DSpace Collection:
http://hdl.handle.net/2115/35410
2024-03-28T11:07:42ZValidation of mitotic harvesting method with human cervical carcinoma HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators for radiation research
http://hdl.handle.net/2115/91324
Title: Validation of mitotic harvesting method with human cervical carcinoma HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators for radiation research
Authors: Seino, Ryosuke; Uno, Hiroto; Fukunaga, Hisanori
Abstract: The cell cycle is a series of events in the process of one cell giving rise to two daughter cells. The mitotic harvesting method, established by Terasima and Tolmach in the 1960s, causes minimal physiological stress on the cells and achieves a high degree of cell cycle synchrony by collecting only mitotic cells from a cultured cell system. The purpose of the present study is to validate the versatility of the mitotic harvesting method using human cervical cell line HeLa cells expressing Fluorescent Ubiquitination-based Cell Cycle Indicators (FUCCI) and to estimate the cell cycle-dependent changes in radiosensitivity in HeLa-FUCCI cells. The image analysis showed that cell cycle synchrony was maintained for at least 24 hours after mitotic cell collection. Also, the clonogenic assay demonstrated changes in radiosensitivity that were cell cycle dependent. These results indicate that the mitotic harvesting method using FUCCI-expressing cells has high versatility in the field of radiation cell biology.2023-09-26T15:00:00ZSeino, RyosukeUno, HirotoFukunaga, HisanoriThe cell cycle is a series of events in the process of one cell giving rise to two daughter cells. The mitotic harvesting method, established by Terasima and Tolmach in the 1960s, causes minimal physiological stress on the cells and achieves a high degree of cell cycle synchrony by collecting only mitotic cells from a cultured cell system. The purpose of the present study is to validate the versatility of the mitotic harvesting method using human cervical cell line HeLa cells expressing Fluorescent Ubiquitination-based Cell Cycle Indicators (FUCCI) and to estimate the cell cycle-dependent changes in radiosensitivity in HeLa-FUCCI cells. The image analysis showed that cell cycle synchrony was maintained for at least 24 hours after mitotic cell collection. Also, the clonogenic assay demonstrated changes in radiosensitivity that were cell cycle dependent. These results indicate that the mitotic harvesting method using FUCCI-expressing cells has high versatility in the field of radiation cell biology.Appearance and modulation of a reactive temporal-lobe 8–10-Hz tau-rhythm
http://hdl.handle.net/2115/91191
Title: Appearance and modulation of a reactive temporal-lobe 8–10-Hz tau-rhythm
Authors: Yokosawa, Koichi; Murakami, Yui; Sato, Hiroaki
Abstract: Spontaneous 8- to 10-Hz “tau-rhythm” in magnetoencephalographic (MEG) recordings has been reported to originate in the auditory cortex and be suppressed by sound. For unknown reasons however, tau-rhythm is often difficult to detect. In this study, we sought to characterize its emergence and auditory reactivity. Using a 306-channel MEG on 26 right-handed participants, we delivered six-second-long, natural, monaural sounds with pleasant, unpleasant, or neutral emotional valence. In eight participants, a clear, sound-related bilateral suppression of 8–10 Hz tau-rhythm occurred in the temporal areas, close to the source of the 100-ms auditory response. Moreover, these eight “tau subjects” exhibited significantly larger temporal-lobe theta-band (4–8 Hz) power over the entire experimental period compared to the remaining 18 “non-tau subjects”. As it is known that larger theta power is one of signs of drowsiness, this result is consistent with a previously proposed idea that tau-rhythm emerges during drowsiness. Tau-rhythm was furthermore significantly affected by emotional valence in the right hemisphere, where it was respectively suppressed by unpleasant and neutral sounds 8% and 6% more than by pleasant sounds, significantly. Altogether, our results reveal characteristics of tau-rhythm appearance and modulation which have hitherto been difficult to detect non-invasively.2019-12-31T15:00:00ZYokosawa, KoichiMurakami, YuiSato, HiroakiSpontaneous 8- to 10-Hz “tau-rhythm” in magnetoencephalographic (MEG) recordings has been reported to originate in the auditory cortex and be suppressed by sound. For unknown reasons however, tau-rhythm is often difficult to detect. In this study, we sought to characterize its emergence and auditory reactivity. Using a 306-channel MEG on 26 right-handed participants, we delivered six-second-long, natural, monaural sounds with pleasant, unpleasant, or neutral emotional valence. In eight participants, a clear, sound-related bilateral suppression of 8–10 Hz tau-rhythm occurred in the temporal areas, close to the source of the 100-ms auditory response. Moreover, these eight “tau subjects” exhibited significantly larger temporal-lobe theta-band (4–8 Hz) power over the entire experimental period compared to the remaining 18 “non-tau subjects”. As it is known that larger theta power is one of signs of drowsiness, this result is consistent with a previously proposed idea that tau-rhythm emerges during drowsiness. Tau-rhythm was furthermore significantly affected by emotional valence in the right hemisphere, where it was respectively suppressed by unpleasant and neutral sounds 8% and 6% more than by pleasant sounds, significantly. Altogether, our results reveal characteristics of tau-rhythm appearance and modulation which have hitherto been difficult to detect non-invasively.Regional assessment of medical care provision system by principal component analysis
