87 results on '"Noriko Yoshikawa"'
Search Results
2. Casiribimab/imdevimab treatment for hemodialysis patients with COVID-19 infection
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Takashi Sakai, Noriko Yoshikawa, Dan Inoue, Takahiro Uchida, Tadasu Kojima, Tomohiro Tomiyasu, Muneharu Yamada, and Takashi Oda
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Computer Networks and Communications ,Hardware and Architecture ,Software - Published
- 2023
3. Exposure of Thomsen-Friedenreich Antigen on the Renal Tubules of a Patient with Capnocytophaga Infection-induced Acute Kidney Injury
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Tomohiro Tomiyasu, Tadasu Kojima, Dan Inoue, Muneharu Yamada, Shuhei Komatsu, Takahiro Uchida, Takashi Oda, and Noriko Yoshikawa
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Pathology ,medicine.medical_specialty ,Thrombotic microangiopathy ,medicine.diagnostic_test ,Thomsen-Friedenreich Antigen ,biology ,urogenital system ,business.industry ,Acute kidney injury ,General Medicine ,urologic and male genital diseases ,medicine.disease ,Capnocytophaga ,biology.organism_classification ,female genital diseases and pregnancy complications ,Antigen ,Internal Medicine ,medicine ,biology.protein ,Etiology ,Renal biopsy ,business ,Neuraminidase - Abstract
Infections with neuraminidase-producing bacteria can lead to acute kidney injury (AKI). We herein report a 74-year-old woman who developed AKI in the course of Capnocytophaga infection, a neuraminidase-producing bacterium. A renal biopsy showed tubulointerstitial injury accompanied by specific binding of fluorescence-conjugated peanut lectin to the tubular epithelial cells, suggesting exposure of Thomsen-Friedenreich antigen (T-antigen) on the tubules. Although AKI is often observed in patients infected with Capnocytophaga, little is known about its etiology and associated pathology. This case suggests that tubulointerstitial injury caused by neuraminidase production and resultant T-antigen exposure is a mechanism of Capnocytophaga infection-induced AKI.
- Published
- 2022
4. Case Report:Upper Side One-lung Ventilation for Bronchial Surgery with High-frequency Jet Ventilation
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Kyohei Nakashin, Arisa Hotta, Motoko Shimizu, Ai Nakamoto, Noriko Yoshikawa, and Naoko Ohira
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medicine.medical_specialty ,High frequency jet ventilation ,business.industry ,Medicine ,business ,One lung ventilation ,Surgery - Published
- 2020
5. Thrombotic microangiopathy with transiently positive direct Coombs test in an adult with poststreptococcal acute glomerulonephritis: a case report
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Dan Inoue, Takashi Oda, Sachiko Iwama, Takahiko Hoshino, Mitsuya Mukae, Takashi Sakai, Aki Kojima, Takahiro Uchida, Tadasu Kojima, Kentaro Sugisaki, Tomohiro Tomiyasu, Noriko Yoshikawa, and Muneharu Yamada
- Subjects
Adult ,Male ,Streptococcus pyogenes ,Thrombotic Microangiopathies ,Neuraminidase ,urologic and male genital diseases ,Diseases of the genitourinary system. Urology ,Coombs Test ,Glomerulonephritis ,Nephrology ,Direct Coombs test ,Streptococcal Infections ,Case report ,Humans ,RC870-923 ,Nephritis-associated plasmin receptor (NAPlr) ,Poststreptococcal acute glomerulonephritis (PSAGN) ,Thomsen–Friedenreich (T) antigen ,Thrombotic microangiopathy (TMA) - Abstract
Background To date, a few case reports have described the association between poststreptococcal acute glomerulonephritis (PSAGN) and hemolytic anemia/thrombocytopenia, both with or without a pathology similar to that of thrombotic microangiopathy (TMA). However, the detailed mechanism leading to the complication of TMA in PSAGN patients remains to be clarified. In contrast, infection with neuraminidase-producing Streptococcus pneumoniae is a well-known cause of TMA, and it has been reported that transient positivity of the direct Coombs test is observed in up to 90% of such patients. Case presentation A 44-year-old man was hospitalized for acute nephritic syndrome 3 weeks after developing pharyngitis. PSAGN was suspected owing to a low complement C3, increased antistreptolysin-O and serum creatinine (5.46 mg/dL), and hematuria/proteinuria. The throat antigen test for group A Streptococcus was positive. He developed hemolytic anemia with thrombocytopenia from hospital day 9. TMA was suspected owing to minimal coagulation abnormalities. ADAMTS-13 activity was normal, whereas the direct Coombs test was transiently positive. Renal biopsy demonstrated glomerular endocapillary proliferation without crescents, but with severe tubulitis and peritubular capillaritis on light microscopy. Immunofluorescence demonstrated C3 deposition along the glomerular capillary walls, and many subepithelial humps were observed on electron microscopy. The deposition of nephritis-associated plasmin receptor (NAPlr), a nephritogenic protein of Streptococcus pyogenes, was observed only in glomeruli. Thus, the histological diagnosis was typical PSAGN, but with atypical severe tubulointerstitial lesions. A positive direct Coombs test is often observed in pneumococcal TMA patients, which is attributed to the exposure of Thomsen–Friedenreich (T) antigen by neuraminidase. As Streptococcus pyogenes is one of the neuraminidase-producing bacteria other than Streptococcus pneumoniae, T-antigen exposure was analyzed in the renal tissue of this patient using labelled peanut lectin as a probe, which has strong and specific binding affinity for T-antigen. Exposure of T-antigen was found on tubular epithelial cells and small vessels in the tubulointerstitial area, but not in the glomeruli of this patient. Conclusion These findings suggest that 2 pathogenic proteins of Streptococcus pyogenes, i.e., NAPlr and neuraminidase, induced glomerular lesions of PSAGN and tubulointerstitial inflammation with TMA, respectively, resulting in severe acute kidney injury in this patient.
- Published
- 2022
6. Increased expression of epimorphin in a peritoneal fibrosis mouse model
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Tomohiro Tomiyasu, Muneharu Yamada, Dan Inoue, Shuhei Komatsu, Noriko Yoshikawa, Tadasu Kojima, Yohei Hirai, Takashi Oda, and Takahiro Uchida
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Pathology ,medicine.medical_specialty ,Membrane Glycoproteins ,business.industry ,medicine.medical_treatment ,Peritoneal membrane ,Peritoneal Fibrosis ,General Medicine ,Fibrosis ,Peritoneal dialysis ,Cell Line ,Rats ,Disease Models, Animal ,Mice ,Nephrology ,Transforming Growth Factor beta ,medicine ,Animals ,Peritoneum ,business ,Peritoneal Dialysis - Abstract
Background: Long-term peritoneal dialysis results in functional and histopathological alterations of the peritoneal membrane, leading to peritoneal fibrosis (PF). The mechanism of PF has not been fully elucidated, and at present there is no effective therapy for PF. Epimorphin is a mesenchymal protein that not only regulates morphogenesis in organ development but is implicated in tissue repair. However, the role of epimorphin in PF has not yet been clarified. Methods: PF was induced in C57/Bl6 mice by intraperitoneal injection of chlorhexidine gluconate (CG-injected mice) three times a week for 3 weeks. The parietal peritoneum was subsequently dissected and assessed by Masson’s trichrome staining, and epimorphin expression was analysed by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). Furthermore, epimorphin-positive regions were analysed by multiple immunofluorescence staining using fibrosis-associated markers. In addition, normal rat fibroblast cells (NRK-49F) were treated with transforming growth factor-β (TGF-β) in the presence or absence of epimorphin. The expression of fibrosis-associated markers was assessed by real-time RT-PCR. Results: In CG-injected mice, Masson’s trichrome staining showed marked thickening of the submesothelial compact zone. Weak epimorphin expression was observed in the narrow submesothelial compact zone beneath the mesothelial cells in control mice; however, epimorphin expression was stronger in the submesothelial compact zone in CG-injected mice. Epimorphin expression was observed mainly in α-smooth muscle actin (α-SMA)-positive myofibroblasts. Epimorphin suppressed the TGF-β-induced upregulation of α-SMA and platelet-derived growth factor receptor-β in cultured cells. Conclusions: Our results suggest that epimorphin may be a therapeutic target for fibrotic diseases of the peritoneum.
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- 2021
7. Exposure of Thomsen-Friedenreich Antigen on the Renal Tubules of a Patient with Capnocytophaga Infection-induced Acute Kidney Injury
- Author
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Takahiro, Uchida, Takashi, Oda, Dan, Inoue, Shuhei, Komatsu, Tadasu, Kojima, Tomohiro, Tomiyasu, Noriko, Yoshikawa, and Muneharu, Yamada
- Subjects
Kidney Tubules ,Humans ,Antigens, Tumor-Associated, Carbohydrate ,Female ,Acute Kidney Injury ,Capnocytophaga ,Aged - Abstract
Infections with neuraminidase-producing bacteria can lead to acute kidney injury (AKI). We herein report a 74-year-old woman who developed AKI in the course of Capnocytophaga infection, a neuraminidase-producing bacterium. A renal biopsy showed tubulointerstitial injury accompanied by specific binding of fluorescence-conjugated peanut lectin to the tubular epithelial cells, suggesting exposure of Thomsen-Friedenreich antigen (T-antigen) on the tubules. Although AKI is often observed in patients infected with Capnocytophaga, little is known about its etiology and associated pathology. This case suggests that tubulointerstitial injury caused by neuraminidase production and resultant T-antigen exposure is a mechanism of Capnocytophaga infection-induced AKI.
