RESUMEN
During early development, the enteric nervous system forms from the migration of enteric neural crest cells (ENCCs) from the foregut to the hindgut, where they undergo proliferation and differentiation facilitated by interactions with enteric mesenchymal cells (EMCs). This study investigates the impact on ENCC migration of EMC-ENCC communication mediated by GFRA1b expressed in EMCs. GFRA1-expressing cells in day 11-12 (E11-12) mouse embryos differentiated into smooth muscle cells from E12 onwards. Observations at E12-13.5 revealed high levels of GFRA1 expression on the anti-mesenteric side of the hindgut, correlating with enhanced ENCC migration. This indicates that GFRA1 in EMCs plays a role in ENCC migration during development. Examining GFRA1 isoforms, we found high levels of GFRA1b, which lacks amino acids 140-144, in EMCs. To assess the impact of GFRA1 isoforms on EMC-ENCC communication, we conducted neurosphere drop assays. This revealed that GFRA1b-expressing cells promoted GDNF-dependent extension and increased neurite density in ENCC neurospheres. Co-culture of ENCC mimetic cells expressing RET and GFRA1a with EMC mimetic cells expressing GFRA1a, GFRA1b, or vector alone showed that only GFRA1b-expressing co-cultured cells sustained RET phosphorylation in ENCC-mimetic cells for over 120 min upon GDNF stimulation. Our study provides evidence that GFRA1b-mediated cell-to-cell communication plays a critical role in ENCC motility in enteric nervous system development. These findings contribute to understanding the cellular interactions and signaling mechanisms that underlie enteric nervous system formation and highlight potential therapeutic targets for gastrointestinal motility disorders.
Asunto(s)
Sistema Nervioso Entérico , Cresta Neural , Animales , Ratones , Diferenciación Celular/fisiología , Movimiento Celular/fisiología , Sistema Nervioso Entérico/fisiología , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Cresta Neural/metabolismo , Isoformas de Proteínas/metabolismoRESUMEN
PURPOSE: Cell-based therapy is a potential treatment option for neurointestinal diseases by serving as a source of neural progenitor cells to replace missing or abnormal enteric neurons. Using an ex vivo transplantation model, we recently demonstrated that treatment with collagenase and fibronectin promotes infiltration of transplanted enteric neural crest cells (ENCCs) toward the colon lumen. The aim of this study was to determine whether this new method also promotes colonization of transplanted ENCCs in vivo. METHODS: Collagenase was applied locally on the anti-mesenteric area of the recipient colon using filter paper, followed by fibronectin. Neurospheres were generated from ENCCs isolated from fetal mouse intestines and transplanted into the collagenase and fibronectin-treated colon. Engraftment of neurospheres was confirmed by immunofluorescence. RESULTS: Neurospheres transplanted onto PBS- or fibronectin-treated colons were not observed to infiltrate to the muscle layer. However, when used in combination with type I collagenase and fibronectin in the recipient colon, transplanted neurospheres reached Auerbach's plexus. CONCLUSION: We demonstrated that transplanted neurospheres grow into Auerbach's plexus in the recipient colon pretreated with collagenase and fibronectin.
Asunto(s)
Sistema Nervioso Entérico , Cresta Neural , Ratones , Animales , Plexo Mientérico , Fibronectinas , Colon , Colagenasas , Sistema Nervioso Entérico/fisiologíaRESUMEN
The enteric nervous system (ENS) regulates gastrointestinal motility, secretion, and absorption. Developmental ENS dysplasia causes intestinal ganglion dysfunction, including Hirschsprung's disease. Given their potential ability to replenish insufficient neurons, transplantation of enteric neural cells provides the prospect of a cure. In this study, we used an ex vivo mouse colon transplant model to demonstrate that treatment with collagenase and fibronectin altered the migration of transplanted cells from the direction of the colon surface toward the lumen. Collagenase-treated colons exhibited enhanced expression of type III and VI collagens, which inhibited fibronectin-induced enteric neural crest cell (ENCC) migration. Invasion of neurospheres into colon was dependent on preoperative treatment of recipient colon with collagenase and fibronectin, which enhanced neurosphere motility towards the direction of colon lumen. Infiltration of transplanted ENCCs into the colon increased proportionally to the degree of dedifferentiation of surrounding smooth muscle cells, which was induced in a neurosphere-dependent manner in collagenase-treated colon. Furthermore, induction of GDNF expression, a Ret ligand that promotes enteric neural cell migration, was observed in treated colons. Our results suggest that the environment provided by the extracellular matrix of the colon surface affects the direction of transplanted ENCC migration. Moreover, these findings demonstrating that ENCCs can be accepted by the recipient colon will help to refine current strategies for cell therapy.
