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Background and Aims: The association between the body mass index (BMI) and the characteristics of coronary plaque in younger type 2 diabetes (T2D) patients with coronary artery disease (CAD) remains to be elucidated., Methods and Results: A total of 138 consecutive younger (<65 years) T2D patients with CAD, who underwent optical coherence tomography imaging of the culprit lesion were included. The patients were classified into either the higher BMI group (n = 68) or the lower BMI group (n = 70) according to the median of BMI (25.9 kg/m 2 ). The prevalence of thin-cap fibroatheroma (TCFA) (35.3 vs. 17.1 %, p = 0.015) was significantly higher in the higher BMI group than in the lower BMI group. The prevalence of TCFA was significantly higher in patients with higher BMI than in those with lower BMI among patients with hemoglobin A1c (HbA1c) ≥7.0 % (odds ratio [OR] 5.40, 95 % confidence interval [CI] 1.72-17.0, p = 0.003) although the significant difference was not observed among patients with HbA1c <7.0 % (OR 0.89, 95 % CI 0.25-3.13, p = 0.851)., Conclusion: Higher BMI was associated with a higher prevalence of TCFA in younger T2D patients with CAD, particularly in patients with HbA1c ≥ 7.0 %., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Severe coronary calcification is a factor for worse outcomes after percutaneous coronary intervention., Aims: To identify factors of pre- and post-stent optical coherence tomography (OCT) for device-oriented clinical endpoints (DoCE) in patients with severely calcified lesions requiring drug-eluting stent (DES) implantation., Methods: A total of 237 consecutive patients with stable coronary disease who underwent OCT imaging of severe coronary lesions were included. Lesions with a maximum calcium angle >180°, maximum calcium thickness > 0.5 mm, and calcium length > 5 mm were defined as having severe calcification., Results: The prevalence of eruptive calcified nodules (41% vs. 18%, p = 0.002) and medial dissection with calcified flaps (59% vs. 26%, p < 0.001) was significantly higher in patients with DoCE (n = 34) than those without DoCE (n = 203). Multivariate analyses demonstrated that the presence of a medial dissection with calcified flap within the DES-implanted segment was independently associated with a higher incidence of DoCE (odds ratio, 3.367; 95% confidence interval, 1.503-7.543; p = 0.003). The combined presence of eruptive calcified nodules and medial dissection with calcified flaps was associated with a higher incidence of DoCE (p < 0.001) during a median of 756 days after DES implantation., Conclusions: OCT-defined severely calcified lesions with eruptive calcified nodules and medial dissection with calcified flaps were associated with a higher incidence of DoCE after DES implantation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Few studies have explored optimal diet quality scores in Japan., Objectives: We developed a Diet Quality Score for Japanese (DQSJ) and examined the associations of DQSJ and existing diet quality scores with inadequacy of nutrient intake in Japanese adults., Methods: Candidate components of the DQSJ were extracted from well-established diet quality scores: Healthy Eating Index-2015 (HEI-2015), Alternate Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet score (AMED), and Dietary Approaches to Stop Hypertension (DASH). From candidates, we selected the components of the DQSJ, considering potential health effects of the components (from the Global Burden of Disease Study) and dietary intake in Japan. The DQSJ included 10 components: fruits, vegetables, whole grain, dairy, nuts, legumes, fish, red and processed meat, sugar-sweetened beverages, and sodium. We calculated the DQSJ, HEI-2015, AHEI-2010, AMED, DASH, and Japanese Food Guide Spinning Top score (JFGST) based on 4-d dietary records of 392 Japanese aged 20-69 y. Inadequate intakes of 21 nutrients were assessed using the DRIs for Japanese. Logistic regression was used to examine the prevalence of inadequate nutrient intake according to quartiles of the scores., Results: All examined scores except the JFGST were moderately to strongly correlated with each other (Spearman correlation coefficients: 0.52-0.84). They were inversely associated with the prevalence of inadequate intake of most nutrients (n = 16 for DQSJ and HEI-2015, n = 13 for AHEI-2010 and DASH, n = 17 for AMED, compared with n = 4 for JFGST). AMED was also positively associated with the prevalence of inadequate sodium intake, whereas no such associations were observed for the other scores., Conclusions: Similar to HEI-2015, AHEI-2010, and DASH, the DQSJ was generally associated with the low prevalence of inadequate intake of most nutrients in Japanese adults. Further evaluations against biomarkers and health outcomes are warranted., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: A low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD)., Objective: To clarify the impact of the EPA/AA ratio on the characteristics of non-culprit coronary plaques in statin-treated patients with CAD., Methods: A total of 370 consecutive stable coronary disease patients treated with statins, who underwent percutaneous coronary intervention for the culprit lesion and optical coherence tomography (OCT) imaging of the non-culprit plaque in a culprit vessel were included. The characteristics of non-culprit plaques assessed using OCT were compared between the lower EPA/AA group (EPA/AA <0.4, n = 255) and the higher EPA/AA group (EPA/AA ≥0.4, n = 115)., Results: The prevalence of lipid-rich plaque (58.8 vs. 41.7%, p = 0.003) and plaque with macrophages (56.5 vs. 31.3%, p <0.001) was significantly higher in the lower EPA/AA group than in the higher EPA/AA group. This association was observed even if the LDL-C level was <100 mg/dL. The prevalence of thin-cap fibroatheroma was significantly higher in patients with lower EPA/AA and higher LDL-C (≥100 mg/dL) than in those with higher EPA/AA and lower LDL-C (<100 mg/dL) (odds ratio: 2.750, 95% confidence interval: 1.182-6.988, p = 0.024). An EPA/AA <0.4 was independently associated with a higher prevalence of lipid-rich plaque, plaque with macrophages, and cholesterol crystals., Conclusion: Lower EPA/AA ratio was associated with higher prevalence of vulnerable characteristics in non-culprit plaques. The present results suggest the importance of EPA/AA ratio on the secondary prevention of CAD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: Salvage surgery is performed for selected patients with relapses of locally advanced lung cancer after definitive chemoradiation therapy (CRT), and it seems to be effective. To assess the feasibility of salvage surgery after definitive CRT, this study compared clinical outcomes of surgery after definitive CRT with those of surgery after induction CRT., Methods: Medical records of patients who underwent surgery from January 2000 to January 2018 were reviewed. The study compared patients with salvage anatomic pulmonary resection after definitive CRT with patients with surgery after induction CRT in terms of perioperative and long-term outcomes., Results: A total of 23 patients underwent salvage surgery after definitive CRT for locally advanced lung cancer (salvage group), and 36 underwent surgery after induction CRT for cN2 stage III non-small cell lung cancer (induction CRT group). The surgical procedures in the salvage group were 2 segmentectomies, 13 lobectomies, 1 bilobectomy, and 7 pneumonectomies, and those in the induction CRT group were 34 lobectomies and 2 bilobectomies. There was no 30-day or 90-day mortality in either group. The 5-year overall survival was 44.7% for the salvage group and 58.6% for the induction CRT group. The 5-year progression-free interval was 42.2% for the salvage group and 47.7% for the induction CRT group., Conclusions: Salvage anatomic pulmonary resection after definitive CRT for locally advanced lung cancer is feasible, with acceptable morbidity and prognosis in highly selected patients., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Treating recurrence after coil embolization of basilar tip aneurysm remains challenging even with the development of endovascular procedures. The present study evaluated long-term durability and recurrence patterns after endovascular treatment of basilar tip aneurysms., Methods: Data of 116 consecutive patients treated with endovascular therapy at 3 regional hospitals from 2002-2019 were retrospectively analyzed. Aneurysms were ruptured in 51 cases and unruptured in 65 cases, with a mean maximal diameter of 7.8 mm (>15 mm in 14 patients) and a mean follow-up period of 5.8 ± 4.3 years., Results: Recurrence was observed in 24 of the 116 patients (21%), and 14 patients were retreated. The 5-year recurrence-free survival rate was 75.3%. Cox proportional hazards analysis found that recurrence correlated significantly with maximal aneurysm diameter >10 mm (P = 0.001; hazard ratio: 3.95, 95% confidence interval: 1.76-8.90) and incomplete occlusion (P = 0.003; hazard ratio: 4.43, 95% confidence interval: 1.63-12.00). Recurrence pattern was classified into 3 types: neck type (9 patients), regrowth type (10 patients), and regrowth type of initially thrombosed aneurysms (3 patients). Rerupture occurred in neck type with de novo aneurysm formation adjacent to the neck (n = 3) and regrowth type with dome filling (n = 4)., Conclusions: Recurrence after coil embolization for basilar tip aneurysms is associated with large aneurysms and incomplete occlusion at initial embolization. Understanding the patterns of recurrence is useful for predicting recurrence and selecting treatment strategies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: High triglyceride (TG) levels have been demonstrated to be a risk factor for coronary artery disease. This study aimed to clarify the impact of TG levels on the characteristics of coronary plaques., Methods: A total of 850 consecutive patients who underwent optical coherence tomography (OCT) imaging of the culprit lesion were included. The morphologies of culprit plaques were compared between the higher TG group (nonfasting TG levels ≥150 mg/dL, n = 337) and the lower TG group (nonfasting TG <150 mg/dL, n = 513)., Results: The prevalence of lipid-rich plaques (43% vs. 33%, p = 0.005), thin-cap fibroatheromas (TCFAs) (24% vs. 17%, p = 0.015) and macrophages (40% vs. 31%, p = 0.006) was significantly higher in the higher TG group than in the lower TG group. In addition to a high low-density lipoprotein cholesterol (LDL-C) level (≥140 mg/dL), high TGs (≥150 mg/dL) were identified as an independent factor for the presence of TCFAs (odds ratio 1.465, 95% confidence interval 1.004-2.137, p = 0.048). Among patients with lower LDL-C levels (<100 mg/dL), the prevalence of macrophages (38% vs. 26%, p = 0.007) and layered plaques (48% vs. 38%, p = 0.019) was significantly higher in the higher TG group than in the lower TG group., Conclusions: Higher TG levels were associated with a higher prevalence of TCFAs in culprit coronary lesions. The prevalence of macrophages and layered plaques was more frequently observed in patients with higher TGs than those with lower TGs among patients with LDL-C < 100 mg/dL., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Reducing low-density lipoprotein cholesterol (LDL-C) levels with statins slows the progression of atherosclerotic plaques and reduces cardiovascular events. The 2019 European Society of Cardiology/European Atherosclerosis Society guidelines recommend absolute LDL-C treatment targets of <100 mg/dL, <70 mg/dL and <55 mg/dL according to coexisting patient risk factors., Objective: To clarify the difference in the plaque characteristics of coronary lesions associated with these LDL-C levels in statin-treated patients., Methods: A total of 685 consecutive statin-treated patients with coronary artery disease (CAD) who underwent optical coherence tomography (OCT) imaging of culprit lesions were enrolled. The characteristics of culprit plaques evaluated by OCT were compared among the high LDL-C group (≥100 mg/dL, n=247), the moderate LDL-C group (70-100 mg/dL, n=289), the low LDL-C group (55-70 mg/dL, n=106) and the very low LDL-C group (<55 mg/dL, n=43)., Results: A significant trend toward a lower prevalence of thin-cap fibroatheroma (TCFA) associated with the LDL-C groups was observed (23.1, 18.3, 9.4 and 11.6%, respectively, in each group; p=0.002). A trend toward a lower prevalence of TCFAs associated with the LDL-C groups was also observed among patients with lower hemoglobin A1c (<6.2%; p=0.003). LDL-C <70 mg/dL (the low/very low group) was independently associated with the lack of TCFAs (odds ratio, 0.50; 95% confidence interval, 0.27-0.87, p=0.014)., Conclusions: Lower LDL-C levels were associated with a lower prevalence of TCFAs in culprit plaques among statin-treated patients with CAD., (Copyright © 2021. Published by Elsevier Inc.)