- Published
- 2021
8. trans-2-Pentenal, an Active Compound in Cigarette Smoke, Identified via Its Ability to Form Adducts with Glutathione
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Mayuko Hatai, Kazumasa Shinozuka, Eriko Kinoshita, Noriko Yoshikawa, Kazuki Nakamura, Satomi Kagota, and Shizuyo Horiyama
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chemistry.chemical_classification ,Ketone ,Antioxidant ,010405 organic chemistry ,medicine.medical_treatment ,Acrolein ,General Chemistry ,General Medicine ,Tripeptide ,Glutathione ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Cell culture ,Drug Discovery ,Methyl vinyl ketone ,medicine ,Cytotoxicity - Abstract
α,β-Unsaturated carbonyl compounds readily form adducts with SH or NH2 residues, which are nucleophilic agents, by Michael addition. Glutathione (GSH) is a tripeptide that contains an SH residue and functions as an antioxidant. We demonstrated previously that acrolein (ACR), crotonaldehyde (CA), and methyl vinyl ketone (MVK) are present in nicotine- and tar-removed cigarette smoke extract (CSE) and reacted with GSH in B16-BL6 mouse melanoma cells to form GSH-ACR, GSH-CA, and GSH-MVK adducts, suggesting a possible mechanism for CSE-induced cytotoxicity. In this study, we searched for novel α,β-unsaturated carbonyl compounds other than ACR, CA, and MVK. We selected candidate compounds in CSE based on accurate mass values generated using LC/MS analysis of products formed between CSE and GSH, and identified these using GC/MS analysis and library screening. As a result, we isolated trans-2-methyl-2-butenal, 2-methyl-2-cyclopenten-1-one, 3-methyl-2-cyclopenten-1-one, and furfural, which were poorly reactive with GSH and only very weakly inhibited growth of Colon-26 mouse carcinoma cells and BALB/3T3 clone A31 mouse normal cells. We also isolated 2-cyclopenten-1-one, trans-2-pentenal, 3-methyl-2-butenal and ethyl vinyl ketone, which were highly reactive with GSH and significantly inhibited the growth of both cell lines. Our data suggest that the reactivity of compounds in CSE with GSH may be positively correlated with the effect on inhibiting cell growth. Notably, trans-2-pentenal showed marked inhibition of carcinoma cells growth, whereas this compound exhibited little inhibitory effect on normal cells. trans-2-Pentenal may be a potent candidate or seed for antitumor agents.
- Published
- 2019
9. Development of pure red cell aplasia by transmission and persistent infection of parvovirus B19 through a kidney allograft
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Muneharu Yamada, Dan Inoue, Y. Kihara, Masaaki Okihara, Makoto Iwase, Hitoshi Iwamoto, Osamu Konno, Sachiko Iwama, Isao Akashi, Tadasu Kojima, Takahiro Uchida, Noriko Yoshikawa, Tomohiro Tomiyasu, and Takashi Oda
- Subjects
medicine.medical_specialty ,Pure red cell aplasia ,030230 surgery ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Biopsy ,medicine ,Kidney transplantation ,Transplantation ,Kidney ,biology ,medicine.diagnostic_test ,Parvovirus ,business.industry ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,medicine.anatomical_structure ,biology.protein ,030211 gastroenterology & hepatology ,Bone marrow ,Antibody ,business - Abstract
We report a case of pure red cell aplasia (PRCA) caused by parvovirus B19 (PVB19) infection, which was transmitted through a kidney allograft. The patient underwent a living-donor kidney transplant from his wife at the age of 60. Despite successful engraftment with a normal creatinine level, he developed severe anemia that required frequent blood transfusions 2 months after transplantation. Renal anemia was unlikely as his serum erythropoietin level was extremely high. A bone marrow aspiration test demonstrated the existence of large proerythroblasts. Although anti-PVB19 IgM antibody levels were not increased, polymerase chain reaction (PCR) detected PVB19 DNA in his serum. Thus, he was diagnosed as having PRCA induced by PVB19 infection. PCR analysis of total DNA isolated from 0-hour biopsy sections showed the existence of PVB19 DNA. Furthermore, PVB19 proteins was detected on renal tubules of 0-hour allograft by immunoperoxidase staining. Thus, transmission of PVB19 through the allograft was confirmed. A single course of intravenous immunoglobulin (IVIG) therapy resulted in substantial improvement; however, the effect was limited, and severe anemia relapsed after 5-6 months. Several courses of IVIG with adjustment of immunosuppressive drugs resulted in long-term remission. Our case demonstrates that donor-transmitted PVB19 infection should be suspected in kidney transplant recipients who develop refractory anemia during the early post-operative phase.
- Published
- 2020
10. 2nd Attitude Survey on Female Students of Shibaura Institute of Technology
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Noriko YOSHIKAWA, Yuka HOSHI, Kyouko YAMAMOTO, Nobuko HENMI, Ariko YOSHIDA, and Soichiro AIHARA
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- 2022
11. The effect of tumor suppressor Pdcd4 knockdown on the malignancy of mouse melanoma cells
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Eriko Kinoshita, Kazuki Nakamura, Satomi Kagota, Kazumasa Shinozuka, Noriko Yoshikawa, and Mayuko Hatai
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Gene knockdown ,law ,business.industry ,Applied Mathematics ,General Mathematics ,Cancer research ,medicine ,Suppressor ,Mouse Melanoma ,Malignancy ,medicine.disease ,business ,law.invention - Published
- 2018
12. Cigarette Smoke Extract Disrupts Transcriptional Activities Mediated by Thyroid Hormones and Its Receptors
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Mayuko Hatai, Noriko Yoshikawa, Kenji Moriyama, Kumi Futawaka, Kazuki Nakamura, Misa Hayashi, Midori Matsushita, and Tetsuya Tagami
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0301 basic medicine ,Thyroid Hormones ,medicine.medical_specialty ,Transcription, Genetic ,Pharmaceutical Science ,Nerve Tissue Proteins ,030209 endocrinology & metabolism ,03 medical and health sciences ,Nuclear Receptor Coactivator 1 ,0302 clinical medicine ,Malate Dehydrogenase ,Smoke ,Internal medicine ,Tobacco ,parasitic diseases ,Gene expression ,medicine ,Humans ,Receptor ,Pharmacology ,Receptors, Thyroid Hormone ,Thyroid hormone receptor ,Chemistry ,Thyroid Hormone Receptors beta ,General Medicine ,Nuclear receptor coactivator 1 ,HEK293 Cells ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Endocrine disruptor ,Nuclear receptor ,Signal transduction ,Carrier Proteins ,Thyroid Hormone Receptors alpha ,Hormone - Abstract
Cigarette smoke contains over 4800 compounds, including at least 200 toxicants or endocrine disruptors. Currently, effects of cigarette smoke on thyroid hormone (TH) levels remains to be clarified. Here, we demonstrate that cigarette smoke extract (CSE) possesses thyroid hormone properties and acts synergistically as a partial agonist for thyroid hormone receptors (TRs) in the presence of TH. In transient gene expression experiments, CSE stimulated transcriptional activity with TH in a dose-dependent manner. Stimulatory effects were observed with physiological TH concentrations, although CSE did not activate TRs without TH. CSE (5%) dissolved in phosphate-buffered saline (PBS) supplemented with 1 nM TH was approximately comparable to 3.2±0.1 and 2.3±0.2 nM of TRα1 and TRβ1, respectively. To illustrate probable mechanisms of the CSE agonistic activity, effects on TR mediated transcriptional functions with cofactors were investigated. With a mammalian two-hybrid assay, CSE recruited the nuclear coactivators glucocorticoid receptor interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC1) to the TR. Unsaturated carbonyl compounds, acrolein, crotonaldehyde, and methyl vinyl ketone, representative constituents of CSE, retained such agonistic properties and possibly contributed to stimulatory effects. The results suggest that CSE recruits a transcriptional activator and may reinforce TH binding to the TR additively, resulting in gene expression. CSE partially agonizes TH action and may disturb the function of various nuclear hormone receptor types and their cofactors to disrupt the physiological processes.
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- 2018
13. A Study on the Platform Supporting the Continuous Employment Support Type B Projects
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Noriko, Yoshikawa
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プラットフォーム ,持続 ,就労継続支援B型事業 ,デザイン変数 - Published
- 2018
14. Effect of α, β-unsaturated carbonylcompounds in cigarette smoke extract on the growth of mouse Colon-26 cancercells
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Mayuko Hatai, Satomi Kagota, Noriko Yoshikawa, Kazumasa Shinozuka, Eriko Kinoshita, Kazuki Nakamura, and Shizuyo Horiyama
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Mouse Colon ,Chemistry ,Applied Mathematics ,General Mathematics ,Cancer research ,Cigarette smoke - Published
- 2018
15. The Otolaryngologist's Role in Providing Gender‐Affirming Care: An Opportunity for Improved Education and Training
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Noriko Yoshikawa, Valerie A. Flanary, Carl G. Streed, Angela Sturm, Stacey L. Ishman, and Scott R. Chaiet
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Gender dysphoria ,medicine.medical_specialty ,Attitude of Health Personnel ,media_common.quotation_subject ,Health Services for Transgender Persons ,Transgender Persons ,03 medical and health sciences ,0302 clinical medicine ,Otolaryngologists ,Health care ,Transgender ,medicine ,Humans ,030212 general & internal medicine ,Cultural Competency ,Physician's Role ,media_common ,Physician-Patient Relations ,business.industry ,Gender Identity ,Gender nonconforming ,medicine.disease ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Family medicine ,Queer ,Surgery ,business ,Cultural competence ,Diversity (politics) - Abstract
Currently, there are limited resources and training available for otolaryngologists and otolaryngology practice personnel to provide gender-affirming care for transgender or gender nonconforming patients. This unique patient population may present to our offices for gender-specific care or with complaints of the ear, nose, and throat unrelated to gender identity. Our current practice has unintentional but direct consequences on our patients care, as transgender patients often report negative experiences in the healthcare setting related to their gender identity. The absence of resources and training is also seen in other specialties. Physicians who create an environment where patients of all gender identities feel welcome can better meet their patients' health care needs. In addition, otolaryngologists can play a role in easing the gender dysphoria experienced by transgender patients. We suggest educational content should be created for and made available to otolaryngologists and office staff to provide gender-affirming care.