http://hdl.handle.net/2115/91135
Title: Regional assessment of medical care provision system by principal component analysis
Authors: Ohashi, Kazuki; Abe, Arisa; Fujiwara, Kensuke; Nishimoto, Naoki; Ogasawara, Katsuhiko
Abstract: Introduction: The Japanese government has promoted policies ensuring standardized medical care across the secondary medical care areas (SMCAs); however, these efforts have not been evaluated, making the current conditions unclear. Multidimensional indicators could identify these differences; thus, this study examined the regional characteristics of the medical care provision system for 21 SMCAs in Hokkaido, Japan, and the changes from 1998 to 2018. Materials and methods: This study evaluated the characteristics of SMCAs by principal component analysis using multidimensional data related to the medical care provision system. Factor loadings and principal component scores were calculated, with the characteristics of each SMCA visually expressed using scatter plots. Additionally, data from 1998 to 2018 were analyzed to clarify the changes in SMCAs' characteristics. Results: The primary and secondary principal components were Medical Resources and Geographical Factors, respectively. The Medical Resources components included the number of hospitals, clinics, and doctors, and an area's population of older adults, accounting for 65.28% of the total variance. The Geographical Factors components included the number of districts without doctors and the population and a land area of these districts, accounting for 23.20% of the variance. The accumulated proportion of variance was 88.47%. From 1998 to 2018, the area with the highest increase in Medical Resources was Sapporo, with numerous initial medical resources (-9.283 to -10.919). Discussion: Principal component analysis summarized multidimensional indicators and evaluated SMCAs in this regional assessment. This study categorized SMCAs into four quadrants based on Medical Resources and Geographical Factors. Additionally, the difference in principal component scores between 1998 and 2018 emphasized the expanding gap in the medical care provision system among the 21 SMCAs.2023-03-31T15:00:00ZOhashi, KazukiAbe, ArisaFujiwara, KensukeNishimoto, NaokiOgasawara, KatsuhikoIntroduction: The Japanese government has promoted policies ensuring standardized medical care across the secondary medical care areas (SMCAs); however, these efforts have not been evaluated, making the current conditions unclear. Multidimensional indicators could identify these differences; thus, this study examined the regional characteristics of the medical care provision system for 21 SMCAs in Hokkaido, Japan, and the changes from 1998 to 2018. Materials and methods: This study evaluated the characteristics of SMCAs by principal component analysis using multidimensional data related to the medical care provision system. Factor loadings and principal component scores were calculated, with the characteristics of each SMCA visually expressed using scatter plots. Additionally, data from 1998 to 2018 were analyzed to clarify the changes in SMCAs' characteristics. Results: The primary and secondary principal components were Medical Resources and Geographical Factors, respectively. The Medical Resources components included the number of hospitals, clinics, and doctors, and an area's population of older adults, accounting for 65.28% of the total variance. The Geographical Factors components included the number of districts without doctors and the population and a land area of these districts, accounting for 23.20% of the variance. The accumulated proportion of variance was 88.47%. From 1998 to 2018, the area with the highest increase in Medical Resources was Sapporo, with numerous initial medical resources (-9.283 to -10.919). Discussion: Principal component analysis summarized multidimensional indicators and evaluated SMCAs in this regional assessment. This study categorized SMCAs into four quadrants based on Medical Resources and Geographical Factors. Additionally, the difference in principal component scores between 1998 and 2018 emphasized the expanding gap in the medical care provision system among the 21 SMCAs.Optimal allocation of physicians improves accessibility and workload disparities in stroke care
http://hdl.handle.net/2115/91134
Title: Optimal allocation of physicians improves accessibility and workload disparities in stroke care
Authors: Ohashi, Kazuki; Osanai, Toshiya; Bando, Kyohei; Fujiwara, Kensuke; Tanikawa, Takumi; Tani, Yuji; Takamiya, Soichiro; Sato, Hirotaka; Morii, Yasuhiro; Ishikawa, Tomoki; Ogasawara, Katsuhiko
