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1.
Am J Otolaryngol ; 44(2): 103765, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36603380

RESUMO

OBJECTIVES: To assess the use of tongue base palpation during cancer screening exams by Oral Healthcare Providers (OHPs) and explore attitudes about (1) the usefulness of oral cancer screening (OCS) in detecting early, asymptomatic lesions and (2) routine OCS of the general population. STUDY DESIGN: Survey study. SETTING: Private and hospital-based clinical practices of OHPs located in Massachusetts and Connecticut, United States. METHODS: An anonymous, online 9-item survey assessing beliefs and practice patterns about cancer screening exams was distributed to OHPs with practices in Massachusetts and Connecticut from August 2020 to June 2021. Data were analyzed using chi-square tests and Pearson correlations. Statistically significant levels were established at P < .050. RESULTS: One hundred seventy-one responses were analyzed (response rate 17 %). Tongue base palpation was performed as part of a routine cancer screening exam by 55 % of otolaryngologists, 34 % of dentists and 29 % of OMFS (P = .030). Providers who palpated the tongue base were also more likely to use palpation as an exam technique in the tonsils (r = 0.52 [95 % CI 0.40-0.62]; P < .001) among other intra-and extra-oral anatomical subsites. Almost all dentists (92 %) and OMFS (98 %) but only 58 % of otolaryngologists considered OCS useful for detection of early, asymptomatic malignant lesions in the oral cavity (P < .001). CONCLUSIONS: While tongue base palpation can detect oropharyngeal cancers in a pre-symptomatic stage, it is underutilized during routine cancer screening exams. Considering the rising incidence of oropharyngeal cancer, tongue base palpation should be established as a routine part of cancer screening by OHPs.


Assuntos
Neoplasias Bucais , Neoplasias Orofaríngeas , Neoplasias da Língua , Humanos , Estados Unidos , Estudos Transversais , Neoplasias Bucais/diagnóstico , Neoplasias Orofaríngeas/diagnóstico , Pessoal de Saúde , Inquéritos e Questionários , Língua , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/epidemiologia
2.
J Clin Med ; 11(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35956123

RESUMO

The aim of this study is to investigate hospital readmissions during 1 year after acute poisoning cases (APC), analyze the temporal behavior of early readmissions (ER) (in the month after the index episode) and predict possible ER. A descriptive analysis of the patients with APC assisted between 2011 and 2016 in the Emergency Department of Hospital La Paz is presented, and various methods of inferential statistics were applied and confirmed by Bayesian analysis in order to evaluate factors associated with total and early readmissions. Out of the 4693 cases of APC included, 968 (20.6%) presented, at least one readmission and 476 (10.1%) of them were ER. The mean age of APC with readmission was 41 years (12.7 SD), 78.9% had previous psychiatric pathology and 44.7% had a clinical history of alcohol addiction. Accidental poisoning has been a protective factor for readmission (OR 0.50; 0.26-0.96). Type of toxin ("drug of abuse" OR 8.88; 1.17-67.25), history of addiction (OR 1.93; 1.18-3.10) and psychiatric history (OR 3.30; 2.53-4.30) are risk factors for readmissions during the first year. Women showed three or more readmissions in a year. The results of the study allow for identification of the predictors for the different numbers of readmissions in the year after the index APC, as well as for ERs.