- Published
- 2018
16. Tumor suppressor Pdcd4 attenuates delta Np73 translation in human breast cancer cells
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Kazumasa Shinozuka, Eriko Kinoshita, Noriko Yoshikawa, Kazuki Nakamura, Mayuko Hatai, and Satomi Kagota
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Delta ,law ,Applied Mathematics ,General Mathematics ,Cancer cell ,Cancer research ,Suppressor ,Translation (biology) ,Biology ,Human breast ,law.invention - Published
- 2018
17. Cigarette Smoke Extract Modulates Functions of Peroxisome Proliferator-Activated Receptors
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Kenji Moriyama, Kumi Futawaka, Noriko Yoshikawa, Kana Murakami, Mana Mitsutani, Midori Matsushita, Mayuko Hatai, Kazuki Nakamura, Tetsuya Tagami, Misa Hayashi, and Yukiko Watamoto
- Subjects
0301 basic medicine ,Peroxisome Proliferator-Activated Receptors ,Pharmaceutical Science ,Peroxisome proliferator-activated receptor ,Receptors, Cytoplasmic and Nuclear ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Smoke ,parasitic diseases ,Tobacco ,Transcriptional regulation ,Humans ,Protein Isoforms ,Liver X receptor ,Receptor ,Liver X Receptors ,Pharmacology ,chemistry.chemical_classification ,General Medicine ,Cholesterol, LDL ,Cell biology ,Nuclear receptor coactivator 1 ,030104 developmental biology ,chemistry ,Nuclear receptor ,Amino Acid Substitution ,Receptors, LDL ,030220 oncology & carcinogenesis ,Low-density lipoprotein ,Signal transduction - Abstract
Cigarette smoke extract (CSE) contains many toxicants and may derange the physiological processes, such as cholesterol metabolism. We examined the impact of CSE on transcriptional regulation mediated peroxisome proliferator-activated receptors (PPARs) and its interaction with cofactors to elucidate differences in the molecular mechanism between CSE and other agonists of PPARs. We constructed several mutant PPARs (mPPARs) with amino acid substitution in the ligand-binding domain, which according to the molecular modeling, may affect the binding of agonists. In transient expression assays, each wild-type peroxisome proliferator-activated receptor (PPAR) mediated transcription stimulated by CSE was faintly yet significantly elevated compared to the control. The CSE-induced transcriptional activation was abolished in the H323A, H323Y, S342A, and H449A mPPARγs, although the activation elevated by pioglitazone was reserved. In the mPPARγ with Y473A and mPPARβ/δs with H286Y and Y436A, the pioglitazone-induced or L165041-activated transcriptional elevations were decreased and were lower than that of CSE-induced stimulation. These results suggested that CSE activated both mutant PPARs to be selectively different from those ligands. Mammalian two-hybrid assay illustrated that CSE could mildly recruit SRC1 or GRIP1 to the wild-type PPARγ. Representative ingredients, such as acrolein and crotonaldehyde present in CSE, could stimulate PPAR isoforms even at the toxicological concentrations and might possibly contribute to stimulatory effects. CSE mildly regulates the cholesterol metabolism-related genes, such as low density lipoprotein (LDL) receptor and Liver X receptor (LXR)β. In conclusion, these CSE effects the nuclear hormone receptors and their cofactors thereby disturbing metabolic phenomena. Therefore, CSE might be involved in cholesterol metabolism.
- Published
- 2019
18. trans-2-Pentenal, an Active Compound in Cigarette Smoke, Identified via Its Ability to Form Adducts with Glutathione
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Mayuko, Hatai, Shizuyo, Horiyama, Noriko, Yoshikawa, Eriko, Kinoshita, Satomi, Kagota, Kazumasa, Shinozuka, and Kazuki, Nakamura
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Aldehydes ,Mice ,Isomerism ,Cell Survival ,Cell Line, Tumor ,Smoke ,Animals ,Glutathione ,Chromatography, High Pressure Liquid ,Gas Chromatography-Mass Spectrometry ,Mass Spectrometry - Abstract
α,β-Unsaturated carbonyl compounds readily form adducts with SH or NH
- Published
- 2019
19. Development of anti-glomerular basement membrane glomerulonephritis during the course of IgA nephropathy: a case report
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Takashi Oda, Shuuhei Komatsu, Kentaro Sugisaki, Go Hirose, Taito Oshima, Muneharu Yamada, Tadasu Kojima, Noriko Yoshikawa, and Tomohiro Tomiyasu
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Pathology ,medicine.medical_specialty ,Anti-Glomerular Basement Membrane Disease ,Glomerulonephritis, Membranoproliferative ,Biopsy ,030232 urology & nephrology ,Renal function ,Mild proteinuria ,Case Report ,030204 cardiovascular system & hematology ,lcsh:RC870-923 ,urologic and male genital diseases ,Methylprednisolone ,Nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Renal Dialysis ,Crescentic glomerulonephritis ,Internal medicine ,medicine ,Humans ,Anti-glomerular basement membrane (GBM) glomerulonephritis ,Autoantibodies ,Plasma Exchange ,medicine.diagnostic_test ,urogenital system ,business.industry ,Glomerular basement membrane ,Rapidly progressive glomerulonephritis (RPGN) ,Glomerulonephritis, IGA ,Glomerulonephritis ,Complement C3 ,IgA nephropathy ,Middle Aged ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,Combined Modality Therapy ,Glomerular Mesangium ,Immunoglobulin A ,medicine.anatomical_structure ,Nephrology ,Mesangium ,Immunoglobulin G ,Mesangial proliferative glomerulonephritis ,Female ,Renal biopsy ,business - Abstract
Background Anti-glomerular basement membrane (GBM) glomerulonephritis does not usually coexist with another glomerulonephritis such as IgA nephropathy. We present a rare case having a combination of these two diseases, and furthermore, histological evaluation could be performed before and after the development of anti-GBM glomerulonephritis over a period of only10 months. Case presentation A 66-year-old woman was admitted with complaints of microscopic hematuria and mild proteinuria for the past 3 years. Serum creatinine level was normal at that time. The first renal biopsy was performed. Light microscopy revealed mesangial proliferative glomerulonephritis with fibro-cellular crescents in one out of 18 glomeruli, excluding one global sclerotic glomerulus. Immunofluorescence (IF) showed IgA and C3 deposition in the mesangium. Therefore, the diagnosis was IgA nephropathy. Eight months later, the patient’s serum creatinine suddenly rose to 4.53 mg/dL and urinalysis showed 100 red blood cells per high power field with nephrotic range proteinuria (12.3 g/gCr). The serological tests revealed the presence of anti-GBM antibody at the titer of 116 IU/mL. Treatments were begun after admission, consisting of hemodialysis, plasma exchange, and intravenous methylprednisolone pulse therapy. At 4 weeks after admission, the second renal biopsy was performed. Light microscopy revealed crescents in 18 of 25 glomeruli, excluding six global sclerotic glomeruli. IF showed linear IgG deposition along the GBM in addition to granular IgA and C3 deposition. Based on these findings, the diagnosis of anti-GBM glomerulonephritis and IgA nephropathy was confirmed. Renal function was not restored despite treatment, but alveolar hemorrhage was prevented. Conclusions We report a patient with a diagnosis of anti-GBM disease during the course of IgA nephropathy. This case strongly suggests that the presence of autoantibodies should be checked to rule out overlapping autoimmune conditions even in patient who have previously been diagnosed with chronic glomerulonephritis, such as IgA nephropathy, who present an unusually rapid clinical course.
- Published
- 2019
20. Mass Spectrometric Approaches to the Identification of Potential Ingredients in Cigarette Smoke Causing Cytotoxicity
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Shizuyo Horiyama, Noriko Yoshikawa, Masaru Kunitomo, and Kazuki Nakamura
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0301 basic medicine ,Cell Survival ,Acetic Anhydrides ,Melanoma, Experimental ,Pharmaceutical Science ,Gas Chromatography-Mass Spectrometry ,Mass Spectrometry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Tar (tobacco residue) ,Liquid chromatography–mass spectrometry ,Cell Line, Tumor ,Smoke ,Animals ,Organic chemistry ,Pharmacology ,chemistry.chemical_classification ,Chemistry ,Acrolein ,Tobacco Products ,General Medicine ,Glutathione ,Butanones ,Amino acid ,Acetic anhydride ,030104 developmental biology ,Biochemistry ,Toxicity ,Tyrosine ,Chromatography, Liquid - Abstract
Cigarette smoke contains many harmful chemicals that contribute to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease, cancer, and cardiovascular disease. Many studies have been done to identify cytotoxic chemicals in cigarette smoke and elucidate the onset of the above-mentioned diseases caused by smoking. However, definitive mechanisms for cigarette smoke toxicity remain unknown. As candidates for cytotoxic chemicals, we have recently found methyl vinyl ketone (MVK) and acetic anhydride in nicotine/tar-free cigarette smoke extract (CSE) using L-tyrosine (Tyr), an amino acid with highly reactive hydroxyl group. The presence of MVK and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS). We also found new reaction products formed in B16-BL6 mouse melanoma (B16-BL6) cells treated with CSE using LC/MS. These were identified as glutathione (GSH) conjugates of α,β-unsaturated carbonyl compounds, MVK, crotonaldehyde (CA), and acrolein (ACR), by the mass value and product ion spectra of these new products. ACR and MVK are type-2 alkenes, which are well known as electron acceptors and form Michael-type adducts to nucleophilic side chain of amino acids on peptides. These α,β-unsaturated carbonyl compounds may have a key role in CSE-induced cell death.
- Published
- 2016
21. Intracellular Metabolism of α,β-Unsaturated Carbonyl Compounds, Acrolein, Crotonaldehyde and Methyl Vinyl Ketone, Active Toxicants in Cigarette Smoke: Participation of Glutathione Conjugation Ability and Aldehyde–Ketone Sensitive Reductase Activity
- Author
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Noriko Yoshikawa, Chie Honda, Shizuyo Horiyama, Kazuki Nakamura, Tsutomu Masujima, Atsushi Ichikawa, Yuta Takahashi, Mayuko Hatai, Masaru Kunitomo, Mitsuo Takayama, and Sachiko Date
- Subjects
0301 basic medicine ,Ketone ,Carbonyl Reductase ,Molecular Conformation ,Adduct ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Smoke ,Drug Discovery ,Tumor Cells, Cultured ,Animals ,Crotonaldehyde ,chemistry.chemical_classification ,Aldehydes ,Acrolein ,Tobacco Products ,General Chemistry ,General Medicine ,Glutathione ,Ketones ,030104 developmental biology ,chemistry ,Biochemistry ,Methyl vinyl ketone ,Oxidoreductases ,Intracellular - Abstract
The major toxicants in cigarette smoke, α,β-unsaturated aldehydes, such as acrolein (ACR) and crotonaldehyde (CA), and α,β-unsaturated ketone, methyl vinyl ketone (MVK), are known to form Michael-type adducts with glutathione (GSH) and consequently cause intracellular GSH depletion, which is involved in cigarette smoke-induced cytotoxicity. We have previously clarified that exposure to cigarette smoke extract (CSE) of a mouse melanoma cell culture medium causes rapid reduction of intracellular GSH levels, and that the GSH-MVK adduct can be detected by LC/MS analysis while the GSH-CA adduct is hardly detected. In the present study, to clarify why the GSH-CA adduct is difficult to detect in the cell medium, we conducted detailed investigation of the structures of the reaction products of ACR, CA, MVK and CSE in the GSH solution or the cell culture medium. The mass spectra indicated that in the presence of the cells, the GSH-CA and GSH-ACR adducts were almost not detected while their corresponding alcohols were detected. On the other hand, both the GSH-MVK adducts and their reduced products were detected. In the absence of the cells, the reaction of GSH with all α,β-unsaturated carbonyls produced only their corresponding adducts. These results show that the GSH adducts of α,β-unsaturated aldehydes, CA and ACR, are quickly reduced by certain intracellular carbonyl reductase(s) and excreted from the cells, unlike the GSH adduct of α,β-unsaturated ketone, MVK. Such a difference in reactivity to the carbonyl reductase might be related to differences in the cytotoxicity of α,β-unsaturated aldehydes and ketones.
