Objectives. We investigated the influence of cytokines on the expression of RANK ligand (RANKL) in fibroblast-like synoviocytes from RA patients (RA-FLS). Methods. RA-FLS were stimulated by IL-6, ...TNF-α, IL-17 and IL-1β with or without soluble IL-6 receptor (sIL-6R) for 24 h. The expression of RANKL was measured by real-time PCR, western blotting and immunostaining. In proliferation assay, RA-FLS were cultured with cytokines for 3 days. RA-FLS were co-cultured with RAW cell in the presence of IL-6/sIL-6R for 3 days and then NFATc1 mRNA expression in RAW cells was examined. RA-FLS was cultured with parthenolide PAR, signal transducer and activator of transcription (STAT) inhibitor or PD98059 (PD, mitogen-activated protein kinase inhibitor) in the presence of IL-6/sIL-6R and then the influence of these drugs on phosphorylation of STAT3 and ERK1/2, and RANKL expression was examined. Results. RANKL expression was induced by IL-6/sIL-6R (but not IL-6 alone) and by IL-1β. On the other hand, TNF-α and IL-17 did not induce RANKL expression, although TNF-α, IL-17 or IL-1β stimulated cell growth and IL-6 production. However, in the presence of sIL-6R, TNF-α or IL-17 induced RANKL expression. By the co-culture of RA-FLS, NFATc1 mRNA expression was induced in RAW cells. Finally, IL-6/sIL-6R induced phosphorylation of STAT3 and ERK1/2 in RA-FLS, and was completely inhibited by PAR and PD, respectively. PAR completely inhibited IL-6/sIL-6R-induced RANKL expression, but PD did not. Conclusions. IL-6/sIL-6R directly induced RANKL expression in RA-FLS and it is essential for RANKL induction by TNF-α and IL-17. Moreover, RANKL induction by IL-6/sIL-6R is mediated by the janus kinase/STAT signalling pathway.
The purpose of this paper is to report on the relationship between lymphoscintigraphic findings and the operative results of lymphaticovenous anastomosis (LVA) as well as the resection of genital ...acquired lymphangiectasia (GAL). Seventeen patients with GAL who underwent lymphoscintigraphy between April 2012 and June 2016 were included in this retrospective study. LVA and GAL resections were performed for 14 patients. The GALs were resected in a spindle shape to the full thickness of the genital skin, and the wounds were closed primarily. Following the procedure, we investigated the recurrence rate and compared the results with the lymphoscintigraphic findings. The average follow-up period was 19.2 months. Six patients were without recurrence, and eight patients experienced a small recurrence of GAL. The average period from operation to recurrence was 16.8 months (range: 1–41 months). Of the six patients who had genital accumulation in lymphoscintigraphy, two patients experienced recurrence (33.3%), whereas six of the eight patients without genital accumulation experienced recurrence (75.0%). The frequency of cellulitis was observed to be reduced postoperatively in all patients, and recurrence was observed in one patient at 11 months postoperatively. In conclusion, lower limb LVA combined with genital skin tumor resection was effective for preventing the recurrence of GAL in patients who demonstrated communication between the lymphatic vessels in the lower limb and genitals. This procedure also had the benefit of reducing the frequency of cellulitis for an average of 19.2 months of follow-up.
•PD is characterized by dopaminergic neurodegeneration and iron overload in the SNpc.•QSM can quantify iron deposition.•Neuromelanin imaging can quantify loss of dopaminergic neurons.•A novel ...automatic volumetric SNpc region of interest selection method was developed.•QSM and neuromelanin imaging are useful for quantifying the SNpc alterations in PD.
To quantify dopaminergic neurodegeneration and iron overload in the substantia nigra pars compacta (SNpc) to evaluate Parkinson’s disease (PD) using both quantitative susceptibility mapping (QSM) and neuromelanin imaging.
We studied 39 PD patients (PD group) and 25 healthy controls (HC group) who underwent brain MRI with QSM and neuromelanin imaging. QSM and neuromelanin values of the SNpc were obtained using a voxel-based automated region segmentation system. The signal-to-noise ratio (SNR) of the SNpc in the neuromelanin images was calculated based on the mean value for the background region. The neuromelanin value was defined as the neuromelanin volume with an SNR higher than that of the background. The significance of the intergroup differences, and according to the severity stages in the PD group was tested for each QSM and neuromelanin value. Receiver-operating characteristic (ROC) analysis for diagnosing PD was performed for QSM and neuromelanin values.
The QSM value was significantly higher in the PD group than in the HC group (P < 0.05). The neuromelanin value was significantly smaller in the PD group than in the HC group (P < 0.05). The areas under the ROC curve were 0.68 and 0.86 for QSM and neuromelanin values, respectively. Using QSM and neuromelanin imaging to classify the PD stage was difficult.
Quantifying the SNpc alterations with our region-based approach is useful for the diagnosis of PD.
Summary
Although dysphagia is a life‐threatening problem in patients with Parkinson's disease (PD), the pathophysiology of oropharyngeal dysphagia is yet to be understood. This study investigated the ...tongue motor function during swallowing in relation to dysphagia and the severity of PD. Thirty patients with PD (14 males and 16 females; average age, 69.4 years), Hoehn and Yahr stage II‐IV, in Osaka University Hospital are participated in this study. During swallowing 5 ml of water, tongue pressure on the hard palate was measured using a sensor sheet with 5 measuring points. The maximal tongue pressure at each measuring point during swallowing was compared between patients with PD and healthy controls. Subjective assessment of oropharyngeal dysphagia was performed using Swallowing Disturbance Questionnaire‐Japanese. The maximal tongue pressure at each measuring point was significantly lower in patients with PD than in healthy controls (8 males and 12 females; average age, 71.6 years). Furthermore, the maximal tongue pressure was significantly lower in dysphagic PD patients than non‐dysphagic PD patients. Loss of tongue pressure production at the anterior part of the hard palate was strongly related to dysphagia in the oral phase as well as in the pharyngeal phase. An abnormal pattern of tongue pressure production was more frequently observed in dysphagic PD patients than in non‐dysphagic PD patients. The results suggest that tongue pressure measurement might be useful for early and quantitative detection of tongue motor disability during swallowing in patients with PD.
