108 results on '"Keisuke Uchida"'
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2. Phonon transports in single-walled carbon nanotube films with different structures determined by tensile tests and thermal conductivity measurements
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Hisatoshi Yamamoto, Yutaro Okano, Keisuke Uchida, Makoto Kageshima, Toru Kuzumaki, Shugo Miyake, and Masayuki Takashiri
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Swcnts ,Tensile test ,Thermal conductivity ,Sound velocity ,Phonon MFP ,Chemistry ,QD1-999 - Abstract
The phonon transport properties of single-walled carbon nanotubes (SWCNTs) undergo significant changes when shaped into individuals, bundles, or films. Among these, SWCNT films are the most useful for industrial applications; however, their phonon transport properties have not been thoroughly investigated. This study estimated the phonon transport properties—specifically, the sound velocity, lattice thermal conductivity, and phonon mean free path (MFP)—of SWCNT films by conducting tensile tests and thermal conductivity measurements. The SWCNT films were prepared through vacuum filtering, with their structures modified by adjusting the ultrasonic dispersion amplitude during SWCNT ink production. The average sound velocity of the SWCNT films reached a maximum of 692 m/s at the lowest dispersion amplitude of 30 % (nominal value of 200 W), decreasing as the dispersion amplitude increased. The maximum values of lattice thermal conductivity and phonon MFP were 50.9 W/(m⋅K) and 119 nm, respectively, observed at dispersion amplitudes of 50 % and 90 %. These results arise from the complex interaction of factors such as defect density, mass density, SWCNT bundle diameter, and SWCNT length. This analytical method provides a straightforward approach to determine the detailed phonon transport properties of CNT films.
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- 2024
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3. Urinary isoxanthopterin as a novel predictor following catheter ablation for atrial fibrillation
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Takahisa Koi, Naoya Kataoka, Keisuke Uchida, Teruhiko Imamura, and Koichiro Kinugawa
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atrial fibrillation ,atrial tachyarrhythmias ,oxidative stress ,urinary isoxanthopterin ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Oxidative stress is associated with atrial fibrillation recurrence following catheter ablation. Urinary isoxanthopterin (U‐IXP) is one of the noninvasive markers which reflect the reactive oxygen species; however, its ability to predict atrial tachyarrhythmias (ATAs) occurrence following catheter ablation remains uncertain. Methods Among the patients who received scheduled catheter ablation for atrial fibrillation, baseline U‐IXP levels were measured just before the procedure. The prognostic impact of baseline U‐IXP upon postprocedural ATAs occurrence was investigated. Results Among 107 patients (71 years old, 68% men), baseline U‐IXP level was 0.33 nmol/gCr on the median. During a mean of 603 days of follow‐up, 32 patients had ATAs. Baseline higher U‐IXP was independently associated with the occurrence of ATAs following catheter ablation with a hazard ratio of 4.69 (95% confidence interval: 1.82–12.37, p = .001) adjusted for the left atrial diameter, a persistent type, and hypertension which were potential confounders, with a cutoff of 0.46 nmol/gCr, which stratified cumulative incidence of ATAs occurrence ( p
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- 2023
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4. Machine learning-assisted medium optimization revealed the discriminated strategies for improved production of the foreign and native metabolites
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Honoka Aida, Keisuke Uchida, Motoki Nagai, Takamasa Hashizume, Shunsuke Masuo, Naoki Takaya, and Bei-Wen Ying
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Production ,Medium ,Synthetic pathway ,Machine learning ,Bacterial growth ,Aromatic compound ,Biotechnology ,TP248.13-248.65 - Abstract
The composition of medium components is crucial for achieving the best performance of synthetic construction in genetically engineered cells. Which and how medium components determine the performance, e.g., productivity, remain poorly investigated. To address the questions, a comparative survey with two genetically engineered Escherichia coli strains was performed. As a case study, the strains carried the synthetic pathways for producing the aromatic compounds of 4-aminophenylalanine (4APhe) or tyrosine (Tyr), common in the upstream but differentiated in the downstream metabolism. Bacterial growth and compound production were examined in hundreds of medium combinations that comprised 48 pure chemicals. The resultant data sets linking the medium composition to bacterial growth and production were subjected to machine learning for improved production. Intriguingly, the primary medium components determining the production of 4PheA and Tyr were differentiated, which were the initial resource (glucose) of the synthetic pathway and the inducer (IPTG) of the synthetic construction, respectively. Fine-tuning of the primary component significantly increased the yields of 4APhe and Tyr, indicating that a single component could be crucial for the performance of synthetic construction. Transcriptome analysis observed the local and global changes in gene expression for improved production of 4APhe and Tyr, respectively, revealing divergent metabolic strategies for producing the foreign and native metabolites. The study demonstrated that ML-assisted medium optimization could provide a novel point of view on how to make the synthetic construction meet the designed working principle and achieve the expected biological function.
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- 2023
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5. Adverse Events Requiring Hospitalization Following Catheter Ablation for Atrial Fibrillation in Heart Failure with versus without Systolic Dysfunction
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Naoya Kataoka, Teruhiko Imamura, Takahisa Koi, Keisuke Uchida, and Koichiro Kinugawa
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heart failure ,atrial fibrillation ,catheter ablation ,major bleeding ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: The safety and efficacy of atrial fibrillation (AF) ablation in individuals with heart failure (HF) with preserved ejection fraction (EF), particularly concerning the occurrence of post-procedural adverse events necessitating hospitalization, including anticoagulant-associated major bleeding, still lack conclusive determination. Methods: Data from patients with HF and AF who underwent catheter ablation for AF between 2019 and 2022 at our institution were retrospectively reviewed. All participants were divided into an EF < 50% group or an EF ≥ 50% group according to their baseline left ventricular EF. The composite incidence of the clinical events following catheter ablation was compared between the two groups: (1) all-cause death, (2) HF hospitalization, (3) stroke or systemic embolism, and (4) major bleeding. Results: A total of 122 patients (75 years old, 68 male) were included. Of them, 62 (50.8%) patients had an EF ≥ 50%. EF ≥ 50% was an independent predictor of the composite endpoint (adjusted odds ratio 6.07, 95% confidence interval 1.37–26.99, p = 0.018). The incidences of each adverse event were not significantly different between the two groups, except for a higher incidence of major bleeding in the EF ≥ 50% group (12.7% vs. 0%, p = 0.026). Conclusions: Among patients with HF coupled with AF, the incidence of adverse events following AF ablation proved notably elevated in patients with EF ≥ 50% in contrast to their counterparts with EF < 50%. This disparity primarily stems from a heightened occurrence of major bleeding within the EF ≥ 50% cohort. The strategy to reduce adverse events, especially in patients with EF ≥ 50%, remains the next concern.
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- 2024
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6. A novel mutation in early‐onset sarcoidosis/Blau syndrome: an association with Propionibacterium acnes
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Fumiko Okazaki, Hiroyuki Wakiguchi, Yuno Korenaga, Tamaki Nakamura, Hiroki Yasudo, Shohei Uchi, Ryoji Yanai, Nobuyuki Asano, Yoshinobu Hoshii, Tsuyoshi Tanabe, Kazushi Izawa, Yoshitaka Honda, Ryuta Nishikomori, Keisuke Uchida, Yoshinobu Eishi, Shouichi Ohga, and Shunji Hasegawa
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D512V mutation ,Granulomatous disease ,Methotrexate ,NF-κB ,NOD2 ,Cutibacterium acnes ,Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Early-onset sarcoidosis (EOS) and Blau syndrome (BS) are systemic inflammatory granulomatous diseases without visible pulmonary involvement, and are distinguishable from their sporadic and familial forms. The diseases are characterized by a triad of skin rashes, symmetrical polyarthritis, and recurrent uveitis. The most common morbidity is ocular involvement, which is usually refractory to conventional treatment. A gain-of-function mutation in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been demonstrated in this disease; however, little is known about the relationship between the activation of NOD2 and the pathophysiology of EOS/BS. Here we describe EOS/BS with a novel mutation in the NOD2 gene, as well as detection of Propionibacterium acnes (P. acnes) in the granulomatous inflammation. Case presentation An 8-year-old Japanese girl presented with refractory bilateral granulomatous panuveitis. Although no joint involvement was evident, she exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis, and P. acnes was detected within the sarcoid granulomas by immunohistochemistry with P. acnes-specific monoclonal (PAB) antibody. Genetic analyses revealed that the patient had a NOD2 heterozygous D512V mutation that was novel and not present in either of her parents. The mutant NOD2 showed a similar activation pattern to EOS/BS, thus confirming her diagnosis. After starting oral prednisolone treatment, she experienced an anterior vitreous opacity relapse despite gradual prednisolone tapering; oral methotrexate was subsequently administered, and the patient responded positively. Conclusions We presented a case of EOS/BS with a novel D512V mutation in the NOD2 gene. In refractory granulomatous panuveitis cases without any joint involvement, EOS/BS should be considered as a differential diagnosis; genetic analyses would lead to a definite diagnosis. Moreover, this is the first report of P. acnes demonstrated in granulomas of EOS/BS. Since intracellular P. acnes activates nuclear factor-kappa B in a NOD2-dependent manner, we hypothesized that the mechanism of granuloma formation in EOS/BS may be the result of NOD2 activity in the presence of the ligand muramyl dipeptide, which is a component of P. acnes. These results indicate that recognition of P. acnes through mutant NOD2 is the etiology in this patient with EOS/BS.