- Published
- 2016
22. The effect of tumor suppressor Pdcd4 knockdown on gene expression on mouse fibroblast cells and mouse melanoma cells
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Satomi Kagota, Noriko Yoshikawa, Eriko Iwata, Kana Nishikaze, Kazumasa Shinozuka, and Kazuki Nakamura
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Gene knockdown ,law ,Applied Mathematics ,General Mathematics ,Gene expression ,Cancer research ,Suppressor ,Mouse Fibroblast ,Biology ,Mouse Melanoma ,law.invention - Published
- 2020
23. Detoxification Mechanism of α,β-Unsaturated Carbonyl Compounds in Cigarette Smoke Observed in Sheep Erythrocytes
- Author
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Shizuyo Horiyama, Masaru Kunitomo, Kazuki Nakamura, Noriko Yoshikawa, Mayuko Hatai, and Atsushi Ichikawa
- Subjects
Erythrocytes ,Reductase ,030226 pharmacology & pharmacy ,Adduct ,Cigarette Smoking ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Smoke ,Drug Discovery ,medicine ,Animals ,Acrolein ,Epalrestat ,Aldose reductase ,Aldehydes ,Sheep ,General Chemistry ,General Medicine ,Glutathione ,Tobacco Products ,Aldose reductase inhibitor ,Butanones ,chemistry ,Biochemistry ,030220 oncology & carcinogenesis ,Toxicity ,medicine.drug - Abstract
Highly reactive α,β-unsaturated carbonyl compounds, such as acrolein (ACR), crotonaldehyde (CA) and methyl vinyl ketone (MVK), are environmental pollutants present in high concentrations in cigarette smoke. We have previously found that these carbonyl compounds in cigarette smoke extract (CSE) react with intracellular glutathione (GSH) to produce the corresponding GSH-ACR, GSH-CA and GSH-MVK adducts via Michael addition reaction. These adducts are then further reduced to the corresponding alcohol forms by intracellular aldo-keto reductases in highly metastatic mouse melanoma (B16-BL6) cells and then excreted into the extracellular fluid. This time, we conducted a similar study using sheep erythrocytes and found analogous changes in the sheep erythrocytes after exposure to CSE as those with B16-BL6 cells. This indicates similarity of the detoxification pathways of the α,β-unsaturated carbonyl compounds in sheep blood cells and B16-BL6 cells. Also, we found that the GSH-MVK adduct was reduced by aldose reductase in a cell-free solution to generate its alcohol form, and its reduction reaction was completely suppressed by pretreatment with epalrestat, an aldose reductase inhibitor, a member of the aldo-keto reductase family. In the presence of sheep blood cells, however, reduction of the GSH-MVK adduct was partially inhibited by epalrestat. This revealed that some member of the aldo-keto reductase superfamily other than aldose reductase is involved in reduction of the GSH-MVK adduct in sheep blood. These results suggest that blood cells, mainly erythrocytes are involved in reducing the inhalation toxicity of cigarette smoke via an aldo-keto reductase pathway other than that of aldose reductase.
- Published
- 2018
24. Invasion-inhibiting Effects of Gaseous Components in Cigarette Smoke on Mouse Rectal Carcinoma Colon-26 Cells
- Author
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Kazumasa Shinozuka, Kazuki Nakamura, Noriko Yoshikawa, Eriko Kinoshita, Shizuyo Horiyama, Satomi Kagota, and Mayuko Hatai
- Subjects
0301 basic medicine ,Cancer Research ,Nicotine ,Cell Survival ,Spleen ,General Biochemistry, Genetics and Molecular Biology ,Metastatic lesion ,03 medical and health sciences ,Mice ,Cell Movement ,Cell Line, Tumor ,Smoke ,Active component ,Rectal carcinoma ,parasitic diseases ,medicine ,Cigarette smoke ,Animals ,Tumor inoculation ,Cell Proliferation ,Pharmacology ,Dose-Response Relationship, Drug ,Chemistry ,Rectal Neoplasms ,Smoking ,Primary lesion ,Butanones ,Tars ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,Female ,medicine.drug ,Research Article - Abstract
We investigated the anti-metastatic action of nicotine- and tar-removed cigarette smoke extract (CSE) on highly metastatic mouse Colon-26 cells using syngeneic BALB/c mice. Colon-26 cells were injected into the spleen of mice, cells were grown in the spleen as the primary lesion, and some metastasized from the spleen to liver and established a metastatic lesion. CSE (10, 30, and 100%) was intraperitoneally administered daily to the mice for 14 days after tumor inoculation. As a result, the relative spleen weights of CSE-administered mice did not differ significantly from those of the control mice. However, the relative liver weights of CSE 30%-administered mice significantly decreased compared to control mice. In order to identify the active component in CSE, we examined the action of methyl vinyl ketone (MVK) on the invasiveness of Colon-26 cells. MVK significantly reduced the invasiveness of cells. MVK may be a candidate active component of CSE.
- Published
- 2018
25. Enhanced Nitric Oxide Synthase Activation via Protease-Activated Receptor 2 Is Involved in the Preserved Vasodilation in Aortas from Metabolic Syndrome Rats
- Author
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Kazumasa Shinozuka, Kazuki Nakamura, Satomi Kagota, Kana Maruyama, John J. McGuire, Hirokazu Wakuda, and Noriko Yoshikawa
- Subjects
Male ,Nitroprusside ,Agonist ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,Physiology ,medicine.drug_class ,Vasodilator Agents ,Aorta, Thoracic ,Vasodilation ,Nitric Oxide ,Rats, Inbred WKY ,Nitric oxide ,chemistry.chemical_compound ,Rats, Inbred SHR ,Internal medicine ,medicine ,Animals ,Receptor, PAR-2 ,Enzyme Inhibitors ,Phosphorylation ,Receptor ,Mesenteric arteries ,Protease-activated receptor 2 ,Metabolic Syndrome ,Dose-Response Relationship, Drug ,biology ,Age Factors ,Acetylcholine ,Enzyme Activation ,Nitric oxide synthase ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,chemistry ,biology.protein ,Cardiology and Cardiovascular Medicine ,Oligopeptides ,Signal Transduction - Abstract
Endothelium-dependent vasodilation via protease-activated receptor 2 (PAR2) is preserved in mesenteric arteries from SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF) with metabolic syndrome even though nitric oxide (NO)-mediated vasodilation is attenuated. Therefore, we examined the PAR2 mechanisms underlying metabolic syndrome-resistant vasodilation in SHRSP.ZF aortas with ageing. In isolated aortas, the PAR2 agonist 2-furoyl-LIGRLO-amide (2fly) caused vasodilation that was sustained in male SHRSP.ZF until 18 weeks of age, but was attenuated afterwards compared with age-matched Wistar-Kyoto rats (controls) at 23 weeks. In contrast, acetylcholine-induced vasodilation was impaired in SHRSP.ZF already at 18 weeks of age. Treatments of aortas with inhibitors of NO synthase and soluble guanylate cyclase abolished the sustained 2fly- and residual acetylcholine-induced vasodilation in SHRSP.ZF at 18 weeks of age. In the aortas of SHRSP.ZF, 8-bromo-cGMP-induced vasodilation, NO production and cGMP accumulation elicited by 2fly were not different from in the controls. PAR2 agonist increased phospho-Ser1177-eNOS protein content only in SHRSP.ZF aortas. These results indicate that vasodilation mediated by PAR2 is sustained even though NO-dependent relaxation is attenuated with ageing/exposure to metabolic disorders in large-caliber arteries from SHRSP.ZF. PAR2 stimulation of NO production via an additional pathway that targets phosphorylation of Ser1177-eNOS suggests a regulatory mechanism for sustaining agonist-mediated vasodilation in metabolic syndrome.
- Published
- 2015
26. Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis
- Author
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Kazuki Nakamura, Noriko Yoshikawa, and Kazumasa Shinozuka
- Subjects
Kupffer Cells ,Adenosine A3 Receptor Antagonists ,Antineoplastic Agents ,Pharmacology ,Models, Biological ,chemistry.chemical_compound ,Adenosine A3 Receptor Agonists ,GSK-3 ,Cell Line, Tumor ,Antimetastatic Agent ,medicine ,Animals ,Humans ,Medicine, Chinese Traditional ,Neoplasm Metastasis ,Adenosine A3 receptor ,Antimetastasis ,Cordycepin (3′-deoxyadenosine) ,Cordyceps ,Deoxyadenosines ,biology ,Cordycepin ,Plant Extracts ,Chemistry ,lcsh:RM1-950 ,Receptor, Adenosine A3 ,Atherosclerosis ,biology.organism_classification ,Adenosine ,lcsh:Therapeutics. Pharmacology ,Methotrexate ,Anticancer ,Cancer cell ,Molecular Medicine ,Drug Therapy, Combination ,Water extract of Cordyceps sinensis (WECS) ,Adenosine Deaminase Inhibitor ,Pentostatin ,Phytotherapy ,Signal Transduction ,medicine.drug - Abstract
Cordyceps sinensis , a fungus that parasitizes on the larva of Lepidoptera, has been used as a valued traditional Chinese medicine. We investigated the effects of water extracts of Cordyceps sinensis (WECS), and particularly focused on its anticancer and antimetastatic actions. Based on in vitro studies, we report that WECS showed an anticancer action, and this action was antagonized by an adenosine A 3 receptor antagonist. Moreover, this anticancer action of WECS was promoted by an adenosine deaminase inhibitor. These results suggest that one of the components of WECS with an anticancer action might be an adenosine or its derivatives. Therefore, we focused on cordycepin (3′-deoxyadenosine) as one of the active ingredients of WECS. According to our experiments, cordycepin showed an anticancer effect through the stimulation of adenosine A 3 receptor, followed by glycogen synthase kinase (GSK)-3β activation and cyclin D 1 suppression. Cordycepin also showed an antimetastatic action through inhibiting platelet aggregation induced by cancer cells and suppressing the invasiveness of cancer cells via inhibiting the activity of matrix metalloproteinase (MMP)-2 and MMP-9, and accelerating the secretion of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 from cancer cells. In conclusion, cordycepin, an active component of WECS, might be a candidate anticancer and antimetastatic agent.
