- Advanced Glycation End Products research
- Immune Response and Inflammation
- Diabetes and associated disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- S100 Proteins and Annexins
- Neuroscience of respiration and sleep
- Sepsis Diagnosis and Treatment
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Alcohol Consumption and Health Effects
- Respiratory Support and Mechanisms
- Neonatal Respiratory Health Research
- Diabetes Management and Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Inflammatory mediators and NSAID effects
- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cancer Treatment and Pharmacology
- Polyoxometalates: Synthesis and Applications
- Meteorological Phenomena and Simulations
- Neurological Disorders and Treatments
- Clinical Nutrition and Gastroenterology
- Adipokines, Inflammation, and Metabolic Diseases
- Acute Kidney Injury Research
- Polyamine Metabolism and Applications
University of Cincinnati
2024
Shino-Test Corporation
2014-2024
Cincinnati Children's Hospital Medical Center
2024
National Sagamihara Hospital
2022
Nagoya University
2015
Kurume University
1997-2014
Nishi Niigata Chuo National Hospital
2011
National Hospital Organization
2011
Kanagawa University
2009
Hamamatsu University School of Medicine
2008
High mobility group box 1 (HMGB1), originally described as a DNA-binding protein, can also be released extracellularly and functions late mediator of inflammatory responses. Although recent reports have indicated that the receptor for advanced glycation end products (RAGE) well Toll-like (TLR)2 TLR4 are involved in cellular activation by HMGB1, there has been little evidence direct association between HMGB1 these receptors. To examine this issue, we used fluorescence resonance energy...
Thrombomodulin (TM) is an endothelial anticoagulant cofactor that promotes thrombin-mediated formation of activated protein C (APC). We have found the N-terminal lectin-like domain (D1) TM has unique antiinflammatory properties. TM, via D1, binds high-mobility group-B1 DNA-binding (HMGB1), a factor closely associated with necrotic cell damage following its release from nucleus, thereby preventing in vitro leukocyte activation, vivo UV irradiation–induced cutaneous inflammation, and...
Abstract Objective High mobility group box chromosomal protein 1 (HMGB‐1), a nuclear DNA binding protein, was recently rediscovered as new proinflammatory cytokine. The purpose of this study to demonstrate HMGB‐1 expression in vivo and identify the role pathogenesis rheumatoid arthritis (RA). Methods concentrations synovial fluid (SF) serum from RA osteoarthritis (OA) patients were measured by immunoblot analysis. protein's specific receptor, receptor for advanced glycation end products...
This study was performed to examine the putative role of high mobility group box (HMGB) protein in pathogenesis acute lung injury (ALI). Observations were made (1) 21 patients who septic with ALI and 15 normal function (2) a mouse model 24 hours after intratracheal instillation lipopolysaccharide (LPS). The concentrations HMGB1 increased plasma epithelial lining fluid mice instilled LPS. LPS-induced mitigated by anti-HMGB1 antibody. Although this not detected control humans or mice,...
High mobility group box 1 (HMGB1) is a novel late mediator of inflammatory responses that contributes to endotoxin-induced acute lung injury and sepsis-associated lethality. Although frequent complication severe blood loss, the contribution HMGB1 organ system dysfunction in this setting has not been investigated. In study, was detected pulmonary endothelial cells macrophages under baseline conditions. After hemorrhage, addition positively staining macrophages, neutrophils expressing were...
Lesion biopsies of 60 fingers from 30 patients with vibration-induced white finger (VWF) and control observations seven five referents demonstrated three main characteristic pathological changes. First, in each case, the muscular layers arteries revealed intense thickening strong hypertrophy individual muscle cells without intimal fibrosis. Periarterial fibrosis was also noted. Arteriosclerosis foamy cells, lipid deposition, fibrous sclerosis occasionally observed. The second change...
High mobility group box 1 protein (HMGB1) was identified as a mediator of endotoxin lethality. We previously reported that thrombomodulin (TM), an endothelial thrombin-binding protein, bound to HMGB1, thereby protecting mice from lethal endotoxemia. However, the fate HMGB1 TM remains be elucidated.TM enhanced thrombin-mediated cleavage HMGB1. N-terminal amino acid sequence analysis degradation product demonstrated thrombin cleaved at Arg10-Gly11 bond. Concomitant with domain proinflammatory...
