Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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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： 10.1186/s12890-023-02776-y

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: The accuracy of nucleic acid amplification tests (NAATs) is affected by various factors; however, studies examining the factors affecting the accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test (QAT) are limited. METHODS: A total of 347 nasopharyngeal samples were collected from patients with coronavirus disease 2019 (COVID-19), and the date of onset was obtained from the electronic medical records. The SARS-CoV-2 antigen level was measured using Lumipulse Presto SARS-CoV-2 Ag (Presto), while NAAT was performed using the Ampdirect 2019-nCoV Detection Kit. RESULTS: Presto had a sensitivity rate of 95.1% (95% confidence interval: 92.8-97.4) in detecting the SARS-CoV-2 antigen in 347 samples. The number of days from symptom onset to sample collection was negatively correlated with the amount of antigen (r = -0.515) and sensitivity of Presto (r = -0.711). The patients' age was lower in the Presto-negative samples (median age, 39 years) compared with that in the Presto-positive samples (median age, 53 years; p < 0.01). A significant positive correlation was observed between age (excluding teenagers) and Presto sensitivity (r = 0.764). Meanwhile, no association was found between the mutant strain, sex, and Presto results. CONCLUSION: Presto is useful for the accurate diagnosis of COVID-19 owing to its high sensitivity when the number of days from symptom onset to sample collection is within 12 days. Furthermore, age may affect the results of Presto, and this tool has a relatively low sensitivity in younger patients.

DOI： 10.1016/j.jiac.2023.04.005

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本環境感染学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本環境感染学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

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： 10.1017/ice.2023.68

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Language：Japanese   Publisher：(公社)日本化学療法学会  

Ichushi

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Early diagnosis and appropriate infection control are important to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we aimed to assess the diagnostic performance of SARS-CoV-2 rapid antigen detection (RAD) tests and the factors that cause nonspecific reactions. METHODS: Nasopharyngeal swab specimens (n = 100), sputum specimens (n = 10), and lithium-heparin plasma samples (n = 100) were collected. We evaluated Espline®SARS-CoV-2 (Espline) and SARS-CoV-2 Rapid Antigen Test that also known as STANDARD Q® (STANDARD Q), with reverse transcription-polymerase chain reaction (RT-PCR) and Lumipulse® Presto SARS-CoV-2 Ag as reference tests. In addition, we investigated the effects of inadequate pretreatment methods and five potential causes of nonspecific reactions. RESULTS: The sensitivities of Espline and STANDARD Q were 60% and 57%, respectively, and their specificity was 100%. It was confirmed that the judgment line for the positive insufficiently mixed specimens was faint. A false-positive result was observed with STANDARD Q when sputum was used as a specimen to investigate judgment the effect of viscosity. CONCLUSIONS: Espline and STANDARD Q show good sensitivity for specimens with Ct values less than 25, but specimens collected within 9 days of symptom onset may still give false negatives. The test should be performed carefully, and the results should be judged comprehensively, taking into account clinical symptoms and patient background.

DOI： 10.1016/j.jiac.2022.10.007

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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： 10.12938/bmfh.2022-042

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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： 10.21873/invivo.13334

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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： 10.21873/invivo.13259

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Language：Japanese   Publisher：日本感染症学会東日本地方会・日本化学療法学会東日本支部  

Ichushi

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Language：Japanese   Publisher：日本感染症学会東日本地方会・日本化学療法学会東日本支部  

Ichushi

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Language：Japanese   Publisher：日本感染症学会東日本地方会・日本化学療法学会東日本支部  

Ichushi

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Language：English  

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： 10.3390/medicina58091151

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Noroviruses (NoVs) are major causes of acute viral gastroenteritis at all ages worldwide. The molecular epidemiology of sporadic cases remains poorly understood, especially in adults. Additionally, no studies have analyzed the transmission route in sporadic acute gastroenteritis. In this study, we investigated cases of very mild sporadic NoV acute gastroenteritis in adults (medical staff) who do not visit the outpatient clinic and child outpatients. We also evaluated genotype differences between adults and children and possible transmission routes in adults during 5 years. The number of NoV positives were 58 in adults and 124 in children. In adults, the NoV positivity rate in this study was higher (64.4%) than that in previous reports of outpatients (10%) and inpatients (5%) in the United State. This finding suggested that the NoV positivity rate might be high in adults with very mild acute gastroenteritis. In adults, human-to-human transmission rates from children and food-borne transmission (raw oysters) were 21.6% (11/51) and 19.6% (10/51), respectively. Among adults, GII.2, GII.4, and GII.17 were the predominant genotypes, with rates of 32.7%, 30.9%, and 21.8%, respectively. Among children, GII.4 and GII.2 were the predominant genotypes, with rates of 45.5% and 40.6%, respectively. GII.17 was only detected in 0.8% (1/123) of children. Trends in NoV genotypes are expected to differ depending on the patient's age. Investigating sporadic cases including the patient's background (age and transmission route) may be helpful to monitor the trend of NoV strains, forecast prevalent NoV GII genotypes, and develop NoV vaccines.

