研究者詳細 - 齋藤　充史

論文 - 齋藤　充史

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Adrenomedullin Therapy for Moderate-to-Severe COVID-19 Pneumonia: Double-Blind Placebo-Controlled Phase 2a Trial

Toshihiro Kita, Norio Ohmagari, Sho Saito, Hiroshi Mukae, Takahiro Takazono, Taka-Aki Nakada, Tadanaga Shimada, Yuji Hirai, Yuichiro Shindo, Kosaku Komiya, Atsushi Saito, Masaya Yamato, Koichiro Homma, Masaki Okamoto, Yoshihiro Yamamoto, Yoshikazu Mutoh, Chihiro Hasegawa, Nobuaki Mori, Fukumi Nakamura-Uchiyama, Mitsuru Honda, Keisuke Tomii, Hiroshi Ishii, Ichiro Takajo, Koji Watanabe, Kazuo Kitamura

Viruses 2025年07月

DOI

Exploring the Potential of a P2X3 Receptor Antagonist: Gefapixant in the Management of Persistent Cough Associated with Interstitial Lung Disease

Tomoyuki Takahashi, Atsushi Saito, Takafumi Yorozuya, Hirotaka Nishikiori, Koji Kuronuma, Hirofumi Chiba

Medicina 2025年05月

DOI

Rapid and Integrated Bacterial Evolution Analysis unveils gene mutations and clinical risk of Klebsiella pneumoniae

Kojiro Uemura, Toyotaka Sato, Soh Yamamoto, Noriko Ogasawara, Jirachaya Toyting, Kotaro Aoki, Akira Takasawa, Masayuki Koyama, Atsushi Saito, Takayuki Wada, Kaho Okada, Yurie Yoshida, Koji Kuronuma, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Kenichi Takano, Satoshi Takahashi, Hirofumi Chiba, Shin-ichi Yokota

Nature Communications 2025年03月

DOI

Management of anti-melanoma differentiation-associated gene 5 antibody-induced refractory dermatomyositis complicated by interstitial pneumonia using tofacitinib and its outcomes: a case report.

Yui Imai, Takafumi Yorozuya, Taku Hatakeyama, Takumi Nishimaki, Tomoyuki Takahashi, Tatsuru Ishikawa, Shun Kondoh, Yuichiro Asai, Yuki Mori, Atsushi Saito, Hirotaka Nishikiori, Michiko Hosaka, Hirofumi Chiba

Journal of medical case reports 18 ( 1 ) 471 - 471 2024年09月 [国際誌]

BACKGROUND: Clinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined. CASE PRESENTATION: A 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient's respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, βD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis. CONCLUSION: The patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected.

DOI PubMed

Therapeutic effect of long-acting muscarinic antagonist for treating uncontrolled asthma assessed using impulse oscillometry.

Hiroyuki Sugawara, Atsushi Saito, Saori Yokoyama, Hirofumi Chiba

Respiratory research 25 ( 1 ) 300 - 300 2024年08月 [国際誌]

BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

DOI PubMed

N-glycan on N262 of FGFR3 regulates the intracellular localization and phosphorylation of the receptor.

Hashimoto, U, Fujitani, N, Uehara, Y, Okamoto, H, Saito, A, Ito, F, Ariki, S, Shiratsuchi, A, Hasegawa, Y, Takahashi, M

Biochim. Biophys. Acta Gen. Subj. 1868 ( 4 ) 130565 - 130565 2024年04月 [査読有り]

DOI

The impact of respiratory reactance in oscillometry on survival in patients with idiopathic pulmonary fibrosis.

