RESUMEN
A patient was born with a mass at the base of the thumb approximately 1.5 cm in diameter on the radial side of the fingers. The mass had globular swelling filled with hemorrhagic fluid and was dark red. X-rays and histology of the excised specimen suggested the diagnosis of gangrene and torsion of polydactyly. Prenatal torsion of polydactyly is not a common occurrence; moreover, prenatal torsion of polydactyly has only been found in ulnar polydactyly. Our case is a novel case of radial polydactyly that was gangrenous at birth owing to prenatal torsion. Diagnosing such a mass at the base of the thumb is important.
Asunto(s)
Polidactilia , Pulgar , Recién Nacido , Humanos , Pulgar/cirugía , Pulgar/patología , Gangrena/cirugía , Polidactilia/diagnóstico por imagen , Polidactilia/cirugía , Dedos/patologíaRESUMEN
The 2019 novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global outbreak of infection. In general, children with coronavirus disease-2019 have been reported to show milder respiratory symptoms than adult patients. Here, we have described a case of a SARS-CoV-2-infected infant who presented to our hospital with a severe episode of an apparent life-threatening event (ALTE). An 8-month-old, otherwise healthy female infant presented to our hospital because of a sudden cardiopulmonary arrest. Approximately 1 h before this episode, the patient showed no symptoms, except a worse humor than usual. On arrival at our hospital, the patient had severe acidosis, but there were no clear signs of inflammatory response. Chest computed tomography showed weak consolidations in the upper right lung and atelectasis in the lower left lung. No signs of congenital heart disease or cardiomyopathy were observed on echocardiography, and no significant arrhythmia was observed during the clinical course. However, SARS-CoV-2 RNA was detected by real-time reverse transcription polymerase chain reaction in tracheal aspirate and urine samples. Although the assessment of further similar cases is indispensable, this case suggests that SARS-CoV-2 infection may be an underlying factor in the pathophysiology of ALTE.
Asunto(s)
Evento Inexplicable, Breve y Resuelto/etiología , COVID-19/etiología , Evento Inexplicable, Breve y Resuelto/diagnóstico por imagen , COVID-19/diagnóstico , Prueba de Ácido Nucleico para COVID-19 , Electrocardiografía , Femenino , Paro Cardíaco/etiología , Pruebas Hematológicas , Humanos , Lactante , Tomografía Computarizada por Rayos XRESUMEN
GH-secreting pituitary adenomas (GHomas) are rare in the pediatric population. Guanine nucleotide-binding protein, alpha stimulating (GNAS) somatic mutations are often found in patients with GHoma. Here, we report an 8-year-old girl with GH-secreting pituitary adenoma successfully treated by operative tumor resection and postoperative treatment with octreotide long-acting release (LAR). Tumor DNA sequence analysis revealed a somatic heterozygous c.680A>T (p.Gln227Leu) mutation in GNAS. We reviewed 1,084 cases of GHomas, 409 (37.7%) of which harbored GNAS mutations. In pediatrics cases, aged 15 years or younger, 11 harbored a GNAS mutation, and GNAS p.Arg201Cys was identified in five cases. No other cases of codon 227 mutation were detected. These cases suggest that, in pediatric patients, the clinical features of GHoma may differ from those observed in adults. This is possibly related to octreotide or dopamine agonist resistance. Of six patients with surgical resistance, only one was reactive when treated with octreotide. Our case shows that octreotide LAR is an effective choice for treating GNAS-induced GHoma. This is the first report detailing the effectiveness of octreotide LAR in a GNAS codon 227 mutation-induced GHoma in a pediatric case. Examination of the relationship between genetic variation and clinical features in pediatric patients will enable us to assess the long-term effects of surgical and medical treatment of GHomas.
