start-ver=1.4
cd-journal=joma
no-vol=25
cd-vols=
no-issue=11
article-no=
start-page=5889
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240528
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components—thrombin, heme, and ferrous ion— prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery.
en-copyright=
kn-copyright=

en-aut-name=GaoShangze
en-aut-sei=Gao
en-aut-mei=Shangze
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WangDengli
en-aut-sei=Wang
en-aut-mei=Dengli
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TomonoYasuko
en-aut-sei=Tomono
en-aut-mei=Yasuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=FuLi
en-aut-sei=Fu
en-aut-mei=Li
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=GaoYuan
en-aut-sei=Gao
en-aut-mei=Yuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakahashiYohei
en-aut-sei=Takahashi
en-aut-mei=Yohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YataMariko
en-aut-sei=Yata
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=epidural hematoma
kn-keyword=epidural hematoma
en-keyword=HMGB1
kn-keyword=HMGB1
en-keyword=inflammatory response
kn-keyword=inflammatory response
END

start-ver=1.4
cd-journal=joma
no-vol=174
cd-vols=
no-issue=6
article-no=
start-page=533
end-page=548
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230919
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Phosphorylated SARM1 is involved in the pathological process of rotenone-induced neurodegeneration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a NAD+ hydrolase that plays a key role in axonal degeneration and neuronal cell death. We reported that c-Jun N-terminal kinase (JNK) activates SARM1 through phosphorylation at Ser-548. The importance of SARM1 phosphorylation in the pathological process of Parkinson’s disease (PD) has not been determined. We thus conducted the present study by using rotenone (an inducer of PD-like pathology) and neurons derived from induced pluripotent stem cells (iPSCs) from healthy donors and a patient with familial PD PARK2 (FPD2). The results showed that compared to the healthy neurons, FPD2 neurons were more vulnerable to rotenone-induced stress and had higher levels of SARM1 phosphorylation. Similar cellular events were obtained when we used PARK2-knockdown neurons derived from healthy donor iPSCs. These events in both types of PD-model neurons were suppressed in neurons treated with JNK inhibitors, Ca2+-signal inhibitors, or by a SARM1-knockdown procedure. The degenerative events were enhanced in neurons overexpressing wild-type SARM1 and conversely suppressed in neurons overexpressing the SARM1-S548A mutant. We also detected elevated SARM1 phosphorylation in the midbrain of PD-model mice. The results indicate that phosphorylated SARM1 plays an important role in the pathological process of rotenone-induced neurodegeneration.
en-copyright=
kn-copyright=

en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=PhooMay Tha Zin
en-aut-sei=Phoo
en-aut-mei=May Tha Zin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OchiToshiki
en-aut-sei=Ochi
en-aut-mei=Toshiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YamamotoKen-ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MiyazakiIkuko
en-aut-sei=Miyazaki
en-aut-mei=Ikuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=AsanumaMasato
en-aut-sei=Asanuma
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=JNK
kn-keyword=JNK
en-keyword=PARK2
kn-keyword=PARK2
en-keyword=Parkinson’sdisease
kn-keyword=Parkinson’sdisease
en-keyword=Phosphorylation
kn-keyword=Phosphorylation
en-keyword=SARM1
kn-keyword=SARM1
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=1
article-no=
start-page=8386
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230524
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Comprehensive hemocompatibility analysis on the application of diamond-like carbon to ePTFE artificial vascular prosthesis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The aim of this study was to obtain comprehensive data regarding the hemocompatibility of diamond-like carbon (DLC)-coated expanded polytetrafluoroethylene (ePTFE). DLC increased the hydrophilicity and smoothened the surface and fibrillar structure, respectively, of the ePTFE. DLC-coated ePTFE had more albumin and fibrinogen adsorption and less platelet adhesion than uncoated ePTFE. There were scarce red cell attachments in in vitro human and in vivo animal (rat and swine) whole blood contact tests in both DLC-coated and uncoated ePTFE. DLC-coated ePTFE had a similar but marginally thicker band movement than uncoated-ePTFE with SDS-PAGE after human whole blood contact test. In addition, survival studies of aortic graft replacement in rats (1.5 mm graft) and arteriovenous shunt in goats (4 mm graft) were performed to compare the patency and clot formation between DLC-coated and uncoated ePTFE grafts. Comparable patency was observed in both animal models. However, clots were observed in the luminal surface of the patent 1.5 mm DLC-coated ePTFE grafts, but not in that of uncoated ePTFE grafts. In conclusions, hemocompatibility of DLC-coated ePTFE was high and comparable to that of uncoated ePTFE. However, it failed to improve the hemocompatibility of 1.5 mm ePTFE graft probably because increased fibrinogen adsorption canceled the other beneficial effects of DLC.
en-copyright=
kn-copyright=

en-aut-name=GoyamaTakashi
en-aut-sei=Goyama
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujiiYasuhiro
en-aut-sei=Fujii
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MuraokaGenya
en-aut-sei=Muraoka
en-aut-mei=Genya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NakataniTatsuyuki
en-aut-sei=Nakatani
en-aut-mei=Tatsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OusakaDaiki
en-aut-sei=Ousaka
en-aut-mei=Daiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ImaiYuichi
en-aut-sei=Imai
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KuwadaNoriaki
en-aut-sei=Kuwada
en-aut-mei=Noriaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TsujiTatsunori
en-aut-sei=Tsuji
en-aut-mei=Tatsunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ShukuTakayuki
en-aut-sei=Shuku
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UchidaHaruhito A.
en-aut-sei=Uchida
en-aut-mei=Haruhito A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=OozawaSusumu
en-aut-sei=Oozawa
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KasaharaShingo
en-aut-sei=Kasahara
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of  Cardiovascular Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and  Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Institute of Frontier Science and Technology,  Okayama University of Science
kn-affil=

affil-num=5
en-affil=Department  of Pharmacology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Institute of Frontier Science and Technology,  Okayama University of Science
kn-affil=

affil-num=7
en-affil=Department of Cardiovascular Surgery, Kawasaki  Medical Hospital
kn-affil=

affil-num=8
en-affil=Department of  Cardiovascular Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Civil Engineering,  Okayama University Graduate School of Environmental and Life Science
kn-affil=

affil-num=10
en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease,  Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Translational Research and Drug Development, Okayama  University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Division of Medical Safety Management, Safety Management Facility, Okayama  University Hospital
kn-affil=

affil-num=13
en-affil=Department of  Cardiovascular Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=3
article-no=
start-page=e0283426
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230329
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Consistently low levels of histidine-rich glycoprotein as a new prognostic biomarker for sepsis: A multicenter prospective observational study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background<br>
Few sepsis biomarkers accurately predict severity and mortality. Previously, we had reported that first-day histidine-rich glycoprotein (HRG) levels were significantly lower in patients with sepsis and were associated with mortality. Since the time trends of HRG are unknown, this study focused on the time course of HRG in patients with sepsis and evaluated the differences between survivors and non-survivors. <br>