3.
Environ Sci Pollut Res Int ; 29(25): 37458-37470, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35066824

RESUMO

Mexico is the top producer of silver and is on the eighth place from producing gold in the world. For instance, the hydrometallurgical extraction process produces wastewater (mining tailing) characterized by being composed with varying concentrations of cyanide and heavy metals. The purpose of this research was to study the biodegradation of cyanide contained in mining tailings by means of a bacterial consortium isolated from a tailings dam. For this purpose, three types of Eckendfelder reactors were used, one with suspended biomass (BS) and two moving bed biofilter reactors, one with biomass immobilized on Kaldnes (BK) supports, and the other on polyurethane cubes (BCP). Three experimental stages were worked; in each of them, the concentrations of total cyanide were varied. In the first one, it was 26 ± 2 mg·L-1; in the second one 40 ± 4 mg·L-1; and the third one 55 ± 4 mg·L-1. During the whole operation, the pH and temperature were maintained at 9.5 units and 25 °C. After 141 days of operation, biodegradation of the total cyanide contained in the mining tailings was 69% (17 mg·L-1) in the BS reactor, while in the BK reactor, it was 93% (3.9 mg·L-1) and in the BCP reactor 95% (2.5 mg·L-1). The predominant families in each of the reactors, as well as their respective relative abundances, were for the BS and for the BK of Cyclobacteriaceae (20.65% and 24.64%) and Rhizobiaceae (18.48% and 14.01%) and Halomonadaceae (46.97%) and Hyphomonadaceae (24.94%) in the BCP.


Assuntos
Cianetos , Metais Pesados , Biodegradação Ambiental , Biomassa , Cianetos/química , Humanos , Mineração
4.
Rev. Univ. Ind. Santander, Salud ; 52(4): 414-421, Octubre 21, 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1340840

RESUMO

Resumen Introducción: La pandemia por COVID-19 es uno de los mayores desafíos globales de la época. Para la mayor comprensión de sus efectos poblacionales es necesario analizar medidas complentarias a la mortalidad. Objetivos: Estimar los años de vida potenciales perdidos en Colombia debido a muertes prematuras por todas las causas de defunción y por COVID-19 en el periodo marzo-julio entre los años 2015 y 2020. Materiales y métodos: Estudio ecológico, longitudinal y retrospectivo, basado en fuentes de información secundaria. Se calcularon los años de vida potencialmente perdidos según sexo y grupo de edad, utilizando la esperanza de vida y las tablas actuariales del DANE. Resultados: Entre marzo y julio de 2020 se perdieron 2 356 420 años por muertes prematuras, para una tasa de 46,8 años perdidos por cada mil habitantes de Colombia, un resultado superior en un 4,8 % respecto a la media de los últimos cinco años. Debido al COVID-19 se dejaron de vivir 237 725,5 años -con mayor pérdida entre los hombres- y un aporte porcentual del 10,5 % al total de años potenciales perdidos en Colombia. Conclusiones: Durante la pandemia se ha presentado un ligero incremento en los años de vida potenciales perdidos en Colombia. Si bien la pérdida de años atribuibles a las muertes confirmadas por COVID-19 no son los responsables directos de la mayor parte de la pérdida total, los cambios sociales y las condiciones de vida durante el confinamiento sí podrían haber incidido en las variaciones de la mortalidad y su distribución entre subgrupos poblacionales.


Abstract Introduction: The COVID-19 pandemic is one of the greatest global challenges of the time. For a better understanding of its population effects, it is necessary to analyze complementary measures to mortality. Objetive: To estimate the potential years of life lost in Colombia due to premature deaths from all causes and from COVID-19 in the March-July period between 2015 and 2020. Materials and methods: We carried out an ecological, longitudinal and retrospective study, based on secondary sources. Years of life potentially lost were calculated according to sex and age group, using life expectancy and the DANE actuarial tables. Results: Between March and July 2020, 2 356 420 years were lost due to premature deaths, for a rate of 46.8 years lost per thousand inhabitants of Colombia, a result that is 4.8% higher than the average of the last five years. Due to COVID-19, 237 725.5 years were lost -with the greatest loss among men- and a percentage contribution of 10.5% to the total potential years of life lost in Colombia. Conclusions: During the pandemic there has been a slight increase in the potential years of life lost in Colombia. Although the loss of years attributable to deaths confirmed by COVID-19 are not directly responsible for most of the total loss, social changes and living conditions during confinement could have had an impact on variations in mortality and its distribution among population subgroups.


