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Background: The purpose of this meta-analysis was to comprehensively investigate the diagnostic ability of 1.5 T and 3.0 T whole heart coronary angiography (WHCA) to detect significant coronary artery disease (CAD) on X-ray coronary angiography., Methods: A literature search of electronic databases, including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE, was performed to retrieve and integrate articles showing significant CAD detectability of 1.5 and 3.0 T WHCA., Results: Data from 1899 patients from 34 studies were included in the meta-analysis. 1.5 T WHCA had a summary area under ROC of 0.88 in the patient-based analysis, 0.90 in the vessel-based analysis, and 0.92 in the segment-based analysis. These values for 3.0 T WHCA were 0.94, 0.95, 0.96, respectively. Contrast-enhanced 3.0 T WHCA had significantly higher specificity than non-contrast-enhanced 1.5 T WHCA on a patient-based analysis (0.87, 95% CI 0.80-0.92 vs. 0.74, 95% CI 0.64-0.82, P = 0.02). There were no differences in diagnostic performance on a patient-based analysis by use of vasodilators, beta-blockers or between Asian and Western countries., Conclusions: The diagnostic performance of WHCA was deemed satisfactory, with contrast-enhanced 3.0 T WHCA exhibiting higher specificity compared to non-contrast-enhanced 1.5 T WHCA in a patient-based analysis. There were no significant differences in diagnostic performance on a patient-based analysis in terms of vasodilator or beta-blocker use, nor between Asian and Western countries. However, further large-scale multicentre studies are crucial for the widespread global adoption of WHCA., (© 2023. The Author(s).)