Methods<br>
A multicenter prospective observational study was conducted involving 200 patients with sepsis in 16 Japanese hospitals. Blood samples were collected on days 1, 3, 5, and 7, and 28-day mortality was used for survival analysis. Plasma HRG levels were determined using a modified quantitative sandwich enzyme-linked immunosorbent assay. <br>

Results<br>
First-day HRG levels in non-survivors were significantly lower than those in survivors (mean, 15.7 [95% confidence interval (CI), 13.4-18.1] vs 20.7 [19.5-21.9] mu g/mL; P = 0.006). Although there was no time x survivors/non-survivors interaction in the time courses of HRG (P = 0.34), the main effect of generalized linear mixed models was significant (P < 0.001). In a univariate Cox proportional hazards model with each variable as a time-dependent covariate, higher HRG levels were significantly associated with a lower risk of mortality (hazard ratio, 0.85 [95% CI, 0.78-0.92]; P < 0.001). Furthermore, presepsin levels (P = 0.02) and Sequential Organ Function Assessment scores (P < 0.001) were significantly associated with mortality. Harrell's C-index values for the 28-day mortality effect of HRG, presepsin, procalcitonin, and C-reactive protein were 0.72, 0.70, 0.63, and 0.59, respectively. <br>

Conclusions<br>
HRG levels in non-survivors were consistently lower than those in survivors during the first seven days of sepsis. Repeatedly measured HRG levels were significantly associated with mortality. Furthermore, the predictive power of HRG for mortality may be superior to that of other singular biomarkers, including presepsin, procalcitonin, and C-reactive protein.
en-copyright=
kn-copyright=

en-aut-name=KawanoueNaoya
en-aut-sei=Kawanoue
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaKosuke
en-aut-sei=Kuroda
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YasudaHiroko
en-aut-sei=Yasuda
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OiwaMasahiko
en-aut-sei=Oiwa
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SuzukiSatoshi
en-aut-sei=Suzuki
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HosoiHiroki
en-aut-sei=Hosoi
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MorimatsuHiroshi
en-aut-sei=Morimatsu
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Data Science Division, Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=
article-no=
start-page=930683
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221005
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histamine induced high mobility group box-1 release from vascular endothelial cells through H-1 receptor
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=BackgroundSystemic allergic reaction is characterized by vasodilation and vascular leakage, which causes a rapid, precipitous and sustained decrease in arterial blood pressure with a concomitant decrease of cardiac output. Histamine is a major mediator released by mast cells in allergic inflammation and response. It causes a cascade of inflammation and strongly increases vascular permeability within minutes through its four G-protein-coupled receptors (GPCRs) on endothelial cells. High mobility group box-1 (HMGB1), a nonhistone chromatin-binding nuclear protein, can be actively secreted into the extracellular space by endothelial cells. HMGB1 has been reported to exert pro-inflammatory effects on endothelial cells and to increase vascular endothelial permeability. However, the relationship between histamine and HMGB1-mediated signaling in vascular endothelial cells and the role of HMGB1 in anaphylactic-induced hypotension have never been studied. Methods and resultsEA.hy 926 cells were treated with different concentrations of histamine for the indicated periods. The results showed that histamine induced HMGB1 translocation and release from the endothelial cells in a concentration- and time-dependent manner. These effects of histamine were concentration-dependently inhibited by d-chlorpheniramine, a specific H-1 receptor antagonist, but not by H-2 or H-3/4 receptor antagonists. Moreover, an H-1-specific agonist, 2-pyridylethylamine, mimicked the effects of histamine, whereas an H-2-receptor agonist, 4-methylhistamine, did not. Adrenaline and noradrenaline, which are commonly used in the clinical treatment of anaphylactic shock, also inhibited the histamine-induced HMGB1 translocation in endothelial cells. We therefore established a rat model of allergic shock by i.v. injection of compound 48/80, a potent histamine-releasing agent. The plasma HMGB1 levels in compound 48/80-injected rats were higher than those in controls. Moreover, the treatment with anti-HMGB1 antibody successfully facilitated the recovery from compound 48/80-induced hypotension. ConclusionHistamine induces HMGB1 release from vascular endothelial cells solely through H-1 receptor stimulation. Anti-HMGB1 therapy may provide a novel treatment for life-threatening systemic anaphylaxis.
en-copyright=
kn-copyright=

en-aut-name=GaoShangze
en-aut-sei=Gao
en-aut-mei=Shangze
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KuWenhan
en-aut-sei=Ku
en-aut-mei=Wenhan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WangDengli
en-aut-sei=Wang
en-aut-mei=Dengli
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=QiaoHandong
en-aut-sei=Qiao
en-aut-mei=Handong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TeshigawaraKiyoshi
en-aut-sei=Teshigawara
en-aut-mei=Kiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Histamine
kn-keyword=Histamine
en-keyword=HMGB1
kn-keyword=HMGB1
en-keyword=vascular endothelial cell
kn-keyword=vascular endothelial cell
en-keyword=H-1 receptor
kn-keyword=H-1 receptor
en-keyword=hypotension
kn-keyword=hypotension
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=19
article-no=
start-page=2970
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220923
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Treatment of Marmoset Intracerebral Hemorrhage with Humanized Anti-HMGB1 mAb
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Intracerebral hemorrhage (ICH) is recognized as a severe clinical problem lacking effective treatment. High mobility group box-1 (HMGB1) exhibits inflammatory cytokine-like activity once released into the extracellular space from the nuclei. We previously demonstrated that intravenous injection of rat anti-HMGB1 monoclonal antibody (mAb) remarkably ameliorated brain injury in a rat ICH model. Therefore, we developed a humanized anti-HMGB1 mAb (OKY001) for clinical use. The present study examined whether and how the humanized anti-HMGB1 mAb ameliorates ICH injury in common marmosets. The results show that administration of humanized anti-HMGB1 mAb inhibited HMGB1 release from the brain into plasma, in association with a decrease of 4-hydroxynonenal (4-HNE) accumulation and a decrease in cerebral iron deposition. In addition, humanized anti-HMGB1 mAb treatment resulted in a reduction in brain injury volume at 12 d after ICH induction. Our in vitro experiment showed that recombinant HMGB1 inhibited hemoglobin uptake by macrophages through CD163 in the presence of haptoglobin, suggesting that the release of excess HMGB1 from the brain may induce a delay in hemoglobin scavenging, thereby allowing the toxic effects of hemoglobin, heme, and Fe2+ to persist. Finally, humanized anti-HMGB1 mAb reduced body weight loss and improved behavioral performance after ICH. Taken together, these results suggest that intravenous injection of humanized anti-HMGB1 mAb has potential as a novel therapeutic strategy for ICH.
en-copyright=
kn-copyright=