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- 2021
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7. Propionibacterium acnes-associated sarcoidosis complicated by acute bird-related hypersensitivity pneumonitis
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Michiru Sawahata, Noritaka Sakamoto, Hideaki Yamasawa, Yuki Iijima, Hirotoshi Kawata, Tetsuo Yamaguchi, Keisuke Uchida, Yoshinobu Eishi, Masashi Bando, and Koichi Hagiwara
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Sarcoidosis ,Hypersensitivity pneumonitis ,Granulomatous disease ,Bird fancier’s lung ,Non-caseating epithelioid granuloma ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background The number of reports on sarcoidosis complicated by hypersensitivity pneumonitis (HP) is limited, and most describe cases complicated by chronic bird-related HP. Here, we present for the first time a case with Propionibacterium acnes-associated sarcoidosis complicated by acute bird-related HP. Case presentation A 62-year-old man with a past medical history of sarcoidosis was admitted to our department, and chest computed tomography showed diffuse ground-glass opacities, which appeared as he rapidly increased the number of pigeons he kept for a competition. Random transbronchial lung biopsy revealed well-formed non-caseating epithelioid granulomas, which contained positively stained substances on immunohistochemistry using the PAB antibody, a specific monoclonal antibody against P. acnes lipoteichoic acid. Poorly formed non-caseating granulomas without positively stained substances were also detected. Conclusion We describe the successful identification of this exceptionally rare case of sarcoidosis complicated by acute bird-related HP in which two morphologically and immunohistologically different types of granulomas were present in the same lung.
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- 2020
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8. Immunohistochemical Differentiation between Western and East Asian Types of CagA-Positive Helicobacter pylori in Gastric Biopsy Samples
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Daisuke Kobayashi, Keisuke Uchida, Asuka Furukawa, Takashi Ito, Luis Masuo Maruta, Heinrich Bender Kohnert Seidler, Aloisio Felipe-Silva, Masaki Sekine, Noboru Ando, Yuka Toyama, Yusuke Chino, Keiko Miura, Kurara Yamamoto, Takumi Akashi, Yoshinobu Eishi, and Kenichi Ohashi
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background. Cag A-positive Helicobacter pylori isolated from human gastric mucosa is categorized as a Western or East Asian allele-type based on whether the cagA gene encodes an EPIYA-C or EPIYA-D motif. We aimed to differentiate between the 2 types of H. pylori by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) gastric biopsy samples. Materials and Methods. We developed 2 monoclonal antibodies (mAbs) that detect either the EPIYA-C or EPIYA-D motif of the H. pylori CagA protein by IHC using FFPE tissues. FFPE tissue sections from 30 Japanese and 39 Brazilian gastric biopsy samples with H. pylori infection confirmed by Giemsa staining (moderate/severe in the Sydney classification system) were examined by IHC with the novel mAbs followed by polymerase chain reaction (PCR) for EPIYA-C or EPIYA-D using DNA extracted from adjacent tissue sections. Results. Differentiation among Western and East Asian types and CagA-negative H. pylori was successful in most (97%) samples by IHC with the novel mAbs and commercially available mAbs that react with a species-specific lipopolysaccharide or a common CagA motif of H. pylori. The detection status of EPIYA-C/D motifs by IHC with the novel mAbs was consistent with the PCR results in 61 (88%) of 69 samples: EPIYA-C(+)/D(−) in zero Japanese and 26 Brazilian samples, EPIYA-C(−)/D(+) in 26 Japanese and 1 Brazilian sample, and EPIYA-C(−)/D(−) in 1 Japanese and 7 Brazilian samples. The detection sensitivity and specificity of IHC with each novel mAb compared with the PCR results were, respectively, 84% and 97% for EPIYA-C, and 97% and 95% for EPIYA-D. Conclusions. The novel mAbs specific to each EPIYA-C or EPIYA-D motif differentiated between Western and East Asian types of CagA-positive H. pylori by IHC using FFPE tissues. Applying these novel mAbs to large numbers of archived pathology samples will contribute to elucidating the association of these allele types with gastric cancer.
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- 2022
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9. Propionibacterium acnes-associated chronic hypertrophic pachymeningitis followed by refractory otitis media: a case report
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Eiichiro Amano, Keisuke Uchida, Tasuku Ishihara, Shinichi Otsu, Akira Machida, and Yoshinobu Eishi
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Propionibacterium acnes ,Otitis media ,Pachymeningitis ,Mastoiditis ,Dura mater ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Hypertrophic pachymeningitis (HP) is a rare disorder that involves localized or diffuse thickening of the dura mater. HP is associated with various inflammatory, infectious, and malignant diseases, such as rheumatic arthritis, sarcoidosis, anti-neutrophil cytoplasmic antibody-associated vasculitis, IgG4-related disorders, syphilis, tuberculosis, bacterial and fungal infections, cancer, and idiopathic diseases, when evaluation fails to reveal a cause. Among them, chronic infection with Propionibacterium acnes is a rare etiology of HP, and its pathology remains unclear. Case presentation An 80-year-old man having refractory otitis media with effusion of the right ear presented with progressive right-sided headache and nausea. Post-contrast brain magnetic resonance imaging revealed right mastoiditis and remarkable thickening of the dura mater and enhancement of pia mater extending from the right middle cranial fossa to the temporal lobe. HP secondary to middle ear infection was suspected, and a biopsy of the right mastoid was performed. An anaerobic culture of the biopsied right mastoid showed the growth of P. acnes, and histopathological examination using P. acnes-specific monoclonal antibody (PAB antibody) revealed the infiltration of inflammatory cells with P. acnes. Moreover, using PAB antibody, P. acnes was detected in the biopsy specimen of the thickening dura mater. No granulomas were identified in either specimen. HP was resolved with long-term administration of antibiotics and steroids. Conclusion This is the first documentation of pathologically demonstrated chronic HP associated with P. acnes infection followed by refractory otitis media. This report showed that chronic latent P. acnes infection induces chronic inflammation.
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- 2020
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10. Presence of Propionibacterium acnes in granulomas associates with a chronic disease course in Dutch sarcoidosis patients
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Els Beijer, Kees Seldenrijk, Yoshinobu Eishi, Keisuke Uchida, Jan Damen, Jan C. Grutters, and Marcel Veltkamp
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Medicine - Abstract
Several studies demonstrated that Propionibacterium acnes may be involved in sarcoidosis pathogenesis. Presence of P. acnes was found in granulomas of the majority of Japanese sarcoidosis patients. However, presence of P. acnes in tissue has never been related to sarcoidosis phenotypes and clinical outcome. Therefore, the aims of our study were to demonstrate whether P. acnes can be detected in granulomas of Dutch sarcoidosis patients and to investigate whether its presence is related to a clinical phenotype and/or course of disease. Sections of formalin-fixed paraffin-embedded tissue blocks of 76 sarcoidosis patients were examined by immunostaining with a P. acnes-specific monoclonal antibody (PAB antibody) using a Ventana BenchMark ULTRA. Clinical outcome status (COS) was determined and classified into two phenotype groups: A: resolved, minimal or persistent disease without treatment (COS 1–6) and B: persistent disease with need for treatment (COS 7–9). P. acnes was detected in samples of 31 patients (41%) and located within granulomas in samples of 13 patients (17%). The frequency of P. acnes detected in granulomas at diagnosis was significantly higher in patients with phenotype B compared to patients with phenotype A (29% versus 0%, p=0.021). Presence of P. acnes in granulomas can be confirmed in Dutch sarcoidosis patients. It is intriguing that presence of P. acnes in granulomas is more frequently found in patients with chronic disease requiring treatment. This adds to the rationale that a subgroup of sarcoidosis patients might benefit from antibiotic therapy.
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- 2021
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11. Pathological and Tissue-Based Molecular Investigation of Granulomas in Cichlids Reared as Ornamental Fish
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Luciana Mandrioli, Victorio Codotto, Giulia D’Annunzio, Enrico Volpe, Francesca Errani, Yoshinobu Eishi, Keisuke Uchida, Maria Morini, Giuseppe Sarli, and Sara Ciulli
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Cutibacterium acnes ,debilitating disease ,granuloma ,immunohistochemistry ,Mycobacteria ,ornamental fish ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Cichlids include hundreds of species with a high economic value for aquaculture. These fish are subjected to intensive trade and farming that expose them to the risk of infectious diseases. This work focuses on ornamental cichlids held in an aquarium commercial facility presenting emaciation, in order to evaluate the presence of lesions in fish skin and organs. The fish were sampled during routine management activities and subjected to pathological and molecular investigations. The presence of lymphocystis disease virus, typically associated with cutaneous nodular disease, was ruled out. Histologically, they presented granulomas in the spleen, sometimes extending to the other visceral organs. Bacterial heat-shock protein 65 PCR products were detected in tissues associated, in the majority of cases, with granulomas; molecular investigation identified Mycobacterium spp. in two cases and Cutibacterium acnes in seven cases. Immunoreactivity to anti-Mycobacterium and anti-C. acnes antibodies was detected within granulomas. The presence of C. acnes within granuloma is elucidated for the first time in fish; however, similarly to what is found in humans, this bacterium could be harmless in normal conditions, whereas other contributing factors would be required to trigger a granulomatogenous response. Further confirmation by bacterial culture, as well as using large-scale studies in more controlled situations, is needed.
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- 2022
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12. Annular Sarcoidosis with Geographic Appearance in a Patient with Systemic Sarcoidosis
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Hiroyuki Takama, Yuichiro Ohshima, Yoriko Ando, Takeshi Yanagishita, Emiko Takahashi, Toyonori Tsuzuki, Keisuke Uchida, Yoshinobu Eishi, Masashi Akiyama, and Daisuke Watanabe
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cutaneous sarcoidosis ,propionibacterium acnes ,elastic fiber ,annular elastolytic giant cell granuloma ,Dermatology ,RL1-803 - Abstract
Abstract is missing (Short communication)
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- 2020
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13. N2 activation on a molybdenum–titanium–sulfur cluster
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Yasuhiro Ohki, Keisuke Uchida, Mizuki Tada, Roger E. Cramer, Takashi Ogura, and Takehiro Ohta
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Science - Abstract
Nitrogenase—whose cofactor consists of a metal–sulfur cluster—catalyzes the production of NH3 from N2, but designing metal–sulfur complexes capable of promoting this conversion remains challenging. Here, the authors report on the activation of N2 by a metal–sulfur cluster containing [Mo3S4Ti] cubes, demonstrating NH3 and N2H4 production.
