Toshihiro Nakajima

Toshihiro Nakajima
Tokyo Medical University | TMU · Institute of Medical Science (IMS)

MD&PhD

About

161
Publications
9,970
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
9,255
Citations
Citations since 2017
14 Research Items
1823 Citations
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
Additional affiliations
April 2010 - present
Tokyo Medical University
Position
  • Professor (Full)
December 2000 - March 2008
St. Marianna University School of Medicine
Position
  • Professor (Full)

Publications

Publications (161)
Article
Rheumatoid arthritis (RA) is one of the most critical articular diseases, which is characterized by synovial hyperplasia and impaired quality of life. The clinical features of RA include chronic inflammation of the joints associated with synovial cell overgrowth. However, the mechanism regulating the outgrowth of fibroblast‑like synoviocytes (FLS)...
Article
Obesity is currently a major medical and societal issue. Synoviolin (SYVN1) is an E3 ubiquitin ligase involved in endoplasmic reticulum (ER) stress. Overexpression of Syvn1 has been found in genetically obese mice (ob/ob and db/db), and treatment with a Syvn1 inhibitor suppresses weight gain in some mouse models (C57BL/6J and db/db). However, SYVN1...
Article
Objective: The aims of the present study were to examine the effects of short-term music interventions among patients with fibromyalgia (FM) and to clarify the alterations in functional connectivity and persistent pain. Design: Pilot study. Setting: All participants were evaluated at Juntendo University from November 2017 to January 2019. Sub...
Article
Full-text available
Objectives To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. Methods In this phase IV, multicentre, double-blind study ( NCT01758198 ), patients were randomised (1:1) to r...
Article
Full-text available
This study was performed to elucidate the molecular function of the synoviocyte proliferation-associated in collagen-induced arthritis (CIA) 1/serum amyloid A-like 1 (SPACIA1/SAAL1) in mice CIA, an animal model of rheumatoid arthritis (RA), and human RA-synovial fibroblasts (RASFs). SPACIA1/SAAL1-deficient mice were generated and used to create mou...
Article
Synoviolin (Syvn1), an E3 ubiquitin ligase in endoplasmic reticulum‑associated protein degradation, is involved in rheumatoid arthritis, fibrosis, liver cirrhosis and obesity. We previously demonstrated that Syvn1 negatively regulates the function of peroxisome proliferator‑activated receptor gamma coactivator‑1β (PGC‑1β). In addition, treatment wi...
Article
Sepsis‑associated encephalopathy (SAE) is a systemic inflammatory response syndrome of which the precise associated mechanisms remain unclear. Synoviolin (Syvn1) is an E3 ubiquitin ligase involved in conditions associated with chronic inflammation, including rheumatoid arthritis, obesity, fibrosis and liver cirrhosis. However, the role of Syvn1 in...
Article
Homocysteine-inducible endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible membrane protein involved in ER-associated degradation. Herp expression is maintained at low levels through a strict regulatory mechanism, but the details of this mechanism and the reasons why Herp expression is restricted in this manner remain unclear. Here,...
Article
Full-text available
Scientific Reports 6: Article number: 36943; published online: 11 November 2016; updated: 11 May 2018 The Publisher is retracting this Article because the experimental approach does not support the objectives of the study. The study was designed to elucidate the maximum implication of human papilloma virus (HPV) vaccine (Gardasil) in the central ne...
Article
Full-text available
Rheumatoid arthritis (RA) is a chronic inflammatory articular disease that is characterized by synovial hyperplasia. A number of signaling pathways are associated with the development and induced symptoms of RA. Notably, patients with RA have increased protein citrullination and generation of auto‑antibodies against citrullinated proteins. Genome w...
Article
Purpose: The aim of the present study was to determine the brain regions with altered metabolism in patients with treatment-naïve fibromyalgia (FM). Methods: We used [(18)F] fluoro-d-glucose positron emission tomography to examine a total of 18 treatment-naïve FM patients and 18 age- and sex-matched healthy controls not suffering from pain. A vo...