DOI： 10.1016/j.meegid.2022.105348

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INTRODUCTION: Compared to nasopharyngeal swabs (NPS), there has been insufficient evaluation of the diagnostic performance of nasal swabs (NS) for the detection of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the nucleic acid amplification test (NAAT) and quantitative SARS-CoV-2 antigen test (QAT). METHODS: We prospectively compared healthcare worker-collected and flocked NS within nine days after symptom onset to paired NPS to detect SARS-CoV-2 in NAAT and QAT on the fully automated Lumipulse system. The agreement between sample types was evaluated, and cycle threshold (Ct) values and antigen levels were used as surrogate viral load measures. RESULTS: Sixty sets of NPS and NS samples were collected from 40 patients with COVID-19. The overall agreements between NAAT and QAT samples were 76.7% and 65.0%, respectively. In NAAT, the Ct value of NS was significantly higher, 5.9, than that of NPS. Thirty-nine (95.1%) NS tested positive in 41 positive-paired NPS with Ct ≤ 30. The negative correlation was observed between antigen levels of NS in QAT and Ct values of NS in NAAT (r = -0.88). In QAT, the antigen level of NS was significantly lower than that of NPS. Thirty-six (90.0%) NS tested positive in 40 positive-paired NPS with antigen levels >100 pg/mL, which were collected significantly earlier than those with antigen levels ≤100 pg/mL. CONCLUSIONS: In NAAT and QAT, NS had limited performance in detecting SARS-CoV-2 compared to NPS. However, NS may be helpful for patients with COVID-19 with high viral loads or those in the early stages of the illness.

DOI： 10.1016/j.jiac.2022.07.023

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INTRODUCTION: This study aimed to evaluate rapid antigen detection (RAD) and rapid nucleic acid amplification tests (NAATs) to detect influenza virus (IV). METHODS: The conventional RAD test (Quick Chaser Flu A, B: QC), using silver amplified immunochromatography (Quick Chaser Auto Flu A, B: QCA), as well as two NAATs (Xpert Xpress Flu/RSV: Xpert, cobas Influenza A/B & RSV: cobas) were evaluated using nasopharyngeal swabs from suspected cases of influenza. A reference method was performed using real-time reverse transcription polymerase chain reaction according to the manual of the Japanese National Institute of Infectious Disease (NIID). RESULTS: From a total of 177 samples, 51 were positive according to the NIID assay. The kappa (κ) coefficient in Xpert and cobas for influenza A virus (IAV)/influenza B virus (IBV) was 1.00, which was the highest among the four detection assays. However, the κ coefficients in QC and QCA for IAV/IBV were 0.71-0.77 and 0.87-0.89, respectively. The sensitivities of the RAD tests were 41.7% in QC and 50.0% in QCA at < 6 h after onset, and 100.0% in both QC and QCA at 24-48 h after onset. The cycle threshold (Ct) values were significantly lower in the group in which all detection assays were positive for IAV. CONCLUSIONS: Xpert and cobas have comparable analytical performances and are highly useful as influenza virus detection assays. QC and QCA could show false negatives frequently in the early stage of infection and when viral load is low.

DOI： 10.1016/j.jiac.2022.04.009

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We evaluated the optimal timing of saliva sample collection to diagnose the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We obtained 150 saliva samples at four specific time points from 13 patients with confirmed SARS-CoV-2 infection. The time points were (1) early morning (immediately after waking), (2) immediately after breakfast before tooth brushing, (3) 2 h after breakfast, and (4) before lunch. On the 2nd hospital day, patients collected saliva at the four time points by themselves. We collected samples at two time points, (1) and (3), from the 3rd hospital day to day 9 following symptom onset. In 52 samples collected at the four time points, there was no significant difference. Meanwhile, there was no significant difference in the positive proportion or the viral load between the two time points in both analyses by the day from symptom onset and by all samples. In this study, there was no difference in the positive proportions in saliva collected at various time points within 9 days after symptom onset. The timing of saliva collection was not affected by the diagnosis of SARS-CoV-2 infection.

DOI： 10.1016/j.jiac.2022.03.009

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Language：Japanese   Publisher：(公社)日本化学療法学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

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： 10.1111/cas.15278

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Language：Japanese   Publisher：(公社)日本化学療法学会  

Ichushi

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BACKGROUND/AIM: Smell and taste disorders are among the most common symptoms of COVID-19. However, the relationship between smell and taste disorders and systemic symptoms is not fully understood in Japan. PATIENTS AND METHODS: Questionnaires were mailed to 105 of 111 COVID-19 patients who were hospitalized at our hospital between March and July 2020 in Japan. RESULTS: A total of 74 patients (response rate: 70.5%) completed the survey. Of these, six patients (8.1%) presented with smell disorders only, 16 (21.6%) presented with taste disorders only, and 17 (23.0%) presented with both smell and taste disorders. The mean Visual Analog Scale for smell and taste was 0.5 and 20, respectively, at the time of the most severe symptoms. CONCLUSION: Among COVID-19 patients in Japan, smell and taste disorders are often followed by fever and may not be the first symptoms. Sense of smell is particularly impaired. These symptoms often improve, although they sometimes persist for a long time as sequelae.

