47 results on '"Tokuhara, Daisuke"'
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2. A comprehensive understanding of the gut mucosal immune system in allergic inflammation.
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Tokuhara, Daisuke, Kurashima, Yosuke, Kamioka, Mariko, Nakayama, Toshinori, Ernst, Peter, and Kiyono, Hiroshi
- Abstract
Abstract Despite its direct exposure to huge amounts of microorganisms and foreign and dietary antigens, the gut mucosa maintains intestinal homeostasis by utilizing the mucosal immune system. The gut mucosal immune system protects the host from the invasion of infectious pathogens and eliminates harmful non-self antigens, but it allows the cohabitation of commensal bacteria in the gut and the entry of dietary non-self antigens into the body via the mucosal surface. These physiological and immunological activities are regulated by the ingenious gut mucosal immune network, comprising such features as gut-associated lymphoid tissue, mucosal immune cells, cytokines, chemokines, antimicrobial peptides, secretory IgA, and commensal bacteria. The gut mucosal immune network keeps a fine tuned balance between active immunity (against pathogens and harmful non-self antigens) and immune tolerance (to commensal microbiota and dietary antigens), thus maintaining intestinal healthy homeostasis. Disruption of gut homeostasis results in persistent or severe gastrointestinal infection, inflammatory bowel disease, or allergic inflammation. In this review, we comprehensively introduce current knowledge of the gut mucosal immune system, focusing on its interaction with allergic inflammation. [ABSTRACT FROM AUTHOR]
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- 2019
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3. Challenges in developing mucosal vaccines and antibodies against infectious diarrhea in children.
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Tokuhara, Daisuke
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DIARRHEA prevention , *THERAPEUTIC use of immunoglobulins , *RICE , *GASTRIC mucosa , *IMMUNE system , *IMMUNIZATION , *CHILDREN , *THERAPEUTICS - Abstract
Abstract: Infectious diarrhea in children can be life‐threatening and imposes a large economic burden on healthcare systems, therefore more effective prophylactic and therapeutic drugs are needed urgently. Because most of the pathogens responsible for childhood diarrhea infect the gastrointestinal mucosa, providing protective immunity at the mucosal surface is an ideal way to control pathogen invasion and toxic activity. Mucosal (e.g. oral, nasal) vaccines are superior to systemic (subcutaneous or intramuscular) vaccination for conferring both mucosal and systemic pathogen‐specific immune responses. Therefore, great efforts has been focused on the development of cost‐effective mucosal vaccines for the past 50 years. Recent progress in plant genetic engineering has revolutionized the production of inexpensive and safe recombinant vaccine antigens. For example, rice plant biotechnology has facilitated the development of a cold‐chain‐free rice‐based oral subunit vaccine against
Vibrio cholerae . Furthermore, this technology has led to the creation of a rice‐based oral antibody for prophylaxis and treatment of rotavirus gastroenteritis. This review summarizes current perspectives regarding the mucosal immune system and the development of mucosal vaccines and therapeutic antibodies, particularly rice‐based products, and discusses future prospects regarding mucosal vaccines for children. [ABSTRACT FROM AUTHOR]- Published
- 2018
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4. Patency Capsule Tolerability in School-Aged Children.
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Tokuhara, Daisuke, Watanabe, Kenji, Cho, Yuki, and Shintaku, Haruo
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CAPSULE endoscopy , *PATIENT monitoring , *OROPHARYNX , *GASTROENTEROLOGISTS , *PEDIATRIC therapy , *ATTITUDE (Psychology) , *CHARTS, diagrams, etc. - Abstract
Background: A patency capsule (PC) can help predict capsule endoscope (CE) retention; however, PC tolerability is unknown in children. We retrospectively evaluated PC tolerability in school-aged children. Methods: Sixty-one patients (median age, 12.9 years; range 7.4-17.3 years) who underwent PC examination were analyzed for occurrence and determinants of ingestion difficulty and relationships between ingestion of the 2 capsules. We defined ingestion difficulty as taking 30 min or more, or failure, to ingest the PC. Results: Thirty-nine patients (64%) successfully ingested the PC without ingestion difficulty. The other 22 had ingestion difficulty and were significantly younger (11.7 ± 2.2 vs. 13.0 ± 1.8 years; p = 0.04) and shorter (143.3 ± 14.0 vs. 154.6 ± 12.5 cm; p = 0.003) than those without ingestion difficulty. Multivariate analysis showed that the most significant factor for predicting PC ingestion difficulty was height (cutoff value, 152 cm). Time to ingest the CE was significantly shorter than that for PC ingestion (8 ± 32 vs. 20 ± 58 min; p = 0.01). All patients indicated that ingestion of the CE was easier because of its smooth surface compared with the PC. Conclusions: PC ingestion is not guaranteed in school-aged children. PC ingestion ability should be evaluated by considering the child's height and lack of experience ingesting capsules prior to PC examination. [ABSTRACT FROM AUTHOR]
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- 2017
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5. Transient Elastography-Based Liver Stiffness Age-Dependently Increases in Children.
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Tokuhara, Daisuke, Cho, Yuki, and Shintaku, Haruo
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ELASTOGRAPHY , *OVERWEIGHT persons , *LIVER diseases , *JUVENILE diseases , *LIVER enzymes , *ANESTHESIA - Abstract
Background and Aims: Pediatric use of liver transient elastography (TE) is attractive for its non-invasiveness, but reference values have not been established. We aimed to determine reference values for TE in children. Methods: In pediatric patients (1 to 18 years), TE (FibroScan®) with an M probe was used for both liver stiffness measurement (LSM) and measurement of hepatic fat deposition by using a controlled attenuation parameter (CAP). The patients were divided into three relevant age groups: preschoolers (1 to 5 years), elementary school children (6 to 11 years), and adolescents (12 to 18 years). Overweight or obese patients or those with known liver disease, elevated serum liver enzymes, or hepatic echogenic abnormality were excluded from the study. Results: Among 139 children, 123 (88.5%; 62 male; median age, 11.7 years; age range, 1.3 to 17.2 years) were successfully subjected to M-probe TE without anesthesia. Median LSM increased with age: it was 3.4 kPa (2.3 to 4.6 kPa, 5th to 95th percentiles) at ages 1 to 5 years; 3.8 (2.5 to 6.1) kPa at ages 6 to 11; and 4.1 (3.3 to 7.9) kPa at ages 12 to 18 (P = 0.001). Median CAP was not age dependent: it was 183 (112 to 242) for ages 1 to 18 years. Conclusions: M-probe TE is suitable in a wide age range of children from age 1 year up. In children without evidence of liver disease, LSM has an age-dependent increase, whereas CAP does not differ between ages 1 and 18. [ABSTRACT FROM AUTHOR]
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- 2016
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6. Double pancreatic tumors in an adolescent: Imaging features.
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Odagiri, Shino, Tokuhara, Daisuke, Nishigaki, Satsuki, Cho, Yuki, and Shintaku, Haruo
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PANCREATIC tumors , *ENDOCRINE gland tumors , *ISLANDS of Langerhans tumors , *MAGNETIC resonance imaging , *PEDIATRICS , *TREATMENT effectiveness , *WERMER syndrome , *DIAGNOSIS - Abstract
Insulinoma is generally identified as a single tumor and seldom occurs in children or adolescents. A 14-year-old girl with difficulty in waking was found to have hyperinsulinemic hypoglycemia. On abdominal ultrasonography two hypoechoic masses (8 and 12 mm in diameter) were seen in the pancreatic body: the larger mass was hypervascular, whereas the smaller one was hypovascular. Contrast-enhanced computed tomography showed enhancement of the larger mass, but did not delineate the smaller mass. On fat-suppressed T1-weighted magnetic resonance imaging, the larger mass was hypointense, but the smaller mass was hyperintense. Pathologically, the larger tumor was normal density, insulin positive, and rich in vascularity, whereas the smaller tumor was high density, insulin negative, and poor in vascularity. The present case suggests that difficulty waking should be considered as a potential etiology in insulinoma, and multiple suspected pancreatic insulinomas should be evaluated using a combination of imaging modalities to characterize each tumor. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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7. Diabetic pregnancy activates the innate immune response through TLR5 or TLR1/2 on neonatal monocyte.
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Yanai, Sakika, Tokuhara, Daisuke, Tachibana, Daisuke, Saito, Mika, Sakashita, Yuko, Shintaku, Haruo, and Koyama, Masayasu
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GESTATIONAL diabetes , *TOLL-like receptors , *NATURAL immunity , *MONOCYTES , *HUMAN abnormalities , *FETAL macrosomia - Abstract
Diabetes mellitus (DM) during pregnancy causes congenital malformation, macrosomia, respiratory distress syndrome, and other abnormalities in neonates, but whether maternal DM affects the neonatal innate immune system is unknown. Therefore we aimed to reveal the influence of DM in pregnancy on the toll-like receptor (TLR)–mediated innate immune response in neonates. Cord blood was collected after full-term vaginal or cesarean delivery and classified into a DM group (n = 8) and non-DM (control) group (n = 7). Mononuclear cells were harvested from cord blood by using density gradient centrifugation, after which anti-CD14 magnetic beads were used to isolate monocytes from the mononuclear population. After monocytes were cultured with lipopolysaccharide (TLR4 ligand), flagellin (TLR5 ligand), Pam3CSK4 (TLR1/TLR2 ligand), zymosan (TLR2/TLR6 ligand), or macrophage-activating lipopeptide (TLR2/TLR6 ligand) for 12 h, the cytokine levels (interleukin [IL]-8, IL-6, IL-1β, IL-10, tumor necrosis factor alpha and IL-12) in the culture supernatants were measured. Compared with the control group, the DM group had higher concentrations of IL-8 ( P = 0.01) and tumor necrosis factor alpha ( P = 0.02) after monocyte cultures were stimulated with Pam3CSK4 and higher concentrations of IL-8 ( P = 0.01) after flagellin treatment. In contrast, stimulation with lipopolysaccharide, zymosan, or macrophage-activating lipopeptide did not lead to any difference in cytokine profiles between the two groups. These data indicate that maternal DM induces excessive inflammatory activation in neonates via a TLR5- or TLR1/2-mediated innate immune response. [ABSTRACT FROM AUTHOR]
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- 2016
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8. Transient Elastography-Based Liver Profiles in a Hospital-Based Pediatric Population in Japan.
