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Yanyan Xu,1,2 Tsuneo Yamashiro,1,3 Hiroshi Moriya,3 Shun Muramatsu,3 Sadayuki Murayama1 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Okinawa, Japan; 2Department of Radiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of Radiology, Ohara General Hospital, Fukushima, JapanCorrespondence: Tsuneo YamashiroDepartment of Radiology, Graduate School of Medical Science, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, JapanTel +81-98-895-1162Fax +81-98-895-1420Email clatsune@yahoo.co.jpPurpose: To evaluate the advantages of ultra-high-resolution computed tomography (U-HRCT) scans for the quantitative measurement of emphysematous lesions over conventional HRCT scans.Materials and methods: This study included 32 smokers under routine clinical care who underwent chest CT performed by a U-HRCT scanner. Chronic obstructive pulmonary disease (COPD) was diagnosed in 13 of the 32 participants. Scan data were reconstructed by 2 different protocols: i) U-HRCT mode with a 1024×1024 matrix and 0.25-mm slice thickness and ii) conventional HRCT mode with a 512×512 matrix and 0.5-mm slice thickness. On both types of scans, lesions of emphysema were quantitatively assessed as percentage of low attenuation volume (LAV%,

Yanyan Xu,1,2 Tsuneo Yamashiro,1 Hiroshi Moriya,3 Maho Tsubakimoto,1 Yukihiro Nagatani,4 Shin Matsuoka,5 Sadayuki Murayama1 On behalf of ACTIve Study Group 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa, Japan; 2Department of Radiology, China-Japan Friendship Hospital, Beijing, Republic of China; 3Department of Radiology, Ohara General Hospital, Fukushima-City, Fukushima, Japan; 4Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, Japan; 5Department of Radiology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Purpose: Strain measurement is frequently used to assess myocardial motion in cardiac imaging. This study aimed to apply strain measurement to pulmonary motion observed by four-dimensional dynamic-ventilation computed tomography (CT) and to clarify motion abnormality in COPD. Materials and methods: Thirty-two smokers, including ten with COPD, underwent dynamic-ventilation CT during spontaneous breathing. CT data were continuously reconstructed every 0.5 seconds. In the series of images obtained by dynamic-ventilation CT, five expiratory frames were identified starting from the peak inspiratory frame (first expiratory frame) and ending with the fifth expiratory frame. Strain measurement of the scanned lung was performed using research software that was originally developed for cardiac strain measurement and modified for assessing deformation of the lung. The measured strain values were divided by the change in mean lung density to adjust for the degree of expiration. Spearman’s rank correlation analysis was used to evaluate associations between the adjusted strain measurements and various spirometric values. Results: The adjusted strain measurement was negatively correlated with FEV1/FVC (ρ=-0.52, P

Yukihiro Nagatani,1 Masayuki Hashimoto,2 Norihisa Nitta,1 Yasuhiko Oshio,2 Tsuneo Yamashiro,3 Shigetaka Sato,1 Shinsuke Tsukagoshi,4 Hiroshi Moriya,5 Tatsuya Kimoto,6 Tomoyuki Igarashi,2 Noritoshi Ushio,1 Akinaga Sonoda,1 Hideji Otani,1 Jun Hanaoka,2 Kiyoshi Murata1On behalf of investigators of the ACTIve Study Group1Department of Radiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; 2Department of Surgery, Division of General Thoracic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; 3Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan; 4CT System Division, Canon Medical Systems, Otawara, Tochigi 324-8550, Japan; 5Department of Radiology, Ohara General Hospital, Fukushima, Fukushima 960-8611, Japan; 6Healthcare IT Development Center, Canon Medical Systems, Otawara, Tochigi 324-8550, JapanPurpose: The purpose of this study was to measure changes in lung density and airway dimension in smokers in the lateral position using four-dimensional dynamic-ventilation computed tomography (CT) during free breathing and to evaluate their correlations with spirometric values.Materials and methods: Preoperative pleural adhesion assessments included dynamic-ventilation CT of 42 smokers (including 22 patients with COPD) in the lateral position, with the unoperated lung beneath (dependent lung). The scanned lungs’ mean lung density (MLD) and the bilateral main bronchi’s luminal areas (Ai) were measured automatically (13–18 continuous image frames, 0.35 seconds/frame). Calculations included cross-correlation coefficients (CCCs) between the MLD and Ai time curves, and correlations between the quantitative measurements and spirometric values were evaluated by using Spearman’s rank coefficient.Results: The ΔMLD1.05 (from the peak inspiration frame to the third expiratory frame, 1.05 seconds later) in the nondependent lung negatively correlated with FEV1/FVC (r=-0.417, P

