319 research outputs found

    Studien über die Permeabilitat der normalen und der veränderten Darmschleimhaut fur Autigenstoff

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    Verfasser studiete diese Frage mit aller Sorgfalt indirekt bei Tieren mittels Antigen und Antikorpernachweis im Blut und direkt mit isoliertem mittels Cholinreation nach Paraffth. Als Versuchstiere benutzte er Kaninchen und Hühner, insgesamt 500 Tiere, dennen gesunde gut gewachsene, junge, verhungerte, verdürstete, diarrhoische Tiere oder solche mit Avitaminose von B waren. Zuerst gab er per os Rinderserum nnd Coliemulsion dem Versuchstier forciert ein und untersuchte den Antigenubergang zertlich. Sodann prüfte er bei jungen Tieren die Permeabilitatssteigerung. Drittens untersuchte er bei verhungerte oder verdurstete Tieren (Hühn.) die Permerbilitatsveranderung. Zum Schluss kam er bei Avitaminose von B in Hühnern und Kaninchen nach langen Versuchen zum Ziel und konnte die Permeabilitatsanderung genau prufen. Die Resultate sind kurz folgende: 1) Gibt man erwachsenen, gesunden Kaninchen und Hühnern grosze Mengen von Rinderserum (200cc in 3 Tagen) per os ein, so ist es möglich, durch die Präcipitinreaktionen die Antigene in der Blutbahn zu erkennen. In solchen Fällen ist es wohl moglich, dass the minimalen Antiköperbildung durch die perorale Immunität untersucht werden kann. Auch bei Colieingabe kann man durch Agglutininreaktionen in der gleichen Weise den Antigenubergang und die An ikorperbildung nachweisen. 2) Diese perorale Immunisierung wird durch Zusatz von Rinderserum mehr oder weniger gesichert. 3) Der Grad des Erwachsenseins der Tiere und der Mobilisation des Antigens scheinen in gegenseitiger Bez ehung zueivander zu stehen, d, h, : Je jünger die Tiere sind, desto starker wird das Antigen mobilisiert. 4) Hunger oder Durst verstarken bei gesunden Tieren die Mobilisierung des Antigens in der Blutbahn, bei Erholung der Tiere geht diese wieder ihren gewohnlichen Gang. 5) Bei Erkrankung der Tiere, insbesondere bei kunstlicher Störung von Magenund Darmkanal und Leber und Niere die Mobilisierung des Antigens verstarkt. 6) Aus den Untersuchungen uber das Verhaltniss der Permeabilität der Darmschleimhaut zum Mangel an Vitamin B ergibt sich, dass auch in dieser Zeit die Mobilisierung des Antigens verstakt wird. Dieser veranderte Zustand des Darms bei Avitaminose kann bei Ende der Versuches als maximal, aber bei Beginn des Versuches nicht nachgewissen werden. Durch Vitamineingabe erholen sich in dieser Zeit etwas. Verfasser hat auch bei einigen Fällen von Hühneravitaminose eine Steigerung des normalen Agglutininwertes für Coli beobachtet. 7) Aus diesen Gründen bestimmte er nach der Methode von Paraffth die Permeabilitat der Darmschleimhaut in jedem einzelnen Falle, wie oben erwähnt, und gelangte zu Resultaten, die mit den serologischen Studien übereinstimmen

    Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma

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    BACKGROUND: The acyclic retinoid, peretinoin, has been shown to be effective for suppressing hepatocellular carcinoma (HCC) recurrence after definitive treatment in a small-scale randomized clinical trial. However, little has been documented about the mechanism by which peretinoin exerts its inhibitory effects against recurrent HCC in humans in vivo. METHODS: Twelve hepatitis C virus-positive patients whose HCC had been eradicated through curative resection or ablation underwent liver biopsy at baseline and week 8 of treatment with either a daily dose of 300 or 600 mg peretinoin. RNA isolated from biopsy samples was subjected to gene expression profile analysis. RESULTS: Peretinoin treatment elevated the expression levels of IGFBP6, RBP1, PRB4, CEBPA, G0S2, TGM2, GPRC5A, CYP26B1, and many other retinoid target genes. Elevated expression was also observed for interferon-, Wnt-, and tumor suppressor-related genes. By contrast, decreased expression levels were found for mTOR- and tumor progression-related genes. Interestingly, gene expression profiles for week 8 of peretinoin treatment could be classified into two groups of recurrence and non-recurrence with a prediction accuracy rate of 79.6% (P<0.05). In the liver of patients with non-recurrence, expression of PDGFC and other angiogenesis genes, cancer stem cell marker genes, and genes related to tumor progression was down-regulated, while expression of genes related to hepatocyte differentiation, tumor suppression genes, and other genes related to apoptosis induction was up-regulated. CONCLUSIONS: Gene expression profiling at week 8 of peretinoin treatment could successfully predict HCC recurrence within 2 years. This study is the first to show the effect of peretinoin in suppressing HCC recurrence in vivo based on gene expression profiles and provides a molecular basis for understanding the efficacy of peretinoin

