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Antifibrotic effects of ambrisentan,an endothelin-A receptor antagonist,in a non-alcoholic steatohepatitis mouse model

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World Journal of Hepatology 2016年第22期8卷 933-941页

作者： Toshiaki Okamoto Masahiko Koda Kennichi Miyoshi Takumi Onoyama Manabu Kishina tomomitsu matono Takaaki Sugihara Keiko Hosho Junichi Okano Hajime Isomoto Yoshikazu Murawaki Division of Medicine and Clinical Science Department of Multidisciplinary Internal Medicine Tottori Univer-sity Second Department of Internal Medicine Tottori University

AIM: To examine the effects of the endothelin type A receptor antagonist ambrisentan on hepatic steatosis and fibrosis in a steatohepatitis mouse ***: Fatty liver shionogi(FLS) FLS-ob/ob mice(male, 12 wk old) received ambrisentan(2.5 mg/kg orally per day; n = 8) or water as a control(n = 5) for 4 wk. Factors were compared between the two groups, including steatosis, fibrosis, inflammation, and endothelin-related gene expression in the ***: In the ambrisentan group, hepatic hydroxyproline content was significantly lower than in the control group(18.0 μg/g ± 6.1 μg/g vs 33.9 μg/g ± 13.5 μg/g liver, respectively, P = 0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, were also significantly lower in the ambrisentan group(0.46% ± 0.18% vs 1.11% ± 0.28%, respectively, P = 0.0003; and 0.12% ± 0.08% vs 0.25% ± 0.11%, respectively, P = 0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1(TIMP-1) were significantly lower by 60% and 45%, respectively, in the ambrisentan group. Inflammation, steatosis, and endothelin-related m RNA expression in the liver were not significantly different between the ***: Ambrisentan attenuated the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.

关键词： Endothelin Ambrisentan Steatohepatitis Hepatic stellate cell Hepatic fibrosis Oxidative stress Hepatic hydroxyproline

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Laboratory efficacy of mycoparasitic fungi(Aspergillus tubingensis and Trichoderma harzianum) against tropical bed bugs(Cimex hemipterus)(Hemiptera:Cimicidae)

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Asian Pacific Journal of Tropical Biomedicine 2017年第4期7卷 288-293页

作者： Zulaikha Zahran Nik Mohd Izham Mohamed Nor Hamady Dieng tomomitsu Satho Abdul Hafiz Ab Majid Household and Structural Urban Entomology Laboratory Vector Control Research UnitSchool of Biological SciencesUniversiti Sains Malaysia Plant Pathology Laboratory School of Biological SciencesUniversiti Sains Malaysia Institute of Biodiversity and Environmental Conservation Universiti Malaysia Sarawak Department of Microbiology Faculty of Pharmaceutical SciencesFukuoka University

Objective: To test the effectiveness of conidial spore formulations [Aspergillus tubingensis(***) and Trichoderma harzianum(***)] against tropical bed bugs, Cimex ***: Spore formulations were made from two fungal strains, *** and *** bed bugs were exposed to the conidial spores placed soaked onto a fabric cloth for 1 h and the mortality counts were recorded daily until 14 ***: Mean survival times based on Kaplan–Meier survival analysis showed no significant differences between all the concentrations in both the fungal isolates:*** and ***, the evaluation of both the isolates in terms of virulence resulted in low lethal hours in all the concentrations except for the high concentration of ***(LT_(50)= 44.629 h) at the conidial exposure of 1 × 10~6 spores/*** mortality of the bed bugs was observed from Day 6 to Day 12, ranging from 13% to 90% in all three concentrations of *** reference to the *** exposure, the concentration of 1 × 10~4 spores/mL displayed a gradual increase in the percentage mortality of 90 on Day ***: Approaches to the bed bugs treatment should be explored in-depth using a natural biological agent like fungus especially *** to reduce this pest population, in order to replace chemical methods.