Article
Full-text available
Introduction: Fibromyalgia is characterized by chronic pain and tenderness throughout the body. Patients with fibromyalgia are treated with pharmacotherapy and many other therapies. However, because the cause of fibromyalgia is unclear, there is currently no clinically effective treatment method. Case presentation: We report the case of a patien...
Article
Full-text available
Mesenchymal stem/stromal cells (MSCs) reside in the bone marrow and maintain their stemness under hypoxic conditions. However, the mechanism underlying the effects of hypoxia on MSCs remains to be elucidated. This study attempted to uncover the signaling pathway of MSC proliferation. Under low-oxygen culture conditions, MSCs maintained their prolif...
Data
ROS expression in hypoxic and normoxic conditions. (A) Cell proliferation under hypoxic and normoxic conditions (blue bar: normoxic, red bar: hypoxic, orange bar: normoxic with NAC, and green bar: hypoxic with BSO). (B) ROS expression analysis by flow cytometry (1% O2: hypoxic, 20% O2: normoxic, control: negative control, and NAC+: normoxic with NA...
Data
Scanning electron microscope photographs of a cell under hypoxic and normoxic conditions. Electron transmission microscopy showed the number of mitochondria under normoxic (top) and hypoxic (bottom) conditions. The area enclosed by the black square is shown at a higher magnification in the image on the right side. (TIF)
Data
List of gene-specific primers used for quantitative RT-PCR. (DOCX)
Article
Full-text available
Vaccination is the most powerful way to prevent human beings from contracting infectious diseases including viruses. In the case of the human papillomavirus (HPV) vaccine, an unexpectedly novel disease entity, HPV vaccination associated neuro-immunopathetic syndrome (HANS), has been reported and remains to be carefully verified. To elucidate the me...
Article
Tetraspanin CD81, which is up-regulated in rheumatoid arthritis (RA) synoviocytes, is a molecule containing four transmembrane domains. We recently showed that small interfering RNA targeting CD81 (CD81 siRNA) ameliorated arthritis in rats. In that study, the expression of synoviolin was decreased in RA joints by CD81 siRNA. We also showed that CD8...
Article
The nuclear factor-κB (NF-κB) transcription factor family members control various biological processes, such as apoptosis and proliferation. The endoplasmic reticulum (ER) has emerged as a major site of cellular homeostasis regulation. The accumulation of misfolded protein in the ER causes stress and ER stress-induced NF-κB activation to protect ce...
Article
Homocysteine-inducible endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible key regulatory component of ER-associated degradation (ERAD) that has been implicated in insulin hypersecretion in diabetic mouse models. Herp expression is tightly regulated. Additionally, Herp is a highly labile protein and interacts with various proteins,...
Article
Full-text available
Obesity is a major global public health problem, and understanding its pathogenesis is critical for identifying a cure. In this study, a gene knockout strategy was used in post-neonatal mice to delete synoviolin (Syvn)1/Hrd1/Der3, an ER-resident E3 ubiquitin ligase with known roles in homeostasis maintenance. Syvn1 deficiency resulted in weight los...
Article
Full-text available
[Purpose] The aim of the study was to determine the effect of xenon irradiation of the stellate ganglion region on fibromyalgia. [Subjects] The study included 5 men and 22 women (age, 56.4 ± 16.3 years [range, 25-84 years]) who were diagnosed with fibromyalgia according to the modified 2010 criteria of the American College of Rheumatology between J...
Article
The deletion mutation of exon 4 in surfactant protein C (SP-C), a lung surfactant protein, has been identified in parent-child cases of familial interstitial pneumonia. It has been shown that this mutation induces endoplasmic reticulum (ER) stress. Synoviolin is an E3 ubiquitin ligase that is localized to the ER and is an important factor in the de...
Article
Full-text available
Background: Human T-lymphotropic virus type 1 (HTLV-1) can cause chronic spinal cord inflammation, known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since CD4(+)CCR4(+) T cells are the main HTLV-1 reservoir, we evaluated the defucosylated humanized anti-CCR4 antibody mogamulizumab as a treatment for HAM/TSP. Methods:...
