Publications by authors named "Fumiya Sato"

41 Publications

Investigations into the Potential of Using Open Source CFD to Analyze the Differences in Hemodynamic Parameters for Aortic Dissections (Healthy versus Stanford Type A and B).

Ann Vasc Surg 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiac Surgery, Asahikawa Medical University, Asahikawa, Japan.

Background: The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters.

Methods: A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated.

Results: The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow.

Conclusions: Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.
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http://dx.doi.org/10.1016/j.avsg.2021.08.007DOI Listing
October 2021

Improvement of knee Joint's range of motion in a patient with posterior thigh lymphedema by lymphaticovenular anastomosis.

Microsurgery 2021 Nov 31;41(8):816-817. Epub 2021 Aug 31.

Department of Plastic and Reconstructive Surgery, National Center for Global Health and Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1002/micr.30801DOI Listing
November 2021

Breast Cancer Treatment in a Patient with Decubitus Ulcer Infection Secondary to Spina Bifida: Surgical Resection versus Neoadjuvant Chemotherapy.

Case Rep Oncol 2021 May-Aug;14(2):944-949. Epub 2021 Jun 18.

Breast Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.

Spina bifida (SB) is a congenital neural tube defect that often presents with neurological disability and decubitus ulcers. A 66-year-old woman with SB presented to our hospital with decubitus ulcers and was treated by a plastic surgeon. She was referred to our department because of a mass measuring 5 × 4 cm in the superolateral quadrant of the right breast. The size of the right axillary lymph node (LN) was 2 × 1 cm. A core-needle biopsy revealed an invasive ductal carcinoma. Total mastectomy and axillary LN dissection were planned. However, 2 days prior to surgery, the size of the mass and the LN rapidly increased to 7 × 4 cm and 3 × 2 cm, respectively. Furthermore, the enlarged LN was close to the thoracodorsal artery. Since complete resection was difficult, neoadjuvant chemotherapy was also administered. On day 11 of neoadjuvant chemotherapy, the patient was febrile and developed a decubitus ulcer infection at the buttock. The neutrophil count was within normal limits; thus, she was not diagnosed with febrile neutropenia. Follow-up computed tomography revealed a shrinking of the mass to 5 × 4 cm after the first cycle of neoadjuvant chemotherapy. After 17 days of antibiotic therapy and drainage, total mastectomy and axillary LN dissection were performed. Due to the risk of recurrence of infection, adjuvant chemotherapy was discontinued and hormone therapy was initiated. In conclusion, indications for chemotherapy should be carefully evaluated in SB patients with lower limb paralysis and decubitus ulcers.
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http://dx.doi.org/10.1159/000515508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255665PMC
June 2021

[Case Report of an Elderly Patient with Interstitial Pneumonia Caused by the Administration of Trastuzumab plus Anastrozole for the Treatment of Inflammatory Breast Cancer].

Gan To Kagaku Ryoho 2021 May;48(5):701-703

Dept. of Surgery, Kasugai Municipal Hospital.

An 83‒year‒old woman received trastuzumab plus anastrozole as first‒line chemotherapy for inflammatory breast cancer in her left breast. Following the treatment, the induration and redness in her breast gradually improved; however, 2 days after receiving the 5th course of chemotherapy, she developed dyspnea and was referred to the emergency room. Her SpO2 was 88%; her KL‒6 level had increased to 2,613 U/mL; and a chest CT scan showed ground‒glass opacity in the bilateral lung fields, yielding a diagnosis of interstitial pneumonia requiring steroid pulse therapy. The dyspnea improved immediately after steroid administration, and the patient was discharged 20 days after hospitalization. Thereafter, the steroid dosage was gradually lowered to 5 mg/day. We discontinued steroid therapy after a chest CT confirmed the reduction of ground‒glass opacity. However, she was later readmitted for interstitial pneumonia for which she was readministered steroid pulse therapy. Trastuzumab‒induced interstitial pneumonia is rare, but we must be aware of the possibility that patients may develop severe pulmonary disorders or experience cardiotoxic effects.
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May 2021

Idiopathic Spontaneous Intrahepatic Hemorrhage Initially Diagnosed as a Liver Neoplasm.

Am Surg 2021 Jan 27:3134820982846. Epub 2021 Jan 27.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, 13805National Center for Global Health and Medicine, Japan.

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http://dx.doi.org/10.1177/0003134820982846DOI Listing
January 2021

Real-time lymph flow projection mapping using near-infrared fluorescence.

J Surg Oncol 2021 Feb 17;123(2):701-702. Epub 2020 Dec 17.

Department of Plastic and Reconstructive Surgery, National Center for Global Health and Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1002/jso.26326DOI Listing
February 2021

Near-infrared spectroscopy carotid plaque characteristics and cerebral embolism in carotid artery stenting.

