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1.
Rev. peru. biol. (Impr.) ; 30(1)ene. 2023.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1450331

RESUMEN

Echiophis brunneus, comúnmente conocida como anguila pecosa, es una especie bentónica costera de la familia Ophichthidae. Su distribución se reporta para el Pacífico Oriental desde el Golfo de California (EE. UU.) hasta el Golfo de Guayaquil (Ecuador). Se reporta por primera vez la presencia de E. brunneus en el norte del Perú a partir de tres ejemplares capturados. Así mismo se registra una nueva talla máxima para la especie y se adiciona la secuencia COI a la base de datos BoldSystems. Una de las principales características para su determinación fue la presencia del diente canino grande localizado en la zona distal del vómer. Las distancias genéticas entre E. brunneus con E. punctifer y E. intertinctus fueron de 0.087±0.013 y 0.095±0.014 respectivamente. Con este trabajo se amplía la distribución geográfica de E. brunneus hasta Salaverry (08°13'28"S, 78°59'22"W), así mismo sugerimos el posible establecimiento de una población de esta especie en la costa norte del Perú.


Echiophis brunneus, commonly known as fangjaw eel, is a coastal benthic species belonging to the Ophichthidae family. Its distribution is reported to be in the Eastern Pacific from the Gulf of California (USA) to the Gulf of Guayaquil (Ecuador). In this study, we report for the first time the presence of E. brunneus based on three specimens captured in northern Peru. Additionally, a new maximum size for the species is recorded, and the first COI sequence is added to the BoldSystems database. One of the main characteristics for its determination was the presence of a large canine tooth located in the distal area of the vomer. The genetic distances between E. brunneus with E. punctifer and E. intertinctus were 0.087±0.013 and 0.095±0.014 respectively. With this work the geographical distribution of E. brunneus is extended to Salaverry (08°13'28"S, 78°59'22"W). We also suggest the possible establishment of a population of this species on the northern coast of Peru.

2.
J Mol Biol ; 435(16): 167889, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-36402224

RESUMEN

p53 exerts its tumour suppressor activity by modulating hundreds of genes and it can also repress viral replication. Such is the case of human papillomavirus (HPV) through targeting the E2 master regulator, but the biochemical mechanism is not known. We show that the C-terminal DNA binding domain of HPV16 E2 protein (E2C) triggers heterotypic condensation with p53 at a precise 2/1 E2C/p53 stoichiometry at the onset for demixing, yielding large regular spherical droplets that increase in size with E2C concentration. Interestingly, transfection experiments show that E2 co-localizes with p53 in the nucleus with a grainy pattern, and recruits p53 to chromatin-associated foci, a function independent of the DNA binding capacity of p53 as judged by a DNA binding impaired mutant. Depending on the length, DNA can either completely dissolve or reshape heterotypic droplets into irregular condensates containing p53, E2C, and DNA, and reminiscent of that observed linked to chromatin. We propose that p53 is a scaffold for condensation in line with its structural and functional features, in particular as a promiscuous hub that binds multiple cellular proteins. E2 appears as both client and modulator, likely based on its homodimeric DNA binding nature. Our results, in line with the known role of condensation in eukaryotic gene enhancement and silencing, point at biomolecular condensation of E2 with p53 as a means to modulate HPV gene function, strictly dependent on host cell replication and transcription machinery.


Asunto(s)
Condensados Biomoleculares , Replicación del ADN , Proteínas de Unión al ADN , Papillomavirus Humano 16 , Proteínas Oncogénicas Virales , Proteína p53 Supresora de Tumor , Replicación Viral , Humanos , Línea Celular Tumoral , Cromatina/química , Cromatina/metabolismo , ADN/química , ADN/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Papillomavirus Humano 16/fisiología , Proteínas Oncogénicas Virales/química , Proteínas Oncogénicas Virales/metabolismo , Infecciones por Papillomavirus/virología , Dominios Proteicos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Replicación Viral/fisiología , Condensados Biomoleculares/metabolismo , Condensados Biomoleculares/virología
3.
PLoS Pathog ; 17(11): e1010032, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34735550

RESUMEN

The ubiquitous host protein, CCCTC-binding factor (CTCF), is an essential regulator of cellular transcription and functions to maintain epigenetic boundaries, stabilise chromatin loops and regulate splicing of alternative exons. We have previously demonstrated that CTCF binds to the E2 open reading frame (ORF) of human papillomavirus (HPV) 18 and functions to repress viral oncogene expression in undifferentiated keratinocytes by co-ordinating an epigenetically repressed chromatin loop within HPV episomes. Keratinocyte differentiation disrupts CTCF-dependent chromatin looping of HPV18 episomes promoting induction of enhanced viral oncogene expression. To further characterise CTCF function in HPV transcription control we utilised direct, long-read Nanopore RNA-sequencing which provides information on the structure and abundance of full-length transcripts. Nanopore analysis of primary human keratinocytes containing HPV18 episomes before and after synchronous differentiation allowed quantification of viral transcript species, including the identification of low abundance novel transcripts. Comparison of transcripts produced in wild type HPV18 genome-containing cells to those identified in CTCF-binding deficient genome-containing cells identifies CTCF as a key regulator of differentiation-dependent late promoter activation, required for efficient E1^E4 and L1 protein expression. Furthermore, our data show that CTCF binding at the E2 ORF promotes usage of the downstream weak splice donor (SD) sites SD3165 and SD3284, to the dominant E4 splice acceptor site at nucleotide 3434. These findings demonstrate that in the HPV life cycle both early and late virus transcription programmes are facilitated by recruitment of CTCF to the E2 ORF.