Rintaro Onoe,1 Tsuneo Yamashiro,2,3 Hiroshi Handa,1 Shinya Azagami,1 Shin Matsuoka,2 Takeo Inoue,1 Teruomi Miyazawa,1 Masamichi Mineshita1 1Division of Respiratory Medicine, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan; 2Department of Radiology, St Marianna University School of Medicine, Kawasaki, Japan; 3Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Japan Purpose: To assess tracheobronchial angles and their changes on combined inspiratory and expiratory thoracic computed tomography (CT) scans and to determine correlations between tracheobronchial angles and several indices of chronic obstructive pulmonary disease (COPD). Materials and methods: A total of 80 smokers underwent combined inspiratory and expiratory CT scans. Of these, 65 subjects also performed spirometry and 55 patients were diagnosed with COPD. On CT scans, 3-dimensinal tracheobronchial angles (trachea–right main bronchus [RMB], trachea–left main bronchus [LMB], and RMB–LMB) were automatically measured by software. Lung volumes at inspiration and expiration were also automatically calculated. Changes in tracheobronchial angles between inspiration and expiration were assessed by the Mann–Whitney test. Correlations of the angles with lung volume, airflow limitation, and CT-based emphysema index were evaluated by Spearman rank correlation. Results: The trachea–LMB angle was significantly smaller and the RMB–LMB angle was significantly larger at expiration than inspiration (P

Yanyan Xu,1,2 Tsuneo Yamashiro,1 Hiroshi Moriya,3 Maho Tsubakimoto,1 Nanae Tsuchiya,1 Yukihiro Nagatani,4 Shin Matsuoka,5 Sadayuki Murayama1 On behalf of the ACTIve Study Group 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Japan; 2Department of Radiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of Radiology, Ohara General Hospital, Fukushima, Japan; 4Department of Radiology, Shiga University of Medical Science, Otsu, Japan; 5Department of Radiology, St Marianna University School of Medicine, Kawasaki, Japan Purpose: The aims of this study were to evaluate dynamic changes in heart size during the respiratory cycle using four-dimensional computed tomography (CT) and to understand the relationship of these changes to airflow limitation in smokers.Materials and methods: A total of 31 smokers, including 13 with COPD, underwent four-dimensional dynamic-ventilation CT during regular breathing. CT data were continuously reconstructed every 0.5 s, including maximum cross-sectional area (CSA) of the heart and mean lung density (MLD). Concordance between the cardiac CSA and MLD time curves was expressed by cross-correlation coefficients. The CT-based cardiothoracic ratio at inspiration and expiration was also calculated. Comparisons of the CT indices between COPD patients and non-COPD smokers were made using the Mann–Whitney test. Spearman rank correlation analysis was used to evaluate associations between CT indices and the forced expiratory volume in 1 s (FEV1.0) relative to the forced vital capacity (FVC).Results: Cardiac CSA at both inspiration and expiration was significantly smaller in COPD patients than in non-COPD smokers (P