EuroIntervention 2021 Sep;17(7):599-606

Department of Neurosurgery, Nara Medical University, Nara, Japan.

Background: Perioperative thromboembolism is the main consideration in carotid artery stenting (CAS). Precise evaluation of carotid plaque components is clinically important to reduce ischaemic complications since CAS mechanically pushes plaque outwards, which releases plaque debris into the bloodstream.

Aims: This study aimed to determine whether high lipid core plaque (LCP) assessed by catheter-based near-infrared spectroscopy (NIRS) is associated with ipsilateral cerebral embolism by diffusion-weighted magnetic resonance imaging during CAS using a first-generation stent.

Methods: Carotid stenosis magnetic resonance (MR) T1-weighted plaque signal intensity ratio (T1W-SIR) followed by NIRS assessment at the time of CAS (using the carotid artery Wallstent) was performed in 117 consecutive patients.

Results: The maximum lipid core burden index (max-LCBI) at minimal luminal areas (MLA; max-LCBIMLA) and the max-LCBI for any 4 mm segment in a target lesion defined as max-LCBIarea were significantly higher for the post-procedural new ipsilateral diffusion-weighted magnetic resonance imaging (DWI)-positive than negative patients (p<0.001 for all). There was a significant linear correlation between max-LCBIarea and the number of new emboli (r=0.544, p<0.0001). We also found that the second quantile (Q2) of T1W-SIRMLA had a significantly higher max-LCBIMLA and a higher incidence of DWI positivity than Q1 and Q3 (p<0.001 for all). Furthermore, max-LCBIMLA appeared to distinguish between patients with and without postoperative new ipsilateral DWI positivity (AUC 0.91, 95% CI: 0.86-0.96; p<0.0001).

Conclusions: High LCP assessed by NIRS is associated with cerebral embolism by diffusion-weighted imaging in CAS using a first-generation stent.
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http://dx.doi.org/10.4244/EIJ-D-20-01050DOI Listing
September 2021

Pancreaticoduodenectomy with malrotation following reoperation due to torsion of efferent loop: a case report.

Surg Case Rep 2020 Sep 25;6(1):223. Epub 2020 Sep 25.

Department of Surgery, Kasugai Municipal Hospital, 1-1-1 Takaki-cho, Kasugai-shi, Aichi, Japan.

Background: Malrotation is a congenital anomaly during the development of the embryonic intestine. Although it is generally considered a pediatric surgical condition, it can have significant implications for adult surgery in terms of reconstruction.

Case Presentation: The patient was an 85-year-old man with pancreatic cancer and intestinal malrotation. He underwent pancreaticoduodenectomy with modified Child's reconstruction. Because the ascending colon and efferent loop twisted easily, we fixed the ascending colon to the abdominal wall. Thereafter, right twist and stenosis of the efferent loop occurred. On the 22nd day after the initial surgery, detorsion and Braun anastomosis were performed for efferent loop fixation. Postoperative oral intake was good, and the patient was discharged from our hospital on the 24th day after the reoperation.

Conclusions: This is a rare case of pancreaticoduodenectomy with malrotation following reoperation due to a complication after Child's reconstruction. In similar cases of intestinal malrotation, it is important to consider avoiding coaxial positioning of intestinal parts and an upper abdominal space while selecting a reconstruction method.
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http://dx.doi.org/10.1186/s40792-020-00991-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519017PMC
September 2020

Lipid Core Plaque Distribution Using Near-infrared Spectroscopy Is Consistent with Pathological Evaluation in Carotid Artery Plaques.

Neurol Med Chir (Tokyo) 2020 Oct 2;60(10):499-506. Epub 2020 Sep 2.

Department of Neurosurgery, Nara Medical University.

Carotid artery stenting (CAS) is performed as a treatment for carotid artery stenosis. However, lipid-rich plaques cause embolic complications and sequelae. Near-infrared spectroscopy (NIRS) can identify lipid components by applying a near-infrared absorption pattern, and the distribution of lipid components can be evaluated as the maximum lipid core burden index (maxLCBI). Intravascular ultrasound (IVUS) equipped with NIRS has been clinically applied recently, and its diagnostic usefulness and validation have been reported for coronary arteries; however, its consistency with actual pathological diagnosis in carotid artery lesions has not been validated. In this study, we investigated the consistency between the maxLCBI values and histopathological diagnoses. Patients with cervical carotid artery stenosis who underwent carotid endarterectomy (CEA) were examined in this prospective study. Pathological diagnosis was determined after NIRS evaluation, which was performed on the extracted plaques ex vivo. The histological slices of decalcified and paraffin-embedded sections were stained by hematoxylin-eosin (HE) and Elastica van Gieson (EVG), and for low-density lipoprotein (LDL), C-reactive protein (CRP), CD68, and glycophorin A. The correlation between maxLCBI values and histological findings. Seventy lesions assessed by NIRS were pathologically analyzed. There was a positive linear correlation between maxLCBI values and pathological findings as determined by HE (angle), HE (area%), EVG, CRP, and CD68 staining (respectively, r = 0.624, p <0.001; r = 0.578, p <0.001; r = 0.534, p <0.001; r = 0.723, p <0.001; r = 0.653, p <0.001). In conclusion, the maxLCBI values assessed by NIRS showed a significant positive linear correlation with pathological evaluations in carotid lesions. The maxLCBI values in carotid arteries are consistent with pathological evaluations.
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http://dx.doi.org/10.2176/nmc.oa.2020-0154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555160PMC
October 2020