Tatsuru Ishikawa, Hirotaka Nishikiori, Yuki Mori, Keiko Fujino, Atsushi Saito, Mamoru Takahashi, Koji Kuronuma, Shiro Hinotsu, Hirofumi Chiba

BMC pulmonary medicine 24 ( 1 ) 10 - 10 2024年01月 [国際誌]

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung diseases has recently been reported. Our previous study showed that respiratory reactance (Xrs) measured by oscillometry reflected disease severity and predicted subsequent lung capacity decline in patients with IPF. However, the direct impact of Xrs on survival needs to be determined, and there are currently no reference values in oscillometry to predict prognosis. Therefore, this study aimed to investigate the association between oscillometry measurements, particularly Xrs, and survival in patients with IPF and to determine the cutoff values of Xrs that predict 3-year survival. METHODS: We analyzed the relationship between the measured values of PFT and oscillometry derived from 178 patients with IPF. Univariate and multivariate Cox proportional hazards analyses were performed to investigate the relationships between clinical indices at the time of the first oscillometry and survival. We performed the time-dependent receiver operating characteristic (ROC) curve analysis to set the optimized cutoff values of Xrs for 3-year survival prediction. We examined the discriminating power of cutoff values of Xrs on survival using the Kaplan-Meier method and the log-rank test. RESULTS: Xrs components, especially in the inspiratory phase (In), significantly correlated with the PFT values. In the multivariate analyses, Xrs (all of reactance at 5 Hz [X5], resonant frequency [Fres], and low-frequency reactance area [ALX] in the inspiratory phase) had a significant impact on survival (X5, p = 0.003; Fres, p = 0.016; ALX, p = 0.003) independent of age, sex, and other prognostic factors derived from the univariate analysis. The area under the ROC curve was 0.765, 0.759, and 0.766 for X5 In, Fres In, and ALX In, with cutoff values determined at - 0.98, 10.67, and 5.32, respectively. We found significant differences in survival after dividing patients using each of the cutoff values of Xrs. CONCLUSIONS: In patients with IPF, Xrs measured by oscillometry significantly impacted survival. We also determined the cutoff values of Xrs to discriminate patients with poor prognoses.

DOI PubMed

Pseudo-outbreak of Mycobacterium lentiflavum at a general hospital in Japan.

Yutaro Nagano, Koji Kuronuma, Yasuo Kitamura, Kanami Nagano, Hayato Yabe, Sayaka Kudo, Toyotaka Sato, Shinya Nirasawa, Mami Nakae, Motohiro Horiuchi, Shin-Ichi Yokota, Yoshihiro Fujiya, Atsushi Saito, Satoshi Takahashi, Hirofumi Chiba

Infection control and hospital epidemiology 44 ( 11 ) 1 - 7 2023年04月 [国際誌]

BACKGROUND: Mycobacterium lentiflavum is a slow-growing nontuberculous mycobacterium that is widely distributed in soil and water systems, but it is sometimes pathogenic to humans. Although cases of M. lentiflavum infections are rare, 22 isolates of M. lentiflavum were identified at a single hospital in Japan. We suspected a nosocomial outbreak; thus, we conducted transmission pattern and genotype analyses. METHODS: Cases of M. lentiflavum isolated at Kushiro City General Hospital in Japan between May 2020 and April 2021 were analyzed. The patient samples and environmental culture specimens underwent whole-genome sequencing (WGS). Additionally, we retrospectively collected clinical data from patient medical records. RESULTS: Altogether, 22 isolates of M. lentiflavum were identified from sputum and bronchoalveolar lavage samples. Clinically, the instances with M. lentiflavum isolates were considered contaminants. In the WGS analysis, 19 specimens, including 18 patient samples and 1 environmental culture from the hospital's faucet, showed genetic similarity. The frequency of M. lentiflavum isolation decreased after we prohibited the use of taps where M. lentiflavum was isolated. CONCLUSIONS: WGS analysis identified that the cause of M. lentiflavum pseudo-outbreak was the water used for patient examinations, including bronchoscopy.

DOI PubMed

ニボルマブおよびイピリムマブ療法における総腫瘍量と重症免疫関連有害事象の関連性

太田雄介, 角俊行, 道又春彦, 永山大貴, 越野友太, 渡辺裕樹, 山田裕一, 齋藤充史, 千葉弘文

日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 12 ( 増刊 ) 382 - 382 2023年03月

ニボルマブおよびイピリムマブ療法における総腫瘍量と重症免疫関連有害事象の関連性

太田雄介, 角俊行, 道又春彦, 永山大貴, 越野友太, 渡辺裕樹, 山田裕一, 齋藤充史, 千葉弘文

日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 12 ( 増刊 ) 382 - 382 2023年03月

Serum Testosterone Is Associated With the Severity of COVID-19.

