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  1. Zainudin NF, Sam ST, Wong YS, Ismail H, Walli S, Inoue K, et al.
    Polymers (Basel), 2023 Jan 03;15(1).
    PMID: 36616587 DOI: 10.3390/polym15010237
    The ability of poly-ferric-silicate-sulphate (PFSS) synthesized via a co-polymerization process has been applied for the removal of diazo Congo red dye. A novel degradation pathway of diazo Congo red dye by using PFSS is proposed based on LC-MS analysis. Diazo Congo red dye was successfully removed using synthesized PFSS at lower coagulant dosages and a wider pH range, i.e., 9 mg/L from pH 5 to 7, 11 mg/L at pH 9, and 50 mg/L at pH 11. The azo bond cleavage was verified by the UV-Vis spectra of diazo Congo red-loaded PFSS and FTIR spectra which showed disappearance of the peak at 1584 cm-1 for -N=N- stretching vibrations. The synchronized results of UV-Vis spectra, FTIR, and the LC-MS analysis in this study confirmed the significance of the Si and Fe bond in PFSS towards the degradation of diazo Congo red dye. The successfully synthesized PFSS coagulant was characterized by FTIR, SEM, TEM, and HRTEM analysis. From this analysis, it was proven that PFSS is a polycrystalline material which is favorable for the coagulation-flocculation process. Based on all these findings, it was established that synthesized PFSS can be employed as a highly efficient polymeric coagulant for the removal of dye from wastewater.
  2. Nishimura A, Sunggip C, Tozaki-Saitoh H, Shimauchi T, Numaga-Tomita T, Hirano K, et al.
    Sci Signal, 2016 Jan 19;9(411):ra7.
    PMID: 26787451 DOI: 10.1126/scisignal.aac9187
    The angiotensin (Ang) type 1 receptor (AT1R) promotes functional and structural integrity of the arterial wall to contribute to vascular homeostasis, but this receptor also promotes hypertension. In our investigation of how Ang II signals are converted by the AT1R from physiological to pathological outputs, we found that the purinergic P2Y6 receptor (P2Y6R), an inflammation-inducible G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR), promoted Ang II-induced hypertension in mice. In mice, deletion of P2Y6R attenuated Ang II-induced increase in blood pressure, vascular remodeling, oxidative stress, and endothelial dysfunction. AT1R and P2Y6R formed stable heterodimers, which enhanced G protein-dependent vascular hypertrophy but reduced β-arrestin-dependent AT1R internalization. Pharmacological disruption of AT1R-P2Y6R heterodimers by the P2Y6R antagonist MRS2578 suppressed Ang II-induced hypertension in mice. Furthermore, P2Y6R abundance increased with age in vascular smooth muscle cells. The increased abundance of P2Y6R converted AT1R-stimulated signaling in vascular smooth muscle cells from β-arrestin-dependent proliferation to G protein-dependent hypertrophy. These results suggest that increased formation of AT1R-P2Y6R heterodimers with age may increase the likelihood of hypertension induced by Ang II.
  3. Yoshida N, Inoue K, Yasuda R, Hirose R, Dohi O, Naito Y, et al.
    Dig Dis Sci, 2018 12;63(12):3457-3464.
    PMID: 30232637 DOI: 10.1007/s10620-018-5275-1
    INTRODUCTION: Previous narrow-band imaging (NBI) was dark and reported not to be useful for polyp detection. In this study, we analyzed the efficacy of an additional 30-s observation of the right-sided colon with the recent bright high-resolution NBI.

    METHODS: We enrolled patients undergoing colonoscopy from February 2015 to May 2017 in two institutions. All procedures were performed with the latest system (EVIS LUCERA ELITE, Olympus). The cecum and ascending colon were first observed with white light imaging (WLI) in both the NBI and WLI group. Then, the colonoscope was re-inserted, and the cecum and ascending colon were observed for an additional 30 s. In this second observation, NBI was performed for the first 130 patients in the NBI group and WLI for the next 130 in the WLI group. The number of adenoma and sessile serrated polyps (ASPs) in the second observation were examined in both groups. According to our initial pilot study, the sample size was estimated at 126.