Asunto(s)
Fibronectinas , Cresta Neural , Animales , Movimiento Celular/fisiología , Colagenasas/metabolismo , Colon/metabolismo , Modelos Animales de Enfermedad , Fibronectinas/metabolismo , Ratones , Plexo Mientérico , Cresta Neural/metabolismoRESUMEN
Hepatoblastoma (HB) is the leading primary hepatic malignancy in children and likely emerges due to failure of hepatic progenitor cells to properly differentiate. The peroxiredoxin (PRDX) family is frequently linked to cancer. In our previous study, we demonstrated that expression of the only secreted family member, PRDX4, was correlated with hepatocellular carcinoma. The aim of this new study was to investigate PRDX4's role in HB. We collected 87 HB specimens and performed PRDX4 immunohistochemistry staining. Clinical analysis was conducted and the effect of PRDX4 overexpression on two HB cell lines (Huh6 and HepG2) was also examined. Clinical data revealed elevated PRDX4 expression in embryonal component was correlated with advanced stage (IV) and metastasis. In comparison, increased PRDX4 expression in fetal component was associated with well differentiation. In vitro experiments showed PRDX4 overexpression enhanced migration in embryonal-like HB cells (Huh6), which was accompanied by epithelial-mesenchymal transition (EMT). By contrast, PRDX4 overexpression inhibited proliferation, decreased stemness markers, and increased hepatic markers in fetal-like HB cells (HepG2), which indicated induction of tumor cell differentiation. In conclusion, PRDX4 promotes embryonal hepatoblastoma cell migration but induces fetal cell differentiation. It can be adopted as an important marker for HB prognosis and a potential treatment target.
RESUMEN
BACKGROUND: Various terms have been used to describe vascular lesions in the intestine, including angiodysplasia, arteriovenous malformation, and telangiectasia. Such lesions are common in adults and are typified by angiodysplasia, a type of arteriovenous malformation. In contrast, these lesions are rarely seen in the pediatric population. Angiodysplasia may cause gastrointestinal bleeding, which is sometimes an indication for treatment. Considering the high rate of recurrence after surgical treatment, conservative treatments are mainly chosen. We herein report an extremely rare case of a prolapsed colon due to an arteriovenous malformation successfully treated by resection in a 1-year-old girl. We also highlight the differences between pediatric and adult cases. CASE PRESENTATION: A girl developed bloody stools at 7 months of age. She visited another hospital at 1 year of age because of continuing moderate hematochezia and recent onset of rectal prolapse. Colonoscopy showed a protruding lesion located 15 cm from the anal verge, suggesting a submucosal vascular abnormality. Contrast-enhanced computed tomography and magnetic resonance imaging at our hospital revealed the localized lesion with dilated blood vessels in part of the sigmoid colon; no other lesions were present in the gastrointestinal tract. Laparoscopic-assisted sigmoidectomy was performed. A subserosal vascular lesion was visualized and resected using end-to-end anastomosis. Pathologic examination of the 2.2 × 2.7-cm segment revealed several abnormally enlarged and ectatic blood vessels in the submucosa extending into the subserosa. The lesion was diagnosed as an arteriovenous malformation. The patient had a good clinical course without recurrence at the 2-year follow-up. CONCLUSIONS: An arteriovenous malformation in the sigmoid colon may rarely cause intussusception and prolapse of the colon. Complete resection is a radical and potentially effective treatment. Computed tomography and colonoscopy were useful for evaluation of the lesion in the present case.