Ema Suzuki, Koji Kuronuma, Ryosei Murai, Yoshihiro Fujiya, Atsushi Saito, Hirofumi Chiba, Satoshi Takahashi

In vivo (Athens, Greece) 37 ( 5 ) 2314 - 2319 2023年 [国際誌]

BACKGROUND/AIM: Coronavirus disease 2019 (COVID-19) is more likely to be severe in men than in women. Its association with sex hormones as an aggravating factor for male patients has been attracting attention. This study aimed to investigate whether serum testosterone is associated with the aggravation of COVID-19. PATIENTS AND METHODS: Serum testosterone concentrations in 116 male patients with COVID-19 and residual serum were measured and examined upon their admission to Sapporo Medical University Hospital between February 1, 2020 and March 31, 2021. RESULTS: Blood samples collected from these patients with COVID-19 were analyzed. The serum testosterone levels were 2.19±1.35, 1.29±0.88, and 0.75±0.58 ng/ml in mild, moderate, and severe groups, respectively. Patients with severe COVID-19 on admission had lower testosterone levels (p<0.001). At a cutoff level of 1.31 ng/ml, the area under the curve for the comparison of severe with non-severe cases was 0.825. Furthermore, serum testosterone levels negatively correlated with C-reactive protein and serum amyloid A levels but positively correlated with calcium, zinc, C3, and C4. CONCLUSION: In male patients with COVID-19, low serum testosterone levels correlated with disease severity, accompanied by a strong inflammatory reaction and proportion of complement consumption.

DOI PubMed

Protective effect of Bifidobacterium longum BB536 against nausea caused by pirfenidone in a mouse model of pellagra.

Koji Kuronuma, Natsumi Susai, Tomohiro Kuroita, Takeshi Yoshioka, Atsushi Saito, Hirofumi Chiba

Bioscience of microbiota, food and health 42 ( 3 ) 195 - 202 2023年 [国内誌]

Pellagra is caused by abnormal intake and/or use of nicotinic acid and is known in part to be induced by the use of medications such as isoniazid or pirfenidone. We previously investigated atypical phenotypes of pellagra, such as nausea, using a mouse model of pellagra and found that gut microbiota play an important role in the development of these phenotypes. Here, we investigated the effect of Bifidobacterium longum BB536 on pellagra-related nausea caused by pirfenidone in our mouse model. Our pharmacological data indicated that pirfenidone (PFD) causes modulation of the gut microbiota profile, which appeared to play an important role in the development of pellagra-related nausea. A gut microbiota-mediated protective effect of B. longum BB536 against nausea caused by PFD was also identified. Finally, the urinary ratio of nicotinamide/N-methylnicotinamide was shown to be a biomarker of pellagra-like adverse effects induced by PFD, and it may contribute to the prevention of these effects in patients with idiopathic pulmonary fibrosis.

DOI PubMed

The Soluble Lectin Families as Novel Biomarkers for COVID-19 Pneumonia.

Haruka Takenaka, Atsushi Saito, Koji Kuronuma, Keigo Moniwa, Hirotaka Nishikiori, Satoshi Takahashi, Hirofumi Chiba

In vivo (Athens, Greece) 37 ( 4 ) 1721 - 1728 2023年 [国際誌]

BACKGROUND/AIM: The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association with other lectins (MBL and FCN1), disease severity, and radiographs in COVID-19 patients. PATIENTS AND METHODS: A total of 131 patients with COVID-19 admitted in the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled in the study. Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients' medical records. Chest computed tomography (CT) scanning was performed at admission. Serum levels of surfactant protein A and D (SP-A and SP-D), mannose-binding lectin (MBL) and ficolin1 (FCN1) were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1 ng/ml; p<0.01). The severe group in COVID-19 had significantly higher serum SP-D and lower MBL levels than the non-severe group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05). SP-D strongly reflected the degree of imaging findings, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings. CONCLUSION: Among soluble serum lectins, SP-A and SP-D may be more sensitive to CT findings than reported disease biomarkers such as IL-6, LDH, and CRP due to their lung-specific characteristics.