Tsuneo Yamashiro,1 Hiroshi Moriya,2 Shin Matsuoka,3 Yukihiro Nagatani,4 Maho Tsubakimoto,1 Nanae Tsuchiya,1 Sadayuki Murayama1 On behalf of the ACTIve Study Group 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa, Japan; 2Department of Radiology, Ohara General Hospital, Fukushima-City, Fukushima, Japan; 3Department of Radiology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan; 4Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, Japan Purpose: Four-dimensional dynamic-ventilation CT imaging demonstrates continuous movement of the lung. The aim of this study was to assess the correlation between interlobar synchrony in lung density and spirometric values in COPD patients and smokers, by measuring the continuous changes in lung density during respiration on the dynamic-ventilation CT. Materials and methods: Thirty-two smokers, including ten with COPD, underwent dynamic-ventilation CT during free breathing. CT data were continuously reconstructed every 0.5 sec. Mean lung density (MLD) of the five lobes (right upper [RU], right middle [RM], right lower [RL], left upper [LU], and left lower [LL]) was continuously measured by commercially available software using a fixed volume of volume of interest which was placed and tracked on a single designated point in each lobe. Concordance between the MLD time curves of six pairs of lung lobes (RU-RL, RU-RM, RM-RL, LU-LL, RU-LU, and RL-LL lobes) was expressed by cross-correlation coefficients. The relationship between these cross-correlation coefficients and the forced expiratory volume in one second/forced vital capacity (FEV1.0/FVC) values was assessed by Spearman rank correlation analysis. Results: In all six pairs of the pulmonary lobes, the cross-correlation coefficients of the two MLD curves were significantly positively correlated with FEV1.0/FVC (ρ =0.60–0.73, P

Teeth consist of 3 mineralized tissues: enamel, dentin, and cementum. Tooth malformation, the most common craniofacial anomaly, arises from complex genetic and environmental factors affecting enamel structure, size, shape, and tooth eruption. Hyaluronic acid (HA), a primary extracellular matrix component, contributes to structural and physiological functions in periodontal tissue. Transmembrane protein 2 (TMEM2), a novel cell surface hyaluronidase, has been shown to play a critical role during embryogenesis. In this study, we demonstrate Tmem2 messenger RNA expression in inner enamel epithelium and presecretory, secretory, and mature ameloblasts. Tmem2 knock-in reporter mice reveal TMEM2 protein localization at the apical and basal ends of secretory ameloblasts. Micro–computed tomography analysis of epithelial-specific Tmem2 conditional knockout (Tmem2 - CKO) mice shows a significant reduction in enamel layer thickness and severe enamel deficiency. Enamel matrix protein expression was remarkably downregulated in Tmem2 - CKO mice. Scanning electron microscopy of enamel from Tmem2 - CKO mice revealed an irregular enamel prism structure, while the microhardness and density of enamel were significantly reduced, indicating impaired ameloblast differentiation and enamel matrix mineralization. Histological evaluation indicated weak adhesion between cells and the basement membrane in Tmem2 - CKO mice. The reduced and irregular expressions of vinculin and integrin β1 suggest that Tmem2 deficiency attenuated focal adhesion formation. In addition, abnormal HA accumulation in the ameloblast layer and weak claudin 1 immunoreactivity in Tmem2 - CKO mice indicate impaired tight junction gate function. Irregular actin filament assembly was also observed at the apical and basal ends of secretory ameloblasts. Last, we demonstrated that Tmem2 -deficient mHAT9d mouse ameloblasts exhibit defective adhesion to HA-containing substrates in vitro. Collectively, our data highlight the importance of TMEM2 in adhesion to HA-rich extracellular matrix, cell-to-cell adhesion, ameloblast differentiation, and enamel matrix mineralization. [ABSTRACT FROM AUTHOR]

Tsuneo Yamashiro,1 Hiroshi Moriya,2 Maho Tsubakimoto,1 Shin Matsuoka,3 Sadayuki Murayama1 On behalf of ACTIve Study Group 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa, 2Department of Radiology, Ohara General Hospital, Fukushima-shi, Fukushima, 3Department of Radiology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Purpose: Four-dimensional dynamic-ventilation computed tomography (CT) imaging demonstrates continuous movement of the airways and lungs, which cannot be depicted with conventional CT. We aimed to investigate continuous changes in lung density and airway dimensions and to assess the correlation with spirometric values in smokers.Materials and methods: This retrospective study was approved by the Institutional Review Board, and informed consent was waived. Twenty-one smokers including six patients with COPD underwent four-dimensional dynamic-ventilation CT during free breathing (160 mm in length). The mean lung density (MLD) of the scanned lung and luminal areas (Ai) of fixed points in the trachea and the right proximal bronchi (main bronchus, upper bronchus, bronchus intermedius, and lower bronchus) were continuously measured. Concordance between the time curve of the MLD and that of the airway Ai values was expressed by cross-correlation coefficients. The associations between these quantitative measurements and the forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) values were assessed by Spearman’s rank correlation analysis.Results: On the time curve for the MLD, the Δ-MLD1.05 values between the peak inspiratory frame to the later third frame (1.05 seconds later) were strongly correlated with the FEV1/FVC (ρ=0.76, P

