Fibromuscular dysplasia (FMD) is a non-atheromatous, non-inflammatory, multifocal segmental angiopathy. FMD is the most common cause of pediatric renovascular hypertension. Aneurysmal formation of the main renal artery and distal branches is a rare complication of FMD in infancy. We report an 8-month-old boy with FMD presenting with shock caused by sudden renal hemorrhage that necessitated removal of one kidney. A diagnosis of renovascular hypertension resulting from intimal type FMD with aneurysmal formation was made on the basis of the presence of hypertension, elevation of PRA and aldosterone activity, pathological findings and the results of renal angiography. Our findings suggest that it is therefore necessary to consider FMD with aneurysmal formation as a possible cause of hypertension and renal hemorrhage in infants.
Abnormal pulmonary venous flow patterns on fetal echocardiography and a nutmeg lung pattern on fetal magnetic resonance imaging are seen in patients with pulmonary venous stenosis. The association between these findings and the degree of pulmonary venous stenosis remains unknown. We report an extremely rare case of a fetus diagnosed with hypoplastic left heart syndrome complicated by an absent atrial septum and supracardiac total anomalous pulmonary venous connection with left pulmonary venous congestion. This case suggests that compared to non-pulsatile continuous pulmonary venous flow, the nutmeg lung pattern can only be observed with severe pulmonary congestion and advanced pulmonary lymphangiectasia.
Cisplatin (CDDP) and doxorubicin (DOX) are chemotherapeutic drugs that trigger apoptosis by inducing DNA-damage. A previous study using breast cancer cells demonstrated the negative feedback modulation of the epidermal growth factor receptor (EGFR) and receptor tyrosine-protein kinase erbB-2 (ErbB2) via extracellular signal-regulated kinase (ERK)-mediated phosphorylation of conserved Thr-669 and Thr-677 residues, respectively, in the juxtamembrane domain. In addition, CDDP has been identified to cause negative feedback inhibition of activated EGFR in lung cancer cells. In the present study, the role of phosphorylation in the feedback control of the ErbB2/ErbB3 heterodimer in human breast and gastric cancer cells was investigated. Phosphorylation of ErbB2 at Thr-677 was induced by CDDP and DOX, which in turn reduced tyrosine autophosphorylation of ErbB2 and ErbB3. Treatment with trametinib, a mitogen-activated protein kinase inhibitor that blocks ERK-mediated Thr-677 phosphorylation, and substitution of Thr-677 to alanine, blocked the feedback inhibition of ErbB2 and ErbB3. In addition, these agents caused the degradation of ErbB proteins through the activation of p38 mitogen-activated protein kinase (p38) and ERK. These results demonstrate that chemotherapeutic agents trigger ERK- and p38-mediated post-translational downregulation of ErbB receptors.
Transseptal puncture (TSP) has become a common approach in catheter ablation of arrhythmia originating from the left atrium. In paediatric patients, however, TSP can be a challenge due to narrower access vessels and small left atrial size, and the safety of TSP in smaller children is yet to be understood. The purpose of this study was to retrospectively evaluate the feasibility and safety of TSP in children weighing below 30 kg.Among 655 paediatric patients who underwent catheter ablation of arrhythmia between July 2009 and April 2015, 43 cases having structurally normal hearts, weighing <30 kg and requiring TSP were included in the study. Age, height, body weight, diagnosis, and complications during TSP and catheter ablation were evaluated. The median age, height, and body weight (range) were 7.0 years (0.3-11.1), 116.8 cm (54.0-138.4 cm) and 21.5 kg (4.3-29.6 kg), respectively. Diagnosis included manifest (n = 27; 62.8%) and concealed accessory pathway (n = 14; 32.6%) and atrial tachycardia (n = 2; 4.6%). In 10 cases (23.2%), TSP using radiofrequency energy was performed. None of the patients had major complications. Pericardial effusion was recorded as a minor complication in one patient (2.3%).TSP was feasible, safe, and of low risk of complications in children weighing <30 kg.
Abstract Background Phosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival and tumorigenesis. The activation of AKT signaling promotes the cellular reprogramming including generation of induced pluripotent stem cells (iPSCs) and dedifferentiation of primordial germ cells (PGCs). Previous studies suggested that AKT promotes reprogramming by activating proliferation and glycolysis. Here we report a line of evidence that supports the notion that AKT signaling is involved in TET-mediated DNA demethylation during iPSC induction. Methods AKT signaling was activated in mouse embryonic fibroblasts (MEFs) that were transduced with OCT4, SOX2 and KLF4. Multiomics analyses were conducted in this system to examine the effects of AKT activation on cells undergoing reprogramming. Results We revealed that cells undergoing reprogramming with artificially activated AKT exhibit enhanced anabolic glucose metabolism and accordingly increased level of cytosolic α-ketoglutarate (αKG), which is an essential cofactor for the enzymatic activity of the 5-methylcytosine (5mC) dioxygenase TET. Additionally, the level of TET is upregulated. Consistent with the upregulation of αKG production and TET, we observed a genome-wide increase in 5-hydroxymethylcytosine (5hmC), which is an intermediate in DNA demethylation. Moreover, the DNA methylation level of ES-cell super-enhancers of pluripotency-related genes is significantly decreased, leading to the upregulation of associated genes. Finally, the transduction of TET and the administration of cell-permeable αKG to somatic cells synergistically enhance cell reprogramming by Yamanaka factors. Conclusion These results suggest the possibility that the activation of AKT during somatic cell reprogramming promotes epigenetic reprogramming through the hyperactivation of TET at the transcriptional and catalytic levels.
An 18-year-old man presented after undergoing multiple investigations for abdominal pain. Retrograde double-balloon enteroscopy showed a protruding red lesion in the ileum with small ulcers, approximately 75 cm proximal to the ileocecal valve, resulting in an intussusception. An inverted Meckel's diverticulum was strongly suspected. Pressure was applied to the protruding lesion using contrast medium injection after wedging the lumen with a balloon. The intussusception partially reduced, avoiding the need for emergent surgery. Endoscopic tattooing was performed to mark the lesion for subsequent resection. Elective laparoscopy-assisted surgery with minimum laparotomy revealed an inverted Meckel's diverticulum, which was resected.
This paper presents a framework for a cluster system that is suited for high-resolution image processing over the Internet during surgery. The system realizes high-performance computing (HPC) assisted surgery, which allows surgeons to utilize HPC resources remote from the operating room. One application available in the system is an intraoperative estimator for the range of motion (ROM) adjustment in total hip replacement (THR) surgery. In order to perform this computation-intensive estimation during surgery, we parallelize the ROM estimator on a cluster of 64 PCs, each with two CPUs. Acceleration techniques such as dynamic load balancing and data compression methods are incorporated into the system. The system also provides a remote-access service over the Internet with a secure execution environment. We applied the system to an actual THR surgery performed at Osaka University Hospital and confirmed that it realizes intraoperative ROM estimation without degrading the resolution of images and limiting the area for estimations.