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- 2018
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14. Propionibacterium acnes-Derived Circulating Immune Complexes in Sarcoidosis Patients
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Keisuke Uchida, Asuka Furukawa, Akiko Yoneyama, Haruhiko Furusawa, Daisuke Kobayashi, Takashi Ito, Kurara Yamamoto, Masaki Sekine, Keiko Miura, Takumi Akashi, Yoshinobu Eishi, and Kenichi Ohashi
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sarcoidosis ,Propionibacterium acnes ,Cutibacterium acnes ,lipoteichoic acid ,infectious antibody ,immune complex ,Biology (General) ,QH301-705.5 - Abstract
Propionibacterium acnes is a potential etiologic agent of sarcoidosis and a dysregulated immune response to the commensal bacterium is suspected to cause granuloma formation. P. acnes-derived insoluble immune complexes were recently demonstrated in sinus macrophages of sarcoidosis lymph nodes, suggesting local proliferation of the bacterium in affected organs. In the present study, we developed a method for detecting P. acnes-derived immune complexes in human blood by measuring the concentration of P. acnes-specific lipoteichoic acid (PLTA) detectable after an antigen retrieval pretreatment of plasma samples. Before pretreatment, anti-PLTA antibody was detected and PLTA could not be detected, in all plasma samples from 51 sarcoidosis patients and 35 healthy volunteers. After pretreatment, however, a significant level of PLTA (>105 ng/mL) was detected in 33 (65%) sarcoidosis patients and 5 (14%) control subjects, with 86% specificity and 65% sensitivity for sarcoidosis. In both groups, plasma anti-PLTA antibody titers did not differ between samples with and without detection of PLTA. PLTA levels were abnormally increased (>202 ng/mL) in 21 (41%) sarcoidosis patients. These findings suggest that P. acnes-derived circulating immune complexes present in human blood are abnormally increased in many sarcoidosis patients, presumably due to local proliferation of the bacterium in the affected organs.
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- 2021
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15. A Simple Predictive Marker in Cardiac Resynchronization Therapy Recipients: Prominent S-Wave in Right Precordial Leads
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Naoya Kataoka, Teruhiko Imamura, Takahisa Koi, Keisuke Uchida, and Koichiro Kinugawa
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heart failure ,cardiac resynchronization therapy ,QRS amplitude ,Medicine (General) ,R5-920 - Abstract
Background and objectives: Current guidelines criteria do not satisfactorily discriminate responders to cardiac resynchronization therapy (CRT). QRS amplitude is an established index to recognize the severity of myocardial disturbance and might be a key to optimal patient selection for CRT. Materials and Methods: (1) Initial R-wave amplitude, (2) S-wave amplitude, and (3) a summation of maximal R- or R′-wave amplitude and S-wave amplitude were measured at baseline. These parameters were averaged according to right (V1 to V3) or left (V4 to V6) precordial leads. The impact of these parameters on response to CRT, which was defined as a decrease in left ventricular end-systolic volume ≥15% at six-month follow-up, was investigated. Results: Among 47 patients (71 years old, 28 men) who received guideline-indicated CRT implantation, 25 (53%) achieved the definition of CRT responder. Among baseline electrocardiogram parameters, only the higher S-wave amplitude in right precordial leads was an independent predictor of CRT responders (odds ratio: 2.181, 95% confidence interval: 1.078–4.414, p = 0.030) at a cutoff of 1.44 mV. The cutoff was independently associated with cumulative incidence of heart failure readmission and appropriate electrical defibrillation following CRT implantation (p < 0.05, respectively). Conclusions: Prominent S-wave in right precordial leads might be a promising index to predict left ventricular reverse remodeling and greater clinical outcomes following CRT implantation.
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- 2021
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16. Immunohistochemical Detection of Propionibacterium acnes in Granulomas for Differentiating Sarcoidosis from Other Granulomatous Diseases Utilizing an Automated System with a Commercially Available PAB Antibody
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Takuma Isshiki, Sakae Homma, Yoshinobu Eishi, Matsuko Yabe, Kazuya Koyama, Yasuhiko Nishioka, Tetsuo Yamaguchi, Keisuke Uchida, Kurara Yamamoto, Kenichi Ohashi, Atsushi Arakawa, Kazutoshi Shibuya, Susumu Sakamoto, and Kazuma Kishi
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sarcoidosis ,granuloma ,pathogenesis ,P. acnes ,Propionibacterium acnes ,Cutibacterium acnes ,Biology (General) ,QH301-705.5 - Abstract
Propionibacterium acnes is implicated in the pathogenesis of sarcoidosis. We investigated the usefulness of immunohistochemistry (IHC) with a commercially available P. acnes-specific monoclonal antibody (PAB antibody) for differentiating sarcoidosis from other granulomatous diseases. Formalin-fixed paraffin-embedded tissue samples from 94 sarcoidosis patients and 30 control patients with other granulomatous diseases were examined by the original manual IHC method. We also compared the detection frequency of P. acnes in sarcoid granulomas between manual and automated IHC methods. P. acnes was detected in sarcoid granulomas of samples obtained by transbronchial lung biopsy (64%), video-associated thoracic surgery (67%), endobronchial-ultrasound-guided transbronchial-needle aspiration (32%), lymph node biopsy (80%), and skin biopsy (80%) from sarcoidosis patients, but not in any non-sarcoid granulomas of the samples obtained from control patients. P. acnes outside granulomas, however, was frequently detected in both groups. The detection status of P. acnes in granulomas did not correlate with the clinical characteristics of sarcoidosis patients. The automated Leica system exhibited the best detection sensitivity (72%) and almost an identical localization for P. acnes in sarcoid granulomas compared with the manual method. IHC with a PAB antibody is useful for differentiating sarcoidosis from other granulomatous diseases by detecting P. acnes in granulomas. An automated method by the Leica system can be used in pathology laboratories for differential diagnosis of granulomas by IHC with the PAB antibody.
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- 2021
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17. Protein antigen of bird-related hypersensitivity pneumonitis in pigeon serum and dropping
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Tsuyoshi Shirai, Haruhiko Furusawa, Asuka Furukawa, Yuki Ishige, Keisuke Uchida, Yasunari Miyazaki, Yoshinobu Eishi, and Naohiko Inase
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Hypersensitivity pneumonitis ,Extrinsic allergic alveolitis ,Bird ,Pigeon ,Antigen ,Protein of immunoglobulin-superfamily ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Avian antigen is a common cause of hypersensitivity pneumonitis (HP). Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits a hypersensitivity reaction in patients with bird-related hypersensitivity pneumonitis (BRHP), but the antigenic components in these materials have yet to be fully elucidated. Method Pigeon serum, pigeon intestine homogenates, and PDE were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers. Among the protein spots found in both pigeon serum and PDE, those that reacted with sera from BRHP patients were identified by mass spectrometry. Immunoassays using recombinant protein were performed to confirm the antigenicity of the identified protein. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant protein was also assessed. Results Immunoglobulin lambda-like polypeptide-1 (IGLL-1) was identified from all spots on 2-DE immunoblots of both pigeon serum and PDE. The BRHP patients exhibited higher levels of serum IgG antibody against the recombinant IGLL-1 (rIGLL-1) compared to the control subjects, as well as a stronger PBMCs proliferative response to rIGLL-1. Cytokine production by PBMCs from BRHP patients after rIGLL-1 exposure indicated that the protein could induce Th1 prone immune responses: an increase in TNF-α and an absence of elevated IL-10 production. Conclusions Pigeon IGLL-1 was identified as the BRHP antigen present in both pigeon serum and PDE.
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- 2017
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18. Primary sarcoidosis of the breast, a case study in connection with Propionibacterium acnes infection
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Yoshifumi Matsushita, Keisuke Uchida, Emi Takazaki, Nobuaki Hirose, and Yoshinobu Eishi
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Pathology ,RB1-214 - Abstract
A 77-year-old female underwent screening mammography with abnormal results. Core needle biopsy revealed a granulomatous lesion without necrosis, and sarcoidosis was considered although tuberculosis and granulomatous mastitis could not be ruled out. Three months later, the patient detected breast and axillary masses. Malignancy was suspected and both lesions were excised. The specimens contained epithelioid cell granulomas with no necrosis. Her angiotensin-converting enzyme level was normal, and radiographic examination revealed no evidence of involvement of other organs, including the lungs and mediastinal lymph nodes. Although sarcoidosis was highly suspected, it was not definitive. Immunohistochemistry with the PAB antibody, which specifically reacts with Propionibacterium acnes, the most commonly implicated causative agent of sarcoidosis, showed positive signals in granulomatous inflammation of the breast and within granulomas of the sentinel lymph node. This is the first case report of primary sarcoidosis of the breast involving the draining lymph node with confirmed P. acnes infection. Keywords: Immunohistochemistry, Mammary sarcoidosis, Isolated sarcoidosis, PAB antibody, Granulomatous mastitis, Tuberculosis mastitis
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- 2017
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19. Propionibacterium acnes-derived insoluble immune complexes in sinus macrophages of lymph nodes affected by sarcoidosis.