Tsuneo Yamashiro,1 Maho Tsubakimoto,1 Yukihiro Nagatani,2 Hiroshi Moriya,3 Kotaro Sakuma,3 Shinsuke Tsukagoshi,4 Hiroyasu Inokawa,5 Tatsuya Kimoto,5 Ryuichi Teramoto,6 Sadayuki Murayama1 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa; 2Department of Radiology, Shiga University of Medical Science, Otsu; 3Department of Radiology, Ohara General Hospital, Fukushima; 4CT Systems Division, 5Center for Medical Research and Development, Toshiba Medical Systems Corporation, Otawara; 6Corporate Manufacturing Engineering Center, Toshiba Corporation, Yokohama, Japan Background: The purpose of this study was to evaluate the feasibility of continuous quantitative measurement of the proximal airways, using dynamic ventilation computed tomography (CT) and our research software. Methods: A porcine lung that was removed during meat processing was ventilated inside a chest phantom by a negative pressure cylinder (eight times per minute). This chest phantom with imitated respiratory movement was scanned by a 320-row area-detector CT scanner for approximately 9 seconds as dynamic ventilatory scanning. Obtained volume data were reconstructed every 0.35 seconds (total 8.4 seconds with 24 frames) as three-dimensional images and stored in our research software. The software automatically traced a designated airway point in all frames and measured the cross-sectional luminal area and wall area percent (WA%). The cross-sectional luminal area and WA% of the trachea and right main bronchus (RMB) were measured for this study. Two radiologists evaluated the traceability of all measurable airway points of the trachea and RMB using a three-point scale. Results: It was judged that the software satisfactorily traced airway points throughout the dynamic ventilation CT (mean score, 2.64 at the trachea and 2.84 at the RMB). From the maximum inspiratory frame to the maximum expiratory frame, the cross-sectional luminal area of the trachea decreased 17.7% and that of the RMB 29.0%, whereas the WA% of the trachea increased 6.6% and that of the RMB 11.1%. Conclusion: It is feasible to measure airway dimensions automatically at designated points on dynamic ventilation CT using research software. This technique can be applied to various airway and obstructive diseases. Keywords: computed tomography, dynamic ventilation CT, airway, luminal area, wall area percent, COPD

Tsuneo Yamashiro,1 Tetsuhiro Miyara,1 Osamu Honda,2 Noriyuki Tomiyama,2 Yoshiharu Ohno,3 Satoshi Noma,4 Sadayuki Murayama1 On behalf of the ACTIve Study Group 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa, Japan; 2Department of Radiology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; 3Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan; 4Department of Radiology, Tenri Hospital, Tenri, Nara, Japan Purpose: To assess the advantages of iterative reconstruction for quantitative computed tomography (CT) analysis of pulmonary emphysema. Materials and methods: Twenty-two patients with pulmonary emphysema underwent chest CT imaging using identical scanners with three different tube currents: 240, 120, and 60 mA. Scan data were converted to CT images using Adaptive Iterative Dose Reduction using Three Dimensional Processing (AIDR3D) and a conventional filtered-back projection mode. Thus, six scans with and without AIDR3D were generated per patient. All other scanning and reconstruction settings were fixed. The percent low attenuation area (LAA%; < -950 Hounsfield units) and the lung density 15th percentile were automatically measured using a commercial workstation. Comparisons of LAA% and 15th percentile results between scans with and without using AIDR3D were made by Wilcoxon signed-rank tests. Associations between body weight and measurement errors among these scans were evaluated by Spearman rank correlation analysis. Results: Overall, scan series without AIDR3D had higher LAA% and lower 15th percentile values than those with AIDR3D at each tube current (P