en-aut-name=WangDengli
en-aut-sei=Wang
en-aut-mei=Dengli
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OusakaDaiki
en-aut-sei=Ousaka
en-aut-mei=Daiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=QiaoHandong
en-aut-sei=Qiao
en-aut-mei=Handong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WangZiyi
en-aut-sei=Wang
en-aut-mei=Ziyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ZhaoKun
en-aut-sei=Zhao
en-aut-mei=Kun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=GaoShangze
en-aut-sei=Gao
en-aut-mei=Shangze
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TeshigawaraKiyoshi
en-aut-sei=Teshigawara
en-aut-mei=Kiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TakadaKenzo
en-aut-sei=Takada
en-aut-mei=Kenzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Research Fellow of Japan Society for the Promotion of Science
kn-affil=

affil-num=5
en-affil=Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=School of Pharmaceutical Sciences, Tsinghua University
kn-affil=

affil-num=7
en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Sapporo Laboratory, EVEC, Inc.
kn-affil=

affil-num=10
en-affil=Department of Translational Research and Drug Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=intracerebral hemorrhage
kn-keyword=intracerebral hemorrhage
en-keyword=HMGB1
kn-keyword=HMGB1
en-keyword=antibody therapy
kn-keyword=antibody therapy
en-keyword=non-human primate
kn-keyword=non-human primate
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=18
article-no=
start-page=10300
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histidine-Rich Glycoprotein Suppresses the S100A8/A9-Mediated Organotropic Metastasis of Melanoma Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8/A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8/A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8/A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8/A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8/A9. Using S100A8/A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8/A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8/A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8/A9 complex. HRG also inhibited the S100A8/A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis.
en-copyright=
kn-copyright=

en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=InoueYusuke
en-aut-sei=Inoue
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=RumaI. Made Winarsa
en-aut-sei=Ruma
en-aut-mei=I. Made Winarsa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=GoharaYuma
en-aut-sei=Gohara
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KomalasariNi Luh Gede Yoni
en-aut-sei=Komalasari
en-aut-mei=Ni Luh Gede Yoni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=JiangFan
en-aut-sei=Jiang
en-aut-mei=Fan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YamamotoKen-Ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SumardikaI. Wayan
en-aut-sei=Sumardika
en-aut-mei=I. Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=YamauchiAkira
en-aut-sei=Yamauchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KuribayashiFutoshi
en-aut-sei=Kuribayashi
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KondoEisaku
en-aut-sei=Kondo
en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pharmacology, Kindai University Faculty of Medicine
kn-affil=

affil-num=4
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=

affil-num=5
en-affil=Faculty of Medicine, Udayana University
kn-affil=

affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Faculty of Medicine, Udayana University
kn-affil=

affil-num=13
en-affil=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University
kn-affil=

affil-num=14
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=15
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=

affil-num=16
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=

affil-num=17
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=20
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=S100A8/A9
kn-keyword=S100A8/A9
en-keyword=HRG
kn-keyword=HRG
en-keyword=metastasis
kn-keyword=metastasis
END

start-ver=1.4
cd-journal=joma
no-vol=150
cd-vols=
no-issue=1
article-no=
start-page=9
end-page=20
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202209
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Novel aspects of sepsis pathophysiology: NETs, plasma glycoproteins, endotheliopathy and COVID-19
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=In 2016, sepsis was newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis remains one of the crucial medical problems to be solved worldwide. Although the world health organization has made sepsis a global health priority, there remain no specific and effective therapy for sepsis so far. Indeed, over the previous decades almost all attempts to develop novel drugs have failed. This may be partly ascribable to the multifactorial complexity of the septic cascade and the resultant difficulties of identifying drug targets. In addition, there might still be missing links among dysregulated host responses in vital organs. In this review article, recent advances in understanding of the complex pathophysiology of sepsis are summarized, with a focus on neutrophil extracellular traps (NETs), the significant role of NETs in thrombosis/embolism, and the functional roles of plasma proteins, histidine-rich glycoprotein (HRG) and inter-alpha-inhibitor proteins (IAIPs). The specific plasma proteins that are markedly decreased in the acute phase of sepsis may play important roles in the regulation of blood cells, vascular endothelial cells and coagulation. The accumulating evidence may provide us with insights into a novel aspect of the pathophysiology of sepsis and septic ARDS, including that in COVID-19. 
en-copyright=
kn-copyright=

en-aut-name=NishiboriM.
en-aut-sei=Nishibori
en-aut-mei=M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Sepsis
kn-keyword=Sepsis
en-keyword=Histidine-rich glycoprotein (HRG)
kn-keyword=Histidine-rich glycoprotein (HRG)
en-keyword=Neutrophil extracellular traps (NETs)
kn-keyword=Neutrophil extracellular traps (NETs)
en-keyword=Endotheliopathy
kn-keyword=Endotheliopathy
en-keyword=COVID-19
kn-keyword=COVID-19
END

start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=6
article-no=
start-page=671
end-page=675
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Multiple Roles of Histidine-Rich Glycoprotein in Vascular Homeostasis and Angiogenesis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Histidine-rich glycoprotein (HRG) is a 75 kDa plasma protein that is synthesized in the liver of many verte-brates and present in their plasma at relatively high concentrations of 100-150 μg/mL. HRG is an abundant and well-characterized protein having a multidomain structure that enable it to interact with many ligands, func-tion as an adaptor molecule, and participate in numerous physiological and pathological processes. As a plasma protein, HRG has been reported to regulate vascular biology, including coagulation, fibrinolysis and angiogenesis, through its binding with several ligands (heparin, FXII, fibrinogen, thrombospondin, and plas-minogen) and interaction with many types of cells (endothelial cells, erythrocytes, neutrophils and platelets). This review aims to summarize the roles of HRG in maintaining vascular homeostasis and regulating angiogen-esis in various pathological conditions.
en-copyright=
kn-copyright=

en-aut-name=GaoShangze
en-aut-sei=Gao
en-aut-mei=Shangze
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=histidine-rich glycoprotein
kn-keyword=histidine-rich glycoprotein
en-keyword=vascular biology
kn-keyword=vascular biology
en-keyword=coagulation
kn-keyword=coagulation
en-keyword=angiogenesis
kn-keyword=angiogenesis
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021829
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objective<br>
High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs).<br>
<br>
Methods<br>
Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively.<br>
<br>
Results<br>
Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs.<br>
<br>
Conclusion<br>
Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.
en-copyright=
kn-copyright=