- Published
- 2015
27. Methyl Vinyl Ketone, a Toxic Ingredient in Cigarette Smoke Extract, Modifies Glutathione in Mouse Melanoma Cells
- Author
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Sachiko Date, Yuta Takahashi, Atsushi Ichikawa, Noriko Yoshikawa, Mitsuo Takayama, Tsutomu Masujima, Shizuyo Horiyama, Mayuko Hatai, Masaru Kunitomo, Chie Honda, Kazuki Nakamura, and Kiyoko Suwa
- Subjects
Programmed cell death ,Antioxidant ,Cell Survival ,medicine.medical_treatment ,medicine.disease_cause ,Mice ,chemistry.chemical_compound ,Cell Line, Tumor ,Smoke ,parasitic diseases ,Drug Discovery ,medicine ,Animals ,Viability assay ,Cytotoxicity ,Aldehydes ,Cytotoxins ,Smoking ,General Chemistry ,General Medicine ,Glutathione ,Butanones ,Biochemistry ,chemistry ,Toxicity ,Intracellular ,Oxidative stress - Abstract
Cigarette smoke contains many harmful chemicals, which contribute to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease, cancer and cardiovascular disease. The cytotoxicity of cigarette smoke is well documented, but the definitive mechanism behind its toxicity remains unknown. Ingredients in cigarette smoke are known to deplete intracellular glutathione (GSH), the most abundant cellular thiol antioxidant, and to cause oxidative stress. In the present study, we investigated the mechanism of cigarette smoke extract (CSE)-induced cytotoxicity in B16-BL6 mouse melanoma (B16-BL6) cells using liquid chromatography-tandem mass spectrometry. CSE and ingredients in cigarette smoke, methyl vinyl ketone (MVK) and crotonaldehyde (CA), reduced cell viability in a concentration-dependent manner. Also, CSE and the ingredients (m/z 70, each) irreversibly reacted with GSH (m/z 308) to form GSH adducts (m/z 378) in cells and considerably decreased cellular GSH levels at concentrations that do not cause cell death. Mass spectral data showed that the major product formed in cells exposed to CSE was the GSH-MVK adduct via Michael-addition and was not the GSH-CA adduct. These results indicate that MVK included in CSE reacts with GSH in cells to form the GSH-MVK adduct, and thus a possible reason for CSE-induced cytotoxicity is a decrease in intracellular GSH levels.
- Published
- 2014
28. Effects of Reinforcement Method of Dissection Physiology Education on the Achievement in Pharmacology
- Author
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Tomoya Kitayama, Kazumasa Shinozuka, Kanae Nishimura, Satomi Kagota, Naomi Yasui, Nobuyuki Kawai, Takeshi Miura, Noriko Yoshikawa, and Toshikatsu Nakabayashi
- Subjects
Class size ,Physiology ,Teaching method ,education ,Pharmaceutical Science ,Pharmacy ,Pharmacology ,0502 economics and business ,Humans ,050207 economics ,Reinforcement ,Medical education ,Class (computer programming) ,Academic year ,business.industry ,Dissection ,05 social sciences ,050301 education ,Students, Pharmacy ,Education, Pharmacy ,Educational Status ,Female ,Anatomy ,business ,Psychology ,0503 education ,Reinforcement, Psychology ,Basic class - Abstract
The Pharmaceutical Education Support Center was established in the Department of Pharmacy at the School of Pharmacy and Pharmaceutical Science of Mukogawa Women's University in 2014. We started teaching first and second years students according to proficiency from the 2014 academic year. Students were divided into two classes: the regular class (high proficiency class) and the basic class (low proficiency class), based on achievement in several basic subjects related to the study of pharmacy. The staffs in the Pharmaceutical Education Support Center reinforce what is taught to students in the basic class. In this reinforcement method of education, the class size is small, consisting of about 15 students, a quiz to review the previous lesson is given at the beginning of each lecture, and an additional five lectures are conducted, compared to the high proficiency class, which receives 15 lectures. In this study, we evaluated the effects of the reinforcement method of physiology education on achievement in pharmacology that was not conducted in the proficiency-dependent teaching method. The students in the basic class in physiology education were chosen based on achievement levels in anatomy. Achievement levels of pharmacology students in the basic class of physiology improved compared with those of students who had the same achievement levels in physiology but were not taught according to proficiency-dependent teaching in the 2013 academic year. These results suggest that the reinforcement method for education in basic subjects in pharmacy, such as physiology, can improve achievement in more advanced subjects, such as pharmacology.
- Published
- 2016
29. IMPAIRMENTS OF PROTEASE-ACTIVATED RECEPTOR 2-MEDIATED VASODILATIONS IN RENAL ARTERIES AND DEVELOPMENT OF KIDNEY DYSFUNCTION IN METABOLIC SYNDROME
- Author
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John J. McGuire, Kazumasa Shinozuka, Kana Maruyama, Kazuki Nakamura, Noriko Yoshikawa, and Satomi Kagota
- Subjects
medicine.medical_specialty ,business.industry ,Kidney dysfunction ,030204 cardiovascular system & hematology ,medicine.disease ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Physiology (medical) ,Internal medicine ,medicine ,Metabolic syndrome ,business ,030217 neurology & neurosurgery ,Protease-activated receptor 2 - Published
- 2018
30. Characteristics of effects of perivascular adipose tissue on vasodilation in metabolic syndrome rats
- Author
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Kazumasa Shinozuka, Kana Maruyama, Kazuki Nakamura, Satomi Kagota, Noriko Yoshikawa, Saki Iwata, and Miho Shimari
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Applied Mathematics ,General Mathematics ,Internal medicine ,Medicine ,Adipose tissue ,Vasodilation ,Metabolic syndrome ,business ,medicine.disease - Published
- 2018
31. Effects of inflammatory stimulation on the migratory ability of mouse Colon-26 cancer cells and B16-BL6 melanoma cells
- Author
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Rio Sugano, Kazuki Nakamura, Noriko Yoshikawa, Mayuko Hatai, Eriko Iwata, Satomi Kagota, Kazumasa Shinozuka, and Natsuki Zushi
- Subjects
Thesaurus (information retrieval) ,Mouse Colon ,business.industry ,Applied Mathematics ,General Mathematics ,Melanoma ,Cancer cell ,medicine ,Cancer research ,Stimulation ,medicine.disease ,business - Published
- 2019
32. A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records
- Author
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Lawrence R. Lustig, Thomas J. Hoffmann, Noriko Yoshikawa, Bronya J.B. Keats, Neil Risch, and Catherine Schaefer
- Subjects
Exonucleases ,Male ,0301 basic medicine ,Oncology ,Aging ,Cancer Research ,Heredity ,Presbycusis ,Otology ,Genome-wide association study ,Deafness ,Mathematical and Statistical Techniques ,0302 clinical medicine ,Medicine and Health Sciences ,Ethnicity ,Ethnicities ,Electronic Health Records ,10. No inequality ,Hearing Disorders ,Genetics (clinical) ,African Americans ,Genetics ,Microfilament Proteins ,Genomics ,Audiology ,Population groupings ,Cochlea ,3. Good health ,Genetic Mapping ,Phenotype ,Meta-analysis ,Physical Sciences ,Inner Ear ,Female ,Anatomy ,medicine.symptom ,Statistics (Mathematics) ,Research Article ,Adult ,Genotyping ,medicine.medical_specialty ,Genotype ,lcsh:QH426-470 ,Hearing loss ,Variant Genotypes ,Receptors, Cell Surface ,Single-nucleotide polymorphism ,Biology ,Research and Analysis Methods ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Internal medicine ,Genome-Wide Association Studies ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Statistical Methods ,Molecular Biology Techniques ,Hearing Loss ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Biology and Life Sciences ,Computational Biology ,Human Genetics ,Odds ratio ,Genome Analysis ,medicine.disease ,lcsh:Genetics ,030104 developmental biology ,Otorhinolaryngology ,Genetic epidemiology ,Ears ,Exoribonucleases ,Trans-Activators ,People and places ,Head ,Mathematics ,030217 neurology & neurosurgery ,Meta-Analysis ,Genome-Wide Association Study - Abstract
Age-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We identified two novel genome-wide significant SNPs: rs4932196 (odds ratio = 1.185, p = 4.0x10-11), 52Kb 3’ of ISG20, which replicated in a meta-analysis of the other GERA race/ethnicity groups (1,025 cases, 12,388 controls, p = 0.00094) and in a UK Biobank case-control analysis (30,802 self-reported cases, 78,586 controls, p = 0.015); and rs58389158 (odds ratio = 1.132, p = 1.8x10-9), which replicated in the UK Biobank (p = 0.00021). The latter SNP lies just outside exon 8 and is highly correlated (r2 = 0.96) with the missense SNP rs5756795 in exon 7 of TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. We further tested these SNPs in phenotypes from audiologist notes available on a subset of GERA (4,903 individuals), stratified by case/control status, to construct an independent replication test, and found a significant effect of rs58389158 on speech reception threshold (SRT; overall GERA meta-analysis p = 1.9x10-6). We also tested variants within exons of 132 other previously-identified hearing loss genes, and identified two common additional significant SNPs: rs2877561 (synonymous change in ILDR1, p = 6.2x10-5), which replicated in the UK Biobank (p = 0.00057), and had a significant GERA SRT (p = 0.00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0.0080), and had a consistent significant result for SRT (p = 0.041) and suggestive result for SDS (p = 0.081). Large cohorts with GWAS data and electronic health records may be a useful method to characterize the genetic architecture of ARHI., Author Summary Age-related hearing impairment (ARHI) is one of the most common sensory disorders. While ARHI effects can be mitigated with current technologies, it cannot be cured or eliminated. It is thus hoped that identification of genetic influences on ARHI may one day lead to curative therapies. Towards this goal, the current study utilized electronic health record data from non-Hispanic whites in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort to conduct a genome-wide association study of ARHI, and tested the significant variants for replication in other GERA race/ethnicity groups, independent GERA phenotypes, and self-reported ARHI from the UK Biobank. We discovered two genome-wide significant SNPs. The first was novel and near ISG20. The second was in TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. Motivated by our TRIOBP results, we also looked at exons in known hearing loss genes, and identified two additional SNPs, rs2877561 in ILDR1 and rs9493672 in EYA4 (at a significance threshold adjusted for number of SNPs in those regions). These results suggest that large cohorts with GWAS data and electronic health records may be a useful method to characterize the genetic architecture of ARHI.
- Published
- 2016
33. [A Case of General Anesthesia for a Cardiac Transplanted Patient Undergoing Inguinal Hernia Repair under Laparoscopic Surgery]
- Author
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Mitsuko, Inoue, Yasue, Hayashi, Yuki, Fujita, Motoko, Shimizu, Arisa, Hotta, Ai, Nakamoto, Noriko, Yoshikawa, Naoko, Ohira, and Shigeki, Tatekawa
- Subjects
Male ,Heart Transplantation ,Humans ,Hernia, Inguinal ,Laparoscopy ,Anesthesia, General ,Middle Aged - Abstract
A 52-year-old man was scheduled for the repair of inguinal hernia recurrence. When he was 48 years of age, he received a heart transplantation due to severe heart failure resulting from ischemic heart disease. When he was 50 years old, he suffered from inguinal hernia, and it was repaired under spinal anesthesia. During this surgery, he experienced pain because of the inadequate effect of anesthesia, but his blood pressure and heart rate were stable. We suspected that this was because of denervation of the heart. On hernia repair for inguinal hernia recurrence, general anesthesia was chosen, induced with midazolam, rocuronium, and fentanyl and maintained with sevoflurane, rocuronium, fentanyl, and remifentanil. The blood pressure was mostly stable during anesthesia, but we noted an increase in the heart rate when the trachea was intubated and extubated and when surgical incision started. This phenomenon may indicate reinnervation of the transplanted heart. We could safely manage anesthesia without invasive monitoring because the transplanted heart functioned favorably and surgery was minimally invasive.