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Yoshimi Suzuki, Keisuke Uchida, Tamiko Takemura, Masaki Sekine, Tomoki Tamura, Asuka Furukawa, Akira Hebisawa, Yumi Sakakibara, Nobuyasu Awano, Tomonari Amano, Daisuke Kobayashi, Mariko Negi, Tomoya Kakegawa, Yuriko Wada, Takashi Ito, Takashige Suzuki, Takumi Akashi, and Yoshinobu Eishi
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Medicine ,Science - Abstract
Propionibacterium acnes is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect P. acnes-derived immune complexes in sarcoid lesions.We evaluated formalin-fixed and paraffin-embedded lymph node samples from 38 sarcoidosis patients and 90 non-sarcoidosis patients (27 patients with necrotizing lymphadenitis, 28 patients with reactive lymphadenitis, 16 patients with colon cancer, 19 patients with gastric cancer) by immunohistochemistry using anti-human immunoglobulins (IgG, IgA, and IgM) and complement (C1q and C3c) antibodies, and a P. acnes-specific monoclonal antibody (PAB antibody) that reacts with the membrane-bound lipoteichoic acid of P. acnes.Small round bodies (SRBs) bound to IgA, IgM, or IgG were detected in sinus macrophages, in 32 (84%), 32 (84%), or 11 (29%) sarcoid samples, respectively, and in 19 (21%), 26 (29%), or no (0%) control samples, respectively. Some of these insoluble immune complexes (IICs) also bound to C1q and C3c. We developed a microwave treatment followed by brief trypsin digestion (MT treatment) to detect PAB-reactive SRBs bound to immunoglobulins (IIC-forming P. acnes). MT treatment revealed abundant IIC-forming P. acnes in most (89%) of the sarcoid samples and sparse distribution in some (20%) of the control samples with lymphadenitis, but no IIC-forming P. acnes was detected in control samples without inflammation. IIC-forming P. acnes were mostly bound to both IgA and IgM. The PAB-reactive antigen and immunoglobulins were both located at the peripheral rim of the IIC-forming P. acnes. Conventional electron microscopy identified many SRBs (0.5-2.0 μm diameter) in sinus macrophages of sarcoid lymph nodes with many IIC-forming P. acnes, some of which were in phagolysosomes with a degraded and lamellar appearance.P. acnes-derived IICs in sinus macrophages were frequent and abundant in sarcoid lymph nodes, suggesting a potential etiologic link between sarcoidosis and this commensal bacterium.
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- 2018
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20. Immunohistochemical identification of Propionibacterium acnes in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients.
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Naoya Asakawa, Keisuke Uchida, Mamoru Sakakibara, Kazunori Omote, Keiji Noguchi, Yusuke Tokuda, Kiwamu Kamiya, Kanako C Hatanaka, Yoshihiro Matsuno, Shiro Yamada, Kyoko Asakawa, Yuichiro Fukasawa, Toshiyuki Nagai, Toshihisa Anzai, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Masanori Hirota, Makoto Orii, Takashi Akasaka, Kenta Uto, Yasushige Shingu, Yoshiro Matsui, Shin-Ichiro Morimoto, Hiroyuki Tsutsui, and Yoshinobu Eishi
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Medicine ,Science - Abstract
BACKGROUND:Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect Propionibacterium acnes, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients. METHODS AND RESULTS:We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P. acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (≥14 inflammatory cells) and minimal (
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- 2017
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21. Frequency of Propionibacterium acnes Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers.
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Tomoya Kakegawa, Yuan Bae, Takashi Ito, Keisuke Uchida, Masaki Sekine, Yutaka Nakajima, Asuka Furukawa, Yoshimi Suzuki, Jiro Kumagai, Takumi Akashi, and Yoshinobu Eishi
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Medicine ,Science - Abstract
Propionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative.We retrospectively collected the first and last prostate biopsy samples from 44 patients that were diagnosed PCa within 4 years after the first negative biopsy and from 36 control patients with no PCa found in repeated biopsy for at least 3 years after the first biopsy. We evaluated P. acnes-positive gland frequency and P. acnes-positive macrophage number using enzyme-immunohistochemistry with a P. acnes-specific monoclonal antibody (PAL antibody).The frequency of P. acnes-positive glands was higher in PCa samples than in control samples in both first biopsy samples and in combined first and last biopsy samples (P < 0.001). A frequency greater than the threshold (18.5 and 17.7, respectively) obtained by each receiver operating characteristic curve was an independent risk factor for PCa (P = 0.003 and 0.001, respectively) with odds ratios (14.8 and 13.9, respectively) higher than those of serum PSA titers of patients just before each biopsy (4.6 and 2.3, respectively). The number of P. acnes-positive macrophages did not differ significantly between PCa and control samples.These results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased PSA titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies.
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- 2017
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22. Biomechanical Study of Lumbar Spine using Unilateral Pedicle Screw with Tadpole Fixation System
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Takamasa YOSHIKAWA, Suguru OI, Yuichi KASAI, Wang ZHUO, Tadashi INABA, Keisuke UCHIDA, Ryuji WATANABE, Takaya KATO, and Tkaaki NAKAMATA
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unilateral pedicle screw and rod system ,tadpole system ,minimally invasive surgery ,spine biomechanics ,unstable lumbar spine ,Science ,Mechanical engineering and machinery ,TJ1-1570 - Abstract
The purpose of this study was to investigate the biomechanical stability of unilateral pedicle screw and rod system fixation (unilateral PS fixation) using the Tadpole system fixation for an unstable lumbar spine. We used 5 lumbar spines (L3/4) of a functional spinal unit (FSU) obtained from wild boar cadaver specimens. Damage or instrumentation was sequentially administered to each specimen, and 6 models were prepared: (1) an intact model, (2) an injury model with facet joint resection, (3) a unilateral PS fixation model, (4) a bilateral PS fixation model, (5) a Tadpole system fixation model, and (6) a combination of the unilateral PS and Tadpole system fixation models. We conducted a bending test in 8 directions by using a 6-axis material tester, and the range of motion (ROM) of each model in all directions was measured. The ROM of the combined fixation model of the unilateral PS and Tadpole system was considerably decreased in all directions. These findings indicate that the combination unilateral PS and Tadpole system fixation is a minimally invasive method that has the same stability as bilateral PS fixation.
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- 2011
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23. Autophagy Induced by Intracellular Infection of Propionibacterium acnes.
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Teruko Nakamura, Asuka Furukawa, Keisuke Uchida, Tomohisa Ogawa, Tomoki Tamura, Daisuke Sakonishi, Yuriko Wada, Yoshimi Suzuki, Yuki Ishige, Junko Minami, Takumi Akashi, and Yoshinobu Eishi
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Medicine ,Science - Abstract
BACKGROUND:Sarcoidosis is caused by Th1-type immune responses to unknown agents, and is linked to the infectious agent Propionibacterium acnes. Many strains of P. acnes isolated from sarcoid lesions cause intracellular infection and autophagy may contribute to the pathogenesis of sarcoidosis. We examined whether P. acnes induces autophagy. METHODS:Three cell lines from macrophages (Raw264.7), mesenchymal cells (MEF), and epithelial cells (HeLa) were infected by viable or heat-killed P. acnes (clinical isolate from sarcoid lymph node) at a multiplicity of infection (MOI) of 100 or 1000 for 1 h. Extracellular bacteria were killed by washing and culturing infected cells with antibiotics. Samples were examined by colony assay, electron-microscopy, and fluorescence-microscopy with anti-LC3 and anti-LAMP1 antibodies. Autophagy-deficient (Atg5-/-) MEF cells were also used. RESULTS:Small and large (≥5 μm in diameter) LC3-positive vacuoles containing few or many P. acnes cells (LC3-positive P. acnes) were frequently found in the three cell lines when infected by viable P. acnes at MOI 1000. LC3-positive large vacuoles were mostly LAMP1-positive. A few small LC3-positive/LAMP1-negative vacuoles were consistently observed in some infected cells for 24 h postinfection. The number of LC3-positive P. acnes was decreased at MOI 100 and completely abolished when heat-killed P. acnes was used. LC3-positive P. acnes was not found in autophagy-deficient Atg5-/- cells where the rate of infection was 25.3 and 17.6 times greater than that in wild-type Atg5+/+ cells at 48 h postinfection at MOI 100 and 1000, respectively. Electron-microscopic examination revealed bacterial cells surrounded mostly by a single-membrane including the large vacuoles and sometimes a double or multi-layered membrane, with occasional undigested bacterial cells in ruptured late endosomes or in the cytoplasm. CONCLUSION:Autophagy was induced by intracellular P. acnes infection and contributed to intracellular bacterial killing as an additional host defense mechanism to endocytosis or phagocytosis.
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- 2016
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24. Intracellular Propionibacterium acnes infection in glandular epithelium and stromal macrophages of the prostate with or without cancer.
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Yuan Bae, Takashi Ito, Tadatsune Iida, Keisuke Uchida, Masaki Sekine, Yutaka Nakajima, Jiro Kumagai, Tetsuji Yokoyama, Hiroshi Kawachi, Takumi Akashi, and Yoshinobu Eishi
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Medicine ,Science - Abstract
BACKGROUND: Recent reports on Propionibacterium acnes (P. acnes) suggest that this bacterium is prevalent in the prostate, is associated with acute and chronic prostatic inflammation, and might have a role in prostate carcinogenesis. METHODS: To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in radical prostatectomy specimens using enzyme immunohistochemistry with a novel P. acnes-specific monoclonal antibody (PAL antibody), together with an anti-nuclear factor-kappa B (NF-κB) antibody. We examined formalin-fixed and paraffin-embedded tissue sections of radical prostatectomy specimens from 28 patients with prostate cancer and 18 age-matched control patients with bladder cancer, but without prostate cancer. RESULTS: Immunohistochemistry with the PAL antibody revealed small round bodies within some non-cancerous glandular epithelium and stromal macrophages in most prostate samples. Prostate cancer samples had higher frequencies of either cytoplasmic P. acnes or nuclear NF-κB expression of glandular epithelium and higher numbers of stromal macrophages with P. acnes than control samples. These parameters were also higher in the peripheral zone than in the transitional zone of the prostate, especially in prostate cancer samples. Nuclear NF-κB expression was more frequent in glands with P. acnes than in glands without P. acnes. The number of stromal macrophages with the bacterium correlated with the grade of chronic inflammation in both the PZ and TZ areas and with the grade of acute inflammation in the TZ area. CONCLUSIONS: Immunohistochemical analysis with a novel monoclonal antibody for detecting P. acnes in the prostate suggested that intraepithelial P. acnes infection in non-cancerous prostate glands and inflammation caused by the bacterium may contribute to the development of prostate cancer.
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- 2014
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25. An autopsy case of an adult woman with Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHAD(NET)) syndrome developing nonalcoholic steatohepatitis and hepatocellular carcinoma: A case report.