Assuntos
Humanos , Causas de Morte , Mortalidade Prematura , COVID-19 , Expectativa de Vida , Colômbia
5.
Technol Cancer Res Treat ; 18: 1533033819870823, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31431135

RESUMO

Successful therapies for patients with breast cancer often lose their initial effectiveness. Thus, identifying new molecular targets is a constant goal in the fight against breast cancer. Gpn3 is a protein required for RNA polymerase II nuclear targeting in both yeast and human cells. We investigated here the effect of suppressing Gpn3 expression on cell proliferation in a progression series of isogenic cell lines derived from the nontumorigenic MCF-10A breast cells that recapitulate different stages of breast carcinogenesis. Gpn3 protein levels were comparable in all malignant derivatives of the nontumorigenic MCF-10A cells. shRNA-mediated inhibition of Gpn3 expression markedly decreased cell proliferation in all MCF-10A sublines. A fraction of the largest RNA polymerase II subunit Rpb1 was retained in the cytoplasm, but most Rpb1 remained nuclear after suppressing Gpn3 in all cell lines studied. Long-term proliferation experiments in cells with suppressed Gpn3 expression resulted in the eventual loss of all isogenic cell lines but MCF-10CA1d.cl1. In MCF-10CA1d.cl1 cells, Gpn3 knockdown reduced the proliferation of breast cancer stem cells as evaluated by mammosphere assays. After the identification that Gpn3 plays a key role in cell proliferation in mammary epithelial cells independent of the degree of transformation, we also analyzed the importance of Gpn3 in other human breast cancer cell lines from different subtypes. Gpn3 was also required for cell proliferation and nuclear translocation of RNA polymerase II in such cellular models. Altogether, our results show that Gpn3 is essential for breast cancer cell proliferation regardless of the transformation level, indicating that Gpn3 could be considered a molecular target for the development of new antiproliferative therapies. Importantly, our analysis of public data revealed that Gpn3 overexpression was associated with a significant decrease in overall survival in patients with estrogen receptor-positive and Human epidermal growth factor receptor 2 (HER2+) breast cancer, supporting our proposal that targeting Gpn3 could potentially benefit patients with breast cancer.


Assuntos
Neoplasias da Mama/genética , Carcinogênese/genética , GTP Fosfo-Hidrolases/genética , Receptor ErbB-2/genética , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Intervalo Livre de Doença , Células Epiteliais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
6.
INSPILIP ; 2(2): 1-18, jul.-dic. 2018.
Artigo em Espanhol | LILACS | ID: biblio-981994

RESUMO

Bordetella pertussises un cocobacilo Gram negativo aerobio estricto agente causal de la enfermedad infectocontagiosa conocida como tosferina que afecta predominantemente a lactantes, produciendo un alto índice de mortalidad. Mediante la elaboración de una curva epidemiológica del número de casos de la patología por Bordetella pertussis en un periodo epidémico dispuesto según etapas del tiempo, se evidenciará la evolución de los brotes en el Ecuador como aporte a la epidemiología nacional. Como objetivo específico se determina la frecuencia de aparición de B. pertussis, mediante el aislamiento de la cepa se procede a describir el comportamiento epidemiológico según la frecuencia de aparicióncomparando los datos epidemiológicos obtenidos en Ecuador con datos en el mundo, para poder destacar la importancia de implementar nuevas técnicas de laboratorio para el diagnóstico de la tosferina. El método aplicado en la investigación es descriptivo de cohorte transversal, siendo analizada la curva epidemiológica con los datos obtenidos de los aislamientos durante los años 1999 al 2014; como resultados del comportamiento epidemiológico de la Bordetella pertussisen el Ecuador se pueden visualizar picos en las gráficas que indican el inicio y el final de un brote, esto ocurre cada 3 a 5 años con la presencia de 0, 1 a 2 casos esporádicos entre cada una, tal como lo describen los reportes epidemiológicos de la OMS.Los resultados obtenidos en el estudio revelan la categoría en cuanto los recursos humanos, educación y comunicación, sus dimensiones, procedimientos clínicos, técnicos para la vigilancia de enfermedades transmisibles, las técnicas de cultivo, serología, y la unidad de análisis de las muestras clínicas recibidas de las diferentes zonas del Ecua