en-aut-name=NambaTakahiro
en-aut-sei=Namba
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TsugeMitsuru
en-aut-sei=Tsuge
en-aut-mei=Mitsuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YashiroMasato
en-aut-sei=Yashiro
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SaitoYukie
en-aut-sei=Saito
en-aut-mei=Yukie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MorishimaTsuneo
en-aut-sei=Morishima
en-aut-mei=Tsuneo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TsukaharaHirokazu
en-aut-sei=Tsukahara
en-aut-mei=Hirokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Pediatrics, Aichi Medical University
kn-affil=

affil-num=8
en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Influenza
kn-keyword=Influenza
en-keyword=Acute respiratory distress syndrome
kn-keyword=Acute respiratory distress syndrome
en-keyword=High mobility group box 1
kn-keyword=High mobility group box 1
en-keyword=Human pulmonary microvascular endothelial cell
kn-keyword=Human pulmonary microvascular endothelial cell
en-keyword=Cytokine
kn-keyword=Cytokine
en-keyword=Tumor necrosis factor-α
kn-keyword=Tumor necrosis factor-α
END

start-ver=1.4
cd-journal=joma
no-vol=39
cd-vols=
no-issue=
article-no=
start-page=1511
end-page=1523
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021821
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=High mobility group box-1 (HMGB1) is a ubiquitous non-histone nuclear protein that plays a key role as a transcriptional activator, with its extracellular release provoking inflammation. Inflammatory responses are essential in methamphetamine (METH)-induced acute dopaminergic neurotoxicity. In the present study, we examined the effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on METH-induced dopaminergic neurotoxicity in mice. BALB/c mice received a single intravenous administration of anti-HMGB1 mAb prior to intraperitoneal injections of METH (4 mg/kg x 2, at 2-h intervals). METH injections induced hyperthermia, an increase in plasma HMGB1 concentration, degeneration of dopaminergic nerve terminals, accumulation of microglia, and extracellular release of neuronal HMGB1 in the striatum. These METH-induced changes were significantly inhibited by intravenous administration of anti-HMGB1 mAb. In contrast, blood-brain barrier disruption occurred by METH injections was not suppressed. Our findings demonstrated the neuroprotective effects of anti-HMGB1 mAb against METH-induced dopaminergic neurotoxicity, suggesting that HMGB1 could play an initially important role in METH toxicity.
en-copyright=
kn-copyright=

en-aut-name=MasaiKaori
en-aut-sei=Masai
en-aut-mei=Kaori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurodaKeita
en-aut-sei=Kuroda
en-aut-mei=Keita
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IsookaNami
en-aut-sei=Isooka
en-aut-mei=Nami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KikuokaRyo
en-aut-sei=Kikuoka
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MurakamiShinki
en-aut-sei=Murakami
en-aut-mei=Shinki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KamimaiSunao
en-aut-sei=Kamimai
en-aut-mei=Sunao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=WangDengli
en-aut-sei=Wang
en-aut-mei=Dengli
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MiyazakiIkuko
en-aut-sei=Miyazaki
en-aut-mei=Ikuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=AsanumaMasato
en-aut-sei=Asanuma
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Medical Neurobiology, Okayama University Medical School
kn-affil=

affil-num=7
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=
kn-affil=

affil-num=11
en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=methamphetamine
kn-keyword=methamphetamine
en-keyword=dopamine neuron
kn-keyword=dopamine neuron
en-keyword=high mobility group box-1
kn-keyword=high mobility group box-1
en-keyword=hyperthermia
kn-keyword=hyperthermia
en-keyword=inflammation
kn-keyword=inflammation
en-keyword=neurotoxicity
kn-keyword=neurotoxicity
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=1
article-no=
start-page=10223
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210513
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histidine-rich glycoprotein as a prognostic biomarker for sepsis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n=16) than in survivors (n=83) (median, 15.1 [interquartile ranges, 12.7-16.6] vs. 30.6 [22.1-39.6] mu g/ml; p<0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p<0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis.
en-copyright=
kn-copyright=

en-aut-name=KurodaKosuke
en-aut-sei=Kuroda
en-aut-mei=Kosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IshiiKenzo
en-aut-sei=Ishii
en-aut-mei=Kenzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MiharaYuko
en-aut-sei=Mihara
en-aut-mei=Yuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KawanoueNaoya
en-aut-sei=Kawanoue
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YoshidaMichihiro
en-aut-sei=Yoshida
en-aut-mei=Michihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MorimatsuHiroshi
en-aut-sei=Morimatsu
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Anesthesiology, Fukuyama City Hospital
kn-affil=

affil-num=3
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University
kn-affil=

affil-num=6
en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University
kn-affil=

affil-num=7
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=133
cd-vols=
no-issue=1
article-no=
start-page=10
end-page=22
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Novel understanding of septic pathophysiology and neutrophil extracellular traps
kn-title=敗血症病態の新しい理解と好中球細胞外トラップ
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=西堀正洋
kn-aut-sei=西堀
kn-aut-mei=正洋
aut-affil-num=1
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=和氣秀徳
kn-aut-sei=和氣
kn-aut-mei=秀徳
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学

affil-num=2
en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University
kn-affil=近畿大学医学部　薬理学
en-keyword=敗血症
kn-keyword=敗血症
en-keyword=histidine-rich glycoprotein（HRG）
kn-keyword=histidine-rich glycoprotein（HRG）
en-keyword=好中球
kn-keyword=好中球
en-keyword=NETs
kn-keyword=NETs
en-keyword=血管内皮細胞
kn-keyword=血管内皮細胞
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=12
article-no=
start-page=2650
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=High Mobility Group Box-1 and Blood-Brain Barrier Disruption
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Increasing evidence suggests that inflammatory responses are involved in the progression of brain injuries induced by a diverse range of insults, including ischemia, hemorrhage, trauma, epilepsy, and degenerative diseases. During the processes of inflammation, disruption of the blood–brain barrier (BBB) may play a critical role in the enhancement of inflammatory responses and may initiate brain damage because the BBB constitutes an interface between the brain parenchyma and the bloodstream containing blood cells and plasma. The BBB has a distinct structure compared with those in peripheral tissues: it is composed of vascular endothelial cells with tight junctions, numerous pericytes surrounding endothelial cells, astrocytic endfeet, and a basement membrane structure. Under physiological conditions, the BBB should function as an important element in the neurovascular unit (NVU). High mobility group box-1 (HMGB1), a nonhistone nuclear protein, is ubiquitously expressed in almost all kinds of cells. HMGB1 plays important roles in the maintenance of chromatin structure, the regulation of transcription activity, and DNA repair in nuclei. On the other hand, HMGB1 is considered to be a representative damage-associated molecular pattern (DAMP) because it is translocated and released extracellularly from different types of brain cells, including neurons and glia, contributing to the pathophysiology of many diseases in the central nervous system (CNS). The regulation of HMGB1 release or the neutralization of extracellular HMGB1 produces beneficial effects on brain injuries induced by ischemia, hemorrhage, trauma, epilepsy, and Alzheimer’s amyloidpathy in animal models and is associated with improvement of the neurological symptoms. In the present review, we focus on the dynamics of HMGB1 translocation in different disease conditions in the CNS and discuss the functional roles of extracellular HMGB1 in BBB disruption and brain inflammation. There might be common as well as distinct inflammatory processes for each CNS disease. This review will provide novel insights toward an improved understanding of a common pathophysiological process of CNS diseases, namely, BBB disruption mediated by HMGB1. It is proposed that HMGB1 might be an excellent target for the treatment of CNS diseases with BBB disruption.
en-copyright=
kn-copyright=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WangDengli
en-aut-sei=Wang
en-aut-mei=Dengli
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OusakaDaiki
en-aut-sei=Ousaka
en-aut-mei=Daiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=high mobility group box-1
kn-keyword=high mobility group box-1
en-keyword=blood-brain barrier
kn-keyword=blood-brain barrier
en-keyword=inflammation
kn-keyword=inflammation
en-keyword=stroke
kn-keyword=stroke
en-keyword=trauma
kn-keyword=trauma
en-keyword=vascular endothelial cell
kn-keyword=vascular endothelial cell
en-keyword=pericyte
kn-keyword=pericyte
en-keyword=monoclonal antibody
kn-keyword=monoclonal antibody
END

