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1.
Clin Exp Dermatol ; 47(5): 903-909, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34826169

RESUMEN

BACKGROUND: The lack of validated and responsive outcome measures in the management of frontal fibrosing alopecia (FFA) significantly limits assessment of disease progression and treatment response over time. AIM: To understand how FFA extent and progression is currently assessed in UK specialist centres, to validate components of the International FFA Cooperative Group (IFFACG) statement on FFA assessment, and to identify pragmatic advice to improve FFA management in clinic. METHODS: Consultant dermatologists with a specialist interest in hair loss (n = 17) were invited to take part. Preferred FFA assessment methods were explored using questionnaires and clinical scenarios. Participants were asked to identify and mark the current hairline in 10 frontal and 10 temporal hairline images (Questionnaire 1), with assessment repeated 3 months later to assess intraindividual variability (Questionnaire 2) and 12 months later to test whether interindividual accuracy could be improved with simple instruction (Questionnaire 3). RESULTS: All 17 clinicians (100%) completed the questionnaire at each time interval. We identified a wide variation in assessment techniques used by our experts. Measurements were perceived as the most accurate method of assessing frontal recession whereas photography was preferred for temporal recession. Inter-rater reliability between clinicians measuring the frontal hairline scenarios indicated a moderate strength of agreement [intraclass coefficient (ICC) = 0.61; 95% CI 0.40-0.85], yet intrarater reliability was found to be poor with wide limits of agreement (-8.71 mm to 9.92 mm) on follow-up. Importantly, when clear guidance was provided on how the hairline should be identified (Questionnaire 3), inter-rater reliability improved significantly, with ICC = 0.70, suggesting moderate agreement (95% CI 0.51-0.89; P < 0.001). A similar pattern was seen with temporal hairline measurements, which again improved in accuracy with instruction. CONCLUSION: We found that accuracy of measurements in FFA can be improved with simple instruction and we have validated components of the IFFACG measurement recommendations.


Asunto(s)
Alopecia , Liquen Plano , Alopecia/diagnóstico , Alopecia/tratamiento farmacológico , Humanos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
2.
Mol Cell ; 49(3): 499-510, 2013 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-23290524

RESUMEN

Transforming growth factor ß (TGF-ß) is a potent antiproliferative factor in multiple types of cells. Deregulation of TGF-ß signaling is associated with the development of many cancers, including leukemia, though the molecular mechanisms are largely unclear. Here, we show that Casitas B-lineage lymphoma (c-Cbl), a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-ß signaling by neddylating and stabilizing the type II receptor (TßRII). Knockout of c-Cbl decreases the TßRII protein level and desensitizes hematopoietic stem or progenitor cells to TGF-ß stimulation, while c-Cbl overexpression stabilizes TßRII and sensitizes leukemia cells to TGF-ß. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TßRII at Lys556 and Lys567. Neddylation of TßRII promotes its endocytosis to EEA1-positive early endosomes while preventing its endocytosis to caveolin-positive compartments, therefore inhibiting TßRII ubiquitination and degradation. We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant TßRII neddylation and leukemia development.


Asunto(s)
Proteínas Serina-Treonina Quinasas/metabolismo , Proteolisis , Proteínas Proto-Oncogénicas c-cbl/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Ubiquitinación , Ubiquitinas/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Compartimento Celular/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Embrión de Mamíferos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Células HEK293 , Humanos , Leucemia/metabolismo , Leucemia/patología , Ratones , Datos de Secuencia Molecular , Mutación/genética , Proteína NEDD8 , Células 3T3 NIH , Unión Proteica/efectos de los fármacos , Proteolisis/efectos de los fármacos , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-cbl/química , Proteínas Proto-Oncogénicas c-cbl/genética , Receptor Tipo II de Factor de Crecimiento Transformador beta , Transducción de Señal/efectos de los fármacos , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Ubiquitinación/efectos de los fármacos
3.
PLoS Genet ; 14(9): e1007697, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30260955