Asunto(s)
Factor de Unión a CCCTC/metabolismo , Diferenciación Celular , Regulación Viral de la Expresión Génica , Papillomavirus Humano 18/genética , Infecciones por Papillomavirus/virología , Empalme del ARN , Proteínas Virales/genética , Factor de Unión a CCCTC/genética , Cromatina/genética , Cromatina/metabolismo , Genoma Viral , Humanos , Queratinocitos/metabolismo , Queratinocitos/virología , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Regiones Promotoras Genéticas , Replicación Viral
4.
Front Immunol ; 12: 643298, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34025655

RESUMEN

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8+ and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/inmunología , Inmunomodulación , Neoplasias de la Boca/inmunología , Proteínas de Neoplasias/inmunología , Receptores CCR8/inmunología , Transducción de Señal/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Microambiente Tumoral/inmunología , Vitamina D/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Linfocitos T Reguladores/patología , Células Th2/patología
5.
Nutr. hosp ; 37(3): 414-421, mayo-jun. 2020. tab, graf
Artículo en Inglés | IBECS | ID: ibc-193848

RESUMEN

INTRODUCTION: nutritional risk is an important prognostic factor in hospitalized patients, but frequently it is underappreciated and not considered as a part of the prognostic evaluation in patients from intensive care units. OBJECTIVE: to evaluate the association between nutritional risk and 28-day mortality and characterize the nutritional support in critically ill patients. METHODS: this was a single-center, prospective cohort study was performed over 7 months in a Medical-surgical ICU of a tertiary hospital in Mexico. From 352 admissions a consecutive sample of 110 patients was included. All of them were ≥ 18 years old, with ≥ 48 h of stay in ICU and with the consent to participate. Nutritional risk assessed by the modified NUTRIC score (mNUTRIC score), 28-day mortality and nutritional support characteristics were recorded. RESULTS: the patient characteristics: mean age 50.7 ± 16.8 years, APACHE II score 15.5 ± 5.8, SOFA score 6.9 ± 3, invasive mechanical ventilation (IMV) 65.5 % and 28-day mortality 23.6 %. High nutritional risk (31.8 %) was associated with 28-day mortality (RR 5.81, 95 % CI 2.69-12.53). In the surviving group, the mNUTRIC score correlated with the length of stay (LOS) in the ICU (r = 0.216, p = 0.049), LOS in the hospital (r = 0.230, p = 0.036) and IMV duration (r = 0.306, p = 0.037). Nutritional support was administered in 55.4 % of the patients, reaching only 52.9 % and 46 % of the energy and protein requirements, respectively. Only 18 % and 21.3 % of the patients achieved the energy and protein requirements, respectively. CONCLUSIONS: high nutritional risk was associated with a higher risk of 28-day mortality. Less than a quarter of the patients receiving nutritional support reached the energy and protein requirements


INTRODUCCIÓN: el riesgo nutricional es un factor pronóstico importante en pacientes hospitalizados, pero frecuentemente es infravalorado y no se considera dentro de la evaluación de los pacientes en unidades de cuidados intensivos. OBJETIVO: evaluar la asociación del riesgo nutricional con la mortalidad al día 28 en pacientes críticos y caracterizar el soporte nutricional. MÉTODOS: se desarrolló un estudio de cohorte prospectivo durante 7 meses en una UCI de tercer nivel en México. Se obtuvo una muestra consecutiva con 110 pacientes de 352 elegibles, con edad ≥ 18 años, estancia ≥ 48 h en UCI, datos completos y consentimiento para participar. El riesgo nutricional fue evaluado con NUTRIC score modificado (mNUTRIC score) y se registró la mortalidad al día 28 y las características del soporte nutricional. RESULTADOS: los pacientes tenían una edad de 50,7 ± 16,8 años; APACHE II, 15,5 ± 5,8; SOFA, 6,9 ± 3; ventilación mecánica invasiva (VMI) en 65,5 % y el 23,6 % de los pacientes falleció al día 28. El alto riesgo nutricional (31,8 %) se asoció con la mortalidad al día 28 (RR 5,81, IC 95 %, 2,69-12,53). En los supervivientes, el mNUTRIC score tuvo correlación con las duraciones de la estancia en UCI (ℓ = 0,216, p = 0,049), estancia hospitalaria (ℓ = 0,230, p = 0,036) y VMI (ℓ = 0,306, p = 0,037). El 55,4 % de los pacientes recibió soporte nutricional. Lograron el 52,9 % y 46 % de las metas energéticas y proteicas, respectivamente. Solo el 18 % alcanzó la meta energética y el 21,3 %, la meta proteica. CONCLUSIONES: los pacientes con alto riesgo nutricional tienen mayor riesgo de morir al día 28. Menos de un cuarto de los pacientes con soporte nutricional alcanzó las metas nutricionales


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Cuidados Críticos/métodos , Estudios de Cohortes , Pronóstico , Apoyo Nutricional , Enfermedad Crítica/epidemiología , Enfermedad Crítica/mortalidad , Desnutrición/epidemiología , Desnutrición/mortalidad , Estudios Prospectivos , Respiración Artificial/métodos , Hospitalización , Nutrición Parenteral Total , Nutrición Enteral
6.
Nutr Hosp ; 34(3): 414-421, 2020 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-32406741