关键词： Tropical bed bug Mycoparasitic fungi Aspergillus tubingensis Trichoderma harzianum Bio-control

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Number and distribution of eosinophils and lymphocytes in the Japanese pediatric gastrointestinal tract:in search of a definition for"abnormally increased eosinophils"

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World Journal of Pediatrics 2023年第3期19卷 251-260页

作者： Mai Iwaya Shota Kobayashi Yoshiko Nakayama Sawako Kato Shingo Kurasawa tomomitsu Sado Yugo lwaya Takeshi Uehara Hiroyoshi Ota Department of Laboratory Medicine Shinshu University Hospital3-1-1 AsahiMatsumotoNaganoJapan Department of Pediatrics Shinshu University School of MedicineMatsumotoJapan Division of Gastroenterology and Hepatology Department of MedicineShinshu University School of MedicineMatsumotoJapan Department of Laboratory Medicine Shinshu University School of MedicineMatsumotoJapan Department of Clinical Laboratory Sciences School of Health SciencesShinshu UniversityMatsumotoJapan

Background Primary eosinophilic gastrointestinal disorders(EGIDs)constitute chronic allergic *** number of eosinophils is one of the diagnostic criteria;more than 20 eosinophils per high-power field(HPF)in the gastrointestinal(GI)tract are considered abnormal in ***,the quantity of eosinophils considered normal varies according to anatomical location and geographical region;such values have not been reported in Japanese pediatric patients,nor have the numbers of lymphocytes in the normal pediatric *** establish a reference for defining diagnostic criteria for EGIDs,we evaluated the number of eosinophils in the normal Japanese pediatric GI *** We examined 131 biopsy cases without significant clinical history,endoscopic abnormality,or histological *** analysis of CD3 and CD20 was *** The mean eosinophil density was highest in the cecum(49.5±22.4 per HPF).Counts of more than 20 eosinophils per HPF were observed in the duodenum[bulb(20.0±9.6)and second portion(30.0±15.8)],terminal ileum(38.3±22.7),cecum(49.5±22.4),ascending colon(42.3±25.3),transverse colon(29.4±17.0),and descending colon(32.2±17.9).Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum;a count of fewer than one eosinophil per HPF was observed in the *** than 100 CD3-positive T cells per HPF were observed in the *** The mean numbers of eosinophils in the bowel were greater than 20 per *** Japanese pediatrics,the cur-rent threshold eosinophil count should be revised.

关键词： Eosinophil Gastrointestinal tract Japanese Lymphocyte Normal Pediatrics

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Long-Term Outcomes of Systemic-to-Pulmonary Artery Shunt in Patients with Functional Single Ventricle and Heterotaxy Syndrome

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Congenital Heart Disease 2023年第4期18卷 399-411页

作者： Shota Kawai Takashi Kido Yuta Teguri Koji Miwa tomomitsu Kanaya Yoichiro Ishii Hisaaki Aoki Futoshi Kayatani Sanae Tsumura Department of Cardiovascular Surgery Osaka Women’s and Children’s HospitalIzumiOsakaJapan Department of Pediatric Cardiology Osaka Women’s and Children’s HospitalIzumiOsakaJapan

Objectives: We sought to determine the long-term outcomes and mortality-associated factors after systemic-topulmonaryartery shunt (SPS) in patients with heterotaxy syndrome. Methods: We retrospectively analyzed allpatients with a functional single ventricle and heterotaxy syndrome who underwent SPS at our center from January2001 to April 2022. Results: This study involved 84 patients. Restrictive pulmonary blood flow requiringearly modulation was presented in 34 (40%) patients. Compared with patients without restrictive pulmonaryblood flow (N = 50 [60%]), the postnatal survival of these 34 patients was significantly lower at 10 years (log rank:p = 0.04), but the statistical significance disappeared at 20 years (log rank: p = 0.18). Among 31 patients whounderwent SPS, 11 (35%) had extracardiac total anomalous pulmonary venous connection (TAPVC). The survivalrate after SPS was 80% at 10 years. Cox regression analysis showed that extracardiac TAPVC (hazard ratio6.44, 95% confidence interval 1.23–33.7, p = 0.03) and pulmonary venous obstruction (PVO) at TAPVC repair(hazard ratio 11.2, 95% confidence interval 2.13–58.5, p = 0.004) were significantly associated with death. In25 patients who underwent bidirectional cavopulmonary shunt (BCPS), surgical interventions on the pulmonaryartery (PA) were performed after SPS in 7 of 9 patients with PA coarctation, 3 of 4 with non-confluent PAs, and4 of 12 with normal PAs. At SPS, primary central PA plasty was performed in three patients with PA coarctationand 2 with non-confluent PAs. There was no significant difference in the PA index before BCPS between patientswith and without primary central PA plasty (p = 0.49). Among 20 patients who underwent total cavopulmonaryconnection (TCPC), adverse events occurred in 7 (35%) patients, including death in 1 (5%), intervention for pulmonaryarteriovenous malformation (PAVM) in 3 (15%), and surgical intervention for PVO in 3 (15%). TheB-type natriuretic peptide concentration was significant