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Cho, Yuki, Tokuhara, Daisuke, Morikawa, Hiroyasu, Kuwae, Yuko, Hayashi, Eri, Hirose, Masakazu, Hamazaki, Takashi, Tanaka, Akemi, Kawamura, Tomoyuki, Kawada, Norifumi, and Shintaku, Haruo
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ELASTOGRAPHY , *LIVER analysis , *PEDIATRICS , *HEPATIC fibrosis , *JAPANESE people , *DISEASES - Abstract
Background & Aims: The utility of transient elastography (FibroScan) is well studied in adults but not in children. We sought to assess the feasibility of performing FibroScans and the characteristics of FibroScan-based liver profiles in Japanese obese and non-obese children. Methods: FibroScan examinations were performed in pediatric patients (age, 1–18 yr) who visited Osaka City University Hospital. Liver steatosis measured by controlled attenuation parameter (CAP), and hepatic fibrosis evaluated as the liver stiffness measurement (LSM), were compared among obese subjects (BMI percentile ≥90%), non-obese healthy controls, and non-obese patients with liver disease. Results: Among 214 children examined, FibroScans were performed successfully in 201 children (93.9%; median, 11.5 yr; range, 1.3–17.6 yr; 115 male). CAP values (mean±SD) were higher in the obese group (n = 52, 285±60 dB/m) compared with the liver disease (n = 40, 202±62, P<0.001) and the control (n = 107, 179±41, P<0.001) group. LSM values were significantly higher in the obese group (5.5±2.3 kPa) than in the control (3.9±0.9, P<0.001), but there were no significant differences in LSM between the liver disease group (5.4±4.2) and either the obese or control group. LSM was highly correlated with CAP in the obese group (ρ = 0.511) but not in the control (ρ = 0.129) or liver disease (ρ = 0.170) groups. Conclusions: Childhood obesity carries a high risk of hepatic steatosis associated with increased liver stiffness. FibroScan methodology provides simultaneous determination of CAP and LSM, is feasible in children of any age, and is a non-invasive and effective screening method for hepatic steatosis and liver fibrosis in Japanese obese children. [ABSTRACT FROM AUTHOR]
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- 2015
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9. Specific Expression of Apolipoprotein A-IV in the Follicle-Associated Epithelium of the Small Intestine.
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Tokuhara, Daisuke, Nochi, Tomonori, Matsumura, Akiko, Mejima, Mio, Takahashi, Yuko, Kurokawa, Shiho, Kiyono, Hiroshi, and Yuki, Yoshikazu
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GENE expression , *APOLIPOPROTEIN A , *EPITHELIUM , *SMALL intestine diseases , *PEYER'S patches , *GASTROINTESTINAL diseases , *IMMUNOPRECIPITATION - Abstract
Background: Peyer's patches (PPs), which are covered by specialized follicle-associated epithelium (FAE) including M cells, play a central role in immune induction in the gastrointestinal tract. This study is to investigate a new molecule to characterize PPs. Methods: We generated a monoclonal antibody (mAb 10-15-3-3) that specifically reacts to the epithelium of PPs and isolated lymphoid follicles. Target antigen was analyzed by immunoprecipitation and mass spectrometry. Localization and expression of target antigen were evaluated by immunofluorescence, in situ hybridization and real-time PCR. Results: Immunoprecipitation and mass spectrometry revealed that mAb 10-15-3-3 recognized apolipoprotein A-IV (ApoA-IV), a well-known lipid transporter; this finding was confirmed by the specific reactivity of mAb 10-15-3-3 to cells transfected with the murine ApoA-IV gene. Immunofluorescence using mAb 10-15-3-3 showed intestinal localization of ApoA-IV, in which strong expression of the ApoA-IV protein occurred throughout the entire intestinal epithelium during developing period before weaning but was restricted to the FAE in adult mice. In support of these findings, in situ hybridization showed strong expression of the ApoA-IV gene throughout the entire intestinal epithelium during developing period before weaning, but this expression was restricted to the FAE predominantly and the tips of villi to a lesser extent in adult mice. Deficiency of ApoA-IV had no effect on the organogenesis of PP in mice. Conclusions: Our current results reveal ApoA-IV as a novel FAE-specific marker especially in the upper small intestine of adult mice. [ABSTRACT FROM AUTHOR]
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- 2014
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10. Potential Roles of CCR5+ CCR6+ Dendritic Cells Induced by Nasal Ovalbumin plus Flt3 Ligand Expressing Adenovirus for Mucosal IgA Responses.
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Fukuyama, Yoshiko, Tokuhara, Daisuke, Sekine, Shinichi, Aso, Kazuyoshi, Kataoka, Kosuke, Davydova, Julia, Yamamoto, Masato, Gilbert, Rebekah S., Tokuhara, Yuka, Fujihashi, Keiko, Kunisawa, Jun, Yuki, Yoshikazu, Kiyono, Hiroshi, McGhee, Jerry R., and Fujihashi, Kohtaro
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DENDRITIC cells , *OVALBUMINS , *IMMUNOGLOBULIN A , *IMMUNE response , *ADENOVIRUSES , *CELLULAR signal transduction , *MOLECULAR biology - Abstract
We assessed the role of CCR5+/CCR6+/CD11b+/CD11c+ dendritic cells (DCs) for induction of ovalbumin (OVA)-specific antibody (Ab) responses following mucosal immunization. Mice given nasal OVA plus an adenovirus expressing Flt3 ligand (Ad-FL) showed early expansion of CCR5+/CCR6+/CD11b+/CD11c+ DCs in nasopharyngeal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLNs). Subsequently, this DC subset became resident in submandibular glands (SMGs) and nasal passages (NPs) in response to high levels of CCR-ligands produced in these tissues. CD11b+/CD11c+ DCs were markedly decreased in both CCR5−/− and CCR6−/− mice. Chimera mice reconstituted with bone marrow cells from CD11c-diphtheria toxin receptor (CD11c-DTR) and CCR5−/− or CD11c-DTR and CCR6−/− mice given nasal OVA plus Ad-FL had elevated plasma IgG, but reduced IgA as well as low anti-OVA secretory IgA (SIgA )Ab responses in saliva and nasal washes. These results suggest that CCR5+CCR6+ DCs play an important role in the induction of Ag-specific SIgA Ab responses. [ABSTRACT FROM AUTHOR]
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- 2013
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11. Flavangenol (pine bark extract) and its major component procyanidin B1 enhance fatty acid oxidation in fat-loaded models
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Shimada, Tsutomu, Tokuhara, Daisuke, Tsubata, Masahito, Kamiya, Tomoyasu, Kamiya-Sameshima, Mayu, Nagamine, Rika, Takagaki, Kinya, Sai, Yoshimichi, Miyamoto, Ken-ichi, and Aburada, Masaki
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PINE bark , *PLANT extracts , *FATTY acids , *OXIDATION , *ANTIOXIDANTS , *CARNITINE , *ACYL-CoA oxidase - Abstract
Abstract: Flavangenol, one of several pine bark extract products, is expected to prevent metabolic diseases with its potent antioxidant effect, its anti-obesity effect and its improvement of insulin sensitivity. In this study, targeting the liver as one of the organs that plays an important role in energy metabolism, Flavangenol was investigated for its effect on non-alcoholic fatty liver disease (NAFLD), its action mechanism and its active ingredients, using in vivo and in vitro experiment systems. Flavangenol suppressed intrahepatic fat accumulation in Western diet-loaded Tsumura Suzuki Obese Diabetes (TSOD) mice, which develop various metabolic diseases. In addition, Flavangenol significantly increased the mRNA expression levels of fatty acid oxidative enzymes (peroxisomal proliferator-activated receptor α, acyl-CoA oxidase, carnitine palmitoyltransferase). In order to investigate the direct effect of Flavangenol on the liver, an in vitro fatty liver model prepared by adding a free fatty acid to human liver cancer cells (HepG2 cells) was used. In this model, Flavangenol significantly suppressed intracellular fat accumulation. Procyanidin B1, one of the major components of Flavangenol, also suppressed fat accumulation and induced mRNA expression of the fatty acid oxidative enzymes. As mentioned above, Flavangenol showed a significant suppressive effect in the NAFLD model, and it was suggested that the molecular mechanism is induction of fatty acid oxidation, with the effect mainly attributed to procyanidin B1. [Copyright &y& Elsevier]
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- 2012
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12. Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses
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Fukuyama, Yoshiko, Tokuhara, Daisuke, Sekine, Shinichi, Kataoka, Kosuke, Markham, Jonathan D., Irwin, Allyson R., Moon, Grace H., Tokuhara, Yuka, Fujihashi, Keiko, Davydova, Julia, Yamamoto, Masato, Gilbert, Rebekah S., and Fujihashi, Kohtaro
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NOTCH genes , *LIGANDS (Biochemistry) , *DENDRITIC cells , *GENE expression , *ADENOVIRUSES , *SEROTYPES , *IMMUNOGLOBULIN A , *MOLECULAR biology - Abstract
Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c+ dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c+ DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FL activated CD11c+ DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c+ DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4+ T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-γ, IL-2 and IL-4 producing CD4+ T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch–Notch-L pathway. These results show that Ad-FL induces CD11c+ DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses. [Copyright &y& Elsevier]
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- 2012
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13. Wireless capsule endoscopy in pediatric patients: the first series from Japan.