Abstract: Background: Inequalities in access to stroke care and the workload of physicians have been a challenge in recent times. This may be resolved by allocating physicians suitable for the expected demand. Therefore, this study analyzes whether reallocation using an optimization model reduces disparities in spatial access to healthcare and excessive workload. Methods: This study targeted neuroendovascular specialists and primary stroke centers in Japan and employed an optimization model for reallocating neuroendovascular specialists to reduce the disparity in spatial accessibility to stroke treatment and workload for neuroendovascular specialists in Japan. A two-step floating catchment area method and an inverted two-step floating catchment area method were used to estimate the spatial accessibility and workload of neuroendovascular specialists as a potential crowdedness index. Quadratic programming has been proposed for the reallocation of neuroendovascular specialists. Results: The reallocation of neuroendovascular specialists reduced the disparity in spatial accessibility and the potential crowdedness index. The standard deviation (SD) of the demand-weighted spatial accessibility index improved from 125.625 to 97.625. Simultaneously, the weighted median spatial accessibility index increased from 2.811 to 3.929. Additionally, the SD of the potential crowdedness index for estimating workload disparity decreased from 10,040.36 to 5934.275 after optimization. The sensitivity analysis also showed a similar trend of reducing disparities. Conclusions: The reallocation of neuroendovascular specialists reduced regional disparities in spatial accessibility to healthcare, potential crowdedness index, and disparities between facilities. Our findings contribute to planning health policies to realize equity throughout the healthcare system.2023-11-06T15:00:00ZOhashi, KazukiOsanai, ToshiyaBando, KyoheiFujiwara, KensukeTanikawa, TakumiTani, YujiTakamiya, SoichiroSato, HirotakaMorii, YasuhiroIshikawa, TomokiOgasawara, KatsuhikoBackground: Inequalities in access to stroke care and the workload of physicians have been a challenge in recent times. This may be resolved by allocating physicians suitable for the expected demand. Therefore, this study analyzes whether reallocation using an optimization model reduces disparities in spatial access to healthcare and excessive workload. Methods: This study targeted neuroendovascular specialists and primary stroke centers in Japan and employed an optimization model for reallocating neuroendovascular specialists to reduce the disparity in spatial accessibility to stroke treatment and workload for neuroendovascular specialists in Japan. A two-step floating catchment area method and an inverted two-step floating catchment area method were used to estimate the spatial accessibility and workload of neuroendovascular specialists as a potential crowdedness index. Quadratic programming has been proposed for the reallocation of neuroendovascular specialists. Results: The reallocation of neuroendovascular specialists reduced the disparity in spatial accessibility and the potential crowdedness index. The standard deviation (SD) of the demand-weighted spatial accessibility index improved from 125.625 to 97.625. Simultaneously, the weighted median spatial accessibility index increased from 2.811 to 3.929. Additionally, the SD of the potential crowdedness index for estimating workload disparity decreased from 10,040.36 to 5934.275 after optimization. The sensitivity analysis also showed a similar trend of reducing disparities. Conclusions: The reallocation of neuroendovascular specialists reduced regional disparities in spatial accessibility to healthcare, potential crowdedness index, and disparities between facilities. Our findings contribute to planning health policies to realize equity throughout the healthcare system.Access to mechanical thrombectomy and ischemic stroke mortality in Japan : a spatial ecological study
http://hdl.handle.net/2115/91133
Title: Access to mechanical thrombectomy and ischemic stroke mortality in Japan : a spatial ecological study
Authors: Ohashi, Kazuki; Osanai, Toshiya; Fujiwara, Kensuke; Tanikawa, Takumi; Tani, Yuji; Takamiya, Soichiro; Sato, Hirotaka; Morii, Yasuhiro; Ogasawara, Katsuhiko
Abstract: Background: Advances in stroke treatment have greatly improved outcomes; however, disparities in access to treatment might increase. Achieving equitable access to stroke treatment is a health policy challenge, as rapid treatment is essential for positive outcomes. This ecological cross-sectional study aimed to determine the relationship between the disparities in spatial accessibility to mechanical thrombectomy (SAMT) and stroke mortality rates in Japan, hypothesizing that disparities in SAMT may increase the differences in stroke mortality between regions. Methods: We used the average number of ischemic stroke (IS) deaths between 2020 and 2021 as the response variable; and SAMT, medical resources, and socioeconomic characteristics of each municipality as explanatory variables. A conditional autoregressive model was used to examine the association between the risk of stroke mortality and SAMT. The standardized mortality ratio (SMR) was mapped to understand the