Dental pulp stem cells (DPSCs) can differentiate into vascular endothelial cells and display sprouting ability. During this process, DPSC responses to the extracellular microenvironment and cell–extracellular matrix interactions are critical in regulating their ultimate cell fate. Heparan sulfate (HS) glycosaminoglycan, a major component of extracellular matrix, plays important roles in various biological cell activities by interacting with growth factors and relative receptors. However, the regulatory function of HS on vasculogenesis of mesenchymal stem cells remains unclear. The objective of this study was to investigate the role of HS in endothelial differentiation and vasculogenesis of DPSCs. Our results show that an HS antagonist suppressed the proliferation and sprouting ability of DPSCs undergoing endothelial differentiation. Furthermore, expression of proangiogenic markers significantly declined with increasing dosages of the HS antagonist; in contrast, expression of stemness marker increased. Silencing of exostosin 1 (EXT1), a crucial glycosyltransferase for HS biosynthesis, in DPSCs using a short hairpin RNA significantly altered their gene expression profile. In addition, EXT1 -silenced DPSCs expressed lower levels of endothelial differentiation markers and displayed a reduced vascular formation capacity compared with control DPSCs transduced with scrambled sequences. The sprouting ability of EXT1 -silenced DPSCs was rescued by the addition of exogenous HS in vitro. Next, we subcutaneously transplanted biodegradable scaffolds seeded with EXT1 -silenced or control DPSCs into immunodeficient mice. Lumen-like structures positive for human CD31 and von Willebrand factor were formed by green fluorescent protein–transduced DPSCs. Numbers of blood-containing vessels were significantly lower in scaffolds loaded with EXT1 -silenced DPSCs than specimens implanted with control DPSCs. Collectively, our findings unveil the crucial role of HS on endothelial differentiation and vasculogenesis of DPSCs, opening new perspectives for the application of HS to tissue engineering and dental pulp regeneration. [ABSTRACT FROM AUTHOR]

Embryonic craniofacial development depends on the coordinated outgrowth and fusion of multiple facial primordia, which are populated with cranial neural crest cells and covered by the facial ectoderm. Any disturbance in these developmental events, their progenitor tissues, or signaling pathways can result in craniofacial deformities such as orofacial clefts, which are among the most common birth defects in humans. In the present study, we show that Rdh10 loss of function leads to a substantial reduction in retinoic acid (RA) signaling in the developing frontonasal process during early embryogenesis, which results in a variety of craniofacial anomalies, including midfacial cleft and ectopic chondrogenic nodules. Elevated apoptosis and perturbed cell proliferation in postmigratory cranial neural crest cells and a substantial reduction in Alx1 and Alx3 transcription in the developing frontonasal process were associated with midfacial cleft in Rdh10 -deficient mice. More important, expanded Shh signaling in the ventral forebrain, as well as partial abrogation of midfacial defects in Rdh10 mutants via inhibition of Hh signaling, indicates that misregulation of Shh signaling underlies the pathogenesis of reduced RA signaling-associated midfacial defects. Taken together, these data illustrate the precise spatiotemporal function of Rdh10 and RA signaling during early embryogenesis and their importance in orchestrating molecular and cellular events essential for normal midfacial development. [ABSTRACT FROM AUTHOR]

Research has been conducted on genetic diversity and genetic differentiation among island populations of endemic species. The authors discuss the study of the genetic diversity and genetic differentiation carried out via the use of allozyme electrophoresis in Suzukia luchuensis.