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Tokuhara, Daisuke, Watanabe, Kenji, Okano, Yoshiyuki, Tada, Akio, Yamato, Kazumi, Mochizuki, Takahiro, Takaya, Junji, Yamano, Tsunekazu, and Arakawa, Tetsuo
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CAPSULE endoscopy , *PEDIATRICS , *INTESTINAL disease diagnosis , *LEUKEMIA , *ULCERS , *PSYCHOLOGICAL stress - Abstract
The aim of our study was to determine the safety and usefulness of capsule endoscopy (CE) in pediatric patients. We prospectively examined children (aged 10–18 years) with suspected small bowel disease and recorded capsule transit times, findings, and complications. We performed 19 CE examinations in 12 patients (median age 11.8 years; range 10–18 years). One of the two patients with obscure gastrointestinal bleeding (OGIB), a 14-year-old girl whose OGIB occurred after cord-blood transplantation due to leukemia, was diagnosed with thrombotic microangiopathy. Repeated CE allowed visualization of real-time mucosal changes, such as the improvement of ulcers and bleeding, and newly emerged lymphangiectasia, without causing the patient physical and mental stress. This information facilitated both subsequent evaluation of the clinical course and determination of the appropriate treatment strategy. In the second patient with chronic OGIB, a 10-year-old girl, the detection of severe ileal stenoses by capsule retention led to the diagnosis of non-specific multiple ulcers of the small intestine. After ileal resection, repeated CE detected the recurrence of multiple ulcers and enabled the optimal treatment strategy to be applied. CE confirmed small bowel involvement in a patient with unresponsive Crohn’s disease (CD) and excluded CD in all five patients with suspected CD. Similarly, CE confirmed the absence of small bowel involvement in three of the four patients with recurrent abdominal pain, although one patient had nodular lymphoid hyperplasia. Based on our results, CE is a valuable tool in the differential diagnoses of small bowel diseases, and repeated examination can provide real-time information that will enable evaluation of the clinical course in pediatric patients. [ABSTRACT FROM AUTHOR]
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- 2010
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14. Protein-losing gastropathy in a child and Guillain–Barré syndrome in a father caused by intrafamilial infection.
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Tokuhara, Daisuke, Hirokawa, Hidetetsu, Yamano, Tsunekazu, and Okano, Yoshiyuki
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GASTROINTESTINAL diseases , *DISEASE complications , *VIRUS diseases , *GUILLAIN-Barre syndrome , *INFECTIOUS disease transmission , *FATHERS , *CHILDREN - Abstract
The article presents a case study of a 3-year-old boy with edema of the eyelids and extremities. The diagnosis revealed that the boy had protein-losing gastropathy (PLG) which was caused by Helicobacter pylori and cytomegalovirus (CMV) infection. The patient's father was also diagnosed with Guillain-Barré syndrome (GBS) after bed-sharing with his son. The article discusses co-infection and intrafamilial transmission of CMV and H. pylori in pediatric PLG.
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- 2010
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15. Secretory IgA-mediated protection against V. cholerae and heat-labile enterotoxin-producing enterotoxigenic Escherichia coil by rice-based vaccine.
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Tokuhara, Daisuke, Yuki, Yoshikazu, Nochi, Tomonori, Kodama, Toshio, Mejima, Mio, Kurokawa, Shiho, Takahashi, Yuko, Nanno, Masanobu, Nakanishi, Ushio, Takaiwa, Fumio, Honda, Takeshi, and Kiyono, Hiroshi
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CHOLERA , *CHOLERA toxin , *ORAL vaccines , *GASTROENTERITIS , *DIARRHEA , *VIBRIO infections , *ENTEROTOXINS , *IMMUNITY , *VACCINATION - Abstract
Cholera and enterotoxigenic Escherichia coil (ETEC) are among the most common causes of acute infantile gastroenteritis globally. We previously developed a rice-based vaccine that expressed cholera toxin B subunit (MucoRice-CTB) and had the advantages of being cold chain-free and providing protection against cholera toxin (CT)- induced diarrhea. To advance the development of MucoRice-CTB for human clinical application, we investigated whether the CTB-specific secretory IgA (SIgA) induced by MucoRice-CTB gives longstanding protection against diarrhea induced by Vibrio cholerae and heat-labile enterotoxin (LT)-producing ETEC (LT-ETEC) in mice. Oral immunization with MucoRice-CTB stored at room temperature for more than 3 y provided effective SIgA-mediated protection against CT- or LT-induced diarrhea, but the protection was impaired in polymeric Ig receptor-deficient mice lacking SIgA. The vaccine gave longstanding protection against CT- or LT-induced diarrhea (for ⩾6 months after primary immunization), and a single booster immunization extended the duration of protective immunity by at least 4 months. Furthermore, MucoRice-CTB vaccination prevented diarrhea in the event of V. cholerae and LT-ETEC challenges. Thus, MucoRice-CrB is an effective long-term cold chain-free oral vaccine that induces GB- specific SIgA-mediated longstanding protection against V. cholera e- or LT-ETEC-induced diarrhea. [ABSTRACT FROM AUTHOR]
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- 2010
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16. Oral MucoRice expressing double-mutant cholera toxin A and B subunits induces toxin-specific neutralising immunity
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Yuki, Yoshikazu, Tokuhara, Daisuke, Nochi, Tomonori, Yasuda, Hiroshi, Mejima, Mio, Kurokawa, Shiho, Takahashi, Yuko, Kataoka, Nobuhiro, Nakanishi, Ushio, Hagiwara, Yukari, Fujihashi, Kohtaro, Takaiwa, Fumio, and Kiyono, Hiroshi
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GENE expression , *MICROBIAL mutation , *CHOLERA toxin , *IMMUNITY , *ORAL drug administration , *ENTEROTOXINS , *WESTERN immunoblotting , *IMMUNOGLOBULIN A ,RICE genetics - Abstract
Abstract: Rice-expressed cholera toxin B (CTB) subunit is a cold-chain-free oral vaccine that effectively induces enterotoxin-neutralising immunity. We created another rice-based vaccine, MucoRice, expressing nontoxic double-mutant cholera toxin (dmCT) with CTA and CTB subunits. Western-blot analysis suggested that MucoRice-dmCT had the shape of a multicomponent vaccine. Oral administration of MucoRice-dmCT induced CTB- but not CTA-specific serum IgG and mucosal IgA antibodies, generating protective immunity against cholera toxin without inducing rice-protein-specific antibody responses. The potency of MucoRice-dmCT was equal to that of MucoRice-CTB vaccine. MucoRice has the potential to be used as a safe multicomponent vaccine expression system. [Copyright &y& Elsevier]
- Published
- 2009
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17. Expression of estrogen receptor α and β in reactive astrocytes at the male rat hippocampus after status epilepticus.
