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Miyazaki H.,Pathology and Laboratory Medicine | Hiroi S.,National Defense Medical College | Shinomiya N.,National Defense Medical College Research Institute | Nakanishi K.,National Defense Medical College Hospital
Journal of Leukocyte Biology | Year: 2012

Although B cells in vertebrates have been thought to lack phagocytic activity, there has been a recent report of such ability by the B cells of early vertebrates such as fish and frogs. Here, we show for the first time that mouse liver IgM+ B cells actively phagocytose microsphere beads and Escherichia coli and that they effectively kill bacterial cells. Such phagocytic activity is not observed in other liver MNCs, except for F4/80+ Kupffer cells. In the presence of fresh mouse serum (but not heat-inactivated serum), the heat-killed E. coli phagocytic activity of liver B cells increased significantly but was inhibited significantly by anticomplement component C3 antibody, suggesting E. coli opsonization by serum factors, including complement components. Upon i.v. injection of FITC-labeled E. coli into mice, a substantial proportion of liver B cells phagocy-tosed the bacteria, as compared with spleen B cells. Functional phagolysosome formation in liver B cells was supported by several reagents showing an acidic change and lysosomes in the phagocytosed vacuoles. Indeed, mouse liver B cells killed viable E. coli more efficiently than did spleen B cells in vitro. Further, E. coli-phagocytic liver B cells produced a substantial amount of IL-12. These results indicate that liver B cells have phagocytic and bactericidal activities similar to those of dedicated phagocytes and may contribute to bacterial clearance. © Society for Leukocyte Biology.


Yamamoto S.,National Defense Medical College | Tsuda H.,Clinical Pathology Laboratories | Takano M.,National Defense Medical College | Tamai S.,National Defense Medical College Hospital | Matsubara O.,National Defense Medical College
Virchows Archiv | Year: 2012

Somatic mutations of PIK3CA and ARID1A are the most common genetic alterations observed in ovarian clear cell adenocarcinomas (CCA). In a previous report, we showed that PIK3CA gene mutations and loss of ARID1A expression occur early during the development of CCA. In the present study, using direct genomic DNA sequencing for exons 9 and 20 of PIK3CA and immunohistochemistry for ARID1A protein expression, we analyzed the association of these molecular alterations with various clinicopathological parameters in a total of 90 cases of primary ovarian CCA, including 42 previously examined cases. The presence of PIK3CA mutations, identified in 34 (39%) of the 88 informative cases, was significantly associated with a grossly cystic tumor, the presence of adjacent endometriosis, prominent papillary architecture of tumor growth, the presence of hyalinized and mucoid stroma, and the absence of clear cell adenofibroma components (P<0.05, each). There was no significant association of PIK3CA mutations with other clinical variables, such as age, clinical stage, or clinical outcome of the patients. The intensity of immunoreactivity for ARID1A was assigned as negative, weakly positive, and strongly positive in 44%, 22%, and 33% of tumors, respectively. Compared to tumors immunoreactive for ARID1A, ARID1A-negative tumors were significantly associated with the presence of adjacent endometriosis (P=0.025), but there was no statistically supported association with other examined clinicopathological parameters. Compared with CCAs strongly positive for ARID1A, CCAs negative for ARID1A more frequently harbor PIK3CA mutations (P=0.013). PIK3CA gene mutations and ARID1A immunohistochemistry lacked prognostic significance. These data further support the idea that these molecular alterations occur as very early events during tumor development of ovarian CCA. © Springer-Verlag 2011.


Yamamoto S.,National Defense Medical College | Tsuda H.,Clinical Pathology Laboratories | Takano M.,National Defense Medical College | Tamai S.,National Defense Medical College Hospital | Matsubara O.,National Defense Medical College
Modern Pathology | Year: 2012

ARID1A is a recently identified tumor suppressor gene that is mutated in 50% of ovarian clear-cell carcinomas. This mutation is associated with loss of ARID1A protein expression as assessed by immunohistochemistry. The present study aimed at determining the timing of the loss of ARID1A protein expression during the development of ovarian clear-cell carcinoma and assessing its relevance in correlation to PIK3CA gene mutations. A total of 42 clear-cell carcinoma cases with adjacent putative precursor lesions (endometriosis-associated carcinoma cases (n28) and (clear-cell) adenofibroma-associated carcinoma cases (n14)) were selected and subjected to immunohistochemical analysis for ARID1A protein expression and direct genomic DNA sequencing of exons 9 and 20 of the PIK3CA gene. ARID1A immunoreactivity was deficient in 17 (61%) of the 28 endometriosis-associated carcinomas and 6 (43%) of the 14 adenofibroma- associated carcinomas. Among the precursor lesions adjacent to the 23 ARID1A-deficient carcinomas, 86% of the non-atypical endometriosis (12 of 14) and 100% of the atypical endometriosis (14 of 14), benign (3 of 3), and borderline (6 of 6) clear-cell adenofibroma components were found to be ARID1A deficient. In contrast, in the 19 patients with ARID1A-intact carcinomas, all of the adjacent precursor lesions retained ARID1A expression regardless of their types and cytological atypia. Analysis of 22 solitary endometrioses and 10 endometrioses distant from ARID1A-deficient carcinomas showed that all of these lesions were diffusely immunoreactive for ARID1A. Among the 42 clear-cell carcinomas, somatic mutations of PIK3CA were detected in 17 (40%) tumors and majority (71%) of these were ARID1A-deficient carcinomas. These results suggest that loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development, similar to the pattern of PIK3CA mutation recently reported by our group, and frequently coexists (not mutually exclusive) with PIK3CA mutations. © 2012 USCAP, Inc. All rights reserved.