DOI： 10.21873/invivo.12781

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Language：Japanese   Publisher：(有)科学評論社  

Ichushi

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Language：Japanese   Publisher：国立感染症研究所  

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: The antiviral drug favipiravir has been shown to have in vitro antiviral activity against severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2). In this study, we investigated the clinical benefits and initiation of favipiravir treatment in patients with non-severe coronavirus-disease-2019 (COVID-19). METHODS: This study was a single-center retrospective cohort study. Receiver operating characteristic curves were drawn to calculate the area under the curve, and the optimal cut-off values for the time to initiate favipiravir treatment were calculated to predict defervescence within seven days. Univariate and multivariate Cox regression analyses were performed to identify potential influencing factors of defervescence. This was defined as a body temperature of less than 37 °C for at least 2 days. RESULTS: Data from 41 patients were used for the efficacy assessment. The days from the onset of fever to defervescence showed a positive correlation with the duration from the onset of fever to initiation of favipiravir treatment (r = 0.548, P < 0.001). The optimal cut-off value was the administration of favipiravir on day 4. Patients were assigned to two groups based on the optimal cut-off value from onset to initiation of favipiravir treatment: early treatment group (within 4-days) and late treatment group (more than 4-days). In the multivariate analysis, when adjusted for age, sex, and days from onset to initiation of favipiravir treatment, the significant factors were male sex and days of initiation of the favipiravir treatment. CONCLUSIONS: We recommend that if favipiravir is to be used for treatment, it should be initiated as early as possible.

DOI： 10.1016/j.jiac.2021.04.013

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A 68-year-old man experienced fever and cough and was referred to a hospital for day 4. He had a positive reverse transcription-polymerase chain reaction result for severe acute respiratory syndrome coronavirus-2. On day 12, his PaO2/FiO2 ratio worsened to 120 and he was transferred to Sapporo Medical University Hospital for treatment using extracorporeal membrane oxygenation. Venous blood cultures were positive for Streptococcus pneumoniae, which were serotype 3, mucoid-type, and penicillin susceptible. Coinfections with coronavirus disease-2019 and invasive pneumococcal disease are rare; however, they are associated with a higher case fatality than either of the conditions manifesting alone.

DOI： 10.1016/j.jiac.2021.04.004

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Language：Japanese   Publisher：COSMIC  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Coronavirus disease (COVID-19) emerged in January 2020 in Sapporo city, and the outbreak has shown two peaks. METHODS: A total of 260 COVID-19 patients were enrolled and categorized into three groups according to the pandemic pattern, jobs and situation, and disease severity. We compared clinical characteristics according to these categories. RESULTS: We found two pandemic peaks, and the proportion of patients and health providers who were infected in other hospitals had increased in the latter two periods (period 2: 49.6%, period 3: 32.7%). Particularly, the proportion of infected health providers was 27% in period 2, and they tended to be younger females with a mild condition. Severity of the disease (requirement of oxygen and/or mechanical ventilation) was associated with advanced age, and all the patients who died during admission were over 60 years old. CONCLUSIONS: We reported the temporal dynamics and characteristics of the COVID-19 pandemic in Sapporo city, Japan. This survey from the viewpoint of the hospital provides a new insight into and a better guide for the further management of the COVID-19 pandemic.

DOI： 10.1016/j.resinv.2020.11.008

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

Ichushi

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Language：English  

We report a case of acute eosinophilic pneumonia (AEP) triggered by coronavirus disease 2019 (COVID-19) infection. A 77-year-old man experienced left-sided chest pain and shortness of breath. Reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) revealed a positive result, and he was treated with favipiravir, ciclesonide, and lascufloxacin, but he showed poor improvement. On the other hand, computed tomography (CT) images were atypical for COVID-19 infection, and the elevation of eosinophil was found in blood and the fluid obtained by bronchoscopy. So, we clinically diagnosed this case as AEP. Administration of prednisolone dramatically improved the patient's clinical condition and chest radiograph findings, which were consistent with the clinical course of AEP. This case suggests the importance of considering the complications of AEP when treating patients with COVID-19 infection.

DOI： 10.1002/rcr2.683

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本化学療法学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s12890-020-1118-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

DOI： 10.1016/j.resp.2020.103386

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Language：Japanese   Publisher：(株)先端医学社  

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central  

DOI： 10.1186/s12890-020-1060-y

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Language：English   Publishing type：Research paper (scientific journal)  