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Sakuma, Satoru, Tokuhara, Daisuke, Hattori, Hideji, Matsuoka, Osamu, and Yamano, Tsunekazu
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ESTROGEN receptors , *ASTROCYTES , *EPILEPSY , *HIPPOCAMPUS (Brain) , *KAINIC acid - Abstract
Estrogen is neuroprotective against status epilepticus (SE)-induced hippocampal damage in female animals. In male animals, estrogen is converted from testosterone via aromatization the activity of which is upregulated by brain damage. However, it is controversial whether estrogen is neuroprotective or neuroinvasive against male hippocampal damage after SE. In order to understand the role of estrogen, it is important to elucidate the distribution manner of estrogen receptor (ER)α and β as the targets of estrogen. In this study, we examined the time course changes of ERs in adult male rat hippocampus after SE using anti-ERα antibodies (MC-20 and PA1-309) and anti-ERβ antibodies (PA1-310B and PA1-311). In control rats, both ERα and β were expressed in the pyramidal cells predominantly at CA1 and CA3. ERα was expressed in the cytoplasm and the nucleus, whereas ERβ was expressed in the cytoplasm of the pyramidal cells. After SE, according to the pyramidal cell loss at CA1, the number of ERα- and β-immunoreactive pyramidal cells decreased up to day 21. On the other hand, reactive astrocytes, which newly appeared after SE and formed gliosis at CA1, were confirmed to express both ERs in the nucleus, cytoplasm, and process. There were no differences in immunoreactivity between antibodies. Our results indicate that endogenous estrogen affects the pyramidal cells through ERα and β under normal circumstances in adult male rats, whereas the targets of estrogen shift to the reactive astrocytes through ERα and β after SE. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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18. Kainic acid dose affects delayed cell death mechanism after status epilepticus
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Tokuhara, Daisuke, Sakuma, Satoru, Hattori, Hideji, Matsuoka, Osamu, and Yamano, Tsunekazu
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CELL death , *APOPTOSIS , *KAINIC acid , *NEUROTOXIC agents , *NECROSIS - Abstract
Abstract: Kainic acid (KA)-induced status epilepticus (SE) produces hippocampal neuronal death, which varies from necrosis to apoptosis or programmed cell death (PCD). We examined whether the type of neuronal death was dependent on KA dose. Adult rats were induced SE by intraperitoneal injection of KA at 9mg/kg (K9) or 12mg/kg (K12). Hippocampal neuronal death was assessed by TUNEL staining, electron microscopy, and Western blotting of caspase-3 on days 1, 3 and 7 after SE induction. K12 rats showed higher a mortality rate and shorter latency to the onset of SE when compared with K9 rats. In both groups, acidophilic and pyknotic neurons were evident in CA1 at 24h after SE and neuronal loss developed from day 3. The degenerated neurons became TUNEL-positive on days 3 and 7 in K9 rats but not in K12 rats. Caspase-3 activation was detected on days 3 and 7 in K9 rats but was undetectable in K12 rats. Ultrastructural study revealed shrunken neurons exhibiting pyknotic nuclei containing small and dispersed chromatin clumps 24h after SE in CA1. No cells exhibited apoptosis. On days 3 and 7, the degenerated neurons were necrotic with high electron density and small chromatin clumps. There were no ultrastructural differences between the K9 and K12 groups. These results revealed that differences in KA dose affected the delayed cell death (3 and 7 days after SE); however, no effect was seen on the early cell death (24h after SE). Moderate-dose KA induced necrosis, while low-dose KA induced PCD. [Copyright &y& Elsevier]
- Published
- 2007
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19. Novel diagnostic approach to citrin deficiency: Analysis of citrin protein in lymphocytes
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Tokuhara, Daisuke, Iijima, Mikio, Tamamori, Akiko, Ohura, Toshihiro, Takaya, Junji, Maisawa, Shunichi, Kobayashi, Keiko, Saheki, Takeyori, Yamano, Tsunekazu, and Okano, Yoshiyuki
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GENETIC mutation , *LEUCOCYTES , *CHOLESTASIS , *LYMPHOCYTES - Abstract
Abstract: Citrin deficiency induces two clinical features; namely neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type II citrullinemia. Hypercitrullinemia is the most characteristic feature, whereas there are non-citrullinemic individuals. Diagnosis of citrin deficiency is performed by genetic analysis, although the 12 known mutations in the alleles are not detected in about 15% of cases. Thus, we aimed to examine citrin protein in lymphocytes isolated from peripheral blood as an alternative diagnostic method. We examined 38 children having an episode of cholestatic liver dysfunction, 8 heterozygotes, and 11 healthy individuals. All subjects were evaluated for citrin protein by Western blotting and for the 12 known mutations by gene analysis. Citrin protein was detected in 15 of 38 children with cholestatic liver dysfunction. Fourteen of them were negative for 12 known mutations in both alleles, whereas one patient was found to have a known mutation in one allele. Citrin protein was absent in 23 of the 38 patients. Among these 23, gene analysis diagnosed citrin deficiency in 19, whereas 2 patients were later revealed to be NICCD with novel mutations. In the remaining 2 patients, who exhibit the clinical features of NICCD, a known mutation was detected in one allele but no mutation was identified in another allele. Citrin protein was also detected in the 8 heterozygotes and 11 healthy individuals. We disclosed that citrin was deficient in lymphocytes among patients with citrin deficiency. Analysis of citrin is useful to diagnose citrin deficiency even in patients without known mutations or hypercitrullinemia. [Copyright &y& Elsevier]
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- 2007
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20. Time course changes of estrogen receptor α expression in the adult rat hippocampus after kainic acid-induced status epilepticus.
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Tokuhara, Daisuke, Yokoi, Toshiaki, Nakajima, Ryouichi, Hattori, Hideji, Matsuoka, Osamu, and Yamano, Tsunekazu
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ESTROGEN , *SEX hormones , *SELECTIVE estrogen receptor modulators , *KAINIC acid , *LABORATORY rats , *WESTERN immunoblotting - Abstract
Although estrogens possess neuroprotective and epileptogenic properties, the expression pattern of the estrogen receptor (ER) following status epilepticus (SE) remains unclear. We therefore examined the expression pattern of ERα in the adult rat hippocampus after SE. SE was induced in rats by kainic acid (KA; 12 mg/kg, i.p.). ERα expression was assessed by immunostaining and Western blotting at various times (24 h, and 7, 14, and 21 days) after SE onset. Immunohistochemistry disclosed ERα expression in the CA1 and CA3 pyramidal cells of control rats, whereas, after SE, ERα-immunoreactive neurons decreased in number due to neuronal death in the CA1 from days 7 to 21. On the other hand, ERα-immunoreactive cells with astrocytic morphology were observed in the CA1 beginning on day 7 after SE. This immunoreactivity increased in proportion to the hypertrophy of astrocytes up to day 21. Western blotting revealed a significant decrease in ERα expression on day 7 after SE in comparison with control level. However, ERα expression on days 14 and 21 were similar when comparing KA-treated and control rats. These results indicate that reactive astrocytes are important sites of estrogen action in the hippocampal CA1 after SE. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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21. Cytomegalovirus and Helicobacter pylori co-infection in a child with Ménétrier disease.
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Tokuhara, Daisuke, Okano, Yoshiyuki, Asou, Kazuyoshi, Tamamori, Akiko, and Yamano, Tsunekazu
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CYTOMEGALOVIRUS diseases , *HELICOBACTER pylori infections , *GASTRIC diseases , *JUVENILE diseases , *PROTEIN-losing enteropathy - Abstract
Ménétrier disease, which is characterized by gastric rugal hypertrophy and hypoproteinemia secondary to a protein-losing gastroenteropathy, is uncommon in childhood. In this report we present the first case of Ménétrier disease in a child with co-infection of cytomegalovirus (CMV) and Helicobacter pylori (H. pylori). [ABSTRACT FROM AUTHOR]
- Published
- 2007
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22. Factors related to recurrence of proteinuria in childhood IgA nephropathy.
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Shima, Yuko, Mukaiyama, Hironobu, Tanaka, Yu, Shimabukuro, Wataru, Nozu, Kandai, Kaito, Hiroshi, Tanaka, Ryojiro, Sako, Mayumi, Iijima, Kazumoto, Tokuhara, Daisuke, Yoshikawa, Norishige, and Nakanishi, Koichi
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CHRONIC kidney failure , *CONFIDENCE intervals , *MULTIVARIATE analysis , *RETROSPECTIVE studies , *DISEASE relapse , *PROTEINURIA , *KAPLAN-Meier estimator , *GLOMERULONEPHRITIS , *HEMATURIA , *PROPORTIONAL hazards models , *DISEASE complications - Abstract
Background: Proteinuria remission is the most significant predictive factor for kidney outcome in childhood IgA nephropathy (c-IgAN). Even if proteinuria remission can be obtained, some patients have recurrence of proteinuria in the long-term. Methods: This is a retrospective analysis of 312 cases of proteinuria remission among 538 consecutive children with biopsy-proven IgAN from 1976 to 2013. To elucidate the incidence and factors related to recurrence of proteinuria in c-IgAN, we compare clinical and pathological findings between patients with and without recurrence of proteinuria. Results: Among 312 patients with remission of proteinuria, 91 (29.2%) had recurrence of proteinuria within the observation period (median 8 years). Using a multivariate Cox regression analysis, significant factors associated with recurrence of proteinuria were onset age (HR 1.13 [95%CI: 1.05–1.22], P = 0.002) and presence of hematuria after proteinuria remission (HR 2.11 [95%CI: 1.30–3.45], P = 0.003). The Kaplan–Meier analysis showed significant differences in CKD G3a-G5-free survival between the patients with no-recurrence of proteinuria, recurrence of proteinuria and non-proteinuria remission (P < 0.0001, log-rank test). Kidney survival was 100% in no-recurrence of proteinuria, 92.2% in recurrence of proteinuria, and 65.6% in non-proteinuria remission at 15 years. Cox analyses adjusted by proteinuria remission showed that recurrence of proteinuria (HR 03.10e9 [95%CI: NA], P = 0.003) was a significant factor associated with progression to CKD G3a-G5 in all patients with c-IgAN. Conclusions: Approximately 30% of patients with proteinuria remission had recurrence of proteinuria regardless of treatment. Both remission and recurrence of proteinuria are significant prognostic factors for kidney outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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23. Letters to the Editor.
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Tokuhara, Daisuke, Yamano, Tsunekazu, and Okano, Yoshiyuki
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LETTERS to the editor , *GASTROESOPHAGEAL reflux - Abstract
A letter to the editor is presented in response to the article on a case of Sandifer's syndrome that was published in the previous issue.
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- 2008
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24. Real-world efficacy and safety of glecaprevir/pibrentasvir in Japanese adolescents with chronic hepatitis C: a prospective multicenter study.
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Mizuochi, Tatsuki, Iwama, Itaru, Inui, Ayano, Ito, Yoshinori, Takaki, Yugo, Mushiake, Sotaro, Tokuhara, Daisuke, Ishige, Takashi, Ito, Koichi, Murakami, Jun, Hishiki, Haruka, Mikami, Hitoshi, Bessho, Kazuhiko, Kato, Ken, Yasuda, Ryosuke, Yamashita, Yushiro, Tanaka, Yasuhito, and Tajiri, Hitoshi
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CHRONIC hepatitis C , *JAPANESE people , *HEPATITIS C virus , *LONGITUDINAL method , *ALANINE aminotransferase - Abstract
Background: Part 1 of the DORA study, a 2019 international clinical trial of glecaprevir and pibrentasvir (G/P) treatment in adolescents with chronic hepatitis C virus (HCV) infection, demonstrated high efficacy and safety. However, few reports have considered real-world experience with G/P treatment in adolescents with chronic HCV. The present prospective multicenter study assessed real-world efficacy and safety of G/P treatment in Japanese adolescents with chronic HCV. Methods: Subjects between 12 and 17 years old who were treatment-naïve or previously managed with interferon-based regimens were prospectively enrolled and treated with G/P (300 mg/120 mg) once daily for 8 or 12 weeks. The primary efficacy endpoint was sustained virologic response at 12 weeks after treatment completion (SVR12). Adverse effects and laboratory abnormalities were assessed. Results: Twenty-five Japanese patients (15 female) were enrolled from 13 pediatric centers in Japan. Median age was 13 years (range 12–17). Numbers of patients with genotypes 1b, 2a, 2b, and 2b/1b were 6, 12, 6, and 1, respectively. Twenty-two were treatment-naïve, while three had experienced interferon-based treatments. All patients completed G/P treatment (24 for 8 weeks and 1 for 12). Twenty-four achieved SVR12 (96%). Most adverse events were mild. None were serious. G/P significantly decreased serum alanine aminotransferase, γ‐glutamyltransferase, and Wisteria floribunda agglutinin-positive Mac-2-binding protein concentrations. No negative effects on growth or maturation were apparent at 12 weeks. Conclusions: Under real-world conditions, G/P treatment of Japanese adolescents with chronic HCV was highly efficacious and well tolerated. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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25. Expert consensus on vaccination in patients with inflammatory bowel disease in Japan.