Shoji T.,Yukisada Hospital | Shoji T.,National Defense Medical College | Nagaoka Y.,Sensho kai Eye Institute | Sato H.,National Defense Medical College Hospital | Chihara E.,Sensho kai Eye Institute
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2012

Background: The aim was to evaluate the effects of high myopia on spectral-domain optical coherence tomography (SDOCT) parameters, as well as on their ability to detect glaucoma. Methods: Ninety-three glaucoma and 86 non-glaucoma patients were divided into highly myopic group (HMG; 90 subjects, ≤-5 diopters [D]) and emmetropic (EG; 89 subjects, spherical equivalent ≤1 D and ≥-1D) groups in this cross-sectional comparative study. Macular ganglion cell complex (GCC) and circumpapillary retinal nerve fiber layer (cpRNFL) measurements obtained from the algorithms of the SD-OCT system were compared. The effects of refractive errors and glaucoma were assessed using a generalized linear model, after adjusting for age. A receiver operating characteristic curve was constructed for each parameter, and the areas under the curves (AUCs) were compared. Results: The all cpRNFL measurements were significantly related to both refractive errors and glaucoma, while all GCC parameters were not significantly related to the refractive errors. The AUC for average GCC thickness was similar between the HMG (AUC, 0.935) and EG (AUC, 0.933), while the AUC for average cpRNFL thickness differed significantly (p=0.028) between the HMG (AUC, 0.827) and EG (AUC, 0.939). Conclusions: Macular GCC parameters showed good ability to detect glaucoma in both groups, whereas the ability of cpRNFL measurement in HMG subjects was inferior to that in EG subjects. Assessment of GCC parameters is a useful technique complementary to cpRNFL thickness assessment, for clinically evaluating patients with concomitant glaucoma and high myopia. © Springer-Verlag 2012.


Yamada Y.,Nippon Koukan Hospital | Yamada Y.,Keio University | Jinzaki M.,Keio University | Hasegawa I.,Kawasaki Municipal Hospital | And 6 more authors.
Investigative Radiology | Year: 2011

Objectives: To evaluate the diagnostic performance of fast scanning tomosynthesis in comparison with that of chest radiography for the detection of pulmonary nodules, using multidetector-row computed tomography (MDCT) as the reference, and to assess the association of the true-positive fraction (TPF) with the size, CT attenuation value, and location of the nodules. Materials and methods: The institutional review board approved this study, and written informed consent was obtained from all patients. Fifty-seven patients with and 59 without pulmonary nodules underwent chest MDCT, fast scanning tomosynthesis, and radiography. The images of tomosynthesis and radiography were randomly read by 3 blinded radiologists; MDCT served as the reference standard. Free-response receiver-operating characteristic (FROC) and receiver-operating characteristic (ROC) analyses, Cochran-Armitage trend or Fisher exact test, a conditional logistic regression model, and McNemar test were used. Results: Both FROC and ROC analyses revealed significantly better performance (P < 0.01) of fast scanning tomosynthesis than radiography for the detection of pulmonary nodules. For fast scanning tomosynthesis, the average TPF and false-positive rate as determined by FROC analysis were 0.80 and 0.10, respectively. For both fast scanning tomosynthesis and radiography, the average TPF increased with increasing nodule size and CT attenuation values, and was lower for subpleural nodules (all P < 0.01). Conclusions: The diagnostic performance of fast scanning tomosynthesis for the detection of pulmonary nodules was significantly superior to that of radiography. The TPF was affected by the size, CT attenuation value, and location of the nodule, in both fast scanning tomosynthesis and radiography. © 2011 Lippincott Williams & Wilkins.