Background: Ground glass opacity (GGO)-dominant lung adenocarcinoma sized 3.0 cm or less in the whole tumor size is widely known to have an excellent prognosis and is regarded as early lung cancer. However, the characteristics and prognosis of lung cancer showing GGO exceeding 3.0 cm remains unclear., Methods: From 2002 through 2012, we reviewed 3,735 lung cancers that underwent complete resection at our institution. We identified 160 lung cancers (4.3%) showing GGO exceeding 3.0 cm on thin-section computed tomography and divided them into three types by the consolidation/tumor ratio (CTR) using cutoff values of 0.25 and 0.5. We compared the characteristics and prognosis among these types., Results: Type A (CTR, 0 to ≤0.25), type B (CTR, >0.25 to ≤0.5), and type C (CTR, >0.5 to <1.0) were found in 16 (10%), 37 (23%), and 107 lesions (67%), respectively. No lymph node metastasis was found in types A and B. Recurrence was not observed in types A and B. The 5-year overall survival and disease-free survival rates were both 100% in type A, both 97.2% in type B, and 88.4% and 66.7% in type C, respectively. Patients with type C had a significantly worse prognosis than those with the other types with respect to overall survival and disease-free survival., Conclusions: A patient with GGO-dominant lung cancer exceeding 3.0 cm can be considered to be in a group of patients with nodal-negative disease and an excellent prognosis., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A 66-year-old woman was referred to our hospital. Computed tomography revealed a partly solid ground-glass nodule located in the left S 1+2 and spread over the left S 6 . Pathologic diagnosis was primary adenocarcinoma (c-T2a N0 M0 c-stage IB). The left B 1+2 arose from the left main bronchus and was displaced superiorly behind the left main pulmonary artery. Severely incomplete lobulation was also recognized. We performed trisegmentectomy, and negative margins were confirmed. The patient is now asymptomatic without recurrence. It is very important to grasp the anatomical structure and consider the surgical procedure preoperatively by making full use of computed tomography and bronchoscopy., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the relationship between clinicopathological prognostic factors, including surgical margin distance and tumor spread through air spaces (STAS), and recurrence after limited resection for primary lung cancer., Methods: We identified 508 cases of limited resection (12.8%) and examined their clinicopathological features. Using Cox regression analysis, we examined the significant prognostic factors for recurrence of limited resection. Finally, we conducted a histopathological evaluation of tumor STAS., Results: Multivariate Cox analysis showed that the risk for local recurrence was significantly associated with STAS (hazard ratio = 12.24, p = 0.001) and a tumor margin less than 1.0 cm (hazard ratio = 6.36, p = 0.02). However, the presence of tumor STAS was not significantly associated with distant recurrence (p = 0.98). This lack of association of STAS with distant recurrence may be due to the small number of distant recurrences. In all, 76 cases (15.0%) (60 adenocarcinomas, nine squamous cell carcinomas, and seven others) were positive for STAS. The morphological STAS patterns were 12 single cells, 45 small cell clusters, and 19 large nests. There was no significant relationship between the recurrence rate and morphological STAS pattern. The STAS-positive group was associated with the presence of micropapillary (p = 0.002) and/or solid components (p = 0.008) in patients with adenocarcinoma and with lymphovascular and pleural invasion (p < 0.001)., Conclusions: The presence of STAS and tumor margins less than 1.0 cm are significant risk factors for local recurrence in early-stage lung cancer after limited resection. Thus, the presence of tumor STAS might be a pathological prognostic factor for patients with lung cancer who have undergone limited resection. However, the pathological and molecular significance of STAS remain to be clarified., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Based on the current World Health Organization classification, adenocarcinoma with a predominantly lepidic pattern larger than 3.0 cm in diameter is considered to be invasive adenocarcinoma, specifically lepidic adenocarcinoma, even if it shows pathologic invasion of 0.5 cm or less. However, we sometimes encounter lepidic adenocarcinomas larger than 3.0 cm with a good prognosis as well as minimally invasive adenocarcinoma., Methods: Of 4,606 resected primary lung cancers at our institute between 1998 and 2011, this study focused on 18 lepidic adenocarcinomas with invasion of 0.5 cm or less. Clinicopathologic characteristics, including epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement status, and prognosis were evaluated., Results: The median maximum pathologic tumor diameter was 3.4 cm (range, 3.1 to 4.7 cm) and the median maximum diameter of the invasive area within the tumor was 0.4 cm (range, 0 to 0.5 cm). No lymph node metastasis, vascular invasion, lymphatic permeation, or pleural invasion was pathologically confirmed in any of the 18 cases. Although epidermal growth factor receptor mutation was detected in 13 cases (72%), none of the patients showed anaplastic lymphoma kinase rearrangement. Recurrence was not observed in any of the 18 patients. The 5-year overall and cancer-specific survival rates were 94.4% and 100%, respectively., Conclusions: Lepidic adenocarcinoma with invasion of 0.5 cm or less had a good prognosis. Adenocarcinoma with a predominantly lepidic pattern and invasion of 0.5 cm or less can be regarded as minimally invasive adenocarcinoma even if the tumor is larger than 3.0 cm in diameter., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are anticipated to be a useful tool for conducting proarrhythmia risk assessments of drug candidates. However, a torsadogenic risk prediction paradigm using hiPSC-CMs has not yet been fully established., Methods: Extracellular field potentials (FPs) were recorded from hiPSC-CMs using the multi-electrode array (MEA) system. The effects on FPs were evaluated with 60 drugs, including 57 with various clinical torsadogenic risks. Actual drug concentrations in medium were measured using the equilibrium dialysis method with a Rapid Equilibrium Dialysis device. Relative torsade de pointes (TdP) scores were determined for each drug according to the degree of FP duration prolongation and early afterdepolarization occurrence. The margins were calculated from the free concentration in medium and free effective therapeutic plasma concentration. Each drug's results were plotted on a two-dimensional map of relative TdP risk scores versus margins., Results: Each drug was categorised as high, intermediate, or low risk based on its location within predefined areas of the two-dimensional map. We categorised 19 drugs as high risk; 18 as intermediate risk; and 17 as low risk. We examined the concordance between our categorisation of high and low risk drugs against the torsadogenic risk categorisation in CredibleMeds®. Our system demonstrated high concordance, as reflected in a sensitivity of 81%, specificity of 87%, and accuracy of 83%., Discussion: These results indicate that our torsadogenic risk assessment is reliable and has a potential to replace the hERG assay for torsadogenic risk prediction, however, this system needs to be improved for the accurate of prediction of clinical TdP risk. Here, we propose a novel drug induced torsadogenic risk categorising system using hiPSC-CMs and the MEA system., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent increasing evidence suggests that the currently-used platforms in vitro I Kr and APD, and/or in vivo QT assays are not fully predictive for TdP, and do not address potential arrhythmia (VT and/or VF) induced by diverse mechanisms of action. In addition, other cardiac safety liabilities such as functional dysfunction of excitation-contraction coupling (contractility) and structural damage (morphological damage to cardiomyocytes) are also major causes of drug attrition, but current in vitro assays do not cover all these liabilities. We organized the Consortium for Safety Assessment using Human iPS cells (CSAHi; http://csahi.org/en/), based on the Japan Pharmaceutical Manufacturers Association (JPMA), to verify the application of human iPS/ES cell-derived cardiomyocytes in drug safety evaluation. The main goal of the CSAHi HEART team has been to propose comprehensive screening strategies to predict a diverse range of cardiotoxicities by using recently introduced platforms (multi-electrode array (MEA), patch clamp, cellular impedance, motion field imaging [MFI], and Ca transient systems) while identifying the strengths and weaknesses of each. Our study shows that hiPS-CMs used in these platforms have pharmacological responses