RESUMEN

Lgr5+ intestinal stem cells are crucial for fast homeostatic renewal of intestinal epithelium and Wnt/ß-catenin signaling plays an essential role in this process by sustaining stem cell self-renewal. The poly(ADP-ribose) polymerases tankyrases (TNKSs) mediate protein poly-ADP-ribosylation and are involved in multiple cellular processes such as Wnt signaling regulation, mitotic progression and telomere maintenance. However, little is known about the physiological function of TNKSs in epithelium homeostasis regulation. Here, using Villin-creERT2;Tnks1-/-;Tnks2fl/fl (DKO) mice, we observed that loss of TNKSs causes a rapid decrease of Lgr5+ intestinal stem cells and magnified apoptosis in small intestinal crypts, leading to intestine degeneration and increased mouse mortality. Consistently, deletion of Tnks or blockage of TNKS activity with the inhibitor XAV939 significantly inhibits the growth of intestinal organoids. We further showed that the Wnt signaling agonist CHIR99021 sustains the growth of DKO organoids, and XAV939 does not cause growth retardation of Apc-/- organoids. Consistent with the promoting function of TNKSs in Wnt signaling, Wnt/ß-catenin signaling is significantly decreased with stabilized Axin in DKO crypts. Together, our findings unravel the essential role of TNKSs-mediated protein parsylation in small intestinal homeostasis by modulating Wnt/ß-catenin signaling.


Asunto(s)
Células Madre Adultas/fisiología , Proliferación Celular/fisiología , Mucosa Intestinal/fisiología , Tanquirasas/metabolismo , Animales , Técnicas de Cultivo de Célula , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Compuestos Heterocíclicos con 3 Anillos/farmacología , Mucosa Intestinal/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Organoides , Poli ADP Ribosilación/fisiología , Receptores Acoplados a Proteínas G/metabolismo , Tanquirasas/antagonistas & inhibidores , Tanquirasas/genética , Vía de Señalización Wnt/fisiología
4.
Public Health ; 196: 158-164, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34224976

RESUMEN

OBJECTIVES: It is important to understand the factors that can substantially decrease mortality rates, as multiple strategies have been implemented to improve economic development and national health in China. We aimed to describe the geographic variations and changes in the all-cause mortality rates in 2005-2015 and to investigate the social factors that tend to decline age-standardized all-cause mortality rates. STUDY DESIGN: Ecological study. METHODS: The data used came from China's National Census Survey in 2005, 2010 and 2015 and China National Statistical Yearbooks. We conducted provincial-level thematic mapping of age-standardized all-cause mortality rate trajectory groups in 2005-2015 by using ArcGIS. Generalized estimating equation (GEE) models were used to clarify the social factors that may have long-term relevance to declining age-standardized all-cause mortality rates. We compared the characteristics of the three provinces with the lowest mortality rates and the three provinces with the highest mortality rates to further understand the health disparities. RESULTS: The age-standardized mortality rates declined from 2000 to 2006 and from 2008 to 2019. Provinces in the low-trajectory tended to be located in the Northeast and Southeast China. The GEE results revealed that the greater the proportion of the population with senior high school education or above, the more families with flushing or pumping toilets that are not shared with other households, the more nurses per 1000 people and a stable economic growth rate were inclined to low age-standardized all-cause mortality rates (P < 0.05). CONCLUSIONS: Health disparities between different regions were still in existence even in 2015. Thus, it is critical to improve equality in economic and educational development, the distribution of healthcare professionals, and sanitation facilities, to ensure the equality of opportunities in terms of healthy lives and well-being for all. Furthermore, for developing countries, the improvement of national health urgently needs to prevent the health risks relevant to rapid industrialization and urbanization.


Asunto(s)
Desarrollo Económico , Factores Sociales , China/epidemiología , Países en Desarrollo , Escolaridad , Humanos , Mortalidad , Dinámica Poblacional
5.
Int Endod J ; 53(6): 733-741, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32009248

