- Systemic Sclerosis and Related Diseases
- Inflammatory Myopathies and Dermatomyositis
- Dermatologic Treatments and Research
- Eosinophilic Disorders and Syndromes
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune Cell Function and Interaction
- Mast cells and histamine
- Skin Diseases and Diabetes
- Autoimmune Bullous Skin Diseases
- Lymphatic System and Diseases
- Psoriasis: Treatment and Pathogenesis
- Sphingolipid Metabolism and Signaling
- Cutaneous lymphoproliferative disorders research
- Immunotherapy and Immune Responses
- Dermatology and Skin Diseases
- Connective Tissue Growth Factor Research
- Systemic Lupus Erythematosus Research
- Biochemical Analysis and Sensing Techniques
- Heart Failure Treatment and Management
- Cancer and Skin Lesions
- Pulmonary Hypertension Research and Treatments
- Genetic and rare skin diseases.
- Protease and Inhibitor Mechanisms
- Urticaria and Related Conditions
- T-cell and Retrovirus Studies
The University of Tokyo
2016-2025
University of Tokyo Hospital
2023-2025
Kawasaki Medical School Hospital
2025
Kawasaki Medical School
2025
Howard Hughes Medical Institute
2014-2018
University of California, San Francisco
2014-2018
University of Tennessee at Knoxville
2012
National Cerebral and Cardiovascular Center
2000
Kumamoto University
1994
B-type or brain natriuretic peptide (BNP) is a novel secreted from the heart that forms family with A-type atrial (ANP), and its plasma level has been shown to be increased in patients congestive failure. This study was designed examine sources mechanisms of secretion BNP comparison those ANP control subjects failure.We measured levels as well 16 dilated cardiomyopathy (11 men 5 women; mean age, 59 years) 18 (9 9 54 by sampling blood femoral vein, aortic root, anterior interventricular vein...
Psoriasis is an inflammatory skin disease with accelerated epidermal cell turnover. Neutrophil accumulation in the one of histological characteristics psoriasis. However, precise mechanism and role neutrophil infiltration remain largely unknown. In this article, we show that orchestrated action CXCR2 leukotriene B4 receptor BLT1 plays a key recruitment during development imiquimod (IMQ)-induced psoriatic lesions mice. Depletion neutrophils anti-Ly-6G Ab ameliorated severity, along reduced...
To the Editor: Systemic sclerosis (SSc) is an autoimmune disease that causes fibrosis of skin and internal organs, a possible relationship exists between activated interleukin-17 (IL-17) pathway pathogenesis SSc.1Chizzolini C. Dufour A.M. Brembilla N.C. Is there role for IL-17 in systemic sclerosis?.Immunol Lett. 2018; 195: 61-67https://doi.org/10.1016/j.imlet.2017.09.007Crossref PubMed Scopus (42) Google Scholar Therefore, this first single-center trial assessed pharmacokinetics, safety,...
Intraepithelial lymphocytes (IELs) play an important role in maintaining the physiology of small intestine. The majority mouse IELs express CD8αα and are either γδ or αβ T cells. Although development homing have been studied some detail, factors controlling their homeostasis positioning incompletely understood. Here we demonstrate that G protein–coupled receptor 18 (GPR18) is abundantly expressed mice lacking this orphan reduced numbers γδT IELs. Mixed bone marrow chimera experiments reveal...
Intraepithelial lymphocytes (IELs) of the small intestine are intimately associated with epithelial cells. Yet, factors controlling their migration and interaction dynamics poorly understood. We demonstrate that GPR55, a receptor mediates inhibition in response to lysophosphatidylinositol (LPI), negatively regulates T cell γδ (TCRγδ) IEL accumulation intestine. Intravital imaging studies show GPR55-deficient IELs migrate faster interact more extensively GPR55 also homing γδT egress from...
Abstract Systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) is the most frequent cause of death for SSc but there still no sufficient treatment available. Although cyclophosphamide (CYC) therapy a common which has shown statistical efficacy against SSc‐ILD to date, its effects are temporary and not enough. Rituximab (RTX), anti‐CD20 monoclonal antibody, recently in many autoimmune diseases. In SSc‐ILD, RTX also considered be one novel candidates. However, studies Japanese...
Previous studies have shown the relationship between higher skin thickness score and existence of organ involvements in systemic sclerosis (SSc). Here, we firstly investigated correlation quantitative measurements each involvement Japanese patients with SSc. All SSc hospitalized to our clinic for initial evaluation were selected. Skin was evaluated by modified Rodnan total (mRSS). Relationship mRSS prevalence or incidence examined logistic analyses. Correlation analyses regression We...
Objectives. Chemerin is a member of adipocytokines with chemoattractant effect on plasmacytoid dendritic cells and macrophages pro-angiogenic properties. We investigated the potential role chemerin in development SSc. Methods. expression was evaluated by immunostaining and/or real-time quantitative RT-PCR human murine skin. The mechanisms regulating dermal fibroblasts endothelial were examined using gene silencing technique chromatin immunoprecipitation. Serum levels determined ELISA 64 SSc...
Cathepsin B (CTSB) is a proteolytic enzyme potentially modulating angiogenic processes and extracellular matrix remodeling. While metalloproteinases are shown to be implicated in tissue fibrosis vasculopathy associated with systemic sclerosis (SSc), the role of cathepsins this disease has not been well studied. The aim study evaluate roles CTSB SSc. Serum pro-CTSB levels were determined by enzyme-linked immunosorbent assay 55 SSc patients 19 normal controls. Since deficiency transcription...