[Liver Herniation through a Diaphragmatic Defect Mimicking Pleural Tumor;Report of a Case].

Kyobu Geka 2020 Mar;73(3):236-239

Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan.

Liver herniation is rare and sometimes difficult to differentiate from pleural or diaphragmatic tumor. A 64-year-old woman was admitted due to a mass-like shadow in the right lower lung field. Computed tomography, coronal view, showed a well-defined mass forming an acute angle with the right diaphragm, mimicking pleural tumor. Video-assisted thoracic surgery was performed, revealing herniated liver through one of the multiple diaphragmatic defects, which was repositioned into the abdominal cavity, and the diaphragmatic defect was repaired. The patient recovered well and was discharged on postoperative day 5.
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March 2020

Photoinduced Cyclizations of -Diisocyanoarenes with Organic Diselenides and Thiols that Afford Chalcogenated Quinoxalines.

J Org Chem 2020 Jun 12;85(11):7258-7266. Epub 2020 May 12.

Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan.

This study describes the syntheses of 2,3-bis(selanyl)quinoxalines via the photoinduced cyclizations of -diisocyanoarenes with diaryl or dialkyl diselenides, in addition to providing a detailed discussion of the corresponding mechanism and revealing that the developed procedure can also be applied to prepare 2-thiolated quinoxaline derivatives from -diisocyanoarenes and thiols. The developed technique does not need the use of additives or metal catalysts and features the advantages of a high conversion, a broad substrate scope, and mild reaction conditions, thereby rendering it a valuable addition to the quinoxaline synthesis toolbox.
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http://dx.doi.org/10.1021/acs.joc.0c00647DOI Listing
June 2020

Long-term survival after surgical resection for recurrent hepatic and pulmonary metastases of intrahepatic cholangiocarcinoma: a case report.

Surg Case Rep 2019 Aug 20;5(1):135. Epub 2019 Aug 20.

Division of Surgery, Kasugai Municipal Hospital, Aichi, Japan.

Background: A few reports to date have described the effectiveness of surgical resection for recurrent intrahepatic cholangiocarcinoma (ICC). We report in this study a patient who achieved long-term survival after surgical resection for recurrent hepatic and pulmonary metastases of ICC.

Case Presentation: A 62-year-old man was referred to our hospital for examination of a tumor in the left lobe of the liver. Computed tomography (CT) scans of the abdomen revealed a hypovascularized tumor, 30 mm in hepatic segment 2 (S2). The patient was diagnosed with a mass-forming type of ICC. A left lateral sectionectomy with regional lymph node dissection was performed. Histopathological examination showed moderately differentiated adenocarcinoma in the hepatic S2 with lymph node metastasis. There were two intrahepatic metastases around the main tumor. The pathological stage of the ICC was pT2pN1M0pStageIIIB. The patient did not receive adjuvant chemotherapy after surgery. Twelve months after surgery, liver lesions in S4/S8 and S7 were detected on CT scans. A partial hepatectomy was performed. The histopathological features were similar to those of the previous ICC. The patient did not receive adjuvant chemotherapy after the repeat hepatectomy. Four years and four months after this repeat hepatectomy, CT scans showed multiple nodes in S4 and S10 of the left lung and in S1 of the right lung. Wedge resection of the left upper lobe and sectionectomy in S10 of the left lung were performed. Histopathological findings of the resected lung nodules were compatible with metastatic ICC. The nodule in S1 of the right lung was too small to be diagnosed as metastasis; therefore, it was not resected. After pulmonary resection, the patient was treated with gemcitabine and cisplatin for 6 months. After chemotherapy, the size of the nodule in S1 increased gradually. One year and ten months after the pulmonary resection, we performed wedge resection of S1 of the right lung, and the histopathological findings were compatible with metastatic ICC. The patient is alive without evidence of disease 8 years after the initial surgery and 8 months after the last pulmonary resection.