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Ishige, Takashi, Shimizu, Toshiaki, Watanabe, Kenji, Arai, Katsuhiro, Kamei, Koichi, Kudo, Takahiro, Kunisaki, Reiko, Tokuhara, Daisuke, Naganuma, Makoto, Mizuochi, Tatsuki, Murashima, Atsuko, Inoki, Yuta, Iwata, Naomi, Iwama, Itaru, Koinuma, Sachi, Shimizu, Hirotaka, Jimbo, Keisuke, Takaki, Yugo, Takahashi, Shohei, and Cho, Yuki
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INFLAMMATORY bowel diseases , *VACCINATION , *COVID-19 , *CROHN'S disease , *PHYSICIANS - Abstract
Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients' IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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26. Oral rice-based vaccine induces passive and active immunity against enterotoxigenic E. coli-mediated diarrhea in pigs.
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Takeyama, Natsumi, Yuki, Yoshikazu, Tokuhara, Daisuke, Oroku, Kazuki, Mejima, Mio, Kurokawa, Shiho, Kuroda, Masaharu, Kodama, Toshiaki, Nagai, Shinya, Ueda, Susumu, and Kiyono, Hiroshi
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IMMUNITY , *ORAL vaccines , *ESCHERICHIA coli , *DIARRHEA , *CHOLERA toxin , *IMMUNOGLOBULINS , *SWINE - Abstract
Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in both neonatal and weaned pigs. Because the cholera toxin B subunit (CTB) has a high level of amino acid identity to the ETEC heat-labile toxin (LT) B-subunit (LTB), we selected MucoRice-CTB as a vaccine candidate against ETEC-induced pig diarrhea. When pregnant sows were orally immunized with MucoRice-CTB, increased amounts of antigen-specific IgG and IgA were produced in their sera. CTB-specific IgG was secreted in the colostrum and transferred passively to the sera of suckling piglets. IgA antibodies in the colostrum and milk remained high with a booster dose after farrowing. Additionally, when weaned minipigs were orally immunized with MucoRice-CTB, production of CTB-specific intestinal SIgA, as well as systemic IgG and IgA, was induced. To evaluate the cross-protective effect of MucoRice-CTB against ETEC diarrhea, intestinal loop assay with ETEC was conducted. The fluid volume accumulated in the loops of minipigs immunized with MucoRice-CTB was significantly lower than that in control minipigs, indicating that MucoRice-CTB-induced cross-reactive immunity could protect weaned pigs from diarrhea caused by ETEC. MucoRice-CTB could be a candidate oral vaccine for inducing both passive and active immunity to protect both suckling and weaned piglets from ETEC diarrhea. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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27. Attenuated brain lesion on magnetic resonance imaging in an adult patient with methionine adenosyltransferase I/III deficiency.
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Maruta, Ubuka, Shimono, Taro, Tokuhara, Daisuke, Hanayama, Yoshiko, and Miki, Yukio
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AMINO acid deficiency , *METHIONINE adenosyltransferase , *MAGNETIC resonance imaging of the brain - Published
- 2017
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28. Preventive Effect of Pine Bark Extract (Flavangenol) on Metabolic Disease in Western Diet-Loaded Tsumura Suzuki Obese Diabetes Mice.
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Shimada, Tsutomu, Kosugi, Mitsutaka, Tokuhara, Daisuke, Tsubata, Masahito, Kamiya, Tomoyasu, Sameshima, Mayu, Nagamine, Rika, Takagaki, Kinya, Miyamoto, Ken-ichi, and Aburada, Masaki
- Abstract
It is known that the metabolic syndrome has a multi-factorial basis involving both genetic and environmental risk factors. In this study, Tsumura Suzuki Obese Diabetes (TSOD) mice, a mouse model of multi-factorial, hereditary, obese type II diabetes, were given aWestern diet (WTD) as an environmental factor to prepare a diseasemodel (TSOD-WTD) and to investigate the preventive effects of Pine bark extract (Flavangenol) against obesity and various features of metabolic disease appearing in this animal model. In contrast to control Tsumura Suzuki Non-obesity (TSNO) mice, TSOD mice were obese and suffered from other metabolic complications.WTD-fed TSOD mice developed additional features such as hyperinsulinemia, abnormal glucose/lipid metabolism and fatty liver. The treatment with Flavangenol had a suppressive effect on increase in body weight and accumulation of visceral and subcutaneous fat, and also showed preventive effects on symptoms related to insulin resistance, abnormal glucose/lipid metabolism and hypertension. Flavangenol also increased the plasma concentration of adiponectin and decreased the plasma concentration of TNF-α. We next investigated the effect of Flavangenol on absorption of meal-derived lipids. Flavangenol suppressed absorption of neutral fat in an olive-oil-loading test (in vivo) and showed an inhibitory effect on pancreatic lipase (in vitro). The above results suggest that Flavangenol has a preventive effect on severe metabolic disease due to multiple causes that involve both genetic and environmental risk factors. The mechanism of action might involve a partial suppressive effect of meal-derived lipids on absorption. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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29. Platelet count and abdominal dynamic CT are useful in predicting and screening for gastroesophageal varices after Fontan surgery.
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Isoura, Yoshiharu, Yamamoto, Akira, Cho, Yuki, Ehara, Eiji, Jogo, Atsushi, Suzuki, Tsugutoshi, Amano-Teranishi, Yuga, Kioka, Kiyohide, Hamazaki, Takashi, Murakami, Yosuke, and Tokuhara, Daisuke
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PLATELET count , *COMPUTED tomography , *GASTRIC varices , *CARDIAC surgery , *ESOPHAGEAL varices , *SURGERY - Abstract
Objective: Patients who undergo Fontan surgery for complex cardiac anomalies are prone to developing liver and gastrointestinal complications. In particular, gastroesophageal varices (GEVs) can occur, but their prevalence is unknown. We aimed to elucidate the occurrence of GEVs and the predicting parameters of GEVs in these patients. Materials and methods: Twenty-seven patients (median age, 14.8 years; median time since surgery, 12.9 years) who had undergone the Fontan surgery and were examined by abdominal dynamic computed tomography (CT) for the routine follow-up were included in the study. Radiological findings including GEVs and extraintestinal complications were retrospectively evaluated by experienced radiologists in a blinded manner. Relationships between blood-biochemical and demographic parameters and the presence of GEVs were statistically analyzed. Results: Dynamic CT revealed gastric varices (n = 3, 11.1%), esophageal varices (n = 1, 3.7%), and gastrorenal shunts (n = 5, 18.5%). All patients with gastric varices had gastrorenal shunts. All gastric varices were endoscopically confirmed as being isolated and enlarged, with indications for preventive interventional therapy. A platelet count lower than 119 × 109 /L was identified as a predictor of GEV (area under the receiver operating curve, 0.946; sensitivity, 100%; and specificity, 87%). Conclusions: GEVs are important complications that should not be ignored in patients who have undergone a Fontan procedure. Platelet counts lower than 119 × 109 /L may help to prompt patient screening by using abdominal dynamic CT to identify GEVs and their draining collateral veins in these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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30. Congenital dilatation of the bile duct: Changes in diagnostic tools over the past 19 years.
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Takaya, Junji, Muneyuki, Masatoshi, Tokuhara, Daisuke, Takada, Kohei, Hamada, Yoshinori, and Kobayashi, Yohnosuke
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BILE duct abnormalities , *GENETIC disorders , *MEDICAL genetics , *DISEASES , *DIAGNOSIS - Abstract
Abstract Background : Because of recent improvements in diagnostic procedures, many cases of congenital dilatation of the bile duct (CDBD) have been diagnosed in early life. To determine the mode of presentation and changes in diagnostic tools, medical records of 34 children (25 girls, nine boys) with CDBD who were treated between 1982 and 2000 were reviewed. Results : The age at presentation ranged from 0 to 16 years (median 4.9 ± 0.7 years), with two patients being diagnosed using prenatal ultrasonography. Of the 32 patients diagnosed post-natally, 21 (66%) complained of abdominal pain. There were also 21 (66%) cases of vomiting. Sixteen patients (50%) experienced both these symptoms. Ten (31%) cases presented with jaundice and three (9%) presented with a palpable mass. Ultrasonography was used as a diagnostic tool in 29 cases (85%). The finding of a dilated common bile duct on abdominal ultrasonography was helpful for early diagnosis. Spiral computed tomography was also a useful and accurate imaging method for diagnosis. Anomalous pancreaticobiliary junction (PBJ) was demonstrated in 44% of patients with CDBD. Magnetic resonance cholangiopancreatography, which can be performed non-invasively, is useful for the diagnosis and pre-operative assessment of CDBD in children. The average length of time from presentation to diagnosis could be shortened from 46 days (1982-1988) to 13 days (1995-2000). Conclusion : Recent improvements in diagnostic procedures make immediate, non-invasive diagnosis of CDBD and PBJ possible. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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31. Assessing liver stiffness with conventional cut‐off values overestimates liver fibrosis staging in patients who received the Fontan procedure.