RESUMEN

INTRODUCTION: Introduction: nutritional risk is an important prognostic factor in hospitalized patients, but frequently it is underappreciated and not considered as a part of the prognostic evaluation in patients from intensive care units. Objective: to evaluate the association between nutritional risk and 28-day mortality and characterize the nutritional support in critically ill patients. Methods: this was a single-center, prospective cohort study was performed over 7 months in a Medical-surgical ICU of a tertiary hospital in Mexico. From 352 admissions a consecutive sample of 110 patients was included. All of them were ≥ 18 years old, with ≥ 48 h of stay in ICU and with the consent to participate. Nutritional risk assessed by the modified NUTRIC score (mNUTRIC score), 28-day mortality and nutritional support characteristics were recorded. Results: the patient characteristics: mean age 50.7 ± 16.8 years, APACHE II score 15.5 ± 5.8, SOFA score 6.9 ± 3, invasive mechanical ventilation (IMV) 65.5 % and 28-day mortality 23.6 %. High nutritional risk (31.8 %) was associated with 28-day mortality (RR 5.81, 95 % CI 2.69-12.53). In the surviving group, the mNUTRIC score correlated with the length of stay (LOS) in the ICU (r = 0.216, p = 0.049), LOS in the hospital (r = 0.230, p = 0.036) and IMV duration (r = 0.306, p = 0.037). Nutritional support was administered in 55.4 % of the patients, reaching only 52.9 % and 46 % of the energy and protein requirements, respectively. Only 18 % and 21.3 % of the patients achieved the energy and protein requirements, respectively. Conclusions: high nutritional risk was associated with a higher risk of 28-day mortality. Less than a quarter of the patients receiving nutritional support reached the energy and protein requirements.


INTRODUCCIÓN: Introducción: el riesgo nutricional es un factor pronóstico importante en pacientes hospitalizados, pero frecuentemente es infravalorado y no se considera dentro de la evaluación de los pacientes en unidades de cuidados intensivos. Objetivo: evaluar la asociación del riesgo nutricional con la mortalidad al día 28 en pacientes críticos y caracterizar el soporte nutricional. Métodos: se desarrolló un estudio de cohorte prospectivo durante 7 meses en una UCI de tercer nivel en México. Se obtuvo una muestra consecutiva con 110 pacientes de 352 elegibles, con edad ≥ 18 años, estancia ≥ 48 h en UCI, datos completos y consentimiento para participar. El riesgo nutricional fue evaluado con NUTRIC score modificado (mNUTRIC score) y se registró la mortalidad al día 28 y las características del soporte nutricional. Resultados: los pacientes tenían una edad de 50,7 ± 16,8 años; APACHE II, 15,5 ± 5,8; SOFA, 6,9 ± 3; ventilación mecánica invasiva (VMI) en 65,5 % y el 23,6 % de los pacientes falleció al día 28. El alto riesgo nutricional (31,8 %) se asoció con la mortalidad al día 28 (RR 5,81, IC 95 %, 2,69-12,53). En los supervivientes, el mNUTRIC score tuvo correlación con las duraciones de la estancia en UCI (ℓ = 0,216, p = 0,049), estancia hospitalaria (ℓ = 0,230, p = 0,036) y VMI (ℓ = 0,306, p = 0,037). El 55,4 % de los pacientes recibió soporte nutricional. Lograron el 52,9 % y 46 % de las metas energéticas y proteicas, respectivamente. Solo el 18 % alcanzó la meta energética y el 21,3 %, la meta proteica. Conclusiones: los pacientes con alto riesgo nutricional tienen mayor riesgo de morir al día 28. Menos de un cuarto de los pacientes con soporte nutricional alcanzó las metas nutricionales.


Asunto(s)
Enfermedad Crítica/epidemiología , Desnutrición/complicaciones , Desnutrición/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Enfermedad Crítica/mortalidad , Proteínas en la Dieta/administración & dosificación , Metabolismo Energético , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Apoyo Nutricional , Prevalencia , Pronóstico , Estudios Prospectivos , Factores de Riesgo
7.
Int. j. med. surg. sci. (Print) ; 6(3): 96-100, sept. 2019. ilus
Artículo en Inglés | LILACS | ID: biblio-1247413

RESUMEN

Introduction: Odontogenic mixomas (OMs) are a locally infiltrating slow-growing intraosseous nonmetastasizing tumors of the maxilla and the mandible that have the potential for bone des-truction and cortical expansion, showing high recurrence rates. Their frequency varies around the world, accounting for 3-20% of all odontogenic tumors, ranking third among odontogenic tumors. They predominantly affect young adults, but may occur in various age groups. Report: A 37-year-old female patient who in August 2005 sought treatment at the Maxillofacial Dental Unit at Hospital Higueras, Talcahuano, Chile, for a left maxillary bone lesion. An increase in vo-lume was observed in the left maxillary region in the clinical analysis of the oral cavity. The neo-plasm was sessile and painless, measuring approximately 3 cm, with a greater diameter in the vestibule, firm on palpation and without signs of gangliopathy. Computed cone beam tomogra-phy imaging showed an extensive infiltrating osteolytic lesion in the left maxillary sinus, with noinvolvement of the orbital bone structure. Analysis of incisional biopsy yielded the diagnosis ofOdontogenic Fibromixoma. It was proposed to perform the conservative treatment of the lesion,consisting of enucleation and surgical curettage, obtaining excellent postoperative results and absence of relapse after 11-year follow-up. Conclusion: The present case report provides eviden-ce that supports the conservative surgical approach for the treatment of odontogenic myxomas, which contributes to a better postoperative quality of life for the patient.