关键词： Heterotaxy syndrome single ventricle total anomalous of pulmonary venous connection pulmonary artery coarctation

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The biology and demographic parameters of Aedes albopictus in northern peninsular Malaysia

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Asian Pacific Journal of Tropical Biomedicine 2011年第6期1卷 472-477页

作者： H Nur Aida Hamady Dieng Abu Hassan Ahmad tomomitsu Satho AT Nurita MR Che Salmah Fumio Miake B Norasmah Medical Entomology Laboratory School of Biological SciencesUniversiti Sains Malaysia Faculty of Pharmaceutical Sciences Fukuoka University

Objective:To generate life table characteristics for the dengue vector Aedes albopictus(A. albopictus) under uncontrolled conditions,incorporating both the aquatic and the adult stages. Methods:Ten females derived from wild pupae were allowed to fully blood-feed on restrained mice.774 eggs were hatched in seasoned water.F1 larvae were followed for development until their F2 counterparts emerged as *** population parameters were monitored(Fl) or estimated(F2).Results:*** exhibited increased fecundity and egg hatch success. Immature development was *** survival was high,with lowest rate in the pupal *** emergence was about 81%and sex ratio was close to 1:*** mortality(K) was about 28%.A high proportion of females completed a reproductive cycle and the obtained parity rate was predicted to lead to higher fecundity in the next ***:It can be concluded that natural *** populations in Penang seem largely determined by quick development in combination with low immature loss and increased oviposition.

关键词： Aedes albopictus Biology Population parameters Life table Life budget

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Genetic polymorphisms of MAFK, encoding a small Maf protein, are associated with susceptibility to ulcerative colitis in Japan

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World Journal of Gastroenterology 2017年第29期23卷 5364-5370页

作者： Tomiyasu Arisawa Masakatsu Nakamura Toshimi Otsuka Wu Jing Naoko Sakurai Hikaru Takano Tasuku Hayashi Masafumi Ota Tomoe Nomura Ranji Hayashi Takeo Shimasaki tomomitsu Tahara Tomoyuki Shibata Department of Gastroenterology Kanazawa Medical University Department of Gastroenterology Fujita Health University

To investigate whether single nucleotide polymorphisms in maf protein K (MAFK), which encodes the MAFK, lead to increased susceptibility to ulcerative colitis in the Japanese population. METHODSThis case control study examined the associations between MAFK single nucleotide polymorphisms (rs4268033 G>A, rs3735656 T>C and rs10226620 C>T) and ulcerative colitis susceptibility in 174 patients with ulcerative colitis (UC) cases, and 748 subjects without no lower abdominal symptoms, diarrhea or hematochezia (controls). In addition, as the second controls, we set 360 subjects, who have an irregular bowel movement without abnormal lower endoscopic findings (IBM controls). RESULTSThe genotype frequency of rs4268033 AA and allelic frequency of the rs4268033A allele were significantly higher in the UC cases than in both controls (P = 0.0005 and < 0.0001, P = 0.015 and 0.0027 vs controls and IBM controls, respectively). Logistic regression analysis after adjustment for age and gender showed that the rs4268033 AA and rs3735656 CC genotypes were significantly associated with susceptibility to UC development (OR = 2.63, 95%CI: 1.61-4.30, P = 0.0001 and OR = 1.81; 95%CI: 1.12-2.94, P = 0.015, respectively). Similar findings were observed by the comparison with IBM controls. In addition, the rs4268033 AA genotype was significantly associated with all phenotypes of UC except early onset. There was no significant association between rs10226620 and ulcerative colitis. CONCLUSIONOur results provide the first evidence that MAFK genetic polymorphisms are significantly associated with susceptibility to UC development. In particular, rs4268033 is closely associated with an increased risk for the development of UC.