Background: These clinical practice guidelines are intended to provide recommendations based on the best evidence obtained to date on key issues in clinical practice to improve the prognosis, diagnostic and therapeutic processes for patients with soft tissue tumors., Methods: The Guidelines Development Committee and Systematic Review Committee were composed of a multidisciplinary team of specialists who play an important role in soft tissue tumor care. Clinical questions (CQs) were determined by choosing key decision-making points based on Algorithms for the diagnosis and treatment of soft tissue tumors. The guidelines were developed according to the "Medical Information Network Distribution Service (Minds) Handbook for Clinical Practice Guideline Development 2014" and "Minds Manual for Clinical Practice Guideline Development 2017." Recommendation strength was rated on two levels and the strength of evidence was rated on four levels. The recommendations were decided based on agreement by 70% or more voters., Results: Twenty-two CQs were chosen by the Guidelines Development Committee. The Systematic Review Committee reviewed the evidence concerning each CQ, a clinical value judgment was added by experts, and the text of each recommendation was determined., Conclusion: We established 22 CQs and recommendations for key decision-making points in the diagnosis and treatment of soft tissue tumors according to the Minds Clinical Practice Guideline development methods. We hope that these guidelines will assist the decision-making of all medical staff engaged in the treatment and diagnosis of soft tissue tumors, and eventually lead to improved soft tissue tumor care in the country., Competing Interests: Declaration of competing Interest Akira Kawai reports research grants from Daiichi-Sankyo, Eli-Lilly, Taiho, Takara-Bio and Japanese Orthopaedic Association. Hirotaka Kawano reports honoraria from Daiichi Sankyo and Hisamitsu, and research grants from Japanese Orthopaedic Association, Nakatomi Foundation, Daiichi-Sankyo, Kyocera, Shionogi, Teijin, Zimmer Biomet, Johnson and Johnson, Smith and Nephew, Peter Blehm Japan and Stryker Japan. Toshiyuki Kunisada reports a research grant from Kuraray, and the Department of Medical Materials for Musculoskeletal Reconstruction is an endowment department, supported with an unrestricted grant from Kyocera. Shunji Takahashi reports honoraria from Eisai, Novartis, Taiho, Astrazeneca, Chugai, Bayer, Daiichi-Sankyo, and research grants from EISAI, Novartis, Taiho, Astrazeneca, Chugai, Bayer, Daiichi-Sankyo, Ono pharmaceutical, IQVIA and Bristol-Myers-Squib. Kazuhiro Tanaka belongs to an endowment department supported with grants from Teijin Nakashima Medical Co., Ltd. and Meditec Co., Ltd. Norio Yamamoto belongs to an endowed department supported with grants from Zimmer Biomet G.K. and Hisamitsu Pharmaceutical Co., Inc., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Successful bipolar radiofrequency catheter ablation (RFCA) of refractory ventricular arrhythmias (VAs) has been reported. However, the efficacy, safety, and long-term outcomes of bipolar RFCA of VAs are not fully determined., Objective: The purpose of this study was to evaluate the effectiveness and safety of bipolar RFCA in treating refractory VAs during long-term follow-up., Methods: Eighteen patients who underwent bipolar RFCA for ventricular tachycardia (VT) at 7 institutions were retrospectively investigated. Underlying heart diseases included remote myocardial infarction (n = 3 [17%]) and nonischemic cardiomyopathy (n = 15 [83%]). Although unipolar RFCA was performed in all patients, either it failed to suppress VT or VT recurred. The interventricular septum, left ventricular free wall, and left ventricular summit were targeted for bipolar RFCA., Results: Acute success (VT termination and/or noninducibility) was achieved with bipolar RFCA in 16 patients (89%). Complications during the procedure included complete atrioventricular block (n = 2) and coronary artery stenosis (n = 1). One patient underwent chemical ablation after bipolar RFCA failure. At 12-month follow-up, VT reoccurred in 8 patients (44%). However, in patients with recurrence, VT burden had decreased: only 4 patients underwent re-RFCA, and only 1 of the 4 required chemical ablation. In the remaining 4 patients, re-RFCA was not required, as VT was controlled by medication or an implantable cardioverter-defibrillator., Conclusion: Bipolar RFCA is useful for acute suppression of refractory VT. Although VT recurrence rates during long-term follow-up were relatively high, we observed a significant reduction in VT burden., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Front face fluorescence spectroscopy of typical Japanese soil powders (soil A: Typic Hapludand; soil H: Typic Hydraquent; soil Y: Typic Paleudult) has been conducted. Three dimensional excitation-emission matrix fluorescence spectra of the 100 wt% soils showed similar fluorescence patterns to each other. The fluorescence patterns were similar between the soil samples and their residues after extraction by NaOH solution for 60 min. In order to examine fluorescence extinction from a view point of whiteness of the soils, the soil powders were mixed with white and black diluents (Al 2 O 3 and Fe 3 O 4 ) and fluorescence spectra of the mixtures were measured at 450 nm excitation. At low levels of dilution with Al 2 O 3 (2-100 wt% of A; 50-100 wt% of H and Y), the fluorescence intensities increased with dilution. At high levels of dilution with Al 2 O 3 , the fluorescence intensities decreased with dilution. On the other hand, fluorescent intensities decreased by dilution with Fe 3 O 4 . These results suggested inner filter effect-like fluorescence extinction by (1) large amount of blackish organic compounds giving high total carbon value and (2) blackish non-fluorescent mineral compounds. In order to correct the fluorescence intensities of the mixtures containing the sample soils and the diluents, we preliminary applied a correction method based on the Kubelka-Munk theory using diffuse reflectance. The corrected fluorescence intensities of samples with white diluents (Al 2 O 3 ) were described by a simple fluorescence response model having saturation values., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Primary osteosarcoma in elderly patients are rare malignant tumors. Its optimal treatment has not yet been determined., Methods: This retrospective study included 104 patients aged >50 years with resectable, non-metastatic osteosarcoma treated by the members of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group. The effects of adjuvant chemotherapy were estimated by comparing outcomes in patients who received surgery plus chemotherapy with those who underwent surgery alone., Results: Median age at presentation was 59 years. Neoadjuvant and adjuvant chemotherapy was administered to 83 (79.8%) patients. Patients who underwent surgery plus chemotherapy and those who underwent surgery alone had 5-year overall survival (OS) rates of 68.6% and 71.7%, respectively (p = 0.780), and 5-year relapse free survival (RFS) rates of 48.2% and 43.6%, respectively (p = 0.64). Univariate analysis showed that resection with wide margins was significantly correlated with better prognosis., Conclusions: The addition of chemotherapy to surgery did not improve OS or RFS in patients aged >50 years with resectable, non-metastatic osteosarcoma. Surgery with wide margins was only significantly prognostic of improved survival. The effect of chemotherapy in elderly osteosarcoma patients was unclear., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: The development of effective chemotherapy regimens and molecular targeting agents are improving the overall survival rates in patients with cancer. However, patients who are non-ambulatory due to metastatic epidural spinal cord compression (MESCC) may be assessed as unable to tolerate chemotherapy secondary to poor performance status. This means that the ambulatory status of patients with cancer might be significant for survival time., Methods: We investigated the functional outcomes and factors influencing overall survival in 31 patients who were non-ambulatory due to MESCC and underwent decompression surgery. The functional outcome was determined by the Frankel grading system., Result: Twenty-one patients (68%) improved by at least 1 Frankel grade; 17 patients (55%) became ambulatory postoperatively. Most of postoperatively ambulatory patients could undergo postoperative chemotherapy (14/17, 82%). On the other hand, only a few postoperatively non-ambulatory patients could undergo postoperative chemotherapy (2/15, 13%). We observed a complication rate of 35.5% with specific complications including wound infection, pneumonia, and deep vein thrombosis/pulmonary embolus. The median survival duration was 7.0 months. Factors that significantly affected the overall survival in univariate analyses were revised Tokuhashi score (RTS) ≥ 4, postoperative chemotherapy, ambulatory status, and complications (RTS ≥ 4, P < 0.05; postoperative chemotherapy, P < 0.001; ambulatory status, P < 0.001; complications, P < 0.01)., Conclusions: Decompression surgery for patients who are non-ambulatory due to MESCC directly contributes to functional outcomes and may indirectly contribute to overall survival. If non-ambulatory patients who are assessed as unable to tolerate chemotherapy due to poor performance status regain the ability to walk by decompression surgery, they will have a chance to receive postoperative chemotherapy, thereby increasing their chances of prolonging survival. However, postoperative complications may shorten their survival; therefore, we should carefully consider the surgical indications. RTS is useful for judging the surgical indication., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Limited data are available regarding the prediction for functional recovery using late gadolinium enhanced magnetic resonance imaging (LGE MRI) after coronary revascularization for chronic total occlusion (CTO PCI)., Methods: We studied 59 patients (mean age, 66±11 years) who underwent successful CTO PCI. Two-dimensional echocardiography and strain measurements were performed before and 8±2 months after CTO PCI. The findings of segmental assessment were compared with the extent of LGE MRI using a 16-segment model., Results: From baseline to follow-up, ejection fraction (54.2±12.1% to 56.1±10.6%, p=0.010), global longitudinal strain (LS) (-15.1±5.1 to -16.7±5.1, p<0.001), global circumferential strain (CS) (-14.0±4.9 to -15.9±4.9, p<0.001), and wall motion score (WMS) index (1.45±0.53 to 1.33±0.39, p=0.014) significantly improved. In the territory of the CTO vessel, LS and CS significantly improved in segments of LGE ≤50%, but not in segments of LGE >50%. However, WMS improved only in segments of LGE 