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Article ; Online: Isoform-Selective NFAT Inhibitor

Noriko Kitamura / Osamu Kaminuma

International Journal of Molecular Sciences, Vol 22, Iss 2725, p

Potential Usefulness and Development

2021 Volume 2725

Abstract: Nuclear factor of activated T cells (NFAT), which is the pharmacological target of immunosuppressants cyclosporine and tacrolimus, has been shown to play an important role not only in T cells (immune system), from which their name is derived, but also in ...

Abstract	Nuclear factor of activated T cells (NFAT), which is the pharmacological target of immunosuppressants cyclosporine and tacrolimus, has been shown to play an important role not only in T cells (immune system), from which their name is derived, but also in many biological events. Therefore, functional and/or structural abnormalities of NFAT are linked to the pathogenesis of diseases in various organs. The NFAT protein family consists of five isoforms, and each isoform performs diverse functions and has unique expression patterns in the target tissues. This diversity has made it difficult to obtain ideal pharmacological output for immunosuppressants that inhibit the activity of almost all NFAT family members, causing serious and wide-ranging side effects. Moreover, it remains unclear whether isoform-selective NFAT regulation can be achieved by targeting the structural differences among NFAT isoforms and whether this strategy can lead to the development of better drugs than the existing ones. This review summarizes the role of the NFAT family members in biological events, including the development of various diseases, as well as the usefulness of and problems associated with NFAT-targeting therapies, including those dependent on current immunosuppressants. Finally, we propose a novel therapeutic strategy based on the molecular mechanisms that enable selective regulation of specific NFAT isoforms.
Keywords	aortic smooth muscle cell ; calcineurin-binding region ; cytokine ; immunoprecipitation ; immunosuppressant ; knockout mouse ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616 ; 570
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Public health and social measures to mitigate the health and economic impact of the COVID-19 pandemic in Turkey, Egypt, Ukraine, Kazakhstan, and Poland during 2020–2021

Noriko Kitamura / Kaja Abbas / Dilip Nathwani

BMC Public Health, Vol 22, Iss 1, Pp 1-

situational analysis

2022 Volume 13

Abstract: Abstract Background The COVID-19 pandemic had a colossal impact on human society globally. There were similarities and differences in the public health and social measures taken by countries, and comparative analysis facilitates cross-country learning of ...

Abstract	Abstract Background The COVID-19 pandemic had a colossal impact on human society globally. There were similarities and differences in the public health and social measures taken by countries, and comparative analysis facilitates cross-country learning of contextual practices and sharing lessons to mitigate the COVID-19 pandemic impact. Our aim is to conduct a situational analysis of the public health and social measures to mitigate the health and economic impact of the COVID-19 pandemic in Turkey, Egypt, Ukraine, Kazakhstan, and Poland during 2020–2021. Methods We conducted a situational analysis of the COVID-19 pandemic response in Turkey, Egypt, Ukraine, Kazakhstan, and Poland from the perspectives of the health system and health finance, national coordination, surveillance, testing capacity, health infrastructure, healthcare workforce, medical supply, physical distancing and non-pharmaceutical interventions, health communication, impact on non-COVID-19 health services, impact on the economy, education, gender and civil liberties, and COVID-19 vaccination. Results Since the onset of the COVID-19 pandemic, Turkey, Egypt, Ukraine, Kazakhstan, and Poland have expanded COVID-19 testing and treatment capacity over time. However, they faced a shortage of healthcare workforce and medical supplies. They took population-based quarantine measures rather than individual-based isolation measures, which significantly burdened their economies and disrupted education. The unemployment rate increased, and economic growth stagnated. Economic stimulus policy was accompanied by high inflation. Despite the effort to sustain essential health services, healthcare access declined. Schools were closed for 5–11 months. Gender inequality was aggravated in Turkey and Ukraine, and an issue was raised for balancing public health measures and civil liberties in Egypt and Poland. Digital technologies played an important role in maintaining routine healthcare, education, and public health communication. Conclusions The COVID-19 pandemic has ...
Keywords	COVID-19 ; Outbreak response ; Vaccine ; Infectious disease ; Health system ; Sustainable development goals ; Public aspects of medicine ; RA1-1270
Subject code	360 ; 306
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Induced Treg Cells Augment the Th17-Mediated Intestinal Inflammatory Response in a CTLA4-Dependent Manner.

Nobumasa Watanabe / Osamu Kaminuma / Noriko Kitamura / Takachika Hiroi

PLoS ONE, Vol 11, Iss 3, p e

2016 Volume 0150244

Abstract: Th17 cells and Foxp3+ regulatory T cells (Tregs) are thought to promote and suppress inflammatory responses, respectively. However, whether they counteract each other or synergize in regulating immune reactions remains controversial. To determine their ... ...