Conclusions: ICC with poor prognostic factors can frequently recur; however, surgical resection for recurrent ICC might, for selected patients, enable long-term survival.
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http://dx.doi.org/10.1186/s40792-019-0693-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702248PMC
August 2019

A long-term survival case after resection of the pancreatic metastasis from lung cancer.

Int J Surg Case Rep 2019 25;61:222-225. Epub 2019 Jul 25.

Division of Surgery, Kasugai Municipal Hospital, Aichi, Japan.

Introduction: Pancreatic metastasis from lung cancer is not an indication for surgical resection because patients with such a condition present with multiple-organ metastases. Therefore, the significance of resection in patients with pancreatic metastasis from lung cancer remains unclear. Here we report a case of a long-term survivor of pancreatic metastasis from lung cancer after pancreatectomy.

Case Presentation: A 67-year-old woman presented with a pancreatic mass. She had undergone left lower lobectomy for stage IIIA lung adenocarcinoma 6 years prior to presentation. Following surgery, she received adjuvant treatment with gefitinib for 7 months. However, this treatment was discontinued due to its side effects. The patient received radiation therapy for mediastinal lymph node metastasis 2 years after resection and she became cancer-free. Six years after the initial pulmonary resection, the patient's tumor marker level increased, and abdominal computed tomography (CT) revealed a 20-mm tumor in the pancreatic tail. Positron emission tomography-CT revealed an abnormal uptake in the pancreatic tail. However, no other abnormal lesions were observed. The diagnosis was primary pancreatic cancer or metastasis from lung cancer. Distal pancreatectomy with lymph node dissection was performed, and the pathological diagnosis was metastasis from lung cancer. The patient survived for more than 5 years without recurrence but she died of acute renal failure after acquiring pneumonia.

Conclusion: Surgical treatment should be considered for pancreatic metastasis from lung cancer if the disease is localized and the patient's condition is good. Additionally, combined therapy, including surgical resection, may be effective for repeated recurrence.
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http://dx.doi.org/10.1016/j.ijscr.2019.07.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698278PMC
July 2019

Seroprevalence and associated factors of Toxoplasma gondii among HIV-infected patients in Tokyo: A cross sectional study.

J Infect Chemother 2020 Jan 23;26(1):33-37. Epub 2019 Jul 23.

Department of Tropical Medicine, The Jikei University School of Medicine, Tokyo, Japan. Electronic address:

HIV infection, in particular in patients with developing AIDS, carries a risk of causing toxoplasmosis with encephalitis, which is mostly caused by a form (bradyzoite) of the protozoan parasite Toxoplasma gondii. HIV/AIDS in Japan has been recognized as a serious health issue in recent years. In this study, to elucidate T. gondii seroprevalence in HIV-positive patients in Japan and associated characteristics with Toxoplasma parasite infection, the titer of T. gondii IgG (Tg-IgG) was measured in 399 HIV-positive patients who visited a hospital in Tokyo, Japan, between 2015 and 2017. A questionnaire survey was also conducted to investigate associations between lifestyle and customs. As a result, the overall prevalence of Tg-IgG-positive serum was 8.27% (33 cases of 399). All the cases positive for Tg-IgG were confirmed using the Sabin-Feldman dye test; the titers between each examination correlated robustly (p < 0.001, r = 0.6). A correlation between Toxoplasma infection rate and age was determined (p < 0.001), whereas there was no significant correlation with lifestyle customs such as consuming undercooked meat or owning a cat. An association between Toxoplasma infection and experience of dwelling in the Hokkaido area, the northern part of Japan, was observed (p = 0.001). These results suggested that the proportion of those who were previously exposed to Toxoplasma parasites in the HIV-positive population has been maintained at a similar level as that of the HIV-negative population in Japan, providing clear information about the potential risk of toxoplasmic encephalitis.
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http://dx.doi.org/10.1016/j.jiac.2019.06.012DOI Listing
January 2020

Genetically encoded orientation probes for F-actin for fluorescence polarization microscopy.

Microscopy (Oxf) 2019 Oct;68(5):359-368

Department of Neuroanatomy and Cellular Neurobiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

Fluorescence polarization microscopy, which can visualize both position and orientation of fluorescent molecules, is useful for analyzing architectural dynamics of proteins in vivo, especially that of cytoskeletal proteins such as actin. Fluorescent phalloidin conjugates and SiR-actin can be used as F-actin orientation probes for fluorescence polarization microscopy, but a lack of appropriate methods for their introduction to living specimens especially to tissues, embryos, and whole animals hampers their applications to image the orientation of F-actin. To solve this problem, we have developed genetically encoded F-actin orientation probes for fluorescence polarization microscopy. We rigidly connected circular permutated green fluorescent protein (GFP) to the N-terminal α-helix of actin-binding protein Lifeact or utrophin calponin homology domain (UtrCH), and normal mEGFP to the C-terminal α-helix of UtrCH. After evaluation of ensemble and single particle fluorescence polarization with the instantaneous FluoPolScope, one of the constructs turned out to be suitable for practical usage in live cell imaging. Our new, genetically encoded F-actin orientation probe, which has a similar property of an F-actin probe to conventional GFP-UtrCH, is expected to report the 3D architecture of the actin cytoskeleton with fluorescence polarization microscopy, paving the way for both the single molecular orientation imaging in cultured cells and the sub-optical resolution architectural analysis of F-actin networks analysis of F-actin in various living systems.
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http://dx.doi.org/10.1093/jmicro/dfz022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933534PMC
October 2019