关键词： Maf protein K Genetic polymorphism Reactive oxygen species Ulcerative colitis Nuclear factor-erythroid 2-related factor 2

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Morphological and molecular characterization of fungus isolated from tropical bed bugs in Northern Peninsular Malaysia, Cimex hemipterus(Hemiptera: Cimicidae)

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Asian Pacific Journal of Tropical Biomedicine 2015年第9期5卷 684-690页

作者： Abdul Hafiz Ab Majid Zulaikha Zahran Abd Hafis Abd Rahim Nor Azliza Ismail Wardah Abdul Rahman Kartiekasari Syahidda Mohammad Zubairi Hamady Dieng tomomitsu Satho Household and Structural Urban Entomology Laboratory School of Biological Sciences Universiti Sains Malaysia Plant Pathology Laboratory School of Biological Sciences Universiti Sains Malaysia Institute of Biodiversity and Environmental Conservation Universiti Malaysia Sarawak Department of Microbiology Faculty of Pharmaceutical Sciences Fukuoka University

Objective:To investigate some morphological and molecular characteristics of fungal parasites isolated from wild tropical bed bug, Cimex ***: A series of culture methods were used to obtain fungal isolates from i eld-collected bed bugs. Characteristics of the isolates such as colony appearance, mycelial texture and pigmentation were studied to explore their morphology. Isolates were also subjected to a PCRbased genotyping ***: There were noticeable dif erences in morphological characteristics among the four isolates. Conidial areas of one isolate were dark green, whereas those of the remaining colonies were olive-green, black or dark brown. Conidia of the dark green isolate were globose, while those of olive-green, black and dark brown isolates were globose to subglobose, globose to spherical and globose to subglobose/i nely roughened, respectively. These morphological specii cities and the molecular analyses showed that the fungal internal transcribed spacer ribosomal region and β-tubulin gene sequences of the isolates shared clade with Trichoderma and Aspergillus ***: Overall, the new discovery of common pathogens in agricultural i eld developed in live bed bugs storage tank may initiate the use of biological agents in later years.

关键词： Cimex hemipterus Aspergillus Trichoderma β-tubulin Internal transcribed spacer Morphological characteristics

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Seasonal Changes in Mayfly Communities and Abundance in Relation to Water Physicochemistry in Two Rivers at Different Elevations in Northern Peninsular Malaysia

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湿地科学 2011年第3期9卷 240-250页

作者： Suhaila Abdul Hamid Mohd Ravi Che Salmah Hamady Dieng Abu Hassan Ahmad tomomitsu Satho Fumio Miake School of Biological Sciences Universiti Sains Malaysia Faculty of Pharmaceutical Sciences Fukuoka University

A field study was performed at rivers in Gunung Jerai forest reserve(Kedah,Malaysia) to assess seasonal changes in mayfly community structure and abundance in relation to altitude and water *** at lower(Batu Hampar River) and higher(Teroi River) elevations were visited through dry and wet seasons in September 2007 to August *** visits were made to 20 sites on each river,and water and aquatic insects were sampled using D-pond aquatic *** was warmer,more acid,and more turbid in Teroi River during wet *** was the only nutrient exhibiting significant seasonal variations(greater during wet season).Chemical oxygen demand content was higher in Teroi River where biochemical oxygen demand content was low during wet *** richness was higher in Batu Hampar River,but displayed seasonal variations only in Teroi *** the eight families encountered,Baetidae was the *** abundance was usually high during wet season,and those belonging to the dominant genus(Baetis) were more abundant in Teroi *** was the second commonest family;its predominant genus,Thalerospyrus was more abundant in Teroi River during dry ***,Leptophlebiidae and Oligoneuriidae were only found in Batu Hampar River where their abundances peaked during dry season,i.e.,Habrophlebiodes *** Isonychia *** and Teloganodidae occurred only in Teroi River,with the first found only during dry *** were recorded under very distinct physicochemical conditions,illustrating their potential usefulness for assessing water ***,leptophlebids,oligoneurids ephemerellids and teloganodids seem to be particularly sensitive to temperature,acidity,turbidity,chemical oxygen demand and biochemical oxygen demand,parameters that varied with river altitude.