Haemophilus influenzae is a pathogenic bacterium that causes respiratory and otolaryngological infections. The increasing prevalence of β-lactamase-negative high-level ampicillin-resistant H. influenzae (high-BLNAR) is a clinical concern. Fluoroquinolones are alternative agents to β-lactams. However, the emergence and increasing prevalence of fluoroquinolone-resistant H. influenzae have been reported. The current risk of fluoroquinolone resistance in H. influenzae (especially in high-BLNAR) has not yet been evaluated. Here, we examined the development of fluoroquinolone resistance in fluoroquinolone-susceptible clinical H. influenzae isolates in vitro during passaging in the presence of moxifloxacin (from 0.03 to 128 mg/liter). Twenty-nine isolates were examined. Seventeen isolates (58.6%) showed reduced moxifloxacin susceptibility, and 10 of these 17 isolates (34.5% of all isolates) exceeded the Clinical and Laboratory Standards Institute breakpoint for moxifloxacin (MIC of >1 mg/liter) after repeat cultivation on moxifloxacin-containing agar. Seven of these ten isolates were high-BLNAR and represented multiple lineages. We identified 56 novel mutations in 45 genes induced during the development of fluoroquinolone resistance, except the defined quinolone resistance-determining regions (Ser84Leu and Asp88Tyr/Gly/Asn in GyrA and Gly82Asp, Ser84Arg, and Glu88Lys in ParC). Glu153Leu and ΔGlu606 in GyrA, Ser467Tyr and Glu469Asp in GyrB, and ompP2 mutations were novel mutations contributing to fluoroquinolone resistance in H. influenzae In conclusion, H. influenzae clinical isolates from multiple lineages can acquire fluoroquinolone resistance by multiple novel mutations. The higher rate of derivation of fluoroquinolone-resistant H. influenzae from high-BLNAR than β-lactamase-negative ampicillin-susceptible isolates (P = 0.01) raises the possibility of the emergence and spread of fluoroquinolone-resistant high-BLNAR in the clinical setting.

DOI： 10.1128/AAC.01500-19

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INTRODUCTION: Interstitial lung disease (ILD) is a heterogeneous group of diseases characterized by varying degrees of lung inflammation and/or fibrosis. We investigated biomarkers to infer whether patients with collagen vascular diseases associated ILD (CVD-ILD) and interstitial pneumonia with autoimmune features (IPAF) benefit from immunosuppressive therapy. MATERIALS AND METHODS: We retrospectively investigated patients with CVD-ILD, IPAF, and idiopathic pulmonary fibrosis (IPF) between June 2013 and May 2017 at our department. First, we assessed differences in serum and bronchoalveolar lavage fluid (BALF) levels of cytokines between groups. Second, we assessed the associations of patient's clinical variables with serum and BALF levels of those cytokines that were different between groups. Finally, we assessed the associations of diagnosis and response to immunosuppressive therapy with serum levels of those cytokines that were different between groups. RESULTS: We included 102 patients (51 with IPF, 35 with IPAF, and 16 with CVD-ILD). Serum and BALF levels of CXCL9, CXCL10, and CXCL11 were significantly elevated in patients with IPAF or CVD-ILD compared with those in patients with IPF. BALF levels of CXCL9 and CXCL10 were correlated with the percentages of lymphocytes and macrophages in BALF. Serum levels of CXCL9 and CXCL10 were correlated with BALF levels. Serum levels of CXCL9, CXCL10, and CXCL11 were correlated C-reactive protein, percent predicted forced vital capacity, alveolar-arterial oxygen difference, and the percentages of lymphocytes and macrophages in BALF. Serum levels of CXCL9, CXCL10, and CXCL11 showed moderate accuracy to distinguish patients with CVD-ILD from those with IPAF and IPF. Pre-treatment serum levels of CXCL9 and CXCL11 showed strong positive correlations with the annual forced vital capacity changes in patients with IPAF and CVD-ILD treated with immunosuppressive drugs. CONCLUSIONS: Serum CXCL9, CXCL10, and CXCL11 are potential biomarkers for autoimmune inflammation and predictors of the immunosuppressive therapy responses in ILD with background autoimmunity.

DOI： 10.1371/journal.pone.0241719

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Language：Japanese   Publisher：日本サルコイドーシス  

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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BACKGROUND: The incidence of infectious disease caused by nontuberculous mycobacteria is increasing worldwide. Pulmonary Mycobacterium avium complex (MAC) disease is difficult to treat with chemotherapy, and its mechanism of infection, infection route, disease onset, and severity remain unknown. Ficolins are oligomeric defense lectins. L-ficolin plays an important role in innate immunity. This study's aim was to identify L-ficolin's role in patients with pulmonary MAC disease. METHODS: Between April 2011 and September 2017, 61 Japanese patients with pulmonary MAC disease were seen at our hospital. A control group, comprising 30 healthy individuals, without respiratory disease were enrolled in our study. The relationship between serum L-ficolin levels and disease severity was assessed, and L-ficolin's antibacterial role was examined. RESULTS: Serum L-ficolin levels were significantly lower in patients with pulmonary MAC disease than in healthy subjects (1.69 ± 1.27 μg/ml vs. 3.96 ± 1.42 μg/ml; p < 0.001). The cut-off value, based on receiver operating characteristic (ROC) analysis results, was 2.48 μg/ml (area under the curve (AUC) 0.90, sensitivity and specificity 83.6 and 86.7%, respectively). Serum L-ficolin levels were significantly lower in the patients with nodular bronchiectatic type disease compared with the patients with fibrocavitary type disease and were lower in the high-resolution computed tomography high-scoring group compared with low-scoring group. An in vitro analysis showed that purified recombinant L-ficolin bound to M. avium and its major cell wall component, lipoarabinomannan, in a concentration-dependent manner. In addition, recombinant L-ficolin suppressed M. avium growth in a concentration-dependent manner. CONCLUSIONS: Insufficient serum L-ficolin is associated with disease progression in pulmonary MAC disease, and the level of serum L-ficolin is a possible biomarker. TRIAL REGISTRATION: This study is registered with UMIN ( UMIN000022392 ).