    RESULTS: In the first observation, the number of ASPs was 72 in the NBI group and 72 in the WLI group (p = 1.0). In the second observation, the number of ASPs was 23 in the NBI group and 10 in the WLI group (p = 0.02). The polyp and adenoma detection rates in the second observation were 16.2% and 12.3% in the NBI group and 7.7% (p = 0.03) and 6.2% (p = 0.09) in the WLI group.

    CONCLUSIONS: The additional 30-s observation with recent NBI decreased missed polyps in the right-sided colon.

  4. Yoshida N, Hirose R, Watanabe M, Yamazaki M, Hashimoto S, Matsubara S, et al.
    JGH Open, 2021 Jan;5(1):160-162.
    PMID: 33490630 DOI: 10.1002/jgh3.12435
    COVID-19 rarely causes lower gastrointestinal bleeding even though its RNA has been detected in patient's stool. Urgent colonoscopy in a COVID-19 patient with massive bloody stool requires various procedural and equipment considerations. Here, we present a case of colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient on heparin for COVID-19 coagulopathy. We also share various management methods for the prevention of COVID-19 contamination. A 71-year-old man was diagnosed with COVID-19 pneumonia and subsequently underwent hemodiafiltration. Heparin was initiated for COVID-19 coagulopathy. At day 42, the patient experienced 2000 mL of bloody stool. An operator performed urgent colonoscopy with three assistants in a negative-pressure room with full personal protective equipment. A hemorrhagic ulceration was detected at the cecum, and endoscopic hemostasis was performed. Immunohistochemistry was positive for cytomegalovirus. Postprocedure, the endoscopic systems were thoroughly cleaned, and specific measures for endoscope reprocessing and disinfection were performed to prevent contamination with COVID-19.
  5. Yoshida N, Dohi O, Inoue K, Yasuda R, Murakami T, Hirose R, et al.
    Gut Liver, 2019 03 15;13(2):140-148.
    PMID: 30513568 DOI: 10.5009/gnl18276
    A laser endoscopy system was developed in 2012. The system allows blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) to be performed as modes of narrow-band light observation; these modes have been reported to be useful for tumor detection and characterization. Furthermore, an innovative endoscopy system using four-light emitting diode (LED) multilight technology was released in 2016 to 2017 in some areas in which laser endoscopes have not been approved for use, including the United States and Europe. This system enables blue light imaging (this is also known as BLI) and LCI with an LED light source instead of a laser light source. Several reports have shown that these modes have improved tumor detection. In this paper, we review the efficacy of BLI and LCI with laser and LED endoscopes in tumor detection and characterization.
  6. Yoshida N, Fukumoto K, Hasegawa D, Inagaki Y, Inoue K, Hirose R, et al.
    J Gastroenterol Hepatol, 2021 Dec;36(12):3337-3344.
    PMID: 34260116 DOI: 10.1111/jgh.15625
    BACKGROUND AND AIM: High-grade dysplasia (HGD) and T1 lesions are accidentally resected by cold snare polypectomy (CSP) and the characteristics, and follow-up of them has not been reported. In this study, we analyzed the histopathological findings and recurrence of them.

    METHODS: This was a multicenter retrospective-cohort study. We collected HGD and T1 lesions of ≤ 10 mm resected by CSP among 15 520 patients receiving CSP from 2014 to 2019 at nine related institutions, and we extracted only cases receiving definite follow-up colonoscopy after CSP of HGD and T1 lesions. We analyzed these tumor's characteristics and therapeutic results such as R0 resection and local recurrence and risk factors of recurrence.