nationwide disparities in stroke mortality risk. Results: The median number of IS deaths was 17.5 persons per year in the municipalities (2020 to 2021). The study also found that municipalities with low SAMT were located in the northern part of Japan. The non-spatial regression model results indicated that poor accessibility, a small proportion of bachelor's degrees or higher, and a high proportion of workers in secondary industries were related to high IS mortality. Three models were evaluated using spatial analysis; Model 1 with accessibility indicators alone, Model 2 with medical resources added to Model 1, and Model 3 with socioeconomic characteristics added to Model 2. In Models 1 and 2, the population-weighted spatial accessibility index (PWSAI) showed a significant negative relationship with stroke mortality. However, this was not evident in Model 3. Mapping using Model 3 showed that the high-risk areas were predominantly located in northern Japan, excluding Hokkaido. Conclusion: Access to mechanical thrombectomy was estimated, and regional differences were observed. The relationship between accessibility and IS mortality is unknown; however, regardless of accessibility, municipalities with a high proportion of workers in secondary industries and a small proportion with bachelor's degrees or above are at risk of death from stroke.2023-09-04T15:00:00ZOhashi, KazukiOsanai, ToshiyaFujiwara, KensukeTanikawa, TakumiTani, YujiTakamiya, SoichiroSato, HirotakaMorii, YasuhiroOgasawara, KatsuhikoBackground: Advances in stroke treatment have greatly improved outcomes; however, disparities in access to treatment might increase. Achieving equitable access to stroke treatment is a health policy challenge, as rapid treatment is essential for positive outcomes. This ecological cross-sectional study aimed to determine the relationship between the disparities in spatial accessibility to mechanical thrombectomy (SAMT) and stroke mortality rates in Japan, hypothesizing that disparities in SAMT may increase the differences in stroke mortality between regions. Methods: We used the average number of ischemic stroke (IS) deaths between 2020 and 2021 as the response variable; and SAMT, medical resources, and socioeconomic characteristics of each municipality as explanatory variables. A conditional autoregressive model was used to examine the association between the risk of stroke mortality and SAMT. The standardized mortality ratio (SMR) was mapped to understand the nationwide disparities in stroke mortality risk. Results: The median number of IS deaths was 17.5 persons per year in the municipalities (2020 to 2021). The study also found that municipalities with low SAMT were located in the northern part of Japan. The non-spatial regression model results indicated that poor accessibility, a small proportion of bachelor's degrees or higher, and a high proportion of workers in secondary industries were related to high IS mortality. Three models were evaluated using spatial analysis; Model 1 with accessibility indicators alone, Model 2 with medical resources added to Model 1, and Model 3 with socioeconomic characteristics added to Model 2. In Models 1 and 2, the population-weighted spatial accessibility index (PWSAI) showed a significant negative relationship with stroke mortality. However, this was not evident in Model 3. Mapping using Model 3 showed that the high-risk areas were predominantly located in northern Japan, excluding Hokkaido. Conclusion: Access to mechanical thrombectomy was estimated, and regional differences were observed. The relationship between accessibility and IS mortality is unknown; however, regardless of accessibility, municipalities with a high proportion of workers in secondary industries and a small proportion with bachelor's degrees or above are at risk of death from stroke.Development and validation of the Care Transitions Scale for Patients with Heart Failure : A tool for nurses to assess patients' readiness for hospital discharge
http://hdl.handle.net/2115/91132
Title: Development and validation of the Care Transitions Scale for Patients with Heart Failure : A tool for nurses to assess patients' readiness for hospital discharge
Authors: Yoshimura, Mai; Kawamura, Masumi; Hasegawa, Satoko; Ito, Yoichi M.; Takahashi, Keita; Sumi, Naomi
Abstract: Aim: This study aimed to develop and assess the validity and reliability of the Care Transitions Scale for Patients with Heart Failure (CTS-HF) as a nurse-reported measure for evaluating patients' readiness for hospital discharge.Methods: We conducted a cross-sectional study of cardiovascular ward nurses from 163 hospitals across Japan. Structural validity was assessed using exploratory factor analysis with development participants and confirmatory factor analysis with validation participants. Convergent validity was assessed by correlation with the Discharge Planning of Ward Nurses scale (DPWN). Hypotheses testing for construct validity was performed as comparisons between subgroups of transitional care practice.Results: Valid responses were obtained from 704 nurses (development participants, n = 352; validation participants, n = 352). The final scale comprised 21 items divided into six