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Cho, Yuki, Kabata, Daijiro, Ehara, Eiji, Yamamoto, Akira, Mizuochi, Tatsuki, Mushiake, Sotaro, Kusano, Hironori, Kuwae, Yuko, Suzuki, Tsugutoshi, Uchida‐Kobayashi, Sawako, Morikawa, Hiroyasu, Amano‐Teranishi, Yuga, Kioka, Kiyohide, Jogo, Atsushi, Isoura, Yoshiharu, Hamazaki, Takashi, Murakami, Yosuke, and Tokuhara, Daisuke
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CENTRAL venous pressure , *CARDIAC catheterization , *VENOUS pressure , *LIVER , *FIBROSIS , *CONGENITAL heart disease , *ACOUSTIC radiation force impulse imaging - Abstract
Aim: Patients who undergo the Fontan procedure for complex congenital heart disease are prone to liver cirrhosis. Liver stiffness (LS) reflects liver fibrosis stage in patients with chronic viral hepatitis; however, its accuracy in predicting liver fibrosis stage in Fontan patients is controversial. We aimed to clarify the correlation between LS and liver fibrosis stage in Fontan patients. Methods: Fifty‐eight Fontan patients were prospectively measured for LS with transient elastography. We undertook liver biopsy, cardiac catheterization, and laboratory tests in 22 of these patients (median age, 14.7 years; range, 9.9–32.1 years) with LS > 11.0 kPa (median, 19.2 kPa; range, 12.2–39.8 kPa); these elevated LS values suggest liver cirrhosis. Results: Histologically, all patients showed mild‐to‐severe portal and sinusoidal fibrosis but no cirrhosis. Statistically, LS did not predict histological liver fibrosis scores (p = 0.175). Liver stiffness was not correlated with central venous pressure (p = 0.456) or with the hepatic venous pressure gradient (HVPG; p = 0.062), although the p value for HVPG was only slightly above the threshold for significance. Conclusions: Fontan patients are prone to developing both portal and sinusoidal fibrosis. Liver stiffness could be influenced by HVPG, and using the conventional cut‐off values for LS overestimates and overtreats liver fibrosis in these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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32. Analysis of daily energy, protein, fat, and carbohydrate intake in citrin-deficient patients: Towards prevention of adult-onset type II citrullinemia.
- Author
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Okano, Yoshiyuki, Okamoto, Miki, Yazaki, Masahide, Inui, Ayano, Ohura, Toshihiro, Murayama, Kei, Watanabe, Yoriko, Tokuhara, Daisuke, and Takeshima, Yasuhiro
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LOW-carbohydrate diet , *HIGH-carbohydrate diet , *CARBOHYDRATES , *FAT , *FOOD diaries - Abstract
Patients with citrin deficiency during the adaptation/compensation period exhibit diverse clinical features and have characteristic diet of high protein, high fat, and low carbohydrate. Japanese cuisine typically contains high carbohydrate but evaluation of diet of citrin-deficient patients in 2008 showed a low energy intake and a protein:fat:carbohydrate (PFC) ratio of 19:44:37, which indicates low carbohydrate consumption rate. These findings prompted the need for diet intervention to prevent the adult onset of type II citrullinemia (CTLN2). Since the publication of the report about 10 years ago, patients are generally advised to eat what they wish under active dietary consultation and intervention. In this study, citrin-deficient patients and control subjects living in the same household provided answers to a questionnaire, filled-up a maximum 6-day food diary, and supplied physical data and information on medications if any. To study the effects of the current diet, the survey collected data from 62 patients and 45 controls comparing daily intakes of energy, protein, fat, and carbohydrate. Food analysis showed that patient's energy intake was 115% compared to the Japanese standard. The confidence interval of the PFC ratio of patients was 20–22:47–51:28–32, indicating higher protein, higher fat and lower carbohydrate relative to previous reports. The mean PFC ratio of female patients (22:53:25) was significantly different from that of male patients (20:46:34), which may explain the lower frequency of CTLN2 in females. Comparison of the present data to those published 10 years ago, energy, protein, and fat intakes were significantly higher but the amount of carbohydrate consumption remained the same. Regardless of age, most patients (except for adolescents) consumed 100–200 g/day of carbohydrates, which met the estimated average requirement of 100 g/day for healthy individuals. Finally, patients were generally not overweight and some CTLN2 patients were underweight although their energy intake was higher compared with the control subjects. We speculate that high-energy of a low carbohydrate diet under dietary intervention may help citrin-deficient patients attain normal growth and prevent the onset of CTLN2. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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33. Tag‐less patency capsule for suspected small bowel stenosis: Nationwide multicenter prospective study in Japan.
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Nakamura, Masanao, Watanabe, Kenji, Ohmiya, Naoki, Hirai, Fumihito, Omori, Teppei, Tokuhara, Daisuke, Nakaji, Konosuke, Nouda, Sadaharu, Esaki, Motohiro, Sameshima, Yukinori, Goto, Hidemi, Terano, Akira, Tajiri, Hisao, and Matsui, Toshiyuki
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INFLAMMATORY bowel diseases , *CROHN'S disease , *LONGITUDINAL method , *LARGE intestine , *STENOSIS , *CAPSULE endoscopy , *DEFECATION - Abstract
Study aims: The PillCam patency capsule (PPC) is an Agile tag‐less patency capsule used to evaluate gastrointestinal (GI) patency. We determined the appropriate use of PPC to preclude subsequent small bowel capsule endoscopy (SBCE) retention. Methods: This prospective multicenter study consecutively enrolled patients indicated for SBCE with suspected or established small bowel stenosis. Excretion of an intact PPC or its radiologic visualization in the large bowel was considered GI patency. Primary and secondary study endpoints were SBCE retention rates in patients with confirmed patency and identification of factors associated with patency and SBCE retention, respectively. Results: Of 1096 patients enrolled in the study, patency was confirmed in 976 (89.1%). PPC excretion occurred in 579 patients. Of the remaining 517 patients, patency was confirmed using imaging modalities in 401 (77.5%). SBCE retention occurred in five (0.51%) of 963 patients who underwent SBCE: 1.0% in established Crohn's disease (CD) patients, 0% in suspected CD, 0% in tumors, and 1.6% in patients with obscure GI bleeding, for which PPC localization had been radiographically misinterpreted. The non‐confirmation of patency was associated with established CD, stenosis identified using imaging modalities, abdominal fullness, serum albumin levels <4.0 g/dL, and previous small bowel obstruction (adjusted odds ratios: 4.21, 2.60, 2.47, 2.12, and 2.00; 95% confidence intervals: 2.62–6.78, 1.62–4.17, 1.43–4.27, 1.32–3.40, and 1.15–3.47, respectively). Conclusions: The PillCam™ patency capsule helped preclude SBCE retention in most patients, but its accurate localization was essential for cases without excretion (Study registered the University Hospital Medical Information Network, #UMIN000010513). [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
34. Normal liver stiffness and influencing factors in healthy children: An individual participant data meta‐analysis.
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Li, Darrick K., Khan, Muhammad Rehan, Wang, Zhen, Chongsrisawat, Voranush, Swangsak, Panida, Teufel‐Schäfer, Ulrike, Engelmann, Guido, Goldschmidt, Imeke, Baumann, Ulrich, Tokuhara, Daisuke, Cho, Yuki, Rowland, Marion, Mjelle, Anders B., Ramm, Grant A., Lewindon, Peter J., Witters, Peter, Cassiman, David, Ciuca, Ioana M., Prokop, Larry D., and Haffar, Samir
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CAUCASIAN race , *LIVER , *CHILDHOOD obesity , *TISSUE mechanics , *HEPATIC fibrosis - Abstract
Background & Aims: Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta‐analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters. Methods: We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and < 3 years of age (younger group). Univariate and multivariate linear regression models predicting liver stiffness were conducted. Results: After excluding children with obesity, diabetes, or abnormal liver tests, 652 children were analysed. Among older children, mean liver stiffness was 4.45 kPa (95% confidence interval 4.34‐4.56), and increased liver stiffness was associated with age, sedation status, and S probe use. In the younger group, the mean liver stiffness was 4.79 kPa (95% confidence interval 4.46‐5.12), and increased liver stiffness was associated with sedation status and Caucasian race. In a subgroup analysis, hepatic steatosis on ultrasound was significantly associated with increased liver stiffness. We define a reference range for normal liver stiffness in healthy children as 2.45‐5.56 kPa. Conclusions: We have established TE‐derived liver stiffness ranges for healthy children and propose an upper limit of liver stiffness in healthy children to be 5.56 kPa. We have identified increasing age, use of sedation, probe size, and presence of steatosis on ultrasound as factors that can significantly increase liver stiffness. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
35. Correction to: Expert consensus on vaccination in patients with inflammatory bowel disease in Japan.
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Ishige, Takashi, Shimizu, Toshiaki, Watanabe, Kenji, Arai, Katsuhiro, Kamei, Koichi, Kudo, Takahiro, Kunisaki, Reiko, Tokuhara, Daisuke, Naganuma, Makoto, Mizuochi, Tatsuki, Murashima, Atsuko, Inoki, Yuta, Iwata, Naomi, Iwama, Itaru, Koinuma, Sachi, Shimizu, Hirotaka, Jimbo, Keisuke, Takaki, Yugo, Takahashi, Shohei, and Cho, Yuki
- Subjects
- *
INFLAMMATORY bowel diseases , *VACCINATION , *WEB portals - Published
- 2023
- Full Text
- View/download PDF
36. Oral esomeprazole in Japanese pediatric patients with gastric acid‐related disease: Safety, efficacy, and pharmacokinetics.