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Satoru Hasuike, Yoshinori Ozono, Keisuke Uchida, Souichiro Ogawa, Hotaka Tamura, Naomi Uchiyama, Hiroshi Hatada, Yuri Komaki, Kenichi Nakamura, Hisayoshi Iwakiri, Mitsue Sueta, Kenji Nagata, Toyoki Nishimura, Misayo Matsuyama, Hirotake Sawada, Toshiyuki Oguri, Yuichiro Sato, and Hiroshi Kawakami
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- 2024
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26. Nitrogen reduction by the Fe sites of synthetic [Mo3S4Fe] cubes
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Yasuhiro Ohki, Kenichiro Munakata, Yuto Matsuoka, Ryota Hara, Mami Kachi, Keisuke Uchida, Mizuki Tada, Roger E. Cramer, W. M. C. Sameera, Tsutomu Takayama, Yoichi Sakai, Shogo Kuriyama, Yoshiaki Nishibayashi, and Kazuki Tanifuji
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Multidisciplinary - Published
- 2022
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27. Development of High-power Infrared Laser Capable Phase-only Spatial Light Modulator.
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Yu Takiguchi, Hiroshi Tanaka, Tsubasa Watanabe, Naoaki Kato, Keisuke Uchida, Munenori Takumi, Tomoko Otsu-Hyodo, Kazuhiro Nakamura, and Haruyoshi Toyoda
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INFRARED lasers ,SPATIAL light modulators ,ULTRASHORT laser pulses ,INDUSTRIAL lasers ,FABRICATION (Manufacturing) ,LIQUID crystal devices ,ULTRA-short pulsed lasers ,HOLOGRAPHY - Abstract
We developed two types of liquid-crystal spatial light modulators: an improved device by modifying each layer of the device and a large active area for industrial infrared lasers to demonstrate innovative manufacturing and fabrication techniques in smart manufacturing. The reconstruction of computer-generated holograms was demonstrated to prove the concept of the proposed device in the IR region. The incident phase performance characteristics of the device under high-power laser irradiation were obtained using a 1030 nm ultrashort pulse laser. [ABSTRACT FROM AUTHOR]
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- 2023
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28. Multimedia survey on mercury status at solid waste landfill facilities in developing countries to estimate human health and the environmental risks
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Mitsugu SAITO, Tatsuya HATTORI, Keisuke UCHIDA, Go SUZUKI, Yoshinobu WATANABE, Toshihiro IIZUKA, and Hiromitsu NAGASAKA
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- 2022
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29. A Solitary Necrotizing Sarcoid Granulomatosis-like Pulmonary Lesion Possibly Associated with Propionibacterium acnes and Mycobacterium avium
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Kazuhiro Murakami, Toshiharu Tabata, Motoki Kubota, Keisuke Uchida, Keigo Murakami, Yoshinobu Eishi, Naoya Ishibashi, Shuko Hata, and Yasuhiro Nakamura
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Pathology ,medicine.medical_specialty ,Solitary pulmonary nodule ,Lung ,biology ,business.industry ,General Medicine ,medicine.disease ,biology.organism_classification ,Pathophysiology ,Lesion ,Propionibacterium acnes ,medicine.anatomical_structure ,Coagulative necrosis ,hemic and lymphatic diseases ,Internal Medicine ,Coinfection ,medicine ,Sarcoidosis ,medicine.symptom ,business - Abstract
We report a case of a pulmonary necrotizing sarcoid granulomatosis (NSG)-like lesion possibly associated with coinfection of Mycobacterium avium and Propionibacterium acnes. A solitary nodule in the right middle lobe of the lung was notable for coagulative necrosis with aggregates of sarcoid-like epithelioid granulomas. Small arteries were damaged by granulomas. Both M. avium and P. acnes were detected in the lesion. Furthermore, more P. acnes genomes were detected in the granulomas than in the non-lesion lung. These findings blur the pathophysiologic boundaries among NSG, sarcoidosis, and mycobacteriosis, and suggest that NSG needs to be recognized as continuous spectra of sarcoidosis/mycobcteriosis.
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- 2021
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30. Implication of Ivabradine Therapy in Up-Titrating Beta-Blocker Dose in Patients with Systolic Dysfunction
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Teruhiko Imamura, Koichiro Kinugawa, Hiroshi Onoda, and Keisuke Uchida
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medicine.medical_specialty ,Systole ,medicine.drug_class ,Adrenergic beta-Antagonists ,Cardiomyopathy ,Diastole ,Walk Test ,Patient Readmission ,Internal medicine ,Natriuretic Peptide, Brain ,Heart rate ,medicine ,Humans ,Ivabradine ,Prospective Studies ,Beta blocker ,Heart Failure ,Ejection fraction ,business.industry ,Cardiovascular Agents ,General Medicine ,medicine.disease ,Blood pressure ,Echocardiography ,Heart failure ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,medicine.drug - Abstract
Ivabradine, which reduces heart rate (HR) without affecting sympathetic nerve activity, improves mortality and morbidity in patients with systolic dysfunction. However, its impact on up-titrating a concomitant beta-blocker dose in such a cohort, via increasing cardiac output and blood pressure and improving tolerability to beta-blockers, remains unknown. In this single-center, prospective, randomized control trial, patients with systolic dysfunction, defined as left ventricular ejection fraction50%, sinus rhythm, heart rate75 bpm, systolic blood pressure between 90 and 110 mmHg, and New York Heart Association functional class III or IV, who are refractory to up-titration of a beta-blocker due to symptomatic hypotension, dizziness, or worsening heart failure, were assigned to the 20 ivabradine arm or the 20 conventional therapy arm and followed-up for 6 months. The primary outcome is the daily dose of beta-blocker at 6-months follow-up. The secondary outcomes are echocardiographic parameters including overlap between E-wave and A-wave in transmitral diastolic filling flow, plasma B-type natriuretic peptide level, 6-minute walk distance, and heart failure readmission rate. By conducting this study, we hope to demonstrate the clinical benefit of ivabradine therapy in up-titrating beta-blockers and improving clinical outcomes in patients with systolic dysfunction.
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- 2021
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31. Bail-out Ablation of Ventricular Tachycardia Electrical Storm in a Patient with a Durable Left Ventricular Assist Device
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Toshihide Izumida, Naoya Kataoka, Teruhiko Imamura, Keisuke Uchida, Takahisa Koi, Masaki Nakagaito, Makiko Nakamura, Yuki Komatsu, Akihiko Nogami, and Koichiro Kinugawa
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Internal Medicine ,General Medicine - Abstract
The therapeutic strategy for sustained ventricular tachycardia (VT) during left ventricular assist device usage remains unclear. We encountered a patient with durable left ventricular assist device who presented sustained VT. Electrophysiological mapping was able to be established appropriately owing to the robust mechanical hemodynamics support despite inter-device interference. The three-dimensional activation map of clinically documented VT demonstrated that the propagation exited from the right ventricular apex through the critical isthmus located at the epicardium or interventricular septum, which was successfully treated by catheter ablation at the exit site. Further experiences like ours should be accumulated to establish a therapeutic strategy.
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- 2022
32. Bail-out Ablation of Ventricular Tachycardia Electrical Storm in a Patient with a Durable Left Ventricular Assist Device.
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Toshihide Izumida, Naoya Kataoka, Teruhiko Imamura, Keisuke Uchida, Takahisa Koi, Masaki Nakagaito, Makiko Nakamura, Yuki Komatsu, Akihiko Nogami, and Koichiro Kinugawa
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- 2023
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33. Liver abscess in advanced hepatocellular carcinoma after atezolizumab plus bevacizumab treatment: A case report
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Keisuke Uchida, Yoshinori Ozono, Naomi Uchiyama, Hiroshi Hatada, Kenichi Nakamura, Yuri Komaki, Hisayoshi Iwakiri, Satoru Hasuike, Kenji Nagata, Yuichiro Sato, and Hiroshi Kawakami
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Bevacizumab ,Male ,C-Reactive Protein ,Carcinoma, Hepatocellular ,Liver Abscess ,Liver Neoplasms ,Humans ,General Medicine ,Antibodies, Monoclonal, Humanized ,Aged ,Anti-Bacterial Agents - Abstract
Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally. Since 2020, combination treatment with atezolizumab and bevacizumab were approved in patients with unresectable HCC in Japan, and atezolizumab plus bevacizumab is the first-line treatment for unresectable HCC.A 73-year-old Japanese man diagnosed with a large HCC was treated with atezolizumab plus bevacizumab. After 2 cycles, he had fever and fatigue and was admitted to the hospital.Abdominal contrast-enhanced computed tomography revealed tumor necrosis in HCC with gas formation in the necrotic area. Laboratory examination revealed a white blood cell (WBC) count of 16,340/μL and C-reactive protein (CRP) level of 33.0 mg/dL. Based on the above findings, he was diagnosed with a liver abscess.Percutaneous transhepatic liver abscess drainage and broad-spectrum antibiotics treatment were performed.Despite liver abscess drainage, persistent fever and no improvement in the WBC count or CRP level was observed. The patient's respiratory condition and renal function gradually worsened; The patient's general condition did not improve despite the ventilator support and continuous hemodiafiltration, and he died on day 37.We report the first case of liver abscess after atezolizumab plus bevacizumab treatment for unresectable HCC.
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- 2022
34. Propionibacterium acnes-associated Sarcoidosis Possibly Initially Triggered by Interferon-alpha Therapy
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Takuji Suzuki, Naomi Nakano, Mamitaro Ohtsuki, Masashi Bando, Yoshinobu Eishi, Michiru Sawahata, Tetsuo Yamaguchi, Yasumaro Fujiki, Koichi Hagiwara, and Keisuke Uchida
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Multiple Pulmonary Nodules ,Pathology ,medicine.medical_specialty ,biology ,medicine.diagnostic_test ,Mediastinal lymphadenopathy ,business.industry ,Ribavirin ,Alpha interferon ,General Medicine ,030204 cardiovascular system & hematology ,biology.organism_classification ,medicine.disease ,03 medical and health sciences ,Propionibacterium acnes ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Biopsy ,Internal Medicine ,medicine ,030211 gastroenterology & hepatology ,Sarcoidosis ,business ,Uveitis - Abstract
A 46-year-old woman with uveitis was referred to our respiratory diseases department in July 2018. Her medical history included transient bilateral hilar mediastinal lymphadenopathy (BHL) and multiple pulmonary nodules in May 2013 during pegylated interferon-alpha and ribavirin treatment for chronic hepatitis C infection. Five years post-treatment, chest X-ray revealed BHL and nodular recurrence. A biopsy of the subcutaneous buttock nodules revealed scattered non-caseating epithelioid granulomas with positive PAB immunohistochemical staining. This seem to be the first report of Propionibacterium acnes-associated sarcoidosis possibly initially triggered by interferon-alpha therapy. Understanding the mechanisms underlying interferon-triggered P. acnes-associated sarcoidosis may clarify the sarcoidosis immunopathogenesis.