RESUMEN
The prevalence of asymptomatic hydronephrosis, now detected by ultrasonography, has increased. However, definitive management guidelines for the management of congenital hydronephrosis have not been established. The Japanese Society of Pediatric Urology created a "medical management guide" based on new findings for physicians practicing pediatric urology. We developed a medical management guide focused on congenital hydronephrosis caused by ureteropelvic junction obstruction. This medical management guide consists of the definition, pathophysiology, epidemiology, diagnosis, classification, treatment using a clinical management algorithm of hydronephrosis and the long-term course of the disease. The aim of hydronephrosis management is to determine whether surgery should be carried out to avoid renal dysfunction, as there is a possibility for improvement without intervention. Ultrasonography is essential to make treatment decisions. Management is determined by a comprehensive assessment, including the degree of hydronephrosis, anterior-posterior diameter of the renal pelvis and, if necessary, a nuclear medicine evaluation of the status of urine drainage and renal function.
Asunto(s)
Hidronefrosis , Obstrucción Ureteral , Niño , Humanos , Hidronefrosis/diagnóstico por imagen , Hidronefrosis/terapia , Lactante , Pelvis Renal/diagnóstico por imagen , Cintigrafía , Ultrasonografía , Obstrucción Ureteral/diagnóstico por imagen , Obstrucción Ureteral/terapiaRESUMEN
We developed treatment guidelines (TGs) for appropriate transitional care of the genitourinary system in patients with persistent cloaca (PC), cloacal exstrophy (CE), or Mayer-Rokitansky-Küster-Häuser syndrome (MRKH). These TGs are in accordance with the Medical Information Network Distribution Service (Minds), published in 2014 in Japan. Clinical questions (CQs) concerning treatment outcomes of the genitourinary system, pregnancy and delivery, and quality of life in adulthood were prepared as six themes for PC and CE and five themes for MRKH. We were able to publish statements on chronic renal dysfunction, hydrometrocolpos, and pregnancy, based on four CQs about PC, four about CE, and two about MRKH, respectively. However, due to the paucity of proper manuscripts, we were unable to make conclusions about the correct timing and method of vaginoplasty for patients with PC, CE, and MRKH or the usefulness of early bladder closure for patients with CE. These TGs may help clarify the current treatments for PC, CE, and MRKH in childhood, which have been carried out on an institutional basis. To improve clinical outcomes, systematic clinical trials revealing comprehensive clinical data of the urinary and reproductive systems, especially the length of the common channel in PC, are essential.
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Trastornos del Desarrollo Sexual 46, XX/cirugía , Malformaciones Anorrectales/cirugía , Ano Imperforado/cirugía , Anomalías Congénitas/cirugía , Hernia Umbilical/cirugía , Conductos Paramesonéfricos/anomalías , Guías de Práctica Clínica como Asunto , Escoliosis/cirugía , Cuidado de Transición , Anomalías Urogenitales/cirugía , Femenino , Humanos , Recién Nacido , Masculino , Conductos Paramesonéfricos/cirugía , Embarazo , Calidad de VidaAsunto(s)
Proteínas de Unión al ADN/genética , Eventración Diafragmática/diagnóstico , Hernias Diafragmáticas Congénitas/diagnóstico , Atrofia Muscular Espinal/diagnóstico , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Factores de Transcripción/genética , Adulto , Diagnóstico Diferencial , Eventración Diafragmática/diagnóstico por imagen , Eventración Diafragmática/genética , Eventración Diafragmática/patología , Femenino , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/genética , Hernias Diafragmáticas Congénitas/patología , Heterocigoto , Humanos , Lactante , Masculino , Atrofia Muscular Espinal/diagnóstico por imagen , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patología , Mutación , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico por imagen , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Síndrome de Dificultad Respiratoria del Recién Nacido/patologíaRESUMEN
Muscle biology is important topic in diabetes research. We have reported that a diet with ketogenic amino acids rich replacement (KAAR) ameliorated high-fat diet (HFD)-induced hepatosteatosis via activation of the autophagy system. Here, we found that a KAAR ameliorated the mitochondrial morphological alterations and associated mitochondrial dysfunction induced by an HFD through induction of the AKT/4EBP1 and autophagy signaling pathways in both fast and slow muscles. The mice were fed with a standard HFD (30% fat in food) or an HFD with KAAR (HFDKAAR). In both the gastrocnemius and the soleus, HFDKAAR ameliorated HFD-impaired mitochondrial morphology and mitochondrial function, characterized by decreased mitofusin 2, optic atrophy 1, peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α and PPARα levels and increased dynamin-related protein 1 levels. The decreased levels of phosphorylated AKT and 4EBP1 in the gastrocnemius and soleus of HFD-fed mice were remediated by HFDKAAR. Furthermore, the HFDKAAR ameliorated the HFD-induced autophagy defects in the gastrocnemius and soleus. These findings suggest that KAAR may be a novel strategy to combat obesity-induced mitochondrial dysfunction, likely through induction of the AKT/4EBP1 and autophagy pathways in skeletal muscle.