start-ver=1.4
cd-journal=joma
no-vol=132
cd-vols=
no-issue=1
article-no=
start-page=39
end-page=40
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 9th International DAMPs and Alarmins Symposium (9th iDEAs)
kn-title=第9回国際DAMPs と Alarmins シンポジウムを 開催して
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=西堀正洋
kn-aut-sei=西堀
kn-aut-mei=正洋
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学
END

start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=7
article-no=
start-page=627
end-page=640
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=201907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes.
en-copyright=
kn-copyright=

en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SumardikaI Wayan
en-aut-sei=Sumardika
en-aut-mei=I Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=InoueYusuke
en-aut-sei=Inoue
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IiokaHidekazu
en-aut-sei=Iioka
en-aut-mei=Hidekazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MitsuiYosuke
en-aut-sei=Mitsui
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SaitoKen
en-aut-sei=Saito
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=RumaI Made Winarsa
en-aut-sei=Ruma
en-aut-mei=I Made Winarsa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SatoHiroki
en-aut-sei=Sato
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YamauchiAkira
en-aut-sei=Yamauchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=YamamotoKen-ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=FutamiJunichiro
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ORCID=

en-aut-name=KuboMiyoko
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aut-affil-num=19
ORCID=

en-aut-name=PutrantoEndy Widya
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kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=MurakamiTakashi
en-aut-sei=Murakami
en-aut-mei=Takashi
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kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=LiuMing
en-aut-sei=Liu
en-aut-mei=Ming
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=HibinoToshihiko
en-aut-sei=Hibino
en-aut-mei=Toshihiko
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=KondoEisaku
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en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
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kn-aut-name=
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kn-aut-mei=
aut-affil-num=26
ORCID=

en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=

affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=

affil-num=6
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=7
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=9
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=

affil-num=12
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=18
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=19
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=20
en-affil=Department of Pediatrics, Dr. Sardjito Hospital/Faculty of Medicine, Universitas Gadjah Mada
kn-affil=

affil-num=21
en-affil=Department of Microbiology, Faculty of Medicine, Saitama Medical University
kn-affil=

affil-num=22
en-affil=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University
kn-affil=

affil-num=23
en-affil=Department of Dermatology, Tokyo Medical University
kn-affil=

affil-num=24
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=25
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=

affil-num=26
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=27
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=8
article-no=
start-page=e73640
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130821
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Neuropathic Pain in Rats with a Partial Sciatic Nerve Ligation Is Alleviated by Intravenous Injection of Monoclonal Antibody to High Mobility Group Box-1
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=High mobility group box-1 (HMGB1) is associated with the pathogenesis of inflammatory diseases. A previous study reported that intravenous injection of anti-HMGB1 monoclonal antibody significantly attenuated brain edema in a rat model of stroke, possibly by attenuating glial activation. Peripheral nerve injury leads to increased activity of glia in the spinal cord dorsal horn. Thus, it is possible that the anti-HMGB1 antibody could also be efficacious in attenuating peripheral nerve injury-induced pain. Following partial sciatic nerve ligation (PSNL), rats were treated with either anti-HMGB1 or control IgG. Intravenous treatment with anti-HMGB1 monoclonal antibody (2 mg/kg) significantly ameliorated PSNL-induced hind paw tactile hypersensitivity at 7, 14 and 21 days, but not 3 days, after ligation, whereas control IgG had no effect on tactile hypersensitivity. The expression of HMGB1 protein in the spinal dorsal horn was significantly increased 7, 14 and 21 days after PSNL; the efficacy of the anti-HMGB1 antibody is likely related to the presence of HMGB1 protein. Also, the injury-induced translocation of HMGB1 from the nucleus to the cytosol occurred mainly in dorsal horn neurons and not in astrocytes and microglia, indicating a neuronal source of HMGB1. Markers of astrocyte (glial fibrillary acidic protein (GFAP)), microglia (ionized calcium binding adaptor molecule 1 (Iba1)) and spinal neuron (cFos) activity were greatly increased in the ipsilateral dorsal horn side compared to the sham-operated side 21 days after PSNL. Anti-HMGB1 monoclonal antibody treatment significantly decreased the injury-induced expression of cFos and Iba1, but not GFAP. The results demonstrate that nerve injury evokes the synthesis and release of HMGB1 from spinal neurons, facilitating the activity of both microglia and neurons, which in turn leads to symptoms of neuropathic pain. Thus, the targeting of HMGB1 could be a useful therapeutic strategy in the treatment of chronic pain.
en-copyright=
kn-copyright=

en-aut-name=NakamuraYoki
en-aut-sei=Nakamura
en-aut-mei=Yoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MoriokaNorimitsu
en-aut-sei=Morioka
en-aut-mei=Norimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AbeHiromi
en-aut-sei=Abe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZhangFang Fang
en-aut-sei=Zhang
en-aut-mei=Fang Fang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=Hisaoka-NakashimaKazue
en-aut-sei=Hisaoka-Nakashima
en-aut-mei=Kazue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NakataYoshihiro
en-aut-sei=Nakata
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University

affil-num=2
en-affil=
kn-affil=Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University

affil-num=3
en-affil=
kn-affil=Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University

affil-num=4
en-affil=
kn-affil=Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University

affil-num=5
en-affil=
kn-affil=Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University

affil-num=6
en-affil=
kn-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmacological Sciences, Okayama University

affil-num=7
en-affil=
kn-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmacological Sciences, Okayama University