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- 2021
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35. Synthesis of Thioxanthones through Formal C–H Thiolation of Benzoic Acid Esters and Acid-mediated Direct Cyclization
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Takamitsu Hosoya, Keisuke Uchida, Suguru Yoshida, Kotaro Mutsuura, and Yuki Sakata
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inorganic chemicals ,chemistry.chemical_compound ,010405 organic chemistry ,Chemistry ,organic chemicals ,Organic chemistry ,General Chemistry ,010402 general chemistry ,Thioxanthone ,01 natural sciences ,Borylation ,0104 chemical sciences ,Benzoic acid - Abstract
An efficient thioxanthone synthesis from benzoic acid esters is disclosed. Various thioxanthones were prepared by iridium-catalyzed C–H borylation of benzoic acid esters followed by copper-catalyze...
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- 2020
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36. Cancer gland rupture as a potential risk factor for lymph node metastasis in early colorectal adenocarcinoma with deep submucosal invasion
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Mariko Negi, Katsumi Oishi, Yoshinobu Eishi, Keiko Miura, Takashi Ito, Daisuke Sakonishi, Daisuke Kobayashi, Keisuke Uchida, Takumi Akashi, and Masaki Sekine
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Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Histology ,Stromal cell ,medicine.medical_treatment ,depth of invasion ,Adenocarcinoma ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Tumor budding ,Risk Factors ,Humans ,Medicine ,Neoplasm Invasiveness ,Colorectal adenocarcinoma ,Endoscopy, Digestive System ,guidelines ,C‐shaped gland ,vascular invasion ,Abscess ,Aged ,algorithm ,business.industry ,risk assessment ,Cancer ,Original Articles ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Mucus ,tumour budding ,030104 developmental biology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Therapeutic endoscopy ,T1 colorectal cancer ,Female ,Original Article ,Colorectal Neoplasms ,business ,Algorithms - Abstract
Aims Lymph node metastasis (LNM) has not been found in more than 85% of patients with early invasive colorectal adenocarcinoma (T1-CRAC) who undergo surgery after therapeutic endoscopy due to the risk for LNM. Better histological risk assessment for LNM of endoscopically resected T1-CRAC is important to avoid unnecessary additional surgery. Methods and results We evaluated cancer gland rupture (CGR), i.e. cancer glands with a discontinuous epithelial lining, at the invasive front, as a potential risk factor for LNM by histological examination of differentiated T1-CRAC from 217 patients who underwent surgery with or without therapeutic endoscopy. CGR was represented by C-shaped neoplastic glands with a variable inflammatory or stromal reaction, and was occasionally accompanied by mucus lake or abscess formation. CGR was observed in 168 (77%) cases, including all 20 cases with LNM, and the odds ratio of LNM was higher for CGR than for deep invasion (depth of submucosal invasion ≥1000 μm). All cases with LNM were found among 148 cases with deep invasion and positive CGR, whereas no LNM was detected in 29 cases with deep invasion and negative CGR, regardless of vascular invasion or tumour budding. In the 148 cases, LNM was detected in 18 (19%) of 93 cases with positive vascular invasion or high-grade tumour budding, and in two (4%) of 55 cases without either. Conclusions Our findings suggest that CGR is an easily applied and objective histological finding for predicting LNM that could be useful for assessing the risk for LNM of endoscopically resected T1-CRAC with deep invasion.
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- 2020
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37. Hematochezia Due to Panitumumab-induced Colitis with Vitamin K Deficiency
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Hiroshi Kawakami, Yoshinori Ozono, Koji Nakashima, Koji Yamamto, Hiroyuki Tanaka, Hiroshi Hatada, Souichiro Ogawa, Hotaka Tamura, Keisuke Uchida, Naoki Yoshida, and Naomi Uchiyama
- Subjects
Male ,Short Bowel Syndrome ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Antineoplastic Agents ,medicine.disease_cause ,Gastroenterology ,Proto-Oncogene Proteins p21(ras) ,Internal medicine ,Vitamin K deficiency ,Antineoplastic Combined Chemotherapy Protocols ,Internal Medicine ,medicine ,Panitumumab ,Humans ,Colitis ,Chemotherapy ,business.industry ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,medicine.disease ,Short bowel syndrome ,Hematochezia ,Mutation ,Vitamin K Deficiency ,KRAS ,medicine.symptom ,Neoplasm Recurrence, Local ,business ,Colorectal Neoplasms ,Gastrointestinal Hemorrhage ,medicine.drug - Abstract
Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has been shown to be useful in treating either advanced or recurrent KRAS/NRAS/BRAF wild-type colorectal cancer. We herein report the case of a 60-year-old man with short bowel syndrome who developed hematochezia due to panitumumab-induced colitis with vitamin K deficiency during third-line chemotherapy. The cause of vitamin K deficiency was the lack of intravenous vitamin K supplementation following a change from central venous nutrition to peripheral venous nutrition. We advise clinicians to carefully check for colitis and manage the infusions of chemotherapy patients with short bowel syndrome.
- Published
- 2021
38. Reconsidering the pathogenesis of chalazion
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Tomo Suzuki, Naomi Katsuki, Ryota Tsutsumi, Keisuke Uchida, Kenichi Ohashi, Yoshinobu Eishi, and Shigeru Kinoshita
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Ophthalmology ,Blepharitis ,Tears ,Chalazion ,Humans ,Meibomian Glands - Published
- 2021
39. Propionibacterium acnes-Derived Circulating Immune Complexes in Sarcoidosis Patients
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Kurara Yamamoto, Keisuke Uchida, Yoshinobu Eishi, Asuka Furukawa, Takashi Ito, Kenichi Ohashi, Haruhiko Furusawa, Takumi Akashi, Daisuke Kobayashi, Masaki Sekine, Akiko Yoneyama, and Keiko Miura
- Subjects
Microbiology (medical) ,infectious antibody ,QH301-705.5 ,immune complex ,Microbiology ,Article ,Propionibacterium acnes ,Immune system ,sandwich ELISA ,Virology ,Cutibacterium acnes ,medicine ,antigen retrieval ,sarcoidosis ,Biology (General) ,biology ,business.industry ,Antibody titer ,medicine.disease ,biology.organism_classification ,Immune complex ,lipoteichoic acid ,Immunology ,biology.protein ,Sarcoidosis ,Lymph ,Lipoteichoic acid ,Antibody ,business - Abstract
Propionibacterium acnes is a potential etiologic agent of sarcoidosis and a dysregulated immune response to the commensal bacterium is suspected to cause granuloma formation. P. acnes-derived insoluble immune complexes were recently demonstrated in sinus macrophages of sarcoidosis lymph nodes, suggesting local proliferation of the bacterium in affected organs. In the present study, we developed a method for detecting P. acnes-derived immune complexes in human blood by measuring the concentration of P. acnes-specific lipoteichoic acid (PLTA) detectable after an antigen retrieval pretreatment of plasma samples. Before pretreatment, anti-PLTA antibody was detected and PLTA could not be detected, in all plasma samples from 51 sarcoidosis patients and 35 healthy volunteers. After pretreatment, however, a significant level of PLTA (>, 105 ng/mL) was detected in 33 (65%) sarcoidosis patients and 5 (14%) control subjects, with 86% specificity and 65% sensitivity for sarcoidosis. In both groups, plasma anti-PLTA antibody titers did not differ between samples with and without detection of PLTA. PLTA levels were abnormally increased (>, 202 ng/mL) in 21 (41%) sarcoidosis patients. These findings suggest that P. acnes-derived circulating immune complexes present in human blood are abnormally increased in many sarcoidosis patients, presumably due to local proliferation of the bacterium in the affected organs.
- Published
- 2021
40. A Simple Predictive Marker in Cardiac Resynchronization Therapy Recipients: Prominent S-Wave in Right Precordial Leads
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Keisuke Uchida, Koichiro Kinugawa, Takahisa Koi, Teruhiko Imamura, and Naoya Kataoka
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Male ,Medicine (General) ,medicine.medical_specialty ,genetic structures ,Defibrillation ,medicine.medical_treatment ,Cardiac resynchronization therapy ,heart failure ,cardiac resynchronization therapy ,QRS amplitude ,Article ,QRS complex ,Electrocardiography ,R5-920 ,Internal medicine ,medicine ,Cutoff ,Humans ,Cumulative incidence ,cardiovascular diseases ,Aged ,Predictive marker ,Ventricular Remodeling ,business.industry ,General Medicine ,medicine.disease ,Confidence interval ,Treatment Outcome ,Heart failure ,Cardiology ,cardiovascular system ,business - Abstract
Background and objectives: Current guidelines criteria do not satisfactorily discriminate responders to cardiac resynchronization therapy (CRT). QRS amplitude is an established index to recognize the severity of myocardial disturbance and might be a key to optimal patient selection for CRT. Materials and Methods: (1) Initial R-wave amplitude, (2) S-wave amplitude, and (3) a summation of maximal R- or R′-wave amplitude and S-wave amplitude were measured at baseline. These parameters were averaged according to right (V1 to V3) or left (V4 to V6) precordial leads. The impact of these parameters on response to CRT, which was defined as a decrease in left ventricular end-systolic volume ≥15% at six-month follow-up, was investigated. Results: Among 47 patients (71 years old, 28 men) who received guideline-indicated CRT implantation, 25 (53%) achieved the definition of CRT responder. Among baseline electrocardiogram parameters, only the higher S-wave amplitude in right precordial leads was an independent predictor of CRT responders (odds ratio: 2.181, 95% confidence interval: 1.078–4.414, p = 0.030) at a cutoff of 1.44 mV. The cutoff was independently associated with cumulative incidence of heart failure readmission and appropriate electrical defibrillation following CRT implantation (p <, 0.05, respectively). Conclusions: Prominent S-wave in right precordial leads might be a promising index to predict left ventricular reverse remodeling and greater clinical outcomes following CRT implantation.