DOI： 10.1186/s12931-019-1185-9

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We herein report a case of autoimmune pulmonary alveolar proteinosis (PAP) diagnosed after one-time exposure to silica powder. Owing to the misuse of a silica-containing fire extinguisher and the inhalation of large amounts of its powder, the patient experienced prolonged cough and visited our hospital. The findings of chest computed tomography and surgical lung biopsy specimens led to the diagnosis of PAP. Interestingly, the presence of anti-GM-CSF antibody was detected; therefore, both autoimmune characteristics and exposure to large amounts of silica may have caused the development of PAP in this patient. This case provides important insight into the mechanisms leading to the onset of PAP.

DOI： 10.2169/internalmedicine.1557-18

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Taylor and Francis Inc.  

DOI： 10.1080/21645515.2018.1564443

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Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：日本サルコイドーシス  

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

β-Lactam-resistant Haemophilus influenzae is a clinical concern. A high prevalence (>40%) of β-lactamase-negative high-level ampicillin-resistant H. influenzae (high-BLNAR) isolates in Japan has been reported. However, the reasons for the expansion are unknown. High-BLNAR strains possess an amino acid substitution, either Asn526Lys (group III) or Arg517His (group III-like) in addition to Ser385Thr, in penicillin-binding protein 3 (PBP3). To determine the current prevalence of high-BLNAR strains and the mechanisms behind their expansion in Japan, their prevalence, PBP3 types, multilocus sequence types, and susceptibilities to quinolones approved in Japan as alternatives were determined. Sixty percent of H. influenzae clinical isolates (62/104 isolates) were β-lactamase-negative ampicillin-resistant H. influenzae (BLNAR) strains. Among BLNAR isolates, 92% (57/62 isolates) were high-BLNAR strains. Most isolates were classified as belonging to group III, which contained many genotypes (11 PBP3 types and 25 sequence types). These results indicated that the expansion of high-BLNAR isolates was multiclonal and such strains are still predominant in Japanese clinical settings. One high-BLNAR isolate harbored the novel amino acid substitution Asn526Met in addition to Ser385Thr in PBP3, suggesting a new group (group IV). No quinolone-resistant H. influenzae isolates were identified. The MICs for the quinolones (moxifloxacin, garenoxacin, and tosufloxacin) were similar to that for levofloxacin, whereas sitafloxacin exhibited a lower MIC. However, we obtained 4 H. influenzae isolates with decreased quinolone susceptibility with the amino acid substitution Ser84Leu in GyrA, and 3 of those isolates were high-BLNAR isolates. In summary, this study shows that multiclonal high-BLNAR strains predominate in a Japanese university hospital. Isolates remain sensitive to quinolones, but vigilance is required to prevent the development of fluoroquinolone resistance in high-BLNAR strains.

DOI： 10.1128/AAC.00851-18

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Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance (mcr) gene-negative colistin-resistant Escherichia coli clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131-H30Rx (isolates SRE34 and SRE44; MIC for colistin = 16 mg/liter), non-x (SME296; MIC = 8 mg/liter), and O18-ST416 (SME222; MIC = 4 mg/liter). In this study, we investigated the colistin resistance mechanism and identified novel amino acid substitutions or deletions in the PmrAB two-component system that activates eptA (encoding a phosphoethanolamine transferase) and arnT (encoding an undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferase) in all colistin-resistant isolates. SRE34 possessed deletion Δ27-45 (LISVFWLWHESTEQIQLFE) in PmrB, SRE44 possessed substitution L105P in PmrA, and both SME222 and SME296 included substitution G206D in PmrB. Matrix-assisted laser desorption ionization-time of flight mass spectrometry revealed that lipid A is modified with phosphoethanolamine in all four isolates. Deletion of pmrAB decreased colistin MICs to 0.5 mg/liter and lowered eptA and arnT expression. Chromosomal replacement of mutated pmrA or pmrB in colistin-susceptible O25b:H4-ST131 strain SME98 (colistin MIC = 0.5 mg/liter) increased the colistin MIC to that of the respective parent colistin-resistant isolate. In addition, SME98 mutants in which pmrAB was replaced with mutated pmrAB showed no significant differences in bacterial growth and competition culture from the parent strain, except for the mutant with L105P in PmrA, whose growth was significantly suppressed in the presence of the parent strain. In conclusion, some O25b:H4-ST131 strains appear to acquire colistin resistance via phosphoethanolamine modification of lipid A through amino acid changes in PmrAB, and the amino acid changes in PmrB do not influence bacterial growth.