Asunto(s)
Aminoácidos/farmacología , Autofagia/fisiología , Proteínas Portadoras/fisiología , Dieta Cetogénica , Mitocondrias/fisiología , Músculo Esquelético/fisiología , Obesidad/dietoterapia , Fosfoproteínas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Transducción de Señal/fisiología , Proteínas Adaptadoras Transductoras de Señales , Aminoácidos/administración & dosificación , Animales , Autofagia/efectos de los fármacos , Sangre , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Proteínas de Ciclo Celular , Factores Eucarióticos de Iniciación , Homeostasis , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Obesidad/fisiopatología , Tamaño de los Órganos/efectos de los fármacos , Transducción de Señal/efectos de los fármacosAsunto(s)
Síndrome de Down/complicaciones , Síndrome de Down/diagnóstico , Obstrucción Duodenal/diagnóstico , Obstrucción Duodenal/etiología , Atresia Intestinal/diagnóstico , Atresia Intestinal/etiología , Síndrome de Down/genética , Obstrucción Duodenal/cirugía , Femenino , Humanos , Lactante , Atresia Intestinal/cirugía , Radiografía Abdominal , Resultado del Tratamiento , UltrasonografíaRESUMEN
The enteric nervous system (ENS) is a network of neurons and glia that are derived from enteric neural crest cells (ENCCs) and essential for regulating peristaltic activity of the colon. ENCCs migrate along the gastrointestinal tract to form the ENS, and disruption of ENCC motility leads to ENS disorders, such as Hirschsprung's disease. Previous ENCC-transplant experiments show that ENCCs can invade into isolated mouse intestines by age E13.5, but not after E15.5. We hypothesized that altered age-specific micro-environments in the intestine are responsible for ENCC invasion/migration. Here, we compared gene expression in the intestine between at E11.5 and E15.5 and identified 1355 differentially expressed transcripts. Among these, we found that genes encoding extracellular matrix (ECM) proteins were enriched. Notably, collagen VI (ColVI) family members were upregulated in the E15.5 mouse intestine at the mRNA and protein levels, whereas fibronectin (FN) was downregulated; however, both proteins showed colocalization at E15.5. To understand the mechanisms of ColVI and FN in ENCC migration, we examined neurosphere or individual ENCC-adherence capabilities toward the ECM. ColVI suppressed FN-induced ENCC spreading/migration, whereas ColVI induced morphologically narrow ENCC spreading and weak stress-fiber formation as compared with those with FN. Additionally, in ENCCs cultured on plates containing ColVI, the expression and phosphorylation of p130Cas, a members of focal adhesion complexes, was reduced. These data indicated an inhibitory role of ColVI in ENCC migration and suggested that ColVI suppression in the intestine might represent a novel therapeutic strategy for aganglionic colonic diseases.