Asunto(s)
Humanos , Femenino , Adulto , Neoplasias Maxilares/cirugía , Tumores Odontogénicos/cirugía , Fibroma/cirugía , Fibroma/diagnóstico , Biopsia/métodos , Tomografía Computarizada por Rayos X/métodos , Maxilar/patología
8.
PLoS Biol ; 16(10): e2005752, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30359362

RESUMEN

The complex life cycle of oncogenic human papillomavirus (HPV) initiates in undifferentiated basal epithelial keratinocytes where expression of the E6 and E7 oncogenes is restricted. Upon epithelial differentiation, E6/E7 transcription is increased through unknown mechanisms to drive cellular proliferation required to support virus replication. We report that the chromatin-organising CCCTC-binding factor (CTCF) promotes the formation of a chromatin loop in the HPV genome that epigenetically represses viral enhancer activity controlling E6/E7 expression. CTCF-dependent looping is dependent on the expression of the CTCF-associated Yin Yang 1 (YY1) transcription factor and polycomb repressor complex (PRC) recruitment, resulting in trimethylation of histone H3 at lysine 27. We show that viral oncogene up-regulation during cellular differentiation results from YY1 down-regulation, disruption of viral genome looping, and a loss of epigenetic repression of viral enhancer activity. Our data therefore reveal a key role for CTCF-YY1-dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis.


Asunto(s)
Factor de Unión a CCCTC/metabolismo , Papillomaviridae/genética , Factor de Transcripción YY1/metabolismo , Factor de Unión a CCCTC/genética , Diferenciación Celular/genética , Cromatina/fisiología , Proteínas de Unión al ADN/genética , Regulación hacia Abajo , Epigénesis Genética/genética , Histonas/genética , Humanos , Regiones Promotoras Genéticas/genética , Proteínas Represoras , Factores de Transcripción , Activación Transcripcional/genética , Replicación Viral/genética , Replicación Viral/fisiología , Factor de Transcripción YY1/genética
9.
J Virol ; 91(1)2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27795438

RESUMEN

In papillomavirus infections, the viral genome is established as a double-stranded DNA episome. To segregate the episomes into daughter cells during mitosis, they are tethered to cellular chromatin by the viral E2 protein. We previously demonstrated that the E2 proteins of diverse papillomavirus types, including bovine papillomavirus (BPV) and human papillomavirus 16 (HPV16), associate with the cellular DNA helicase ChlR1. This virus-host interaction is important for the tethering of BPV E2 to mitotic chromatin and the stable maintenance of BPV episomes. The role of the association between E2 and ChlR1 in the HPV16 life cycle is unresolved. Here we show that an HPV16 E2 Y131A mutant (E2Y131A) had significantly reduced binding to ChlR1 but retained transcriptional activation and viral origin-dependent replication functions. Subcellular fractionation of keratinocytes expressing E2Y131A showed a marked change in the localization of the protein. Compared to that of wild-type E2 (E2WT), the chromatin-bound pool of E2Y131A was decreased, concomitant with an increase in nuclear matrix-associated protein. Cell cycle synchronization indicated that the shift in subcellular localization of E2Y131A occurred in mid-S phase. A similar alteration between the subcellular pools of the E2WT protein occurred upon ChlR1 silencing. Notably, in an HPV16 life cycle model in primary human keratinocytes, mutant E2Y131A genomes were established as episomes, but at a markedly lower copy number than that of wild-type HPV16 genomes, and they were not maintained upon cell passage. Our studies indicate that ChlR1 is an important regulator of the chromatin association of E2 and of the establishment and maintenance of HPV16 episomes. IMPORTANCE: Infections with high-risk human papillomaviruses (HPVs) are a major cause of anogenital and oropharyngeal cancers. During infection, the circular DNA genome of HPV persists within the nucleus, independently of the host cell chromatin. Persistence of infection is a risk factor for cancer development and is partly achieved by the attachment of viral DNA to cellular chromatin during cell division. The HPV E2 protein plays a critical role in this tethering by binding simultaneously to the viral genome and to chromatin during mitosis. We previously showed that the cellular DNA helicase ChlR1 is required for loading of the bovine papillomavirus E2 protein onto chromatin during DNA synthesis. Here we identify a mutation in HPV16 E2 that abrogates interaction with ChlR1, and we show that ChlR1 regulates the chromatin association of HPV16 E2 and that this virus-host interaction is essential for viral episome maintenance.


Asunto(s)
ARN Helicasas DEAD-box/genética , ADN Helicasas/genética , ADN Viral/genética , Proteínas de Unión al ADN/genética , Genoma Viral , Papillomavirus Humano 16/genética , Proteínas Oncogénicas Virales/genética , Cromatina/química , Cromatina/metabolismo , ARN Helicasas DEAD-box/metabolismo , ADN/genética , ADN/metabolismo , ADN Helicasas/metabolismo , ADN Viral/metabolismo , Proteínas de Unión al ADN/metabolismo , Dosificación de Gen , Silenciador del Gen , Interacciones Huésped-Patógeno , Papillomavirus Humano 16/metabolismo , Humanos , Queratinocitos/metabolismo , Queratinocitos/virología , Mitosis , Modelos Moleculares , Mutación , Proteínas Oncogénicas Virales/metabolismo , Plásmidos/genética , Plásmidos/metabolismo , Cultivo Primario de Células , Unión Proteica , Estructura Secundaria de Proteína , Puntos de Control de la Fase S del Ciclo Celular , Activación Transcripcional
10.
J Virol ; 91(5)2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28031358