RESUMEN

AIM: To investigate whether the timing of root canal treatment (primary aim) or other endodontic parameters (secondary aim) is associated with the survival probability of autotransplanted third molars, using a nationwide population-based database. METHODOLOGY: A total of 1811 third molars autotransplanted between 2000 and 2013 met the inclusion criteria and were followed until the end of 2016. The teeth were classified into three groups on the basis of timing between root canal treatment and the autotransplantation: preoperative, extraoral and postoperative treatment groups. Univariate and multivariate Cox proportional hazards models were used to estimate the association between the timing of root canal treatment and the risk of tooth extraction after autotransplantation. RESULTS: Of the 1811 autotransplanted third molars, 462 were extracted, yielding a 17-year survival probability of 0.578. The survival probability of autotransplanted teeth that received postoperative root fillings after 17 years was 0.583, which was significantly higher than the 0.434 and 0.566 for teeth that received preoperative and extraoral root fillings, respectively (P = 0.0013). After adjustment for potential confounding factors, teeth that received postoperative root fillings were associated with a significantly lower tooth extraction hazard ratio (HR) compared with those that received extraoral root fillings (adjusted HR, 1.43; 95% confidence interval [CI], 1.14-1.78) and those that received preoperative root fillings (adjusted HR, 2.13; 95% CI, 1.19-3.82). Furthermore, the use of a rubber dam during postoperative root filling was associated with a significantly lower extraction rate after autotransplantation (adjusted HR, 0.54; 95% CI, 0.43-0.69). CONCLUSIONS: Postoperative root canal treatment resulted in a significantly lower extraction rate than did preoperative or extraoral root canal treatment amongst autotransplanted third molars during a mean follow-up period of 8.33 years. Rubber dam use is recommended during postoperative root canal treatment to improve the outcomes of autotransplantation.


Asunto(s)
Tercer Molar , Tratamiento del Conducto Radicular , Estudios de Seguimiento , Tasa de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento
6.
Gac Med Mex ; 155(Suppl 1): S1-S5, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31638604

RESUMEN

INTRODUCTION: An integral diagnosis of population contemplates within its components the population demographic analysis that is indispensable in the formulation of public policies. Population policy has a clearly transversal nature, since all actions in the economic, social, political, cultural, geographical, and obviously, demographic fields, have direct or indirect repercussions on it. OBJECTIVES: To determine the population dynamics and the global growth of the older adult population (OAP) of 60 years and more. MATERIALS AND METHODS: Cross-sectional, retrospective study. The information was obtained from the statistical yearbooks of the institute of security and social services of state workers, Mexico (1999-2015). Several demographic ageing indicators were analyzed. RESULTS: There was a constant increase in percentage points in the proportion of OAP, index of ageing, demographic dependency ratio of old age, global index of dependence, index of dependence of old people, and index of the active population structure (6, 19.2, 15.5, 8.5, 8.2 and 31.2%, respectively). The indicator global index of dependence and masculinity showed a decrease (0.6 and 3.1%, respectively). CONCLUSIONS: Our data provide evidence that suggests modifying and generating public policies according to OAP.


Asunto(s)
Envejecimiento , Política de Salud , Dinámica Poblacional/tendencias , Academias e Institutos/estadística & datos numéricos , Anciano , Estudios Transversales , Femenino , Transición de la Salud , Humanos , Masculino , México , Persona de Mediana Edad , Evaluación de Necesidades , Estudios Retrospectivos , Distribución por Sexo , Seguridad Social
7.
Gac Med Mex ; 155(Suppl 1): S10-S15, 2019.
Artículo en Español | MEDLINE | ID: mdl-31182880

RESUMEN

INTRODUCTION: An integral diagnosis of population contemplates within its components the population demographic analysis that is indispensable in the formulation of public policies. Population policy has a clearly transversal nature, since all actions in the economic, social, political, cultural, geographical, and obviously, demographic fields, have direct or indirect repercussions on it. OBJECTIVES: To determine the population dynamics and the global growth of the older adult population (OAP) of 60 years and more. MATERIALS AND METHODS: Cross-sectional, retrospective study. The information was obtained from the statistical yearbooks of the institute of security and social services of state workers, Mexico (1999-2015). Several demographic ageing indicators were analyzed. RESULTS: There was a constant increase in percentage points in the proportion of OAP, index of ageing, demographic dependency ratio of old age, global index of dependence, index of dependence of old people, and index of the active population structure (6, 19.2, 15.5, 8.5, 8.2 and 31.2%, respectively). The indicator global index of dependence and masculinity showed a decrease (0.6 and 3.1%, respectively). CONCLUSIONS: Our data provide evidence that suggests modifying and generating public policies according to OAP.