Asunto(s)
Cromograninas/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Adenoma Hipofisario Secretor de Hormona del Crecimiento/genética , Mutación , Neoplasias Hipofisarias/genética , Prolactinoma/genética , Niño , Análisis Mutacional de ADN , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Humanos , Neoplasias Hipofisarias/patología , Prolactinoma/patologíaRESUMEN
Accumulating evidence indicates that the Notch signaling pathway has crucial roles in the control of fate decision and differentiation in numerous cell types. However, the role of Notch signaling in regulating proliferation and differentiation of myeloid progenitor cells remains controversial. To elucidate this issue, we modulated Notch activity through transducing a constitutively activated form of Notch1 and/or a dominant-negative form of MAML1 (DNMAML1) into myeloid progenitor 32D cells and assessed their effects on cell proliferation and differentiation. We found that Notch1 activation enhances proliferation and delays granulocytic differentiation of 32D cells. The enhanced proliferation due to activated Notch1 signaling was associated with upregulation of c-Myc, followed by decreased expression of p21 and p27, and increased cdc2 kinase activity, through a mechanism that was not blocked by DNMAML1. Conversely, Notch1 activation significantly delayed granulocytic differentiation and maintained a part of myeloid progenitor cells in an immature stage, and this Notch1-mediated effect was dependent on MAML. The Notch1-induced effects on mye myeloid cell proliferation and differentiation were likely mediated by induction of c-Myc and repression of PU.1, respectively. Thus, Notch1 signaling plays an important part in modulating proliferation and differentiation in MAML-independent and -dependent manners and promoting expansion of myeloid progenitors.
Asunto(s)
Proteína Quinasa CDC2/metabolismo , Diferenciación Celular , Proliferación Celular , Células Progenitoras Mieloides/metabolismo , Receptor Notch1/metabolismo , Transducción de Señal , Proteína Quinasa CDC2/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Granulocitos/citología , Granulocitos/metabolismo , Células HL-60 , Humanos , Células Progenitoras Mieloides/citología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Receptor Notch1/genética , Transactivadores/genética , Transactivadores/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
In many cancers, somatic mutations confer tumorigenesis and drug-resistance. The recently established clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is a potentially elegant approach to functionally evaluate mutations in cancers. To reproduce mutations by homologous recombination (HR), the HR pathway must be functional, but DNA damage repair is frequently impaired in cancers. Imatinib is a tyrosine kinase inhibitor for BCR-ABL1 in Philadelphia chromosome-positive (Ph+) leukemia, and development of resistance due to kinase domain mutation is an important issue. We attempted to introduce the T315I gatekeeper mutation into three Ph+ myeloid leukemia cell lines with a seemingly functional HR pathway due to resistance to the inhibitor for poly (ADP) ribose polymerase1. Imatinib-resistant sublines were efficiently developed by the CRISPR/Cas9 system after short-term selection with imatinib; resulting sublines acquired the T315I mutation after HR. Thus, the usefulness of CRISPR/Cas9 system for functional analysis of somatic mutations in cancers was demonstrated.
Asunto(s)
Sistemas CRISPR-Cas , Proteínas de Fusión bcr-abl/genética , Recombinación Homóloga , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Humanos , Mesilato de Imatinib/farmacología , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Ftalazinas/farmacología , Piperazinas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Bases de Schiff/farmacologíaRESUMEN
The effect and safety of combination prophylaxis for hepatic veno-occlusive disease (VOD) following stem cell transplantation (SCT) was retrospectively evaluated in a total of 53 children who survived until day 30. Prophylaxis was started on the day before conditioning, and heparin (10 unit/kg/hr) alone was used in 6 patients, PGE1 (5 ng/kg/min) plus heparin plus PTX (200 mg/day) in 17 patients, lipo-PGE1 (0.5 ng/kg/min) plus heparin plus PTX in 7 patients, and lipo-PGE1 plus heparin in 23 patients. Diagnosis of VOD was made based on McDonald's criteria in 5 cases (9.4%), but not on Jones' criteria. No statistically significant difference was observed in the incidence of VOD among each prophylaxis group. The degree of VOD was mild in all of 5 cases, and all recovered with continuation of the prophylactic procedure. Each prophylactic procedure was performed without any significant adverse effect except for seizure induced by lipo-PGE1 in one patient with Lennox syndrome. Since both the incidence and fatality rate of VOD in children undergoing SCT are approximately 20% according to most of the previous reports, the present study suggests the effectiveness of combination prophylaxis.