9CrODS steel, a candidate fission and fusion structural material, was subjected to hot-rolling with varying parameters of surface temperature and cooling rate just after hot-rolling. The deformation-induced dynamic ferrite transformation was confirmed at the rolling temperature 805 °C above Ar3 (780 °C). This transformation exhibits three characteristic features: transformation for extremely short duration (0.044 second), retaining carbon content equal to the original without long-distance carbon diffusion, and elongated coarse ferrite grains (10 μm). The massive transformation was proposed for the dynamic ferrite transformation from the hot-rolled austenite. The driving force for massive transformation was quantitatively estimated considering dislocations accumulated by hot-rolling. It was also shown that the oxide particles in 9CrODS steel play a critical role for dynamic ferrite transformation by suppressing the dynamic recrystallization at hot-rolling. [ABSTRACT FROM AUTHOR]

Interleukin-1alpha(IL-1alpha) stimulates the production of prostaglandin E(2) (PGE(2)) in odontogenic keratocyst fibroblasts. However, the signaling pathways remain obscure. In this study, we investigated IL-1alphasignaling pathways that regulate cyclooxygenase-2 (COX-2) expression in odontogenic keratocyst fibroblasts. IL-1alphaincreased the expression of COX-2 mRNA and protein, and PGE(2) secretion in the fibroblasts. IL-1alphaincreased the phosphorylation of extracellular signal-regulated protein kinase-1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK). PD-98059, SB-203580, SP-600125, and PDTC-which are inhibitors of ERK1/2, p38, JNK, and nuclear factor-kappaB (NF-kappaB), respectively-attenuated the IL-1alpha-induced COX-2 mRNA expression and activated protein kinase C PGE(2) secretion. IL-1alpha(PKC), and PKC inhibitor staurosporine inhibited IL-1alpha-induced phosphorylation of ERK1/2, p38, and JNK, and decreased IL-1alpha-induced COX-2 mRNA expression. Thus, in odontogenic keratocyst fibroblasts, IL-1alphamay stimulate COX-2 expression both through the PKC-dependent activation of ERK1/2, p38, and JNK signaling pathways, and through the NF-kappaB cascade. [ABSTRACT FROM AUTHOR]

Periodontal tissue homeostasis depends on a complex cellular network that conveys cell-cell communication. Gap junctions (GJs), one of the intercellular communication systems, are found between adjacent human periodontal ligament (hPDL) cells; however, the functional GJ coupling between hPDL cells has not yet been elucidated. In this study, we investigated functional gap-junction-mediated intercellular communication in isolated primary hPDL cells. SEM images indicated that the cells were in contact with each other via dendritic processes, and also showed high anti-connexin43 (Cx43) immunoreactivity on these processes. Gap-junctional intercellular communication (GJIC) among hPDL cells was assessed by fluorescence recovery after a photobleaching (FRAP) analysis, which exhibited dye coupling between hPDL cells, and was remarkably down-regulated when the cells were treated with a GJ blocker. Additionally, we examined GJs under hypoxic stress. The fluorescence recovery and expression levels of Cx43 decreased time-dependently under the hypoxic condition. Exposure to GJ inhibitor or hypoxia increased RANKL expression, and decreased OPG expression. This study shows that GJIC is responsible for hPDL cells and that its activity is reduced under hypoxia. This is consistent with the possible role of hPDL cells in regulating the biochemical reactions in response to changes in the hypoxic environment. [ABSTRACT FROM PUBLISHER]

Although human deciduous teeth are an ideal source of adult stem cells, no method for identifying deciduous periodontal ligament (D-PDL) stem cells has so far been developed. In the present study, we investigated whether stage-specific embryonic antigen (SSEA)-4 is a marker that could be used to isolate D-PDL stem cells. The isolated D-PDL cells met the minimum criteria for mesenchymal stem cells (MSCs): They showed plastic adherence, specific-surface antigen expression, and multipotent differentiation potential. SSEA-4+ D-PDL cells were detected in vitro and in vivo. A flow cytometric analysis demonstrated that 22.7% of the D-PDL cells were positive for SSEA-4. SSEA-4+ clonal D-PDL cells displayed multilineage differentiation potential: They were able to differentiate into adipocytes, osteoblasts, and chondrocytes in vitro. A clonal assay demonstrated that 61.5% of the SSEA-4+ D-PDL cells had adipogenic, osteogenic, and chondrogenic potential. Our present study demonstrated that SSEA-4+ D-PDL cells are a subset of multipotent stem cells. Hence, SSEA-4 is a specific marker that can be used to identify D-PDL stem cells. [ABSTRACT FROM PUBLISHER]