factors: Clear preparation for how to manage health at home, Adjusting to home care/support system, Transitions of medication management from hospital to home, Dealing with patients' concerns and questions, Transitions of disease management from hospital to home, and Family support. Indices of fit supported these results (comparative fit index = 0.944, root mean square error of approximation = 0.057). The CTS-HF was significantly correlated with the DPWN. The nurses' subgroup with higher transitional care practice had higher CTS-HF scores. Cronbach's alpha was .93 for the CTS-HF.Conclusions: The CTS-HF showed sufficient reliability and validity for use in evaluating discharge care. Further studies are needed regarding the usefulness of this scale in nursing practice.2023-02-07T15:00:00ZYoshimura, MaiKawamura, MasumiHasegawa, SatokoIto, Yoichi M.Takahashi, KeitaSumi, NaomiAim: This study aimed to develop and assess the validity and reliability of the Care Transitions Scale for Patients with Heart Failure (CTS-HF) as a nurse-reported measure for evaluating patients' readiness for hospital discharge.Methods: We conducted a cross-sectional study of cardiovascular ward nurses from 163 hospitals across Japan. Structural validity was assessed using exploratory factor analysis with development participants and confirmatory factor analysis with validation participants. Convergent validity was assessed by correlation with the Discharge Planning of Ward Nurses scale (DPWN). Hypotheses testing for construct validity was performed as comparisons between subgroups of transitional care practice.Results: Valid responses were obtained from 704 nurses (development participants, n = 352; validation participants, n = 352). The final scale comprised 21 items divided into six factors: Clear preparation for how to manage health at home, Adjusting to home care/support system, Transitions of medication management from hospital to home, Dealing with patients' concerns and questions, Transitions of disease management from hospital to home, and Family support. Indices of fit supported these results (comparative fit index = 0.944, root mean square error of approximation = 0.057). The CTS-HF was significantly correlated with the DPWN. The nurses' subgroup with higher transitional care practice had higher CTS-HF scores. Cronbach's alpha was .93 for the CTS-HF.Conclusions: The CTS-HF showed sufficient reliability and validity for use in evaluating discharge care. Further studies are needed regarding the usefulness of this scale in nursing practice.Methylprednisolone pulse-enhanced neutrophil extracellular trap formation in mice with imiquimod-induced lupus-like disease, resulting in ischaemia of the femoral head cartilage
http://hdl.handle.net/2115/91026
Title: Methylprednisolone pulse-enhanced neutrophil extracellular trap formation in mice with imiquimod-induced lupus-like disease, resulting in ischaemia of the femoral head cartilage
Authors: Ogawa, Hodaka; Yokota, Shunichi; Hosoi, Yumeka; Shindo, Ayano; Ogawa, Naho; Yamamura, Ryodai; Shimizu, Tomohiro; Nakade, Issei; Arai, Suishin; Taniguchi, Mai; Nishibata, Yuka; Masuda, Sakiko; Nakazawa, Daigo; Tomaru, Utano; Iwasaki, Norimasa; Ishizu, Akihiro
Abstract: Objectives: Methylprednisolone (mPSL) pulse therapy is an essential option for patients with active systemic lupus erythematosus, but there is a risk of adverse events related to microcirculation disorders, including idiopathic osteonecrosis of the femoral head (ONFH). Recent studies have revealed that excessive neutrophil extracellular traps (NETs) are involved in microcirculation disorders. This study aimed to demonstrate that mPSL pulse could induce NETs in lupus mice and identify the factors contributing to this induction. Methods: Six mice with imiquimod (IMQ)-induced lupus-like disease and six normal mice were intraperitoneally injected with mPSL on days 39 to 41, and five mice with IMQ-induced lupus-like disease and six normal mice were injected with phosphate-buffered saline. Pathological examinations were conducted to evaluate the ischaemic state of the femoral head and tissue infiltration of NET-forming neutrophils. Proteome analysis was performed to extract plasma proteins specifically elevated in mPSL-administered mice with IMQ-induced lupus-like disease, and their effects on NET formation were assessed in vitro. Results: Mice with IMQ-induced lupus-like disease that received mPSL pulse demonstrated ischaemia of the femoral head cartilage with tissue infiltration of NET-forming neutrophils. Proteome analysis suggested that prenylcysteine oxidase 1 (PCYOX1) played a role in this phenomenon. The reaction of PCYOX1-containing very low-density lipoproteins (VLDL) with its substrate farnesylcysteine (FC) induced NETs in vitro. The combined addition of IMQ and mPSL synergistically enhanced VLDL-plus-FC-induced NET formation. Conclusion: PCYOX1 and related factors are worthy of attention to understand the underlying mechanisms and create novel therapeutic strategies for mPSL-mediated microcirculation disorders, including ONFH.2023-12-27T15:00:00ZOgawa, HodakaYokota, ShunichiHosoi, YumekaShindo, AyanoOgawa, NahoYamamura, RyodaiShimizu, TomohiroNakade, IsseiArai, SuishinTaniguchi, MaiNishibata, YukaMasuda, SakikoNakazawa, DaigoTomaru, UtanoIwasaki, NorimasaIshizu, AkihiroObjectives: Methylprednisolone (mPSL) pulse therapy is an essential option for patients with active systemic lupus erythematosus, but there is a risk of adverse events related to microcirculation disorders, including idiopathic osteonecrosis of the femoral head (ONFH). Recent studies have revealed that excessive neutrophil extracellular traps (NETs) are involved in microcirculation disorders. This study aimed to demonstrate that mPSL pulse could induce NETs in lupus mice and identify the factors contributing to this induction. Methods: Six mice with imiquimod (IMQ)-induced lupus-like disease and six normal mice were intraperitoneally injected with mPSL on days 39 to 41, and five mice with IMQ-induced lupus-like disease and six normal mice were injected with phosphate-buffered saline. Pathological examinations were conducted to evaluate the ischaemic state of the femoral head and tissue infiltration of NET-forming neutrophils. Proteome analysis was performed to extract plasma proteins specifically elevated in mPSL-administered mice with IMQ-induced lupus-like disease, and their effects on NET formation were assessed in vitro. Results: Mice with IMQ-induced lupus-like disease that received mPSL pulse demonstrated ischaemia of the femoral head cartilage with tissue infiltration of NET-forming neutrophils. Proteome analysis suggested that prenylcysteine oxidase 1 (PCYOX1) played a role in this phenomenon. The reaction of PCYOX1-containing very low-density lipoproteins (VLDL) with its substrate farnesylcysteine (FC) induced NETs in vitro. The combined addition of IMQ and mPSL synergistically enhanced VLDL-plus-FC-induced NET formation. Conclusion: PCYOX1 and related factors are worthy of attention to understand the underlying mechanisms and create novel therapeutic strategies for mPSL-mediated microcirculation disorders, including ONFH.Fully automatic software for detecting radiographic joint space narrowing progression in rheumatoid arthritis : phantom study and comparison with visual assessment
http://hdl.handle.net/2115/90999
Title: Fully automatic software for detecting radiographic joint space narrowing progression in rheumatoid arthritis : phantom study and comparison with visual assessment
Authors: Okino, Taichi; Ou, Yafei; Ikebe, Masayuki; Tamura, Kenichi; Sutherland, Kenneth; Fukae, Jun; Tanimura, Kazuhide; Kamishima, Tamotsu
Abstract: Purpose We have developed an in-house software equipped with partial image phase-only correlation (PIPOC) which can automatically quantify radiographic joint space narrowing (JSN) progression. The purpose of this study was to evaluate the software in phantom and clinical assessments. Materials and methods In the phantom assessment, the software's performance on radiographic images was compared to the joint space width (JSW) difference using a micrometer as ground truth. A phantom simulating a finger joint was scanned underwater. In the clinical assessment, 15 RA patients were included. The software measured the radiological progression of the finger joints between baseline and the 52nd week. The cases were also evaluated with the Genant-modified Sharp score (GSS), a conventional visual scoring method. We also quantitatively assessed these joints' synovial vascularity (SV) on power Doppler ultrasonography (0, 8, 20 and 52 weeks). Results In the phantom assessment, the PIPOC software could detect changes in JSN with a smallest detectable difference of 0.044 mm at 0.1 mm intervals. In the clinical assessment, the JSW change of the joints with GSS progression detected by the software was significantly greater than those without GSS progression (p = 0.004). The JSW change of joints with positive SV at baseline was significantly higher than those with negative SV (p = 0.024). Conclusion Our in-house software equipped with PIPOC can automatically and quantitatively detect slight radiographic changes of JSW in clinically inactive RA patients.2022-12-19T15:00:00ZOkino, TaichiOu, YafeiIkebe, MasayukiTamura, KenichiSutherland, KennethFukae, JunTanimura, KazuhideKamishima, TamotsuPurpose We have developed an in-house software equipped with partial image phase-only correlation (PIPOC) which can automatically quantify radiographic joint space narrowing (JSN) progression. The purpose of this study was to evaluate the software in phantom and clinical assessments. Materials and methods In the phantom assessment, the software's performance on radiographic images was compared to the joint space width (JSW) difference using a micrometer as ground truth. A phantom simulating a finger joint was scanned underwater. In the clinical assessment, 15 RA patients were included. The software measured the radiological progression of the finger joints between baseline and the 52nd week. The cases were also evaluated with the Genant-modified Sharp score (GSS), a conventional visual scoring method. We also quantitatively assessed these joints' synovial vascularity (SV) on power Doppler ultrasonography (0, 8, 20 and 52 weeks). Results In the phantom assessment, the PIPOC software could detect changes in JSN with a smallest detectable difference of 0.044 mm at 0.1 mm intervals. In the clinical assessment, the JSW change of the joints with GSS progression detected by the software was significantly greater than those without GSS progression (p = 0.004). The JSW change of joints with positive SV at baseline was significantly higher than those with negative SV (p = 0.024). Conclusion Our in-house software equipped with PIPOC can automatically and quantitatively detect slight radiographic changes of JSW in clinically inactive RA patients.Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts
http://hdl.handle.net/2115/90789
Title: Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts
Authors: Gowda, Siddabasave Gowda B.; Gowda, Divyavani; Hou, Fengjue; Chiba, Hitoshi; Parcha, Vibhu; Arora, Pankaj; Halade, Ganesh V.; Hui, Shu-Ping
Abstract: Background and aims: Myocardial infarction (MI) is a leading cause of heart failure (HF). After MI, lipids undergo several phasic changes implicated in cardiac repair if inflammation resolves on time. However, if inflammation continues, that leads to end stage HF progression and development. Numerous studies have analyzed the traditional risk factors; however, temporal lipidomics data for human and animal models are limited. Thus, we aimed to obtain sequential lipid profiling from acute to chronic HF. Methods: Here, we report the comprehensive lipidome of the hearts from diseased and healthy subjects. To induce heart failure in mice, we used a non-reperfused model of coronary ligation, and MI was confirmed by echo-cardiography and histology, then temporal kinetics of lipids in different tissues (heart, spleen, kidney), and plasma was quantitated from heart failure mice and compared with naive controls. For lipid analysis in mouse and human samples, untargeted liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (LC-LTQ-Orbitrap MS) was performed. Results: In humans, multivariate analysis revealed distinct cardiac lipid profiles between healthy and ischemic subjects, with 16 lipid species significantly downregulated by 5-fold, mainly phosphatidylethanolamines (PE), in the ischemic heart. In contrast, PE levels were markedly increased in mouse tissues and plasma in chronic MI, indicating possible cardiac remodeling. Further, fold change analysis revealed site-specific lipid biomarkers for acute and chronic HF. A significant decrease in sulfatides (SHexCer (34:1; 2O)) and sphingomyelins (SM (d18:1/ 16:0)) was observed in mouse tissues and plasma in chronic HF. Conclusions: Overall, a significant decreased lipidome in human ischemic LV and differential lipid metabolites in the transition of acute to chronic HF with inter-organ communication could provide novel insights into targeting integrative pathways for the early diagnosis or development of novel therapeutics to delay/prevent HF.2022-11-30T15:00:00ZGowda, Siddabasave Gowda B.Gowda, DivyavaniHou, FengjueChiba, HitoshiParcha, VibhuArora, PankajHalade, Ganesh V.Hui, Shu-PingBackground and aims: Myocardial infarction (MI) is a leading cause of heart failure (HF). After MI, lipids undergo several phasic changes implicated in cardiac repair if inflammation resolves on time. However, if inflammation continues, that leads to end stage HF progression and development. Numerous studies have analyzed the traditional risk factors; however, temporal lipidomics data for human and animal models are limited. Thus, we aimed to obtain sequential lipid profiling from acute to chronic HF. Methods: Here, we report the comprehensive lipidome of the hearts from diseased and healthy subjects. To induce heart failure in mice, we used a non-reperfused model of coronary ligation, and MI was confirmed by echo-cardiography and histology, then temporal kinetics of lipids in different tissues (heart, spleen, kidney), and plasma was quantitated from heart failure mice and compared with naive controls. For lipid analysis in mouse and human samples, untargeted liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (LC-LTQ-Orbitrap MS) was performed. Results: In humans, multivariate analysis revealed distinct cardiac lipid profiles between healthy and ischemic subjects, with 16 lipid species significantly downregulated by 5-fold, mainly phosphatidylethanolamines (PE), in the ischemic heart. In contrast, PE levels were markedly increased in mouse tissues and plasma in chronic MI, indicating possible cardiac remodeling. Further, fold change analysis revealed site-specific lipid biomarkers for acute and chronic HF. A significant decrease in sulfatides (SHexCer (34:1; 2O)) and sphingomyelins (SM (d18:1/ 16:0)) was observed in mouse tissues and plasma in chronic HF. Conclusions: Overall, a significant decreased lipidome in human ischemic LV and differential lipid metabolites in the transition of acute to chronic HF with inter-organ communication could provide novel insights into targeting integrative pathways for the early diagnosis or development of novel therapeutics to delay/prevent HF.Bruton's tyrosine kinase is a possible therapeutic target in microscopic polyangiitis
http://hdl.handle.net/2115/90705
Title: Bruton's tyrosine kinase is a possible therapeutic target in microscopic polyangiitis