Abstract	Th17 cells and Foxp3+ regulatory T cells (Tregs) are thought to promote and suppress inflammatory responses, respectively. However, whether they counteract each other or synergize in regulating immune reactions remains controversial. To determine their interactions, we describe the results of experiments employing mouse models of intestinal inflammation by transferring antigen-specific Th cells (Th1, Th2, and Th17) differentiated in vitro followed by the administration of the cognate antigen via enema. We show that cotransfer of induced Tregs (iTregs) suppressed Th1- and Th2-mediated colon inflammation. In contrast, colon inflammation induced by transfer of Th17 cells, was augmented by the cotransfer of iTregs. Furthermore, oral delivery of antigen potentiated Th17-mediated colon inflammation. Administration of a blocking antibody against cytotoxic T lymphocyte-associated antigen 4 (CTLA4) abrogated the effects of cotransfer of iTregs, while the injection of a soluble recombinant immunoglobulin (Ig) fusion protein, CTLA4-Ig substituted for the cotransfer of iTregs. These results suggest that antigen-specific activation of iTregs in a local environment stimulates the Th17-mediated inflammatory response in a CTLA4-dependent manner.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Potential Mechanisms of T Cell-Mediated and Eosinophil-Independent Bronchial Hyperresponsiveness

Mayumi Saeki / Tomoe Nishimura / Noriko Kitamura / Takachika Hiroi / Akio Mori / Osamu Kaminuma

International Journal of Molecular Sciences, Vol 20, Iss 12, p

2019 Volume 2980

Abstract: Bronchial asthma is a chronic disease characterized by reversible airway obstruction, mucus production, and bronchial hyperresponsiveness (BHR). Although Th2 cell-mediated eosinophilic inflammation is an important disease mechanism in the majority of ... ...

Abstract	Bronchial asthma is a chronic disease characterized by reversible airway obstruction, mucus production, and bronchial hyperresponsiveness (BHR). Although Th2 cell-mediated eosinophilic inflammation is an important disease mechanism in the majority of patients with bronchial asthma, recent studies suggest the possible development of Th2-independent airway inflammation and BHR. These non-Th2 endotype patients seem to consist of multiple subgroups, and often do not respond to inhaled corticosteroids. Therefore, to understand the pathogenesis of asthma, it is important to characterize these non-Th2 subgroups. Recently, we demonstrated that Th9 cells induce eosinophil infiltration and eosinophil-independent BHR, and Th9 cells-mediated BHR may be resistant to glucocorticoid. In this review, we summarize the contribution of several T cell subsets in the development of bronchial asthma and introduce our recent study demonstrating Th9 cell-mediated and eosinophil-independent BHR.
Keywords	allergy ; asthma ; airway inflammation ; bronchial hyper responsiveness ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2019-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Association of pneumococcal carriage in infants with the risk of carriage among their contacts in Nha Trang, Vietnam

George Qian / Michiko Toizumi / Sam Clifford / Lien Thuy Le / Tasos Papastylianou / Catherine Satzke / Billy Quilty / Chihiro Iwasaki / Noriko Kitamura / Mizuki Takegata / Minh Xuan Bui / Hien Anh Thi Nguyen / Duc Anh Dang / Albert Jan van Hoek / Lay Myint Yoshida / Stefan Flasche

PLoS Medicine, Vol 19, Iss 5, p e

A nested cross-sectional survey.

2022 Volume 1004016

Abstract: Background Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission ... ...

Abstract	Background Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam. Methods and findings In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant's carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly. ...
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Socio-demographic factors of cesarean births in Nha Trang city, Vietnam

Mizuki Takegata / Carine Ronsmans / Hien Anh T. Nguyen / Noriko Kitamura / Chihiro Iwasaki / Michiko Toizumi / Hiroyuki Moriuchi / Duc Anh Dang / Lay-Myint Yoshida

Tropical Medicine and Health, Vol 48, Iss 1, Pp 1-

a community-based survey

2020 Volume 8

Abstract: Abstract Background The cesarean section rate in Vietnam has been increasing especially in urban area. However, limited evidence identified regarding socio-demographic factors of the cesarean section birth. The objective of this study was to determine ... ...