1-25%. At baseline and at follow-up, CS allowed better discrimination of segments of LGE >50% than WMS [at baseline; area under the curve (AUC) 0.79 vs. 0.68, respectively, p=0.001: at follow-up; AUC 0.84 vs. 0.69, respectively, p<0.001). Discriminatory ability of LS for segments of LGE >50% significantly improved from baseline to follow-up (AUC 0.73 vs. 0.83, p<0.001)., Conclusions: The cut-off value of the extent of LGE MRI is 50% to detect segments that will functionally recover after CTO PCI. Change in LS was more sensitive for removal of ischemia by CTO PCI, indicating the utility of LS to monitor the therapeutic effects of CTO recanalization., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to report the clinical outcomes for patients with osteoid osteoma (OO) treated by radiofrequency ablation (RFA) using a three-dimensional (3D) navigation system., Methods: We performed RFA using a 3D navigation system on 32 patients with clinically and radiologically diagnosed OO. This study included 25 males and 7 females with a median age of 20 years (range, 10-39 years). The median duration of follow-up was 18 months (range, 1-65 months). We investigated technical specifications, tumor localization, technical success, clinical success, biopsy success, complications, incomplete treatment, and recurrences., Results: Eighteen tumors were located in the femur, seven in the tibia, two in the humerus, and one each in the fibula, scapula, patella, lumbar vertebra, and acetabula. All procedures were technically successful, and pain relief was achieved in all patients. However, local recurrence developed in one patient, needing additional RFA. The clinical success rate was 96.8%. Biopsy showed OO in 12 patients (37%). Complications occurred in three patients (9%), two cases of fractures and one of osteomyelitis., Conclusions: A 3D navigation provides real-time imaging and enables us to set the RFA needle in the correct position, particularly in case of OO-aroused complex anatomical structures. Our initial results indicated that radiofrequency ablation using a 3D navigation system is feasible and safe for patients with OO., (Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: The presence of myocardial scar detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging has been described as a good independent predictor of mortality in patients with hypertrophic cardiomyopathy (HCM). Time-domain T-wave alternans (TWA) is also a potential predictor of cardiac mortality in patients with left ventricular dysfunction., Objective: The purpose of this study was to elucidate the relationship between LGE distribution and TWA in patients with HCM., Methods: CMR and TWA analyses using Holter monitoring were performed in 42 patients with HCM. The average transmural extent of LGE was scored as 1-4 in each segment, and the sum of the LGE scores (total LGE score) was calculated for each patient. The correlation between the maximal time-domain TWA voltage and LGE findings was analyzed, and the differences in time-domain TWA voltage, total LGE score, and cardiac function assessed by CMR imaging in the presence or absence of ventricular tachycardia (VT) were also compared., Results: The total LGE score was significantly and positively correlated with the maximal time-domain TWA voltage (r = 0.59; P < .001). Furthermore, the total LGE score and maximal time-domain TWA voltage were significantly greater in patients who had episodes of VT (n = 21) than in those without VT (23 ± 7 vs. 10 ± 8; P < .001 and 87 ± 26 μV vs. 62 ± 12 μV; P < .001, respectively). However, the left ventricular ejection fraction did not statistically differ between patients with VT and those without VT (56% ± 14% vs. 61% ± 7%; P = .102)., Conclusion: The magnitude of the localized LGE was significantly correlated with abnormalities in ventricular repolarization as assessed by TWA and QT dispersion., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the prognostic value of myocardial focal fibrosis quantified by late gadolinium enhanced (LGE) magnetic resonance imaging (MRI) in patients with heart failure with preserved ejection fraction (HFpEF)., Methods: One-hundred eleven HFpEF patients (mean age: 70 ± 14 years, 55 (50%) female) were enrolled. We excluded patients with previous history of coronary artery disease and/or ischemic pattern of hyper enhancement on LGE MRI. Myocardial enhancement was defined using signal intensity >2SD above the mean signal intensity of a remote myocardium. Major adverse cardiovascular events were defined as cardiovascular death and heart failure requiring hospitalization., Results: During a mean follow up period of 851 ± 609 days, 10 events (2 cardiovascular death, 8 hospitalization for heart failure decompensation) were observed. Area under the receiver operating characteristics curve of LGE% for the detection of future events was 0.721 (95% CI: 0.628-0.802). Multivariate Cox proportional hazard analysis showed that LGE% is an independent predictor of future events after the adjustment with prognostic 5 factors - age, diabetes mellitus, New York Heart Association classification, history of heart failure hospitalization and left ventricular ejection fraction - which were identified in the I-PRESERVE study (Irbesartan in Heart Failure with Preserved Ejection Fraction Study) (hazard ratio=7.913, 95% CI: 1.603-39.05, P=0.012)., Conclusions: Larger size of LGE was significantly associated with high rate of future cardiovascular death and heart failure hospitalization, suggesting that the quantification of myocardial focal fibrosis by LGE MRI could be useful for the risk stratification in HFpEF patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The presence of a myocardial scar detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been described as a predictor of all-cause mortality in hypertrophic cardiomyopathy (HCM). However, the detailed spatial relationship between LGE site and electrical abnormality is unclear in high-risk HCM with malignant arrhythmia., Objective: The purpose of this study was to elucidate the detailed relationship between the site on CMR imaging and the electrically damaged site, a potential origin of ventricular arrhythmias in patients with HCM., Methods: Fifty consecutive HCM patients underwent contrast-enhanced CMR. Of those patients, 18 patients with ventricular tachycardia underwent electrophysiology study including endocardial mapping of the left ventricle (LV). The LGE area was calculated at 12 different LV sites: anterior, lateral, posterior, and septal segments of the basal, middle, and apical portions. At each LV site, the bipolar electrogram, effective refractory period (ERP), and monophasic action potential were recorded., Results: LGE-positive segments demonstrated a significantly lower amplitude (4.0 ± 2.8 mV vs 7.3 ± 3.6 mV; P < .001), longer duration (54.7 ± 17.8 vs 40.6 ± 7.8 ms; P < .001), longer ERP (320 ± 42 ms vs 284 ± 37 ms; P = .001), and longer monophasic action potential duration measured at 90% repolarization (321 ± 19 ms vs 283 ± 25 ms; P < .001) than did LGE-negative segments. The LGE area negatively correlated with the amplitude (r = -0.59; P < .001) and positively correlated with the duration (r = 0.64; P < .001), ERP (r = 0.44; P < .001), and action potential duration measured at 90% repolarization (r = 0.63; P < .001). All the observed VTs originated from LGE-positive segments., Conclusion: The spatial distribution of LGE significantly correlates with depolarizing and repolarizing electrical damage in high-risk HCM with malignant ventricular arrhythmia., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The surgical management of soft tissue sarcoma (STS) in elderly patients has only been addressed in a few studies. The objective of the current study was to assess surgical outcomes in patients with STS aged 70 years and older and the association of older age with the survival after complete resection., Methods: A retrospective analysis was conducted in 158 elderly patients with localized STS who visited 11 institutions participating in Japanese Musculoskeletal Oncology Group between 1995 and 2006 and were treated by surgical resection. Univariate and multivariate analyses were performed to identify prognostic factors., Results: Median follow-up period was 38 months. Histologically high-grade tumors were detected in 71% of the patients. Wide resection with adequate margins was performed in 66% of the cases. Systemic chemotherapy was performed in only 5 patients. Univariate analysis identified histological grade and gender as statistically significant prognostic factors for sarcoma-specific survival. Multivariate analysis did not identify significant prognostic factors for sarcoma-specific survival, although high grade sarcoma emerged as a potentially significant prognostic factor (P = 0.050). Local recurrence was detected in 19% of the patients. Multivariate analysis of local recurrence-free survival showed that tumor site and surgical margins were statistically significant prognostic factors., Conclusions: Older age was not identified as a prognostic factor for sarcoma-specific survival, which is not consistent with the findings of previous studies showing that older age was associated with decreased sarcoma-specific survival. Complete resection should be indicated and can lead to optimal treatment outcome for properly selected elderly patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Treatment of soft-tissue sarcomas involving the inguinal region remains challenging because of difficulties in achieving wide surgical margins due to anatomical features. The study aimed to analyze the oncologic and functional outcomes of wide resection with vascular reconstruction for inguinal soft-tissue sarcomas., Methods: Three men and seven women were treated for inguinal soft-tissue sarcomas by wide surgical resection with vascular reconstruction., Results: Arteries and veins were replaced in nine patients, and artery replacement alone was carried out in one patient. Femoral nerve resections were performed in six patients. One patient and five patients developed local recurrence and distant metastases, respectively. Limb salvage was achieved in 9 of 10 patients (90%). Six patients and one patient developed vascular (arterial graft occlusion [n = 1], lymphedema [n = 5]) and nonvascular (hematoma [n = 1]) complications, respectively. Five-year arterial primary patency was 77%. Five-year disease-free and overall survival rates were 45% and 77%, respectively. Functional outcome scores at latest follow-up averaged 87.5% for Musculoskeletal Tumor Society 1993., Conclusions: En-bloc resection of major critical structures along with tumor and vascular reconstructions using synthetic grafts is a feasible option in limb salvage surgery for inguinal soft-tissue sarcomas., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