Molecular chaperone prefoldin-assisted biosynthesis of gold nanoparticles with improved size distribution and dispersion.

Biomater Sci 2019 Apr;7(5):1801-1804

Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, Motooka 744, Nishi-ku, Fukuoka 819-0395, Japan.

Here we report a novel aspect of molecular chaperone prefoldin (PFD) as a biomaterial in the biocatalytic synthesis of gold nanoparticles (AuNPs) using glycerol dehydrogenase (GLD). We found that PFD could inhibit the aggregation of AuNPs during the biosynthesis, leading to the formation of AuNPs with controlled size distribution.
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http://dx.doi.org/10.1039/c8bm01026aDOI Listing
April 2019

Intraductal papillary neoplasm of the bile duct with rapidly progressive multicentric recurrence: A case report.

Int J Surg Case Rep 2018 19;51:102-106. Epub 2018 Aug 19.

Division of Surgery, Kasugai Municipal Hospital, Aichi, Japan.

Introduction: Knowledge on the pattern of recurrence and prognosis of intraductal papillary neoplasms of the bile duct (IPNB) is limited. Few studies have reported IPNB recurrence in the remnant intrahepatic bile duct, which is indicative of the true multicentricity of IPNB. Herein, we report a case of IPNB with rapidly progressive recurrence in the remnant intrahepatic bile duct and review the literature for discussing the prognosis of IPNB with multicentricity.

Case Presentation: A 72-year-old male was diagnosed with IPNB in the hepatic duct of segment 3 that had spread to the left hepatic duct. The patient underwent left hepatectomy, total caudate lobectomy, and extra-hepatic bile duct resection with biliary reconstruction. Histologically, the tumor was IPNB with noninvasive adenocarcinoma with a negative surgical margin. Although dilatation of B8 and biliary enzyme elevation were observed beginning at 7-10 months postoperatively, there was no evidence of recurrence. At 17 months postoperatively, the recurrent tumor diffusely spread throughout the remnant intrahepatic bile duct. Internal drainage stents were placed within the intrahepatic bile ducts with relapsed IPNB to relieve jaundice, and a course of chemotherapy was considered. However, the patient did not receive any therapies up to his death at 21 months postoperatively because of rapid disease progression.

Conclusion: According to a literature review, some cases of multicentric IPNB have shown rapidly progressive recurrence and poor prognosis. We should consider multicentricity of IPNB even a few months after curative resection, and narrow examinations should also be considered.
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http://dx.doi.org/10.1016/j.ijscr.2018.08.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111009PMC
August 2018

Broad impact of extracellular DNA on biofilm formation by clinically isolated Methicillin-resistant and -sensitive strains of Staphylococcus aureus.

Sci Rep 2018 02 2;8(1):2254. Epub 2018 Feb 2.

Department of Bacteriology, The Jikei University School of Medicine 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan.

Staphylococcus aureus is a major causative agent for biofilm-associated infections. Inside biofilms, S. aureus cells are embedded in an extracellular matrix (ECM) composed of polysaccharide-intercellular adhesins (PIA), proteins, and/or extracellular DNA (eDNA). However, the importance of each component and the relationship among them in biofilms of diverse strains are largely unclear. Here, we characterised biofilms formed by 47 S. aureus clinical isolates. In most (42/47) of the strains, biofilm formation was augmented by glucose supplementation. Sodium chloride (NaCl)-triggered biofilm formation was more prevalent in methicillin-sensitive S. aureus (15/24) than in methicillin-resistant strain (1/23). DNase I most effectively inhibited and disrupted massive biofilms, and Proteinase K was also effective. Anti-biofilm effects of Dispersin B, which cleaves PIA, were restricted to PIA-dependent biofilms formed by specific strains and showed significant negative correlations with those of Proteinase K, suggesting independent roles of PIA and proteins in each biofilm. ECM profiling demonstrated that eDNA was present in all strains, although its level differed among strains and culture conditions. These results indicate that eDNA is the most common component in S. aureus biofilms, whereas PIA is important for a small number of isolates. Therefore, eDNA can be a primary target for developing eradication strategies against S. aureus biofilms.
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http://dx.doi.org/10.1038/s41598-018-20485-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797107PMC
February 2018

Ubiquitination of stalled ribosome triggers ribosome-associated quality control.

