural changes are not sufficiently understood. In this paper, the influence of the normal load and the size of the counter body on the initiation of a tribologically induced microstructure in copper after a single sliding pass is revealed. A systematic variation in the normal load and sphere diameter resulted in maximum Hertzian contact pressures between 530 MPa and 1953 MPa. Scanning electron microscopy, focused ion beam, and transmission electron microscopy were used to probe the subsurface deformation. Irrespective of the normal load and the sphere diameter, a sharp line-like feature consisting of dislocations, the so-called dislocation trace line, was identified in the subsurface area at depths between 100 nm and 400 nm. For normal loads below 6.75 N, dislocation features are formed below this line. For higher normal loads, the microstructure evolution directly underneath the surface is mainly confined to the area between the sample surface and the dislocation trace line, which itself is located at increasing depth. Transmission Kikuchi diffraction and transmission electron microscopy demonstrate that the misorientation is predominantly concentrated at the dislocation trace line. The results disclose a material rotation around axes roughly parallel to the transverse direction. This study demonstrates the generality of the trace line phenomena over a wide range of loads and contact pressures and the complexity of subsurface processes under a sliding contact and provides the basis for modeling the early stages in the microstructure evolution.

19.
J Appl Crystallogr ; 54(Pt 1): 80-86, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33833642

RESUMEN

This article reports on energy-dispersive micro Laue (µLaue) diffraction of an individual gold nanowire that was mechanically deformed in three-point bending geometry using an atomic force microscope. The nanowire deformation was investigated by scanning the focused polychromatic X-ray beam along the nanowire and recording µLaue diffraction patterns using an energy-sensitive pnCCD detector that permits measurement of the angular positions of the Laue spots and the energies of the diffracted X-rays simultaneously. The plastic deformation of the nanowire was shown by a bending of up to 3.0 ± 0.1°, a torsion of up to 0.3 ± 0.1° and a maximum deformation depth of 80 ± 5 nm close to the position where the mechanical load was applied. In addition, extended Laue spots in the vicinity of one of the clamping points indicated the storage of geometrically necessary dislocations with a density of 7.5 × 1013 m-2. While µLaue diffraction with a non-energy-sensitive detector only gives access to the deviatoric strain, the energy sensitivity of the employed pnCCD offers absolute strain measurements with a resolution of 1%. Here, the residual strain after complete unloading of the nanowire amounted to maximum tensile and compressive strains of the order of +1.2 and -3%, which is comparable to the actual resolution limit. The combination of white-beam µLaue diffraction using an energy-sensitive pixel detector with nano-mechanical testing opens up new possibilities for the study of mechanical behavior at the nanoscale.

20.
Genes Immun ; 11(1): 45-54, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19829306

RESUMEN

Periodontal diseases are complex inflammatory diseases and affect up to 20% of the worldwide population. An unbalanced reaction of the immune system toward microbial pathogens is considered as the key factor in the development of periodontitis. Defensins have a strong antimicrobial function and are important contributors of the immune system toward maintaining health. Here, we present the first systematic association study of DEFB1. Using a haplotype-tagging single nucleotide polymorphism (SNP) approach, including described promoter SNPs of DEFB1, we investigated the associations of the selected variants in a large population (N=1337 cases and 2887 ethnically matched controls). The 3' untranslated region SNP, rs1047031, showed the most significant association signal for homozygous carriers of the rare A allele (P=0.002) with an increased genetic risk of 1.3 (95% confidence interval: 1.11-1.57). The association was consistent with the specific periodontitis forms: chronic periodontitis (odds ratio=2.2 (95% confidence interval: 1.16-4.35), P=0.02), and aggressive periodontitis (odds ratio=1.3 (95% confidence interval 1.04-1.68), P=0.02). Sequencing of regulatory and exonic regions of DEFB1 identified no other associated variant, pointing toward rs1047031 as likely being the causative variant. Prediction of microRNA targets identified a potential microRNA-binding site at the position of rs1047031.


Asunto(s)
Regiones no Traducidas 3'/genética , Periodontitis Agresiva/genética , Periodontitis Crónica/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , beta-Defensinas/genética , Adulto , Periodontitis Agresiva/metabolismo , Periodontitis Agresiva/patología , Periodontitis Crónica/metabolismo , Periodontitis Crónica/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , beta-Defensinas/metabolismo
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