INTRODUCCIÓN: Un diagnóstico integral de población contempla dentro de sus componentes el análisis demográfico poblacional, que es indispensable en la formulación de las políticas públicas. La política de población tiene una naturaleza claramente transversal, pues todas las acciones en los ámbitos económico, social, político, cultural, geográfico, y obviamente, el demográfico, repercuten de una manera directa o indirecta en ella. OBJETIVOS: Determinar la dinámica poblacional y el crecimiento global de la población adulta mayor (PAM) de 60 años y más. MATERIALES Y MÉTODOS: Estudio transversal, retrospectivo. La información se obtuvo de los anuarios estadísticos institucionales del Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, México (de 1999-2015). Se analizaron varios indicadores demográficos de envejecimientoDE). RESULTADOS: Se observó un incremento constante en puntos porcentuales en la proporción de PAM, el índice de envejecimiento, la razón de dependencia demográfica de la vejez, índice global de dependencia, índice dependencia de viejos e índice de estructura de la población activa (6, 19.2, 15.5, 8.5, 8.2 y 31.2%, respectivamente). El indicador global de ancianidad y el índice de masculinidad mostraron una disminución (0.6 y 3.1%, respectivamente). CONCLUSIONES: Nuestros datos aportan evidencia que sugiere modificar y generar políticas públicas acordes a la PAM.


Asunto(s)
Dinámica Poblacional , Salud Pública , Política Pública , Academias e Institutos , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo
8.
J Acoust Soc Am ; 143(1): 538, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29390793

RESUMEN

The acoustic performance of a microperforated panel (MPP) absorber array in the nonlinear regime is investigated both numerically and experimentally. The MPP absorber array is constructed by three parallel-arranged MPP absorbers with different cavity depths. A finite element model is used to simulate the acoustic response of the MPP absorber array by adopting the nonlinear impedance model. The results show that the absorption of the MPP absorber array is affected by the incident sound pressure when it is beyond around 100 dB. With appropriate structural and perforation property of MPP, the MPP absorber array in non-linear regime outperforms that in linear regime due to the improvement of equivalent acoustic impedance matching with ambient air over wide frequency range. However, when the sound pressure excitation is too high, the local resonance effect of the resonating component MPP absorber is diminished and the sound absorption is decreased. With the carefully chosen properties of MPP, the performance degradation induced by panel vibration can be avoided. An optimal set of MPP properties to avoid the performance degradation induced by panel vibration is determined. The measured normal absorption coefficients of a prototype MPP absorber array compare well with the numerical prediction in both linear and nonlinear regimes.

9.
Eur J Immunol ; 46(10): 2401-2408, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27469439

RESUMEN

Expression of Lck, a T-cell lineage-specific tyrosine kinase critical for T-cell development and activation, can be mediated by either proximal or distal lck promoter. We generated BAC transgenic mice in which BAC lck promoter was deleted and bred these transgenes to an Lck knockout background. Lck-PROX mice, in which only the proximal promoter is functional, have maximal Lck protein and normal thymic development through CD4- CD8- double negative (DN) and CD4+ CD8+ double positive (DP) stages, but undetectable Lck later in development and reduced mature single positive thymocytes. In contrast, Lck-DIST mice, in which only distal promoter was functional, are deficient in Lck protein in DN and DP thymocytes and severely defective in early T-cell development, with a block at the DN3-DN4 beta checkpoint equivalent to complete Lck knockouts. The ability of the proximal lck promoter to support thymic development is independent of Fyn; while, in contrast, the distal lck promoter alone is completely unable to support development in the absence of Fyn. Notably, normal thymocyte development is restored by presence of both proximal and distal promoters, even when independently expressed on different lck genes. These results define distinct and complementary requirements for proximal and distal lck promoters during T-cell development.


Asunto(s)
Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/metabolismo , Proteínas Proto-Oncogénicas c-fyn/metabolismo , Linfocitos T/fisiología , Timocitos/fisiología , Timo/inmunología , Animales , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Diferenciación Celular , Linaje de la Célula , Células Cultivadas , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Regiones Promotoras Genéticas/genética , Unión Proteica , Proteínas Proto-Oncogénicas c-fyn/genética
10.
Eur J Clin Microbiol Infect Dis ; 36(12): 2343-2353, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28741095