DOI PubMed

Pneumocystis jirovecii Pneumonia Associated with COVID-19 in Patients with Interstitial Pneumonia.

Tomoyuki Takahashi, Atsushi Saito, Koji Kuronuma, Hirotaka Nishikiori, Hirofumi Chiba

Medicina (Kaunas, Lithuania) 58 ( 9 ) 2022年08月 [国際誌]

Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed Pneumocystis jirovecii pneumonia (PJP) following coronavirus disease 2019 (COVID-19) infection. Case 1: A 69-year-old man on 10 mg of prednisolone (PSL) daily for IP developed new pneumonia shortly after his COVID-19 infection improved and was diagnosed with PJP based on chest computed tomography (CT) findings and elevated serum β-D-glucan levels. Trimethoprim-sulfamethoxazole (TMP-SMZ) was administered, and the pneumonia resolved. Case 2: A 70-year-old woman taking 4 mg/day of PSL for IP and rheumatoid arthritis developed COVID-19 pneumonia, which resolved mildly, but her pneumonia flared up and was diagnosed as PJP based on CT findings, elevated β-D-glucan levels, and positive polymerase chain reaction for P. jirovecii DNA in the sputum. The autopsy revealed diffuse alveolar damage, increased collagen fiver and fibrotic foci, mucinous component accumulation, and the presence of a P. jirovecii cyst. In conclusion, steroids and immunosuppressive medications are well-known risk factors for PJP. Patients with IP who have been taking these drugs for a long time are frequently treated with additional steroids for COVID-19; thus, PJP complications should be avoided in such cases.

DOI PubMed

Association between annual change in FEV1 and comorbidities or impulse oscillometry in chronic obstructive pulmonary disease.

Hiroyuki Sugawara, Atsushi Saito, Saori Yokoyama, Kazunori Tsunematsu, Hirofumi Chiba

BMC pulmonary medicine 22 ( 1 ) 185 - 185 2022年05月 [国際誌]

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. The decline in forced expiratory volume in one second (FEV1) is considered to be one of the most important outcome measures for evaluating disease progression. However, the only intervention proven to improve COPD prognosis is smoking cessation. This study therefore investigated the factors associated with annual FEV1 decline in COPD. METHODS: This retrospective study followed up 65 patients treated for COPD for 5 years: 13 current smokers and 52 former smokers, 25 with pneumonia, 24 with asthma, 18 with cancer, and 17 with cardiovascular disease. The patients were divided into groups based on clinical cutoff parameters of the impulse oscillometry system (IOS): 11 high and 54 low R5, 8 high and 57 low R20, 21 high and 44 low R5-R20, 26 high and 39 low X5, 38 high and 27 low Fres, and 36 high and 29 low AX. We investigated whether the decline in FEV1 was associated with comorbidities and IOS parameters. RESULTS: The annual change in FEV1 over 5 years was significantly affected by smoking status (current - 66.2 mL/year vs. former - 5.7 mL/year, p < 0.01), pneumonia (with - 31.5 mL/year vs. without - 8.9 mL/year, p < 0.05), asthma (with - 30.2 mL/year vs. - 10.8 mL/year, p < 0.01), but not by cancer and cardiovascular disease. In the groups defined by IOS results, only the high AX group had significantly more annual decline in FEV1 and %FEV1 than the low AX group (- 22.1 vs. - 12.8, p < 0.05 and - 0.20 vs. 0.40, p < 0.05, respectively). CONCLUSIONS: Continuing smoking as well as complications in pneumonia and asthma would be risk factors for the progression of COPD. AX might be a suitable parameter to predict the prognosis of patients with COPD.

DOI PubMed

COVID-19肺炎重症度予測マーカーとしてのIL-6、INF-λ3、NGALの検討

黒沼幸治, 中江舞美, 藤谷好弘, 高橋聡, 齋藤充史, 安田健人, 千葉弘文

日本化学療法学会雑誌 ( (公社)日本化学療法学会 ) 70 ( Suppl.A ) 299 - 299 2022年05月

COVID-19 臨床経過予測因子 COVID-19肺炎重症度予測マーカーとしてのIL-6、INF-λ3、NGALの検討

齋藤充史, 安田健人, 黒沼幸治, 中江舞美, 藤谷好弘, 高橋聡, 千葉弘文

日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 11 ( 増刊 ) 153 - 153 2022年04月

N-glycosylation regulates MET processing and signaling.