Abstract	Abstract Background The cesarean section rate in Vietnam has been increasing especially in urban area. However, limited evidence identified regarding socio-demographic factors of the cesarean section birth. The objective of this study was to determine the current cesarean birth rate and the associated socio-demographic factors among mothers in Nha Trang city, south-central Vietnam. Methods A community-based cross-sectional study was conducted between October and November in 2016 as part of a Streptococcus pneumoniae carriage survey conducted in 27 communes of Nha Trang city. From each commune, 120 mothers and their children less than 2 years old were randomly selected. Mothers were asked to answer standardized questions regarding socio-demographic information and mode of birth. Multivariate logistic regression was adopted to examine associations between socio-demographic variables and mode of birth. Results Of 3148 participants, the number of cesarean births was 1396 (44.3 %). Older maternal age (≥ 30 years old), having another child going to school or kindergarten, monthly income more than 644 USD, gestational weeks at birth over 42 weeks, and low (< 2500 g) or high (≥ 3500 g) birth weight were associated with higher likelihood of cesarean births. Conclusion The CS rate obtained in this study was more than twice of what is recommended by the World Health Organization, which is consistent with the previous nation-wide study in Viet Nam. Further monitoring is suggested to examine the non-medical reason for the increased CS rate.
Keywords	Cesarean birth rate ; Community-based mothers ; Socio-demographic factors ; Urban city ; Vietnam ; Arctic medicine. Tropical medicine ; RC955-962
Subject code	300
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Selective Suppression of Th2 Cell-Mediated Lung Eosinophilic Inflammation by Anti-Major Facilitator Super Family Domain Containing 10 Monoclonal Antibody

Tomoe Nishimura / Mayumi Saeki / Yuji Motoi / Noriko Kitamura / Akio Mori / Osamu Kaminuma / Takachika Hiroi

Allergology International, Vol 63, Iss S1, Pp 29-

2014 Volume 35

Abstract: Background: The eosinophil is deeply associated with the pathogenesis of bronchial asthma and other allergic diseases. We recently identified a novel eosinophil-specific cell surface molecule, major facilitator super family domain containing 10 (Mfsd10). ...

Abstract	Background: The eosinophil is deeply associated with the pathogenesis of bronchial asthma and other allergic diseases. We recently identified a novel eosinophil-specific cell surface molecule, major facilitator super family domain containing 10 (Mfsd10). A monoclonal antibody (mAb) against Mfsd10 (M2) showed selective binding and neutralizing activities for eosinophils. However, the relative potency of the blockage of Mfsd10 and other eosinophil-specific molecules for the treatment of allergic diseases has not been evaluated. Therefore, in this study, the effects of M2 and an anti-Siglec-F mAb on antigen-immunized and antigen-specific Th2 cell-transferred murine eosinophilic inflammation models were comparatively investigated. Methods: Ovalbumin (OVA)-specific Th2 cells were differentiated from naïve CD4+ T cells of DO11.10/RAG-2−/− mice in vitro and cytokine producing activity of the Th2 cells was examined. OVA-immunized and Th2 cell- transferred BALB/c mice were treated with M2 or anti-Siglec-F and challenged with OVA. Then the number of inflammatory cells and the concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) were determined. Results: Antigen-specific Th2 cells produced large amounts of IL-4, IL-5 and IL-13 but not IL-17A or IFN-γ. Administration of M2 significantly suppressed antigen-induced lung eosinophil infiltration both in OVA-immunized and Th2 cell-transferred mice. The potency as well as selectivity of M2 for down-regulating eosinophils was quite similar to that of anti-Siglec-F. Both mAbs did not affect antigen-induced IL-5 production in the lungs. Conclusions: Mfsd10 as well as Siglec-F could be an effective target to treat eosinophil-related disorders including bronchial asthma.
Keywords	asthma ; eosinophil ; Mfsd10 ; monoclonal antibody ; T cell ; Medicine ; R ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951 ; Immunologic diseases. Allergy ; RC581-607
Subject code	570
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Asthma, Rhinoconjunctivitis, Eczema, and the Association with Perinatal Anthropometric Factors in Vietnamese Children

Michiko Toizumi / Masahiro Hashizume / Hien Anh T. Nguyen / Michio Yasunami / Noriko Kitamura / Chihiro Iwasaki / Mizuki Takegata / Hiroyuki Moriuchi / Duc Anh Dang / Koya Ariyoshi / Lay-Myint Yoshida

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 10

Abstract: Abstract Few studies have investigated possible causative and protective factors associated with allergic diseases in resource-limited countries, Southeast Asia. We estimated the current prevalence of asthma, rhinoconjunctivitis, and eczema among 6-year- ... ...

