| 1.
論文 |
論文
|
Uesato, Ryoko ; Ishibashi, Yasuyuki ; Ohshika, Shusa ; Naraoka, Takuya ; Toh, Satoshi
概要:
Proteoglycans are one of the most important components of the extracellular matrix in the cartilage and the levels of proteoglycans. such as versican and aggrecan, increase during chondrogenesis. The purpose of this study was to
…
investigate the effect of exogenous proteoglycans from salmon nasal cartilage on chondrogenesis of mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow aspiration of rabbit femurs were induced to chondrogenic lineage using a pellet culture technique. Pellets were cultured in the medium with or without cell growth factors. with or without proteoglycans. or a combination of these agents. Pellets treated with cell growth factors became hypertrophic and showed lacuna formation. and synthesis of cartilage matrix was recognized histologically. The expression of type II collagen and aggrecan mRNA were decreased in pellets incubated with a combination of cell growth factors and proteoglycans, compared to those incubated with only cell growth factors. Exogenous proteoglycans may down-regulate the expression of cartilage-specific mRNA directly, or may interact with growth factors in the culture medium. As the increase of glycoprotein during chondrogenesis is important for determining the direction and degree of differentiation. exogenous proteoglycans may have a similar effect.
続きを見る
|
||||
| 2.
論文 |
論文
|
対馬, 史泰 ; 小野, 修一 ; 清野, 浩子 ; 森本, 公平 ; 大畑, 崇 ; 長畑, 守雄 ; 三浦, 弘行 ; 阿部, 由直 ; 対馬, 敬夫 ; 鎌田, 義正
概要:
肺癌診断に対して薄層CT (thin-sliceCT)による胸膜播種の術前診断が可能となってきたが,胸膜の良性病変との鑑別が困難な症例が存在する.肺癌の胸膜播種の診断能向上目的に.術前CTにて胸膜に病的所見の見られる症例について原発巣胸膜浸
…
潤所見を検討した.対象は2003年1月より2005年12月までに肺癌として手術が施行され,術前CTが施行された138例(男性84名,女性54名,38-82歳,平均66歳)である.肺癌の術前CTを2名の放射線科医で評価した.葉間あるいは胸壁胸膜(臓側/壁側)の病的所見(不整な肥厚,′ト粒状影,結節影)の有無を検討した.胸膜に所見の見られた症例について,原発巣の進展,周囲浸潤を示す所見を検討した.肺癌138例中,術中に播種の判明した例は6例(4.3%)であった.6例全例に病理組織学的に原発巣の胸膜浸潤が見られた.術前CTでは31例(22.5%)に胸隈に所見が見られ,実際に播種のあった6例中5例は葉間胸膜に小結節影を認めた.また,胸膜播種陽性例には術前の薄層CTにて全例に原発巣と胸膜との接触が認められ,特に原発巣の胸壁胸膜浸潤および肥厚所見は偽陽性例に対し胸膜播種例で高頻度であった.術前の薄層CTにおける播種陽性例と陰性例の原発巣胸膜所見に差を認めたことから,胸膜に病的所見が見られた場合,原発巣を詳細に評価することが肺癌術前の胸膜播種診断に有用と思われた.
続きを見る
|
||||
| 3.
論文 |
論文
|
佐藤, 江里 ; 田村, 綾女 ; 丹藤, 雄介 ; 須田, 俊宏 ; 中村, 光男 ; 山岸, 昌一
概要:
病歴の長い糖尿病患者において,アミラーゼ分泌の低下や障萎縮･線維化を呈する症例があることが報告されている.しかしこのような病態の動物モデルは現在確立されていない.また,終末糖化産物AGE,その受容体であるRAGEは糖尿病血管合併症に関与して
…
いるとされているが,陣-の影響は不明である.糖尿病における障外分泌障害とその機序を明らかにするため,加齢により障ラ氏島の線維化を生じる自然発症2型糖尿病モデル,SpontaneouslyDiabeticTorii(SDT)ラットにcaerulein急性輝炎を発症させ,糖尿病の発症および程度,降の線維化に変化を生じるか否か,同時に,RAGEの発現をRT-PCRにより検討した.結果,障炎による糖尿病発症および降の線維化,糖尿病発症前後および輝炎の有無によるRAGEの発現に変化は認めず,糖尿病ラットモデルにおける障障害とRAGEの関連は明らかではなかった.
続きを見る
|
||||
| 4.
論文 |
論文
|
Nakai, Makoto ; Yoshihara, Shuichi ; Morohashi, Hajime ; Ishido, Keinosuke ; Sasaki, Mutsuo
概要:
Hyaluronan (HA) is a major component of the pericellular matrix, and is implicated in cell adhesion, invasion. and tumor metastasis. We have reported that 4-methylumbelliferone (MU) inhibits HA synthesis by cultured skin
…
fibroblasts, melanoma cells, and pancreatic cancer cells. We focused in the present study, on mesothelioma which has an extremely poor prognosis, and in which no effective therapy has yet been established. We investigated dealing with this neoplasm whether MU and 4-methylesculetin (ME), a MU derivative, are able to inhibit HA synthesis by the mesothelioma cell line NCI-H2052. MU inhibited HA synthesis by about 20%, and ME by about 40%, in comparison with the control group. MU inhibited the adhesion of NCI-H2052 cells by about 30%, and ME by about 50%, compared with the untreated control. MU inhibited cell locomotion by about 30%. and ME by about 40%. It is suggested through these results suggest that MU and ME inhibit HA synthesis. adhesion, and locomotion by human mesothelioma cells and weaken their pericellular matrix, and that the inhibitory effect of ME on HA synthesis is stronger than that of MU. It is presumed that both MU and ME may have potential as new therapeutic or prophylactic medicines against mesothelioma.
続きを見る
|
||||
| 5.
論文 |
論文
|
Matsukura, Daisuke ; Yokoyama, Yoshihito ; Tanaka, Kanji ; Ozaki, Takashi ; Mizunuma, Hideki
概要:
The changes in proteoglycan (PG) expression and glycosaminoglycan (GAG) constituents in the intervillous space of the pregnancy-induced hypertension (PIR) placenta were investigated. PGs and GAGs were purified from the extract of
…
the placental intervillous space by the DEAE-Sephacel column and salt-concentration gradient method. and the GAG sugar chains were released by the actinase and cellulase treatments. The sugar chains from the placentas of normal pregnancy and PIR were compared by cellulose-acetate membrane electrophoresis. No difference was observed in the expressions of hyaluronic acid. heparan sulfate, and chondroitin sulfate. but a clear increase in the expression of dermatan sulfate (DS) in the placenta of the PIR was confirmed. An increase of the DS that specifically activates anticoagulants can be a body reaction to counteract the hemostatic condition observed in PIR.
続きを見る
|
||||
| 6.
論文 |
論文
|
Maruyama, Ikuro ; Ito, Takashi ; Hashiguchi, Teruto
概要:
Responses to stimuli in cellar level are diverse and such hierarchical as secretion of stored factors,synthesis of lipid
…
mediators and protein synthesis through genomic transcription. However, how can the cellsrespond in the case of necrosis? Recently a characteristic intranuclear protein, high-mobility group box 1 protein（HMGB1） is released from necrotic cells. The protein is an abundant nuclear protein with a dual functionboth inside and outside the cells. In physiological state, HMGB1 is present in the nucleus, and binds to DNA,playing a variety of crucial functions, including transcription and keeping the characteristic DNA architecture.However, the protein is released to extracellular space from most of necrotic cells, activated macrophages anddendritic cells. Out of the cells, HMGB1 acts as a signal of tissue damage and can promote infl ammation, immuneresponses, and results tissue regeneration. During sepsis and/or disseminated intravascular coagulation （DIC）,however, massive accumulation of HMGB1 in the systemic circulation will cause multiple organ failure （MOF）and subsequent lethal outcome. Thus HMGB1 in the systemic circulation has been considered as a lethalmediator of sepsis, and a promising therapeutic target for sepsis. Recently we identified that thrombomodulin（TM）, a natural anticoagulant glycoprotein expressed on the surface of endothelial cells, plays an importantrole in sequestering HMGB1. TM may prevent HMGB1 from reaching remote organs, thereby restrictingthe spectrum of HMGB1 action in the site of injury. Here we review recent progress made in defining thephysiological and pathological roles of HMGB1 and therapeutic strategies aimed at blocking circulatory HMGB1.
続きを見る
|
||||
| 7.
論文 |
論文
|
Sasaki, Takeshi
概要:
Human parvovirus B19 （B19） is single stranded DNA virus, that causes erythema infectinosum in infantand/or acute onset p
…
olyarthritis in adult. We present the evidence showing the role of B19 on the etiopathogy ofrheumatoid arthritis（ RA）.（ 1） B19 DNA could be frequently amplifi ed in the samples from rheumatoid joints. Thedetection B19 RNA and B19 protein VP1 was specific for RA, and positive at T cells, B cells, macrophages andfollicular dendritic cells in rheumatoid synovium. （ 2） B19 infection or transduction of B19 NS1gene caused TNFα,IL-6 and IL-8 production through activating AP1 and AP2 in macrophages or macrophage celll line U937. We alsofound Ku80 as a novel receptor for B19 on T cells, macrophages or erythroblasts. B19 used clathrin on the surface attheir cell entry and caused enhanced actin polymerization, resulting in the migration of T cells. （ 3） B19-transgenicmice became susceptible to type II collagen-induced polyarthritis that is a model of RA. We also experienced 12cases who developed RA after acute B19 infection. （ 4） Half of RA cases had a defective neutralizing ability to B19.