- Published
- 2016
34. [Anesthetic Management with Propofol Alone in a Patient with Hereditary Sensory and Autonomic Neuropathy]
- Author
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Yuki, Fujita, Ai, Nakamoto, Mitsuko, Inoue, Yasue, Hayashi, Motoko, Shimizu, Arisa, Hotta, Noriko, Yoshikawa, Naoko, Ohira, and Shigeki, Tatekawa
- Subjects
Catecholamines ,Humans ,Anesthesia ,Female ,Hereditary Sensory and Autonomic Neuropathies ,Middle Aged ,Propofol - Abstract
Hereditary sensory and autonomic neuropathy (HSAN) is a rare peripheral nerve disorder associated with sensory dysfunction (pain, touch, and pressure) and various degrees of autonomic dysfunction. We administered general anesthesia for a 54-year-old woman with HSAN type II undergoing amputation of the left hallux. She had reduced sensation for pain, pressure, and temperature since birth and frequently injured her hands and legs. Before the operation, she did not report pain in the hallux. Only propofol was given for anesthesia without use of analgesia. Intraoperatively, her vital signs were stable. To evaluate the sympathetic nervous response to surgical stimulation, we measured the plasma catecholamine levels before tracheal intubation and just before and during surgery. Plasma catecholamine levels were normal at all time points, indicating no sympathetic responses to surgical stimulation. This case suggests that anesthesia for HSAN II patients can be safely managed with propofol alone.
- Published
- 2016
35. Effect of Cordyceps sinensis on TIMP-1 secretion from mouse melanoma cell
- Author
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Erika Kubo, Satomi Kagota, Kazumasa Shinozuka, Noriko Yoshikawa, Kazuki Nakamura, and Ayuko Sato
- Subjects
timp-1 ,QH301-705.5 ,Cell ,Spleen ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,cordyceps sinensis ,medicine ,Secretion ,Biology (General) ,neoplasms ,Cordyceps ,cordycepin ,General Immunology and Microbiology ,biology ,Cordycepin ,General Neuroscience ,Tissue inhibitor of metalloproteinase ,biology.organism_classification ,In vitro ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Cancer research ,b16-f0 mouse melanoma cell ,Hepatocyte growth factor ,General Agricultural and Biological Sciences ,medicine.drug - Abstract
Cordyceps sinensis is a Chinese medicinal fungus traditionally used in cancer treatments. In a previous study, we investigated the antimetastatic activity of Cordyceps sinensis (WECS) extract using liver metastatic model mice injected with B16-F0 mouse melanoma cells into the spleen. WECS reduced the number of metastatic nodules of B16-F0 cells in the liver of C57BL/6 mice, and significantly prolonged survival of the mice. Furthermore, we examined the effects of WECS on hepatocyte growth factor (HGF)-accelerated invasion of B16-F0 cells using a chemo-invasion assay in vitro. WECS was shown to significantly reduce HGF-accelerated B16-F0 cell invasion. In the present study, we investigated the effect of WECS on Tissue Inhibitor of Metalloproteinase (TIMP)-1 secretion from B16-F0 cells in order to identify clues to the mechanism underlying the anti-invasive action of WECS. As a result, WECS significantly increased the secretion of TIMP-1 from B16-F0 cells. Moreover, we investigated the effect of cordycepin (3′-deoxyadenosine), a component of WECS, on TIMP-1 secretion from B16-F0 cells to potentially identify the pharmacologically active ingredient in WECS extract. Cordycepin was shown to significantly accelerate the release of TIMP-1 from cells. These findings suggest that WECS exerts anti-invasive activity, in part by increasing TIMP-1 secretion from melanoma cells, and that cordycepin potentially functions as the effective component.
- Published
- 2012
36. Inhibitory Effect of Cigarette Smoke Extract on Experimental Lung Metastasis of Mouse Melanoma by Suppressing Tumor Invasion
- Author
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Masaru Kunitomo, Kazuki Nakamura, Kazumasa Shinozuka, Noriko Yoshikawa, Yoko Kimoto, Shizuyo Horiyama, Yuta Takahashi, and Satomi Kagota
- Subjects
Pathology ,medicine.medical_specialty ,Lung ,Experimental metastasis ,business.industry ,Lung metastasis ,Invasion and migration ,Mouse Melanoma ,In vitro ,medicine.anatomical_structure ,parasitic diseases ,medicine ,Cancer research ,Cigarette smoke ,business ,Inhibitory effect - Abstract
We investigated the effect of a nicotine-and tar-free cigarette smoke extract (CSE) using an experimental metastasis mouse model which was intravenously injected with B16-BL6 mouse melanoma cells. Three-hour pretreatment of cells with various concentrations of CSE (0, 0.1, 0.3, and 1%) dose-dependently reduced the number of lung metastatic nodules 14 days after tumor injection. To elucidate the mechanism of this anti-metastatic effect of CSE, we examined the invasion and migration activities of B16-BL6 cells pretreated with CSE for three hours in vitro. CSE significantly reduced the invasion of cells at 1% and the migration at 0.3% and 1%. Under the same pretreatment conditions, CSE had no effect on the proliferation of cells. These findings suggest that CSE contains some ingredients that suppress hematogenic lung metastasis via inhibition of the invasion and migration activities of mouse melanoma cells.
- Published
- 2012
37. Program for Fostering Human Resources with Sigma-type Integrative Ability
- Author
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Chiaki Nakayama, Eiji Watanabe, Masato Murakami, and Noriko Yoshikawa
- Subjects
Knowledge management ,business.industry ,Management science ,Sigma ,Human resources ,business ,Strategic human resource planning - Published
- 2011
38. Perioperative Management of Patients with Drug-eluting Coronary Stents for Elective Non-cardiac Surgery
- Author
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Ai Nakamoto, Kumiko Hirakawa, Naoko Ohira, Arisa Hotta, Noriko Yoshikawa, and Shigeki Tatekawa
- Subjects
Drug ,medicine.medical_specialty ,Perioperative management ,business.industry ,media_common.quotation_subject ,Internal medicine ,Non cardiac surgery ,medicine ,Cardiology ,business ,media_common ,Surgery - Published
- 2011
39. Cordyceps sinensis Acts As an Adenosine A3 Receptor Agonist on Mouse Melanoma and Lung Carcinoma Cells, and Human Fibrosarcoma and Colon Carcinoma Cells
- Author
-
Erika Kubo, Kazuki Nakamura, Satomi Kagota, Arisa Nishiuchi, Kazumasa Shinozuka, Masaru Kunitomo, Noriko Yoshikawa, and Yu Yamaguchi
- Subjects
medicine.medical_specialty ,Cordyceps ,biology ,Cordycepin ,Lewis lung carcinoma ,medicine.disease ,Adenosine A3 receptor ,biology.organism_classification ,Molecular biology ,Adenosine ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Cell culture ,Internal medicine ,medicine ,HT1080 ,Fibrosarcoma ,medicine.drug - Abstract
Cordyceps sinensis, a parasitic fungus on the larva of Lapidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells and mouse Lewis lung carcinoma (LLC) cells was inhibited by cordycepin (3’-deoxyadenosine), an ingredient of Cordyceps sinensis, and its effect was antagonized by MRS1191, a selective adenosine A3 receptor (A3-R) antagonist although adenosine (up to 100 μM) had no effect on the growth of B16-BL6 and LLC cells. In this study, we investigated whether water extracts of Cordyceps sinensis (WECS) inhibit the growth of B16-BL6 cells, LLC cells, HT1080 human fibrosarcoma (HT1080) cells and CW-2 human colon carcinoma (CW-2) cells via their A3-R. As a result, the growth of all cell lines were potently inhibited by WECS (10 μg/mL) and the inhibitory effect of WECS was significantly antagonized by MRS1191 (1 μM). Furthermore, WECS included 2.34% w/w cordycepin and 0.12% w/w adenosine as components according to the HPLC- ECD system. In conclusion, WECS inhibited the proliferation of four cancer cell lines by stimulation of A3-R and the main component in WECS with anticancer action might be cordycepin instead of adenosine.
- Published
- 2011
40. Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase
- Author
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Tomoko Ishiko, Takeshi Taguchi, Nobuyuki Tanaka, Noriko Yoshikawa, Masaharu Yoshida, Kazunori Nanri, Masatake Kobayashi, and Kentaro Sugisaki
- Subjects
medicine.medical_specialty ,Neuromyelitis optica ,biology ,business.industry ,medicine.medical_treatment ,Myelitis ,Hematology ,General Medicine ,medicine.disease ,Gastroenterology ,Transverse myelitis ,Steroid therapy ,Neuromyelitis Optica Spectrum Disorders ,Internal medicine ,Immunology ,medicine ,biology.protein ,Plasmapheresis ,Antibody ,business ,Immunoadsorption - Abstract
Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.
- Published
- 2014
41. Remifentanil increases the incidence of mesenteric traction syndrome: preliminary randomized controlled trial
- Author
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Ai Nakamoto, Yusuke Funai, Yohei Fujimoto, Shigeki Tatekawa, Arisa Hotta, Naoto Hori, Yuki Nomura, Kumiko Hirakawa, Noriko Yoshikawa, and Naoko Ohira
- Subjects
Tachycardia ,medicine.medical_specialty ,medicine.medical_treatment ,Remifentanil ,6-Ketoprostaglandin F1 alpha ,macromolecular substances ,Anesthesia, General ,law.invention ,Piperidines ,Randomized controlled trial ,law ,Laparotomy ,Anesthesiology ,Abdomen ,Flushing ,Humans ,Medicine ,Mesentery ,Prospective Studies ,Splanchnic Circulation ,Intraoperative Complications ,Prospective cohort study ,Aged ,urogenital system ,business.industry ,Hemodynamics ,Syndrome ,Middle Aged ,Traction (orthopedics) ,Surgery ,Anesthesiology and Pain Medicine ,Anesthesia ,Anesthesia Recovery Period ,Hypotension ,medicine.symptom ,business ,Anesthetics, Intravenous ,Abdominal surgery ,medicine.drug - Abstract
The use of remifentanil is often associated with the observation of mesenteric traction syndrome (MTS) soon after manipulation of the intestine during abdominal surgery. MTS symptoms include facial flushing, hypotension, and tachycardia. In the study reported here, we prospectively investigated the effects of remifentanil on the incidence of MTS in abdominal surgery.One hundred patients scheduled for abdominal surgery were randomly assigned to two groups. In one group (n = 50), fentanyl alone was used as intravenous analgesic (control, group C); in the second group (n = 50), both fentanyl and remifentanil were used (remifentanil group, group R). In all patients, anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane inhalation. Remifentanil was continuously infused for patients in group R as an analgesic. Plasma concentration of 6-keto-PGF(1α) was measured before surgery and 20 min after the skin incision was made in six patients of group R and seven patients of group C.MTS occurred in 20 cases in group R (40.0%), but in only five cases in group C (10.0%). In both groups, the incidence of MTS was higher in laparotomy than in laparoscopic surgery. The plasma concentration of 6-keto-PGF(1α) was low in both groups before surgery and was elevated 20 min after skin incision in both groups in patients in whom MTS appeared.The results of this study suggest that the use of remifentanil in laparotomy facilitates MTS.