RESUMEN

Rad50-interacting protein 1 (Rint1) associates with the DNA damage response protein Rad50 during the transition from the S phase to the G2/M phase and functions in radiation-induced G2 checkpoint control. It has also been demonstrated that Rint1 is essential in vesicle trafficking from the Golgi apparatus to the endoplasmic reticulum (ER) through an interaction with Zeste-White 10 (ZW10). We have isolated a novel interaction between Rint1 and the human papillomavirus 16 (HPV16) transcription and replication factor E2. E2 binds to Rint1 within its ZW10 interaction domain, and we show that in the absence of E2, Rint1 is localized to the ER and associates with ZW10. E2 expression results in a disruption of the Rint1-ZW10 interaction and an accumulation of nuclear Rint1, coincident with a significant reduction in vesicle movement from the ER to the Golgi apparatus. Interestingly, nuclear Rint1 and members of the Mre11/Rad50/Nbs1 (MRN) complex were found in distinct E2 nuclear foci, which peaked during mid-S phase, indicating that the recruitment of Rint1 to E2 foci within the nucleus may also result in the recruitment of this DNA damage-sensing protein complex. We show that exogenous Rint1 expression enhances E2-dependent virus replication. Conversely, the overexpression of a truncated Rint1 protein that retains the E2 binding domain but not the Rad50 binding domain acts as a dominant negative inhibitor of E2-dependent HPV replication. Put together, these experiments demonstrate that the interaction between Rint1 and E2 has an important function in HPV replication.IMPORTANCE HPV infections are an important driver of many epithelial cancers, including those within the anogenital and oropharyngeal tracts. The HPV life cycle is tightly regulated and intimately linked to the differentiation of the epithelial cells that it infects. HPV replication factories formed in the nucleus are locations where viral DNA is copied to support virus persistence and amplification of infection. The recruitment of specific cellular protein complexes to these factories aids efficient and controlled viral replication. We have identified a novel HPV-host interaction that functions in the cellular response to DNA damage and cell cycle control. We show that the HPV E2 protein targets Rad50-interacting protein 1 (Rint1) to facilitate virus genome replication. These findings add to our understanding of how HPV replicates and the host cell pathways that are targeted by HPV to support virus replication. Understanding these pathways will allow further research into novel inhibitors of HPV genome replication.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Replicación del ADN , Proteínas de Unión al ADN/metabolismo , Papillomavirus Humano 16/fisiología , Proteínas Oncogénicas Virales/metabolismo , Replicación Viral , Secuencia de Aminoácidos , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , ADN Viral/biosíntesis , Humanos , Proteínas Asociadas a Microtúbulos/metabolismo , Unión Proteica , Conformación Proteica en Hélice alfa , Dominios y Motivos de Interacción de Proteínas , Transporte de Proteínas , Origen de Réplica , Puntos de Control de la Fase S del Ciclo Celular
11.
Arch Med Res ; 42(3): 195-8, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21722814

RESUMEN

BACKGROUND AND AIMS: The etiology of preeclampsia (PE) is unknown and the only treatment is removal of the fetus and placenta. The critical changes of this state include the increase of vascular resistance and hypoperfusion in the uteroplacental microcirculation that predispose to hypoxia and ischemia and, therefore, increased oxidative stress through 8-isoprostane, which is characterized by damage to the placenta and endothelium. We undertook this study to compare oxidative stress in pregnant women with PE. METHODS: A case-control, cross-sectional and comparative study was undertaken. Pregnant women between 28 and 38 weeks of gestation with and without PE were recruited. Venous blood samples were taken for determination of 8-isoprostane. Obstetrical variables were measured and 8-isoprostane by radioimmunoassay. SPSS v.11 for Windows was used for descriptive statistics. Mean ± standard deviation, correlation and χ(2) were used for comparison between groups. RESULTS: We studied 45 patients: 20 with PE (44.6%) and 25 without PE (55.4%). The average for 8-isoprostane in preeclamptic patients was 699.2 ± 38.6 pg/dl and without PE was 113.9 ± 52.4 pg/dL (p <0.01), gestational age 32.1 ± 2.6 and 35.1 ± 1.8 weeks, birth weight 1880 ± 238 g and 2787 ± 312 g, respectively. Apgar at birth was similar in both groups. CONCLUSIONS: We found statistical differences in the 8-isoprostane levels in both groups. There was no correlation in perinatal results in both groups according to 8-isoprostane levels. These results could be the basis for the use of antioxidants in the management of PE to counteract tissue damage.


Asunto(s)
Dinoprost/análogos & derivados , Estrés Oxidativo , Preeclampsia/fisiopatología , Adulto , Puntaje de Apgar , Biomarcadores/sangre , Peso al Nacer , Estudios de Casos y Controles , Dinoprost/sangre , Femenino , Humanos , Recién Nacido , Preeclampsia/sangre , Embarazo , Estadísticas no Paramétricas , Adulto Joven
12.
Nucleic Acids Res ; 39(7): 2969-80, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21131281

RESUMEN

Although DNA flexibility is known to play an important role in DNA-protein interactions, the importance of protein flexibility is less well understood. Here, we show that protein dynamics are important in DNA recognition using the well-characterized human papillomavirus (HPV) type 6 E2 protein as a model system. We have compared the DNA binding properties of the HPV 6 E2 DNA binding domain (DBD) and a mutant lacking two C-terminal leucine residues that form part of the hydrophobic core of the protein. Deletion of these residues results in increased specific and non-specific DNA binding and an overall decrease in DNA binding specificity. Using (15)N NMR relaxation and hydrogen/deuterium exchange, we demonstrate that the mutation results in increased flexibility within the hydrophobic core and loop regions that orient the DNA binding helices. Stopped-flow kinetic studies indicate that increased flexibility alters DNA binding by increasing initial interactions with DNA but has little or no effect on the structural rearrangements that follow this step. Taken together these data demonstrate that subtle changes in protein dynamics have a major influence on protein-DNA interactions.