DOI： 10.1128/AAC.00864-18

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BACKGROUND: Interstitial lung diseases (ILD) are severe respiratory diseases, and ILD patients are treated with corticosteroid and immunosuppressive agents. However, it is unclear whether these medications influence the response of pneumococcal vaccine. OBJECTIVES: We examined the immunogenicity of pneumococcal vaccines (PPSV23 and PCV13) in ILD patients undergoing immunosuppressive treatment. METHODS: ILD patients who were regularly followed at the outpatient clinic were enrolled. Sera were collected before and 4-8 weeks after vaccination. Serotype-specific immunoglobulin G (IgG) concentrations against pneumococcal serotype 19F were measured by ELISA. RESULTS: IgG concentrations to serotype 19F were increased in all groups in response to the vaccine. Both PCV13 and PPSV23 induced IgG concentrations in patients immunized for the first time. Response rates for the ILD group were comparable with those for the ILD group undergoing corticosteroid therapy. Only idiopathic pulmonary fibrosis patients undergoing immunosuppressive therapy had a significantly lower response.

DOI： 10.1016/j.vaccine.2018.06.062

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Multidrug-resistant Streptococcus pneumoniae strains were isolated from blood and sputum of a patient with disseminated intravascular coagulation in Sapporo city, Japan. These antibiograms were only susceptible to vancomycin, linezolid, daptomycin, some carbapenems, and some fluoroquinolones. Identical antibiograms, serotypes (19F), and sequence types (ST10017) suggested a shared origin of these isolates. Only one ST10017 strain has been isolated in the same city in Japan previously (2014), and the 2014 isolate is still susceptible to macrolides. The whole genome of the blood-derived isolate was sequenced. The strain harbored resistance mutations in parC, gyrA, pbp1a, pbp2a, pbp2b, and pbp2x, and harbored the resistance genes, ermB and tetM. The nucleotide sequences of parC and pbp2x genes of strain MDRSPN001 were clearly different from those of other S. pneumoniae strains and were similar to those of oral streptococci strains. These findings suggest that strain MDRSPN001 has been rapidly and drastically evolving multidrug resistance by gene replacement and accumulation of genes originating from other strains, such as oral streptococci, Streptococcus mitis.

DOI： 10.1016/j.jiac.2018.01.012

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Language：Japanese   Publisher：(公社)日本化学療法学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本化学療法学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本内科学会  

Ichushi

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DOI： 10.1186/s12931-018-0736-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

DOI： 10.1155/2018/6043053

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DOI： 10.1038/onc.2017.253

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We recently reported that the lectin surfactant protein D (SP-D) suppresses epidermal growth factor receptor (EGFR) signaling by interfering with ligand binding to EGFR through an interaction between the carbohydrate-recognition domain (CRD) of SP-D and N-glycans of EGFR. Here, we report that surfactant protein A (SP-A) also suppresses EGF signaling in A549 human lung adenocarcinoma cells and in CHOK1 cells stably expressing human EGFR and that SP-A inhibits the proliferation and motility of the A549 cells. Results with 125I-EGF indicated that SP-A interferes with EGF binding to EGFR, and a ligand blot analysis suggested that SP-A binds EGFR in A549 cells. We also found that SP-A directly binds the recombinant extracellular domain of EGFR (soluble EGFR or sEGFR), and this binding, unlike that of SP-D, was not blocked by EDTA, excess mannose, or peptide:N-glycosidase F treatment. We prepared a collagenase-resistant fragment (CRF) of SP-A, consisting of CRD plus the neck domain of SP-A, and observed that CRF directly binds sEGFR but does not suppress EGF-induced phosphorylation of EGFR in or proliferation of A549 cells. These results indicated that SP-A binds EGFR and down-regulates EGF signaling by inhibiting ligand binding to EGFR as well as SP-D. However, unlike for SP-D, SP-A lectin activity and EGFR N-glycans were not involved in the interaction between SP-A and EGFR. Furthermore, our results suggested that oligomerization of SP-A is necessary to suppress the effects of SP-A on EGF signaling.

DOI： 10.1074/jbc.M117.800771

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.rmed.2017.08.021

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DOI： 10.1183/1393003.congress-2017.PA911

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00298&link_issn=&doc_id=20171026310004&doc_link_id=%2Fcf0brond%2F2017%2F003905%2F005%2F0386-0391%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2017%2F003905%2F005%2F0386-0391%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00408-017-9979-3

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Human β-defensin 3 (hBD3) is known to be involved in mast cell activation. However, molecular mechanisms underlying the regulation of hBD3-induced mast cell activation have been poorly understood. We previously reported that SP-A and SP-A-derived peptide 01 (SAP01) regulate the function of hBD3. In this study, we focused on the effects of SP-A and SAP01 on the activation of mast cells induced by hBD3. SAP01 directly bound to hBD3. Mast cell-mediated vascular permeability and edema in hBD3 administered rat ears were decreased when injected with SP-A or SAP01. Compatible with the results in rat ear model, both SP-A and SAP01 inhibited hBD3-induced chemotaxis of mast cells in vitro. Direct interaction between SP-A or SAP01 and hBD3 seemed to be responsible for the inhibitory effects on chemotaxis. Furthermore, SAP01 attenuated hBD3-induced accumulation of mast cells and eosinophils in tracheas of the OVA-sensitized inflammatory model. SP-A might contribute to the regulation of inflammatory responses mediated by mast cells during infection.