Article
Full-text available
Human T-lymphotropic virus type 1 (HTLV-1) is linked to multiple diseases, including the neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia/lymphoma. Evidence suggests that HTLV-1, via the viral protein Tax, exploits CD4+ T cell plasticity and induces transcriptional changes in in...
Article
Full-text available
Increased endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) are the salient features of end-stage liver diseases. Using liver tissues from liver cirrhosis patients, we observed up-regulation of the XBP1-Hrd1 arm of the ER stress response pathway and down-regulation of the Nrf2-mediated antioxidant response pathway. We further conf...
Article
Objective: Thymidine phosphorylase (TP) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) is induced by tumor necrosis factor α (TNFα) and other cytokines that have been reported to be major inflammation mediators in RA. We previously demonstrated that TP plays an important role in angiogenesis and tumor growth, invasion, and metasta...
Article
Full-text available
Human T-lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare chronic neuroinflammatory disease. Since the disease course of HAM/TSP varies among patients, there is a dire need for biomarkers capable of predicting the rate of disease progression. However, there have been no studies to date that h...
Article
Full-text available
The aim of this study was to investigate vulnerability and long-term influence of traumatic stress caused by the Great East Japan Disaster which occurred on March 11, 2011, in patients with fibromyalgia, which is a chronic pain syndrome probably involving central sensitization. A total of 60 female patients with fibromyalgia were compared with fema...
Article
Full-text available
Human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare neurodegenerative disease characterized by chronic inflammation in the spinal cord. We hypothesized that a positive feedback loop driven by chemokines may be responsible for the chronic inflammation in HAM/TSP. We aimed to determine the identity...
Article
Full-text available
Alzheimer disease (AD) is characterized by the deposition of Aβ, which is generated from the amyloid precursor protein (APP) through its cleavage by β- and γ-secretases. The γ-secretase complex component nicastrin (NCT) plays significant roles in the assembly and proper trafficking of the γ-secretase complex and in the recognition of APP. NCT is in...
Article
Full-text available
Purpose The aim of this study is to investigate the reliability and validity of the Japanese version of the modified American College of Rheumatology (ACR) Preliminary Diagnostic Criteria for Fibromyalgia (mACR 2010-J) and the Fibromyalgia Symptom Scale (mFS-J). Methods According to the ACR 1990 classification criteria, patients with chronic pain...
Article
Full-text available
Rheumatoid arthritis (RA) significantly affects quality of life. We recently cloned synoviolin, a RING-type E3 ubiquitin ligase implicated in the endoplasmic reticulum-associated degradation (ERAD) pathway. Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of RA. Inhibition of synoviolin activity is...
Article
Full-text available
The symptoms of rheumatoid arthritis (RA) are based on the many processes; chronic inflammation, overgrowth of synovial cells, bone and joint destruction and fibrosis. To clarify the mechanism of outgrowth of synovial cells, we carried out immunoscreening using anti-rheumatoid synovial cell antibody, and cloned 'Synoviolin'. Synoviolin, a mammalian...
Article
Full-text available
Rheumatoid arthritis (RA) is consists of multiple processes such as chronic inflammation, overgrowth of synovial cells, joint destruction and fibrosis. To clarify the mechanism of outgrowth of synovial cells, we carried out immunoscreening using anti-rheumatoid synovial cell antibody, and cloned 'Synoviolin' [1]. Synoviolin is endoplasmic reticulum...
Article
To identify novel genes associated with dysregulated proliferation of activated synovial fibroblasts, which are involved in arthritic joint destruction. We performed transcriptome analysis to identify genes that were up-regulated in the foot joints of mice with collagen-induced arthritis (CIA). The effect of candidate genes on proliferation of syno...
Article
The aim of this study was to investigate the reliability and the validity of the Japanese version of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010-J), and its quantification scale, the Fibromyalgia Symptom Scale (FS-J). In this study, we divided patients with chronic pain without psychiatric di...