Abstract	Abstract Few studies have investigated possible causative and protective factors associated with allergic diseases in resource-limited countries, Southeast Asia. We estimated the current prevalence of asthma, rhinoconjunctivitis, and eczema among 6-year-old children, and identified anthropometric factors associated with asthma, rhinoconjunctivitis and eczema, in South-Central Vietnam. A birth cohort study recruited 1,999 children born at a provincial hospital in Nha Trang, Vietnam between May 2009 and May 2010. A 6-year follow-up survey was conducted where clinical, familial, and environmental information was collected by interviewing caregivers using a standardized form based on the International Study of Asthma and Allergies in Childhood, Phase Three Core and Environmental Questionnaire for 6–7-year-old children. The odds ratios of asthma, rhinoconjunctivitis, and eczema for anthropometric factors were estimated using logistic regression analysis. In total, 1202 children participated in the follow-up survey. The proportions of children who had current asthma, rhinoconjunctivitis, and eczema were 5.1% (95% confidence interval [CI] 3.9–6.5%), 11.5% (9.7–13.4%), and 6.7% (5.3–8.2%), respectively. Low birthweight (adjusted odds ratio 5.12, 95% CI 1.92–13.64) was independently associated with increased risk of eczema. Further studies are necessary to understand the involved mechanism.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unexpected discovery of a diffuse astrocytoma of the conus medullaris in an elderly NF1 patient

Takamistu Uchi, MD / Tsutomu Inaoka, MD, PhD / Noriko Kitamura, MD, PhD / Rumiko Ishikawa, MD, PhD / Tomoya Nakatsuka, MD, PhD / Shusuke Kasuya, MD / Wataru Tokuyama, MD, PhD / Nobuyuki Hiruta, MD, PhD / Hiroshi Takahashi, MD, PhD / Hitoshi Terada, MD, PhD

Radiology Case Reports, Vol 15, Iss 6, Pp 784-

2020 Volume 788

Abstract: Neurofibromatosis type 1 (NF1) is one of the most common genetic neurocutaneous disorders, and it is well known to be associated with peripheral or central nervous system malignancies. The most common malignant tumors are malignant peripheral nerve ... ...

Abstract	Neurofibromatosis type 1 (NF1) is one of the most common genetic neurocutaneous disorders, and it is well known to be associated with peripheral or central nervous system malignancies. The most common malignant tumors are malignant peripheral nerve sheath tumors (MPNSTs); MPNSTs are the most common cause of death in patients with NF1. Central nervous system malignancies rarely occur. So far, the occurrence of spinal cord malignancies is exceedingly rare. Herein, we report a rare case of a 69-year-old male with NF1 following tumor resection twice for cutaneous MPNSTs developing intramedullary diffuse astrocytoma in the conus medullaris, which initially presented with traumatic spinal cord injury associated with a compression fracture from fall. Contrast-enhanced magnetic resonance imaging and biopsy of the spinal cord were required to establish the final diagnosis.
Keywords	Diffuse astrocytoma ; Spinal cord ; Neurofibromatosis ; Follow-up MRI ; Biopsy ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Essential Contribution of CD4+ T Cells to Antigen-Induced Nasal Hyperresponsiveness in Experimental Allergic Rhinitis.

Tomoe Nishimura / Osamu Kaminuma / Mayumi Saeki / Noriko Kitamura / Kunie Matsuoka / Hiromichi Yonekawa / Akio Mori / Takachika Hiroi

PLoS ONE, Vol 11, Iss 1, p e

2016 Volume 0146686

Abstract: Nasal hyperresponsiveness (NHR) is a characteristic feature of allergic rhinitis (AR); however, the pathogenesis of NHR is not fully understood. In this study, during the establishment of an experimental AR model using ovalbumin-immunized and -challenged ...

Abstract	Nasal hyperresponsiveness (NHR) is a characteristic feature of allergic rhinitis (AR); however, the pathogenesis of NHR is not fully understood. In this study, during the establishment of an experimental AR model using ovalbumin-immunized and -challenged mice, augmentation of the sneezing reaction in response to nonspecific proteins as well as a chemical stimulant was detected. Whether NHR is independent of mast cells and eosinophils was determined by using mast cell- and eosinophil-deficient mice. NHR was suppressed by treatment with anti-CD4 antibody, suggesting the pivotal contribution of CD4+ T cells. Furthermore, antigen challenge to mice to which in vitro-differentiated Th1, Th2, and Th17 cells but not naïve CD4+ T cells had been adoptively transferred led to the development of equivalent NHR. Since antigen-specific IgE and IgG were not produced in these mice and since antigen-specific IgE-transgenic mice did not develop NHR even upon antigen challenge, humoral immunity would be dispensable for NHR. CD4+ T cells play a crucial role in the pathogenesis of AR via induction of NHR, independent of IgE-, mast cell-, and eosinophil-mediated responses.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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