Bordetellapertussis is a strict aerobic Gram negative coccobacillus, causative agent of the infectious disease known as pertussis, which predominantly affects infants, producing a high mortality rate. By means of the elaboration of an epidemiological curve of the number of cases of the pathology by Bordetella Pertussis in an epidemic period arranged according to time stages, the evolution of the outbreaks in Ecuador as a contribution to the National Epidemiology will be evidenced.As a specific objective, the frequency of appearance of B. pertussis is determined by means of the isolation of the strain, we proceed to describe the epidemiological behavior according to the frequency of appearance, comparing the epidemiological data obtained in Ecuador with data obtainedin the world, in order to highlight the importance of implementing new laboratory techniques for the diagnosis of whooping cough.The method applied in the research is descriptive of a transversal cohort, the epidemiological curve being analyzed with the data obtained from the isolations during the years 1999 to 2014, as results of the epidemiological behavior of the Bordetella pertussis in Ecuador can be seen peaks in the graphs that indicate the beginning and end of an outbreak, this occurs every 3 to 5 years with the presence of 0, 1 to 2 sporadic cases between each, as described in the WHO epidemiological reports.The results obtained in the study reveal the category in terms of human resources, education and communication, its dimensions, clinical, technical procedures for the surveillance of communicable diseases, culture techniques, serology, and the unit of analysis of the clinical samples received of the different zones of Ecuador.


Assuntos
Humanos , Recém-Nascido , Bacilos e Cocos Aeróbios Gram-Negativos , Lactente , Estudos Epidemiológicos , Doença , Estágios do Ciclo de Vida
7.
INSPILIP ; 2(1): 1-22, ene.-jun. 2018.
Artigo em Espanhol | LILACS | ID: biblio-987228

RESUMO

Aprovechando la realización de las XL Jornadas Nacionales de Biología Espol en la ciudad de Guayaquil, se realizó una sesión dedicada a la epidemiología del virus de papiloma humano (VPH) y del cáncer cervical. Esta sesión tuvo la participación de varios investigadores provenientes de diferentes zonas del Ecuador. El presente artículo tiene como objeto presentar un resumen de estas charlas, junto a un análisis de la información mostrada además de una reflexión sobre las preguntas que quedan aún por responder en cuanto al perfil epidemiológico de esta patología en el país.


Taking advantage of the realization of theXL National Conference on Espol Biology in the city of Guayaquil, a session was held dedicated to the epidemiology of Human Papilloma Virus (HPV) and cervical cancer. This session was attended by several researchers from different areas of Ecuador. The object of this article is to present a summary of these talks, together with an analysis of the information shown in addition to a reflection on the questions still to be answered regarding the epidemiological profile of this pathology in the country.


Assuntos
Humanos , Papillomaviridae , Neoplasias do Colo do Útero , Papillomavirus Humano 16 , Patologia , Pesquisadores , Epidemiologia , Técnicas de Laboratório Clínico , Equador , Consórcios de Saúde , Povos Indígenas
8.
FEBS Lett ; 591(22): 3757-3770, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29029378

RESUMO

Gpn1 associates with Gpn3, and both are required for RNA polymerase II nuclear targeting. Global studies have identified by mass spectrometry that human Gpn3 is ubiquitinated on lysines 189 and 216. Our goals here were to determine the type, physiological importance, and regulation of Gpn3 ubiquitination. After inhibiting the proteasome with MG132, Gpn3-Flag was polyubiquitinated on K216, but not K189, in HEK293T cells. Gpn3-Flag exhibited nucleo-cytoplasmic shuttling, but polyubiquitination and proteasomal degradation of Gpn3-Flag occurred only in the cell nucleus. Polyubiquitination-deficient Gpn3-Flag K216R displayed a longer half-life than Gpn3-Flag in two cell lines. Interestingly, Gpn1-EYFP inhibited Gpn3-Flag polyubiquitination in a dose-dependent manner. In conclusion, Gpn1-inhibitable, nuclear polyubiquitination on lysine 216 regulates the half-life of Gpn3 by tagging it for proteasomal degradation.