続きを見る
|
||||
| 8.
論文 |
論文
|
Kido, Hiroshi ; Mizuno, Dai ; Le, Quang Trong ; Chida, Junji ; Yamada, Hiroshi ; Okumura, Yuushi ; Yano, Mihiro
概要:
Human infl uenza virus causes an annual epidemic infection. After infl uenza virus infection in the airway,infection som
…
etimes spreads with severe neurologic complication and multiple organ failure, resulting in highmortality. In the process of viral spread from the lungs to other organs, signifi cant up-regulated trpsin was observedin various organs. Up-regulated trypsin eff ectively converted precursor of the viral envelope hemagglutinin（ HA） intoHA1 and HA2 subunits. The proteolytic activation of HA is a prerequisite for virus multiplication. Administration ofthe inhibitors of trypsin as new approaches for the treatment of infl uenza virus infection eff ectively suppressed viralmultiplication. Almost vaccines for infl uenza virus infection are administered i.m. or s.c., which induce IgG-mediatedprotection in the systemic immune compartment, but this immunization off ers insuffi cient protection on the mucosalsurface at the initial site of viral multiplication. To improve protective mucosal immunity, intranasal vaccinationhas been studied. The powerful mucosal adjuvants reported are toxin based, such as cholera toxin and Escherichiacoli heat-labile toxin, but these enterotoxins cause severe side eff ects. We recently found natural mucosal adjuvant,pulmonary surfactant, in the lungs. Intranasal administration of infl uenza vaccine combined with Surfacten, a modifi edpulmonary surfactant free of antigenic c-type lectins, induced high protective mucosal immunity in the airway andsystemic immune responses in the blood, the effi cacy of both protective immunities by Surfacten being equivalent tothose by cholera toxin. In this symposium, we reported the eff ects of Surfacten on mucosal and systemic immunities.
続きを見る
|
||||
| 9.
論文 |
論文
|
Kurachi, Makoto ; Kakimi, Kazuhiro ; Ueha, Satoshi ; Matsushima, Kouji
概要:
Memory CD8+ T cells generated during an immune response are long-lived and self-renewing, off eringenhanced host protect
…
ion against re-infection. However, how an antigen-specific population of memory T cells ismaintained throughout repetitive infections over potentially a lifetime is not known. Here we review the generationand maintenance of antigen-specifi c CD8+ T cells and introduce our recent data showing dynamic turnover of anantigen-specific memory T cell population during repeated antigen challenge in vivo. We demonstrated that aprimary response potentially occurs upon every recall response and fi nd that the skewed T-cell receptor （TCR）repertoire of pre-existing memory T cells is partly corrected by diversity in a newly formed （primary） population.Importantly, memory T cells generated in a more recent antigen encounter expand more vigorously in a subsequentrecall response. A primary response during re-challenge therefore restores both the TCR diversity and proliferativepotential of the memory T cell population. These findings indicate that memory T cell populations evolve overmultiple challenges, favoring memory T cells generated in more recent encounters, and suggest that these primarypopulations have essential roles in the perpetuation of antigen-specifi c T cell populations.
続きを見る
|
||||
| 10.
論文 |
論文
|
Ohteki, Toshiaki ; Kuwajima, Seiichi
概要:
Unmethylated CpG oligodeoxynucleotides （CpG） prevalent in bacteria and DNA viruses bind Toll-likereceptor（ TLR） 9 and di
…
rectly stimulate DCs, thereby activating the innate and adaptive immune responses. CpG ispotentially a powerful reagent for protective immunity against infection by a wide variety of pathogens, for cancerand allergy therapies, and for the development of prophylactic and therapeutic vaccines. Here we investigated therole of interleukin （IL）-15 in the activation of CpG-induced immune responses. We show that upon CpG-priming,both wild-type（ WT） and NK cell-depleted WT mice produce interleukin（ IL）-12 p70 and become resistant to a lethaldose of Listeria monocytogenes（ LM）, whereas IL-15-/- mice impair IL-12 p70 production and succumb to the infection.Notably, CpG-stimulated conventional dendritic cells （cDCs） are the major producer of both IL-15 and IL-12 p70,but cDCs do not produce IL-12 in the absence of plasmacytoid DCs（ pDCs） in vivo. Importantly, cDC-derived IL-15induces CD40 expression on cDCs, which interacts with CD40 ligand on pDCs, leading to CD40 cross-linking and IL-12production. Collectively, these fi ndings show that IL-15-dependent cross-talk between cDCs and pDCs is essential forCpG-induced immune activation（ recently published in Nat Immunol 2006;7:740-6）
続きを見る
|
||||
| 11.
論文 |
論文
|
Seya, Tsukasa ; Matsumoto, Misako ; Ebihara, Takashi ; Akazawa, Takashi
概要:
Double-stranded （ds）RNA-recognition receptors reside in the cytoplasm and membranes of cells. Thesereceptors are implica
…
ted in the differential screening of microbes by the host. Myeloid dendritic cells （mDCs）recognize and respond to polyI:C, an analog of dsRNA, by endosomal TLR3 and cytoplasmic MDA5. NK cells areinduced in vivo by the administration of polyI:C to mice and in vitro are reciprocally activated by mDCs, although themolecular mechanisms as yet undetermined. Here, we show that the TLR adapter TICAM-1 （TRIF） participates inmDC-derived antitumor NK activation. In a syngeneic mouse tumor implant model, intraperitoneal administration ofpolyI:C led to the retardation of tumor growth, which eff ect relied largely on NK activation. This NK-dependent tumorregression did not occur in TICAM-1-/- or IFNAR-/- mice, while a normal NK antitumor response was induced in PKR-/-,MyD88-/-, IFN-β-/- and wild-type mice. IFNAR was a prerequisite for the induction of IFN-α/β and TLR3. The lackof TICAM-1 did not aff ect IFN production but resulted in unresponsiveness to IL-12 production, mDC maturation andpolyI:C-mediated antitumor activity. This NK activation required NK-mDC contact in in vitro transwell analysis. NKantitumoractivity was successfully introduced into tumor-implanted mice by transferring mDCs expressing TICAM-1.Implanted tumor growth in IFNAR-/- mice was retarded by adoptively transferring polyI:C-treated TICACM-1-positivemDCs but not TICAM-1-/- mDCs. Thus, TICAM-1 rather than MDA5 in mDCs critically facilitated mDC-NK contactand activation of antitumor NK, resulting in the regression of low MHC-expressing tumors
続きを見る
|
||||
| 12.
論文 |
論文
|
Fujita, Takashi
概要:
Recent studies show the involvement of cytoplasmic RNA helicase family, RIG-I, MDA5 and LGP2 inantiviral innate immune r
…
esponses. RIG-I and MDA5 are primarily responsible for the detection of viral infectionand triggering activation cascade for type I interferon genes in many cell types. RIG-I consists of N-terminalCAspase Recruitment Domain (CARD) and a domain with signatures of DExD/H box helicase (helicase domain).Functional analyses revealed that the helicase domain detects viral RNA and CARD triggers the activation ofdownstream signaling cascade, including activation of transcription factors, NF-κB, IRF-3 and IRF-7. RIG-I bindsto double stranded (ds)RNA, however it does not simply function as a binding receptor for dsRNA, since RIG-Iwith disrupted ATP binding site is incapable of signaling. A model is proposed that in the absence of dsRNA,RIG-I forms “closed” conformation and upon binding to dsRNA, it conforms into “open” structure exposing CARD.We produced recombinant RIG-I protein using Baculo virus system and purified it to homogeneity. Biochemicalproperties, including dsRNA binding activity, ATPase activity and helicase activity, of recombinant RIG-I wereinvestigated. The results suggested that RIG-I requires certain structure of ligand RNA that is specifi c to viral (ornon-self) origin. Furthermore, we found evidence that RIG-I conforms a certain structure upon binding to dsRNA inthe presence of ATP. These results were consistent with the above model for activation of RIG-I. Furthermore, weobserved that RIG-I forms oligomers in virus-infected cells and artifi cial oligomerization of RIG-I CARD mimics virusinducedsignaling, resulting in the activation of interferon and other cytokine genes. These results highlight how viralreplication in cytoplasm is detected by RIG-I helicase and switch on signal cascades for initial antiviral responses.
続きを見る
|
||||
| 13.
論文 |
論文
|
Iwasaki, Yasumasa ; Tsugita, Makoto ; Taniguchi, Yoshimori ; Nigawara, Takeshi ; Takayasu, Shinobu ; Kawahara, Masayuki ; Suda, Toshihiro ; Hashimoto, Kozo
概要:
Cytokines is known to infl uence hormone synthesis and secretion. Indeed, some of the proinfl ammatorycytokines stimulat
…
e hormone release at the hypothalamic, pituitary, and peripheral endocrine organs. Recently, a newparadigm of immune-endocrine interaction has been emerging. We and others have shown that cytokines modify theeff ectiveness of hormone action. This is occurring via enhancement of receptor-mediated signaling, or modifi cation ofintracellular metabolism of hormones. In the latter case, we found that representative cytokines such as interleukin 1βand TNFα stimulate the expression of the glucocorticoid-activating enzyme 11β- ~ hydroxysteroid dehydrogenase type1（ 11βHSD1） and suppress that of the inactivating enzyme 11βHSD2, thus increasing the intracellular concentrationand action of glucocorticoids. In vascular smooth muscle cells, this mechanism is advantageous in preventing vascularcollapse during sepsis. We also found that, in hepatocytes, cytokines suppress the expression of the thyroid hormoneactivatingenzyme 5’-deiodinase type I. This may be responsible for the low T3 syndrome in critical illness.
続きを見る
|
||||
| 14.
論文 |
論文
|
Kageyama, Kazunori ; Hanada, Komaki ; Iwasaki, Yasumasa ; Sakihara, Satoru ; Nigawara, Takeshi ; Kasckow, John ; Suda, Toshihiro
概要:
Corticotropin-releasing factor （CRF） plays a central role in controlling the hypothalamic-pituitary-adrenalaxis during s
…
tressful periods. CRF, produced in the hypothalamic paraventricular nucleus （PVN） in response tostress, stimulates adrenocorticotropic hormone （ACTH） release in the anterior pituitary. ACTH then stimulatesglucocorticoid release from the adrenal glands. Glucocorticoid in turn inhibits hypothalamic PVN production of CRFand pituitary production of ACTH. We previously demonstrated that protein kinase A（ PKA） pathway takes a mainpart in producing CRF in the hypothalamus. A functional cAMP-response element（ CRE） on the 5’-promoter region isimportant to increase CRF gene expression. Glucocorticoids inhibit CRF promoter activity in the pituitary cells, whilein the placenta and the bed nucleus of the stria terminalis, glucocorticoids stimulate it. The eff ect of glucocorticoids onCRF gene, therefore, would be tissue specifi c. Although to study the mechanism regulating CRF transcription in thePVN has been the lack of availability of a representative cell line, a rat fetal hypothalamic cell line has been recentlyavailable. We found that forskolin-stimulated CRF gene transcription is mediated by CRE on the CRF 5’-promoterregion in the hypothalamic cells. Both PKA and, in part, p38 mitogen-activated protein kinase pathways contribute tothe forskolin-induced CRF promoter activity. Glucocorticoid-dependent repression of forskolin-stimulated CRF promoteractivity was localized to promoter sequences between －278 and －249 bp. Taken together, these fi ndings indicate thata negative glucocorticoid regulatory element is critical for the repression of CRF gene in the hypothalamic cells.
続きを見る
|
||||
| 15.
論文 |
論文
|
Sashinami, Hiroshi ; Kageyama, Kazunori ; Suda, Toshihiro ; Nakane, Akio
概要:
It is well known that corticotropin releasing factor （CRF） modulates immune response duringinfl ammation. We investigate
…
d the eff ect of CRF family peptides on host resistance to Listeria monocytogenes infectionin mice. The numbers of L. monoctyogenes in the organs of Ucn2-treated mice were dramatically increased comparedwith CRF- or Ucn-treated mice. CRF receptor type 2 is involved in the suppressive eff ect of Ucn2 on L. monocytogenesinfection. Interferon （IFN）-γ and tumor necrosis factor （TNF）-α production were decreased and interleukin （IL）-10 production was signifi cantly increased in the spleens of Ucn2-treated mice compared with those in Ucn2-untreatedcontrol mice. The eff ect of Ucn2 was canceled by depleting endogenous IL-10 using anti-IL-10 monoclonal antibodyand in IL-10 deficient mice. The expression and activation of signal transducers and activators of transcription3 （STAT3） were up-regulated and the expression and activation of STAT1 were down-regulated in the spleensfrom Ucn2-treated mice compared with vehicle-treated mice. Moreover, suppression of TNF-α production andaugmentation of IL-10 production and expression and activation of STAT3 by Ucn2 treatment were observed in heatkilledL. monocytogenes-stimulated macrophages. These results suggested that Urn2 suppresses host resistance to L.monocytogenes infection via up-regulation of IL-10 production.
続きを見る
|
||||
| 16.
論文 |
論文
|
Warner, Margaret ; Gustafsson, Jan-Åke
概要:
Estrogen has distinct functions in the immune system where it acts via ERα and HERβ respectively.Surprisingly, the defec
…
ts in the immune system which develop in the absence of either ERα or ERβ are quitedistinct from what develops in the absence of estrogen. We have found by studying mice in which either or bothestrogen receptors have been inactivated that the two estrogen receptors play distinct roles in the immune system.Loss of ERβ leads to chronic myeloid leukemia and loss of ERα leads to autoimmune disease. In mice which cannotsynthesize estrogen there is also autoimmune disease resembling Sjögren’s Syndrome. We plan to study these micefurther with the aim of fi nding the exact sites of action of the two receptors in the immune system and by usingspecifi c ligands for ERα. or ERβ to examine how specifi c parts of the immune system can be modifi ed. These studiesshould lead to improved treatment of patients with diseases of the immune system.
続きを見る
|
||||
| 17.
論文 |
論文
|
Cosgrove, Karen E. ; Shepherd, Ruth M. ; Dunne, Mark J.
概要:
Congenital Hyperinsulinism in Infancy （HI） is a potentially-lethal condition of neonates and duringearly childhood. For
…
many years the pathophysiology of this disorder was unknown. Recent advances in genetics,histopathology and molecule physiology have now revealed the causes of HI in a large cohort of patients. From defectsin ion channel subunit genes to lesions in the control of pancreatic B-cell metabolism and anaplerosis, the causes ofHI are both varied and numerous. However, in all cases they appear to share a common target protein - the ATPsensitiveK-channel. The function of these channels is not only critical to the control of healthy normal insulin-secretingcell function, but “activating” defects in these channels lead to permanent neonatal diabetes and type 2 diabetes. HIcan therefore arise through “channelopathies” of K-ATP channels: HI-KATP through gene defects in ABCC8 andKCNJ11 （Ch11.p15）; or as a result of “metabolopathies” through defects in the genes encoding glucokinase HI-GK（GCK, Ch.7p15-p13）, glutamate dehydrogenase HI-GDH （GLUD1, Ch.10q23.3） and Short-chain L-3-hydroxyacyl-CoAdehydrogenase HI-SCHAD（ HADHSC, Ch.4q22-q26）. Advances in the integration of genetic medicine and cell biologyhave provided key insights into the causes of HI, and this has been of key importance to the defi nition of pathogenesis.However, medical therapy for HI remains largely unchanged due to the availability of limited agents that are selectiveand specifi c for the termination of insulin release from β-cells. CHI can be a devastating disease, and in this reviewfocuses upon the relationship between the basis of HI and current / future therapies, including stem cells.
続きを見る
|
||||
| 18.
論文 |
論文
|
Wakui, Makoto ; Misaki, Naoko ; Suga, Sechiko ; Mao, Xia ; Lin, Yu-Fung ; Wu, Jie
概要:
Diabetes mellitus is a group of diseases characterized by high levels of blood glucose resulting from defectsin insulin
…
production, insulin action, or both. Diabetes patients usually have accompanying cardiovascular disorders.Sulfonylureas have been the leading oral antihyperglycemic agents for type 2 diabetes treatment, which currently stillconstitute the most popular anti-diabetic drugs. Nevertheless, concern has arisen over the side eff ects of sulfonylureason the cardiovascular system. Here we report that iptakalim, a novel cardiovascular ATP-sensitive potassium（ KATP）channel opener, closed rat pancreatic β-cell KATP channels and increased insulin release. Using whole-cell patch-clamprecordings, iptakalim depolarized β-cells, induced action potential fi ring and reduced pancreatic KATP channel currents.Using single-channel recordings, iptakalim reduced KATP channel open-probability independently of intracellular ATPconcentrations. We demonstrated that iptakalim elevated intracellular Ca2+ concentrations and increased insulin release asrevealed by fl uorescence imaging（ fura-2） and biochemical measurements, respectively. In addition, iptakalim signifi cantlyinhibited the open-probability of recombinant Kir6.2/SUR1 and Kir6.2FL4A（ a traffi cking mutant of the Kir6.2） channelsexpressed in transfected human embryonic kidney （HEK） 293 cells. Collectively, iptakalim, a cardiovascular KATPchannel opener, closes rat pancreatic β-cell KATP channels, which may result from direct inhibition of the Kir6.2 subunit.Therefore, iptakalim bi-directionally regulates KATP channels in cardiovascular and pancreatic tissues, and this uniquepharmacological property suggests iptakalim could be used as a new therapeutic strategy for the treatment of type 2diabetes with the potential benefi t in alleviating cardiac and/or vascular disorders frequently associated with diabetes.
続きを見る
|
||||
| 19.
論文 |
論文
|
Yagihashi, Soroku ; Yamagishi, Shin-Ichiro ; Mizukami, Hiroki ; Wada, Ryuichi
概要:
Accumulating evidence supports that proinflammatory processes are implicated in the establishmentof characteristic patho
…
logy in diabetic vascular and neurological complications. Altered cellular signaling duringinflammatory processes is a new target for the treatment of diabetic complications and there appear to be someattempts to explore the eff ects of thiazolidinedione, a ligand of peroxisome proliferating activator receptor（ PPAR）-γfor not only the treatment of diabetes itself but for the application to diabetic complications. We therefore explored theeff ects of PPAR-γ agonist, pioglitazone, on the experimental model of diabetic neuropathy. We found that pioglitazonesignifi cantly improved nerve conduction velocities and depressed protein kinase C activity. This is a new area for theexploration of eff ective treatment of diabetic complications that pose a considerable socioeconomic burden in the currentworld.
続きを見る
|
||||
| 20.
論文 |
論文
|
Lambert, David G. ; Williams, John P. ; Thompson, Jonathan P.
概要:
Clinically opioids are immunomodulatory where a general depression is reported. In addition, immunecells carry endogenou
…
s opioid peptides to sites of inflammation where opioid receptors on peripheral nerves areupregulated. Release of these endogenous opioids produces a degree of analgesia and completes the neuroimmune axis.The expression of opioid receptors on immune cells that deliver these opioid peptides, is contentious and is the basis ofthis short review. There are several papers reporting expression of opioid receptors on peripheral blood mononuclearcells （PBMCs） using a variety of in vitro biochemical/pharmacological techniques. Equally there are studies failingto detect these receptors. We have recently undertaken a detailed volunteer study to determine the expression ofclassical naloxone sensitive MOP, DOP and KOP and non-classical naloxone insensitive NOP receptors. We initiallyfocused our attention on the MOP receptor as the main clinical analgesic target. Using radioligand binding, FACSwith opioid receptor antibodies and PCR we have failed to detect all classical opioid receptors. In contrast, using PCRtechniques the non-classical NOP receptor is present in all volunteer samples examined along with its endogenouspeptide ligand nociceptin/orphanin F/Q （N/OFQ）. As both the peptide （N/OFQ） and receptor （NOP） are presentwe suggest that there may be a feedback loop such that peripherally delivered N/OFQ（ to infl ammatory site） wouldproduce both a classical analgesic response and then feedback to modulate PMBC function. The nature of that functionremains to be determined but could include release of further N/OFQ, activation of other immune cells or chemotaxis.Opioids have been used by man for centuries for the relief of pain. Morphine is the most widely used opioid in theclinic and is considered the gold standard to which all others are compared. In addition to producing analgesia, opioidadministration also produces other eff ects including; respiratory depression, gastrointestinal-inhibition, tolerance anddependence and immunomodulationbasic summaries see1-4）. Patients receiving long term opioid treatment display signs ofimmunodepression; it has been suggested that this may occur either as a direct eff ect of opioids on circulating immunecells or via a central action （see below）. Neuronal opioid receptors are up-regulated in peripheral infl ammation andStein and colleagues（ in particular） have shown that release of these endogenous opioids from circulating immune cellsproduces a degree of analgesia and complete the neuroimmune axis5）, i.e., immunomodulation of neuronal activity. Theexpression of opioid receptors on the circulating immune cells that deliver these opioid peptides remains unclear and isthe focus of this short review.
続きを見る
|
||||
| 21.
論文 |
論文
|
Hasan, Kazi N. ; Shoji, Masaru ; Sugimoto, Kazuhiro ; Tsutaya, Shoji ; Matsuda, Eriko ; Kudo, Ryoko ; Saito, Junko ; Nakaji, Shigeyuki ; Suda, Toshihiro ; Yasujima, Minoru
概要:
Candidate gene SNP study is a promising genetic approaches to complex common disorders. Argininevasopressin （AVP）, a pep
…
tide hormone released from the posterior pituitary, has been suggested to play importantroles in the regulation of blood pressure, glycogenolysis and platelet aggregation through G protein coupled V1areceptor （V1aR）. Thus, polymorphisms in the V1aR gene have been prospective as possible genetic markers foressential hypertension, type 2 diabetes mellitus and divergent platelet aggregation response to AVP. We identifi ed 4novel single nucleotide polymorphisms（ SNPs） in the promoter region of the V1aR gene and named according to theupstream locations such as, -6951G/A, -4112A/T, -3860T/C, and -242C/T. We investigated the association of 4 SNPs ofthe V1aR gene in 365 hypertensive and 255 healthy subjects, 186 T2DM patients and 188 non-diabetic control subjects（CS）, and 33 young healthy volunteers living in the Aomori prefecture. Signifi cant association was identifi ed betweenSNP at -6951 and hypertension in nonobese individuals, at -6951 and type 2 diabetes mellitus. Positive association wasalso identifi ed between nonobese hypertension and haplotype H3. Signifi cant association was demonstrated betweenSNP at -6951 and glycemic status in young healthy subjects. However, there was no signifi cant association in the AVPinducedplatelet aggregation with V1aR gene variants. The study suggests V1aR gene variants as increased riskfor hypertension in nonobese and type 2 diabetes mellitus in the Aomori population; however, might not be useful asgenetic markers for platelet aggregation heterogeneity.
続きを見る
|
||||
| 22.
論文 |
論文
|
Tsubo, Toshihito ; Fujita, Ayaka ; Hashiba, Eiji ; Ishihara, Hironori ; Hirota, Kazuyoshi
概要:
To investigated the eff ect of high volume continuous hemofi ltration（ HVHF） on the lung lesion observedwith transesopha
…
geal echocardiography （TEE） in endotoxin-induced acute lung injury in piglets. Piglets weighing20-30kg. Interventions: After endotoxin of 20 μg/kg intravenous administration, animals were randomly assigned tocontrol group（ n=7） and HVHF group（ n=7）. In both group, fi ltration was performed for fi ve hours and zero balanced.Filtration fl ow was 150 ml/hr in HVHF group and 0ml/hr in control group. The area of the lesion, resistive indexand maximal blood velocity in regional pulmonary artery were estimated using TEE. High mobility group B1 protein（HMGB1）, cortisol and catecholamine concentrations were measured in plasma at endotoxin 5 hours. Measurements ofblood gas, hemodynamics and TEE images were obtained every hour. The value of PaO2, density area and resistiveindex were 70.0±8.8 mmHg, 10.7±4.5 cm2 and 0.61±0.23 in control group and 120.4±20.3 mmHg, 3.3±2.0 cm2 and 0.88±0.22 in HVHF group at endotoxin 5 hours respectively（ mean±SD）. PaO2 and resistive index increased, and densityarea decreased in HVHF group than those of control group signifi cantly（ p<0.05, respectively）. There was signifi cantrelationship between PaO2 and density area （r=0.76, p<0.01）. There was no signifi cant diff erence in hemodynamics,HMGB1, cortisol and catecholamines concentration in plasma and morphometry between control group and HVHFgroup. In conclusion, these results suggest that non-specifi c blood purifi cation with HVHF improves arterial oxygenationand lung image observed with TEE in endotoxin-induced acute lung injury in piglets.
続きを見る
|
||||
| 23.
論文 |
論文
|
Imaizumi, Tadaatsu ; Mori, Fumiaki ; Yagihashi, Norito ; Kitamura, Hideo ; Sashinami, Hiroshi ; Suzuki, Koichi ; Yamashita, Koji ; Taima, Kageaki ; Kubota, Kosei ; Tanji, Kunikazu ; Sakaki, Hirotaka ; Matsumiya, Tomoh ; Yoshida, Hidemi ; Mariya, Yasushi ; Nakane, Hajime ; Tanaka, Hiroshi ; Takanashi, Shingo ; Wakabayashi, Koichi ; Yagihashi, Soroku ; Nakane, Akio ; Ito, Etsuro ; Okumura, Ken ; Kimura, Hiroto ; Satoh, Kei
概要:
Retinoic acid-inducible gene-I （RIG-I） is a cytoplasmic protein regarded as putative RNA helicase.Immunohistochemical st
…
udies revealed high levels of RIG-I expression in epidermic cells in psoriasis, in macrophagesin atherosclerotic lesions and in glomeruli of lupus nephritis. RIG-I expression was also demonstrated in macrophagesand vascular endothelial cells in experimental animals with Listeria or Hanta virus infection. In vitro studies using cellcultures revealed the expression of RIG-I, in various cells including endothelial cells, macrophages and astroglial cells, inresponse to the stimulation with cytokines, lipopolysaccharide, double-stranded RNA, Listeria monocytogenes, etc. Thestudies employing the overexpression or RNA interference suggested that RIG-I is involved in the regulation of cytokineexpression including CXCL10/IP-10 and CCL5/RANTES. These results suggest that RIG-I constitutes a part of theintracellular pathway for the regulation of infl ammatory and immune responses.
続きを見る
|
||||
| 24.
論文 |
論文
|
Tanji, Kunikazu ; Mori, Fumiaki ; Takahashi, Hitoshi ; Kamitani, Tetsu ; Wakabayashi, Koichi
概要:
NEDD8 is developmentally down-regulated ubiquitin-like protein, which can conjugate covalently to their target proteins
…
. Recently, we identifi ed NUB1 as a NEDD8-interacting protein, which is composed of 601 amino acid residues with a calculated molecular mass of 69.1 kDa. More recently, we showed that NUB1 is an interferon-induced protein and also recruits NEDD8 to the proteasome for degradation. Here, we performed a yeast two-hybrid screening using NUB1 as bait and isolated the cDNA of synphilin-1 from a human testis cDNA library. Synphilin-1 is a major component of inclusion bodies found in the brains of patients with α-synucleinopathies, including Parkinson’s disease. Our biochemical study showed that NUB1 directly interacts with synphilin-1 through its NEDD8-binding site. In addition, our immunohistochemical study showed that NUB1, as well as synphilin-1, accumulates in the inclusion bodies found in the brains of patients with α-synucleinopathies. These fi ndings imply that NUB1 plays a role in the formation of synphilin-1-positive inclusions.
続きを見る
|
||||
| 25.
論文 |
論文
|
Suzuki, Yasuyuki ; Daitoku, Kazuyuki ; Minakawa, Masahito ; Fukui, Kozo ; Fukuda, Ikuo
概要:
We have proved that Sivelestat preserved lung function after cardiopulmonary bypass（ CPB） in the rabbit model. We now r
…
eport the therapeutic efficacy of Sivelestat in the clinical case. From July 2005, 16 patients who underwent aortic arch replacements were enrolled in this study. Diagnosis included dissected aortic aneurysm in 6 patients, true aortic arch aneurysm in 8, and traumatic aortic arch aneurysm in 1 patient. We randomly divided these patients into two groups. In the Pre-Group（ Pre:n=8）, infusion of Sivelestat（ 0.2mg/kg/hr） was started before the operation; in the Post-Group（ Post:n=8）, it was started after the operation. Serum elastase activity, interleukin-8（ IL-8） levels were measured before the operation, before cessation of CPB and at the end of operation. Blood gas analyses were measured before the operation, at one and three hours after the CPB and the next morning. Because the preoperative P/F ratio（ arterial PO2/FiO2） varies with each case, the value of the P/F ratio at one hour after the CPB was calculated for 100%. Elastase activity of both groups were increased at the end of CPB（ Pre:8.9±10.6, Post:4.6± 3.5）, then returned to baseline level at end of operation（ NS）. IL-8 of both groups were increased at end of CPB, then in the Pre-Group decreased to 59.3± 25.0 pg/ml, but in the Post-Group increased to 97.9±45.7 pg/ml（ p=0.09）. The P/F ratio in the Pre- Group was well maintained from post CPB to next morning, but in the Post-Group was decreased three hours after the CPB （p<0.05）. In conclusion, these fi ndings showed that Sivelestat reduced the infl ammatory reaction associated with cardiopulmonary bypass, and prevented the pulmonary dysfunction caused by infl ammatory reaction.
続きを見る
|
||||
| 26.
論文 |
論文
|
Kon, Atsushi ; Igarashi, Manami ; Yamaguchi, Masanori ; Kojima, Kaoru
概要:
Chronic ultraviolet （UV） radiation results in photoaged skin characterized by deep wrinkle formation.Recent studies sugg
…
est that diminishment of anchoring fi brils（ AF）, stabilizing the association of the basement membraneto the underlying dermis, are involved in photoaged skin. Expression of COL7A1, encoding type VII collagen that is amajor component of AF, is also decreased in photoaged skin. In this study, we have investigated COL7A1 transcriptionby UV and UV-related cytokines involved in photoaged skin. Nuclear run-on assay, luciferase assay and gel shift assayrevealed that UV and UV-related cytokines（ TNF-α, IL-1β） tissue specifi cally downregulated COL7A1 transcription inepidermal keratinocytes, whereas COL7A1 transcription was upregulated by each modulator in dermal fi broblasts. Theresponsive element of each modulator was located between nucleotide -524 and -22 of COL7A1 promoter and AP-1 andNF-κB families band to this region. Taken together, these data strongly suggest that the downregulation of COL7A1transcription in epidermal keratinocytes, main cells expressing COL7A1 in the skin, and subsequent diminishment of AFare involved in photoaged skin. We also have discussed relation between these results and pathophysiology of wrinkleformation, characteristic feature of photoaged skin.
続きを見る
|
||||
| 27.
論文 |
論文
|
Mori, Kazuyuki ; Yoshikawa, Kazuaki ; Saitoh, Hideki ; Kudoh, Seiji ; Okamoto, Akiko ; Imai, Atsushi ; Ishimura, Hirofumi ; Hatakeyama, Shingo ; Hagisawa, Shigeru ; Iwabuchi, Ikuya ; Yoneyama, Takahiro ; Koie, Takuya ; Yamato, Takashi ; Yokomizo, Hidehiro ; Naka, Takashi ; Yano, Ikuya ; Ohyama, Chikara
概要:
Bacillus Calmette-Guerin（ BCG） has been widely accepted as an eff ective treatment for CIS and superfi cial carcinoma o
…
f the bladder. However, it has considerable side eff ects and toxicity. We thought if eff ective bacterial cell wall elements as substitutes for live bacteria were identifi ed, useful treatment with lower toxicity while maintaining strong anti-tumor eff ects might be possible. For these reasons we generated a nano-particulated BCG complex, which does not contain live bacteria. Here, we present its direct in vitro anti-tumor eff ect on bladder cancer cell lines. Tokyo 172 BCG sub-strain was disrupted by French press with monitoring the particle distribution by the particle analyzer. After removing the not-disrupted bacteria by centrifuge at 6,800×g, supernatant was centrifuged at 18,000×g. Then the supernatant（ Sup） and the precipitate（ CW） were lyophilyzed to obtain nano-particulated BCG complex. Bladder cancer cell lines, J82 and KK47, were co-cultured with BCG, Sup, CW or Sup+CW（ mix） for 5 days, then viable cell numbers were counted. In J82 cells, when separately added to the culture medium, both CW and Sup reduced cell number to about 70% of control cells. While they were mixed together, they reduced cell number equally compared with BCG; 59.2% （mix） vs 60.2%（ BCG） in J82 cells, 67.3% vs 68.8% in KK47 cells. These preliminary in vitro experiments demonstrated the identical direct anti-tumor eff ect of nano-particulated BCG to that of live BCG. In vivo tumor assays are warranted for clinical application of nano-particulated BCG.
続きを見る
|
||||
| 28.
論文 |
論文
|
Maruyama, Atsushi ; Itoh, Ken
概要:
NF-E2-related factor 2 （Nrf2） regulates the coordinate induction of phase 2 detoxifying and antioxidantenzymes in respon
…
se to xenobiotics and oxidative stress via antioxidant responsive element. Nrf2 knockout mice arehighly susceptible to the acute toxicity generated by acetaminophen, butylated hydroxytoluene or hyperoxia and tocarcinogenesis induced by benzo[a]pyrene. Recently, it becomes increasingly evident that Nrf2 also plays essential rolesin the protection against infl ammation. Nrf2 regulates the infl ammation during carrageenin-induced pleurisy and lunginfl ammation, wound healing in skin, and dextran sulfate-induced colitis. Nrf2 knockout mice are also susceptible toendotoxin-induced septic shock and allergen-induced asthma. Using carrageenin-induced pleurisy and porcine neutrophilelastase-induced lung injury models, we proposed that this anti-infl ammatory action of Nrf2 relies on the activities inmacrophages. In macrophages, Nrf2 modulates the infl ammatory response by up-regulating a range of anti-oxidative andanti-infl ammatory enzymes, such as CD36 and secretory leukoprotease inhibitor（ SLPI）. CD36 is a macrophage classB scavenger receptor involved in the uptake of apoptotic neutrophils and microorganisms such as Staphylococcus aureus.Thus, Nrf2 may play important roles in the protection of infl ammation and innate immune response.
続きを見る
|
||||
| 29.
論文 |
論文
|
Kusumi, Akinori ; Sakaki, Hirotaka ; Kusumi, Tomomi ; Nakagawa, Hiroshi ; Kubota, Kosei ; Oda, Mitsuo ; Satoh, Hisashi ; Kimura, Hiroto
概要:
The application of mechanical stress is known to be the unique method of analyses on bone metabolismand remodeling in vi
…
tro and in vivo. We have investigated on the effects of the application of cyclic tensile strain（CTS） on the syntheses of bone metabolic factors from the normal human osteoblasts in vitro. In this study, we foundthat diff erent passage numbers aff ected synthesis of CTS-induced factors from osteoblasts in vitro. Osteoblasts werestimulated with the application of CTS for 3 days, 4 hrs a day. Then, it was found that the application of CTS increasednitric oxide（ NO） production, the expression of cyclooxygenase 2（ Cox-2） mRNA, and synthesis of osteopontin（ OPN）from osteoblasts during serial passage. However, CTS-induced osteoprotegerin（ OPG） synthesis from osteoblasts wasshown to change at diff erent passage numbers. In short, increasing at the 3rd passage, CTS-induced OPG synthesis fromosteoblasts decreased at the 5th passage. While, though soluble RANKL（ sRANKL） release by the application of CTSdecreased at 1st passage and did not change at the 5th passage, the expression of receptor activator of nuclear factor-κBligand（ RANKL） mRNA increased in osteoblasts at the 5th passage, decreasing in those at the 3rd passage. The increaseon OPN synthesis the expression of Cox-2 mRNA, and NO production from osteoblasts by the application of CTS wasnot aff ected during serial passage. Analyzing on the activity of the p38 mitogen-activated protein kinase（ p38 MAPK）in osteoblasts with or without the application of CTS, the p38 MAPK activity in osteoblasts at the 3rd passage inhibitedin compared with that at the 3rd passage. From these results, we should use osteoblasts at the 1st passage whenanalyzing on CTS-induced OPG synthesis with normal human osteoblasts. It is suggested that the regulation of CTSinducedOPG synthesis might be aff ected by aging of osteoblasts.
続きを見る
|
||||
| 30.
論文 |
論文
|
Noto, Yuka ; Kudo, Mihoko ; Sato, Tetsumi ; Ebina, Masako ; Hirota, Kazuyoshi
概要:
Massage therapy promotes psychosocial relaxation and reduce stress. In addition, this therapy has beenreported to improv
…
e immune function. Although evaluation of psychosocial status has been performed with subjectivepsychological tests such as State-Trait Anxiety Inventory （STAI）, subjective psychological tests are of limited valueif the subjects fail to report reliably. Salivary biomarkers have been recently suggested as useful objective indicatorsfor assessing psychosocial status. To determine whether salivary biomarkers are useful objective indices for assessingeff ects of back massage on psychological status in 25 young healthy female volunteers, we measured heart rate andsalivary biomarkers（ α-amylase, cortisol and chromogranin-A） and assessed STAI score before and after back massage.Back massage significantly reduced heart rate from 73.4±11.8 to 69.8±11.2 and STAI from 41.0±6.0 to 32.3±4.9. Incontrast salivary chromogranin-A signifi cantly increased from 2.93±2.21 to 5.29±5.46 pmol/mg protein whilst salivaryα-amylase and cortisol did not change. Therefore, salivary biomarkers tested may not indicate changes in psychologicalrelaxation following back massage. Massage therapy has been reported to not only reduce psychosocial stress butalso enhance immune functions in cancer patients. In the present study, massage therapy significantly increasedchromogranin-A release. As several reports clearly show that chromogranin-A has antibacterial and antifungalactivities, back massage may increase host defense with salivary chromogranin-A release against oral microbial invasion.
続きを見る
|
||||
| 31.
論文 |
論文
|
Sakihara, Satoru ; Kageyama, Kazunori ; Nigawara, Takeshi ; Hanada, Komaki ; Suda, Toshihiro
概要:
Corticotropin-releasing factor （CRF） is primary regulator of hypothalamus-pituitary-adrenal（ HPA） axis,which is activate
…
d by various types of stress. Starvation is also a potent activating factor of CRF. Because theperipheral energy store refl ects on plasma levels of leptin, secreted from adipose tissue, it is presumed that leptin maybe involved in the CRF activity during starvation. Indeed, the attenuation of CRF or HPA axis activity by leptintreatment has been demonstrated in several reports. While many studies indicate the leptins involvement in CRFactivity, its precise regulation has not been elucidated. The aim of this study is to determine the impact of leptin onthe hypothalamic CRF neuron. To exclude the other hypothalamic factors, associated with leptins central eff ect, weemployed the in vitro study using immortalized CRF expressing neuron（ IVB cell）. Since the mRNA expression of longformleptin receptor was detected clearly in IVB cell with RT-PCR, we next investigated the impact of leptin on this cell.IVB cell was treated with leptin in diff erent concentrations and periods, then, the mRNA expression and the promoteractivity of CRF were analyzed with real-time PCR and luciferase assay, respectively. In result, leptin suppressed CRFpromoter activity with dose- and time- dependent manner in IVB cell. This indicates that leptin can suppress the CRFtranscription directly in hypothalamus. Our result might explain the mechanism partially how leptin attenuate theactivation of CRF or HPA axis induced by stress or starvation.
続きを見る
|
||||
| 32.
論文 |
論文
|
Nigawara, Takeshi ; Sakihara, Satoru ; Kageyama, kazunori ; Terui, Ken ; Fukuda, Yoshiko ; Kawashima, Shoko ; Takayasu, Shinobu ; Moriyama, Takako ; Kawahara, Masayuki ; Korekawa, Ayumi ; Yamashita, Maki ; Kohsaka, Akira ; Kakizaki, Yoshifumi ; Suda, Toshihiro
|
||||
| 33.
論文 |
論文
|
Tonosaki, Yoshikazu ; Sugiura, Yasuo ; Roubos, Eric W.
概要:
It is well-known that α-melanophore-stimulating hormone （α-MSH） release from the amphibian parsintermedia（ PI） depends o
…
n the light condition of the animal’s background. In the present study, we present two newfunctions of α-MSH in amphibians and mammals. In Xenopus laevis, we show that temperatures below 8 ℃ stimulateα-MSH secretion of the PI and skin darkening, with a maximum at 5 ℃, under regulation of the hypothalamus rule,independently from the illumination state of the background. The cold-induced α-MSH release of the PI was inhibited byneuropeptide-Y-producing suprachiasmatic-melanotrope-inhibiting neurons in the ventrolateral area of the suprachiasmaticnucleus but increasely in thyrotropin-releasing-hormene-containing neurons of the magnocellular nucleus. It is knownthat intracerebroventricular（ ICV） administration of a low dose of interleukin-1β（ IL-1β） induces hyperalgesia in ratand that this eff ect can be inhibited by α-MSH. To identify the part of the brain that is aff ected by hyperalgesiainducingIL-1β and the site of α-MSH concerned, we have examined Fos expression in the brain in response to ICVmicroinjection of α-MSH and/or IL-1β. Following injection of 10 pg IL-1β, hyperalgesia was induced and Fos becameexpressed in the paraventricular nucleus（ PVN） of the hypothalamus and in the arcuate nucleus（ ARC）, which containsα-MSH-producing neurons. ICV co-injection of IL-1β ・ with 30 ng α-MSH fully inhibited both hyperalgesia and Fosexpression in the PVN and the ARC. We conclude that PVN neurons are activated by hyperalgesic IL-1β and proposethat this eff ect is abolished by α-MSH released from the ARC but not from the pituitary gland.
続きを見る
|
||||
| 34.
論文 |
論文
|
Hu, Dong-Liang ; Omoe, Katsuhiko ; Narita, Koji ; Shinagawa, Kunihiro ; Nakane, Akio
概要:
To develop a Staphylococcus aureus vaccine, we constructed and expressed a non-toxic mutant staphylococcalenterotoxin C（
…
mSEC） and investigated whether immunization with mSEC can protect against S. aureus infection. Micewere immunized with mSEC and challenged with viable S. aureus. Bacteria counts in the organs in mSEC-immunizedmice were significantly lower and the survival rate was higher than those of the control group. mSEC vaccinationinduced the production of T-helper 2 type antibodies. The production of interleukin-10（ IL-10） and IL-4 in vaccinatedmice was signifi cantly higher compared with the control group, whereas the production of gamma interferon （IFN-γ.）was signifi cantly decreased in the vaccinated mice. Furthermore, IFN-γ.and tumor necrosis factor-α・ production in vitrowas signifi cantly inhibited by the sera from mSEC-vaccinated mice but not by those from control mice. These resultssuggest that vaccination with mSEC provides protection against S. aureus infection. SEC neutralizing antibodies and theIL-10 and IL-4 induction might play important role for the protection.
続きを見る
|
||||
| 35.
論文 |
論文
|
Hu, Dong-Liang ; Suga, Yochiko ; Omoe, Katsuhiko ; Abe, Yoshinao ; Shinagawa, Kunihiro ; Wakui, Makoto ; Nakane, Akio
概要:
To clarify whether SEA can aff ect any changes of cellular signalling pathways in intestinal epithelial cells, weperform
…
ed experiments to see if SEA can modulate the intracellular signaling pathway in intestinal epithelial cells. Wedemonstrate here that SEA induces an increase in intracellular calcium（ ［Ca2+］i） in human intestinal epithelial cells andthe［ Ca2+］i is released from intracellular stores. SEA-induced increase of［ Ca2+］i was clearly inhibited by treatment witha nitric oxide synthase（ NOS） inhibitor, NG-monomethyl-L-arginine. Intestinal epithelial cells express endothelial NOS（eNOS） in resting cell condition, and express inducible NOS（ iNOS） after stimulating with tumor necrosis factor（ TNF）-α. TNF-α-pretreated cells showed a signifi cant increase in［ Ca2+］i that was also inhibited by the NOS inhibitor. Theseresults demonstrate that SEA induces an increase in intracellular Ca2+ concentration in human intestinal epithelial cells,and the expressions of both eNOS and iNOS could be responsible for the increase in intracellular Ca2+ concentration inthe cells induced by SEA. It is important to study the relationship of NOS expression, Ca2+ signal pathway and emesisfor understanding the mechanism of SEA-induced food poisoning.
続きを見る
|
||||
| 36.
論文 |
論文
|
Narita, Koji ; Hu, Dong-Liang ; Tsuji, Takao ; Nakane, Akio
概要:
Infection caused by methicillin-resistant Staphylococcus aureus （MRSA） has been the most commonlyacquired types of nosoc
…
omial infections. It was reported that anterior nares are the major reservoir of S. aureus andthe source of 80% of S. aureus bacteremia is endogenous. Considering these facts, elimination and reduction of nasalcarriage are thought to be eff ective protection against systemic S. aureus infection and nosocomial infection. Toxic shocksyndrome toxin 1（ TSST-1） is one of superantigens secreted by S. aureus. Previously, it was reported that mutant form（H135A） of TSST-1（ mTSST-1） was shown to be nontoxic, and subcutaneous vaccination with mTSST-1 could protectagainst systemic S. aureus infection in a mouse model. In this study, we investigated the protective eff ect of intranasalvaccination with mTSST-1 supplemented with non-toxic mutant（ H44A） Escherichia coli heat labile toxin（ mLT） as amucosal adjuvant. The results demonstrated that intranasal immunization with mTSST-1 plus mLT could efficientlyinduce production of anti-TSST-1 antibodies in sera and also induce anti-TSST-1 IgA production in bronchoalveolar lavagefl uids（ BALF） of vaccinated mice. In nasal-associated lymphoid tissues（ NALT） of vaccinated mice, anti-TSST-1 IgAsecreting cells were signifi cantly increased. To evaluate of the protective eff ect of this vaccine against systemic S. aureusinfection, BALB/c mice were vaccinated with mTSST-1 plus mLT and challenged with clinical isolated S. aureus 834intravenously. Bacterial numbers in spleen and liver, and cumulative mortality rate of vaccinated mice were lower thanthose of control mice. We further developed a mouse model of nasal S. aureus colonization. S. aureus bacterial numbers innasal cavity of vaccinated mice were signifi cantly reduced compared with those of control mice. These results indicatethat intranasal immunization with mTSST-1 plus mLT is able to induce systemic and mucous immune responses and ofprovide protection against systemic S. aureus infection and nasal colonization.
続きを見る
|
||||
| 37.
論文 |
論文
|
Sashinami, Hiroshi ; Takagaki, Keiichi ; Nakane, Akio
概要:
Proteoglycans （PGs） are complex glycohydrates, which are widely distributed in connective tissues andon the cell surface
…
of mammalian tissues. We investigated the effect of PG extracted from salmon cartilage oncytokine responses to stimulation with heat-killed Escherichia coli（ HKEC） in a mouse macrophage cell line, RAW264.7.PG exhibited the suppression of tumor necrosis factor（ TNF）-α production and enhancement of interleukin（ IL）-10production compared with chondroitin 4 sulfate（ C4S） and chondroitin 6 sulfate（ C6S）. PG, C4S and C6S suppressedHKEC-induced Toll-like receptor 4（ TLR4） and inducible nitric oxide synthase（ iNOS） expression dose-dependentlyand the PG showed the strongest suppressive effect among 3 compounds. Only PG dramatically up-regulated theexpression of signal transducers and activators of transcription 3（ STAT3） and the phosphorylation of STAT3 in mousemacrophages. Our results showed strong suppression of PG on infl ammatory response and suggested that the novelinteraction might exist between the extracellular matrix and immune system.
続きを見る
|
||||
| 38.
論文 |
論文
|
Hiraga, Hiroto ; Sashinami, Hiroshi ; Hu, Dong-Liang ; Ishiguro, Yoh ; Wakabayashi, Koichi ; Munakata, Akihiro ; Nakane, Akio
概要:
Dietary vitamin A is an essential precursor of tissue retinol, which participates in a variety of biological processes
…
including innate immunity. Functions of vitamin A mainly depend on retinoic acid（ RA）, principally all-trans- RA （atRA） and 9-cis-RA. We assessed whether atRA is benefi cial in host resistance against bacterial infections or not. Vitamin A-defi cient（ VAD） mice were highly susceptible to infection with Listeria monocytogenes. Pre-treatment with atRA enhanced host resistance against L. monocytogenes infection in both VAD and VAS mice. Interferon（ IFN） -γ production in atRA pre-treated VAS mice was not higher compared with the control VAD mice. The eff ect of atRA was independent of T cells and B cells. The bactericidal activity in macrophages obtained from atRA pre-treated VAS mice was almost the same level compared with the control VAS mice. Our results demonstrated that the treatment with atRA is benefi cial for host resistance against L. monocytogenes infection in the early phase and suggested a new therapeutic possibility of atRA in bacterial infections.
続きを見る
|
||||
| 39.
論文 |
論文
|
Kachi, Takashi
概要:
Various aspects of pineal structures and functions have been reviewed. mainly relating to our ownobservations and experiments. The pineal gland shows high amplitude circadian rhythms in cellular and metabolicactivities. which are
…
changeable under various circumstances. The pineal hormone appears to participate in the body'sadaptive regulatory system mostly by cooperative and modulatory mechanisms. particularly in relation to environmentalchanges including stress/invasion. timing of physiological processes including reproductive activities. and possiblyexogenous and endogenous pathological changes such as inflammatory disease and tumor. Pineal effects are variabledue to the sensitivity/state of target mechanisms. For example. the pinealectomy effects on adreno-medullary adrenalinecells were more evident in comparison with the 'sham-pinealectomy' group than the normal group, and the pinealectomyeffects on female reproductive activities were age-dependent. In any case, the pineal hormone retains physiologicalfunctions at least till middle age. Pineal actions are mainly inhibitory. but can be also stimulatory as shown in immuneregulatory mechanisms. It has long been known that big differences in pineal structures and functions exist betweenmammals and submammals and that mammals show characteristic development of the brain, autonomic nervous systemand unique style of reproduction including pregnancy and suckling. These and other related results seem to support ahypothetical view that the pineal hormone was involved in drastic reorganization of the regulatory system occurred inthe evolutional process from submammals to mammals and became participated in the system which regulates complexbody mechanisms in mammals.
続きを見る
|
||||
| 40.
論文 |
論文
|
Sakuma, Yasuo
概要:
Distinctive sex diff erences in reproductive behavior and physiology have been attributed not to diff erencesin hormones gonad secretes in each sex but differences in particular brain structures. Interestingly enough, brainsex
…
difference is determined mostly by gonadal hormones during ontogeny independent of genetic sex. In manylaboratory mammals, brain sex can be manipulated at a particular stage of ontogeny called critical period for brain sexdiff erentiation, by endocrine treatments. Thus, neonatal orchidectomy or administration of gonadal hormones to femalepups reverses brain sex phenotype which culminates in sex-specifi c functions. The early, transient exposure to gonadalhormones or its absence leaves indelible marks on brain phenotype. This organizing action of gonadal hormones,combined with activational action of the hormones after puberty, accomplishes sex specific functions. Brain wouldundergo sex diff erentiation through neurogenesis, migration, or survival in addition to regulation of ion channels andother functional molecule. Two distinct structures, the sexually dimorphic nucleus of the preoptic area, which is largerin male rats than in males and the anteroventral periventricular nucleus, which furnish opposite characteristics, willprovide good opportunity to understand the mechanism of brain sex diff erentiation.
続きを見る
|
||||
| 41.
論文 |
論文
|
Kachi, Takashi ; Kachi, Hitomi
概要:
Our primary concern in this review is to give possible explanations and pose new questions on the phenomenaconcerning effects of neonatal estrogen exposure on the development and functions of reproductive organs and immunemechanisms
…
particularly in male animals, in the light of new findings and cencepts. At first, our own experimental resultson the pathological changes in the epididymis and testis in neonatally estrogenized mice have been presented. The resultsof our first experiment showed that neonatal single injection of 10 flg of estradiol benzoate induced marked inflammatorychanges in the epididymis and testis, in which the initial pathological change occurred concomitantly with the appearanceof sperms in the epididymal duct. The second experiment showed that such epididymo-testicular changes did not occurwhen the testis was removed or neonatal estrogen was followed by testosterone. From these results, a possibility wassuggested that a hormone-related autoimmune mechanism might participate in such changes. Relating to these, variousreports concerning effects of neonatal estrogen treatment, either alone or with concommitent treatment with androgen.on the development and functions of reproductive organs and immune mechanisms in the adolescent or adult have beenreviewed. In addition, advances in the related areas, such as estrogen-related mechanisms in the development andfunctions of reproductive organs and immune mechanisms including autoimmune disease mechanisms. gender differencesand the role of CD25+ CD4+ T lymphocytes have also been reviewed briefly.
続きを見る
|
||||
| 42.
論文 |
論文
|
Takemori, Nobuo
概要:
The omentum contains peculiar lymphoid tissues termed omental milky spots. In NZB mice, omental milkyspots show extramed
…
ullary neutrophilic myelopoiesis and mgakaryopoiesis. Similar milky spots（ splenoportal milkyspots）, which also show similar hematopoiesis, are present in the splenoportal fat band developing along the splenicartery. The splenoportal fat band contains sporadic aberrant spleens. In addition, transitional forms between splenoportalmilky spots and aberrant spleens are occasionally present in the fat band. These three types of lymphoid tissues inthe fat band are supplied by branches of the splenic artery. Based upon the blood vessel supply, the extramedullaryhematopoiesis and the morphological transition from aberrant spleens via transitional forms to splenoportal milky spots,splenoportal milky spots seem to represent splenoid lymphoid tissues. Taking into account the similarity betweenomental and splenoportal milky spots, the deduction that omental milky spots also represent splenoid lymphoid tissuesmay be made. The function and the signifi cance of milky spots are described in this paper.
続きを見る
|
||||
| 43.
論文 |
論文
|
Takano, Hiroko
概要:
We divided the mouse epididymis into 5 segments（ Segments I-V） based on regional diff erences in histologyto obtain a fu
…
ndamental division that refl ects the functions of this organ. Segments I-III are contained in the caputepididymidis, Segment IV in the corpus epididymidis, and Segment V in the cauda epididymidis. For this classifi cation,we observed morphological features of the epididymal duct in adult mice by light and electron microscopy, and examinedpostnatal development of the epididymal duct qualitatively and quantitatively. We also performed experimental studiesto examine the eff ects of ligation/cutting of the eff erent ducts, epididymal duct ligation at the border between SegmentsIII-IV, testis irradiation, cryptorchidism, and estrogen administration on epididymis histology. In these studies, we foundthat the epididymal duct in each segment responds as a functional unit when the epididymis is subjected to pathologicalconditions. In conclusion, the present histological division is useful as a basic division for studies on the mouse epididymis.
続きを見る
|
||||
| 44.
論文 |
論文
|
Akita, Miki ; Nanashima, Naoki ; Yamada, Toshiyuki ; Nakano, Hajime ; Shimizu, Takeshi ; Fan, Yang ; Tsuchida, Shigeki
概要:
The Hirosaki hairless rat （HHR） is a mutant strain spontaneously derived from the Sprague-Dawley rat（SDR） and its inheri
…
tance is autosomal recessive. Our recent study has revealed that an 80-kb genomic DNA on 7q36containing basic hair keratin genes, Kb21, Kb23, Kb26 and Krt2-25, is deleted in HHR. To characterize hair follicles inHHR, progression of hair cycle and expression profi les of basic hair keratins were immunohistochemically studied andcompared with those of SDR. The HHR exhibited sparse hairs and their twisted hairs were shorter than SDR hairs.HHR hair follicles entered the catagen phase earlier than SDR and massive destruction of HHR hair follicles andinfi ltration of infl ammatory cells occurred in the catagen phase. In HHR the hair medulla was enlarged and the innerroot sheath was thinned while the hair cortex was formed where Kb25 was expressed. In SDR Kb25 was expressedin the hair matrix and medulla. Electron microscopy indicated loss of the cuticle in HHR. These results suggest thathypotrichosis of HHR is due to the deletion of hair keratin genes and expression of a keratin fusion gene. Thus, HHRseems to be a useful model to examine the role of hair keratins in the hair follicle formation.
続きを見る
|
||||
| 45.
論文 |
論文
|
千葉, 貴子 ; 大森, 厚子 ; 高橋, 賢次 ; 柏倉, 幾郎
概要:
全ての血球の源となる造血幹細胞を豊富に含む臍帯血は，幹細胞研究，再生医療研究さらには臍帯血移植へとその応用が進み，今や単なる医療廃棄物ではなく，社会の多様な需要の中でその重要性は益々高まっている．本研究では，造血幹細胞の基礎医学研究に資した
…
臍帯血採取を実施した単一助産所における過去10年間の取組みから，助産所の臍帯血採取施設としての可能性の可否を含め，その内容を検討した．研究には，1998年から2007年の単胎正期産児を経膣分娩した585名を対象とした．その結果，助産所出産の母子の概要は，国内における平均的な出産と大差なかった．平均臍帯血採取量は54.2 g であり，重回帰分析の結果，胎盤重量，胎盤体積，出生体重，羊水混濁及び臍帯の長さと採取臍帯血量との間に関連が見られ，これまでの報告と一致した．以上の結果から，助産所においても安全かつ確実に臍帯血採取が行えることが実証された．
続きを見る
|
||||
| 46.
論文 |
論文
|
Ashitate, Toshihiro ; Osanai, Tomohiro ; Tanaka, Makoto ; Magota, Koji ; Echizen, Takashi ; Tomita, Hirofumi ; Okumura, Ken
概要:
We showed that endogenous prostacyclin inhibitor coupling factor 6 （CF6） is released from vascularendothelial cells and
…
its release is stimulated by tumor necrosis factor-α, which is related to congestive heart failure（CHF）. We also showed that CF6 increases the gene expression related to CHF. To investigate the role of CF6 inthe genesis of CHF, we generated CF6-overexpressing transgenic（ TG） mice, and characterized the phenotype. DNAfragment consisting of human elongation factor 1α promoter, and human calcitonin/CF6 fused gene was injected intothe embryo of C57BL/6J mouse, and homozygous TG mice were generated. In TG mice, CF6 gene was overexpressedby two fold in overall tissues compared with wild type（ WT） mice. Under normal salt diet, blood pressure, heart rate,and the expression of energy metabolism-related genes were similar between TG and WT mice. When the mice werefed with 8% -salt diet for 35 weeks, the mortality of TG mice was higher than that of WT mice（ survival rate; 50% inTG versus 92% in WT, p<0.05 by log-rank test）. This preliminary report indicates that further examination, especiallyanalysis of the cardiac function, is needed to clarify the cause of high mortality of TG mice under high salt intake.
続きを見る
|
||||
| 47.
論文 |
論文
|
Niwa, Hidetomo ; Sakai, Tetsuhiro ; Furukawa, Ken-Ichi ; Kanemaru, Kota ; Hirota, Kazuyoshi
概要:
In the present study, we have conducted cDNA microarray in C6, rat brain glioma cell line, to assess anti-infl ammatory
…
eff ects of ketamine and sevofl urane in the central nervous system. The cultured C6 cells were treated with ketamine （0-100 μM） and sevofl urane （0 and 0.66 mM）. Total RNA was extracted from the cells and labeled with fl uorescent dye and then hybridized with microarray slide, containing 1936 genes. Quantitative analysis of each gene expression was confi rmed by real-time polymerase chain reaction （PCR）. Microarray analyses showed that ketamine downregulated the expression of 4 proinfl ammatory cytokine genes and upregulated that of 2 antiinfl ammatory cytokine genes. On the other hand, sevofl urane downregulated the expression of 2 proinfl ammatory cytokines but upregulated that of two other proinfl ammatory cytokines. Furthermore, sevofl urane failed to stimulate the expressions of anti-infl ammatory cytokines. Although patterns of cytokine expression in response to ketamine and sevofl urane were diff erent from each other described above, both anesthetics downregulated a key cytokine, interleukin（ IL）-1β remarkably in microarray analysis, which was confi rmed by real time PCR. These results suggest that both ketamine and sevofl urane show mainly anti-infl ammatory properties through the inhibition of IL-1β.
続きを見る
|
||||
| 48.
論文 |
論文
|
Kato, Chisato ; Osanai, Tomohiro ; Shibutani, Shuji ; Hanada, Kenji ; Okumura, Ken
概要:
Insulin-like growth factor （IGF）-1 is known to exert benefi cial eff ects on the heart, but its source andfunction under
…
hypoxia are unknown. We investigated the eff ect of hypoxia on IGF-1 expression and its role in theregeneration in the heart. Cardiac myocytes and fi broblasts obtained from neonate mice heart were cultured andexposed to hypoxia. mRNA of IGF-1, IGF-binding protein 3 （IGFBP3）, and vascular endothelial growth factor-A（VEGF-A） was measured by real-time PCR. In cardiac myocytes, IGF-1 mRNA was increased by 3.5±1.1 fold at 3hours after hypoxia concomitantly with the increase in IGFBP3 and VEGF-A mRNA, and returned to the baseline at24 hours. In contrast, IGF-1 mRNA in cardiac fi broblasts was unchanged by hypoxia, although VEGF-A mRNA wasincreased. To investigate the role of IGF-1 in the heart regeneration, we measured the gene expressions of stromalcell-derived factor-1（ SDF-1）, its receptor CXCR4, and matrix metalloproteinase（ MMP）-14 related to cell homing. Incardiac myocytes, SDF-1 and MMP-14 mRNA were increased at 3 hours after hypoxia and tended to be positivelycorrelated with IGF-1 mRNA. These suggest that hypoxia increases IGF-1 expression in cardiac myocytes, and thisendogenous IGF-1 may exert benefi cial eff ects on regeneration in the heart.
続きを見る
|
||||
| 49.
論文 |
論文
|
Horiuchi, Daisuke ; Osanai, Tomohiro ; Echizen, Takashi ; Ashitate, Toshihiro ; Kato, Chisato ; Yokoyama, Hiroaki ; Hanada, Kenji ; Shibutani, Shuji ; Itoh, Taihei ; Okumura, Ken
概要:
Structural remodeling occurs in diverse heart diseases and affects their clinical courses. We reportedthat amiodarone su
…
ppresses both electrical and structural remodeling in a canine persistent atrial fi brillation model.As a mechanism for amiodarone’s effect on structural remodeling, we suggested its inhibitory effect on matrixmetalloproteinase（ MMP） activity. To elucidate it, we investigated the eff ect of amiodarone on MMP activity in a ratmyocardial infarction model created by left coronary artery（ LCA） ligation. Adult Sprague-Dawley rats were dividedinto sham-operated （Sham）, sham-operated with amiodarone （Sham+AMD）, LCA-ligated without amiodarone （MI）and LCA-ligated with amiodarone rats （MI+AMD）. Amiodarone （20 mg/kg/day） was administered for 2 weeksbefore and for 4 weeks after operation. The hearts were excised at 4 weeks after operation. MMP-2 activity wasmeasured by gelatin zymography. At 4 weeks after surgery, left ventricular fractional shortening was decreased inMI but not in MI+AMD rats. There was no diff erence in the infarct size between MI and MI+AMD rats （P=NS）.As compared with Sham, MMP-2 activity was increased in MI （P<0.01）, but not in MI+AMD （P=NS versus Sham;P<0.05 versus MI）. MMP-2 activity was not increased in Sham+AMD（ P=NS）. Thus, amiodarone exerts an inhibitoryeff ect on MMP activity. This may be related to the improvement left ventricular function in MI rats.
続きを見る
|
||||
| 50.
論文 |
論文
|
Tomotsune, Ken ; Ogawa, Yoshiji ; Hasegawa, Noriyuki ; Kudo, Takanori ; Naraoka, Maki ; Chikazawa, Shinji ; Tamasawa, Naoki ; Suda, Toshihiro
概要:
The aim of this study was to determine the time course and mechanism of hypoxia-induced pancreaticislet dysfunction. Isl
…
ets isolated from Sprague Dawley rats were cultured in 1％ O2（ hypoxia）. Glucose stimulatedinsulin secretion（ GSIS） was then examined for islets in either static or perifused cultures, followed by an evaluation ofmitochondrial activity and islet cell death. Additionally, we examined the eff ect of culturing previously hypoxic islets foran additional 24 h under normoxia to determine whether the hypoxic eff ects were reversible and to assess the eff ects ofre-oxygenation on GSIS. In the static islet culture, insulin secretion declined signifi cantly after 24 h. In perifused islets,the area under the curve（ AUC） of fi rst-phase GSIS declined signifi cantly after 6 h, while the AUC of second-phase GSISdecreased signifi cantly after 12 h. Mitochondrial activity dropped markedly after 48 h, but cell death assays revealedthat apoptosis did not increase in the time period from 6 h to 48 h. However, necrosis increased signifi cantly after 24 h.In the re-oxygenation study, the return to normoxia signifi cantly worsened the decline in GSIS. In conclusion, exposureto hypoxia fi rst causes functional disorder in the islets, followed by cell death due to necrosis rather than apoptosis.Furthermore, re-oxygenation aggravated islet dysfunction.
続きを見る
|