Authors: Nakade, Issei; Tamura, Yuto; Hashimoto, Fuyu; Ariza, Yuko; Hotta, Shingo; Fujigaya, Hirofumi; Arai, Suishin; Taniguchi, Mai; Ogawa, Hodaka; Nishibata, Yuka; Masuda, Sakiko; Nakazawa, Daigo; Tomaru, Utano; Ishizu, Akihiro
Abstract: Background: Bruton's tyrosine kinase (Btk) is an enzyme expressed in leukocytes other than T lymphocytes and plasma cells and involved in B-cell receptor- and Fcγ receptor (FcγR)-mediated signal transduction. Btk inhibitors potentially suppress autoantibody production due to the expected inhibitory ability of B lymphocyte differentiation into antibody-producing plasma cells and reduce FcγR-mediated neutrophil activation, including the release of neutrophil extracellular traps (NETs). Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis characterized by the pathogenic autoantibody, antineutrophil cytoplasmic antibody (ANCA) that reacts with myeloperoxidase (MPO). MPO and MPO-ANCA immune complex (IC)-induced FcγR-mediated NETs are critically involved in MPA pathogenesis. This study aimed to demonstrate the therapeutic efficacy of the Btk inhibitor tirabrutinib on MPA. Methods: Various doses of tirabrutinib or vehicle were orally administered to Sprague-Dawley rats daily. Four weeks later, the number of peripheral B lymphocytes was counted, and Btk phosphorylation in B lymphocytes was evaluated by flow cytometry. Human peripheral blood neutrophils were stimulated by MPO and anti-MPO antibody ICs (MPO and anti-MPO-ICs), and Btk and its downstream Vav phosphorylation were assessed by western blotting. The effects of tirabrutinib on MPO and anti-MPO-IC-induced NET formation were examined in vitro. Wistar Kyoto rats were immunized with human MPO to induce experimental MPA and given drug-free or tirabrutinib-containing feed (0.0037% or 0.012%) from day 0 or 28. All rats were euthanized on day 42 for serological and histological evaluation. Results: Tirabrutinib inhibited Btk phosphorylation without decreasing B lymphocytes in vivo. Neutrophil Btk and Vav were phosphorylated when stimulated with MPO and anti-MPO-ICs. Tirabrutinib suppressed MPO and anti-MPO-IC-induced NET formation in vitro and ameliorated experimental MPA in a dose-dependent manner in vivo. Although MPO-ANCA production was not affected, NET-forming neutrophils in the blood were significantly reduced by tirabrutinib. Conclusions: The Btk inhibitor tirabrutinib suppressed MPO and anti-MPO-IC-induced NET formation in vitro and ameliorated experimental MPA by reducing NET-forming neutrophils but not decreasing MPO-ANCA titer in vivo. This study suggests that Btk is a possible therapeutic target in MPA.2023-11-05T15:00:00ZNakade, IsseiTamura, YutoHashimoto, FuyuAriza, YukoHotta, ShingoFujigaya, HirofumiArai, SuishinTaniguchi, MaiOgawa, HodakaNishibata, YukaMasuda, SakikoNakazawa, DaigoTomaru, UtanoIshizu, AkihiroBackground: Bruton's tyrosine kinase (Btk) is an enzyme expressed in leukocytes other than T lymphocytes and plasma cells and involved in B-cell receptor- and Fcγ receptor (FcγR)-mediated signal transduction. Btk inhibitors potentially suppress autoantibody production due to the expected inhibitory ability of B lymphocyte differentiation into antibody-producing plasma cells and reduce FcγR-mediated neutrophil activation, including the release of neutrophil extracellular traps (NETs). Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis characterized by the pathogenic autoantibody, antineutrophil cytoplasmic antibody (ANCA) that reacts with myeloperoxidase (MPO). MPO and MPO-ANCA immune complex (IC)-induced FcγR-mediated NETs are critically involved in MPA pathogenesis. This study aimed to demonstrate the therapeutic efficacy of the Btk inhibitor tirabrutinib on MPA. Methods: Various doses of tirabrutinib or vehicle were orally administered to Sprague-Dawley rats daily. Four weeks later, the number of peripheral B lymphocytes was counted, and Btk phosphorylation in B lymphocytes was evaluated by flow cytometry. Human peripheral blood neutrophils were stimulated by MPO and anti-MPO antibody ICs (MPO and anti-MPO-ICs), and Btk and its downstream Vav phosphorylation were assessed by western blotting. The effects of tirabrutinib on MPO and anti-MPO-IC-induced NET formation were examined in vitro. Wistar Kyoto rats were immunized with human MPO to induce experimental MPA and given drug-free or tirabrutinib-containing feed (0.0037% or 0.012%) from day 0 or 28. All rats were euthanized on day 42 for serological and histological evaluation. Results: Tirabrutinib inhibited Btk phosphorylation without decreasing B lymphocytes in vivo. Neutrophil Btk and Vav were phosphorylated when stimulated with MPO and anti-MPO-ICs. Tirabrutinib suppressed MPO and anti-MPO-IC-induced NET formation in vitro and ameliorated experimental MPA in a dose-dependent manner in vivo. Although MPO-ANCA production was not affected, NET-forming neutrophils in the blood were significantly reduced by tirabrutinib. Conclusions: The Btk inhibitor tirabrutinib suppressed MPO and anti-MPO-IC-induced NET formation in vitro and ameliorated experimental MPA by reducing NET-forming neutrophils but not decreasing MPO-ANCA titer in vivo. This study suggests that Btk is a possible therapeutic target in MPA.