Asunto(s)
Proteínas de Unión al ADN/química , ADN/metabolismo , Papillomavirus Humano 6 , Proteínas Virales/química , ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Modelos Moleculares , Mutación , Resonancia Magnética Nuclear Biomolecular , Unión Proteica , Estructura Terciaria de Proteína , Proteínas Virales/genética , Proteínas Virales/metabolismo
13.
Rev. peru. med. exp. salud publica ; 25(4): 374-379, oct.-dic. 2008. tab
Artículo en Español | LILACS, LIPECS | ID: lil-563978

RESUMEN

Objetivos. Determinar la situación sociofamiliar, valoración funcional y enfermedades prevalentes de los adultos mayores que acuden a los establecimientos de salud del primer nivel de atención de la Dirección de Salud del Callao. Materiales y métodos: Estudio transversal, realizado con 301 adultos mayores, a quienes se evaluó con un cuestionario basado en la ficha única de Valoración Clínica del AdultoMayor establecida por el Ministerio de Salud del Perú. Resultados. La mayoría (69,8 por ciento) de la población eran mujeres (44,5 por ciento) entre 60 y 69 años, 31,9 por ciento fueron categorizados como adulto mayor frágil. Un 79,4 por ciento de adultos mayores es independiente, 46,2 por ciento se encuentra en situación de riesgo social y 28,9 por ciento tiene problema social. La mayoría (66,1 por ciento) carece de un seguro de salud. Las enfermedades prevalentes fueron hipertensión arterial (42,5 por ciento), artrosis (33,6 por ciento) y el antecedente de tuberculosis estuvo presente en el 6,6 por ciento. Las mujeres tuvieron una peor situación sociofamiliar (p menor que 0,05) y la valoración funcional y clínica se deterioró con la edad (p mneor que 0,05). Conclusión. La mayoría de los adultos mayores evaluados se encuentran en riesgo sociofamiliar, por lo que es necesario establecer estrategias de intervención como programas de seguridad social que contribuyan al mejoramiento de la atención integral de salud de las personas adultas mayores.


Objectives. To determine social and familiy situation performing a functional assesment and looking for prevalent diseases in elderly subjects attending primary care health centres in Callao, Peru. Materials and methods. A cross-sectional study performed in 301 elderlysubjects who were administered a questionnaire based on the form for the clinical assessment of aged persons established by the Peruvian Ministry of Health. Results. Most of the subjects were women, 44.5 per cent were between 60 and 69 years old, and 31.9 per cent were classified as frail elderly subjects. 79.4 per cent of this elderly population is independent, 46.2 per cent are at social risk, and 28.9 per cent actually have social problems. Most subjects (66.1 per cent) do not have any health insurance. Most prevalent diseases were hypertension (42.5 per cent) and osteoarthritis (33.6 per cnent), and a past history of tuberculosis (TB) was found in 6.6 per cent. Women had a worse social and family situation (p minor that 0.05), and their functional and clinical assessments findings worsened with age (p minor that 0.05). Conclusion. Most elderly subjects are at a social and familyrisk, so it is necessary to establish interventional strategies, such as social security programs aiming to contribute with the improvement of integrated health care in this population.


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano de 80 o más Años , Anciano Frágil , Atención Primaria de Salud , Relaciones Familiares , Epidemiología Descriptiva , Estudios Transversales , Estudios Observacionales como Asunto , Perú
14.
Rev. peru. med. exp. salud publica ; 22(2): 139-144, abr.-jun. 2005. tab, ilus
Artículo en Español | LILACS, LIPECS | ID: biblio-1111674

RESUMEN

Entre los años 2000-2002 la provincia de Callao presentó las tasas más elevadas de infección humana por Brucella mellitensis en el Perú, además la crianza de caprinos representa una actividad económica local importante. Con el objetivo de conocer la seroprevalencia de Brucelosis en el ganado caprino analizamos una muestra de 175 animales de nueve hatos de los distritos del Callao y Ventanilla, usando la prueba de Rosa de Bengala (RB) para descarte y el 2-mercapto-etanol para confirmación. El 53,7 por ciento (94) de las cabras fue mayor de seis meses; el antecedente de vacunación fue de 38,3 por ciento y 81,9 por ciento, respectivamente. Con RB se obtuvo 10/148 cabras positivas en Callao y 0/27 en Ventanilla; finalmente sólo siete fueron confirmadas. Persiste el riesgo de Brucelosis humana en el Callao ante la presencia de ganado caprino infectado con dicho mal.


Between years 2000 and 2002 Callao province had the highest rates of Brucella melitensis infection in Peru, andgoat breeding is an important economic activity. In order to know Brucellosis seroprevalence in goats, we analyzed a 175 animal sample from nine farms in Callao and Ventanilla districts, using the Bengal Rose test for screening and2-mercapto-ethanol for confirmation. 53,7 per cent (94) goats were more than six months old; history of vaccination was positive in 38,3 per cent and 81,9 per cent respectively. Using Bengal Rose test, 10/148 goats were positive in Callao, and 0/27 in Ventanilla; and, finally, only seven animals had a confirmed diagnosis of Brucella infection. Risk for human brucellosis is latent in Callao because of the presence of infected goats.