Rationale and Objectives: To evaluate pulmonary findings on computed tomography (CT) scans in carriers of human T-lymphotropic virus type 1 (HTLV-1). Materials and Methods: This retrospective study was approved by the Institutional Review Board at each institution, and informed consent was waived. Patients who were diagnosed with adult T-cell lymphoma/leukemia or collagen vascular disease were excluded from the study. Chest CT of 106 HTLV-1 carriers (54 females and 52 males; age range 44-94 years) were initially evaluated by two chest radiologists. Assessed CT findings included centrilobular nodules, thickening of bronchovascular bundles, ground-glass opacity, bronchiectasis, interlobular septal thickening, consolidation, honeycombing, crazy-paving appearance, enlarged lymph nodes, pleural effusion, and pericardial effusion. Three chest radiologists secondarily evaluated the CT scans with the abnormal findings to judge the presence of interstitial pneumonia patterns or a bronchiolitis/bronchitis pattern. Results: Abnormal CT findings were found in 65 (61.3%) patients, including ground-glass opacity (n = 33), bronchiectasis (n = 28), centrilobular nodules (n = 25), and interlobular septal thickening (n = 19). Honeycombing (n = 5) and crazy-paving appearance (n = 3) were also observed. Based on the CT findings, 10 subjects were diagnosed with interstitial pneumonia (usual interstitial pneumonia pattern, n = 3; nonspecific interstitial pneumonia pattern, n = 5; organizing pneumonia pattern, n = 2; respectively). Twenty subjects were diagnosed with the bronchitis/bronchiolitis pattern. Conclusion: Although the bronchiolitis/bronchitis pattern is predominant on chest CT in HTLV-1 carriers, the HTLV-1 infection is associated with various interstitial pneumonias. [ABSTRACT FROM AUTHOR]

Rationales and Objectives: To evaluate the image quality of 320-row wide-volume (WV) computed tomography (CT) scans in comparison with 64-row helical scans for the lung. Materials and Methods: The Institutional Review Board of each institution approved this prospective, multicenter study and informed consent was obtained. A total of 73 subjects underwent two types of chest CT, including 320-row WV scans and 64-row helical scans. Both scans used the same tube voltage, tube current, exposure time setting, and slice thickness. The helical scans were not electrocardiogram (ECG)-gated. For the WV scans, prospective ECG-gating was used for 38 subjects, whereas the other 35 subjects did not have ECG-gating. Using a 5-point scale from 1 (nondiagnostic) to 5 (excellent), three blinded observers independently evaluated image quality for five lobes and the lingula. The differences in the scores between WV scans and helical scans were compared using Wilcoxon's signed-rank test. Results: The WV scans with ECG-gating had significantly higher scores than 64-row helical scans for all lobes and lingula (right lower lobe, P < .01; other lobes and lingula, P < .0001, respectively). The 320-row WV scans without ECG-gating also had significantly higher scores than 64-row helical scans (P < .05), except for nonsignificant differences for the left upper lobe. Conclusions: Lung image quality of ECG-gated WV scans, which do not require any additional radiation exposure, is better than that of non-ECG-gated 64-row helical scans. Non-ECG-gated 320-row WV scans are comparable or slightly superior to non-ECG-gated 64-row helical scans. [ABSTRACT FROM AUTHOR]

