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Cancer Causes Control ; 25(10): 1379-86, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25048604


PURPOSE: Previous studies suggest that solar UV exposure in early life is predictive of cutaneous melanoma risk in adulthood, whereas the relation of BRAF mutation with sun exposure and disease prognosis has been less certain. We investigated the associations between BRAF(V600E) and NRAS(Q61R) mutations and known risk factors, clinicopathologic characteristics and clinical outcomes of melanoma in a case series of primary invasive cutaneous melanoma from the Nurses' Health Study (NHS). METHODS: Somatic BRAF(V600E) and NRAS(Q61R) mutations of 127 primary invasive melanomas from the NHS cohort were determined by pyrosequencing using formalin-fixed, paraffin-embedded block tissues. Logistic regression analyses were performed to detect the associations of mutations with melanoma risk factors, and Kaplan-Meier method was used to examine associations between mutations and survival. RESULTS: The odds ratios for harboring BRAF(V600E) mutations were 5.54 (95% CI 1.19-25.8, p(trend) = 0.02) for women residing in states with UV index ≥ 7 versus those residing in states with UV index ≤5 at 30 years of age. Patients with BRAF(V600E) mutations tended to have shorter melanoma-specific survival when compared to patients with wild type at both loci (median survival time 110 vs. 159 months) (p = 0.03). No association was found between NRASQ61R mutation and melanoma risk factors or melanoma-specific survival. CONCLUSIONS: BRAF(V600E) mutations in primary cutaneous melanomas were associated with residence in locations with medium and high UV indices in mid-life. BRAF(V600E) mutation may be associated with an unfavorable prognosis among melanoma patients.

GTP Fosfohidrolasas/genética , Melanoma/genética , Proteínas de la Membrana/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Melanoma/diagnóstico , Melanoma/mortalidad , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/mortalidad , Tasa de Supervivencia , Resultado del Tratamiento , Rayos Ultravioleta/efectos adversos
Blood ; 117(6): 1966-76, 2011 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-21148332


In early-stage cutaneous T-cell lymphoma (CTCL), malignant T cells are confined to skin and are difficult to isolate and discriminate from benign reactive cells. We found that T cells from CTCL skin lesions contained a population of large, high-scatter, activated skin homing T cells not observed in other inflammatory skin diseases. High-scatter T (T(HS)) cells were CD4(+) in CD4(+) mycosis fungoides (MF), CD8(+) in CD8(+) MF, and contained only clonal T cells in patients with identifiable malignant Vß clones. T(HS) cells were present in the blood of patients with leukemic CTCL, absent in patients without blood involvement, and contained only clonal malignant T cells. The presence of clonal T(HS) cells correlated with skin disease in patients followed longitudinally. Clonal T(HS) cells underwent apoptosis in patients clearing on extracorporeal photopheresis but persisted in nonresponsive patients. Benign clonal T-cell proliferations mapped to the normal low-scatter T-cell population. Thus, the malignant T cells in both MF and leukemic CTCL can be conclusively identified by a unique scatter profile. This observation will allow selective study of malignant T cells, can be used to discriminate patients with MF from patients with other inflammatory skin diseases, to detect peripheral blood involvement, and to monitor responses to therapy.

Linfoma Cutáneo de Células T/inmunología , Linfoma Cutáneo de Células T/patología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/patología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Proliferación Celular , Separación Celular , Proteínas de Escherichia coli , Citometría de Flujo , Factores de Transcripción Forkhead/metabolismo , Genes Codificadores de la Cadena beta de los Receptores de Linfocito T , Humanos , Activación de Linfocitos , Linfoma Cutáneo de Células T/genética , Linfoma Cutáneo de Células T/metabolismo , Micosis Fungoide/genética , Micosis Fungoide/inmunología , Micosis Fungoide/metabolismo , Micosis Fungoide/patología , Estadificación de Neoplasias , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , Factores de Transcripción
Pediatr Radiol ; 39(8): 854-6, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19381626


We report a 6-year-old boy with large duplicated müllerian duct remnant who presented with recurrent urinary tract infections and dysuria. His prior urological problems included proximal hypospadias (repaired), urachal cyst, and a unilateral undescended testis. Imaging evaluation included US, MRI, and cystoscopy. Laparoscopic resection was performed via a retrovesical approach. The patient was free of symptoms after surgery.

Cistoscopía , Imagen por Resonancia Magnética , Conductos Paramesonéfricos , Ultrasonografía , Niño , Humanos , Laparoscopía , Masculino , Conductos Paramesonéfricos/anomalías , Conductos Paramesonéfricos/diagnóstico por imagen , Conductos Paramesonéfricos/patología , Conductos Paramesonéfricos/cirugía , Resultado del Tratamiento
Urology ; 63(4): 778-9, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15072907
Brain Res ; 924(2): 133-40, 2002 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-11750898


The dementia in Alzheimer disease (AD) is usually attributed to widespread neuronal loss in conjunction with the pathologic hallmarks of intracellular neurofibrillary tangles and extracellular plaques containing amyloid (A beta) in fibrillar form. Recently it has been demonstrated that non-fibrillar assemblies of A beta possess electrophysiologic activity, with the corollary that they may produce dementia by disrupting neuronal signaling prior to cell death. We therefore examined the effects of soluble oligomers of A beta(1-42) on long-term potentiation (LTP) and long-term depression (LTD), two cellular models of memory, in the dentate gyrus of rat hippocampal slices. Compared with vehicle controls, slices pre-incubated 60 min in the presence of A beta-derived diffusible ligands (ADDLs) showed no differences in threshold intensity to evoke a synaptic response, slope of field excitatory post-synaptic potentials (EPSPs), or the input/output function. Tetanus-induced LTP and reversal of LTD were strongly inhibited in ADDLs-treated slices whereas LTD was unaffected. These data suggest that soluble non-fibrillar amyloid may contribute to the pathogenesis of AD both by impairing LTP/memory formation at the cellular level and by creating 'neuroplasticity imbalance' manifested by unopposed LTD in the setting of impaired capacity for neural repair via reversal of LTD or LTP.

Péptidos beta-Amiloides/farmacología , Giro Dentado/fisiología , Potenciación a Largo Plazo/efectos de los fármacos , Inhibición Neural/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Animales , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Femenino , Masculino , Plasticidad Neuronal/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Solubilidad , Sinapsis/fisiología