Article
Full-text available
Matrix metalloproteinase (MMP) 13 is a pathogenic collagenase that causes cartilage destruction and plays a leading role in causing osteoarthritis. This study focused on 114 genes that are differentially expressed between intact and damaged osteoarthritis cartilage, in order to determine which molecules are involved in suppressing MMP-13 expression...
Article
Full-text available
Human T-lymphotropic virus type-1 (HTLV-1) is a human retrovirus that causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia (ATL). A higher viral load in individuals with HTLV-1 infection increases their risk of developing HAM/TSP and ATL. Moreover, the high proviral load is associated with the clinic...
Data
HE staining of liver tissue and serum biochemical tests for wt and Syno+/− mice in natural conditions. (A) HE staining of mouse liver sections from wt and Syno+/− mice in natural conditions. Scale bar = 200 µm. (B) The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total bilirubin (T-b...
Data
Serum biochemical tests for wt and Syno+/− mice in the CCl4-induced chronic hepatic injury model. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total bilirubin (T-bil), total protein, albumin (Alb), and the serum albumin/globulin (A/G) ratio for wt (n = 14) and Syno+/− mice (n = 1...
Data
Double-labeled fluorescent immunohistochemical analysis of rat mammary tissue sections as positive and negative controls for TUNEL staining. The expression and localization of TUNEL (green) and α-SMA (red) were analyzed using an in situ apoptosis assay kit and α-SMA antibodies in positive (right panels) and negative controls (left panels) using rat...
Data
Double immunofluorescence staining was performed in wt and Syno−/− MEFs using antibodies against synoviolin and PDI. Fluorescent images were visualized using a Zeiss LSM 510 META confocal fluorescence microscope (Carl Zeiss, Jena, Germany). The results were derived from 3 independent experiments. Scale bar = 20 µm. (0.78 MB TIF)
Data
The expression and localization of the laminin protein in wt and Syno−/− MEFs. (A) Effect of synoviolin on the expression of laminin. The amount of laminin in whole cell lysates of wt and Syno−/− MEFs was analyzed by immunoblot analysis using anti-laminin, synoviolin, and β-actin antibodies. The antibodies used in this study were as follows: anti-l...
Article
Full-text available
Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno)...
Article
Full-text available
Rheumatic fever (RF) is well known disease as a result of frequent complication of the group A b-hemolytic streptococcal (GABHS) tonsillopharyngitis, have noticeably grown for the last 15 years among young generation in the Kyrgyz Republic. It is important to hold a study about the prevalence of RF and GABHS and their susceptibility to antibiotics...
Article
Prostaglandin E2 (PGE2) is a proinflammatory mediator that is synthesized by cyclooxygenases (COX-1 and COX-2) and prostaglandin E synthases (cPGES-1 and mPGES-1); PGE2 exerts its biological effects by binding to specific receptors. Although non-steroidal anti-inflammatory drugs(NSAIDs), which are non-selective COX inhibitors, have been very often...
Article
Full-text available
Sophisticated quality control mechanisms prolong retention of protein-folding intermediates in the endoplasmic reticulum (ER) until maturation while sorting out terminally misfolded polypeptides for ER-associated degradation (ERAD). The presence of structural lesions in the luminal, transmembrane, or cytosolic domains determines the classification...
Article
Rheumatologic and public health services of Central Asia's republics have suffered hugely as a result of social and economic declines following the dissolution of the Union of Soviet Socialist Republics (USSR) and transition of these republics to market economies. Between 1990 and 2000 there was a mass outflow of highly skilled rheumatologists and...
Article
Full-text available
Isaac's syndrome is a movement disorder characterized by hyperexcitability of peripheral motor nerves. Patients with Isaac's syndrome often develop auto-antibodies to voltage-gated potassium channels (VGKCs) which block their function. However, anti-VGKC antibodies are not detected in all patients with Isaac's syndrome, suggesting the existence of...