Assuntos
Núcleo Celular/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Lisina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Linhagem Celular , GTP Fosfo-Hidrolases/genética , Proteínas de Ligação ao GTP/genética , Células HEK293 , Meia-Vida , Humanos , Leupeptinas/farmacologia , Mutação , Ubiquitinação
9.
FEBS Lett ; 591(21): 3555-3566, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28940195

RESUMO

Gpn3 is required for RNA polymerase II (RNAPII) nuclear targeting. Here, we investigated the effect of a cancer-associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi-resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity were markedly decreased in cells expressing only Gpn3R Q279*. Wild-type Gpn3R localized to the cytoplasm but a fraction of Gpn3R Q279* entered the cell nucleus and inhibited Gpn1-EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*-expressing cells required a PDZ-binding motif generated by the Q279* mutation. We conclude that an acquired PDZ-binding motif in Gpn3 Q279* caused Gpn3 nuclear entry, and inhibited Gpn1 nuclear export and Gpn3-mediated RNAPII nuclear targeting.


Assuntos
Neoplasias da Mama/enzimologia , Núcleo Celular/enzimologia , Códon sem Sentido , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Polimerase II/metabolismo , Transporte Ativo do Núcleo Celular/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Núcleo Celular/genética , Citoplasma/enzimologia , Citoplasma/genética , Feminino , GTP Fosfo-Hidrolases/genética , Proteínas de Ligação ao GTP/genética , Células HEK293 , Humanos , Proteínas de Neoplasias/genética , Domínios PDZ , RNA Polimerase II/genética
10.
Rev. colomb. reumatol ; 23(3): 213-217, jul.-set. 2016. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-960214

RESUMO

Se reporta el caso de un hombre de 47 arios con intoxicación crónica por plomo, secundaria a exposición laboral de 5 años, con sintomatología típica de saturnismo. Consultó por debilidad muscular generalizada, disfagia y parestesias en extremidades. Se documentaron altos niveles de plomo en sangre, asociados a neuropatía periférica, confirmada por electromiografía, y disminución de la fuerza muscular en cintura escapular y pélvica (deltoides y vasto medial), así como atrofia de músculos del cuello (flexores y extensores) manifestada como cefaloparesia. Adicional al cuadro de saturnismo se diagnosticó miopatía inflamatoria con base en la elevación de enzimas musculares, miositis por resonancia magnética nuclear y biopsia muscular compatible, siendo, hasta donde se sabe, el primer reporte conocido de la coexistencia de estas 2 enfermedades


A case is presented on a 47-year-old man with chronic lead poisoning with typical symptoms after 5 years of occupational exposure. He consulted for generalised muscle weakness, early dysphagia, cephaloparesia, and paresthesias in upper and lower limbs. He also had atrophy and decreased proximal muscle strength (deltoid and medial vast) and in both flexor and extensor muscles of the neck. He had a history of high blood lead levels and peripheral neuropathy documented by electromyography. In addition to the diagnosis of lead poisoning, inflammatory myopathy was confirmed based on muscle enzyme elevation, muscular inflammation in magnetic resonance imaging, and typical findings in a muscle biopsy. To our knowledge, this is the first report where both conditions are documented in one patient


Assuntos
Humanos , Polimiosite , Doenças do Sistema Nervoso Periférico , Intoxicação por Chumbo
11.
FEBS Lett ; 588(21): 3823-9, 2014 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-25241168

RESUMO

Gpn1 and Gpn3 are GTPases individually required for nuclear targeting of RNA polymerase II. Here we show that whereas Gpn3-EYFP distributed between the cytoplasm and cell nucleus, it was mainly cytoplasmic when coexpressed with Gpn1-Flag. Gpn3-Flag retained Gpn1-EYFP in the cytoplasm. However, Gpn3-EYFP/Gpn1-Flag nucleocytoplasmic shuttling was revealed after inhibiting nuclear export with leptomycin B. All Gpn3-EYFP coimmunoprecipitated with Gpn1-Flag, and all Gpn1-EYFP with Gpn3-Flag. Importantly, most endogenous Gpn1 and Gpn3 also associate. Gpn1-Gpn3 interaction was essential to maintain steady-state protein levels of both GTPases. We propose that most Gpn1 and Gpn3 associate, are mobilized, and function as a protein complex.