RESUMEN

Acinetobacter baumannii is a nosocomial pathogen capable of resistance to multiple antimicrobials. The AdeRS two-component system (TCS) is associated with antimicrobial resistance by controlling the AdeABC efflux pump. To elucidate modulation by AdeRS, we made an A. baumannii mutant lacking the AdeRS TCS and characterized it using phenotype microarray (PM) analysis. After disrupting the adeRS operon, lower expression of AdeABC efflux pump was observed in the mutant strain. PM analysis showed that the AdeRS deletion strain and parental strain presented different tolerances to 91 compounds. Tolerance to 54 of the 91 compounds could be restored by complementing the AdeRS deleted strain with a plasmid carrying the adeRS gene. Compared to the parental strain, the AdeRS deletion strain was more sensitive to various inhibitors that target on-protein synthesis and function of cell membrane permeability. Tolerance to phleomycin of the AdeRS deletion strain reduced greatly and was further confirmed with minimum inhibitory concentration (MIC) determination and spot assay. The efflux pump inhibitor, NMP, could reduce phleomycin MIC four-fold at least for 29 (34.8%) of 81 tigecycline-resistant extensively drug-resistant A. baumannii (TGC-resistant XDRAB) clinical isolates. Our results suggested that the AdeRS TCS of A. baumannii was important for both elimination of antibiotics and tolerance to particular compounds.


Asunto(s)
Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/fisiología , Farmacorresistencia Bacteriana , Proteínas de Transporte de Membrana/genética , Fenotipo , Infecciones por Acinetobacter/microbiología , Antibacterianos/farmacología , Sinergismo Farmacológico , Orden Génico , Prueba de Complementación Genética , Humanos , Proteínas de Transporte de Membrana/metabolismo , Análisis por Micromatrices , Pruebas de Sensibilidad Microbiana , Operón , Eliminación de Secuencia
11.
J Eur Acad Dermatol Venereol ; 31(3): 405-413, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27662522

RESUMEN

Dermal fillers are increasingly used for soft tissue augmentation of the face and hands. The widespread use of dermal fillers for rejuvenation has led to a rise in reports of associated complications. Although the majority of complications are mild and transient, serious and long-lasting complications have been observed. This article discusses the key complications including pigmentary changes, hypersensitivity reactions, infections, nodule formation, granulomatous reactions, vascular occlusion and migration of filler material. A thorough literature review was performed in addition to the combined extensive authors' (GP and FA) experience. Complications from fillers are increasingly being recognized and highlighted in the literature partly reflecting the growth in the market. This article provides a comprehensive overview of the filler complications with mechanisms of prevention and treatment per complication. A thorough understanding of the preventative and management strategies for the associated dermal filler complications will help the physician to prepare the patient well, and deal with complications that may arise effectively.


Asunto(s)
Arteriopatías Oclusivas/inducido químicamente , Rellenos Dérmicos/efectos adversos , Edema/inducido químicamente , Reacción a Cuerpo Extraño/inducido químicamente , Piel/patología , Arteriopatías Oclusivas/complicaciones , Arteriopatías Oclusivas/terapia , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/terapia , Equimosis/inducido químicamente , Equimosis/terapia , Edema/terapia , Eritema/inducido químicamente , Eritema/terapia , Reacción a Cuerpo Extraño/terapia , Humanos , Inyecciones Intradérmicas/efectos adversos , Necrosis/etiología , Oclusión de la Arteria Retiniana/inducido químicamente , Oclusión de la Arteria Retiniana/terapia
12.
J Acoust Soc Am ; 141(3): 1999, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28372134

RESUMEN

The noise attenuation of fan-ducted noise at low blade-passage frequency remains a challenge. The present study investigates the noise reduction mechanism of a tensioned membrane housing device that directly controls the sound radiation from the doublet which is enclosed in an infinitely long duct with a point vortex. The time dependent sound radiation mechanism and the vibro-acoustics coupling mechanism of the systems are studied by adopting the potential theory and matched asymptotic expansion technique. The silencing performance of such a passive approach depends on the amplitude and phase of the sound field created by the doublet and the acoustic pressure induced by the membrane oscillation in order to achieve sound cancellation. Results show that the response of membrane vibration is strongly associated with the flow field induced by the grazing uniform flow and also the fluid loading generated by the inviscid vortex. The geometrical property of the cavity and the mechanical properties of the flexible membranes play important roles in controlling the performance of the proposed device.