关键词： river ephemeroptera abundance altitude season physicochemistry

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Household survey of container-breeding mosquitoes and climatic factors influencing the prevalence of Aedes aegypti(Diptera:Culicidae)in Makkah City,Saudi Arabia

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Asian Pacific Journal of Tropical Biomedicine 2012年第11期2卷 849-857页

作者： Al Thabiany Aziz Hamady Dieng Abu Hassan Ahmad Jazem A Mahyoub Abdulhafis M Turkistani Hatabbi Mesed Salah Koshike tomomitsu Satho MR Che Salmah Hamdan Ahmad Wan Fatma Zuharah Ahmad Saad Ramli Fumio Miake Medical Entomology Laboratory School of Biological SciencesUniversiti Sains Malaysia Department of Biological Science King Abdul-Aziz University Ministry of Health Kingdom of Saudi Arabia Ministry of Municipal Saudi Arabia Faculty of Pharmaceutical Sciences Fukuoka University

Objective:To investigate the prevalence of container breeding mosquitoes with emphasis on the seasonality and larval habitats of Aedes aegypti(***) in Makkah City,adjoining an environmental monitoring and dengue ***:Monthly visits were performed between April 2008 and March 2009 to randomly selected *** each visit,mosquito larvae were collected from indoors and outdoors containers by either dipping or pipetting. Mosquitoes were morphologically *** on temperature,relative humidity,rain/ precipitations during the survey period was retrieved from governmental sources and analyzed. Results:The city was warmer in dry season(DS) than wet season(WS).No rain occurred at all during DS and even precipitations did fall,wetting events were much greaterduring *** survey revealed the co-breeding of Aedes,Culex and Anopheles in a variety of artificial containers in and around homes.32109 larvae representing 1st,2nd,3rd,and 4th stages were collected from 22618 container *** was far the commonest and Aedes genus was as numerous as the Culex *** larval abundance exhibited marked temporal variations,overall, being usually more abundant during *** types of artificial containers were found with developing larvae.70%of these habitats were located indoors.71.42%of indoor containers were permanent and 28.58* was semi-permanent during *** tanks was the only container type permanent during *** larval indices(CI,HI,Bl) recorded were greater during WS. Conclusions:Taken together,these results indicate a high risk of dengue transmission in the holy city.

关键词： Aedes aegypti Larval indices Environmental factors Dengue incidence

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Human CD4^- CD8^- Invariant Natural Killer T Cells Promote IgG Secretion from B Cells Stimulated by Cross-Linking of Their Antigen Receptors

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World Journal of Vaccines 2016年第2期6卷 34-41页

作者： tomomitsu Miyasaka Yurie Watanabe Yukiko Akahori Namiko Miyamura Keiko Ishii Yuki Kinjo Yoshitsugu Miyazaki Tian-Yi Liu Yasushi Uemura Kazuyoshi Kawakami Department of Medical Microbiology Mycology and Immunology Tohoku University Graduate School of Medicine Sendai Japan Department of Chemotherapy and Mycoses National Institute of Infectious Diseases Tokyo Japan Division of Immunology Aichi Cancer Center Research Institute (ACCRI) Nagoya Japan Key Laboratory of Cancer Center Chinese PLA General Hospital Beijing China Division of Cancer Immunotherapy Exploratory Oncology Research & Clinical Trial Center National Cancer Center (NCC) Kashiwa Japan

Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4+ CD8β- (CD4) and CD4- CD8β- [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19+CD27- (naïve) and CD19+CD27+ (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.

关键词： Invariant Natural Killer T Cells TI-2 Antigen B Cells IgM IgG

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