Assuntos
GTP Fosfo-Hidrolases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Humanos , Ligação Proteica
12.
Dermatol. peru ; 22(4): 171-173, oct.-dic. 2012. ilus
Artigo em Espanhol | LILACS, LIPECS | ID: lil-712845

RESUMO

La balanitis plasmocitaria de Zoon o balanitis plasmocelular es una dermatosis crónica benigna y poco frecuente, más frecuente en varones de mediana edad y adultos mayores. Se presenta el caso de un paciente varón de 68 años con tiempo de enfermedad de un año que acude a consulta por presentar un parche eritematoso, de superficie lustrosa, lisa, de bordes irregulares y con algunas zonas exudativas, localizada en glande, surco balanoprepucial y cuerpo del pene, asintomático. Se procede a toma de biopsia y se observa en dermis superficial un infiltrado en banda de células plasmáticas y se confirma el diagnóstico de balanitis plasmocitaria de Zoon.


Plasma cell balanitis of Zoon or balanitis plasma cell is a benign chronic dermatoses and infrequent, more common in middle-aged men and elderly. We report the case of a male patient aged 68 with sick time a year who come to the office due erythematous patch, glossy surface, smooth, irregular borders and some oozing areas, located in glans, coronal sulcus and penile shaft, asymptomatic. We proceed to biopsy and is observed in superficial dermis band infiltrate of plasma cells and confirmed the diagnosis of plasma cell balanitis of Zoon.


Assuntos
Humanos , Masculino , Idoso , Plasmócitos , Balanite (Inflamação) , Dermatopatias
13.
Dermatol. peru ; 22(4): 174-177, oct.-dic. 2012. ilus
Artigo em Espanhol | LILACS, LIPECS | ID: lil-712846

RESUMO

La acrodermatitis continua de Hallopeau (ACH) es una enfermedad inflamatoria crónica que afecta a los dedos de las manos y/o pies, se caracteriza por una placa eritematodescamativa con erupciones pustulosas estériles. Es una patología rara o quizá subdiagnosticada y más frecuente en mujeres de edad mediana, según los pocos casos reportados. Se presenta el siguiente caso clínico de una adolescente de 15 años de edad, que presentó una placa eritematodescamativa con pústulas estériles, en tres oportunidades a lo largo de dos años. El diagnóstico de ACH se realizó por la clínica y la histología. Se indicó tratamiento con acitretina vía oral y se tiene mejoría clínica importante.


The acrodermatitis continua of Hallopeau (ACH) is a chronic inflammatory disease that affects the fingers and toes, is characterized by erythematous scaly plaque with sterile pustular eruptions. It is a rare condition or perhaps underdiagnosed, according the few reported cases is more common in middle aged women. We report the case of a 15 year-old woman which presented an erythematous plaque with sterile pustules on three occasions along two years, the diagnosis of ACH was made by clinical and histology. Acitretin therapy is indicated orally and has significant clinical improvement.


Assuntos
Humanos , Adolescente , Feminino , Acrodermatite , Epidermólise Bolhosa Distrófica , Psoríase
14.
Biochim Biophys Acta ; 1823(10): 1756-66, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22796641