13.
Gene Ther ; 23(1): 38-49, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26262583

RESUMEN

Ovarian cancer is a gynecologic malignancy with a high mortality rate. In the present study, we developed a novel cell-based vaccine, Meso-VAX, to generate mesothelin antigen-specific immune responses and immunotherapy against ovarian cancer. Mesothelin, a secreted protein anchored at the cell membrane, has recently been identified as a potential new tumor antigen for ovarian cancer. In this study, mice vaccinated with Meso-VAX and adeno-associated virus (AAV)-IL-12 exhibited dramatic increases in the number of mesothelin-specific CD4(+) helper and CD8(+) cytotoxic T-cell precursors, higher titers of anti-mesothelin Abs and in vitro tumor killing activity, and all of these mice were tumor-free after 60 days of tumor challenge. In addition, a significant reduction in peritoneal tumors and longer survival were noted in the mice vaccinated with Meso-VAX combined with AAV-IL-12. CD4(+) helper and CD8(+) cytotoxic T lymphocytes were essential for the antitumor effect generated by Meso-VAX combined with AAV-IL-12. The post-vaccination sera of the mice vaccinated with Meso-VAX and AAV-IL-12 also showed mesothelin-specific complement-dependent cell-mediated cytotoxicity. Our results suggest that a Meso-VAX cell-based vaccine combined with AAV-IL-12 can generate antigen-specific immunological responses and antitumor effects on ovarian cancer.


Asunto(s)
Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Proteínas Ligadas a GPI/inmunología , Interleucina-12/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Animales , Anticuerpos Antineoplásicos/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Citotoxicidad Inmunológica , Dependovirus/genética , Femenino , Humanos , Inmunoterapia , Interleucina-12/inmunología , Interleucina-2/inmunología , Mesotelina , Ratones , Ratones Endogámicos C57BL , Linfocitos T Citotóxicos/inmunología , Vacunación
14.
Int Immunol ; 27(5): 245-51, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25477210

RESUMEN

A canonical pre-TCR/TCR signaling pathway critical for thymic T cell development involves sequential phosphorylation and signaling through Lck, Zap70, Lat and Slp76. However, we and others have previously reported that genomic deletion of c-Cbl (Cbl) partially or completely reverses the defects in thymic development in mice deficient in Zap70, Slp76, Lat or Vav1, indicating the presence of alternative pathways normally suppressed by Cbl. To further elucidate pre-TCR/TCR signaling pathways involved in thymic development, we characterized the effect of Cbl inactivation on developmental and signaling defects in mice deficient in proximal signaling molecules Lck and Zap70. Inactivation of Cbl partially reversed defective T cell development in Zap70 (-/-) mice and reversed defects in phosphorylation of Erk, Plc-γ1, Vav1 and Akt, in TCR-stimulated Cbl (-/-) Zap70 (-/-) thymocytes. Recent reports identified an essential role of Lck in associating with CD4 and CD8 coreceptors and mediating the requirement for MHC restriction in TCR recognition. Since TCR recognition has been shown to be MHC-restricted in Cbl (-/-) mice, it was of interest to determine whether the requirement for Lck remained unmodified by Cbl deletion. Indeed, in contrast to the effect of Cbl inactivation in partially or fully bypassing requirements for other TCR signaling components, inactivation of Cbl did not reverse either defective T cell development or defective phosphorylation of TCR signaling molecules in Lck (-/-) mice. Thus, Lck, which plays a unique role in enforcing MHC restriction, is essential for thymic development in presence or absence of Cbl, ensuring MHC restriction of T cells derived from either pathway.


Asunto(s)
Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/metabolismo , Proteínas Proto-Oncogénicas c-cbl/metabolismo , Linfocitos T/inmunología , Timocitos/inmunología , Proteína Tirosina Quinasa ZAP-70/metabolismo , Animales , Diferenciación Celular/genética , Células Cultivadas , Antígenos de Histocompatibilidad/metabolismo , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/genética , Ratones , Ratones Noqueados , Fosforilación/genética , Proteínas Proto-Oncogénicas c-cbl/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Transducción de Señal/genética , Proteína Tirosina Quinasa ZAP-70/genética
15.
Clin Exp Dermatol ; 41(4): 386-9, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26620295

RESUMEN

Angioimmunoblastic T-cell lymphoma (AITL) is a rare, aggressive form of peripheral T-cell lymphoma that has a variety of cutaneous manifestations. To our knowledge, saggy skin has not been documented as one of these manifestations. We report a case of a patient with angioimmunoblastic T-cell lymphoma presenting initially with pruritus and saggy skin, which later progressed into erythroderma despite chemotherapy; the disease eventually resolved with autologous stem cell transplant. Appreciating the cutaneous manifestations of AITL may allow for earlier diagnosis and treatment.