more relevant to humans in comparison with existent hERG, APD or Langendorff (MAPD/contraction) assays, and not only MEA but also other methods such as impedance, MFI, and Ca transient systems would offer paradigm changes of platforms for predicting drug-induced QT risk and/or arrhythmia or contractile dysfunctions. Furthermore, we propose a potential multi-parametric platform in which field potential (MEA)-Ca transient-contraction (MFI) could be evaluated simultaneously as an ideal novel platform for predicting a diversity of cardiac toxicities, namely whole effects on the excitation-contraction cascade., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: An association between usual interstitial pneumonia (UIP) and carcinogenesis has been well established. However, few detailed analyses have investigated the clinicopathological, immunohistochemical, and genetic features of patients with primary lung adenocarcinoma (ADC) with UIP (UIP-ADC)., Methods: We identified 44 patients with ADC in the setting of UIP (the UIP-ADC group) (1.9%) from 2309 patients with primary ADC and compared clinicopathological, immunohistochemical, and genetic features between the UIP-ADC group and patients with ADC without UIP (the non-UIP-ADC group)., Results: Clinicopathological features of UIP-ADC included an older age at occurrence; male predominance; smoking history; predilection for the lower lobe; large tumor size; high incidence of lymph vessel invasion, pleural invasion, and lymph node metastasis; and poor survival rate. However, the cause of death of patients with UIP-ADC was largely influenced by respiratory complications. Histologically, patients in the UIP-ADC group could be stratified according to invasive mucinous-predominant subtype. Genetically, patients in the UIP-ADC group had lower EGFR and higher KRAS mutation rates compared with patients in the non-UIP-ADC group., Conclusions: UIP-ADC was associated with a poor prognosis owing to the high frequency of perioperative complications rather than the malignancy of the tumor itself. There was a high prevalence of the invasive mucinous-predominant subtype in cases of UIP-ADC. UIP-ADC also had a low prevalence of EGFR mutations and a high prevalence of KRAS mutations. These findings suggest that UIP-ADC should be distinct from non-UIP-ADC., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objective: Acute multifocal embolic infarction (AMEI) is conventionally caused by etiologies such as cardioembolism due to atrial fibrillation (Af), but can also be caused by serious underlying diseases such as cancer. We characterized cancer-related AMEI and identified useful indicators for cancer-associated strokes., Methods: A retrospective analysis was performed on 35 patients with Af-related AMEI and 35 patients with cancer-related AMEI selected from 1235 consecutive patients with acute infarcts. All patients received diffusion-weighted magnetic resonance (MR) imaging. Cerebral MR angiography, carotid and cardiac ultrasonography, electrocardiogram-monitoring and whole body computed tomography were also performed on these patients. D-dimer levels were evaluated on admission, and were measured during the sub-acute phase in 19 of the patients with Af and 27 of the patients with cancer., Results: Acute phase D-dimer levels were significantly higher in patients with cancer than in patients with Af alone. The cut-off D-dimer value to identify cancer-associated infarcts was 2.0μg/mL. D-dimer levels during the sub-acute phase remained elevated in the cancer patients., Conclusions: We may differentiate cancer-associated AMEI from Af using a D-dimer level≥2.0μg/mL, which does not decrease during the sub-acute phase., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We present the case of a 50-year-old man with Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting tumor. A small nodule was located in close association with the lateral segmental branch of the pulmonary artery in the left upper lobe. Blood samples were obtained from various branches of the pulmonary artery by balloon-occluded retrograde sampling for the measurement of location-specific serum ACTH levels. After confirmation that the pulmonary nodule was responsible for the increased ACTH secretion, lobectomy was performed. This report demonstrates the usefulness of balloon-occluded retrograde pulmonary arterial sampling for the preoperative diagnosis of an ACTH-producing tumor whose diagnosis is difficult to confirm., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Although most patients with Parkinson's disease (PD) show decreased cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, some exhibit normal uptake. We evaluated the clinical characteristics of such patients., Methods: We enrolled 154 non-demented patients showing parkinsonism with normal cardiac MIBG uptake and had been clinically followed up during 29.9 ± 27.6 months. We defined the patients who did not fit the exclusion criteria for PD and demonstrated ≥ 30% reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score after anti-Parkinson agent administration as probable PD. We compared clinical characteristics and the cardiac MIBG heart-to-mediastinum (H/M) ratio between the probable PD group (N=37) and other groups (N=117)., Results: The probable PD group showed significantly higher UPDRS motor scores and greater incidence of tremor/rigidity than those of other groups. In addition, they showed a significantly lower cardiac MIBG H/M ratio in the delayed phase (delayed, p<0.0001). Washout-rate (WR) was significantly higher in probable PD cases (p<0.0001). Among 16 probable PD patients undergoing serial cardiac MIBG scintigraphy, the delayed phase cardiac MIBG H/M ratio showed a significant decrease and WR significantly increased during follow-up periods., Conclusions: An increase in WR and lower delayed phase cardiac MIBG uptake were found to be characteristics of such patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Spontaneous regression of tumors is very unusual and is defined as a partial or complete disappearance of metastatic tumors without any treatment. This phenomenon has been reported in almost all types of cancer. The patient was a 25-year-old woman who presented with multiple pulmonary nodules on her bilateral lungs on the annual chest roentgenograph. Simultaneously, a swelling mass on her subcutaneous inguinal region was observed. The diagnosis of the inguinal mass was extraskeletal myxoid chondrosarcoma. The inguinal mass and pulmonary nodules spontaneously regressed without any treatment after biopsy. The patient was doing well without evidence of recurrence at 1 year after the operation without any additional therapy. Our case is the first clinical one that indicated a possibility of histologic regression of extraskeletal myxoid chondrosarcoma., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Multi-electrode array (MEA) systems and human induced pluripotent stem (iPS) cell-derived cardiomyocytes are frequently used to characterize the electrophysiological effects of drug candidates for the prediction of QT prolongation and proarrhythmic potential. However, the optimal experimental conditions for obtaining reliable experimental data, such as high-pass filter (HPF) frequency and cell plating density, remain to be determined., Methods: Extracellular field potentials (FPs) were recorded from iPS cell-derived cardiomyocyte sheets by using the MED64 and MEA2100 multi-electrode array systems. Effects of HPF frequency (0.1 or 1Hz) on FP duration (FPD) were assessed in the presence and absence of moxifloxacin, terfenadine, and aspirin. The influence of cell density on FP characteristics recorded through a 0.1-Hz HPF was examined. The relationship between FP and action potential (AP) was elucidated by simultaneous recording of FP and AP using a membrane potential dye., Results: Many of the FP waveforms recorded through a 1-Hz HPF were markedly deformed and appeared differentiated compared with those recorded through a 0.1-Hz HPF. The concentration-response curves for FPD in the presence of terfenadine reached a steady state at concentrations of 0.1 and 0.3μM when a 0.1-Hz HPF was used. In contrast, FPD decreased at a concentration of 0.3μM with a characteristic bell-shaped concentration-response curve when a 1-Hz HPF was used. The amplitude of the first and second peaks in the FP waveform increased with increasing cell plating density. The second peak of the FP waveform roughly coincided with AP signal at 50% repolarization, and the negative deflection at the second peak of the FP waveform in the presence of E-4031 corresponded to early afterdepolarization and triggered activity., Discussion: FP can be used to assess the QT prolongation and proarrhythmic potential of drug candidates; however, experimental conditions such as HPF frequency are important for obtaining reliable data., (Copyright © 2015. Published by Elsevier Inc.)