The proximal tibia is a common site for primary bone tumors. Proximal tibial tumors may invade the adjacent soft-tissue by destroying the cortex and may further invade neurovascular bundles. We treated a patient with primary bone tumor of the proximal tibia with neurovascular invasion by extracorporeally irradiated autograft-prosthetic composite arthroplasty with vascular reconstruction. In cases of concomitant allograft arthroplasty and vascular reconstruction, we recommend that vascular reconstruction be performed before arthroplasty to minimize ischemia time. Good oncological and functional outcomes were achieved 75 months after surgery. Therefore, this reconstruction technique can be considered as a good treatment option., (Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Swelling, pain, and discoloration in the affected extremities are classic symptoms of deep vein thrombosis (DVT), although these symptoms are often unreliable for diagnosis, and wide differential diagnoses exist. Soft-tissue sarcomas arising in the inguinal region may encompass or be adjacent to femoral vessels and result in venous obstruction, mimicking symptoms of DVT. We present two cases of soft-tissue sarcomas in the inguinal region that were initially misdiagnosed as spontaneous DVT and administered unnecessary long-term anticoagulation therapy. In patients diagnosed with unprovoked DVT, especially young patients aged <45 years, we recommend a careful physical examination and ultrasonography in the inguinal region to prevent overlooking possible underlying malignancy, as delays in diagnosis may affect prognosis., (Copyright © 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Vascular lesions associated with neurofibromatosis type 1 (NF1) are rare but can lead to catastrophic complications if disrupted. Ruptured aneurysms in NF1 patients are difficult to treat surgically because of vascular wall fragility. We describe a female NF1 patient with a ruptured aneurysm of her brachial artery. This is the first published case of successful reconstruction of a ruptured brachial aneurysm associated with NF1, using a saphenous vein graft.

