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Hitoshi Aizawa,Takenari Yamashita,Haruhisa Kato,Takashi Kimura,Shin Kwak 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.1
Background and Purpose Disruption of nucleoporins has been reported in the motor neurons of patients with sporadic amyotrophic lateral sclerosis (sALS). However, the precise changes in the morphology of nucleoporins associated with the pathology of the 43-kDa TAR DNA-binding protein (TDP-43) in the disease process remain unknown. We investigated the expression of nucleoporins that constitute the nuclear pore complex (NPC) in spinal motor neurons that exhibit sALS in relation to TDP-43 pathology, which is a reliable neuropathological hallmark of sALS. Methods Paraffin-embedded sections of the lumbar spinal cord were obtained for immunofluorescence analysis from seven control subjects and six sALS patients. Anti-TDP-43 antibody, anti-nucleoporin p62 (NUP62) antibody, and anti-karyopherin beta 1 (KPNB1) antibody were applied as primary antibodies, and then visualized using appropriate secondary antibodies. The sections were then examined under a fluorescence microscope. Results NUP62 and KPNB1 immunoreactivity appeared as a smooth round rim bordering the nuclear margin in normal spinal motor neurons that exhibited nuclear TDP-43 immunoreactivity. sALS spinal motor neurons with apparent TDP-43 mislocalization demonstrated irregular, disrupted nuclear staining for NUP62 or KPNB1. Some atrophic sALS spinal motor neurons with TDP-43 mislocalization presented no NUP62 immunoreactivity. Conclusions Our findings suggest a close relationship between NPC alterations and TDP-43 pathology in the degenerative process of the motor neurons of sALS patients.
Advances in ultrasound diagnosis in chronic liver diseases
Hitoshi Maruyama,Naoya Kato 대한간학회 2019 Clinical and Molecular Hepatology(대한간학회지) Vol.25 No.2
Chronic liver disease is a major disorder worldwide. A better understanding of anatomy, blood flow, and pathophysiology may be a key issue for their proper management. Ultrasound (US) is a simple and non-invasive diagnostic tool in the abdominal field. Doppler mode offers real-time hemodynamic evaluation, and the contrast-enhanced US is one of the most frequently used modalities for the detailed assessment. Further development in digital technology enables threedimensional (3D) visualization of target images with high resolution. This article reviews the wide ranges of application in the abdominal US and describes the recent progress in the diagnosis of chronic liver diseases.
Essential protocols for in vitro evaluation of nanoparticle
Hitoshi Iwahashi,Masanori Horie,Keiko Nishio,Shigehisa Endoh,Haruhisa Kato,Katsuhide Fujita,Shinichi Kinugasa,Arisa Miyauchi,Ayako Nakamura,Junko Takahashi,Etsuo Niki,Yasukazu Yoshida,Junko Nakanishi 한국환경독성학회 2010 한국독성학회 심포지움 및 학술발표회 Vol.2010 No.11
Effect of Serum Perampanel Concentration on Sporadic Amyotrophic Lateral Sclerosis Progression
Haruhisa Kato,Makiko Naito,Tomoko Saito,Takuto Hideyama,Hiroo Terashi,Shin Kwak,Hitoshi Aizawa 대한신경과학회 2023 Journal of Clinical Neurology Vol.19 No.3
Background and Purpose To clarify the effect of perampanel (PER) on sporadic amyotrophic lateral sclerosis (sALS) progression, the relationship between the changes in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores and serum PER concentrations was investigated. Methods 12 patients with sALS from our hospital who agreed to participate and completed the PER for sALS randomized phase 2 study were included. After completing the study, we retrospectively obtained serum PER concentration data from the patients. Based on their mean PER concentrations, we divided the patients who had been taking PER into two groups: four patients with a mean PER concentration of ≥400 ng/mL were assigned to the H group, and three with a mean PER concentration of <400 ng/mL were assigned to the L group. The control group consisted of five patients who had been taking a placebo. We obtained the ALSFRS-R scores of each patient at 36 and 48 weeks after randomization. The differences in ALSFRS-R scores at baseline (0 weeks) and each subsequent week were used in the analysis. Results At 48 weeks, there were no differences in the degree of deterioration of the bulbar, upper and lower limb, and respiratory ALSFRS-R subscores and total ALSFRS-R score. However, at 36 weeks, the bulbar subscore was significantly lower in the H group than in the control group (p=0.032). Conclusions Because high PER concentrations may exacerbate bulbar symptoms in patients with sALS, serum PER measurements may be beneficial when patients with sALS are taking PER.
DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers
Masafumi Kato,Masashi Takano,Morikazu Miyamoto,Naoki Sasaki,Tomoko Goto,Hitoshi Tsuda,Kenichi Furuya 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.1
Objective: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study. Methods: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively. Results: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers. Conclusion: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.
Haruhisa Kato,Makiko Naito,Tomoko Saito,Takuto Hideyama,Yasuhiro Suzuki,Takashi Kimura,Shin Kwak,Hitoshi Aizawa 대한신경과학회 2022 Journal of Clinical Neurology Vol.18 No.4
Background and Purpose Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Selective deficiency of edited adenosine deaminase acting on RNA 2 (ADAR2), a key molecule in the acquisition of Ca2+ resistance in motor neurons, has been reported in sporadic ALS (sALS) spinal motor neurons. Since ADAR2 activity is positively regulated by prolyl isomerase Protein never in mitosis gene A interacting-1 (Pin1), a known phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, we investigated Pin1 expression in spinal motor neurons in sALS. Methods Specimens of the spinal cord were obtained from the lumbar region in eight sALS patients and age-matched five controls after postmortem examinations. The specimens were double stained with anti-Pin1 and anti-TAR DNA-binding protein of 43 kDa (TDP-43) antibodies, and examined under a fluorescence microscope. Results This study analyzed 254 and 422 spinal motor neurons from 8 sALS patients and 5 control subjects, respectively. The frequency of motor neurons with high cytoplasmic Pin1 expression from the spinal cord did not differ significantly between sALS specimens without cytoplasmic TDP-43 inclusions and control specimens. However, in sALS specimens, neurons for which the Pin1 immunoluminescence intensity in the cytoplasm was at least twice that in the background were more common in specimens with cytoplasmic TDP-43 inclusions (p<0.05 in χ2 test). Conclusions In sALS, neurons with higher expression levels of Pin1 levels had more TDP-43 inclusions. Despite the feedback mechanism between Pin1 and ADAR2 being unclear, since Pin1 positively regulates ADAR2, our results suggest that higher Pin1 expression levels in motor neurons with TDP-43 pathology from sALS patients represent a compensatory mechanism
Miyatake, Tomohiro,Kato, Syuusaku,Tamiaki, Hitoshi,Fujiwara, Manabu,Matsushita, Takayuki Korean Society of Photoscience 2002 Journal of Photosciences Vol.9 No.2
Synthetic zinc chlorins possessing a hydrophylic polyoxyethylene chain at the 17 -position were prepared. An amphiphilic zinc chlorin possessing a single chIorin moiety showed absorption maxima at 675 nm in an aqueous medium, indicating that the zinc chIorin did not form large aggregates but a dimeric structure. In contrast, amphiphilic zinc chlorin dyads in which two zinc chlorin moieties were connected with a hydrophilic polyoxyethylene linkage showed red-shifted absorption band around 720-740 nm in an aqueous medium. The result indicated that the amphiphilic zinc chlorin dyad self-aggregated to form chlorosome-like oligomer.