Clioquinol is considered to be a causative agent of subacute myelo-optico neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. We have previously shown that clioquinol inhibits nerve growth factor (NGF)-induced Trk autophosphorylation in PC12 cells transformed with human Trk cDNA. To explore the further mechanism of neuronal damage by clioquinol, we evaluated the acetylation status of histones in PC12 cells. Clioquinol reduced the level of histone acetylation, and the histone deacetylase (HDAC) inhibitor Trichostatin A upregulated acetylated histones and prevented the neuronal cell damage caused by clioquinol. In addition, treatment with HDAC inhibitor decreased neurite retraction and restored the inhibition of NGF-induced Trk autophosphorylation by clioquinol. Thus, clioquinol induced neuronal cell death via deacetylation of histones, and HDAC inhibitor alleviates the neurotoxicity of clioquinol. Clioquinol is now used as a potential medicine for malignancies and neurodegenerative diseases. Therefore, HDAC inhibitors can be used as a candidate medicine for the prevention of its side effects on neuronal cells., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Some unfavorable prognostic factors for stage I non-small-cell lung cancers have been reported; however, they are not reflected in the current Tumor-Node-Metastasis classification., Methods: We retrospectively reviewed 629 patients who underwent complete resection of pathological stage I adenocarcinomas (ADs) or squamous cell carcinomas (SQs) at two institutes between 1996 and 2011. The correlation between clinicopathological characteristics and survival rates was analyzed to identify prognostic factors., Results: Multivariate analysis indicated that among ADs, high serum carcinoembryonic antigen levels (p = 0.04 for overall survival [OS]; p < 0.01 for recurrence-free survival [RFS]; p = 0.02 for disease-specific survival [DSS]), lymphatic permeation (p < 0.01 for RFS and DSS), and vascular invasion (p < 0.01 for OS and RFS; p = 0.03 for DSS) were independent prognostic factors. Among SQs, high squamous cell carcinoma antigen (SCC) (p < 0.05 for OS), and vascular invasion (p < 0.05 for RFS and DSS) were independently prognostic. We suggest that among completely resected tumors less than or equal to 5 cm without lymph node metastasis, the current stages IA and IB AD with high serum carcinoembryonic antigen levels, lymphatic permeation, or vascular invasion should be upgraded to stage IB and IIA, respectively. The current stage IA SQ with high SCC antigen levels or vascular invasion should be upgraded to stage IB. These reclassifications accurately reflect survival status (p < 0.04 in all comparisons)., Conclusions: Some important differences in prognostic factors were observed between AD and SQ. High preoperative serum tumor marker levels and lymphovascular invasion should be included as additional criteria in the forthcoming Tumor-Node-Metastasis staging.

Objective: Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but evidence from prospective cohort studies is sparse. Therefore, we examined the association between serum DHEAS levels and depressive symptoms in older community-dwelling Japanese., Design: A community-based cohort study., Setting: Kurabuchi Town, Gunma Prefecture, Japan., Participants: A total of 554 residents (248 men and 306 women) age 65 years or older without depressive symptoms at baseline., Measurements: We performed a baseline examination of the subjects between 2005 and 2006 to determine serum DHEAS levels. The subjects were categorized into three groups based on age strata- and sex-specific tertiles of DHEAS. Depressive symptoms were assessed with the Geriatric Depression Scale 15-item version (GDS-15) in face-to-face home visit interviews carried out once in 2007 and once in 2008. The association of DHEAS with depressive symptoms (GDS-15 ≥ 6) was analyzed with the use of logistic regression models., Results: The incidence of depressive symptoms was 12.1% in men and 19.6% in women. In men, the multiadjusted odds ratio of depressive symptoms was 0.24 (95% confidence interval: 0.06-0.94, Wald χ2 = 4.20, degrees of freedom = 1, p = 0.04) for the highest tertile compared with the lowest. The association observed for the highest versus the lowest remained significant even after adjustment for physical performance and cognitive function. In women, DHEAS was not associated with depressive symptoms., Conclusions: In this study, higher serum DHEAS levels were found to be protectively and independently associated with the risk of developing depressive symptoms in men, but not in women., (Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

A growing body of literature has highlighted the increased prevalence of body image concerns and associations with health outcomes among gay and bisexual men (GBM). Little research, however, has examined the link between body image and social oppression for ethnoracialized GBM. Using an intersectionality lens and qualitative inductive analysis, data were collected through focus groups and interviews with GBM (n=61) who identify with one of four ethnoracial groups (Black, East/Southeast Asian, South Asian, Latino/Brazilian). Three main themes emerged: (1) body image idealization in gay/bisexual male culture, (2) negotiating a racialized body image, and (3) negotiating the impact of body image on relationship with self and others. The study results highlighted how multiple forms of oppression (e.g., racism, sexism) intersected with one another to impact the body image and overall well-being among ethnoracialized GBM., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We report the case of a 35-year-old man with tracheal stenosis caused by relapsing polychondritis. The disease began at age 17, and he underwent steroid therapy and tracheostomy. After 2 years, owing to inflammation and fibrosis, a T-tube was inserted from the glottis to the tracheal bifurcation. Besides hospitalization for mild pneumonia, the patient was able to lead a normal sedentary life with satisfactory communication. T-tubes are an effective and low-risk treatment measure for preserving airway function in patients with tracheal stenosis due to polychondritis. In this report we discuss the advantages and disadvantages of different stents in treating relapsing polychondritis., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Malignant pleural mesothelioma is known to be widely resistant to therapy and new treatment strategies are needed. Both statins and valproic acid are known to suppress the growth of multiple cancer lines, but the effects on mesothelioma cells are not well defined. In the present study we examined the