Asunto(s)
Animales , Bovinos , Brucella melitensis , Brucelosis , Enfermedades de las Cabras , Estudios Seroepidemiológicos , Rosa Bengala , Perú
15.
Acta Trop ; 94(1): 55-9, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15777720

RESUMEN

We evaluated the use of polymerase chain reaction (PCR) for diagnosis of mucosal leishmaniasis (ML) in an endemic area in Acre, Brazil, where Leishmania braziliensis is present. Leishmania DNA was detected 34 of 35 cases, yielding a positivity rate of 97.1%, which was higher than the positivity rates for all of the other diagnostic methods studied, namely Montenegro skin test (MST), anti-Leishmania serological testing and microscopic examination of lesion biopsy specimens. These findings have led us to propose guidelines for the diagnosis of ML that use PCR as the principal method of parasitological confirmation of cases.


Asunto(s)
Leishmania braziliensis/genética , Leishmaniasis Cutánea/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Antiprotozoarios/sangre , Antiprotozoarios/uso terapéutico , Biopsia , Brasil , Niño , ADN Protozoario/química , ADN Protozoario/genética , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Masculino , Meglumina/uso terapéutico , Antimoniato de Meglumina , Persona de Mediana Edad , Compuestos Organometálicos/uso terapéutico , Sensibilidad y Especificidad , Pruebas Cutáneas
16.
Ginecol Obstet Mex ; 66: 474-9, 1998 Nov.
Artículo en Español | MEDLINE | ID: mdl-9823706

RESUMEN

Breast feeding frequency in our country is between 13 and 80% and it is diminishing. One of the purposes of the Program called Hospital Friend of the Child and the Mother is to favor breast feeding but this has not been evaluated as yet. Frequency of breast feeding among the mothers who received the program, and the ones without it, in the influence area of HGZ 1-A; and the ones factors that could influenced for breast feeding. An analytic transversal study, was carried out, in mothers with a child between 6 and 12 months of age who assisted to the Outpatient consultation at HGZ 1-A and MME 10, 15 and 43, during the study period. The were invited to participate to have an interview, to know the mother's age, civil status, socioeconomical level, schooling and amount of sons. The place where her last delivery took place, was asked for. It was asked if breast feeding took place during the adequate time; the causes for not do it, and other points about breast feeding. The questionnaire in a first phase was prepared in order to be easily understood at the time of its application, and it was carried out by only one person. At the time of interview it was not known if the mother had used breast feeding or not. The amount in the sample was 261 mothers. The statistical analysis was of a descriptive type, for comparison of averages; it was used for comparison of square chi and calculations of reason of momios with IC at 95%. Two hundred and sixty two mothers were interviewed. The interview was done in 211/262, (80.5%) in the UMF and the rest at HGZ. Average age 26 years, 78.6% were married; average schooling, 8 years (74; good socioeconomical level, 70%, home labor. Amount of children was 1 to 6, 48% had only one child; average age of the last child at the time of interview, 11 moths. The resolution of the last pregnancy occurred in 73% of the cases in a IMSS hospital; 15.3% in a private hospital, and the rest in another institution. The program was given, more frequently at the IMSS, than in the rest 232/262; (88%) were breast fed. Average of time of breast feeding, 9 moths. There were no difference of sociodemographic variables in the group with breast feeding, and the one without breast feeding. The common causes (75%) for no breast feeding, were of maternal origin (infections, lack of milk production, work, etc.); the rest mentioned rejection to breast feeding. There was a better knowledge of breast feeding among the mothers who used it. The factors statistically associated to breast feeding were: conjoint lodging; to offer breast during the first hour of life; and have received information about this Program. The Program in the influence area of HGZ 1-A favors breast feeding. The factors for this were: improvement of mother-Child relation and the better knowledge of the advantages of breast feeding.


Asunto(s)
Lactancia Materna/estadística & datos numéricos , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Recién Nacido , México , Evaluación de Programas y Proyectos de Salud
17.
Ginecol. obstet. Méx ; 66(11): 474-9, nov. 1998. tab
Artículo en Español | LILACS | ID: lil-232600

RESUMEN

La frecuencia de lactancia en nuestro país varía entre 13 y 80 por ciento y se ha observado que existe una tendencia a la diminución con el transcurso del tiempo. Uno de los propósitos del Programa Hospital Amigo del Niño y de la Madre (PHANM) es favorecer la lactancia pero hasta el momento no se ha evaluado su impacto. Se comparó la frecuencia de lactancia entre las madres que recibieron el PHANM y las que no lo recibieron, en el área de influencia del HGZ 1-A "Los Venados", e identificar los factores que pudieron haber influido para la lactancia. Se realizó un estudio transversal analítico, con madres que tenían un hijo entre 6 y 12 meses de edad, que acudieron a la consulta externa del HGZ 1-A y las UMNF 10, 15 y 43, durante el periodo de estudio. A las madres se les invitó a participar para llevar a cabo una entrevista donde se investigó la edad de la madre, estado civil, nivel socioeconómico, escolaridad y número de hijos. Se interrogó sobre el sitio de atención de la resolución del últim embarazo, sobre los puntos del PHANM, si se amamantó, el tiempo de amamantamiento, las causas de no realizarlo, además de algunos conocimientos sobre la lactancia. El cuestionario en una primera fase se validó para que fuera comprensible al momento de su aplicación y se llevó a cabo por una sola persona. En el momento de la entrevista no se conocía si la madre había amamantado o no. Se calculó el tamaño de muestra con 261 madres. El análisis estadístico fue de tipo descriptivo; para comparación de promedio se utilizó, para la comparación de proporciones chi-cuadrada y cálculo de razón de momios con IC al 95 por ciento. Se entrevistaron 262 madres. La entrevista se realizó en 211/262 (80.5 por ciento) en la UMF y el resto en el HGZ. Mediana de edad 26 años, 78.6 por ciento eran casadas, mediana de escolaridad, ocho años; 74 por ciento, nivel socioeconómico bueno ; 70 por ciento amas de casa. El número de hijos varió de 1 a 6, 48 por ciento tenían sólo un hijo; la edad promedio del último hijo al momento de la entrevista, 11 meses. La resolución del último embarazo ocurrió en el 76.3 por ciento en un hospital del IMSS...


