RESUMEN
Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.
Asunto(s)
Anemia de Diamond-Blackfan/patología , Células Madre Hematopoyéticas/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Anemia de Diamond-Blackfan/dietoterapia , Anemia de Diamond-Blackfan/genética , Animales , Benzamidas/farmacología , Benzamidas/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Proliferación Celular , Células Cultivadas , Dioxoles/farmacología , Dioxoles/uso terapéutico , Modelos Animales de Enfermedad , Eritropoyesis/efectos de los fármacos , Eritropoyesis/genética , Humanos , Ratones , Ratones Transgénicos , Mutación , Cultivo Primario de Células , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Pirazoles/farmacología , Pirazoles/uso terapéutico , Quinolinas/farmacología , Quinolinas/uso terapéutico , ARN Interferente Pequeño/metabolismo , Proteínas Ribosómicas/genéticaRESUMEN
Malignant melanoma of the scrotum is the rarest of primary genitourinary melanomas, with only 3 cases reported previously. We present an additional case of this often aggressive malignancy. The pertinent literature is reviewed and the current management strategies are discussed.
Asunto(s)
Neoplasias de los Genitales Masculinos/epidemiología , Melanoma/epidemiología , Escroto , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Aorta , Hematuria/etiología , Arterias Mesentéricas , Venas Renales , Adulto , Angiografía , Femenino , Humanos , Venas Renales/diagnóstico por imagenRESUMEN
Two boys with acute urinary retention were found to have a persistent pelvic mass after bladder decompression. Evaluation in each disclosed a large pelvic abscess secondary to a ruptured appendix. The diagnosis of appendicitis may be difficult and appendiceal abscess presenting with acute urinary retention in children has been reported previously in only 7 instances. History, physical examination, laboratory studies, and radiographic and ultrasonic evaluations should lead to the correct diagnosis, and surgical intervention restores normal voiding.
Asunto(s)
Absceso/diagnóstico , Apéndice , Trastornos Urinarios/diagnóstico , Absceso/diagnóstico por imagen , Absceso/cirugía , Enfermedad Aguda , Adolescente , Apéndice/diagnóstico por imagen , Enfermedades del Ciego/diagnóstico , Enfermedades del Ciego/diagnóstico por imagen , Enfermedades del Ciego/cirugía , Diagnóstico Diferencial , Humanos , Masculino , Radiografía , Ultrasonografía , Trastornos Urinarios/etiologíaRESUMEN
Three cases of acute penile injury are presented. Corpus cavernosography at the time of presentation was obtained, confirming the diagnosis. Radiologic evaluations including cavernosography and when indicated urethrography are discussed. Management modalities are reviewed including our preference for surgical exploration when a cavernosal tear has been documented.
Asunto(s)
Pene/lesiones , Adolescente , Adulto , Coito , Edema/etiología , Edema/patología , Edema/cirugía , Hematoma/etiología , Hematoma/patología , Hematoma/cirugía , Humanos , Masculino , Masturbación , Enfermedades del Pene/etiología , Enfermedades del Pene/patología , Enfermedades del Pene/cirugía , Pene/diagnóstico por imagen , Pene/cirugía , RadiografíaRESUMEN
Accurate diagnosis and successful management depend on knowledge of the anatomy and regulatory physiology of micturition. Incontinence is classified according to its mechanisms--passive incontinence, active incontinence with or without complete emptying, and overflow incontinence. Approaches to management include pharmacotherapy, surgical procedures and important steps in supportive care. This is a problem of any age. Educating the patient is essential.