effects of lovastatin and valproic acid on ACC-MESO-1, which is a human derived mesothelioma cell line. We found that lovastatin (2 μM) and/or valproic acid (5 mM) did not reduce cell viability nor induce apoptosis, but reduced cell invasion. The effect was additive when combined. Furthermore it was speculated that induction of autophagic changes was at least in part involved in this process., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: This study compared the impact of pattern of sirolimus eluting stent restenosis (SES ISR) on the angiographic outcomes following conventional modalities of treatment., Methods: A total of 344 consecutive patients who underwent treatment for SES ISR were included in the study. Lesions were divided into focal< 10 mm, 156 (45.3%)); and non focal> 10 mm, 188 (54.7%). The endpoints analysed were angiographic restenosis and target lesion revascularisation. A total of 31%, 41%, and 23% patients were treated with cutting balloon angioplasty, balloon angioplasty, and repeat stenting., Results: Baseline characteristics were similar for two patterns, except for young age, more AMI and severe angina, more CTO lesions, long lesions, and more use of repeat stenting in non focal ISR group. Follow up angiography shows binary restenosis was significantly lower in the focal group (32.4% vs. 49.2; p = 0.012) and target lesion revascularisation were also lower with focal pattern ISR (30.6 vs. 42.9; p = 0.06). Restenosis rates are similar between balloon angioplasty and repeat stenting (28 vs. 23%) in focal ISR group, and repeat stenting showed better outcomes in the non focal group (60% vs. 36%)., Conclusion: The recurrent ISR remains high with available treatments and the pattern of SES ISR predicted the outcomes, with lower restenosis rates with focal pattern of ISR., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

The lyotropic behavior and glass-forming properties of octyl β-D-glucoside (C8Glu) and octyl β-D-thioglucoside (C8SGlu)/water binary mixtures were evaluated using differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). The results clearly indicate that the mixture forms a glass in the supercooling state of liquid crystalline phases such as cubic, lamellar, and smectic. The glass transition temperature (T(g)) of the mixture was strongly dependent on solute concentration, with a higher concentration correlating with a higher T(g). The experimental T(g) was consistent with the predicted value calculated using the Couchman-Karasz equation in both the C8Glu and C8SGlu/water mixtures. The change of heat capacity at T(g) showed the two bending points under variation of concentrations. And the highest temperature of phase transition from lamellar to isotropic solution was observed at around 50% molar concentration. It was expected that non-percolated state of water existed in extremely higher concentration ranges., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objectives: We performed this study to investigate with optical coherence tomography (OCT) the vascular response after sirolimus-eluting stent (SES) implantation between patients with and those without diabetes mellitus (DM)., Background: The difference in vascular response after SES implantation between patients with and those without DM has not been fully evaluated with OCT., Methods: Optical coherence tomography was performed to examine 74 nonrestenotic SES implanted in 63 patients (32 with DM and 31 without DM) at 9 months after SES implantation. For struts showing neointimal coverage, the neointimal thickness on the luminal side of each strut section was measured, and neointimal characteristics were classified into high, low, and layered signal pattern., Results: Baseline patient characteristics and lesion and procedural characteristics data were similar between the 2 groups. In total, 11,422 struts were analyzed. High signal neointima was observed in 90.2 ± 13.9%, low signal neointima in 7.3 ± 10.0%, and layered neointima in 2.7 ± 5.8%/stents. There was higher incidence of low signal neointima (10.5 ± 10.3% vs. 4.5 ± 5.6%, p = 0.003), neointimal thickness was larger (median: 106.8 μm, interquartile range: 79.3 to 130.4 μm vs. median: 83.5 μm, interquartile range: 62.3 to 89.3 μm; p < 0.0001), and neointimal coverage of stent struts was higher (92.1 ± 6.2% vs. 87.2 ± 11.9%; p = 0.03) in DM patients., Conclusions: High signal neointimal pattern was predominantly observed, and low or layered signal pattern was observed in some cases. In DM patients, low signal neointima was observed with high frequency. Neointimal coverage and neointimal thickness was also higher in DM patients as compared with non-DM patients., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Among 15 patients with primary mediastinal nonseminomatous germ cell tumors experienced during the past 12 years, 5 were diagnosed with germ cell tumors with somatic-type malignancy. The pretreatment stages were stage I in 2 patients and stage II in 3. All 5 patients received perioperative chemotherapy plus surgical resection, and 4 remain alive without relapse, with a mean follow-up of 60 months., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the safety and feasibility of a new concept for chronic total occlusion (CTO) recanalization-using a bilateral approach that utilizes a Controlled Antegrade and Retrograde subintimal Tracking (CART) technique., Background: Successful percutaneous recanalization of coronary CTOs results in improved long-term outcomes. The recanalization of CTOs in native coronary arteries no doubt represents one of the most technically challenging of interventional procedures., Methods: A total of 224 consecutive patients (mean age 61 +/- 9 years; 86.2% men) were enrolled in this prospective multicenter registry. This technique combines the simultaneous use of antegrade and retrograde approaches. A subintimal dissection is created in both antegrade and retrograde fashion, thereby limiting the extension of the subintimal dissection within the CTO portion., Results: Of 224 CTO lesions (>3 months in duration) undergoing attempted recanalization using the CART technique, 145 cases (64.7%) had undergone previous CTO recanalization attempts. The success rates of crossing in a retrograde fashion with a wire and a balloon were 87.9% and 79.9%, respectively. The overall technical and procedural success rates achieved in this registry were 92.4% and 90.6%, respectively., Conclusions: A bilateral approach for CTO lesions using the CART technique is feasible, safe, and has a higher success rate than previous approaches. These results indicate that a bilateral technique can solve a major dilemma that commonly affects CTO procedures.