Nat Commun 2017 07 31;8(1):159. Epub 2017 Jul 31.

Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.

Translation arrest by polybasic sequences induces ribosome stalling, and the arrest product is degraded by the ribosome-mediated quality control (RQC) system. Here we report that ubiquitination of the 40S ribosomal protein uS10 by the E3 ubiquitin ligase Hel2 (or RQT1) is required for RQC. We identify a RQC-trigger (RQT) subcomplex composed of the RNA helicase-family protein Slh1/Rqt2, the ubiquitin-binding protein Cue3/Rqt3, and yKR023W/Rqt4 that is required for RQC. The defects in RQC of the RQT mutants correlate with sensitivity to anisomycin, which stalls ribosome at the rotated form. Cryo-electron microscopy analysis reveals that Hel2-bound ribosome are dominantly the rotated form with hybrid tRNAs. Ribosome profiling reveals that ribosomes stalled at the rotated state with specific pairs of codons at P-A sites serve as RQC substrates. Rqt1 specifically ubiquitinates these arrested ribosomes to target them to the RQT complex, allowing subsequent RQC reactions including dissociation of the stalled ribosome into subunits.Several protein quality control mechanisms are in place to trigger the rapid degradation of aberrant polypeptides and mRNAs. Here the authors describe a mechanism of ribosome-mediated quality control that involves the ubiquitination of ribosomal proteins by the E3 ubiquitin ligase Hel2/RQT1.
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http://dx.doi.org/10.1038/s41467-017-00188-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534433PMC
July 2017

Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

Brain Res 2017 Sep 21;1670:165-172. Epub 2017 Jun 21.

Department of Neurosurgery, Nara Medical University, Japan.

Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH.
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http://dx.doi.org/10.1016/j.brainres.2017.06.017DOI Listing
September 2017

Sugar-sensitive dendrimer films as a sacrificial layer for the preparation of freestanding multilayer films.

Mater Sci Eng C Mater Biol Appl 2017 Mar 17;72:118-122. Epub 2016 Nov 17.

Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan. Electronic address:

Multilayer thin films composed of poly(vinyl alcohol) (PVA) and phenylboronic acid-bearing poly(amidoamine) dendrimer (PBA-PAMAM) were used as a sacrificial layer for constructing freestanding polyelectrolyte films consisting of poly(styrenesulfonate) (PSS) and poly(allylamine hydrochloride) (PAH). Freestanding (PSS/PAH) films were successfully released from substrate by exposing composite (PVA/PBA-PAMAM)/(PSS/PAH) films (n=5 and 10) to sorbitol solutions under mild conditions at pH7.0-9.0. The film release was accelerated in solutions of higher sorbitol concentrations at pH9.0 as well as in solutions with lower concentration of NaCl. The results were rationalized based on the scission of boronate ester bonds between PBA-PAMAM and PVA in the (PVA/PBA-PAMAM) layer due to a competitive binding of sorbitol to PBA-PAMAM.
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http://dx.doi.org/10.1016/j.msec.2016.11.061DOI Listing
March 2017

Semi-in situ atomic force microscopy imaging of intracellular neurofilaments under physiological conditions through the 'sandwich' method.

Microscopy (Oxf) 2016 08 8;65(4):316-24. Epub 2016 Mar 8.

Department of Neuroanatomy and Cellular Neurobiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

Neurofilaments are intermediate filament proteins specific for neurons and characterized by formation of biochemically stable, obligate heteropolymers in vivo While purified or reassembled neurofilaments have been subjected to morphological analyses by electron microscopy and atomic force microscopy, there has been a need for direct imaging of cytoplasmic genuine intermediate filaments with minimal risk of artefactualization. In this study, we applied the modified 'cells on glass sandwich' method to exteriorize intracellular neurofilaments, reducing the risk of causing artefacts through sample preparation. SW13vim(-) cells were double transduced with neurofilament medium polypeptide (NF-M) and alpha-internexin (α-inx). Cultured cells were covered with a cationized coverslip after prestabilization with tannic acid to form a sandwich and then split into two. After confirming that neurofilaments could be deposited on ventral plasma membranes exposed via unroofing, we performed atomic force microscopy imaging semi-in situ in aqueous solution. The observed thin filaments, considered to retain native structures of the neurofilaments, exhibited an approximate periodicity of 50-60 nm along their length. Their structural property appeared to reflect the morphology formed by their constituents, i.e. NF-M and α-inx. The success of semi-in situ atomic force microscopy of exposed bona fide assembled neurofilaments through separating the sandwich suggests that it can be an effective and alternative method for investigating cytoplasmic intermediate filaments under physiological conditions by atomic force microscopy.
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http://dx.doi.org/10.1093/jmicro/dfw006DOI Listing
August 2016

Associations of HIV testing and late diagnosis at a Japanese university hospital.