Rationale: The role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the development or progression of interstitial lung disease (ILD) is controversial.Objectives: To evaluate the association between statin use and ILD.Methods: We used regression analyses to evaluate the association between statin use and interstitial lung abnormalities (ILA) in a large cohort of smokers from COPDGene. Next, we evaluated the effect of statin pretreatment on bleomycin-induced fibrosis in mice and explored the mechanism behind these observations in vitro.Measurements and Main Results: In COPDGene, 38% of subjects with ILA were taking statins compared with 27% of subjects without ILA. Statin use was positively associated in ILA (odds ratio, 1.60; 95% confidence interval, 1.03-2.50; P = 0.04) after adjustment for covariates including a history of high cholesterol or coronary artery disease. This association was modified by the hydrophilicity of statin and the age of the subject. Next, we demonstrate that statin administration aggravates lung injury and fibrosis in bleomycin-treated mice. Statin pretreatment enhances caspase-1-mediated immune responses in vivo and in vitro; the latter responses were abolished in bone marrow-derived macrophages isolated from Nlrp3(-/-) and Casp1(-/-) mice. Finally, we provide further insights by demonstrating that statins enhance NLRP3-inflammasome activation by increasing mitochondrial reactive oxygen species generation in macrophages.Conclusions: Statin use is associated with ILA among smokers in the COPDGene study and enhances bleomycin-induced lung inflammation and fibrosis in the mouse through a mechanism involving enhanced NLRP3-inflammasome activation. Our findings suggest that statins may influence the susceptibility to, or progression of, ILD. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764). [ABSTRACT FROM AUTHOR]

Purpose: Pulmonary vascular alterations are not exclusive to pulmonary vascular disorders; they are also present in patients with mild chronic obstructive pulmonary disease (COPD) with normal pulmonary function. Moreover, vascular alteration is closely related to lung ventilation. We hypothesized that pulmonary vascular alterations might occur even in nonsmokers with subtle airflow limitation, and there could be a significant correlation between pulmonary vascular alterations and airflow impairment. The purpose of this study was to evaluate the correlation between the vascular alterations measured by cross-sectional area (CSA) and airflow impairment in nonsmokers with normal pulmonary function.Materials and Methods: Thirty patients (1 man, 29 women; mean age 55 ± 14 years, range 33-81 years) underwent pulmonary function tests (PFTs) within 2 weeks of undergoing multidetector computed tomography (CT) scans. Total vessel CSA < 5 mm(2) was calculated by a threshold technique using imaging software. Forced expiratory volume in 1 s (FEV(1)), the ratio of FEV(1) to FVC (FEV(1)/FVC), and the mid-expiratory phase of the forced expiratory flow (FEF(25%-75%)) were obtained from PFTs. We calculated Spearman correlation coefficients between %CSA < 5 and the results of PFTs.Results: %CSA < 5 had a significant positive correlation with FEV(1)/FVC (r = 0.651, P < 0.0001) and FEF(25%-75%) (r = 0.627, P = 0.0002), whereas CSA < 5% had no significant correlation with FEV(1) (r = 0.172, P = 0.362).Conclusion: There was a significant correlation between pulmonary small vascular alteration and airflow impairment even in nonsmokers without airway obstruction. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To evaluate the correlations of tracheal volume and collapsibility on inspiratory and end-expiratory computed tomography (CT) with lung volume and with lung function in smokers.Materials and Methods: The institutional review board approved this study at each institution. 85 smokers (mean age 68, range 45-87 years; 40 females and 45 males) underwent pulmonary function tests and chest CT at full inspiration and end-expiration. On both scans, intrathoracic tracheal volume and lung volume were measured. Collapsibility of the trachea and the lung was expressed as expiratory/inspiratory (E/I) ratios of these volumes. Correlations of the tracheal measurements with the lung measurements and with lung function were evaluated by the linear regression analysis.Results: Tracheal volume showed moderate or strong, positive correlations with lung volume on both inspiratory (r = 0.661, P < .0001) and end-expiratory (r = 0.749, P < .0001) scans. The E/I ratio of tracheal volume showed a strong, positive correlation with the E/I ratio of lung volume (r = 0.711, P < .0001). A weak, negative correlation was found between the E/I ratio of tracheal volume and the ratio of forced expiratory volume in the first second to forced vital capacity (r = -0.436, P < .0001). Also, a weak, positive correlation was observed between the E/I ratio of tracheal volume and the ratio of residual volume to total lung capacity (r = 0.253, P = .02).Conclusions: Tracheal volume and collapsibility, measured by inspiratory and end-expiratory CT scans, is related to lung volume and collapsibility. The highly collapsed trachea on end-expiratory CT does not indicate more severe airflow limitation or air-trapping in smokers. [ABSTRACT FROM AUTHOR]