Sterol regulatory element binding proteins (SREBPs) are transcription factors that activate transcription of the genes involved in cholesterol and fatty acid biosynthesis. In the present study, we show that a small synthetic molecule we previously discovered to block adipogenesis is an inhibitor of the SREBP activation. The diarylthiazole derivative, now called fatostatin, impairs the activation process of SREBPs, thereby decreasing the transcription of lipogenic genes in cells. Our analysis suggests that fatostatin inhibits the ER-Golgi translocation of SREBPs through binding to their escort protein, the SREBP cleavage-activating protein (SCAP), at a distinct site from the sterol-binding domain. Fatostatin blocked increases in body weight, blood glucose, and hepatic fat accumulation in obese ob/ob mice, even under uncontrolled food intake. Fatostatin may serve as a tool for gaining further insights into the regulation of SREBP.

Objectives: The aim of this study was to evaluate the effect of treatment with statins on the progression of coronary atherosclerotic plaques of a nonculprit vessel by serial volumetric virtual histology (VH) intravascular ultrasound (IVUS)., Background: Recent clinical trials have demonstrated a reduction of atherosclerotic plaque, yet whether statin therapy affects the change in components of plaque remains unknown., Methods: This study was a nonrandomized and nonblinded design. Eighty patients with stable angina pectoris were divided into either the fluvastatin group (n = 40) or the control group (n = 40) according to their total or low-density lipoprotein (LDL) cholesterol level. The volume of each plaque component (dense calcium, fibrous tissue, fibro-fatty, or necrotic core) was evaluated at baseline and at 12-month follow-up., Results: The LDL cholesterol and high-sensitivity C-reactive protein (hsCRP) levels in the fluvastatin group were significantly decreased at time of follow-up. In VH IVUS findings, fibro-fatty volume was significantly decreased (baseline 80.1 +/- 57.9 mm(3) vs. follow-up 32.5 +/- 27.7 mm(3), p < 0.0001) and fibrous tissue volume was increased (baseline 146.5 +/- 85.6 mm(3) vs. follow-up 163.3 +/- 94.5 mm(3), p < 0.0001) in the fluvastatin group. In the control group, the volumes of all plaque components without fibrous tissue were significantly increased. Change in fibro-fatty volume has a significant correlation with a change in LDL cholesterol level (R = 0.703, p < 0.0001) and change in hsCRP level (R = 0.357, p = 0.006)., Conclusions: One-year lipid-lowering therapy by fluvastatin showed significant regression of plaque volume and alterations in atherosclerotic plaque composition with a significant reduction of fibro-fatty volume.

To evaluate trace element emissions from modern coal-fired power plants into the atmospheric environment in Japan, trace elements in the coal used in electric utility boilers, stack concentrations, emission rates and emission ratios of coal-fired power plants, and proportions of trace elements in coal-fired power plants were studied. The elements were As, B, Be, Cd, Co, Cr, F, Hg, Mn, Ni, Pb, Sb, Se and V, which are designated in the Law of Pollutant Release and Transfer Register. The particulate trace elements were collected in an electrostatic precipitator and a wet desulfurization scrubber. Emissions into the atmosphere were lower than 1% of the quantity in coal, but the volatile trace elements showed somewhat higher emission ratios. For mercury, the mean concentration in coal was 0.045 ppm, the mean emission rate was 4.4 microg/kW h, and the mean emission ratio was 27%, the highest ratio among all elements in this study. The total annual emission of mercury from coal-fired power plants of the electric power industry in Japan was estimated to be 0.63 t/y. On the basis of these data, the atmospheric environment loads from a coal-fired power station were investigated. The calculation of stack gas dispersion showed that maximum annual mean ground level concentrations were in the order of 10(-2) to 10(-5) of the background concentrations, and that the adverse effect of the emissions from the coal-fired power station was small.

Background: The purpose of this study was to examine the postoperative outcomes of patients with Mycobacterium avium complex (MAC) lung lesions persisting despite treatment with multiple antibiotics., Methods: Patients with localized pulmonary lesions persisting despite extensive state-of-the art antimicrobial chemotherapy became candidates for surgical resection. Twenty-two patients who were expected to retain sufficient postoperative pulmonary function were included in this study. These patients received chemotherapy for 2 to 37 months (mean, 17). Surgical procedures were lobectomy (n = 15), segmentectomy (n = 4), and partial lung resection (n = 6). Three patients underwent bilateral resections., Results: Mycobacterium avium complex causing bronchiectasis or cavitary lesions was detected preoperatively in all 22 patients. There was no major operative morbidity or mortality. Postoperative chemotherapy was continued for 6 to 35 months. All patients were alive and well at follow-ups ranging from 6 to 164 months (median, 46). Both vital capacity and forced expiratory volume in 1 second after surgery were maintained at 89% and 84% of the preoperative values, respectively. Mycobacterium avium complex disappeared from sputum after surgery in all patients. In 1 patient, 4 months after resection of a cavitary lesion, MAC-positive sputum presumed to be from the contralateral lung lesion became negative during continuation of chemotherapy., Conclusions: The long-term outcomes of patients operated on for MAC resistant to antimicrobial chemotherapy were excellent. For such patients, we recommend surgery before the disease becomes exceedingly advanced and nonresectable. Additionally, in extensive disease, the excision of large cavitary bacterial foci may assist the medical management of contralateral lesions.

Objectives: The indications for concurrent intervention for stenosis of a side branch during the treatment for stenosis of the main vessel were investigated using quantitative coronary angiography., Methods: The retrospective study included 451 patients treated for a stenotic main vessel incorporating a side branch, who underwent follow-up angiography within 6 months. Patients were divided into Group I with the side branch treated by coronary angioplasty, and Group II with the side branch left untreated. Quantitative coronary angiography was used to measure the minimum luminal diameter (MLD) and percentage diameter stenosis (%DS) of the main vessel and the side branch., Results: The MLD of the side branch after treatment was larger in Group I (1.4 +/- 0.1 mm) than in Group II (0.7 +/- 0.1 mm), and the %DS of the side branch after treatment was smaller in Group I (34 +/- 3%) than in Group II (63 +/- 2%). These differences decreased at follow-up to 1.1 +/- 0.1 mm, 48 +/- 2% in Group I; 0.9 +/- 0.04 mm, 46 +/- 2% in Group II, respectively. The MLD and %DS of the side branch at follow-up in Groups I and II were affected by the presence of main vessel restenosis[Restenosis(+): 0.9 +/- 0.1 mm, 57 +/- 4%; restenosis(-): 1.2 +/- 0.1 mm (p < 0.05), 43 +/- 3% (p < 0.05) in Group I; Restenosis(+): 0.9 +/- 0.1 mm, 51 +/- 8%; restenosis(-): 1.0 +/- 0.1 mm, 44 +/- 3% in Group II]. Multivariate analysis showed that %DS of the main vessel at follow-up was the only powerful predictor of restenosis of the side branch (p = 0.0249, odds ratio = 1.031, confidence interval = 1.004-1.059) in Groups I and II., Conclusions: Restenosis of the main vessel rather than the initial outcome of the side branch is the major influence on restenosis of the side branch.