Patients with systemic sclerosis (SSc) have an increased risk of malignancy compared the general population. Recently, SSc patients anti-RNA polymerase III antibody been reported to as those other disease-specific autoantibodies in US, European and Australian populations. Therefore, we studied relationship between 261 Japanese patients. The prevalence was significantly higher (7/22, 31.8%) than anti-topoisomerase I (2/82, 2.4%) anticentromere (8/137, 5.8%). Importantly, among seven...
Objectives. Cathepsin V (CTSV) is a proteolytic enzyme potentially modulating angiogenic processes, collagen degradation and keratinocyte differentiation. We aimed to investigate the clinical association of serum CTSV levels mechanism by which expression altered in SSc. Methods. Serum were determined ELISA 51 SSc 18 healthy subjects. was evaluated immunostaining normal skin RT–real-time PCR dermal fibroblasts, fibroblasts treated with TGF-β1 or Fli1 siRNA human microvascular endothelial...
Background Lipocalin-2 is an adipocytokine implicated in apoptosis, innate immunity, angiogenesis, and the development of chronic kidney disease. Objectives To investigate role lipocalin-2 systemic sclerosis (SSc). Materials methods Serum levels were determined by enzyme-linked immunosorbent assay 50 patients with SSc 19 healthy subjects. expression was evaluated skin bleomycin (BLM)-treated mice Fli1-deficient endothelial cells reverse transcriptase-real time polymerase chain reaction,...
Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrotic, inflammatory, and vascular dysfunction. Danger-associated molecular patterns (DAMPs)-mediated inflammasome activation has been reported to be involved in the pathogenesis of SSc. Cold-inducible RNA-binding protein (CIRP) newly identified as DAMP. Here we examined clinical significance serum levels CIRP 60 patients with SSc 20 healthy control (HCs) using an enzyme-linked immunosorbent assay. Serum diffuse...
Abstract Digital ulcers in patients with systemic sclerosis (SSc) can be complicated by SSc-related osteomyelitis (SRO). The microbiological data and optimal management of SRO remain unclear. This single-center retrospective study involved SSc aged 18 or older from April 2005 to March 2022. Diagnosis was based on clinical presentation MRI findings. accuracy the superficial swab culture results estimated using bone as a reference. Temporal changes local signs for up year were collected, their...
Abstract Background Baloxavir marboxil (baloxavir) is a new anti-influenza drug that works as cap-dependent endonuclease inhibitor. It approved for prophylactic use against influenza in Japan, but there are few reports on this usage hospitalized in-patients. reportedly reduces patient susceptibility to through mechanism involving amino acid substitution. Methods Between August 2023 and July 2024, we investigated the efficacy of baloxavir among in-patients at our hospital who had close...
Plasma concentrations of A type or atrial natriuretic peptide (ANP) and B brain (BNP) are increased in patients with congestive heart failure (CHF).To examine the haemodynamic hormonal responses, especially ANP BNP, to oral administration an angiotensin-converting enzyme (ACE) inhibitor CHF controls.12 11 controls.Haemodynamic variables plasma ANP, other hormones were serially measured for 24 hours after alacepril (37.5 mg) was given by mouth.Pulmonary capillary wedge pressure systemic...
Abstract Background Early lesions of localized scleroderma are histologically characterized by perivascular lymphocytic infiltrate in the reticular dermis and swollen endothelial cells. However, there have been few information regarding histological features other than these findings scleroderma. Objective Since en coup de sabre ( ECDS ) is a certain subset with relatively uniform clinical manifestation, we focused on this disease evaluated its histopathological features. Methods A total 16...
Visfatin is a member of the adipocytokines with pro-fibrotic, pro-inflammatory and immunomodulating properties potentially implicated in pathogenesis certain fibrotic inflammatory autoimmune diseases. In this study, we investigated THE CLINICAL SIGNIFICANCE OF SERUM VISFATIN LEVELS AND ITS CONTRIBUTION TO DEVELOPMENTAL PROCESS IN SSC.Serum visfatin levels were determined by specific ELISA 57 SSc patients 19 healthy controls. The mRNA target genes normal fibroblasts real-time RT-PCR. IL-12p70...
The requirements for effector and memory CD8 T cell development are incompletely understood. Recent work has revealed a role G-protein coupled receptor 18 (GPR18) in establishment of the intestinal CD8αα intra-epithelial lymphocyte compartment. Here we report that GPR18 is also functionally expressed conventional CD8αβ cells. When lacking, mice develop fewer CD8+ KLRG1+ Granzyme B+ effector-memory Bone marrow chimera studies show requirement intrinsic. not required T-bet expression Gene...
Abstract There have been no established parameters to predict responsiveness i.v. cyclophosphamide ( IVCY ) pulse therapy in combination with corticosteroids patients interstitial lung disease ILD related systemic sclerosis SS c). This retrospective study was conducted determine predictive factors for efficacy of at the time before and during treatment. Thirty‐two Japanese c patients, ever treated prednisolone, were analyzed retrospectively. We performed detailed time‐course analyses derived...
Abstract Bitter taste receptors (T2Rs) are G protein-coupled involved in the perception of bitter on tongue. In humans, T2Rs have been found several sites outside oral cavity. Although T2R38 has reported to be expressed peripheral lymphocytes, it is poorly understood whether plays immunological roles inflammatory skin diseases such as atopic dermatitis (AD). Then, we first confirmed that gene expression was higher lesional AD subjects than healthy controls. Furthermore, levels were...
Bosentan is an oral dual endothelin receptor antagonist, which has been shown to be efficacious for preventing new digital ulcers in patients with systemic sclerosis (SSc) two high-quality randomized controlled trials. However, its efficacy nondigital SSc remains unknown.To evaluate the of bosentan on SSc.Bosentan was administered five pulmonary arterial hypertension, who also had refractory conventional treatments. The and association clinical features were analysed.The treatments...