affil-num=8
en-affil=
kn-affil=Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University
END

start-ver=1.4
cd-journal=joma
no-vol=125
cd-vols=
no-issue=2
article-no=
start-page=97
end-page=102
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Anti‒high mobility group box-1 antibody therapy for traumatic brain injury
kn-title=外傷性脳傷害に対する抗HMGB-1抗体治療
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=OkumaYu
en-aut-sei=Okuma
en-aut-mei=Yu
kn-aut-name=大熊佑
kn-aut-sei=大熊
kn-aut-mei=佑
aut-affil-num=1
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=劉克約
kn-aut-sei=劉
kn-aut-mei=克約
aut-affil-num=2
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=和気秀徳
kn-aut-sei=和気
kn-aut-mei=秀徳
aut-affil-num=3
ORCID=

en-aut-name=HarumaJun
en-aut-sei=Haruma
en-aut-mei=Jun
kn-aut-name=春間純
kn-aut-sei=春間
kn-aut-mei=純
aut-affil-num=4
ORCID=

en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=吉野正
kn-aut-sei=吉野
kn-aut-mei=正
aut-affil-num=5
ORCID=

en-aut-name=OhtsukaAiji
en-aut-sei=Ohtsuka
en-aut-mei=Aiji
kn-aut-name=大塚愛二
kn-aut-sei=大塚
kn-aut-mei=愛二
aut-affil-num=6
ORCID=

en-aut-name=TakahashiHideo
en-aut-sei=Takahashi
en-aut-mei=Hideo
kn-aut-name=高橋英夫
kn-aut-sei=高橋
kn-aut-mei=英夫
aut-affil-num=7
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=森秀治
kn-aut-sei=森
kn-aut-mei=秀治
aut-affil-num=8
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=西堀正洋
kn-aut-sei=西堀
kn-aut-mei=正洋
aut-affil-num=9
ORCID=

en-aut-name=DateIsao
en-aut-sei=Date
en-aut-mei=Isao
kn-aut-name=伊達勲
kn-aut-sei=伊達
kn-aut-mei=勲
aut-affil-num=10
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 脳神経外科学

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 薬理学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 薬理学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 脳神経外科学

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 病理学（腫瘍病理）

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 人体構成学

affil-num=7
en-affil=
kn-affil=近畿大学医学部 薬理学

affil-num=8
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 就実大学薬学部

affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科薬理学

affil-num=10
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 脳神経外科学
en-keyword=HMGB-1
kn-keyword=HMGB-1
en-keyword=traumatic brain injury （頭部外傷）
kn-keyword=traumatic brain injury （頭部外傷）
en-keyword=secondary injury （二次的損傷）
kn-keyword=secondary injury （二次的損傷）
en-keyword=blood brain barrier （血液脳関門）
kn-keyword=blood brain barrier （血液脳関門）
END

start-ver=1.4
cd-journal=joma
no-vol=65
cd-vols=
no-issue=6
article-no=
start-page=369
end-page=377
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2011
dt-pub=201112
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Gene Expression and Localization of High-mobility Group Box Chromosomal Protein-1 (HMGB-1) in Human Osteoarthritic Cartilage
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We investigated the expression and localization of high-mobility group box chromosomal protein-1 (HMGB-1) in human osteoarthritic (OA) cartilage in relation to the histopathological grade of cartilage destruction, and examined the role of HMGB-1 in the regulation of proinflammatory cytokine expression in chondrocytes. An immunohistochemical study demonstrated that total HMGB-1-positive cell ratios increase as the Osteoarthritis Research Society International (OARSI) histological grade increased. The population of cytoplasmic HMGB-1-positive chondrocytes was especially increased in the deep layers of higher-grade cartilage. The ratios and localization of receptors for advanced glycation end products (RAGE) expression by chondrocytes in Grade 2, 3, and 4 were significantly higher than those in Grade 1. In vitro stimulation with IL-1β, but not TNFα, significantly upregulated the expression of HMGB-1 mRNA by human OA chondrocytes. Both IL-1β and TNFα promoted the translocation of HMGB-1 from nuclei to cytoplasm. IL-1β and TNFα secretions were stimulated at higher levels of HMGB-1. The results of our study suggest the involvement of HMGB-1 in the pathogenesis of cartilage destruction in OA.
en-copyright=
kn-copyright=

en-aut-name=TeradaChuji
en-aut-sei=Terada
en-aut-mei=Chuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YoshidaAki
en-aut-sei=Yoshida
en-aut-mei=Aki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NasuYoshihisa
en-aut-sei=Nasu
en-aut-mei=Yoshihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TomonoYasuko
en-aut-sei=Tomono
en-aut-mei=Yasuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TanakaMasato
en-aut-sei=Tanaka
en-aut-mei=Masato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakahashiHideo K.
en-aut-sei=Takahashi
en-aut-mei=Hideo K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NishidaKeiichiro
en-aut-sei=Nishida
en-aut-mei=Keiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Shigei Medical Research Institute

affil-num=6
en-affil=
kn-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=9
en-affil=
kn-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=10
en-affil=
kn-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=HMGB-1
kn-keyword=HMGB-1
en-keyword=RAGE
kn-keyword=RAGE
en-keyword=chondrocyte
kn-keyword=chondrocyte
en-keyword=osteoarthritis
kn-keyword=osteoarthritis
en-keyword=cartilage
kn-keyword=cartilage
END

start-ver=1.4
cd-journal=joma
no-vol=122
cd-vols=
no-issue=3
article-no=
start-page=275
end-page=277
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2010
dt-pub=20101201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Okayama Prefectural Culture Prize (Academic Category)
kn-title=岡山県文化賞（学術部門，医学分野）を受賞して
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=西堀正洋
kn-aut-sei=西堀
kn-aut-mei=正洋
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学
END

start-ver=1.4
cd-journal=joma
no-vol=59
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=9
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2005
dt-pub=200502
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Role of recA/RAD51 family proteins in mammals.
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=<p>DNA damage causes chromosomal instability leading to oncogenesis, apoptosis, and severe failure of cell functions. The DNA repair system includes base excision repair, nucleotide excision repair, mismatch repair, translesion replication, non-homologous end-joining, and recombinational repair. Homologous recombination performs the recombinational repair. The RAD51 gene is an ortholog of Esherichia coli recA, and the gene product Rad51 protein plays a central role in the homologous recombination. In mammals, 7 recA-like genes have been identified: RAD51, RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, XRCC3, and DMC1. These genes, with the exception of meiosis-specific DMC1, are essential for development in mammals. Disruption of the RAD51 gene leads to cell death, whereas RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, and XRCC3 genes (RAD51 paralogs) are not essential for viability of cells, but these gene-deficient cells exhibit a similar defective phenotype. Yeast two-hybrid analysis, co-immunoprecipitation, mutation analysis, and domain mapping of Rad51 and Rad51 paralogs have revealed protein-protein interactions among these gene products. Recent investigations have shown that Rad51 paralogs play a role not only in an early step, but also in a late step of homologous recombination. In addition, identification of alternative transcripts of some RAD51 paralogs may reflect the complexity of the homologous recombination system.</p>