Asunto(s)
Movimiento Celular/fisiología , Colágeno Tipo VI/metabolismo , Sistema Nervioso Entérico/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Adhesiones Focales/metabolismo , Cresta Neural/metabolismo , Animales , Células Cultivadas , Regulación hacia Abajo/fisiología , Sistema Nervioso Entérico/citología , Ratones , Ratones Endogámicos C57BL , Cresta Neural/citologíaRESUMEN
Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis, and we have reported that the anti-EndMT effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is associated with restoring expression of diabetes-suppressed fibroblast growth factor receptor (FGFR), the key anti-EndMT molecule. FGFR1 is the key inhibitor of EndMT via the suppression of the transforming growth factor ß (TGFß) signaling pathway, and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibits integrin ß1, a key factor in activating TGFß signaling and EndMT. Here, we showed that the close proximity between AcSDKP and FGFR1 was essential for the suppression of TGFß/smad signaling and EndMT associated with MAP4K4 phosphorylation (P-MAP4K4) in endothelial cells. In cultured human dermal microvascular endothelial cells (HMVECs), the anti-EndMT and anti-TGFß/smad effects of AcSDKP were lost following treatment with a neutralizing FGFR1 antibody (N-FGFR1) or transfection of FRS2 siRNA. The physical interaction between FGFR1 and P-MAP4K4 in HMVECs was confirmed by proximity ligation analysis and an immunoprecipitation assay. AcSDKP induced P-MAP4K4 in HMVECs, which was significantly inhibited by treatment with either N-FGFR1 or FRS2 siRNA. Furthermore, MAP4K4 knockdown using specific siRNAs induced smad3 phosphorylation and EndMT in HMVECs, which was not suppressed by AcSDKP. Streptozotocin-induced diabetic CD-1 mice exhibited suppression of both FGFR1 and P-MAP4K4 expression levels associated with the induction of TGFß/smad3 signaling and EndMT in their hearts and kidneys; those were restored by AcSDKP treatment. These data demonstrate that the AcSDKP-FGFR1-MAP4K4 axis has an important role in combating EndMT-associated fibrotic disorders.
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Células Endoteliales/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Oligopéptidos/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Animales , Células Cultivadas , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Sistema de Señalización de MAP Quinasas/genética , Ratones , Proteínas Serina-Treonina Quinasas/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Quinasa de Factor Nuclear kappa BRESUMEN
BACKGROUND: We have performed transanal pull-through (TAPT) for Hirschsprung disease since 1998. Some of our patients after TAPT showed a patulous anus and suffered from severe true fecal incontinence. We performed anal canal plasty for these patients and evaluated its efficacy in restoring anorectal function. METHODS: Thirty-one patients who were ≥5years old were previously operated on for Hirschsprung disease, and seven (22.5%) of these were indicated for this procedure. Anorectal function was evaluated using the Japanese Study Group of Anorectal Anomalies (JSGA) clinical assessment of defecation function score. For surgery, the patients were positioned in the prone jackknife posture. The posterior half of the anal canal was exposed and folded inward until the anal canal lumen was as narrow as the surgeon's index finger. External anal sphincter muscles were repaired, and the wound was closed vertically. RESULTS: The mean preoperative JSGA score was 1.42±0.4. The mean JSGA scores at 2-6months and 2years after this procedure were 5±2.1 and 5.8±2.1, respectively. Postoperatively, the JSGA score significantly improved at both times (p<0.05). CONCLUSIONS: Anal canal plasty may be effective for true fecal incontinence and a patulous anus after TAPT. This surgical approach may be useful for these conditions. LEVEL OF EVIDENCE: Type of study: Treatment study, Level IV.