Asunto(s)
Linfadenopatía Inmunoblástica/patología , Linfoma de Células T Periférico/patología , Piel/patología , Anciano , Antineoplásicos/uso terapéutico , Biopsia , Eritema/patología , Pie/patología , Humanos , Masculino , Prurito , Linfocitos T/fisiología
16.
Br J Dermatol ; 172(1): 130-7, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25039441

RESUMEN

BACKGROUND: While alopecia has been shown to have substantial psychological consequences, previous studies have not explicitly explored the key beliefs of patients with primary cicatricial alopecia (PCA) and the relationship between clinical and psychological measures. OBJECTIVES: To identify the key psychological factors and quality of life (QoL) of patients with PCA and the relationship between these factors and established clinical measures. METHODS: In total 105 patients with PCA were recruited from a specialist hair research clinic in Manchester, U.K. Patients completed the revised Illness Perception Questionnaire, Hospital Anxiety and Depression Scale (HADS) and Dermatology Life Quality Index. These psychological measures were correlated with disease activity in patients with lichen planopilaris (LPP) and frontal fibrosing alopecia, using the LPP Activity Index (LPPAI). RESULTS: Patients perceived PCA as a chronic condition with significant personal consequences and emotional impact, and reported that they had low levels of control over the condition and its treatment. Considerable levels of psychological distress were observed (mean HADS total score 11·3 ± 8·1). Impaired QoL was associated with strong beliefs that the symptoms were attributed to their disease (P < 0·001), and that alopecia had serious consequences (P < 0·001) and was distressing (P < 0·001). Disease activity (LPPAI) showed a significant positive correlation with HADS-Depression (r = 0·343, P = 0·026). CONCLUSIONS: Patients with PCA experience significant psychological distress and impaired QoL, both of which are associated with key beliefs about illness. Management of PCA should involve assessment of the beliefs and emotions that drive patients' psychological distress, as well as giving access to psychological therapy.


Asunto(s)
Alopecia/psicología , Actitud Frente a la Salud , Calidad de Vida , Estrés Psicológico/etiología , Trastornos de Ansiedad/etiología , Trastorno Depresivo/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Percepción , Proyectos Piloto , Encuestas y Cuestionarios
17.
Eur J Cancer Care (Engl) ; 24(5): 724-33, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25809989

RESUMEN

We assessed the impact of lymphoedema (defined as ≥ 10% limb volume change) on quality of life (QOL), ability to perform activities of daily living (ADLs) and coping in 277 melanoma patients. Limb volume was measured prospectively, pre-operatively and every 3-6 months for 18 months post-operatively using a perometer. Three questionnaires were administered to measure QOL, coping and impact on ADLs. Statistical analyses were conducted using longitudinal logistic regression models. At 18 months, the cumulative incidence of lymphoedema was 31% in patients with upper extremity nodal basin treatment and 40% in lower extremity nodal basin treatment patients. Patients with lower extremity lymphoedema reported lower QOL scores than those with upper extremity lymphoedema. Over 18 months, both groups with mild and moderate lymphoedema showed improvement in coping [odds ratio (OR): 6.67, 95% confidence interval (CI): 3.30-13.47] and performance of ADLs (OR: 7.46, CI: 3.38-16.47). Over the course of 18 months, men were found to have poorer coping scores than women (OR: 2.91, CI: 1.35-6.27). Lymphoedema was associated with improvement in coping over time (P = 0.08) and a higher reported interference with ADLs (OR: 2.53, CI: 1.29-4.97). Patient education about lymphoedema at the time of surgical consent may improve self-efficacy and coping ability. Effective management of lymphoedema may improve patient QOL and reduce interference with ADLs.