Background: The radiographic evaluation of the response to preoperative chemotherapy for bone and soft tissue sarcomas is based mostly on the change in primary tumor size before and after chemotherapy, as is done for many solid cancers. Its prognostic correlation, however, has hardly been validated., Methods: We conducted a retrospective validation study of the Japanese Orthopaedic Association (JOA) radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas as a JOA Committee on Musculoskeletal Tumors cooperative study. A total of 125 consecutive patients with high-grade bone (n = 77) and soft tissue (n = 48) sarcomas treated with neoadjuvant chemotherapy and definitive surgery in 25 tertiary referral hospitals were selected for the study. We investigated the correlation between the tumor size-based radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas provided by the JOA Committee on Musculoskeletal Tumors (hereafter called the JOA criteria) and the patients' overall survival using the Kaplan-Meier method and the log-rank test., Results: The JOA criteria correlated relatively well with survival for malignant bone tumors (mostly comprising osteosarcoma and Ewing's sarcoma) but not for soft tissue sarcomas, suggesting that the tumor size-based radiographic evaluation criteria for the response to preoperative chemotherapy in patients with soft tissue sarcomas is invalid., Conclusions: The JOA criteria, based on the change in primary tumor size, is valid for malignant bone tumors but invalid for soft tissue sarcomas. Other new evaluation modalities of the response to preoperative chemotherapy using innovative functional imaging techniques are needed for soft tissue sarcomas.

