AXIS FOR ROTATION AT THE INTERVERTEBRAL JOINT IN JAPANESE MONKEYS

The position of axis for rotation at the intervertebral joint was investigated using ten Japanese monkeys. The position of axis for rotation at the intervertebral joint was shifted from dorsal to ventral direction on the superior and inferior views of the 1st thoracic vertebra and was next shifted from ventral to dorsal direction on the superior and inferior views of the 10th thoracic vertebra, with some exceptions. X-ray examination demonstrated that in the Japanese monkeys, lordosis was seen in both the cervical and lower lumbar(L5-L7) spine, whereas kyphosis was seen in the thoracic and upper lumbar (L1-L4) spine. Therefore, the possibility that the position of axis for rotation at the intervertebral joint was related to the curvature of the spinal column was not supported by the present study

限局性腎細胞癌における腫瘍浸潤性リンパ球と関連サイトカインの予後因子としての意義

Renal cell carcinoma (RCC) is an immunogenic tumor and pathological specimen generally contain large quantities of tumor-infiltrating lymphocytes (TILs). Numerous cell types and cytokines could affect the immune escape mechanism of tumor cells. The aim of the present study was to investigate the prognostic impact of TILs and the associated circulating cytokines on localized clear cell RCC following radical nephrectomy. A total of 87 patients who had undergone radical nephrectomy and were pathologically diagnosed with localized clear cell RCC were included. The present study evaluated the profile of TILs with immunohistochemical analysis of tumor specimens using a panel of antibodies [cluster of differentiation (CD)-4, CD8, CD80, CD86, CD276, and Forkhead box p3 (Foxp3)]. Counts of each TIL were compared with clinicopathological variables. Based on the results of immunohistochemical analyses, putative cytokines, including interleukin (IL)-6, IL-10, IL-17, interferon-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, were selected, and their levels in preoperative serum were measured by ELISA. The levels were compared with TIL counts in tumor specimens. High counts of the CD276+ and Foxp3+ TILs were identified as independent factors for poor prognosis for metastasis and local recurrence following radical nephrectomy (P=0.033 and 0.006, respectively). A high CD276+ TIL count was associated with preoperative serum levels of TNF-α and IFN-γ (P=0.027 and P=0.035, respectively), whereas a high count of Foxp3+ TILs was associated with preoperative serum levels of TGF-β (P=0.021). High levels of TNF-α and TGF-β were associated with recurrence-free survival (P=0.035 and P=0.031, respectively). Topical intra-tumoral immunoreaction and systemic immune status may be associated with patients with localized RCC. The topical induction of the CD276+ and Foxp3+ TILs was suggested to be associated with high levels of serum TNF-α and IFN-γ. Preoperative serum levels of TNF-α and TGF-β could be simple and non-invasive biomarkers for risk stratification before radical surgery.博士（医学）・甲第741号・令和2年3月16日Copyright © Spandidos Publications 2019. All rights reserved.Articles from Oncology Letters are provided here courtesy of Spandidos Publications

AXIS FOR ROTATION AT THE INTERVERTEBRAL JOINT IN JAPANESE MONKEYS

The position of axis for rotation at the intervertebral joint was investigated using ten Japanese monkeys. The position of axis for rotation at the intervertebral joint was shifted from dorsal to ventral direction on the superior and inferior views of the 1st thoracic vertebra and was next shifted from ventral to dorsal direction on the superior and inferior views of the 10th thoracic vertebra, with some exceptions. X-ray examination demonstrated that in the Japanese monkeys, lordosis was seen in both the cervical and lower lumbar(L5-L7) spine, whereas kyphosis was seen in the thoracic and upper lumbar (L1-L4) spine. Therefore, the possibility that the position of axis for rotation at the intervertebral joint was related to the curvature of the spinal column was not supported by the present study

尿路上皮癌微小環境内におけるDisabled Homolog 2 (DAB2) は腫瘍細胞上皮間葉転換を介して遊走能・浸潤能を高める

Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.博士（医学）・甲第768号・令和3年3月15日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