Asunto(s)
Canal Anal/cirugía , Incontinencia Fecal/cirugía , Enfermedad de Hirschsprung/cirugía , Complicaciones Posoperatorias/cirugía , Adolescente , Niño , Incontinencia Fecal/etiología , Femenino , Estudios de Seguimiento , Enfermedad de Hirschsprung/complicaciones , Humanos , Masculino , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of this study is to identify the current clinical features of neonatal gastrointestinal perforation in Japan. METHODS: A questionnaire about cases of neonatal gastrointestinal perforation treated in recent 5 years was sent to participating institutions of the Japanese Society of Pediatric Surgeons (JSPS). RESULTS: Five hundred and thirty-six neonates with gastrointestinal perforation were treated. They consisted of 42 patients with gastric rupture/perforation (GR), 33 patients with intestinal atresia/stenosis (IA), 3 patients with malrotation (ML), 118 patients with necrotizing enterocolitis (NEC), 160 patients with focal intestinal perforation (FIP), 46 patients with meconium-related ileus (MRI), 77 patients with meconium peritonitis (MP), and 57 patients with other conditions. The total mortality rate was 20.5 %. The mortality rates of the patients with GR, IA, ML, NEC, FIP, MRI, and MP were 9.5, 9.1, 0, 33.1, 20.6, 28.2, and 9.1 %, respectively. In 263 cases involving extremely low-birth-weight neonates (ELBW), 108 died (mortality rate 41.1 %). The mortality rates for ELBW with GR, NEC, FIP, MRI, MP, and other conditions were 27.3 % (3/11), 58.5 % (48/82), 21.6 % (24/111), 70.6 % (24/34), 57.1 % (4/7), and 27.8 % (5/18), respectively. CONCLUSIONS: The mortality rates for ELBW decreased from 62.8 % in the previous survey to 41.1 % by the time of this survey.
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Perforación Intestinal/epidemiología , Vigilancia de la Población , Enterocolitis Necrotizante/complicaciones , Femenino , Humanos , Recién Nacido , Perforación Intestinal/etiología , Japón/epidemiología , MasculinoRESUMEN
Cartilage-hair hypoplasia is a rare metaphyseal chondrodysplasia characterized by diverse clinical manifestations and a high incidence of Hirschsprung disease. We present a male patient with cartilage-hair hypoplasia associated with severe intestinal obstruction. Genetic analysis of ribonuclease mitochondrial RNA-processing complex gene identified compound heterozygous mutations consisted with previously reported mutations: n.-14_3dupGAAGCTGAGGACGTGGT and n.183G > T. First, we considered that intestinal obstruction was due to an extensive type of Hirschsprung disease, but it was later confirmed as isolated hypoganglionosis. Isolated hypoganglionosis is rare and its therapeutic strategies are not well established. In cases of cartilage-hair hypoplasia associated with severe intestinal obstruction, the differential diagnosis of not only Hirschsprung disease, but also isolated hypoganglionosis, should be considered.
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Cabello/anomalías , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/diagnóstico , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/diagnóstico , Osteocondrodisplasias/congénito , Biopsia , Análisis Mutacional de ADN , Heterocigoto , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/cirugía , Humanos , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/cirugía , Recién Nacido , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Masculino , Mutación , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Osteocondrodisplasias/cirugía , Enfermedades de Inmunodeficiencia Primaria , ARN Largo no Codificante/genética , Radiografía AbdominalRESUMEN
Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.
Asunto(s)
Insuficiencia Suprarrenal/genética , Cromosomas Humanos Par 7/genética , Trastornos del Crecimiento/genética , Mutación/genética , Síndromes Mielodisplásicos/genética , Proteínas/genética , Adolescente , Insuficiencia Suprarrenal/patología , Niño , Endosomas/metabolismo , Receptores ErbB/genética , Femenino , Genotipo , Trastornos del Crecimiento/patología , Humanos , Insuficiencia Corticosuprarrenal Familiar , Lactante , Recién Nacido , Péptidos y Proteínas de Señalización Intracelular , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Linaje , FenotipoRESUMEN
BACKGROUND: The aim of this study was to investigate the incidence and risk factors of peripherally inserted central venous catheter (PICC)-related complications using a multicenter case survey. METHOD: A prospective cohort study was carried out by 19 neonatal intensive care units (NICUs) in Japan from February 2005 to March 2007. A total of 975 case records were collected. PICC-related complications including pericardial effusion/cardiac tamponade pleural effusion/ascites, catheter removal difficulties, catheter-related bloodstream infection (CR-BSI), and symptomatic catheter-related thrombosis were collected from case record forms. As for precautions during insertion, institutions were classified into three groups: those with maximum barrier precautions; standard precautions; and no specific precautions. RESULTS: PICC complications occurred in 27 cases (2.9%) among 946 PICC. The incidence was 1.6% for CR-BSI, and 0.1% for cardiac tamponade. CR-BSI rate per 1000 catheter-days was 1.1 with maximum barrier precautions at catheter insertion, 1.2 with standard precautions, and 1.8 with no specific precautions. Multiple logistic regression analysis showed that proximal placement (odds ratio [OR], 3.88; 95% confidence interval [CI]: 1.42-10.60, P = 0.008) and longer placement duration (OR, 1.35; 95%CI: 1.14-1.60, for each week, P = 0.0005) independently contributed to overall complications. CONCLUSION: The incidence of cardiac tamponade was rare in this multicenter prospective study. Longer duration and proximal placement may be risk factors for PICC complications. In this cohort, the CR-BSI rate was low irrespective of the degree of barrier precautions at insertion.
