RESUMEN
The pancreas is derived from a pool of multipotent progenitor cells (MPCs) that co-express Pdx-1 and Ptf1a. To more precisely define how the individual and combined loss of Pdx-1 and Ptf1a affects pancreatic MPC specification and differentiation we derived and studied mice bearing a novel Ptf1a(YFP) allele. While the expression of Pdx-1 and Ptf1a in pancreatic MPCs coincides between E9.5 and 12.5 the developmental phenotypes of Pdx-1 null and Pdx-1; Ptf1a double null mice are indistinguishable, and an early pancreatic bud is formed in both cases. This finding indicates that Pdx-1 is required in the foregut endoderm prior to Ptf1a for pancreatic MPC specification. We also found that Ptf1a is neither required for specification of Ngn3-positive endocrine progenitors nor differentiation of mature beta-cells. In the absence of Pdx-1 Ngn3-positive cells were not observed after E9.5. Thus, in contrast to the deletion of Ptf1a, the loss of Pdx-1 precludes the sustained Ngn3-based derivation of endocrine progenitors from pancreatic MPCs. Taken together, these studies indicate that Pdx-1 and Ptf1a have distinct but interdependent functions during pancreatic MPC specification.
Asunto(s)
Diferenciación Celular , Proteínas de Homeodominio/metabolismo , Células Madre Multipotentes/citología , Páncreas/embriología , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Alelos , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/fisiología , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Proteínas de Homeodominio/análisis , Proteínas de Homeodominio/genética , Islotes Pancreáticos/citología , Islotes Pancreáticos/embriología , Islotes Pancreáticos/metabolismo , Proteínas Luminiscentes/análisis , Proteínas Luminiscentes/genética , Ratones , Ratones Mutantes , Microscopía Fluorescente , Células Madre Multipotentes/metabolismo , Proteínas del Tejido Nervioso/fisiología , Páncreas/citología , Páncreas/metabolismo , Transactivadores/análisis , Transactivadores/genética , Factores de Transcripción/análisis , Factores de Transcripción/genéticaRESUMEN
PURPOSE: We sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT). MATERIALS AND METHODS: We retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (131I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic 131I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions. RESULTS: Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral 131I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive. In vitro, dental amalgam and Argenco HP 77 bound 131I in a time-dependent manner over 1-16 days of exposure. Despite subsequent washings with normal saline, significant 131I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced 131I from amalgam, with near-total displacement of I from Argenco HP 77. CONCLUSION: SPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to common dental metals.