Developmental pattern of the neuronal intermediate filament inaa in the zebrafish retina

α‐Internexin is a member of the neuronal intermediate filament (nIF) protein family, which also includes peripherin and neurofilament (NF) triplet proteins. Previous studies found that expression of α‐internexin precedes that of the NF triplet proteins in mammals and suggested that α‐internexin plays a key role in the neuronal cytoskeleton network during development. In this study, we aimed to analyze the expression patterns and function of internexin neuronal intermediate filament protein‐alpha a (inaa), the encoding gene of which is a homolog of the mammalian α‐internexin, during retinal development in zebrafish. Via in vitro and in vivo studies, we demonstrated that zebrafish inaa is an α‐internexin homolog that shares characteristics with nIFs. An immunohistochemical analysis of zebrafish revealed that inaa was distributed dynamically in the developing retina. It was widely localized in retinal neuroepithelial cells at 1 day postfertilization (dpf), and was mainly found in the ganglion cell layer (GCL) and inner part of the inner nuclear layer (INL) from 3–9 dpf; after 14 dpf, it was restricted to the outer nuclear layer (ONL). Moreover, we demonstrated for the first time that inaa acted distinctively from the cytoskeletal scaffold of zebrafish cone photoreceptors during development. In conclusion, we demonstrated the morphological features of a novel nIF, inaa, and illustrated its developmental expression pattern in the zebrafish retina. J. Comp. Neurol. 524:3810–3826, 2016. © 2016 Wiley Periodicals, Inc.     

Scale‐up of MSC under hypoxic conditions for allogeneic transplantation and enhancing bony regeneration in a rabbit calvarial defect model

To realize the therapeutic potential of mesenchymal stem cells (MSCs), we aimed to develop a method for isolating and expanding New Zealand rabbit MSCs in a great scale. Rabbit MSCs expanded under hypoxic and normoxic conditions were compared in terms of replication capacity, differentiation potential, and the capacity for allogeneic transplantation in a calvarial defect model. The cells from all tested rabbits were expanded more rapidly when plated at low‐density under hypoxic conditions compared to under normoxic conditions. Moreover, cells expanded under hypoxic conditions increased in the potential of osteoblastic, adipocytic, and chondrocytic differentiation. More importantly, radiographic analysis and micro‐CT measurement of bone volume revealed the hypoxic cells when transplanted in the calvarial defects of another rabbit increased in the ability to repair bone defect compared to the normoxic cells. Six weeks after allogeneic transplantation of hypoxic MSCs, histological analysis revealed a callus spanned the length of the defect, and several bone tissues spotted in the implant. At 12 weeks, new bone had formed throughout the implant. Using BrdU labeling to track the transplanted cells, the hypoxic cells were more detected in the newly formed bone compared to the normoxic cells. For defects treated with allogeneic MSCs, no adverse host response could be detected at any time‐point. In conclusion, we have developed a robust method for isolation and expansion of rabbit MSCs by combining low‐density with hypoxic culture, which can be applied for the design of clinical trials in allogeneic transplantation of MSCs for bone healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1213–1220, 2012     

Repeatability of hypoxia PET imaging using [<Superscript>18</Superscript>F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [¹⁸F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [¹⁸F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV_max and SUV_mean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV_1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [¹⁸F]HX4 uptake were significantly correlated between scans: SUV_max (r?=?0.958, p?<?0.001), SUV_mean (r?=?0.946, p?<?0.001), TBR_max (r?=?0.962, p?<?0.001) and HV_1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUV_mean), 17 % (SUV_max) and 17 % (TBR_max). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [¹⁸F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [¹⁸F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

     

前列腺增生症术后性功能障碍

前列腺增生症术后性功能障碍孔良王伟明叶敏我们调查了２４７例因良性前列腺增生症（ＢＰＨ）行耻骨上前列腺摘除术（ＳＰＰ）或经尿道前列腺切除术（ＴＵＲＰ）患者术后性功能障碍的发生率，并探讨其可能的原因。病人与方法：本组２４７例中ＳＰＰ１１４例，ＴＵＲＰ１３...     

Multi‐lineage differentiation and angiogenesis potentials of pigmented villonodular synovitis derived mesenchymal stem cells ‐ pathological implication

Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation characterized by its hyper‐vascularity within the lesion. The true etiology and cell source of this disease entity still remain unclear. Mesenchymal stem cells (MSCs) exist in various tissues of human body. However, it has not been clarified whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from PVNS (PVNS‐SCs), and by comparing to the MSCs from normal synovium (Syn‐SCs) of the same individual, we investigated whether PVNS‐SCs differed in the capacity for multi‐differentiation and inducing angiogenesis. We first demonstrated that PVNS‐SCs existed in the lesion of PVNS of three individuals. Moreover, we showed PVNS‐SCs had better osteogenic differentiation potential than Syn‐SCs, whereas Syn‐SCs had better capacity for adipogenic and chondrogenic differentiation. By genome–wide analysis of gene expression profile using a complementary DNA microarray and comparing to Syn‐SCs, we identified in PVNS‐SCs a distinct gene expression profile characterized by up‐regulation of genes involved in angiogenesis. In vitro and in vivo studies further confirmed that PVNS‐SCs had better capacities for promoting angiogenesis. In summary, the identification of PVNS‐SCs in PVNS tissue and their distinct angiogenic potential may help elucidate the underlying etiology of this disease. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:395–403, 2016.     

Quantitative comparison of the dynamic flow waveform changes in 12 ruptured and 29 unruptured ICA–ophthalmic artery aneurysms

Introduction

Studies have reported a correlation between blood flow dynamics in the cardiac cycle and vascular diseases, but research to analyze the dynamic changes of flow in cerebral aneurysms is limited. This quantitative study investigates the temporal changes in flow during a cardiac cycle (flow waveform) in different regions of aneurysms and their association with aneurysm rupture.

Methods

Twelve ruptured and 29 unruptured aneurysms from the internal carotid artery–ophthalmic artery segment were studied. Patient-specific aneurysm data were implemented to simulate blood flow. The temporal flow changes at different regions of the aneurysm were recorded to compare the flow waveforms.

Results

In more than 60 % of the cases, peak flow in the aneurysm sac occurred after peak flow in the artery. Flow rate varied among cases and no correlation with rupture, aneurysm flow rate, and aneurysm size was found. Higher pulsatility within aneurysm sacs was found when comparing with the parent artery (P?<?0.001). Pulsatility was high throughout ruptured aneurysms, but increased from neck to dome in unruptured ones (P?=?0.021). Significant changes between inflow and outflow flow profile were found in unruptured aneurysms (P?=?0.023), but not in ruptured aneurysms.

Conclusion

Quantitative analysis which considers temporal blood flow changes appears to provide additional information which is not apparent from aneurysmal flow at a single time point (i.e., peak of systole). By considering the flow waveform throughout the cardiac cycle, statistically significant differences were found between ruptured and unruptured cases — for flow profile, pulsatility and timing of peak flow.