Clinics (Sao Paulo) 2016 Feb;71(2):73-7

Department of Infectious Diseases and Infection Control, Jikei University School of Medicine, Tokyo, Minato-ku, Japan.

Objectives: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis.

Methods: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed.

Results: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis.

Conclusions: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.
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http://dx.doi.org/10.6061/clinics/2016(02)04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760363PMC
February 2016

[Two cases of Paragonimiasis westermani in a Chinese family diagnosed with the Ouchterlony double diffusion method].

Kansenshogaku Zasshi 2014 Nov;88(6):866-70

We report two cases of Paragonimus westermani infection in a Chinese family in Japan. A 41-year-old husband and his 40-year-old wife were infected with P. westermani after consuming a homemade Chinese traditional "Drunken Crab." They were a family with two children who had lived in Japan for 19 years. The crabs were Eriocheir japonica sent from the Kyusyu area that they had pickled at home with soy sauce and Chinese liquor for 5 days. Their children did not eat any of the crabs. One month after consuming the crabs, the husband came to our outpatient clinic with fever and chest pain and his wife also presented with a persistent cough. Both patients had a high peripheral blood eosinophil count (husband:18,900/μL, wife:10,600/μL) with pulmonary effusion, nodular shadow, and pneumothorax in chest X-ray findings. Paragonimiasis was suspected from the episode of consuming the crabs. No parasite eggs were seen in their sputum and stool samples. A multiple-dot ELISA was performed with the sera to screen for parasitic infections, but the result was only weakly positive for P. westermani antigen in the husband and a slightly positive reaction in the wife. The diagnosis of P. westermani was achieved with the double diffusion Ouchterlony method using P. westermani antigen and P. miyazakii antigen. Praziquantel administration for three days improved the symptoms in both patients. The Ouchterlony method proved useful in diagnosing paragonimiasis in these cases.
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http://dx.doi.org/10.11150/kansenshogakuzasshi.88.866DOI Listing
November 2014

Predictive factors for metastatic infection in patients with bacteremia caused by methicillin-sensitive Staphylococcus aureus.

Am J Med Sci 2015 Jan;349(1):24-8

Department of Infectious Diseases and Infection Control, Jikei University School of Medicine, Tokyo, Japan.

Background: Metastatic infections such as infective endocarditis and psoas abscess are serious complications of Staphylococcus aureus bacteremia because failure to identify these infections may result in bacteremia relapse or poor prognosis. In the present study, we determined the predictive factors for metastatic infection due to methicillin-sensitive S. aureus bacteremia.

Methods: A retrospective cohort study was conducted among patients with methicillin-sensitive S. aureus bacteremia at the Jikei University Hospital between January 2008 and December 2012. Factors analyzed included the underlying disease, initial antimicrobial treatment and primary site of infection.

Results: During the 5-year study period, 73 patients met the inclusion criteria and were assessed. The most common primary site of bacteremia was catheter-related bloodstream infection (25/73 [34.2%]). Metastatic infection occurred in 14 of 73 patients (19.2%) (infective endocarditis [3], septic pulmonary abscess [3], spondylitis [4], psoas abscess [4], epidural abscess [3] and septic arthritis [1]). Six patients had multiple metastatic infections. Multivariate analysis revealed that the predictive factors associated with the development of metastatic infection were a delay in appropriate antimicrobial treatment of >48 hours, persistent fever for >72 hours after starting antibiotic treatment and lowest C-reactive protein levels of >3 mg/dL during 2 weeks after the onset of bacteremia.

Conclusions: This study demonstrated that additional diagnostic tests should be conducted to identify metastatic infection, particularly in patients with delayed antimicrobial treatment, persistent fever and persistently high C-reactive protein levels.
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http://dx.doi.org/10.1097/MAJ.0000000000000350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281166PMC
January 2015

A refined technique for extraction of extracellular matrices from bacterial biofilms and its applicability.

Microb Biotechnol 2015 May 23;8(3):392-403. Epub 2014 Aug 23.