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- 2021
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41. Propionibacterium acnes-associated chronic hypertrophic pachymeningitis followed by refractory otitis media: a case report
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Shinichi Otsu, Eiichiro Amano, Akira Machida, Yoshinobu Eishi, Tasuku Ishihara, and Keisuke Uchida
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Male ,Mastoiditis ,Pathology ,medicine.medical_specialty ,Dura mater ,Anti-Inflammatory Agents ,Case Report ,lcsh:RC346-429 ,03 medical and health sciences ,Propionibacterium acnes ,0302 clinical medicine ,Recurrence ,Biopsy ,medicine ,Humans ,Meningitis ,Gram-Positive Bacterial Infections ,Otitis media ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,biology ,medicine.diagnostic_test ,Pia mater ,business.industry ,General Medicine ,Hypertrophy ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,Chronic infection ,medicine.anatomical_structure ,Otitis ,Neurology (clinical) ,medicine.symptom ,Pachymeningitis ,business ,Vasculitis ,030217 neurology & neurosurgery - Abstract
Background: Hypertrophic pachymeningitis (HP) is a rare disorder that involves localized or diffuse thickening of the dura mater. HP is associated with various inflammatory, infectious, and malignant diseases, such as rheumatic arthritis, sarcoidosis, anti-neutrophil cytoplasmic antibody-associated vasculitis, IgG4-related disorders, syphilis, tuberculosis, bacterial and fungal infections, cancer, and idiopathic diseases, when evaluation fails to reveal a cause. Among them, chronic infection with Propionibacterium acnes is a rare etiology of HP, and its pathology remains unclear. Case Presentation: An 80-year-old man having refractory otitis media with effusion of the right ear presented with progressive right-sided headache and nausea. Post-contrast brain magnetic resonance imaging revealed right mastoiditis and remarkable thickening of the dura mater and enhancement of pia mater extending from the right middle cranial fossa to the temporal lobe. HP secondary to middle ear infection was suspected, and a biopsy of the right mastoid was performed. An anaerobic culture of the biopsied right mastoid showed the growth of P. acnes, and histopathological examination using P. acnes-specific monoclonal antibody (PAB antibody) revealed the infiltration of inflammatory cells with P. acnes. Moreover, using PAB antibody, P. acnes was detected in the biopsy specimen of the thickening dura mater. No granulomas were identified in either specimen. HP was resolved with long-term administration of antibiotics and steroids. Conclusion: This is the first documentation of pathologically demonstrated chronic HP associated with P. acnes infection followed by refractory otitis media. This report showed that chronic latent P. acnes infection induces chronic inflammation, which cannot be controlled without administering steroids. Keywords: Propionibacterium acnes, otitis media, pachymeningitis, mastoiditis, dura mater
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- 2020
42. Immunohistochemical Detection of
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Takuma, Isshiki, Sakae, Homma, Yoshinobu, Eishi, Matsuko, Yabe, Kazuya, Koyama, Yasuhiko, Nishioka, Tetsuo, Yamaguchi, Keisuke, Uchida, Kurara, Yamamoto, Kenichi, Ohashi, Atsushi, Arakawa, Kazutoshi, Shibuya, Susumu, Sakamoto, and Kazuma, Kishi
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PAB antibody ,hemic and lymphatic diseases ,pathogenesis ,immunohistochemistry ,sarcoidosis ,Propionibacterium acnes ,Cutibacterium acnes ,granuloma ,Article ,P. acnes - Abstract
Propionibacterium acnes is implicated in the pathogenesis of sarcoidosis. We investigated the usefulness of immunohistochemistry (IHC) with a commercially available P. acnes-specific monoclonal antibody (PAB antibody) for differentiating sarcoidosis from other granulomatous diseases. Formalin-fixed paraffin-embedded tissue samples from 94 sarcoidosis patients and 30 control patients with other granulomatous diseases were examined by the original manual IHC method. We also compared the detection frequency of P. acnes in sarcoid granulomas between manual and automated IHC methods. P. acnes was detected in sarcoid granulomas of samples obtained by transbronchial lung biopsy (64%), video-associated thoracic surgery (67%), endobronchial-ultrasound-guided transbronchial-needle aspiration (32%), lymph node biopsy (80%), and skin biopsy (80%) from sarcoidosis patients, but not in any non-sarcoid granulomas of the samples obtained from control patients. P. acnes outside granulomas, however, was frequently detected in both groups. The detection status of P. acnes in granulomas did not correlate with the clinical characteristics of sarcoidosis patients. The automated Leica system exhibited the best detection sensitivity (72%) and almost an identical localization for P. acnes in sarcoid granulomas compared with the manual method. IHC with a PAB antibody is useful for differentiating sarcoidosis from other granulomatous diseases by detecting P. acnes in granulomas. An automated method by the Leica system can be used in pathology laboratories for differential diagnosis of granulomas by IHC with the PAB antibody.
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- 2021
43. Nitrogen Reduction by the Fe Sites of Synthetic [Mo3S4Fe] Cubes
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Yasuhiro Ohki, Roger E. Cramer, Keisuke Uchida, Kenichiro Munakata, Ryota Hara, Yoshiaki Nishibayashi, Yoichi Sakai, W. M. C. Sameera, Tsutomu Takayama, Mizuki Tada, Shogo Kuriyama, Mami Kachi, and Kazuki Tanifuji
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Reduction (complexity) ,chemistry ,Inorganic chemistry ,chemistry.chemical_element ,Nitrogen - Abstract
N2 fixation by Nature, which is a crucial process to supply bio-available forms of nitrogen, is performed by nitrogenase. This enzyme employs a unique transition metal-sulfur-carbon cluster as its active-site cofactor ([(R-homocitrate)MoFe7S9C], FeMoco), and the sulfur-surrounded Fe atoms have been postulated to capture and reduce N2. Whereas synthetic counterparts of FeMoco, metal-sulfur clusters, have displayed binding of N2 in a few examples, the reduction of N2 by any synthetic metal-sulfur clusters or even by the extracted form of FeMoco have remained elusive despite a near-50-year history of research. Here we show that the Fe atoms in our synthetic [Mo3S4Fe] cubes capture an N2 molecule and catalyze N2 silylation to form N(SiMe3)3 under treatment with excess Na and Me3SiCl. These results exemplify the first catalytic N2 reduction by a synthetic metal-sulfur cluster with an Fe center supported only by S ligands. This work demonstrates the N2-reducing capability of Fe atoms in a S-rich environment, which Nature has selected to accomplish a similar purpose. This work also suggests some critical features for successful by metal-sulfur compounds, which serve as clues to understand the origin of N2 fixation on Earth.