    RESULTS: We collected 103 patients (0.63%) and extracted 80 lesions in 74 patients receiving follow-up colonoscopy for CSP scar. Mean age was 68.4 ± 12.0, and male rate was 68.9% (51/80). The mean tumor size (mm) was 6.6 ± 2.5, and the rate of polypoid morphology and rectum location was 77.5% and 25.0%. The rate of magnified observation was 53.8%. The rates of en bloc resection and R0 resection were 92.5% and 37.5%. The local recurrence rate was 6.3% (5/80, median follow-up period: 24.0 months). The recurrence developed within 3 months after CSP for four out of five recurrent cases. Comparing five recurrent lesions to 75 non-recurrent lesions, a positive horizontal margin was a significant risk factor (60.0% vs 10.7%, P 

  7. Iwata H, Masuda N, Kim SB, Inoue K, Rai Y, Fujita T, et al.
    Future Oncol, 2019 Jul;15(21):2489-2501.
    PMID: 31140297 DOI: 10.2217/fon-2019-0143
    Aim: To evaluate the efficacy and safety of neratinib as extended adjuvant therapy in patients from Asia based on exploratory analyses of the Phase III ExteNET trial. Patients & methods: A total of 2840 women with early stage HER2-positive breast cancer were randomly assigned to neratinib 240 mg/day or placebo for 1 year after trastuzumab-based adjuvant therapy. Results: A total of 341 patients were from Asia (neratinib, n = 165; placebo, n = 176). 2-year invasive disease-free survival rates were 92.8 and 90.8% with neratinib and placebo, respectively (HR: 0.70; 95% CI: 0.31-1.55), and 5-year rates were 91.9 and 87.2%, respectively (HR: 0.57; 95% CI: 0.27-1.13). Diarrhea was the most common adverse event with neratinib. Conclusion: Extended adjuvant therapy with neratinib reduces disease recurrences in Asian women with HER2-positive breast cancer. Trial registration: Clinicaltrials.gov NCT00878709.
  8. Tomie A, Yoshida N, Kugai M, Hirose R, Dohi O, Inoue K, et al.
    Gastroenterol Res Pract, 2020;2020:9656040.
    PMID: 32411210 DOI: 10.1155/2020/9656040
    Materials and Methods: This was a multicenter retrospective cohort study. The subjects were patients aged ≥20 years treated for chronic constipation from May 2018 to November 2019 at 12 related institutions. Patients were divided into ≤74 years and ≥75 years old. Elobixibat at 10 mg/day was prescribed for two weeks. We then analyzed the discontinuation due to ineffectiveness, change of spontaneous bowel movements (SBM), stool consistency, the time until the first SBM, adverse events, and effect-related factors.

    Results: There were 140 cases (61 males) evaluated, with an average age of 72.1 ± 13.6 years (≤74 years: 71 cases; ≥75 years: 69 cases). The discontinuation rate was 7.9%. The SBM (times/week) increased from 2.86 to 6.08 (p < 0.001). The overall SBM improvement rate was 74.0% (≤74 years: 78.2% vs. ≥75 years: 68.9%, p = 0.31; male: 75.0% vs. female: 73.3%, p = 0.78). The overall improvement rate of stool consistency was 59.6% (≤74 years: 62.9%, ≥75 years: 56.1%, p = 0.42). The time until the first SBM (hours) for those ≤74 years and ≥75 years was 17.2 ± 14.3 and 11.2 ± 8.4 (p = 0.04). Adverse event rates for those ≤74 years and ≥75 years were 28.2% and 10.1% (p < 0.01). There were no significant effect-related factors for gender, age, and use of laxatives.

    Conclusions: Short-period elobixibat is shown to be effective also for the elderly and male.

  9. Yoshida N, Draganov PV, John S, Neumann H, Rani RA, Hsu WH, et al.
    Dig Dis Sci, 2023 Oct;68(10):3943-3952.
    PMID: 37558800 DOI: 10.1007/s10620-023-08057-2
    INTRODUCTION: In light-emitting diode (LED) and LASER colonoscopy, linked color imaging (LCI) and blue light/laser imaging (BLI) are used for lesion detection and characterization worldwide. We analyzed the difference of LCI and BLI images of colorectal lesions between LED and LASER in a multinational study.

    METHODS: We prospectively observed lesions with white light imaging (WLI), LCI, and BLI using both LED and LASER colonoscopies from January 2020 to August 2021. Images were graded by 27 endoscopists from nine countries using the polyp visibility score: 4 (excellent), 3 (good), 2 (fair), and 1 (poor) and the comparison score (LED better/similar/LASER better) for WLI/LCI/BLI images of each lesion.