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Shimizu, Toshiaki, Nakayama, Yoshiko, Ishii, Eizaburo, Ida, Shinobu, Satou, Tomoki, Tokuhara, Daisuke, Arai, Katsuhiro, Nii, Masahiro, Rydholm, Hans, and Yajima, Toshitaka
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BODY weight , *PHARMACEUTICAL encapsulation , *GASTRIC acid , *GASTROINTESTINAL diseases , *JAPANESE people , *MEDICAL cooperation , *ORAL drug administration , *PATIENT safety , *PEDIATRICS , *RESEARCH , *SUSPENSIONS (Chemistry) , *ESOMEPRAZOLE , *RANDOMIZED controlled trials , *TREATMENT effectiveness , *GENOTYPES , *CYTOCHROME P-450 , *PHARMACODYNAMICS - Abstract
Background: Proton pump inhibitors (PPI) are widely used for the treatment of gastric acid‐related disease, but they are not approved for use in children in Japan. To assess the safety, pharmacokinetics, pharmacodynamics, and efficacy (gastrointestinal symptom improvement) of PPI in Japanese pediatric patients with gastric acid‐related disease, we conducted an 8 week, open‐label, parallel‐group, multicenter, phase I/III study of once‐daily oral esomeprazole use. Methods: Japanese children, aged 1–14 years with gastric acid‐related disease, were stratified by weight and age into five groups (10 patients/group) to receive esomeprazole as granules for suspension (10 mg) or capsules (10 mg or 20 mg) once daily. Results: Esomeprazole was absorbed and eliminated rapidly in all groups, with a median time to reach maximum plasma concentration of 1.47–1.75 h, an arithmetic mean terminal elimination half‐life of 0.80–1.37 h, and a weight‐correlated apparent total body clearance of 0.216–0.343 L/h/kg. Area under the plasma concentration–time curve during a dosage interval and maximum plasma drug concentration were generally higher in groups given a higher dose (20 mg) or with a lower age/weight, but also in patients identified as poor metabolizers on cytochrome P450 2C19 genotype. Most patients who had any upper gastrointestinal symptoms at baseline were asymptomatic at the end of the study. Thirty‐three patients (66%) reported ≥1 adverse events, including three patients who reported serious adverse events not judged to be causally related to esomeprazole. Conclusions: Oral esomeprazole, at 10 mg or 20 mg once daily, had a similar safety, efficacy, and pharmacokinetic profile in Japanese pediatric patients to that previously seen in adults and Caucasian children. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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37. Differential analyses of major allergen proteins in wild-type rice and rice producing a fragment of anti-rotavirus antibody.
- Author
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Yuki, Yoshikazu, Kurokawa, Shiho, Kozuka-Hata, Hiroko, Tokuhara, Daisuke, Mejima, Mio, Kuroda, Masaharu, Oyama, Masaaki, Nishimaki-Mogami, Tomoko, Teshima, Reiko, and Kiyono, Hiroshi
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WILD rice , *ALLERGENS , *ROTAVIRUSES , *ORAL drug administration , *THERAPEUTIC use of immunoglobulins , *RICE seeds - Abstract
To develop oral antibody therapy against rotavirus infection, we previously produced a recombinant fragment of llama heavy-chain antibody to rotavirus (ARP1) in rice seeds (MucoRice-ARP1). We intend to use a purification-free rice powder for clinical application but needed to check whether MucoRice-ARP1 had increased levels of known allergen proteins. For this purpose, we used two-dimensional fluorescence difference gel electrophoresis to compare the allergen protein levels in MucoRice-ARP1 and wild-type rice. We detected no notable differences, except in the levels of α-amylase/trypsin inhibitor–like family proteins. Because by this approach we could not completely separate ARP1 from the proteins of this family, we confirmed the absence of changes in the levels of these allergens by using shotgun mass spectrometry as well as immunoblot. By using immunoelectron microscopy, we also showed that RAG2, a member of the α-amylase/trypsin inhibitor–like protein family, was relocated from protein bodies II to the plasma membrane or cell wall in MucoRice-ARP1 seed. The relocation did not affect the level of RAG2. We demonstrated that most of the known rice allergens were not considerably upregulated by the genetic modification in MucoRice-ARP1. Our data suggest that MucoRice-ARP1 is a potentially safe oral antibody for clinical application. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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38. Hepatic focal nodular hyperplasia with congenital portosystemic shunt.
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Cho, Yuki, Shimono, Taro, Morikawa, Hiroyasu, Shintaku, Haruo, and Tokuhara, Daisuke
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LIVER diseases , *HEPATIC portal system - Abstract
Hepatic focal nodular hyperplasia (FNH) is a rare benign tumor in children. Vascular anomalies have been identified as pathological features of FNH, but the etiology remains unclear. We describe a rare case including the time course of formation of hepatic FNH in response to congenital portosystemic shunt (PSS). A 4-month-old girl was identified on newborn mass screening to have hypergalactosemia, but no inherited deficiencies in galactose-metabolizing enzymes were found. Ultrasonography and per-rectal portal scintigraphy showed intrahepatic PSS of the right lobe as a cause of the hypergalactosemia. At age 12 months, the patient had elevated hepatic enzymes and small hypoechoic hepatic lesions around the shunt. On abdominal contrast-enhanced ultrasonography spoke-wheel sign and central stellate scar were seen, which are typical features of hepatic FNH without biopsy. Congenital intrahepatic PSS should be evaluated on abdominal contrast-enhanced ultrasonography and observed over time because of its potential to develop into hepatic FNH. [ABSTRACT FROM AUTHOR]
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- 2014
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39. A case of TUBA1A mutation presenting with lissencephaly and Hirschsprung disease.
- Author
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Hikita, Norikatsu, Hattori, Hideji, Kato, Mitsuhiro, Sakuma, Satoru, Morotomi, Yoshiki, Ishida, Hiroshi, Seto, Toshiyuki, Tanaka, Katsuji, Shimono, Taro, Shintaku, Haruo, and Tokuhara, Daisuke
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GENETIC mutation , *LISSENCEPHALY , *HIRSCHSPRUNG'S disease , *TUBULINS , *MICROTUBULES , *CYTOSKELETON - Abstract
Abstract: Gene mutation of tubulin alpha-1A (TUBA1A), a critical component of microtubules of the cytoskeleton, impairs neural migration and causes lissencephaly (LIS). The approximately 45 cases of disease-associated TUBA1A mutations reported to date demonstrate a wide spectrum of phenotypes. Here we describe an 8-year-old girl with lissencephaly, microcephaly, and early-onset epileptic seizures associated with a novel mutation in the TUBA1A gene. The patient developed Hirschsprung disease and the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which had not previously been described in TUBA1A mutation-associated disease. Our case provides new insight into the wide spectrum of disease phenotypes associated with TUBA1A mutation. [Copyright &y& Elsevier]
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- 2014
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40. Induction of toxin-specific neutralizing immunity by molecularly uniform rice-based oral cholera toxin B subunit vaccine without plant-associated sugar modification.