- Published
- 2010
42. Have Tumor Suppressor PDCD4 and its Counteragent Oncogenic miR-21 Gone Rogue?
- Author
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Nancy H. Colburn, Matthew R. Young, Noriko Yoshikawa, and Arti N. Santhanam
- Subjects
Regulation of gene expression ,Suppressor of cytokine signaling 1 ,medicine.medical_treatment ,RNA-Binding Proteins ,Biology ,Models, Biological ,law.invention ,Viewpoints ,MicroRNAs ,Cytokine ,Gene Expression Regulation ,Downregulation and upregulation ,law ,Neoplasms ,microRNA ,Cancer research ,medicine ,Humans ,Molecular Medicine ,Suppressor ,SOCS5 ,SOCS6 ,Apoptosis Regulatory Proteins - Abstract
A recent article suggests that the well known tumor suppressor PDCD4 also functions as a pro-inflammatory agent. The PDCD4 counteragent miR-21, a pro-oncogenic micro-RNA, is described as an anti-inflammatory agent. The authors of this research article provide evidence that mice lacking PDCD4 are protected from the lethal effects of lipopolysaccharide (LPS). This report also confirms miR-21 as a negative regulator of PDCD4 expression after LPS stimulation. Downstream mediators of the pro-inflammatory activity of PDCD4 include IL-10, an anti-inflammatory cytokine that is negatively regulated by PDCD4, and IL-6, a pro-inflammatory cytokine that appears to be upregulated in a PDCD4 dependent manner, possibly through an increase in NF-κB activity. Is it possible that a tumor-suppressor protein and an oncogenic micro-RNA can be oppositely targeted to control inflammatory disease?
- Published
- 2010
43. Changes in vasodilation via protease-activated receptor-2 with ageing differ between animal models of metabolic syndrome
- Author
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Kazumasa Shinozuka, Noriko Yoshikawa, John J. McGuire, Kana Maruyama, Kazuki Nakamura, and Satomi Kagota
- Subjects
medicine.medical_specialty ,Endocrinology ,Ageing ,Chemistry ,Applied Mathematics ,General Mathematics ,Internal medicine ,medicine ,Vasodilation ,Metabolic syndrome ,medicine.disease ,Protease-activated receptor 2 - Published
- 2018
44. Rapid decrease of anti-β-glucan antibody as an indicator for early diagnosis of carinii pneumonitis and deep mycotic infections following immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis
- Author
-
Tomohiro Tomiyasu, Noriko Yoshikawa, Shunsuke Hida, Masakazu Akashi, Iwao Nakabayashi, Ken-ichi Ishibashi, Masaharu Yoshida, Taeko Watanabe, and Naohito Ohno
- Subjects
Male ,Vasculitis ,Antifungal Agents ,beta-Glucans ,Opportunistic infection ,medicine.medical_treatment ,Enzyme-Linked Immunosorbent Assay ,Antibodies, Antineutrophil Cytoplasmic ,Rheumatology ,Candida albicans ,Humans ,Medicine ,Anti-neutrophil cytoplasmic antibody ,Pneumonitis ,Aged, 80 and over ,biology ,business.industry ,Remission Induction ,Antibody titer ,Reproducibility of Results ,Pneumonia ,General Medicine ,Immunotherapy ,Middle Aged ,medicine.disease ,Titer ,Aspergillus ,Mycoses ,Immunology ,biology.protein ,Female ,Antibody ,business ,Immunosuppressive Agents - Abstract
Deep mycosis (aspergillus pneumonia (AsP)) and carinii pneumonitis (PCP) are complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The objective was to clarify the clinical significance of plasma titer of antibody against beta-glucans (anti-BG antibody) as a predictor of complications such as AsP or PCP and the prognosis of patients. Enzyme-linked immunosorbent assay was used to measure the plasma titer of antibodies against beta-glucans (BG) from Candida albicans in 22 healthy subjects and 52 patients with various stages of AAV. The mean plasma titer of the anti-BG antibody was 2,677 +/- 1,686 U in healthy subjects, 691 +/- 522 U in patients with untreated active vasculitis (n = 14), and 547 +/- 416 U in patients soon after immunosuppressive treatment (n = 24). Healthy subjects had significantly higher antibody titers than the other two groups (P0.05). Repeated measurements over the clinical course of AAV revealed an increase during remission to 1,180 +/- 130 U (n = 11), while there was a significant rapid decrease to 369 +/- 441 U (P0.01) concomitantly with elevation in plasma C-reactive protein and BG levels in patients with AAV that had AsP or PCP infection. Antifungal therapy resulted in a rapid rise of anti-BG antibody titer. Experiments in mice suggested that the anti-BG antibody neutralizes BG. Rapid decrease of the anti-BG antibody titer may be a useful indicator for diagnosis of the presence of AsP or PCP and for estimating the prognosis of patients with these opportunistic infections during immunosuppressive treatment of AAV.
- Published
- 2009
45. Biochemical Evidence of Atherosclerosis Progression Mediated by Increased Oxidative Stress in Apolipoprotein E–Deficient Spontaneously Hyperlipidemic Mice Exposed to Chronic Cigarette Smoke
- Author
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Kazumasa Shinozuka, Satomi Kagota, Kazuki Nakamura, Yu Yamaguchi, Noriko Yoshikawa, and Masaru Kunitomo
- Subjects
Male ,Apolipoprotein E ,medicine.medical_specialty ,Antioxidant ,Apolipoprotein B ,medicine.medical_treatment ,Hyperlipidemias ,medicine.disease_cause ,Antioxidants ,Nicotine ,Mice ,Apolipoproteins E ,Tar (tobacco residue) ,Smoke ,Internal medicine ,Tobacco ,Hyperlipidemia ,medicine ,Animals ,Vitamin E ,Pharmacology ,biology ,business.industry ,lcsh:RM1-950 ,Atherosclerosis ,medicine.disease ,Disease Models, Animal ,Oxidative Stress ,Endocrinology ,lcsh:Therapeutics. Pharmacology ,Disease Progression ,biology.protein ,Molecular Medicine ,Tobacco Smoke Pollution ,business ,Oxidative stress ,medicine.drug - Abstract
Cigarette smoking is a major risk factor for cardiovascular disease. The induction of oxidative stress by smoking plays a key role in the progression of atherosclerosis. However, the underlying mechanisms are not fully understood. In the present study, we investigated whether long-term smoking can accelerate the progression of atherosclerosis and whether oxidative stress is implicated in its pathogenesis. Apolipoprotein E–deficient spontaneously hyperlipidemic mice, a model of atherosclerosis, were exposed to the gas-phase of smoke, from which tar and nicotine had been removed, for 15 min a day, 6 days a week, for 16 weeks. Exposure to cigarette smoke significantly increased the serum levels of oxidative stress markers such as thiobarbituric acid–reactive substances, oxidatively modified low-density lipoproteins, and 3-nitrotyrosine, but it did not affect serum cholesterol and triglyceride levels. Exposure to smoke also accelerated the accumulation of total cholesterol levels in the aorta that was accompanied by an increase in 3-nitrotyrosine levels of the atherosclerotic mice. These changes in the serum and aorta that progressed with exposure to smoke were prevented by vitamin E administration. Our data suggest that chronic cigarette smoking promotes and aggravates atherosclerosis and that the antioxidant vitamin E exerts an anti-atherogenic effect via reduction of oxidative stress. Keywords:: cigarette smoking, atherosclerosis, oxidative stress, apolipoprotein E–deficient spontaneously hyperlipidemic mice, vitamin E
- Published
- 2009
46. Relationship between plasma leptin or soluble cleaved leptin-receptor concentrations and glucocorticoid sensitivity of peripheral blood mononuclear cells in patients with nephrotic syndrome
- Author
-
Masaharu Yoshida, Noriko Yoshikawa, Kayo Henmi, Toshihiko Hirano, and Iwao Nakabayashi
- Subjects
Adult ,Leptin ,Male ,medicine.medical_specialty ,Nephrotic Syndrome ,Prednisolone ,medicine.medical_treatment ,Immunology ,Adipokine ,Peripheral blood mononuclear cell ,Internal medicine ,Blood plasma ,medicine ,Humans ,Immunology and Allergy ,Pharmacology ,Leptin receptor ,business.industry ,Middle Aged ,Cytokine ,Endocrinology ,Leukocytes, Mononuclear ,Receptors, Leptin ,Female ,business ,Immunosuppressive Agents ,Glucocorticoid ,medicine.drug - Abstract
Leptin is a small peptide hormone which centrally regulates weight. Leptin receptor (OB-R) is expressed in hematopoietic cells, the central nervous, and immune systems. OB-R bears a homology similar to members of the class Iota cytokine family, and therefore, leptin appears to modulate immune responses. The aim of this study was to examine the effect of plasma leptin, soluble OB-R (sOB-R), and the free leptin index (FLI), the ratio between leptin and sOB-R levels, on the sensitivities of peripheral blood mononuclear cells (PBMCs) to prednisolone and cyclosporine in 16 healthy subjects and seven nephrotic syndrome (NS) patients. The NS patients had significantly higher serum sOB-R and lower FLI, compared with the healthy subjects (respectively, P=0.0026, P=0.0383). Whereas, the NS patients had significantly lower PBMC sensitivity to prednisolone (P=0.0049). PBMCs sensitivity to cyclosporine was not significantly different between the healthy subjects and the NS patients. In addition, when the data from all subjects were analyzed, there was a significantly positive correlation between plasma sOB-R concentrations and the IC50 values of prednisolone (P=0.0478). In contrast, plasma leptin concentrations and FLIs did not correlate significantly with the prednisolone and cyclosporine IC50 values. From these observations it can be suggested that plasma leptin has little effect on PBMC sensitivity to immunosuppressive drugs in NS patients. Molecular background(s) for the influence of sOB-R on the PBMC sensitivity to glucocorticoids remain(s) to be elucidated.