The Japanese Clinical Practice Guideline for acute kidney injury 2016

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search

Composite pheochromocytoma associated with neurofibromatosis type 1

Introduction Composite pheochromocytoma is a rare tumor, occurring in only 3% of pheochromocytomas. We report a case of composite pheochromocytoma with neurofibromatosis type 1. Case presentation A 42‐year‐old man was referred to our department for further evaluation of an incidentally detected right adrenal tumor. He was a patient at another hospital for neurofibromatosis type 1. The serum and urinary catecholamine levels exceeded the normal range. Abdominal computed tomography and magnetic resonance imaging showed a 2.8 cm diameter right adrenal tumor, and 123I‐metaiodobenzyguanidine scintigraphy showed radioisotope uptake. He was diagnosed with pheochromocytoma and underwent a right laparoscopic adrenalectomy. Histopathological examination revealed that the tumor consisted of a pheochromocytoma and ganglioneuroma. The final diagnosis was composite pheochromocytoma‐ganglioneuroma. Five years after surgery, no recurrence was observed. Conclusion Preoperative diagnosis of composite pheochromocytoma‐ganglioneuroma is difficult; therefore, histopathological examination is necessary for a definitive diagnosis. Pheochromocytoma management requires lifelong follow‐up

Relation between Lineal Energy Distribution and Relative Biological Effectiveness for Photon Beams according to the Microdosimetric Kinetic Model

Our cell survival data showed the obvious dependence of RBE on photon energy: The RBE value for 200 kV X-rays was approximately 10% greater than those for mega-voltage photon beams. In radiation therapy using mega-voltage photon beams, the photon energy distribution outside the field is different with that in the radiation field because of a large number of low energy scattering photons. Hence, the RBE values outside the field become greater. To evaluate the increase in RBE, the method of deriving the RBE using the Microdosimetric Kinetic model (MK model) was proposed in this study. The MK model has two kinds of the parameters, tissue-specific parameters and the dose-mean lineal energy derived from the lineal energy distributions measured with a Tissue-Equivalent Proportional Counter (TEPC). The lineal energy distributions with the same geometries of the cell irradiations for 200 kV X-rays, 60Co ganma-rays, and 6 MV X-rays were obtained with the TEPC and Monte Carlo code GEANT4. The measured lineal energy distribution for 200 kV X-rays was quite different from those for mega-voltage photon beams. The dose-mean lineal energy of 200 kV X-rays showed the greatest value, 4.51 keV/micro-m, comparing with 2.34 and 2.36 keV/micro-m for 60Co ganma-rays and 6 MV X-rays, respectively. By using the results of the TEPC and cell irradiations, the tissue-specific parameters in the MK model were determined. As a result, the RBE of the photon beams (yD: 2~5 keV/micro-m) in arbitrary conditions can be derived by the measurements only or the calculations only of the dose-mean lineal energy

Microdosimetric study on influence of low energy photons on relative biological effectiveness under therapeutic conditions using 6 MV linac

Purpose: Microdosimetry has been developed for the evaluation of radiation quality, and single- event dose-mean lineal energy y_x1113088_D is well-used to represent the radiation quality. In this study, the changes of the relative biological effectiveness (RBE) values under the therapeutic conditions using a 6 MV linac were investigated with a microdosimetric method.Methods: The y_x1113088_D values under the various irradiation conditions for x-rays from a 6 MV linac were measured with a tissue-equivalent proportional counter (TEPC) at an extremely low dose rate of a few tens of lGy=min by decreasing the gun grid voltage of the linac. According to the micro- dosimetric kinetic model (MK model), the RBEMK values for cell killing of the human salivary gland (HSG) tumor cells can be derived if the y_x1113088_D values are obtained from TEPC measurements. The Monte Carlo code GEANT4 was also used to calculate the photon energy distributions and to investigate the changes of the y_x1113088_D values under the various conditions.Results: The changes of the y_x1113088_D values were less than approximately 10% when the field size and the depth in a phantom varied. However, in the measurements perpendicular to a central beam axis, large changes were observed between the y_x1113088_D values inside the field and those outside the field. The maximum increase of approximately 50% in the y_x1113088_D value outside the field was obtained compared with those inside the field. The GEANT4 calculations showed that there existed a large relative num- ber of low energy photons outside of the field as compared with inside of the field. The percentages of the photon fluences below 200 keV outside the field were approximately 40% against approxi- mately 8% inside the field. By using the MK model, the field size and the depth dependence of the RBEMK values were less than approximately 2% inside the field. However, the RBEMK values out- side the field were 6.6% higher than those inside the field.Conclusions: The increase of the RBEMK values by 6.6% outside the field was observed. This increase is caused by the change of the photon energy distributions, especially the increase of the relative number of low energy photons outside the field.Conclusions: The increase of the RBEMK values by 6.6% outside the field was observed. This increase is caused by the change of the photon energy distributions, especially the increase of the relative number of low energy photons outside the field