Genetic variation in human N-acetyltransferases (NAT) has been implicated in susceptibility to aromatic amine and hydrazine carcinogens and therapeutic drugs. There are mouse models for variability of human NAT1; however mice with genetic differences in Nat1 (corresponding to human NAT2), have not been available. N-Ethyl-N-nitrosourea (ENU) mutagenesis was used to create genetic variation in Nat1. Among a number of mutations identified, a base-pair change substituting threonine for isoleucine at position 95 was recovered and studied. Molecular models suggested that this substitution would alter substrate binding. Analysis of hepatic Nat1 activity with the selective substrate isoniazid showed that there was a significant reduction in enzymatic activity in the homozygous mutants compared to the parental strain.

Numerous numbers of pre-, peri- and postnatal damages cause West syndrome in early infancy, however, etiology in many cases are not still elucidated despite intensive biochemical and neuroradiologic investigations. We described four patients having early onset epileptic encephalopathy with severe hypomyelination and reduction in cerebral white matter. The clinical symptoms of these patients are impaired visual attention, acquired microcephaly, spastic tetraplegia, profound psychomotor delay and infantile spasms since early infancy. All patients had striking hypomyelination of cerebrum, reduced volume of white matter and cortical atrophy on MRI. Serial MRI investigations in three patients showed absence of myelination of the white matter. On EEG, one patient revealed suppression-burst and other three had hypsarrhythmia. Despite having intractable seizures, no patient showed deterioration of neurological development. The group of these findings is mimicking to clinical manifestations of 3-phosphoglycerate dehydrogenase deficiency, and has some overlap with progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) like syndrome, however it is not compatible with these two conditions. The findings observed in our patients can be regarded as a new clinical condition associated with early onset West syndrome.

DNA methylation is an epigenetic mark on the mammalian genome. There are numerous tissue-dependent and differentially methylated regions (T-DMRs) in the unique sequences distributed throughout the genome. To determine the epigenetic changes during adipocyte differentiation, we investigated the sequential changes in DNA methylation status of 3T3-L1 cells at the growing, confluent, postconfluent and mature adipocyte cell stages. Treatment of 3T3-L1 cells with 5-aza-2'-deoxycytidine inhibited differentiation in a stage-dependent manner, supporting the idea that formation of accurate DNA methylation profile, consisting of methylated and unmethylated T-DMRs, may be involved in differentiation. Analysis by methylation-sensitive quantitative real-time PCR of the 65 known T-DMRs which contain NotI sites detected 8 methylations that changed during differentiation, and the changes in the patterns of these methylations were diverse, confirming that the differentiation process involves epigenetic alteration at the T-DMRs. Intriguingly, the dynamics of the methylation change vary depending on the T-DMRs and differentiation stages. Restriction landmark genomic scanning detected 32 novel T-DMRs, demonstrating that differentiation of 3T3-L1 cells involves genome-wide epigenetic changes by temporal methylation/demethylation, in addition to maintenance of a static methylated/demethylated state, and both depend on differentiation stage.