DOI： 10.1016/j.bbrc.2017.02.028

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：(株)医学書院  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/01902148.2017.1354946

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DOI： 10.2169/internalmedicine.56.7590

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

DOI： 10.1016/j.resinv.2016.02.009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Taylor and Francis Ltd  

DOI： 10.1080/01902148.2016.1215570

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J03102&link_issn=&doc_id=20160414600034&doc_link_id=%2Fae6bkybd%2F2016%2F002001%2F034%2F0120-0123%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6bkybd%2F2016%2F002001%2F034%2F0120-0123%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND AND PURPOSE: According to recent news, patients with concurrent tuberculosis (TB) and human immunodeficiency virus (HIV) infection are increasingly common worldwide. This study aimed to investigate whether TB/HIV co-infected patients are visiting Hokkaido. METHOD: We conducted a questionnaire survey regarding foreign patients infected with TB or TB/HIV who visited Hokkaido between January 2001 and September 2014. We mailed questionnaires to health centers, AIDS treatment care hospitals, and TB hospitals in Hokkaido prefecture. RESULTS: Seventy-one TB patients were of foreign nationality according to the answers obtained from health centers. Most of them were foreign students or occupational trainees between 20-30 years old. Approximately half these patients were from East Asia, and 7 patients were from Africa. As 21 % of the patients with TB who visited medical examination were over 1 month from disease onset, and the delay in visiting was recognized. The TB infection was mostly detected coincidentally during the physician visit. In the hospital survey, four TB patients with HIV were of foreign nationality. They were also of the age group from 20-30 years and hailed from sub-Saharan Africa. DISCUSSION: During immigration, medical examination by performing a chest radiograph is important. If the immigrant hails from an area where TB and HIV co-infection is common, it is necessary to confirm whether HIV infection is present.

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Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00407&link_issn=&doc_id=20160229460002&doc_link_id=40020740423&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40020740423&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Ichushi

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Language：Japanese   Publisher：The Japan Society for Respiratory Endoscopy  

Background. Cryptogenic organizing pneumonia (COP) usually responds well to corticosteroid treatment and typically has a good prognosis. However, a few cases are refractory to corticosteroid treatment. Immunosuppressant drugs are associated with an increased risk of malignant lymphoproliferative disorders. Case. A 63-year-old man presented with a history of cough for a month. High resolution computed tomography (HRCT) of the chest showed air-space consolidation predominantly in both lungs. We diagnosed COP by transbronchial lung biopsy (TBLB) specimens. Clinical data and HRCT findings were improved by prednisolone therapy, but recurrent exacerbation occurred during steroid tapering. Although, we re-examined the abnormal lesions in the left lower lobe by video-assisted thoracoscopy and those in the right lower lobe by TBLB, histopathological examinations of all lesions revealed organizing pneumonia. We continued immunosuppressive therapy with a combination of prednisolone and immunosuppressive agents. However, lung lesions gradually deteriorated. In order to obtain a histopathological diagnosis again, we performed TBLB from the right lower lobe. Histopathological examination revealed lung invasion of diffuse large B cell type lymphoma. Conclusion. We experienced a rare case of recurrent COP complicated by primary pulmonary malignant lymphoma. It is necessary to pay attention to the possibility that malignant lymphoma may be involved in recurrent COP during immunosuppressive therapy.

Other Link： http://search.jamas.or.jp/link/ui/2016212248

DOI： 10.18907/jjsre.38.2_134

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Language：Japanese   Publisher：ライフサイエンス出版(株)  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01759&link_issn=&doc_id=20150713050007&doc_link_id=issn%3D0289-8020%26volume%3D36%26issue%3D6%26spage%3D557&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0289-8020%26volume%3D36%26issue%3D6%26spage%3D557&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00298&link_issn=&doc_id=20150521230412&doc_link_id=%2Fcf0brond%2F2015%2F0037s1%2F412%2F5290-5290%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2015%2F0037s1%2F412%2F5290-5290%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00298&link_issn=&doc_id=20150521230295&doc_link_id=%2Fcf0brond%2F2015%2F0037s1%2F295%2F5247-5247%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2015%2F0037s1%2F295%2F5247-5247%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00298&link_issn=&doc_id=20150213260017&doc_link_id=%2Fcf0brond%2F2015%2F003701%2F019%2F0087-0093%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2015%2F003701%2F019%2F0087-0093%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/1471-2466-14-196

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00298&link_issn=&doc_id=20141218320058&doc_link_id=%2Fcf0brond%2F2014%2Fs03606%2F041%2F0681-0682%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2014%2Fs03606%2F041%2F0681-0682%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00298&link_issn=&doc_id=20140415290281&doc_link_id=%2Fcf0brond%2F2014%2F0036s1%2F11a%2F5216-5216%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2014%2F0036s1%2F11a%2F5216-5216%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Ichushi