RESUMO

XAB1/Gpn1 is a GTPase that associates with RNA polymerase II (RNAPII) in a GTP-dependent manner. Although XAB1/Gpn1 is essential for nuclear accumulation of RNAPII, the underlying mechanism is not known. A XAB1/Gpn1-EYFP fluorescent protein, like endogenous XAB1/Gpn1, localized to the cytoplasm but it rapidly accumulated in the cell nucleus in the presence of leptomycin B, a chemical inhibitor of the nuclear transport receptor Crm1. Crm1 recognizes short peptides in substrate proteins called nuclear export sequences (NES). Here, we employed site-directed mutagenesis and fluorescence microscopy to assess the functionality of all six putative NESs in XAB1/Gpn1. Mutating five of the six putative NESs did not alter the cytoplasmic localization of XAB1/Gpn1-EYFP. However, a V302A/L304A double mutant XAB1/Gpn1-EYFP protein was clearly accumulated in the cell nucleus, indicating the disruption of a functional NES. This functional XAB1/Gpn1 NES displays all features present in most common and potent NESs, including, in addition to Φ1-Φ4, a critical fifth hydrophobic amino acid Φ0. Therefore, in human Gpn1 this NES spans amino acids 292-LERLRKDMGSVAL-304. XAB1/Gpn1 NES is remarkably conserved during evolution. XAB1/Gpn1 NES was sufficient for nuclear export activity, as it caused a complete exclusion of EYFP from the cell nucleus. Molecular modeling of XAB1/Gpn1 provided a mechanistic reason for NES selection, as functionality correlated with accessibility, and it also suggested a mechanism for NES inhibition by intramolecular masking. In conclusion, we have identified a highly active, evolutionarily conserved NES in XAB1/Gpn1 that is critical for nucleo-cytoplasmic shuttling and steady-state cytoplasmic localization of XAB1/Gpn1.


Assuntos
Núcleo Celular/enzimologia , Sinais de Exportação Nuclear , RNA Polimerase II/metabolismo , Transporte Ativo do Núcleo Celular , Sequência de Aminoácidos , Sequência Conservada/genética , Evolução Molecular , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/metabolismo , Genes Reporter , Células HEK293 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Secundária de Proteína , Proteínas Recombinantes de Fusão/metabolismo , Relação Estrutura-Atividade
15.
Dermatol. peru ; 22(2): 115-117, abr.-jun. 2012. ilus
Artigo em Espanhol | LILACS, LIPECS | ID: lil-671800

RESUMO

La dermatitis liquenoide anular es una entidad clínica recientemente descrita que se presenta como placas circularesceritematosas con centro hipopigmentado y evolución crónica. A pesar de que los diagnósticos diferenciales puedencser diversos la histopatología es muy característica. Siendo la mayor parte de los casos descritos en niños, se le dio el nombre de ALDY, aunque se han visto casos en la adultez. Presentamos el caso de un paciente varón adulto, de 41 años, como aporte al conocimiento de esta patología.


Annular lichenoid dermatitis of youth is a clinical entity recently described that presents as circular plaques hipopigmented centre and chronic evolution. Despite of several differential diagnoses, this pathology is characterized by its histopathology. As most cases has been described in children, it was named as ALDY;but has seen cases in adults. A case of a 41 years old male is presented as a contribution for the knowledge of this pathology.


Assuntos
Humanos , Masculino , Adulto , Dermatite , Ilustração Médica , Inflamação , Relatos de Casos
18.
Dermatol. peru ; 21(3): 126-129, jul.-sept. 2011. ilus
Artigo em Espanhol | LILACS, LIPECS | ID: lil-671772

RESUMO

El linfoma tipo hidroa es un linfoma cutáneo primario T/NK raro, que viene siendo reportado en países de Asia y Latinoamérica, en la que se ha hallado asociación con infección crónica activa por virus de Epstein-Barr. Se presenta el caso de una paciente de 14 años con un tiempo de enfermedad de tres años, en el que inicialmente presenta eritema y vesiculación de áreas fotoexpuestas de manera episódica y que posteriormente presenta edema facial marcado con zonas violáceas, disminución de peso y falla multiorganica a la que se le hace diagnóstico post mórtem de linfoma tipo hidroa.


Hydroa like-lymphoma is a rare T/NK primary cutaneous lymphoma, which has been reported in people from Asia and Latin-America and has been associated to Epstein-Barr virus (EBV) chronic latent infection. We present the case of a 14 year-old patient with a time since diagnosis of illness of three years. She initially has erythema and vesiculation in sun-exposed areas that appears in a episodic way and then adds overt facial edema and purpuric patches, wasting, weight loss and multiorganic failure. The diagnosis of hydroa-like lymphoma was done post-mortem.