Atsushi Saitou, Yoshihiro Hasegawa, Naoki Fujitani, Shigeru Ariki, Yasuaki Uehara, Ukichiro Hashimoto, Atsushi Saito, Koji Kuronuma, Kunio Matsumoto, Hirofumi Chiba, Motoko Takahashi

Cancer science 113 ( 4 ) 1292 - 1304 2022年04月 [国際誌]

MET, the receptor for the hepatocyte growth factor (HGF), is strongly associated with resistance to tyrosine kinase inhibitors, key drugs that are used in the therapy of non-small cell lung cancer. MET contains 11 potential N-glycosylation sites, but the site-specific roles of these N-glycans have not been elucidated. We report herein that these N-glycans regulate the proteolytic processing of MET and HGF-induced MET signaling, and that this regulation is site specific. Inhibitors of N-glycosylation were found to suppress the processing and trafficking of endogenous MET in H1975 and EBC-1 lung cancer cells and exogenous MET in CHO-K1 cells. We purified the recombinant extracellular domain of human MET and determined the site-specific N-glycan structures and occupancy using mass spectrometry. The results indicated that most sites were fully glycosylated and that the dominant population was the complex type. To examine the effects of the deletion of N-glycans of MET, we prepared endogenous MET knockout Flp-In CHO cells and transfected them with a series of N-glycan-deletion mutants of MET. The results showed that several N-glycans are implicated in the processing of MET. The findings also suggested that the N-glycans of the SEMA domain of MET positively regulate HGF signaling, and the N-glycans of the region other than the SEMA domain negatively regulate HGF signaling. Processing, cell surface expression, and signaling were significantly suppressed in the case of the all-N-glycan-deletion mutant. The overall findings suggest that N-glycans of MET affect the status and the function of the receptor in a site-specific manner.

DOI PubMed

Treatment of air leakage using the VIO soft coagulation system: a mouse pulmonary air leak model.

Yuki Takahashi, Atsushi Saito, Yuji Sakuma, Makoto Tada, Ryunosuke Maki, Motoko Takahashi, Atsushi Watanabe

Surgery today 51 ( 9 ) 1521 - 1529 2021年09月 [国内誌]

PURPOSE: We aimed to compare the efficacy of the VIO soft coagulation system (VSCS) for the treatment of air leaks by sealing with fibrin glue, and also assess the histological alterations that occur after soft coagulation. METHODS: A mouse pulmonary air leak model was designed. The pulmonary fistula was subsequently coagulated with the VSCS or sealed with fibrin glue with polyglycolic acid (PGA) sheets. The burst pressure at air leak recurrence was measured in each group, and the results were compared. We also evaluated the histological alterations in the mouse pulmonary air leak model after soft coagulation with the VSCS. RESULTS: The burst pressure in the soft coagulation group (80 W/Effect 5) (median 42.8; range 35.4-53.8 cmH2O) was similar to that in the fibrin glue group (median 41.5; range 34.6-43.9 cmH2O) (p = 0.21). Histological examinations revealed that the visceral pleura remained torn, the structure of the pulmonary alveolus was maintained, and the coagulated fistula was covered with a fibrin membrane in the soft coagulation group. CONCLUSIONS: The pressure resistance following soft coagulation was equivalent to that after sealing using fibrin glue with PGA sheets. The air leaks were likely controlled by covering the fistula with a fibrin membrane after soft coagulation with the VSCS.

DOI PubMed

Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.

Naoki Fujitani, Shigeru Ariki, Yoshihiro Hasegawa, Yasuaki Uehara, Atsushi Saito, Motoko Takahashi

Biochemistry 60 ( 21 ) 1708 - 1721 2021年06月 [国際誌]

Endoplasmic reticulum (ER) stress has been reported in a variety of diseases. Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress. The ER is the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated. This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress. Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress. The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone. Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress. Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics. Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.

DOI PubMed

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