Asunto(s)
Humanos , Femenino , Adolescente , Adulto , Lactancia Materna/estadística & datos numéricos , Evaluación de Programas y Proyectos de Salud , México , Alojamiento Conjunto
18.
Rev. méd. hered ; 7(3): 125-31, sept. 1996. tab
Artículo en Español | LILACS, LIPECS | ID: lil-224653

RESUMEN

La hipercolesterolemia es frecuente en las personas mayores de 65 años. Objetivo: determinar la prevalencia de hipercolesterolemia y de los factores de riesgo para enfermedad cardiovascular en personas mayores de 65 años residentes en Lima. Material y Métodos: se evaluaron en forma prospectiva 214 gerontes (187 mujeres y 27 hombres) no institucionalizados, determinándose los niveles séricos de colesterol total, LDL-colesterol, HDL-colesterol, VLDL-colesterol y triglicéridos por un método enzimático-colorimétrico (Laboratorio Human). Resultados y Conclusiones: el valor promedio de colesterol total en el grupo sin factores de riesgo para enfermedad cardiovascular fue de 222.48+ 42.60 mg/dl. La prevalencia de hipercolesterolemia fue de 39 por ciento (41 por ciento en mujeres y 26 por ciento en hombres). El 40 por ciento presentó LDL-colesterol>160mg/dl y solo un participante tuvo HDL-colesterol<35mg/dl. Los factores de riesgo de enfermedad cardiovascular más frecuentes fueron: hipertensión arterial 49.5 por ciento, obesidad 22.4 por ciento y diabetes mellitus 10.2 por ciento. La prevalencia de hipercolesterolemia en nuestra población geronte es similar a lo reportado en la literatura. La aplicación de los criterios del National Cholesterol Education Program en nuestra muestra nos permitió establecer que el 57 por ciento necesita un análisis completo de lípidos.


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Enfermedades Cardiovasculares , Colesterol , Anomalías Cardiovasculares , Hipercolesterolemia , Prevalencia , Factores de Riesgo
19.
Rev. méd. hered ; 6(1): 5-10, mar. 1995. tab, ilus
Artículo en Español | LILACS, LIPECS | ID: lil-176324

RESUMEN

La prevalencia de hipotiroidismo aumenta con el envejecimiento y clinicamente es muy difícil de diagnosticarlo en los adultos mayores. En este trabajo investigamos la prevalencia y etiología de hipotiroidismo oculto en un grupo de 190 gerontes supuestamente eutiroideos de Lima. Veinte pacientes (10.47 por ciento) tuvieron niveles elevados de tirotrofina: 2 de ellos (1.04 por ciento) tenían hipotiroidismo "clásico" y 18 (9.42 por ciento) "hipotiroidismo sub clínico" (con valores normales de T4 libre pero significativamente mas bajosque en los eutiroideos). No se encontró diferencias en la frecuencia de síntomas y signos clínicos entre los gerontes hipotiroideos y eutiroideos. De las 20 personas hipotiroideas, 13 (65 por ciento) presentaron títulos positivos de anticuerpos antitiroideos (antimicrosomales), 1 había recibido radioterapia cervical y 2 yodo radioactivo en el pasado y en 4 no se pudo definir la etiología. En conclusión, existe una alta prevalencia de insuficiencia tiroidea entre los adultos mayores "supuestamente eutiroideos" que hemos estudiado, siendo la etiología más frecuente la secundaria a tiroiditis autoinmune


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano , Hipotiroidismo/diagnóstico , Hipotiroidismo/etiología , Tiroiditis Autoinmune/diagnóstico , Tiroiditis Autoinmune/etiología , Signos y Síntomas
20.
Rev Gastroenterol Mex ; 55(1): 25-9, 1990.
Artículo en Español | MEDLINE | ID: mdl-2291063

RESUMEN

A case of hepatic fascioliasis in the common bile duct is reported in a 54 years female. Upon surgical exploration of the biliary tract, one adult form of hepatic Fasciola was found, without evidence of cholelithiasis. Retrospectively we reviewed the oral cholecystography and the image originally believed to be gallstone, in fact was a hepatic Fasciola. Reviewing past literature, we have not encountered any previous case in which hepatic Fasciola was diagnosed by oral cholecystography.


Asunto(s)
Enfermedades del Conducto Colédoco/parasitología , Fascioliasis/diagnóstico , Enfermedades del Conducto Colédoco/diagnóstico , Femenino , Humanos , Persona de Mediana Edad
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