AimsHigh-mobility group box 1 protein (HMGB1) is one of the recently defined damage-associated molecular pattern molecules derived from necrotic cells and activated macrophages. We investigated clinical implications serum HMGB1 elevation in patients with acute myocardial infarction (MI). Then, we evaluated effect blockade on post-MI left ventricular (LV) remodelling a rat MI model.
Recent studies have shown that histones, the chief protein component of chromatin, are released into extracellular space during sepsis, trauma, and ischemia-reperfusion injury, act as major mediators death an organism. This study was designed to elucidate cellular molecular basis histone-induced lethality assess protective effects recombinant thrombomodulin (rTM). rTM has been approved for treatment disseminated intravascular coagulation (DIC) in Japan, is currently undergoing a phase III...
Islet transplantation for the treatment of type 1 diabetes mellitus is limited in its clinical application mainly due to early loss transplanted islets, resulting low efficiency. NKT cell-dependent IFN-gamma production by Gr-1(+)CD11b(+) cells essential this loss, but upstream events process remain undetermined. Here, we have demonstrated that high-mobility group box (HMGB1) plays a crucial role initial islets mouse model diabetes. Pancreatic contained abundant HMGB1, which was released into...
Abstract The timing and characteristics of neuronal death in Alzheimer’s disease (AD) remain largely unknown. Here we examine AD mouse models with an original marker, myristoylated alanine-rich C-kinase substrate phosphorylated at serine 46 (pSer46-MARCKS), reveal increase necrosis during pre-symptomatic phase a subsequent decrease symptomatic phase. Postmortem brains mild cognitive impairment (MCI) rather than patients remarkable necrosis. In vivo imaging reveals instability endoplasmic...
Proinflammatory cytokines play an important role in ventilator-induced lung injury (VILI). High-mobility group box-1 (HMGB1) is a macrophage-derived proinflammatory cytokine that can cause injury.This study tested the hypothesis HMGB1 released intact lungs ventilated with large Vt. A second objective was to identify source of HMGB1. third examine effects blocking on subsequent development VILI.Bronchoalveolar lavage fluid (BALF) and tissues were obtained from rabbits mechanically for 4 h...
Abstract Objective Tissue hypoxia is closely associated with arthritis pathogenesis, and extracellular high mobility group box chromosomal protein 1 (HMGB‐1) released from injured cells also has a role in development. This study was thus undertaken to investigate the hypothesis that HMGB‐1 may be coupling factor between inflammation arthritis. Methods Concentrations of tumor necrosis α, interleukin‐6, vascular endothelial growth factor, lactic acid, lactate dehydrogenase, were measured...
Abstract The high mobility group box 1 protein (HMGB1) is an alarmin that plays important role in sepsis and has been recognized as a promising target with wide therapeutic window; however, no drugs devices are currently practical use. We hypothesized hemofilters composed of porous membranes or cytokine‐adsorbing could remove HMGB1 from the blood. performed experimental hemofiltration vitro using four types different specifically designed for continuous hemofiltration. test solution was...
Psoriasis is a systemic inflammatory skin disease associated with cardiovascular and lipid dysfunction. However, traditional parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this driven condition may capture additional risk. Recently, study showed that psoriasis was increased lipid-rich coronary plaques; therefore, investigating potential relationships speed understanding of psoriasis.To understand whether associate phenotypes, cardiometabolic...
High mobility group protein 1 (HMGB1) has been implicated in diverse cellular functions, including determination of nucleosomal structure and stability binding transcription factors to their cognate DNA sequences (1)(2)(3)(4). HMGB1 is also present a membrane-associated form, termed amphoterin, that mediates neurite outgrowth (5). Amphoterin can interact with macrophage cell surface receptors for advanced glycation end products enhance expression tissue-type plasminogen activator...
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. However, molecular cellular mechanisms driving inflammation not been fully elucidated.To elucidate roles high mobility group box 1 protein (HMGB1), a ubiquitous DNA-binding with extracellular pro-inflammatory activity, rat model PAH.Male...