Wakisaka H.,National Defense Medical College Hospital
Transactions of Japanese Society for Medical and Biological Engineering | Year: 2014

The present report suggests that Apple iPod touch is one of the best devices at bedside for the hospital nurse so far. Validation of the patient at each medication or treatment at bedside is required in these days. The notebook PC, the dedicated handheld terminal, Wi Fi tablet and smartphone-like device were weighed in usability, cost and security. Multiple functions and space-saving design of the smartphone is most favorable in usability. The iPod touch is most inexpensive among smartphone-type devices in spite of approximately two-year battery replacement cycle. The popular operability of iOS, whose market share was dominant in Japan, will reduce time to master its operation. Through this device the nurse also can read patient barcode ID constantly and take bedside clinical pictures with intrinsic camera. The larger tablet devices, which are comparable in cost, were pointed out that bedside action to the patient might break it between the bed frame and nurse body. © 2014, Japan Soc. of Med. Electronics and Biol. Engineering. All rights reserved.


Yamamoto S.,National Defense Medical College | Tsuda H.,National Cancer Center Hospital | Miyai K.,National Defense Medical College | Takano M.,National Defense Medical College | And 2 more authors.
Modern Pathology | Year: 2012

Our previous study demonstrated that, among ovarian carcinomas, amplification of the MET gene and overexpression of MET specifically and commonly occur in clear-cell adenocarcinoma histology. This study was conducted to address how these alterations contribute to development and progression of this highly chemoresistant form of ovarian cancer. We histologically reviewed 21 previously described MET amplification-positive clear-cell adenocarcinoma cases, and selected 11 tumors with synchronous endometriosis and 2 tumors with adjacent clear-cell adenofibroma (CCAF) components. Using double in situ hybridization and immunohistochemistry, copy number alterations of the MET gene and levels of MET protein expression were analyzed in these putative precursor lesions and the corresponding invasive carcinoma components in this selected cohort. All of the non-atypical precursor lesions analyzed (ie, non-atypical endometrioses and the benign CCAFs) were negative for MET gain. However, low-level (≥3 MET copies in ≥10% and ≥4 MET copies in 10-40% of tumor cells) gain of MET was detected in 4 (40%) of the 10 atypical endometrioses and 1 of the 2 borderline CCAFs. Moreover, high-level (≥4 MET copies in ≥40% of tumor cells) gain of MET were detected in five (50%) of the atypical endometrioses. In 4 (31%) of the 13 cases enrolled, intratumoral heterogeneity for MET gain was documented in invasive carcinoma components, wherein all the relatively differentiated carcinoma components showed low-level gain of MET and all the corresponding poorly differentiated carcinomas showed high-level gain. The overall incidence of MET overexpression gradually increased from the precursors of non-atypical form (0%), through those of atypical form (67%) and the relatively differentiated carcinoma components (92%), to the poorly differentiated carcinoma components (100%). These results suggest that accumulative MET gene copy number alterations causing MET overexpression are associated with higher tumor grade and might drive the development and progression of the MET amplification-positive ovarian clear-cell adenocarcinoma. © 2012 USCAP, Inc. All rights reserved.


Yamamoto S.,National Defense Medical College | Tsuda H.,National Cancer Center Hospital | Miyai K.,National Defense Medical College | Takano M.,National Defense Medical College | And 2 more authors.
Modern Pathology | Year: 2011

The aim of this study was to assess protein overexpression and gene copy number alterations of MET in ovarian clear-cell adenocarcinoma, and to assess its potential as a novel therapeutic target. Ninety cases of clear-cell adenocarcinoma were analyzed for MET protein overexpression and copy number alterations of the MET gene by immunohistochemistry and brightfield double in situ hybridization, respectively. In addition, 101 cases of the non-clear-cell type ovarian carcinomas at advanced stages were also evaluated for comparison. MET overexpression was assigned when complete membrane staining with moderate or strong intensity was observed in at least 10% of the tumor cells examined. Double in situ hybridization was determined as positive when the tumor exhibited high-level polysomy (4 copies in 40% of tumor cells) or MET gene amplification. MET overexpression was detected in 20 of 90 clear-cell adenocarcinomas (22%) and none of 111 non-clear-cell type ovarian carcinomas. Double in situ hybridization was positive in 21 of 89 informative clear-cell adenocarcinomas (24%) and only 3 non-clear-cell type ovarian carcinomas (3%). In the whole population, true amplification of the MET gene was detected only in the clear-cell adenocarcinoma histology (five cases, 6%). In clear-cell adenocarcinomas, double in situ hybridization positivity was highly correlated with the presence of MET overexpression and a poorly differentiated histology of tumors (P0.0105 and 0.00038, respectively). For the patients with clear-cell adenocarcinomas, MET overexpression, as well as advanced clinical stage and the poorly differentiated histology of tumors, was identified as an independent unfavorable prognostic factor for overall survival. In conclusion, among ovarian carcinomas, the amplification of the MET proto-oncogene is highly selective and commonly occurs in clear-cell adenocarcinoma. MET could serve as a biomarker for the prognostication of patients with clear-cell adenocarcinoma and tumor progression, and has potential as a novel therapeutic target for this carcinoma. © 2011 USCAP, Inc. All rights reserved.