The emissions study for mercury was conducted at a 700 MW coal-fired plant for the combustion of three types of coal with mercury concentrations of 0.0063, 0.0367 and 0.065 mg/kg. The power plant is equipped with a cold-side electrostatic precipitator and wet type flue gas desulfurization system. During full load operation of the boilers, samples of the input and output streams such as coal, coal ash, ESP ash and post-ESP particulates and flue gas were collected. The Hg concentrations in solid were measured by cold-vapor atomic absorption spectrometry (AAS) after appropriate preparation and acid digestion. Gaseous Hg was collected using a mixed solution of potassium permanganate and sulfuric acid and the Hg concentrations in the samples were measured using cold-vapor AAS. The results were used to examine: (1) overall mass balances; (2) relative distribution in the power plant; (3) equilibrium of Hg species using MALT-2 calculation program; and (4) Hg concentrations in stack emissions. The mass balances estimated in this study were 100, 138 and 89%, respectively, for the coals. Total Hg concentrations in stack gas were 1.113, 0.422 and 0.712 microg(m3N), respectively, for the coals. More than 99.5% of the Hg in the stack emissions were in gaseous form and the proportion in particulate form was extremely low. The relative distribution of Hg in ESP, FGD and Stack ranged from 8.3 to 55.2%, 13.3 to 69.2% and 12.2% to 44.4%, respectively. The results indicated that factors other than the Hg concentration of coals and efficiency of pollution control devices might affect Hg emissions from coal-fired plant. The calculated equilibrium of the distribution of Hg species using the MALT2 program suggest that it is necessary to consider condensation mechanism to interpret the affect of Hg species on the variations of the removal efficiencies of Hg in the ESP.

Ag-specific T cell activation requires the engagement of T cell receptor (TCR) with antigen in the context of MHC, and the engagement of appropriate costimulatory molecules. It is well established that B7/CD28-CTLA4 costimulatory pathway plays an important role in the induction of T helper (Th) cells in T-cell dependent immune reactions. In this study, we evaluated the effects of blocking the costimulatory pathway by systemic administration of CTLA4-Ig during repeated nasal antigen challenges in systemically presensitized mouse. The antigen-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine and nasal eosinophilia were significantly suppressed by CTLA4-Ig treatment. Elevation of serum level of antigen-specific IgE, but not IgG1 or IgG2a was inhibited by the treatment. In relation to cytokine levels in the tissue extracts of the nasal mucosa, an up-regulation of IL-4 was significantly inhibited, however, the levels of IL-5 and IFN-gamma were not affected by the treatment. These results suggest that B7/CD28-CTLA4 costimulatory pathway plays an important role in on-going Th2-related allergic reactions in the nose.

Background: The incidence of and mortality from lung cancer have increased steadily. Most lung cancers are not localised when first detected, but early detection is mandatory to improve prognosis. Since curable early cases are hard to visualise with conventional chest radiography, a new diagnostic means must be found. We assessed whether population-based mass screening with a spiral computed tomography scanner could contribute substantially to detection of smaller cancers, and decrease mortality., Methods: In 1996, we screened in a mobile unit 5483 individuals from the general population of Matsumoto, Japan, aged between 40 years and 74 years who had undergone annual chest radiography (miniature fluorophotography) and cytological assessment of sputum. All participants had a low-dose X-ray spiral computed tomography (CT) scan of the thorax; 3967 also underwent miniature fluorophotography. We compared smokers and non-smokers. Further assessments were done for probably benign but suspicious lesions; suspicion of cancer; and indeterminate small nodules by chest radiography and conventional CT, with additional transbronchial biopsy when possible. Thoracotomy was recommended when it was strongly suspected that the patients had lung cancer., Findings: 19 patients were diagnosed as having lung cancer--14 with suspicion of lung cancer, three with benign but suspicious lesions, and two with indeterminate small nodules. 18 cases were surgically confirmed, and one was clinically diagnosed. The mean size of lesions was 17 mm (range 6-47). In four of 19 patients, lung abnormality was seen on CT and miniature fluorophotography. The lung-cancer detection rate with CT was 0.48%, significantly higher than the 0.03-0.05% for standard mass assessments done previously in the same area. CT missed one case that was found solely on a sputum cytology examination., Interpretation: Our results show that miniature fluorophotography or conventional chest radiography, which have been the main diagnostic techniques for lung cancer, showed few small cancers. CT was more accurate in mass screening for lung cancer and led to early detection and an accurate diagnosis of lung cancer, and should be considered in future health plans.

The "Cardiophone System" is a system designed to expand the relationship between patients and medical services using a transtelephonic electrocardiogram and computer-assisted answering system. The transtelephonic electrocardiogram, or so-called "Cardiophone", developed by Nihon Kohden, Inc., allows the patients to carry a "Cardiophone" to record electrocardiograms during paroxysmal occurrences of palpitation, chest pain, and other symptoms. The Cardiophone may function as a terminal of the host computer at the hospital, which stores the electrocardiogram and print it as soon as the computer receives the electrocardiogram over the phone. Cardiologists can examine the electrocardiogram immediately after it is printed. Cardiologists and operators are on duty 24 hours a day. Judgments based on the electrocardiogram are made by the cardiologist on duty, and stored in the computer by the operator. The patients may listen to the judgment over the phone within 30 min of sending the electrocardiogram. In the case of potentially lethal findings on the electrocardiogram, the cardiologist on duty calls the patient directly to give a medical advice. We studied 184 outpatients who were enrolled in the Cardiophone System of our hospital. The average number of transtelephonic electrocardiograms was 10 per day. Abnormal electrocardiographic changes were observed in 42 patients, and the diagnoses were as follows: paroxysmal supraventricular tachycardia in 18 patients, paroxysmal atrial fibrillation in 17, ventricular tachycardia in 3, and angina in 7. Among seven patients in whom ST changes were documented by Cardiophone, six were diagnosed as variant angina. In several patients with diagnoses already made by Holter monitoring, the Cardiophone was used to monitor the drug effects and the correlations between symptoms and arrhythmic events. We conclude that the Cardiophone System is useful for diagnosing the causes of paroxysmal cardiac symptoms in some patients and for improving home medical services.