Assuntos
Humanos , Adolescente , Feminino , Hidroa Vaciniforme , Ilustração Médica , Insuficiência de Múltiplos Órgãos , Linfoma Cutâneo de Células T , Relatos de Casos
19.
Dermatol. peru ; 21(3): 130-133, jul.-sept. 2011. ilus
Artigo em Espanhol | LILACS, LIPECS | ID: lil-671773

RESUMO

La parapsoriasis retiforme es una variedad muy rara de parapsoriasis en grandes placas, también considerada como un estadio premicotico. Se caracteriza por presentarse como pápulas milimétricas que confluyen formando placas reticuladas eritemato violaceas con piel corrugada y finamente descamativa entre ellas con apariencia poiquilotermia. Se presenta el caso de un paciente anciano con compromiso extenso de la superficie corporal.


Retiform parapsoriasis is a very rare variety of large plaque parapsoriasis. It was also considerate by some authors like a premycotic state. This entity its characterized by present like milimetric papules that confluid to form eritemato-violaceous plaques that have between poikilodermatous skin. We present a case of an older man with wide compromise of body superface area.


Assuntos
Humanos , Masculino , Idoso , Ilustração Médica , Linfoma Cutâneo de Células T , Micose Fungoide , Parapsoríase , Relatos de Casos
20.
Biochim Biophys Acta ; 1813(10): 1708-16, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21782856

RESUMO

Parcs/Gpn3 is a putative GTPase that is conserved in eukaryotic cells from yeast to humans, suggesting that it plays a fundamental, but still unknown, cellular function. Suppression of Parcs/Gpn3 expression by RNAi completely blocked cell proliferation in MCF-12A cells and other mammary epithelial cell lines. Unexpectedly, Parcs/Gpn3 knockdown had a more modest effect in the proliferation of the tumorigenic MDA-MB-231 and SK-BR3 cells. RNA polymerase II (RNAP II) co-immunoprecipitated with Parcs/Gpn3. Parcs/Gpn3 depletion caused a reduction in overall RNA synthesis in MCF-12A cells but not in MDA-MB-231 cells, demonstrating a role for Parcs/Gpn3 in transcription, and pointing to a defect in RNA synthesis by RNAP II as the possible cause of halted proliferation. The absence of Parcs/Gpn3 in MCF-12A cells caused a dramatic change in the sub-cellular localization of Rpb1, the largest subunit of RNAP II. As expected, Rpb1 was present only in the nucleus of MCF-12A control cells, whereas in Parcs/Gpn3-depleted MCF-12A cells, Rpb1 was detected exclusively in the cytoplasm. This effect was specific, as histones remained nuclear independently of Parcs/Gpn3. Rpb1 protein levels were markedly increased in Parcs/Gpn3-depleted MCF-12A cells. Interestingly, Rpb1 distribution was only marginally affected after knocking-down Parcs/Gpn3 in MDA-MB-231 cells. In conclusion, we report here, for the first time, that Parcs/Gpn3 plays a critical role in the nuclear accumulation of RNAP II, and we propose that this function explains the relative importance of Parcs/Gpn3 in cell proliferation. Intriguingly, at least some tumorigenic mammary cells have evolved mechanisms that allow them to proliferate in a Parcs/Gpn3-independent manner.


Assuntos
Núcleo Celular/metabolismo , GTP Fosfo-Hidrolases/fisiologia , RNA Polimerase II/metabolismo , Mama/metabolismo , Núcleo Celular/genética , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/metabolismo , Feminino , GTP Fosfo-Hidrolases/antagonistas & inibidores , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Humanos , Imunoprecipitação , Ligação Proteica , Transporte Proteico/genética , Interferência de RNA/fisiologia , RNA Interferente Pequeno/farmacologia , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética
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