Department of Bacteriology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

Biofilm-forming bacteria embedded in polymeric extracellular matrices (ECMs) that consist of polysaccharides, proteins and/or extracellular DNAs (eDNAs) acquire high resistance to antimicrobial agents and host immune systems. To understand molecular mechanisms of biofilm formation and maintenance and to develop therapeutic countermeasures against chronic biofilm-associated infections, reliable methods to isolate ECMs are inevitable. In this study, we refined the ECM extraction method recently reported and evaluated its applicability. Using three Staphylococcus aureus biofilms in which proteins, polysaccharides or eDNAs are major contributors to their integrity, ECMs were extracted using salts and detergents. We found that extraction with 1.5 M sodium chloride (NaCl) could be optimum for not only ECM proteins but also polysaccharides and eDNAs. In addition, long-time incubation was not necessary for efficient ECM isolation. Lithium chloride (LiCl) was comparative to NaCl but is more expensive. In contrast to SDS, NaCl hardly caused leakage of intracellular proteins and did not affect viability of bacterial cells within biofilms. Furthermore, this method is applicable to other bacteria such as Gram-positive Staphylococcus epidermidis and Gram-negative Escherichia coli and Pseudomonas aeruginosa. Thus, this refined method is very simple, rapid, low cost and non-invasive and could be used for a broad range of applications.
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http://dx.doi.org/10.1111/1751-7915.12155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408173PMC
May 2015

A study of the right intersectional plane (right portal scissura) of the liver based on virtual left hepatic trisectionectomy.

World J Surg 2014 Dec;38(12):3181-5

Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, Japan.

Background: Left hepatic trisectionectomy is a challenging procedure. For an anatomically correct resection, it is necessary to have understanding of the right intersectional plane; however, little is known on this issue. The purpose of this study was to investigate the 3D anatomy of the right intersectional plane and to enable safe and precise left trisectionectomy.

Methods: A virtual left trisectionectomy was performed using 3D-processing software, in patients who underwent computed tomography. The reconstructed images were reviewed, and attention was paid to the extent of the right hepatic vein (RHV) exposure on the transected plane and the type of the inferior right hepatic vein (IRHV).

Results: Of the 200 study patients, 109 (54.5 %) patients showed complete exposure of the RHV on the transected plane, whereas the remaining 91 exhibited partial exposure. In the 109 patients with complete exposure, 58 (53.2 %) patients had no IRHV and the remaining 51 had a small IRHV. None of the patients had a large IRHV. In contrast, of the 91 patients with partial exposure, only 10 (11.0 %) patients had no IRHV, 35 (38.5 %) had a small IRHV, and 46 (50.5 %) patients had a large IRHV. The incidence of IRHV types was significantly different between the two groups (P < 0.001).

Conclusions: The RHV does not always run along the right intersectional plane, i.e., the vein is not always fully exposed on the transected plane even after anatomically correct left trisectionectomy. The extent of the RHV exposure is closely related to the type of the IRHV.
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http://dx.doi.org/10.1007/s00268-014-2718-5DOI Listing
December 2014

A case of NDM-1-producing Acinetobacter baumannii transferred from India to Japan.

J Infect Chemother 2013 Apr 12;19(2):330-2. Epub 2012 Sep 12.

Department of Infection Control and Infectious Disease, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minatoku-ku, Tokyo, Japan.

A 52-year-old male Japanese businessman with massive cerebral bleeding was transferred from India to Japan and was admitted to our hospital. Multidrug-resistant Acinetobacter baumannii was isolated from his sputum. The minimum inhibitory concentrations for this strain were as follows: imipenem, 64 μg/ml; meropenem, 32 μg/ml; ciprofloxacin, 16 μg/ml; amikacin, 16 μg/ml; aztreonam, 16 μg/ml; colistin, <1 μg/ml. This A. baumannii strain had both bla NDM-1 and bla OXA-23 by polymerase chain reaction analysis. In Japan, NDM-1-producing bacteria are extremely rare in clinical specimens. To date, three NDM-1-positive cases have been detected in Japan, and this is the first case of A. baumannii-producing NDM-1 in Japan. Our case suggests that NDM-1-producing bacteria could be introduced into our country easily. There is concern that various resistant bacteria may be transferred from epidemic countries as a result of international medical care.
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http://dx.doi.org/10.1007/s10156-012-0469-5DOI Listing
April 2013

An HIV patient with hepatic flare after the initiation of HBV-active antiretroviral therapy.

Intern Med 2012 15;51(12):1623-6. Epub 2012 Jun 15.

Department of Infectious Diseases and Infection Control, The Jikei University School of Medicine, Japan.

A 39-year-old man presented a CD4 T cell count of 78/µL and HIV-RNA at 6.6 × 10(5) copies/mL at his first medical examination. After the 58th day, we initiated HBV-active antiretroviral therapy. Three months after the start of antiretroviral therapy, he was diagnosed with hepatic flare on the basis of elevated AST and ALT levels without detecting HBV-DNA. Although after continuing the medication his AST and ALT levels increased to 700 IU/L and 1,400 IU/L, respectively, he showed improvement following a natural course and was discharged from hospital after the 169th day. This is a case of hepatic flare likely caused by immune reconstitution associated with resolved HBV infection.
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http://dx.doi.org/10.2169/internalmedicine.51.7244DOI Listing
November 2012
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