Background
One of the complications of lymphoedema is recurrent cellulitis. The aim was to determine whether lymphaticovenous anastomosis (LVA) was effective at reducing cellulitis in patients with ...lymphoedema.
Methods
This was a retrospective review of patients with arm/leg lymphoedema who underwent LVA. The frequency of cellulitis was compared before and after surgery. The diagnostic criteria for cellulitis were a fever of 38·5°C or higher, and warmth/redness in the affected limb(s).
Results
A total of 95 patients were included. The mean number of episodes of cellulitis in the year preceding surgery was 1·46, compared with 0·18 in the year after surgery (P < 0·001).
Conclusion
LVA reduced the rate of cellulitis in these patients with lymphoedema.
Possible treatment for lymphoedema
The nuclear shell structure, which originates in the nearly independent motion of nucleons in an average potential, provides an important guide for our understanding of nuclear structure and the ...underlying nuclear forces. Its most remarkable fingerprint is the existence of the so-called magic numbers of protons and neutrons associated with extra stability. Although the introduction of a phenomenological spin-orbit (SO) coupling force in 1949 helped in explaining the magic numbers, its origins are still open questions. Here, we present experimental evidence for the smallest SO-originated magic number (subshell closure) at the proton number six in
C obtained from systematic analysis of point-proton distribution radii, electromagnetic transition rates and atomic masses of light nuclei. Performing ab initio calculations on
C, we show that the observed proton distribution radii and subshell closure can be explained by the state-of-the-art nuclear theory with chiral nucleon-nucleon and three-nucleon forces, which are rooted in the quantum chromodynamics.
Summary Objective We previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) aggravated cartilage degeneration and that hyaluronate (HA) reversed the cartilage destruction accelerated ...by NSAIDs in a rabbit osteoarthritis (OA) model. In the present study, we analyzed the mechanisms of these effects of NSAIDs and HA. Method An experimental rabbit model of OA was induced by partial meniscectomy and treated with NSAIDs, HA and the combination of NSAIDs and HA over 2 weeks. After sacrifice, cartilage degeneration and the levels of matrix metalloproteases (MMP)-1, MMP-3 and MMP-13 in synovial lavage fluid were measured. In an in vitro study, human articular chondrocytes were cultured with NSAIDs and HA in the presence of interleukin (IL)-1β or IL-6 + sIL-6 for 24 h. After culture, the production of MMPs, IL-1β, and IL-6 was measured. Results The levels of MMP-1, MMP-3 and MMP-13 in synovial fluid from the NSAID-treated group were significantly higher than in controls. The increased production of MMPs induced by NSAIDs was counteracted by the concomitant administration of HA. In vitro studies showed that NSAIDs augmented IL-1β- and IL-6-induced production of MMPs from human chondrocytes, while completely inhibiting the IL-1β- and IL-6/sIL-6R-induced production of prostaglandin E2 (PGE2 ). The addition of PGE2 did not reduce the augmentation of MMP production. HA inhibited the promotion of cytokine-induced MMP and cytokine production by NSAIDs. Conclusions Our data clearly showed that HA inhibited NSAID-accelerated MMP production which was followed by inflammatory cytokine production from cytokine-activated chondrocytes. The results warrant further evaluation of the potential chondroprotective effects of co-administration of HA with NSAIDs.
BACKGROUND
For women with congenital uterine infertility, or for those who have undergone hysterectomy, uterine transplantation is one of the potential treatments to regain fertility. In this study, ...we utilized a primate model of uterine transplantation, and evaluated the patency of our microsurgical anastomoses, and the perfusion of the transplanted uterus.
METHODS
Two female cynomolgus monkeys underwent surgery. We anastomosed two arteries and one vein in Case 1 and two arteries and two veins in Case 2. The arteries used were the uterine arteries and the anastomosis was done to the external iliac artery. We used one of the ovarian veins in both animals, but resected the ovary from the Fallopian tube. Uterine arterial blood flow and uterine size were determined by intraoperative indocyanine green (ICG) angiography and ultrasonography. The biopsy of the uterine cervix was performed after surgery.
RESULTS
ICG angiography showed that the unilateral uterine artery perfused the bilateral uterine bodies and cervix. In Case 1, ICG angiography showed the occlusion of one of the anastomosed arteries during the operation and the uterus appeared atrophied 2 months after operation. In Case 2, the transplanted uterus survived and normal menstruation occurred. The animal achieved a natural pregnancy and was delivered by the Caeserean section due to early separation of the placenta. The newborn suffered fetal distress.
CONCLUSIONS
These results show the anastomosis of at least the bilateral uterine arteries and the unilateral ovarian vein is required for uterus transplantation. This is the first report of a natural pregnancy in a primate following uterine autotransplantation.
Rare earth oxide nanotubes (see Figure) templated by dodecylsulfate assemblies have been fabricated for the first time by the homogeneous precipitation method using urea. Conversion into hollow ...nanotubes with an inner diameter of 3 nm and outer diameter of 6 nm can then be effected by anion exchange treatment to remove the surfactant.
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