Yamada Y.,Keio University | Jinzaki M.,Keio University | Tanami Y.,Keio University | Shiomi E.,National Defense Medical College Hospital | And 3 more authors.
Investigative Radiology | Year: 2012

Objectives: The aim of this study was to assess the effectiveness of a model-based iterative reconstruction (MBIR) in improving image quality and diagnostic performance of ultralow-dose computed tomography (ULDCT) of the lung. Materials and Methods: The institutional review board approved this study, and all patients provided written informed consent. Fifty-two patients underwent low-dose computed tomography (LDCT) (screening-dose, 50 mAs) and ULDCT (4 mAs) of the lung simultaneously. The LDCT images were reconstructed with filtered back projection (LDCT-FBP images) and ULDCT images were reconstructed with both MBIR (ULDCT-MBIR images) and FBP (ULDCT-FBP images). On all the 156 image series, objective image noise was measured in the thoracic aorta, and 2 blinded radiologists independently assessed subjective image quality. Another 2 blinded radiologists independently evaluated the ULDCT-MBIR and ULDCT-FBP images for the presence of noncalcified and calcified pulmonary nodules; LDCT-FBP images served as the reference. Paired t test, Wilcoxon signed rank sum test, and free-response receiver-operating characteristic analysis were used for statistical analysis of the data. Results: Compared with LDCT-FBP and ULDCT-FBP, ULDCT-MBIR had significantly reduced objective noise (both P <; 0.001). Subjective noise on the ULDCT-MBIR images was comparable with that on the LDCT-FBP images but lower than that on the ULDCT-FBP images (P <; 0.001). Artifacts on ULDCT-MBIR images were more numerous than those on the LDCT-FBP images (P = 0.007) but fewer than those on the ULDCT-FBP images (P <; 0.001). Compared with the LDCT-FBP images, ULDCT-MBIR and ULDCT-FBP images showed reduced image sharpness (both P <; 0.001). All the ULDCT-MBIR images showed a blotchy pixelated appearance; however, the performance of ULDCT-MBIR was significantly superior to that of ULDCT-FBP for the detection of noncalcified pulmonary nodules (P = 0.002). The average true-positive fractions for significantly sized noncalcified nodules (≈4 mm) and small noncalcified nodules (<4 mm) on the ULDCT-MBIR images were 0.944 and 0.884, respectively, when LDCT-FBP images were used as reference. All of the calcified nodules were detected by both the observers on both the ULDCT-MBIR and ULDCT-FBP images. Conclusion: As compared with FBP, MBIR enables significant reduction of the image noise and artifacts and also better detection of noncalcified pulmonary nodules on ULDCT of the lung. Compared with LDCT-FBP images, ULDCT-MBIR images showed significantly reduced objective noise and comparable subjective image noise. Almost all of the noncalcified nodules and all of the calcified nodules could be detected on the ULDCT-MBIR images, when LDCT-FBP images were used as the reference. © 2012 by Lippincott Williams & Wilkins.


Keiko T.,National Defense Medical College Hospital | Yanagawa Y.,National Defense Medical College Hospital | Isoda S.,National Defense Medical College Hospital
American Journal of Emergency Medicine | Year: 2012

An 81-year-old woman became unconsciousness after complaining of a backache, and then, an ambulance was called. She was suspected to have an aortic dissection by the emergency medical technicians and was transferred to our department. On arrival, she was in shock. Emergency cardiac ultrasound disclosed good wall motion with cardiac tamponade but no complication of aortic regurgitation. Computed tomography of the trunk revealed a type A aortic dissection with cardiac tamponade. During performance of pericardial drainage, she lapsed into cardiopulmonary arrest. Immediately after sterilization of the patient's upper body with compression of the chest wall, we performed a thoracotomy and dissolved the cardiac tamponade by pericardiotomy and obtained her spontaneous circulation. Fortunately, blood discharge was ceased immediately after controlling her blood pressure aggressively. As she complicated pneumonitis, conservative therapy was performed. Her physical condition gradually improved, and she finally could feed herself and communicate. In cases of acute cardiac tamponade, simple pericardiocentesis often is not effective due to the presence of the clot, and a cardiac tamponade by a Stanford type A aortic dissection is highly possible to complicate cardiac arrest, so emergency physicians should be ready to provide immediate open cardiac massage to treat such patients. © 2012 Elsevier Inc. All rights reserved.

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