en-copyright=
kn-copyright=

en-aut-name=KawabataMasahiro
en-aut-sei=Kawabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KawabataTeruyuki
en-aut-sei=Kawabata
en-aut-mei=Teruyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama University

affil-num=2
en-affil=
kn-affil=Okayama University

affil-num=3
en-affil=
kn-affil=Okayama University
en-keyword=RAD51
kn-keyword=RAD51
en-keyword=RAD51 paralogs
kn-keyword=RAD51 paralogs
en-keyword=recA
kn-keyword=recA
en-keyword=recombination
kn-keyword=recombination
en-keyword=DNA repair
kn-keyword=DNA repair
END

start-ver=1.4
cd-journal=joma
no-vol=63
cd-vols=
no-issue=1
article-no=
start-page=65
end-page=69
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2009
dt-pub=200902
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Specific Removal of Monocytes from Peripheral Blood of Septic Patients by Polymyxin B-immobilized Filter Column
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Lipopolysaccharide (LPS) is one of the major causes of septic shock. The polymyxin B-immobilized filter column (PMX) was developed for the adsorption of endotoxin by direct hemoperfusion and has been used for the treatment of LPS-induced septic shock. In this study, we demonstrated that PMX also specifically bound monocytes from the peripheral blood leukocytes of septic patients by mean of an analysis of bound cells using immunocytochemical and electron microscopic techniques. The specific removal of monocytes from septic patients may produce beneficial effects by reducing the interaction between monocytes and functionally associated cells including vascular endothelial cells.
en-copyright=
kn-copyright=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakahashiHide K.
en-aut-sei=Takahashi
en-aut-mei=Hide K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KatayamaHiroshi
en-aut-sei=Katayama
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SaitoShinya
en-aut-sei=Saito
en-aut-mei=Shinya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IwagakiHiromi
en-aut-sei=Iwagaki
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TanakaNoriaki
en-aut-sei=Tanaka
en-aut-mei=Noriaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MoritaKiyoshi
en-aut-sei=Morita
en-aut-mei=Kiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OhtsukaAiji
en-aut-sei=Ohtsuka
en-aut-mei=Aiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Department of Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Department of Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Department of Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Departments of Anesthesiology and Resuscitology,  Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=9
en-affil=
kn-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=septic shock
kn-keyword=septic shock
en-keyword=polymixin B-immobilized column
kn-keyword=polymixin B-immobilized column
en-keyword=monocyte
kn-keyword=monocyte
en-keyword=adsorptive removal
kn-keyword=adsorptive removal
END

start-ver=1.4
cd-journal=joma
no-vol=63
cd-vols=
no-issue=5
article-no=
start-page=249
end-page=262
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2009
dt-pub=200910
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=High mobility group box 1 complexed with heparin induced angiogenesis in a matrigel plug assay
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=<p>Angiogenesis involves complex processes mediated by several factors and is associated with inflammation and wound healing. High mobility group box 1 (HMGB1) is released from necrotic cells as well as macrophages and plays proinflammatory roles. In the present study, we examined whether HMGB1 would exhibit angiogenic activity in a matrigel plug assay in mice. HMGB1 in combination with heparin strongly induced angiogenesis, whereas neither HMGB1 nor heparin alone showed such angiogenic activity. The heparin-dependent induction of angiogenesis by HMGB1 was accompanied by increases in the expression of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor-A120 (VEGF-A120). It is likely that the dependence of the angiogenic activity of HMGB1 on heparin was due to the efficiency of the diffusion of the HMGB1-heparin complex from matrigel to the surrounding areas. VEGF-A165 possessing a heparin-binding domain showed a pattern of heparin-dependent angiogenic activity similar to that of HMGB1. The presence of heparin also inhibited the degradation of HMGB1 by plasmin in vitro. Taken together, these results suggested that HMGB1 in complex with heparin possesses remarkable angiogenic activity, probably through the induction of TNF-alpha and VEGF-A120.</p>
en-copyright=
kn-copyright=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakahashiHideo K.
en-aut-sei=Takahashi
en-aut-mei=Hideo K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Shujitsu University, School of Pharmacy

affil-num=3
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=angiogenesis
kn-keyword=angiogenesis
en-keyword=HMGB1
kn-keyword=HMGB1
en-keyword=heparin
kn-keyword=heparin
END

start-ver=1.4
cd-journal=joma
no-vol=63
cd-vols=
no-issue=4
article-no=
start-page=203
end-page=211
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2009
dt-pub=200908
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Establishment of in Vitro Binding Assay of High Mobility Group Box-1 and S100A12 to Receptor for Advanced Glycation Endproducts: Heparin's Effect on Binding
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=<p>Interaction between the receptor for advanced glycation end products (RAGE) and its ligands has been implicated in the pathogenesis of various inflammatory disorders. In this study, we establish an in vitro binding assay in which recombinant human high-mobility group box 1 (rhHMGB1) or recombinant human S100A12 (rhS100A12) immobilized on the microplate binds to recombinant soluble RAGE (rsRAGE). The rsRAGE binding to both rhHMGB1 and rhS100A12 was saturable and dependent on the immobilized ligands. The binding of rsRAGE to rhS100A12 depended on Ca2 and Zn2, whereas that to rhHMGB1 was not. Scatchard plot analysis showed that rsRAGE had higher affinity for rhHMGB1 than for rhS100A12. rsRAGE was demonstrated to bind to heparin, and rhS100A12, in the presence of Ca2, was also found to bind to heparin. We examined the effects of heparin preparations with different molecular sizesunfractionated native heparin (UFH), low molecular weight heparin (LMWH) 5000Da, and LMWH 3000Da on the binding of rsRAGE to rhHMGB1 and rhS100A12. All 3 preparations concentration-dependently inhibited the binding of rsRAGE to rhHMGB1 to a greater extent than did rhS100A12. These results suggested that heparin's anti-inflammatory effects can be partly explained by its blocking of the interaction between HMGB1 or S100A12 and RAGE. On the other hand, heparin would be a promising effective remedy against RAGE-related inflammatory disorders.</p>
en-copyright=
kn-copyright=

en-aut-name=LiuRui
en-aut-sei=Liu
en-aut-mei=Rui
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZhangJiyong
en-aut-sei=Zhang
en-aut-mei=Jiyong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IzushiYasuhisa
en-aut-sei=Izushi
en-aut-mei=Yasuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TakahashiHideo K.
en-aut-sei=Takahashi
en-aut-mei=Hideo K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=PengBo
en-aut-sei=Peng
en-aut-mei=Bo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Shujitsu University, School of Pharmacy

affil-num=3
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Shanghai University of Traditional Chinese Medicine

affil-num=9
en-affil=
kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=RAGE
kn-keyword=RAGE
en-keyword=HMGB1
kn-keyword=HMGB1
en-keyword=S100A12
kn-keyword=S100A12
en-keyword=heparin
kn-keyword=heparin
en-keyword=inflammation
kn-keyword=inflammation
END

start-ver=1.4
cd-journal=joma
no-vol=38
cd-vols=
no-issue=4
article-no=
start-page=367
end-page=374
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1984
dt-pub=198408
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The inhibition of substance P-induced histamine release from mast cells by 6, 7-dihydro-6, 8, 8, 10-tetramethyl-8H-pyrano-[3, 2-g] chromone-2-carboxylic acid (EAA).
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=<p>In the presence of extracellular Ca2+, 6,7-dihydro-6,8,8, 10-tetramethyl-8H-pyrano [3, 2-g] chromone-2-carboxylic acid (EAA) had an inhibitory effect on the substance P-induced histamine release from rat peritoneal mast cells. Not only Ca2+ but also Mg2+, Sr2+ and Ba2+ were effective in enhancing the activity of EAA. Marked tachyphylaxis to EAA developed irrespective of the presence or absence of extracellular Ca2+. Cross-tachyphylaxis was observed between EAA and disodium cromoglycate (DSCG). These results indicate that the mode of action of EAA is similar, but not identical, with that of DSCG.</p>

en-copyright=
kn-copyright=

en-aut-name=TsutsumiKoji
en-aut-sei=Tsutsumi
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SaekiKiyomi
en-aut-sei=Saeki
en-aut-mei=Kiyomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama  University

affil-num=2
en-affil=
kn-affil=Okayama University

affil-num=3
en-affil=
kn-affil=Okayama Univresity
en-keyword=6
kn-keyword=6
en-keyword=7-dihydro-6
kn-keyword=7-dihydro-6
en-keyword=8
kn-keyword=8
en-keyword=8
kn-keyword=8
en-keyword=10-tetramethyl-8H-pyrano(3
kn-keyword=10-tetramethyl-8H-pyrano(3
en-keyword= 2-g) chromone-2-carboxylic acid (EAA)
kn-keyword= 2-g) chromone-2-carboxylic acid (EAA)
en-keyword=disodium cromoglycate
kn-keyword=disodium cromoglycate
en-keyword=histamine release
kn-keyword=histamine release
en-keyword=alkaline-earth metal ions
kn-keyword=alkaline-earth metal ions
en-keyword=substance P
kn-keyword=substance P
END

start-ver=1.4
cd-journal=joma
no-vol=120
cd-vols=
no-issue=3
article-no=
start-page=271
end-page=277
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2008
dt-pub=20081201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats
kn-title=ラット中脳動脈閉塞・再灌流モデルにおける抗 HMGB1 単クローン抗体の治療効果
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=LiuKeyue
en-aut-sei=Liu
en-aut-mei=Keyue
kn-aut-name=劉克約
kn-aut-sei=劉
kn-aut-mei=克約
aut-affil-num=1
ORCID=

en-aut-name=MoriShuji
en-aut-sei=Mori
en-aut-mei=Shuji
kn-aut-name=森秀治
kn-aut-sei=森
kn-aut-mei=秀治
aut-affil-num=2
ORCID=

en-aut-name=TakahashiHideo
en-aut-sei=Takahashi
en-aut-mei=Hideo
kn-aut-name=高橋英夫
kn-aut-sei=高橋
kn-aut-mei=英夫
aut-affil-num=3
ORCID=

en-aut-name=TomonoYasuko
en-aut-sei=Tomono
en-aut-mei=Yasuko
kn-aut-name=友野靖子
kn-aut-sei=友野
kn-aut-mei=靖子
aut-affil-num=4
ORCID=

en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=和気秀徳
kn-aut-sei=和気
kn-aut-mei=秀徳
aut-affil-num=5
ORCID=

en-aut-name=KankeToru
en-aut-sei=Kanke
en-aut-mei=Toru
kn-aut-name=菅家徹
kn-aut-sei=菅家
kn-aut-mei=徹
aut-affil-num=6
ORCID=

en-aut-name=SatoYasuharu
en-aut-sei=Sato
en-aut-mei=Yasuharu
kn-aut-name=佐藤康晴
kn-aut-sei=佐藤
kn-aut-mei=康晴
aut-affil-num=7
ORCID=

en-aut-name=HiragaNorihito
en-aut-sei=Hiraga
en-aut-mei=Norihito
kn-aut-name=平賀憲人
kn-aut-sei=平賀
kn-aut-mei=憲人
aut-affil-num=8
ORCID=

en-aut-name=AdachiNaoto
en-aut-sei=Adachi
en-aut-mei=Naoto
kn-aut-name=足立尚登
kn-aut-sei=足立
kn-aut-mei=尚登
aut-affil-num=9
ORCID=

en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=吉野正
kn-aut-sei=吉野
kn-aut-mei=正
aut-affil-num=10
ORCID=

en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=西堀正洋
kn-aut-sei=西堀
kn-aut-mei=正洋
aut-affil-num=11
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学

affil-num=4
en-affil=
kn-affil=重井医学研究所

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学

affil-num=7
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　病理学（腫瘍病理）

affil-num=8
en-affil=
kn-affil=愛媛大学大学院　麻酔蘇生学

affil-num=9
en-affil=
kn-affil=愛媛大学大学院　麻酔蘇生学

affil-num=10
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　病理学（腫瘍病理）

affil-num=11
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　薬理学
en-keyword=抗体医薬
kn-keyword=抗体医薬
en-keyword=炎症
kn-keyword=炎症
en-keyword=HMGB1
kn-keyword=HMGB1
en-keyword=脳梗塞
kn-keyword=脳梗塞
en-keyword=血液脳関門
kn-keyword=血液脳関門
END

start-ver=1.4
cd-journal=joma
no-vol=113
cd-vols=
no-issue=2
article-no=
start-page=179
end-page=180
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2001
dt-pub=20010831
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=貯蔵型と誘導性ヒスタミン
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=西堀正洋
kn-aut-sei=西堀
kn-aut-mei=正洋
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯学総合研究科 機能制御学講座薬理学
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1985
dt-pub=19851231
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=異なった哺乳動物種の脳内ヒスタミン代謝回転:神経性ヒスタミン半減期の暗示
kn-title=Histamine turnover in the brain of different mammalian species: Implications for neuronal histamine half-life
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=西堀正洋
kn-aut-sei=西堀
kn-aut-mei=正洋
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
END