- Published
- 2008
47. P-Glycoprotein Functions in Peripheral-Blood CD4+ Cells of Patients with Systemic Lupus Erythematosus
- Author
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Noriko Yoshikawa, Masaharu Yoshida, Toshihiko Hirano, and Kayo Henmi
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,medicine.medical_specialty ,CD3 Complex ,CD3 ,Anti-Inflammatory Agents ,Drug Resistance ,Pharmaceutical Science ,CD8-Positive T-Lymphocytes ,Peripheral blood mononuclear cell ,Internal medicine ,Humans ,Lupus Erythematosus, Systemic ,Medicine ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Glucocorticoids ,Fluorescent Dyes ,P-glycoprotein ,Pharmacology ,biology ,Rhodamines ,business.industry ,Transporter ,General Medicine ,Middle Aged ,Peripheral blood ,Endocrinology ,Cyclosporine ,biology.protein ,Prednisone ,Female ,Efflux ,business ,Immunosuppressive Agents ,CD8 ,Glucocorticoid ,medicine.drug - Abstract
Over-expression of P-glycoprotein (P-gp) in lymphocytes is implicated in the failure of immunosuppressant therapy. We investigated P-gp function in peripheral-blood CD3+, CD4+, and CD8+ cells of 14 healthy subjects and 12 patients with systemic lupus erythematosus (SLE). P-gp function was estimated by the transporter activity of the cells based on the efflux of Rhodamine-123 (Rh123) from the cells in the presence or absence of a P-gp inhibitor, cyclosporine A. P-gp function in the CD8+ cells of the healthy subjects was significantly higher than that of the SLE patients (p=0.0318), whereas the function in CD3+ cells and CD4+ cells were not significantly different between the healthy subjects and the SLE patients. The patients were divided into two subgroups according to their clinical response to glucocorticoid (GC) therapy, i.e., a high-response group (HR) (n=6) and a low-response group (LR) (n=6). In contrast, P-gp function in CD4+ cells of the LR group was significantly higher than that of the HR group (p=0.0432). Further, no significant differences in the P-gp function in CD3+ and CD8+ cells were observed between the two groups. The data showed a relationship between clinical sensitivity to GC therapy and P-gp function of CD4+ cells in SLE patients. Thus, the estimation of P-gp function in peripheral-blood CD4(+) cells might be useful for the estimation of clinical response to GC therapy.
- Published
- 2008
48. Cordycepin (3′-deoxyadenosine) inhibits the growth of B16-BL6 mouse melanoma cells through the stimulation of adenosine A3 receptor followed by glycogen synthase kinase-3β activation and cyclin D1 suppression
- Author
-
Shizuo Yamada, Noriko Yoshikawa, Masaru Kunitomo, Kazumasa Shinozuka, Chihiro Takeuchi, Kazuki Nakamura, and Satomi Kagota
- Subjects
Melanoma, Experimental ,Gene Expression ,Antineoplastic Agents ,Biology ,Glycogen Synthase Kinase 3 ,Mice ,Radioligand Assay ,chemistry.chemical_compound ,Deoxyadenosine ,Cell Line, Tumor ,medicine ,Animals ,Cyclin D1 ,Receptor ,Cell Proliferation ,Pharmacology ,Glycogen Synthase Kinase 3 beta ,Adenosine A3 Receptor Antagonists ,Deoxyadenosines ,Cordycepin ,Receptor, Adenosine A3 ,General Medicine ,Purinergic signalling ,Adenosine A3 receptor ,Adenosine ,Molecular biology ,Wnt Proteins ,chemistry ,Cordyceps ,Adenosine A2B receptor ,Protein Binding ,Signal Transduction ,medicine.drug - Abstract
Cordyceps sinensis, a parasitic fungus on the larvae of Lepidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells was inhibited by cordycepin (3'-deoxyadenosine), an active ingredient of C. sinensis, and its effect was antagonized by MRS1191, a selective adenosine A3 receptor antagonist. In this study, the radioligand binding assay using [125I]-AB-MECA (a selective adenosine A3 receptor agonist) has shown that B16-BL6 cells express adenosine A3 receptors and that cordycepin binds to these receptors. We also confirmed the involvement of adenosine A3 receptors in the action of cordycepin using MRS1523 and MRS1220, specific adenosine A3 receptor antagonists. Next, indirubin, a glycogen synthase kinase-3beta (GSK-3beta) inhibitor, antagonized the growth suppression induced by cordycepin. Furthermore, the level of cyclin D1 protein in B16-BL6 cells was decreased by cordycepin using Western blot analysis. In conclusion, this study demonstrated that cordycepin inhibits the proliferation of B16-BL6 cells by stimulating adenosine A3 receptors followed by the Wnt signaling pathway, including GSK-3beta activation and cyclin D1 inhibition.
- Published
- 2007
49. Myeloperoxidase anti-neutrophil cytoplasmic antibody affinity is associated with the formation of neutrophil extracellular traps in the kidney and vasculitis activity in myeloperoxidase anti-neutrophil cytoplasmic antibody-associated microscopic polyangiitis
- Author
-
Muneharu Yamada, Noriko Yoshikawa, Yasuyo Sudo, Tomohiro Tomiyasu, Tadasu Kojima, Michiyuki Yamada, Masaharu Yoshida, and Takashi Oda
- Subjects
0301 basic medicine ,Male ,Pathology ,Hydrolases ,Neutrophils ,Biopsy ,Fluorescent Antibody Technique ,Microscopic Polyangiitis ,Birmingham Vasculitis Activity Score ,urologic and male genital diseases ,Kidney ,Extracellular Traps ,Histones ,0302 clinical medicine ,Protein-Arginine Deiminase Type 4 ,Rapidly progressive glomerulonephritis ,vasculitis activity ,biology ,General Medicine ,Middle Aged ,medicine.anatomical_structure ,Nephrology ,Myeloperoxidase ,renal histopathology ,Female ,Vasculitis ,Microscopic polyangiitis ,medicine.medical_specialty ,neutrophil extracellular traps ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,Enzyme-Linked Immunosorbent Assay ,Brief Communication ,Antibodies, Antineutrophil Cytoplasmic ,03 medical and health sciences ,Predictive Value of Tests ,medicine ,Humans ,cardiovascular diseases ,myeloperoxidase anti‐neutrophil cytoplasmic antibody affinity ,Anti-neutrophil cytoplasmic antibody ,Aged ,Peroxidase ,030203 arthritis & rheumatology ,business.industry ,Neutrophil extracellular traps ,medicine.disease ,030104 developmental biology ,Immunology ,biology.protein ,Protein-Arginine Deiminases ,Citrulline ,business ,Biomarkers - Abstract
Anti‐neutrophil cytoplasmic antibody (ANCA) is associated with small‐vessel vasculitis particularly in the kidneys and can induce the formation of neutrophil extracellular traps (NETs) from primed neutrophils. Recently we have reported that the induction of NETs correlates with ANCA affinity for myeloperoxidase (MPO) and disease activity in patients with MPO‐ANCA‐associated microscopic polyangiitis. To investigate whether MPO‐ANCA affinity is associated with the formation of NETs in vivo, we examined the occurrence of NETs in the renal tissues of patients with MPO‐ANCA‐associated microscopic polyangiitis and ANCA affinity by double immunofluorescence staining for NET components of citrullinated histone, MPO and PAD4 and by ELISA competition with MPO, respectively. We divided 30 MPO‐ANCA‐associated microscopic polyangiitis patients into 2 groups based on their ANCA affinity levels (IC50 for the high: 0.11 ± 0.04 µg/mL (Group1) and IC50 for the low: 0.66 ± 0.24 µg/mL (Group2)). Group1 showed a higher Birmingham vasculitis activity score (15.6 ± 5.7) and 73% of the patients presented clinically with rapidly progressive glomerulonephritis and histologically with focal/crescentic glomerulonephritis (GN). Group 2 showed a lower Birmingham vasculitis activity score (9.2 ± 4.9) and 73% of the patients presented clinically with chronic renal failure and histologically with mixed/sclerotic GN. Group 1 showed a much higher occurrence of NETs than Group 2. Our findings indicate that ANCA affinity was associated with the in vivo formation of NETs, which might be involved in the pathophysiology of patients with MPO‐ANCA‐associated microscopic polyangiitis.
- Published
- 2015
50. Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with antineutrophil cytoplasmic antibody-associated vasculitis and nephrosis
- Author
-
Noriko Yoshikawa, Toshihiko Hirano, Kitaro Oka, Hisayo Fukushima, Masaharu Yoshida, and Yoshinobu Sasaki
- Subjects
Adult ,Male ,Vasculitis ,Prednisolone ,Nephrosis ,Bacterial Toxins ,Calcineurin Inhibitors ,Immunology ,Lymphocyte Activation ,Methylprednisolone ,Peripheral blood mononuclear cell ,Tacrolimus ,Antibodies, Antineutrophil Cytoplasmic ,Enterotoxins ,Inhibitory Concentration 50 ,Concanavalin A ,Humans ,Immunology and Allergy ,Medicine ,Glucocorticoids ,Aged ,Cell Proliferation ,Anti-neutrophil cytoplasmic antibody ,Aged, 80 and over ,Pharmacology ,Superantigens ,business.industry ,Middle Aged ,medicine.disease ,Calcineurin ,Cyclosporine ,Leukocytes, Mononuclear ,Female ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Successful immunosuppressive therapy is critical for the treatment of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and nephrosis. However, a considerable number of patients have shown clinical resistance to therapy. Bacterial infection might influence the clinical response of patients to immunosuppressive drugs, but few studies have been carried out to investigate the effect of bacterial superantigens on the efficacy of the drugs in these patients. We evaluated the suppressive efficacy of prednisolone, methylprednisolone, cyclosporine, and tacrolimus on the blastogenesis of PBMCs obtained from 12 ANCA-associated vasculitis patients (ANCA patients), eight patients with nephrotic syndrome, and eight healthy subjects. PBMC-stimulation index was calculated from the formula: [3H]thymidine incorporated in the presence of stimulant (dpm)/[3H]thymidine incorporated in the absence of stimulant (dpm). In vitro drug concentrations giving 50% inhibition (IC50s) of PBMC blastogenesis stimulated with concanavalin A (con A) or toxic shock syndrome toxin 1 (TSST-1) derived from Staphylococcus aureus (S. aureus) were calculated. The IC50 values for the four drugs evaluated in TSST-1-stimulated PBMCs were significantly higher than those evaluated in con A-stimulated PBMCs in both ANCA patients and nephrosis patients (p
- Published
- 2006
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