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Taponamiento Cardíaco/epidemiología , Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Venoso Central/efectos adversos , Catéteres de Permanencia/efectos adversos , Unidades de Cuidado Intensivo Neonatal , Derrame Pericárdico/epidemiología , Trombosis/epidemiología , Taponamiento Cardíaco/etiología , Taponamiento Cardíaco/cirugía , Remoción de Dispositivos , Femenino , Humanos , Incidencia , Recién Nacido , Japón/epidemiología , Masculino , Derrame Pericárdico/etiología , Derrame Pericárdico/cirugía , Estudios Prospectivos , Factores de Riesgo , Trombosis/etiología , Trombosis/cirugíaRESUMEN
Lymphangioma rarely presents as a solitary pulmonary lesion. We encountered a case of solitary cystic lymphangioma and present its clinicopathologic and immunohistochemical findings. A 2-month-old boy was referred to the hospital after developing a persistent cough. Chest X-ray showed a large cyst in the right lung. Under the preoperative diagnosis of bronchogenic cyst, he underwent right lower lobectomy at the age of 11 months. The resected specimen contained a 5.5-cm septate cystic lesion. Microscopically, the lesion consisted of a large cystic space and interconnected slit-like spaces surrounding bronchovascular islands. The cyst was lined by a monolayer of flat cells with focal multinucleated giant cells. Immunohistochemically, the cells lining the cystic lesion were positive for D2-40, Prox1, CD34, and CD31, and weakly positive for VEGFR-3, but were negative for AE1/3, HMB45, VEGF-A, VFGF-C, VEGFR-1. Differential diagnoses included lobar or interstitial emphysema, bronchogenic cyst, congenital pulmonary airway malformation and alveolar adenoma. D2-40 and Prox1 were useful in differentiation and in determining the extent of the lesion. A review of the literature found only 15 cases of solitary pulmonary lymphangioma. In younger patients, the lesions tend to occupy more of the lung. Focal giant cell reaction has not been described in the reported papers.
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Quiste Broncogénico/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfangioma Quístico/diagnóstico , Enfisema Pulmonar/diagnóstico , Anticuerpos Monoclonales , Anticuerpos Monoclonales de Origen Murino , Antígenos CD34 , Quiste Broncogénico/diagnóstico por imagen , Quiste Broncogénico/patología , Tos , Diagnóstico Diferencial , Células Gigantes/patología , Proteínas de Homeodominio , Humanos , Inmunohistoquímica , Lactante , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Linfangioma Quístico/diagnóstico por imagen , Linfangioma Quístico/patología , Masculino , Molécula-1 de Adhesión Celular Endotelial de Plaqueta , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/cirugía , Tomografía Computarizada por Rayos X , Proteínas Supresoras de TumorRESUMEN
Gastroenteric duplication rarely occurs in locations such as the pancreas. We report a case of gastroenteric duplication of the pancreatic tail, which was noncontiguous with the stomach and had no communication with the pancreatic duct, in a 3-year-old girl. The cyst was enucleated by laparoscopy, without the need for pancreatic resection. The optimal treatment procedures vary considerably, depending on where the gastroenteric duplication is located in the pancreas and, most importantly, whether there is communication with the pancreatic duct.