A 47-year-old man was admitted to our hospital complaining of chest pain at rest in the early morning. Electrocardiography showed ST segment elevation in leads II, III and aVF. Emergency coronary angiography revealed total occlusion of the right coronary artery at the proximal portion. Intracoronary administration of isosorbide dinitrate successfully recanalized the right coronary artery. However, there was a thrombus image at the culprit lesion. Intracoronary administration of urokinase caused the residual thrombus to disappear completely. Follow-up coronary angiography at 1 week and 3 months revealed no organic stenotic lesion. Intravascular ultrasound showed only a little plaque without signs of ruptured plaque in the right coronary artery. Provocation coronary angiography revealed remarkable spasm causing total occlusion at the proximal portion of the right coronary artery. This case suggests that only severe coronary spasm without plaque rupture could form a thrombus causing acute coronary syndrome.

Arginine kinase (AK), catalyzing the reversible transfer of phosphate from MgATP to arginine yielding phosphoarginine and MgADP, is widely distributed throughout the invertebrates and is also present in certain protozoa. Typically, these proteins are found as monomers targeted to the cytoplasm, but true dimeric and contiguous dimeric AKs as well as mitochondrial AK activities have been observed. In the present study, we have obtained the sequences of the genes for AKs from two distantly related molluscs-the cephalopod Nautilus pompilius and the bivalve Crassostrea gigas. These new data were combined with available gene structure data (exon/intron organization) extracted from EST and genome sequencing project databases. These data, comprised of 23 sequences and gene structures from Protozoa, Cnidaria, Platyhelminthes, Mollusca, Arthropoda and Nematoda, provide great insight into the evolution and divergence of the AK family. Sequence and phylogenetic analyses clearly show that the AKs are homologous having arisen from some common ancestor. However, AK gene organization is highly divergent and variable. Molluscan AK genes typically have a highly conserved six-exon/five-intron organization, a structure that is very similar to that of the platyhelminth Schistosoma mansoni Arthropod and nematode AK genes have fewer introns, while the cnidarian and protozoan genes each display unique exon/intron organization when compared to the other AK genes. The non-conservative nature of the AK genes is in sharp contrast to the relatively high degree of conservation of intron positions seen in a homologous enzyme creatine kinase (CK). The present results also show that gene duplication and subsequent fusion events forming unusual two-domain AKs occurred independently at least four times as these contiguous dimers are present in Protozoa, Cnidaria, Platyhelminthes and Mollusca. Detailed analyses of the amino acid sequences indicate that two AKs (one each from Drosophila and Caenorhabditis) have what appear to be N-terminal mitochondrial targeting sequences, providing the first evidence for true mitochondrial AK genes. The AK gene family is ancient and the lineage has undergone considerable divergence as well as multiple duplication and fusion events.

Proliferation related acidic leucine-rich protein PAL31 (PAL31) is expressed in proliferating cells and consists of 272 amino acids with a tandem structure of leucine-rich repeats in the N-terminus and a highly acidic region with a putative nuclear localization signal in the C-terminus. We previously reported that PAL31 is required for cell cycle progression. In the present study, we found that the antisense oligonucleotide of PAL31 induced apoptosis to the transfected Nb2 cells. Stable transfectants, in which PAL31 was regulated by an inducible promoter, were generated to gain further insight into the signaling role of PAL31 in the regulation of apoptosis. Expression of PAL31 resulted in the marked rescue of Rat1 cells from etoposide and UV radiation-induced apoptosis and the cytoprotection was correlated with the levels of PAL31 protein. Thus, cytoprotection from apoptosis is a physiological function of PAL31. PAL31 can suppress caspase-3 activity but not cytochrome c release in vitro, indicating that PAL31 is a direct caspase-3 inhibitor. In conclusion, PAL31 is a multifunctional protein working as a cell cycle progression factor as well as a cell survival factor.

Herein, we report a rare case of a 59-year-old man in whom a partial anomalous pulmonary venous connection was found during an operation for coexisting lung cancer and tuberculosis. It was observed that the anomalous vein drained only from the right upper lobe into the right superior vena cava. The middle and lower pulmonary veins connected normally, and there was no atrial septal defect or any other anomalous condition. An upper lobectomy for coexisting lung cancer and tuberculosis with ligation of the partial anomalous pulmonary venous connection was successfully performed.