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Yuki, Yoshikazu, Mejima, Mio, Kurokawa, Shiho, Hiroiwa, Tomoko, Takahashi, Yuko, Tokuhara, Daisuke, Nochi, Tomonori, Katakai, Yuko, Kuroda, Masaharu, Takeyama, Natsumi, Kashima, Koji, Abe, Michiyo, Chen, Yingju, Nakanishi, Ushio, Masumura, Takehiro, Takeuchi, Yoji, Kozuka‐Hata, Hiroko, Shibata, Hiroaki, Oyama, Masaaki, and Tanaka, Kunisuke
- Subjects
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DISEASE resistance of plants , *GENE expression in plants , *CHOLERA toxin , *CHOLERA vaccines , *GLYCOSYLATION , *ORAL diseases , *RICE seeds - Abstract
Plants have been used as expression systems for a number of vaccines. However, the expression of vaccines in plants sometimes results in unexpected modification of the vaccines by N-terminal blocking and sugar-chain attachment. Although MucoRice- CTB was thought to be the first cold-chain-free and unpurified oral vaccine, the molecular heterogeneity of MucoRice- CTB, together with plant-based sugar modifications of the CTB protein, has made it difficult to assess immunological activity of vaccine and yield from rice seed. Using a T- DNA vector driven by a prolamin promoter and a signal peptide added to an overexpression vaccine cassette, we established MucoRice- CTB/Q as a new generation oral cholera vaccine for humans use. We confirmed that MucoRice- CTB/Q produces a single CTB monomer with an Asn to Gln substitution at the 4th glycosylation position. The complete amino acid sequence of MucoRice- CTB/Q was determined by MS/ MS analysis and the exact amount of expressed CTB was determined by SDS- PAGE densitometric analysis to be an average of 2.35 mg of CTB/g of seed. To compare the immunogenicity of MucoRice- CTB/Q, which has no plant-based glycosylation modifications, with that of the original MucoRice- CTB/N, which is modified with a plant N-glycan, we orally immunized mice and macaques with the two preparations. Similar levels of CTB-specific systemic IgG and mucosal IgA antibodies with toxin-neutralizing activity were induced in mice and macaques orally immunized with MucoRice- CTB/Q or MucoRice- CTB/N. These results show that the molecular uniformed MucoRice- CTB/Q vaccine without plant N-glycan has potential as a safe and efficacious oral vaccine candidate for human use. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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41. RNAi suppression of rice endogenous storage proteins enhances the production of rice-based Botulinum neutrotoxin type A vaccine
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Yuki, Yoshikazu, Mejima, Mio, Kurokawa, Shiho, Hiroiwa, Tomoko, Kong, Il Gyu, Kuroda, Masaharu, Takahashi, Yoko, Nochi, Tomonori, Tokuhara, Daisuke, Kohda, Tomoko, Kozaki, Shunji, and Kiyono, Hiroshi
- Subjects
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RNA interference , *RICE proteins , *ENZYME-linked immunosorbent assay , *BOTULINUM toxin , *CHOLERA toxin , *LIPOPOLYSACCHARIDES , *SODIUM dodecyl sulfate , *POLYACRYLAMIDE gel electrophoresis - Abstract
Abstract: Mucosal vaccines based on rice (MucoRice) offer a highly practical and cost-effective strategy for vaccinating large populations against mucosal infections. However, the limitation of low expression and yield of vaccine antigens with high molecular weight remains to be overcome. Here, we introduced RNAi technology to advance the MucoRice system by co-introducing antisense sequences specific for genes encoding endogenous rice storage proteins to minimize storage protein production and allow more space for the accumulation of vaccine antigen in rice seed. When we used RNAi suppression of a combination of major rice endogenous storage proteins, 13kDa prolamin and glutelin A in a T-DNA vector, we could highly express a vaccine comprising the 45kDa C-terminal half of the heavy chain of botulinum type A neurotoxin (BoHc), at an average of 100μg per seed (MucoRice-BoHc). The MucoRice-Hc was water soluble, and was expressed in the cytoplasm but not in protein body I or II of rice seeds. Thus, our adaptation of the RNAi system improved the yield of a vaccine antigen with a high molecular weight. When the mucosal immunogenicity of the purified MucoRice-BoHc was examined, the vaccine induced protective immunity against a challenge with botulinum type A neurotoxin in mice. These findings demonstrate the efficiency and utility of the advanced MucoRice system as an innovative vaccine production system for generating highly immunogenic mucosal vaccines of high-molecular-weight antigens. [Copyright &y& Elsevier]
- Published
- 2012
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42. A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging
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Asanuma, Hideki, Zamri, Normaiza Binti, Sekine, Shinichi, Fukuyama, Yoshiko, Tokuhara, Daisuke, Gilbert, Rebekah S., Fukuiwa, Tatsuya, Fujihashi, Keiko, Sata, Tetsutaro, Tashiro, Masato, and Fujihashi, Kohtaro
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INFLUENZA , *AGING , *LIGANDS (Biochemistry) , *LABORATORY mice , *PLASMIDS , *LYMPH nodes , *NASAL cavity - Abstract
Abstract: Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN)3 as a dendritic cell (DC)-targeting double mucosal adjuvant elicited ovalbumin-specific secretory IgA (S-IgA) antibody (Ab) responses, we examined whether this double adjuvant could induce influenza-specific protective immunity in aged mice. A double adjuvant plus A/Puerto Rico/8/34 (PR8) hemagglutinin (HA) induced increased numbers of CD11b+ CD11c+ DCs and both CD4+ Th1- and Th2-type responses in the nasopharyngeal-associated lymphoreticular tissue, nasal passages and cervical lymph nodes. Further, increased levels of PR8 HA-specific S-IgA Ab responses were detected in the upper respiratory tact (URT) of aged and young adult mice given nasal PR8 HA with this double adjuvant. Thus, when mice were challenged with PR8 virus via the nasal route, both aged and young adult mice given nasal vaccine exhibited complete protection. Further, IgA-deficient mice nasally immunized with a double adjuvant influenza vaccine failed to provide protection against PR8 challenge. These results indicate that a nasal double adjuvant successfully induces PR8 HA-specific IgA Ab responses in both young adult and aged mice, which are essential for the prevention of influenza infection in the murine URT. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
43. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.
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Nochi, Tomonori, Yuki, Yoshikazu, Takahashi, Haruko, Sawada, Shin-ichi, Mejima, Mio, Kohda, Tomoko, Harada, Norihiro, Kong, Il Gyu, Sato, Ayuko, Kataoka, Nobuhiro, Tokuhara, Daisuke, Kurokawa, Shiho, Takahashi, Yuko, Tsukada, Hideo, Kozaki, Shunji, Akiyoshi, Kazunari, and Kiyono, Hiroshi
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NANOTECHNOLOGY , *MUCOSAL diseases in cattle , *VACCINATION , *DENDRITIC cells , *TETANUS toxin - Abstract
Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (‘nanogel’) consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP–BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP–BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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- View/download PDF
44. Immunoglobulin A vasculitis with characteristic capsule endoscopy findings.
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Ng, Chantel TY, Isoura, Yoshiharu, Cho, Yuki, and Tokuhara, Daisuke
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ANTIBIOTICS , *C-reactive protein , *DIFFERENTIAL diagnosis , *GASTROENTERITIS , *IMMUNOGLOBULINS , *LEUCOCYTES , *LYMPHADENITIS , *PURPURA (Pathology) , *ULTRASONIC imaging , *VASCULITIS , *WEIGHT loss , *CAPSULE endoscopy , *METHYLPREDNISOLONE , *SYMPTOMS - Abstract
The article presents a case study of an11-year-old boy presented with a 2 week history of fever, vomiting, abdominal pain, anorexia, and massive melena. Topics include capsule endoscopy showed multiple hematoma-like protrusions over the duodenum and proximal jejunum; and palpable purpura has the common manifestation of immunoglobulin A vasculitis, but abdominal symptoms precede the purpuric rash typical of IgA vasculitis in 14–36% of patients.
- Published
- 2019
- Full Text
- View/download PDF
45. Cell surface antigens of neonatal monocytes are selectively impaired in basal expression, but hyperresponsive to lipopolysaccharide and zymosan.
- Author
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Hikita, Norikatsu, Cho, Yuki, Tachibana, Daisuke, Hamazaki, Takashi, Koyama, Masayasu, and Tokuhara, Daisuke
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CELL surface antigens , *CORD blood , *MONOCYTES , *ANTIGEN presentation , *TOLL-like receptors , *KI-67 antigen - Abstract
• Neonates have limited innate immune responses to infection. • We compared cord blood (CD14+CD16high) and adult (CD14+CD16intermediate) monocytes. • Cord blood monocytes had low basal expression of MHC class II, CD80, and CD11b. • TLR4 or TLR2/6 stimulation increased the antigens more in cord than adult monocytes. • TLR agonists may have utility as vaccine adjuvants in infants. Toll-like receptors (TLRs) are important components of the innate immune system, but how neonatal TLR-mediated immune responses differ from those of adults is unknown. We aimed to clarify the TLR-mediated expression profiles of cell surface antigens related to antigen presentation in neonates. CD14-positive monocytes were isolated from human cord blood and adult peripheral blood and then stimulated with lipopolysaccharide (LPS; TLR4 agonist) or zymosan (TLR2/6 agonist) or left unstimulated. Expression levels of the surface antigens major histocompatibility (MHC)-class II, CD80, CD86, CD11b, CD11c, CD14, and CD16 were then evaluated by flow cytometry. Cord blood CD14+CD16high monocytes (CBM) showed significantly lower basal levels of MHC-class II, CD80, and CD11b than adult blood CD14+CD16intermediate monocytes (ABM) (P < 0.01, P < 0.001, P < 0.001, respectively). LPS stimulation enhanced expression of MHC class II, CD80, and CD11b significantly more in CBM than in ABM (P < 0.001, P < 0.01, P < 0.01, respectively), resulting in levels that did not differ between CBM and ABM. Zymosan stimulation also enhanced expression of MHC class II, CD86, CD11b, and CD11c significantly more in CBM than in ABM (P < 0.001, P < 0.01, P < 0.001, P < 0.01, respectively), resulting in levels of CD86 and CD11c that did not differ in CBM and ABM. However, MHC class II, CD80, and CD11b remained significantly higher in ABM than in CBM (P < 0.05, P < 0.01, P < 0.05, respectively). These data indicate that CBM and ABM have distinct phenotypes and responses to stimulation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
46. Case of adult-onset type II citrullinemia treated as schizophrenia for a long time.
- Author
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Kyo, Masatoshi, Mii, Hiroshi, Takekita, Yoshiteru, Tokuhara, Daisuke, Yazaki, Masahide, Nakamori, Yasushi, Kono, Satoshi, and Kinoshita, Toshihiko
- Subjects
- *
SCHIZOPHRENIA treatment , *DRUG-induced abnormalities , *MEMORY loss , *DROWSINESS - Abstract
The article presents a case study of a 40-year-old woman who experienced loss of memory, and drowsiness due to aversion to alcoholic beverages, and cereal. It mentions that the patient has been admitted and discharged from the Departments of Psychiatry, and Internal Medicine for schizophrenia treatment and drug-induced liver injury due to erratic behavior, hyperactivity, and liver dysfunction. It notes that the patient was diagnosed with adult-onset type II citrullinemia (CTLN2).
- Published
- 2015
- Full Text
- View/download PDF
47. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.
- Author
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Nochi, Tomonori, Yuki, Yoshikazu, Takahashi, Haruko, Sawada, Shin-ichi, Mejima, Mio, Kohda, Tomoko, Harada, Norihiro, Kong, Il Gyu, Sato, Ayuko, Kataoka, Nobuhiro, Tokuhara, Daisuke, Kurokawa, Shiho, Takahashi, Yuko, Tsukada, Hideo, Kozaki, Shunji, Akiyoshi, Kazunari, and Kiyono, Hiroshi
- Subjects
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PREVENTIVE medicine - Abstract
A correction to the article "Nanogel Antigenic Protein-Delivery System for Adjuvant-Free Intranasal Vaccines," that was published in the June 23, 2010, issue of the journal is presented.
- Published
- 2010
- Full Text
- View/download PDF
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