    RESULTS: Finally, 32 lesions (polyp size: 20.0 ± 15.2 mm) including 9 serrated lesions, 13 adenomas, and 10 T1 cancers were evaluated. The polyp visibility scores of LCI/WLI for international and Japan-expert endoscopists were 3.17 ± 0.73/3.17 ± 0.79 (p = 0.92) and 3.34 ± 0.78/2.84 ± 1.22 (p 

  10. Inoue K, Chieh JTW, Yeh LC, Chiang SJ, Phrommintikul A, Suwanasom P, et al.
    Trials, 2022 Dec 07;23(1):986.
    PMID: 36476401 DOI: 10.1186/s13063-022-06907-4
    BACKGROUND: More than half of the world's population lives in Asia. With current life expectancies in Asian countries, the burden of cardiovascular disease is increasing exponentially. Overcrowding in the emergency departments (ED) has become a public health problem. Since 2015, the European Society of Cardiology recommends the use of a 0/1-h algorithm based on high-sensitivity cardiac troponin (hs-cTn) for rapid triage of patients with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). However, these algorithms are currently not recommended by Asian guidelines due to the lack of suitable data.

    METHODS: The DROP-Asian ACS is a prospective, stepped wedge, cluster-randomized trial enrolling 4260 participants presenting with chest pain to the ED of 12 acute care hospitals in five Asian countries (UMIN; 000042461). Consecutive patients presenting with suspected acute coronary syndrome between July 2022 and Apr 2024 were included. Initially, all clusters will apply "usual care" according to local standard operating procedures including hs-cTnT but not the 0/1-h algorithm. The primary outcome is the incidence of major adverse cardiac events (MACE), the composite of all-cause death, myocardial infarction, unstable angina, or unplanned revascularization within 30 days. The difference in MACE (with one-sided 95% CI) was estimated to evaluate non-inferiority. The non-inferiority margin was prespecified at 1.5%. Secondary efficacy outcomes include costs for healthcare resources and duration of stay in ED.

    CONCLUSIONS: This study provides important evidence concerning the safety and efficacy of the 0/1-h algorithm in Asian countries and may help to reduce congestion of the ED as well as medical costs.

  11. Miyake N, Tsurusaki Y, Fukai R, Kushima I, Okamoto N, Ohashi K, et al.
    Eur J Hum Genet, 2023 Mar 27.
    PMID: 36973392 DOI: 10.1038/s41431-023-01335-7
    Autism spectrum disorder (ASD) is caused by combined genetic and environmental factors. Genetic heritability in ASD is estimated as 60-90%, and genetic investigations have revealed many monogenic factors. We analyzed 405 patients with ASD using family-based exome sequencing to detect disease-causing single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variations (CNVs) for molecular diagnoses. All candidate variants were validated by Sanger sequencing or quantitative polymerase chain reaction and were evaluated using the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines for molecular diagnosis. We identified 55 disease-causing SNVs/indels in 53 affected individuals and 13 disease-causing CNVs in 13 affected individuals, achieving a molecular diagnosis in 66 of 405 affected individuals (16.3%). Among the 55 disease-causing SNVs/indels, 51 occurred de novo, 2 were compound heterozygous (in one patient), and 2 were X-linked hemizygous variants inherited from unaffected mothers. The molecular diagnosis rate in females was significantly higher than that in males. We analyzed affected sibling cases of 24 quads and 2 quintets, but only one pair of siblings shared an identical pathogenic variant. Notably, there was a higher molecular diagnostic rate in simplex cases than in multiplex families. Our simulation indicated that the diagnostic yield is increasing by 0.63% (range 0-2.5%) per year. Based on our simple simulation, diagnostic yield is improving over time. Thus, periodical reevaluation of ES data should be strongly encouraged in undiagnosed ASD patients.
  12. Sakamoto M, Iwama K, Sasaki M, Ishiyama A, Komaki H, Saito T, et al.
    Genet Med, 2022 Dec;24(12):2453-2463.
    PMID: 36305856 DOI: 10.1016/j.gim.2022.08.007
    PURPOSE: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects.

    METHODS: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated.

    RESULTS: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments.

    CONCLUSION: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.

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