The SSX family proteins have been considered new members of the cancer/testis antigens because of the restricted expression in testis among normal tissues and the activation in a wide range of cancers. Thus, they would be potential molecular targets for immunotherapeutic strategies. We have developed a competitive nucleic acid sequence-based amplification (NASBA) assay to analyze SSX mRNA expression in 211 bone and soft tissue tumors. The copy numbers of SSX mRNA per mug of total RNA in tumor tissues were widely distributed, ranging logarithmically from 0.6 to 6.6. We found that malignant tumors showed significantly higher expression of SSX mRNA than benign tumors (P < 0.0001). Further, SSX mRNA expression in stage III tumors was significantly higher than that in stage I or II tumors (P < 0.005). This NASBA assay was also more sensitive compared to immunohistochemistry using newly affinity-purified polyclonal antibody against SSX. Collectively, these results suggest that the SSX quantitative NASBA assay could provide useful information to select eligible patients for SSX-specific cancer vaccines.

The formation of DNA methylation patterns is one of the epigenetic events that underlie mammalian development. The Sphk1 CpG island is a target for tissue-dependent DNA methylation as well as a template for generating multiple subtypes. The number of mammalian non-coding RNA genes is rapidly expanding. In this study, we found endogenous antisense transcripts, Khps1 subtypes with different sizes (600-20,000nt). A subtype, Khps1a, was a 1290-bp, non-coding, 5'-capped and 3'-polyadenylated RNA that originated from the CpG island and overlapped with a tissue-dependent differentially methylated region (T-DMR) of Sphk1. Intriguingly, overexpression of two fragments of Khps1 caused demethylation of CG sites in the T-DMR. Furthermore, this RNA-directed demethylation was associated with DNA methylation at three CC(A/T)GG sites in the T-DMR. The link between the RNA-directed CG demethylation and non-CG methylation provides a novel mechanism of epigenetic regulation and potential tool for epigenetic manipulation of mammalian cells.

In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P<0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders.

Differentiation of embryonic stem (ES) cells into embryoid bodies (EBs) provides an in vitro system for the study of early lineage determination during mammalian development. We have previously reported that there are 247 CpG islands that potentially have tissue-dependent and differentially methylated regions (T-DMRs). This provided evidence that the formation of DNA methylation patterns at CpG islands is a crucial epigenetic event underlying mammalian development. Here we present an analysis by the restriction landmark genomic scanning (RLGS) using NotI as a landmark enzyme of the genome-wide methylation status of CpG islands of ES cells and EBs and of teratomas produced from ES cells. These results are considered in relation to the methylation status of CpG islands of genomic DNA from normal fetus (10.5dpc) and adult tissues. We have prepared a DNA methylation panel that consists of 259 T-DMRs and includes novel T-DMRs that are distinctly methylated or unmethylated in the teratomas. The DNA methylation pattern was complex and differed for the ES cells, EBs, and teratomas, providing evidence that differentiation of cells involves both de novo DNA methylation as well as demethylation. Comparison of the numbers of T-DMRs, that were differentially methylated or unmethylated among the cells and tissue types studied, revealed that the teratomas were the most epigenetically different from ES cells. Thus, analysis of the DNA methylation profiles prepared in this study provides new insights into the differentiation of ES cells and development of fetus, EB, teratoma, and somatic tissues.

Our previous study has shown that the placenta and kidney had different genomic methylation patterns regarding CpG island loci detected by restriction landmark genomic scanning (RLGS). To investigate whether differentiation involves changes in DNA methylation, we analyzed the rat Rcho-1 cell line, which retains trophoblast cell features and differentiates from stem cells into trophoblast giant cells in vitro. By RLGS, a total of 1,232 spots were identified in the Rcho-1 stem and differentiated giant cells. Four spots (0.3%) were detected only in giant cells, implying that the loci were originally methylated, but became demethylated during differentiation. Another four spots (0.3%) were detected only in stem cells, implying that these loci, originally unmethylated, became methylated during differentiation. DNAs from three loci that became methylated during differentiation were cloned and sequenced. All showed high homologies with expressed sequence tags (ESTs) or with genomic DNA of other species, suggesting that these loci are biologically important. Thus, the eight differentially methylated loci should be good tools to study epigenetic modification specific to differentiation of trophoblast giant cells.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which works as a target molecule for the cell-mediated immune response. As systemic immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1 derived was not expected to be fully developed. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however, neither expressed latent TGF-beta-binding protein mRNA at a detectable level by Northern blot analysis. Because TGF-beta expresses its functions in cooperation with latent TGF-beta-binding protein, the biological functions of TGF-beta 1 could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1 mRNA, a viral gene product that is partly homologous to human IL-10 and shares biological activities of IL-10. Although IL-10 is reported to promote the growth of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL-10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic T-cell response, the production of an immuno-suppressive cytokine, IL-10, might contribute to the development of overt lymphoma by inducing locally immunosuppressive circumstances. The present study suggests that an immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.