Asunto(s)
Actividades Cotidianas , Adaptación Psicológica , Linfedema , Melanoma/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfedema/etiología , Linfedema/fisiopatología , Linfedema/psicología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Calidad de Vida , Análisis de Regresión , Autoeficacia , Encuestas y Cuestionarios
18.
Genet Mol Res ; 14(4): 13013-21, 2015 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-26505454

RESUMEN

Syzygium samarangense (Blume) Merr. & Perry (wax apple) is an important commercial fruit tree in Southeast Asia. Here, microsatellite markers were developed to evaluate genetic diversity and distinguish cultivars in this species. In total, 161 microsatellite loci with sufficient flanking sequences to design primer sets were isolated from wax apple using a magnetic bead-enrichment method. Fifty-eight primer sets were designed based on the flanking sequences of each single sequence repeat (SSR) locus and were tested using 14 wax apple cultivars/lines. Twenty SSR loci were found to be polymorphic and transferable across the 14 wax apple cultivars/lines. The number of alleles and effective number of alleles detected per locus ranged from 4 to 12 and from 1.697 to 9.800, respectively. The expected heterozygosity ranged from 0.150 to 0.595 (mean = 0.414). Polymorphism information content values ranged from 0.502 to 0.866 (mean = 0.763). These new microsatellite loci will be of value for characterization of genetic diversity in wax apples and for the identification of cultivars.


Asunto(s)
ADN de Plantas/genética , Repeticiones de Microsatélite/genética , Myrtaceae/genética , Variación Genética/genética , Polimorfismo Genético/genética , Poliploidía
19.
Nano Lett ; 14(3): 1484-91, 2014 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-24548146

RESUMEN

Nanoparticle LiFePO4, the basis for an entire class of high power Li-ion batteries, has recently been shown to exist in binary lithiated/delithiated states at intermediate states of charge. The Mn-bearing version, LiMn(y)Fe(1-y)PO4, exhibits even higher rate capability as a lithium battery cathode than LiFePO4 of comparable particle size. To gain insight into the cause(s) of this desirable performance, the electrochemically driven phase transformation during battery charge and discharge of nanoscale LiMn0.4Fe0.6PO4 of three different average particle sizes, 52, 106, and 152 nm, is investigated by operando synchrotron radiation powder X-ray diffraction. In stark contrast to the binary lithiation states of pure LiFePO4 revealed in recent investigations, the formations of metastable solid solutions covering a remarkable wide compositional range, including while in two-phase coexistence, are observed. Detailed analysis correlates this behavior with small elastic misfits between phases compared to either pure LiFePO4 or LiMnPO4. On the basis of time- and state-of-charge dependence of the olivine structure parameters, we propose a coherent transformation mechanism. These findings illustrate a second, completely different phase transformation mode for pure well-ordered nanoscale olivines compared to the well-studied case of LiFePO4.

20.
Br J Dermatol ; 171(2): 370-5, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24673302

RESUMEN

BACKGROUND: Photoprotection including sunscreen use in children is encouraged by health campaigns. While sunscreen chemicals are common causes of photoallergic (PA) contact reactions in adults, limited data are available in children. OBJECTIVES: To assess the frequency of PA and contact allergy (CA) to sunscreens in children aged < 18 years undergoing investigation for suspected photosensitivity. METHODS: Retrospective analysis of data on children who underwent photopatch testing to a standard series of nine ultraviolet (UV) filters and to sunscreen products in a single photoinvestigation centre (2000-11). Duplicate series of UV filters and the children's own sunscreen products were applied to the back, with readings taken at sample removal, and at 24 and 48 h after 5 J cm(-2) UVA exposure of one series. RESULTS: The analysis comprised 157 children (aged 3-17 years, 69 male and 88 female). In total 10 children (6·4%) showed positive photopatch responses to UV filters and/or their sunscreen products (4·5% to UV filters, 5·7% to their sunscreen products). The responsible UV filters most often identified were benzophenone-3 and octyl methoxycinnamate. Additionally, CA reactions were observed in nine children (5·7%), with 16 children (10·2%) showing PA and/or CA to UV filters and/or sunscreen products. CONCLUSIONS: This is the largest series of photopatch testing reported in children, and shows that both sunscreen PA and CA are quite frequent in those undergoing photoinvestigation. Photopatch testing should be considered in children presenting with features of photosensitivity.


Asunto(s)
Dermatitis Fotoalérgica/etiología , Protectores Solares/efectos adversos , Adolescente , Niño , Preescolar , Dermatitis Fotoalérgica/diagnóstico , Femenino , Humanos , Masculino , Pruebas del Parche , Estudios Retrospectivos , Rayos Ultravioleta/efectos adversos
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