手関節伸展荷重時の遠位橈尺関節の3次元動態解析

PURPOSE: To assess the wrist joints of healthy volunteers in extended and loaded states versus the unloaded state by using computed tomography (CT) to analyze the in vivo 3-dimensional movements in the distal radioulnar joint (DRUJ). METHODS: The dominant arms of 9 volunteers with healthy wrists were studied. We mounted a compression device onto the elbows in an inverted position. A 0-kg and 7-kg load each was applied during low-dose radiation CT imaging and a bone model was produced. We marked the insertion sites for the 4 radioulnar ligaments stabilizing the DRUJ: palmar superficial radioulnar ligament (PS-RUL), dorsal superficial radioulnar ligament (DS-RUL), dorsal deep radioulnar ligament (DD-RUL), and palmar deep radioulnar ligament (PD-RUL). Using Marai's method, each ligament was virtualized and the length of each simulated ligament was measured. We also computed the 3-dimensional displacement and corresponding rotation of the distal ulna where it comes into contact with the radius in the sigmoid notch. RESULTS: The lengths of palmar ligaments (PS-RUL and PD-RUL) increased significantly under loaded conditions, and although not significant, the length of dorsal ligaments (DS-RUL and DD-RUL) tended to increase. When the wrist was loaded, the ulna rotated toward the open palmar side. CONCLUSIONS: The length of simulated radioulnar ligaments increased when the wrist joint was loaded in an extended position. This kinematic movement of DRUJ separation under a loading condition is different from physiological active movement. CLINICAL RELEVANCE: The 3-dimensional kinematic analysis revealed that palmar radioulnar ligaments were stretched during axial loading, suggesting that a tear of the palmer ligament can result from a fall on an outstretched hand.博士（医学）・甲第704号・平成31年3月15日© 2019 by the American Society for Surgery of the Hand. All rights reserved

Spin and charge transport induced by gauge fields in a ferromagnet

We present a microscopic theory of spin-dependent motive force ("spin motive force") induced by magnetization dynamics in a conducting ferromagnet, by taking account of spin relaxation of conduction electrons. The theory is developed by calculating spin and charge transport driven by two kinds of gauge fields; one is the ordinary electromagnetic field $A^{\rm em}_{\mu}$, and the other is the effective gauge field $A^{z}_{\mu}$ induced by dynamical magnetic texture. The latter acts in the spin channel and gives rise to a spin motive force. It is found that the current induced as a linear response to $A^{z}_{\mu}$ is not gauge-invariant in the presence of spin-flip processes. This fact is intimately related to the non-conservation of spin via Onsager reciprocity, so is robust, but indicates a theoretical inconsistency. This problem is resolved by considering the time dependence of spin-relaxation source terms in the "rotated frame", as in the previous study on Gilbert damping [J. Phys. Soc. Jpn. {\bf 76}, 063710 (2007)]. This effect restores the gauge invariance while keeping spin non-conservation. It also gives a dissipative spin motive force expected as a reciprocal to the dissipative spin torque ("$\beta$-term").Comment: 13 pages, 3 figures, submitted to PR

Differentiating between Primary Central Nervous System Lymphoma and Glioblastoma: The Diagnostic Value of Combining 18F-fluorodeoxyglucose Positron Emission Tomography with Arterial Spin Labeling

Using conventional magnetic resonance imaging (MRI) methods, the differentiation of primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is often difficult due to overlapping imaging characteristics. This study aimed to evaluate the diagnostic value of combining 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with arterial spin labeling (ASL) for differentiating PCNSL from GBM. In all, 20 patients with PCNSL and 55 with GBM were retrospectively examined. From the FDG-PET data, the maximum standardized uptake values (SUVmax) and the ratio of tumor to normal contralateral gray matter (T/N_SUVmax) were calculated. From the ASL data, the T/N ratio of the maximum tumor blood flow (relative TBFmax: rTBFmax) was obtained. Diagnostic performance of each parameter was analyzed using univariate and multivariate logistic regression analyses and receiver-operating characteristic (ROC) curve analyses. A generalized linear model was applied for comparing the performance of FDG-PET and ASL individually, and in combination. In univariate analysis, SUVmax and T/N_SUVmax were statistically higher in patients with PCNSL and rTBFmax was higher in patients with GBM. In the multivariate analysis, T/N_SUVmax and rTBFmax were statistically independent. The sensitivity, specificity, and area under the curve (AUC) for discriminating PCNSL from GBM were 100%, 87.3%, and 0.950 in T/N_SUVmax; 90%, 72.7%, and 0.824 in rTBFmax; and 95%, 96.4%, and 0.991 in the combined model, respectively. The combined use of T/N_SUVmax and rTBFmax may contribute to better differentiation between PCNSL and GBM

Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3–like protein 1

BackgroundDisease heterogeneity in patients with severe asthma and its relationship to inflammatory mechanisms remain poorly understood.ObjectiveWe aimed to identify and replicate clinicopathologic endotypes based on analysis of blood and sputum parameters in asthmatic patients.MethodsOne hundred ninety-four asthmatic patients and 21 control subjects recruited from 2 separate centers underwent detailed clinical assessment, sputum induction, and phlebotomy. One hundred three clinical, physiologic, and inflammatory parameters were analyzed by using topological data analysis and Bayesian network analysis.ResultsSevere asthma was associated with anxiety and depression, obesity, sinonasal symptoms, decreased quality of life, and inflammatory changes, including increased sputum chitinase 3–like protein 1 (YKL-40) and matrix metalloproteinase (MMP) 1, 3, 8, and 12 levels. Topological data analysis identified 6 clinicopathobiologic clusters replicated in both geographic cohorts: young, mild paucigranulocytic; older, sinonasal disease; obese, high MMP levels; steroid resistant TH2 mediated, eosinophilic; mixed granulocytic with severe obstruction; and neutrophilic, low periostin levels, severe obstruction. Sputum IL-5 levels were increased in patients with severe particularly eosinophilic forms, whereas IL-13 was suppressed and IL-17 levels did not differ between clusters. Bayesian network analysis separated clinical features from intricately connected inflammatory pathways. YKL-40 levels strongly correlated with neutrophilic asthma and levels of myeloperoxidase, IL-8, IL-6, and IL-6 soluble receptor. MMP1, MMP3, MMP8, and MMP12 levels were associated with severe asthma and were correlated positively with sputum IL-5 levels but negatively with IL-13 levels.ConclusionIn 2 distinct cohorts we have identified and replicated 6 clinicopathobiologic clusters based on blood and induced sputum measures. Our data underline a disconnect between clinical features and underlying inflammation, suggest IL-5 production is relatively steroid insensitive, and highlight the expression of YKL-40 in patients with neutrophilic inflammation and the expression of MMPs in patients with severe asthma

HSP‐enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells

Cancer cells often secrete extracellular vesicles (EVs) that carry heat shock proteins (HSPs) with roles in tumor progression. Oral squamous cell carcinoma (OSCC) belongs to head and neck cancers (HNC) whose lymph-node-metastases often lead to poor prognosis. We have examined the EV proteome of OSCC cells and found abundant secretion of HSP90-enriched EVs in lymph-node-metastatic OSCC cells. Double knockdown of HSP90α and HSP90β, using small interfering RNA significantly reduced the survival of the metastatic OSCC cells, although single knockdown of each HSP90 was ineffective. Elevated expression of these HSP90 family members was found to correlate with poor prognosis of HNC cases. Thus, elevated HSP90 levels in secreted vesicles are potential prognostic biomarkers and therapeutic targets in metastatic OSCC

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence