1.

論文

論文
Uesato, Ryoko ; Ishibashi, Yasuyuki ; Ohshika, Shusa ; Naraoka, Takuya ; Toh, Satoshi
出版情報: 弘前医学.  59  pp.98-103,  2008-03-31.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/702
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
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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
出版情報: 弘前医学.  59  pp.104-109,  2008-03-31.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/703
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.

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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
出版情報: 弘前医学.  59  pp.110-117,  2008-03-31.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/704
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
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論文
Nakai, Makoto ; Yoshihara, Shuichi ; Morohashi, Hajime ; Ishido, Keinosuke ; Sasaki, Mutsuo
出版情報: 弘前医学.  59  pp.118-127,  2008-03-31.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/705
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
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論文
Matsukura, Daisuke ; Yokoyama, Yoshihito ; Tanaka, Kanji ; Ozaki, Takashi ; Mizunuma, Hideki
出版情報: 弘前医学.  59  pp.128-135,  2008-03-31.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/706
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
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論文
Maruyama, Ikuro ; Ito, Takashi ; Hashiguchi, Teruto
出版情報: 弘前医学.  59  pp.S1-S11,  2007-11-29.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/2210
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
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論文
Sasaki, Takeshi
出版情報: 弘前医学.  59  pp.S12-S18,  2007-11-29.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/2211
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
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Kido, Hiroshi ; Mizuno, Dai ; Le, Quang Trong ; Chida, Junji ; Yamada, Hiroshi ; Okumura, Yuushi ; Yano, Mihiro
出版情報: 弘前医学.  59  pp.S19-S25,  2007-11-29.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/2212
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
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Kurachi, Makoto ; Kakimi, Kazuhiro ; Ueha, Satoshi ; Matsushima, Kouji
出版情報: 弘前医学.  59  pp.S26-S34,  2007-11-29.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/2213
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
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論文
Ohteki, Toshiaki ; Kuwajima, Seiichi
出版情報: 弘前医学.  59  pp.S35-S42,  2007-11-29.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/2214
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