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Language：English  

Gangliosides are glycosphingolipids found on the cell surface. They act as recognition molecules or signal modulators and regulate cell proliferation and differentiation. N-glycolylneuraminic acid (NeuGc)-containing gangliosides have been detected in some neoplasms in humans, although they are usually absent in normal human tissues. Our aim was to evaluate the presence of NeuGc-containing gangliosides including GM3 (NeuGc) and assess their relationship with the prognosis of non-small-cell lung cancer (NSCLC). NeuGc-containing ganglioside expression in NSCLC tissues was analyzed immunohistochemically using the mouse monoclonal antibody GMR8, which is specific for gangliosides with NeuGc alpha 2,3Gal-terminal structures. On the basis of NeuGc-containing ganglioside expression, we performed survival analysis. We also investigated the differences in the effects of GM3 (N-acetylneuraminic acid [NeuAc]) and GM3 (NeuGc) on inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase in A431 cells. As a result, the presence of NeuGc-containing gangliosides was evident in 86 of 93 (93.5%) NSCLC samples. The NSCLC patients with high NeuGc-containing ganglioside expression had a low overall survival rate and a significantly low progression-free survival rate. In the in vitro study, the inhibitory effect of GM3 on EGFR tyrosine kinase in A431 cells after exposure to GM3 (NeuGc) was lower than that after exposure to GM3 (NeuAc). In conclusion, NeuGc-containing gangliosides including GM3 (NeuGc) are widely expressed in NSCLC, and NeuGc-containing ganglioside expression is associated with patient survival. The difference in the effects of GM3 (NeuGc) and GM3 (NeuAc) on the inhibition of EGFR tyrosine kinase might contribute to improvement in the prognosis of NSCLC patients.

DOI： 10.1111/cas.12027

PubMed

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

Ichushi

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Publisher：18  

DOI： 10.1074/jbc.M111.308056

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2169/internalmedicine.50.5930

Web of Science

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(株)先端医学社  

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Ichushi

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J-GLOBAL

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Language：Japanese   Publisher：日本呼吸器内視鏡学会  

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：The Japan Lung Cancer Society  

DOI： 10.2482/haigan.53.329

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Language：Japanese   Publisher：日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.34.6_642_2

Ichushi

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Language：Japanese  

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Language：Japanese   Publisher：日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.34.1_85_2

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Language：Japanese  

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Language：Japanese   Publisher：日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.33.Special_S276_1

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Language：Japanese  

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Language：Japanese  

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Language：Japanese   Publisher：Japan Society for Bronchology  

The importance of innate immunity that functions as the first line defense has been well recognized since infections have been increased in patients with AIDS or maligant tumors. Innate immunity is the most fundamental host defense that distinguishes self from nonseif, protects self and eliminate nonself by recognizing pathogen associated molecular patterns (PAMPs). CD14 and Toll-like receptors (TLRs), and lectins are the pattern recognition molecules that recognize pathogen components including lipopolysaccharide (LPS) and peptidoglycan (PGN). CD 14 and TLRs functions as endotoxin receptors. They are essential for the signal transduction induced by endotoxin and are called as pattern recognition receptors. Mannose-binding proteins (MBP) , pulmonary surfactant proteins A and D (SP-A and SP-D) and conglutinin belong to the collectin subgroup of C-type lectin superfamily that possess a collagen-ilke domain. Collectins directly bind to microorganism including gram-negative bacteria, mycobacterium tuberculosis, Pneummocystis carinii, influenza virus and function against pathogens as the first line defense. Since the respiratory system is always open to the external circumstances and is exposed to high risk of pathogens&#039; invasion, the innate immune functions mediated by lung colectins SP-A and SP-D are crucially important.

DOI： 10.18907/jjsre.24.8_595

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Language：Japanese   Publisher：日本呼吸器内視鏡学会  

間質性肺炎・急性肺傷害では, 肺胞中隔への炎症細胞浸潤と線維芽細胞の増加による末梢肺組織の線維化が認められる。肺胞I型上皮細胞(type I cell)が傷害されると肺胞II型上皮細胞(type II cell)が肥大・増生し、type I cellへと分化, 肺胞壁を被覆し修復する方向へ働く。type II cellから合成・分泌される肺サーファクタント蛋白質(Surfactant Protein;SP)のうち, 疎水性であるSP-B, SP-Cは, 末梢肺組織の線維化の契機の1つと考えられている肺胞の虚脱を防ぐ機能を担う。我々は間質性肺炎における血清マーカーとしてのSP-A, SP-Dの有用性を報告してきたが, 放射線起因急性肺傷害動物モデルを用いて生体内での各SPの推移を検討した結果, 放射線照射後にサーファクタント産生の増加を認めたが, SPのmRNA発現においては, SP-A mRNAに対するSP-B, SP-C mRNA発現の相対的低下を認めた。このことから, 急性肺傷害における肺サーファクタント組成の変化は肺胞表面張力上昇を惹起させ, 肺胞虚脱による呼吸状態の悪化や末梢肺組織の線維化の一因となることが推測された。最近ではARDSに対するサーファクタント補充療法等が報告され, 今後, type II cellからみた間質性肺炎・急性肺傷害の病態に関する新たな検討が期待される。

DOI： 10.18907/jjsre.23.8_721

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Language：Japanese   Publisher：日本肺癌学会  

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Language：Japanese  

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