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- 2021
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44. Nitrogen reduction by the Fe sites of synthetic [Mo
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Yasuhiro, Ohki, Kenichiro, Munakata, Yuto, Matsuoka, Ryota, Hara, Mami, Kachi, Keisuke, Uchida, Mizuki, Tada, Roger E, Cramer, W M C, Sameera, Tsutomu, Takayama, Yoichi, Sakai, Shogo, Kuriyama, Yoshiaki, Nishibayashi, and Kazuki, Tanifuji
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Molybdenum ,Trimethylsilyl Compounds ,Nitrogen ,Iron ,Nitrogenase ,Sodium ,Biocatalysis ,Tricarboxylic Acids ,Carbon ,Sulfur - Abstract
Nitrogen (N
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- 2021
45. Presence of Propionibacterium acnes in granulomas associates with a chronic disease course in Dutch sarcoidosis patients
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Jan C. Grutters, Jan Damen, Els Beijer, Marcel Veltkamp, Kees Seldenrijk, Yoshinobu Eishi, and Keisuke Uchida
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,medicine.drug_class ,lcsh:Medicine ,Monoclonal antibody ,Interstitial Lung Disease ,Pathogenesis ,03 medical and health sciences ,Propionibacterium acnes ,0302 clinical medicine ,Medicine ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,lcsh:R ,Original Articles ,medicine.disease ,biology.organism_classification ,Phenotype ,Chronic disease ,030228 respiratory system ,biology.protein ,Sarcoidosis ,Antibody ,business ,Immunostaining - Abstract
Several studies demonstrated that Propionibacterium acnes may be involved in sarcoidosis pathogenesis. Presence of P. acnes was found in granulomas of the majority of Japanese sarcoidosis patients. However, presence of P. acnes in tissue has never been related to sarcoidosis phenotypes and clinical outcome. Therefore, the aims of our study were to demonstrate whether P. acnes can be detected in granulomas of Dutch sarcoidosis patients and to investigate whether its presence is related to a clinical phenotype and/or course of disease. Sections of formalin-fixed paraffin-embedded tissue blocks of 76 sarcoidosis patients were examined by immunostaining with a P. acnes-specific monoclonal antibody (PAB antibody) using a Ventana BenchMark ULTRA. Clinical outcome status (COS) was determined and classified into two phenotype groups: A: resolved, minimal or persistent disease without treatment (COS 1–6) and B: persistent disease with need for treatment (COS 7–9). P. acnes was detected in samples of 31 patients (41%) and located within granulomas in samples of 13 patients (17%). The frequency of P. acnes detected in granulomas at diagnosis was significantly higher in patients with phenotype B compared to patients with phenotype A (29% versus 0%, p=0.021). Presence of P. acnes in granulomas can be confirmed in Dutch sarcoidosis patients. It is intriguing that presence of P. acnes in granulomas is more frequently found in patients with chronic disease requiring treatment. This adds to the rationale that a subgroup of sarcoidosis patients might benefit from antibiotic therapy., Significantly more sarcoidosis patients with a chronic disease course requiring treatment have presence of P. acnes in granulomas. This contributes to the premise that it is relevant to further explore antibacterial therapy in sarcoidosis. https://bit.ly/36wCbbw
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- 2021
46. A novel mutation in early‐onset sarcoidosis/Blau syndrome: an association with Propionibacterium acnes
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Ryuta Nishikomori, Yoshinobu Hoshii, Yoshitaka Honda, Yoshinobu Eishi, Shunji Hasegawa, Nobuyuki Asano, Yuno Korenaga, Shouichi Ohga, Keisuke Uchida, Fumiko Okazaki, Kazushi Izawa, Tsuyoshi Tanabe, Sho-Hei Uchi, Tamaki Nakamura, Hiroyuki Wakiguchi, Hiroki Yasudo, and Ryoji Yanai
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Pathology ,lcsh:Diseases of the musculoskeletal system ,Biopsy ,Nod2 Signaling Adaptor Protein ,Dermatitis ,Case Report ,NF-κB ,PAB antibody ,030207 dermatology & venereal diseases ,0302 clinical medicine ,NOD2 ,Panuveitis ,Immunology and Allergy ,Medicine ,Child ,Skin ,Granulomatous disease ,Granuloma ,Synovitis ,biology ,medicine.diagnostic_test ,lcsh:RJ1-570 ,Immunohistochemistry ,Treatment Outcome ,Antirheumatic Agents ,Prednisolone ,Female ,Polyarthritis ,Sarcoidosis ,Granulomatous Dermatitis ,medicine.drug ,medicine.medical_specialty ,Uveitis ,03 medical and health sciences ,Propionibacterium acnes ,Rheumatology ,D512V mutation ,Humans ,Blau syndrome ,030203 arthritis & rheumatology ,business.industry ,Arthritis ,lcsh:Pediatrics ,medicine.disease ,biology.organism_classification ,Methotrexate ,Mutation ,Pediatrics, Perinatology and Child Health ,Skin biopsy ,Cutibacterium acnes ,lcsh:RC925-935 ,business - Abstract
BackgroundEarly-onset sarcoidosis (EOS) and Blau syndrome (BS) are systemic inflammatory granulomatous diseases without visible pulmonary involvement, and are distinguishable from their sporadic and familial forms. The diseases are characterized by a triad of skin rashes, symmetrical polyarthritis, and recurrent uveitis. The most common morbidity is ocular involvement, which is usually refractory to conventional treatment. A gain-of-function mutation in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been demonstrated in this disease; however, little is known about the relationship between the activation ofNOD2and the pathophysiology of EOS/BS. Here we describe EOS/BS with a novel mutation in theNOD2gene, as well as detection ofPropionibacterium acnes(P. acnes) in the granulomatous inflammation.Case presentationAn 8-year-old Japanese girl presented with refractory bilateral granulomatous panuveitis. Although no joint involvement was evident, she exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis, andP. acneswas detected within the sarcoid granulomas by immunohistochemistry withP. acnes-specific monoclonal (PAB) antibody. Genetic analyses revealed that the patient had aNOD2heterozygous D512V mutation that was novel and not present in either of her parents. The mutantNOD2showed a similar activation pattern to EOS/BS, thus confirming her diagnosis. After starting oral prednisolone treatment, she experienced an anterior vitreous opacity relapse despite gradual prednisolone tapering; oral methotrexate was subsequently administered, and the patient responded positively.ConclusionsWe presented a case of EOS/BS with a novel D512V mutation in theNOD2gene. In refractory granulomatous panuveitis cases without any joint involvement, EOS/BS should be considered as a differential diagnosis; genetic analyses would lead to a definite diagnosis. Moreover, this is the first report ofP. acnesdemonstrated in granulomas of EOS/BS. Since intracellularP. acnesactivates nuclear factor-kappa B in aNOD2-dependent manner, we hypothesized that the mechanism of granuloma formation in EOS/BS may be the result ofNOD2activity in the presence of the ligand muramyl dipeptide, which is a component ofP. acnes.These results indicate that recognition ofP. acnesthrough mutantNOD2is the etiology in this patient with EOS/BS.
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- 2021
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47. Annular Sarcoidosis with Geographic Appearance in a Patient with Systemic Sarcoidosis
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Yuichiro Ohshima, Hiroyuki Takama, Yoriko Ando, Yoshinobu Eishi, Toyonori Tsuzuki, Emiko Takahashi, Keisuke Uchida, Daisuke Watanabe, Takeshi Yanagishita, and Masashi Akiyama
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Pathology ,medicine.medical_specialty ,Hardware_MEMORYSTRUCTURES ,Sarcoidosis ,biology ,Cutaneous Sarcoidosis ,Systemic sarcoidosis ,business.industry ,General Medicine ,cutaneous sarcoidosis ,Dermatology ,medicine.disease ,biology.organism_classification ,annular elastolytic giant cell granuloma ,propionibacterium acnes ,elastic fiber ,Propionibacterium acnes ,Granuloma, Giant Cell ,RL1-803 ,medicine ,Humans ,Annular elastolytic giant-cell granuloma ,business - Abstract
is missing (Short communication)
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- 2020
48. Development of Human Hair Reference Material Supporting the Biomonitoring of Methylmercury
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Mineshi Sakamoto, Hirokatsu Akagi, Flemming Nielsen, Byoung-Gwon Kim, Hing Man Chan, Dang T Hung, Keisuke Uchida, Nikolay Mashyanov, Megumi Yamamoto, Nikolai Panichev, Tomoaki Watanabe, Jun Yoshinaga, Ciprian M Cirtiu, Ranny F Herwati, Matthew D. Rand, Yasunori Ito, Koichi Haraguchi, Naoki Kaneko, Hitoshi Kodamatani, Alfrida E Suoth, Milena Horvat, Akito Matsuyama, Elena G. Panova, Hiromitsu Nagasaka, and Akane Yamakawa
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Male ,Mercury speciation ,chemistry.chemical_element ,Methylmercury ,Zinc ,Methylmercury Compounds ,Analytical Chemistry ,Mercury (element) ,Human biomonitoring ,chemistry.chemical_compound ,Certified reference materials ,chemistry ,Vietnam ,Environmental chemistry ,Biomonitoring ,Humans ,Reference material ,Coverage factor ,Arsenic ,Selenium ,Hair - Abstract
A certified reference material. NIMD-01, was developed for the analysis of mercury speciation in human hair. We collected the hair of Vietnamese males from a barbershop in Hanoi in 2016 and prepared 1200 bottles containing 3 g of sieved and blended hair powder. The certified value was given on a dry-mass basis, with the moisture content obtained by drying at 85°C for 4 h. Certified values with the expanded uncertainties (coverage factor, k = 2) were as follows: methylmercury, 0.634 ±0.071 mg kg -1 as mercury; total mercury. 0.794 ± 0.050 mg kg -1; copper, 12.8 ± 1.4 mgkg -1; /inc. 234 ± 29 mg kg -1; selenium, 1.52 ± 0.29 mg kg -1. An indicative arsenic concentration of 0.17 ± 0.03 mg kg 1 was measured. Extended uncertainties were estimated by sample homogeneity, long-and short-term stabilities, and a characterization from measurements made by collaborating laboratories.
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- 2020
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49. N2 activation on a molybdenum–titanium–sulfur cluster
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Mizuki Tada, Yasuhiro Ohki, Keisuke Uchida, Takehiro Ohta, Takashi Ogura, and Roger E. Cramer
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inorganic chemicals ,Reducing agent ,Science ,General Physics and Astronomy ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Article ,General Biochemistry, Genetics and Molecular Biology ,Transition metal ,Polymer chemistry ,parasitic diseases ,Moiety ,lcsh:Science ,Multidisciplinary ,010405 organic chemistry ,Nitrogenase ,General Chemistry ,Sulfur ,0104 chemical sciences ,chemistry ,Molybdenum ,lcsh:Q ,Brønsted–Lowry acid–base theory ,Titanium - Abstract
The FeMo-cofactor of nitrogenase, a metal–sulfur cluster that contains eight transition metals, promotes the conversion of dinitrogen into ammonia when stored in the protein. Although various metal–sulfur clusters have been synthesized over the past decades, their use in the activation of N2 has remained challenging, and even the FeMo-cofactor extracted from nitrogenase is not able to reduce N2. Herein, we report the activation of N2 by a metal–sulfur cluster that contains molybdenum and titanium. An N2 moiety bridging two [Mo3S4Ti] cubes is converted into NH3 and N2H4 upon treatment with Brønsted acids in the presence of a reducing agent., Nitrogenase—whose cofactor consists of a metal–sulfur cluster—catalyzes the production of NH3 from N2, but designing metal–sulfur complexes capable of promoting this conversion remains challenging. Here, the authors report on the activation of N2 by a metal–sulfur cluster containing [Mo3S4Ti] cubes, demonstrating NH3 and N2H4 production.
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- 2018
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50. Synthesis of Diverse Phenothiazines by Direct Thioamination of Arynes with S-(o-Bromoaryl)-S-methylsulfilimines and Subsequent Intramolecular Buchwald–Hartwig Amination
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Takamitsu Hosoya, Keisuke Uchida, Tsubasa Matsuzawa, and Suguru Yoshida
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chemistry.chemical_compound ,chemistry ,010405 organic chemistry ,Phenothiazine ,Intramolecular force ,General Chemistry ,Buchwald–Hartwig amination ,010402 general chemistry ,01 natural sciences ,Aryne ,Combinatorial chemistry ,0104 chemical sciences - Abstract
A facile method for the synthesis of diverse phenothiazines has been achieved by direct thioamination of aryne intermediates with S-(o-bromoaryl)-S-methylsulfilimines and subsequent intramolecular ...
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- 2018
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