    Increased serum levels of the carrier molecules of the carbohydrate antigen sialyl Lewis X in liver diseases

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    The serum levels of the carbohydrate antigen sialyl Lewis X (SLEX) increase in liver diseases (Sunayama T, Okada Y, Tsuji T., J Hepatol 1994; 19: 451-458). However, it is not known whether the increased serum SLEX levels are associated with the increased levels of its carrier molecules and/or the increased density of SLEX per carrier molecule. By using of rabbit antibody against an SLEX-positive fraction from HepG2 culture supernatant, we developed an enzyme-linked immunosorbent assay to determine the serum levels of the carrier molecules of SLEX (CMSLEX). The CMSLEX-levels in patients with hepatocellular carcinoma were significantly higher than those of normal controls (P &#60; 0.001) and benign chronic liver diseases, i.e., chronic active hepatitis, mild and severe form, and liver cirrhosis (P &#60; 0.05). Patients with chronic persistent hepatitis and chronic active hepatitis, mild form, had higher CMSLEX-levels than normal controls (P &#60; 0.05). The serum CMSLEX-levels did not differ significantly among benign liver diseases. We concluded that serum CMSLEX-levels increase nonspecifically in liver diseases. This is a possible molecular mechanism for the increased serum SLEX levels in liver diseases.</p

    免疫担当細胞の遺伝子発現プロファイル解析による癌免疫の解明

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    金沢大学附属病院C57BL/6マウス由来の大腸癌細胞株MC38を同系マウスへ経脾経門脈的に接種し成立させた肝内播種巣には浸潤リンパ球がほとんど認められなかった。そのため、よりヒト悪性腫瘍に類似した免疫応答を伴う癌モデルの開発を試みた。C57Lマウス由来の肝細胞癌株Hepa1-6を経脾経門脈的に2x10^6個のHepa1-6細胞を投与したC57B1/6マウスの一部に、56日後にHepa1-6腫瘍の肝への著明な播種を認め播種癌部へのリンパ球浸潤が認められた。このHepa1-6肝内播種巣を回収し、in vitroにて、2種類の細胞株Hepa1-6clone Aおよびclone Bを樹立した。Hepa1-6 clone Aは、ケモカインCCL20、CCL2、またinterleukin 13 receptor,alpha、IL-4 receptor,alpha、IL-12 receptor,beta、CDld、CD81の発現低下が認められ、宿主の免疫防御機構に対する抵抗性が推測された。Hepa 1-6 clone Aを脾臓へ5x10^6個接種させたC57BL/6マウス(♀、8週齢)を接種後23日後に開腹、肝内に播種された腫瘍には組織学的にリンパ球の浸潤が認められた。本研究において、免疫担当細胞の遺伝子発現プロファイル解析による癌に対する免疫応答を解析するより有用なモデルが確立された。同マウスの末梢血液をRNA安定化剤へ収集しRNAを抽出し、DNAマイクロアレイを用いて担癌状態におけるマウスの末梢血液細胞の遺伝子発現を解析中である。研究課題/領域番号:18790452, 研究期間(年度):2006 – 2007出典:「免疫担当細胞の遺伝子発現プロファイル解析による癌免疫の解明」研究成果報告書 課題番号18790452(KAKEN:科学研究費助成事業データベース(国立情報学研究所))(https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-18790452/)を加工して作

    α-フェトプロテインプロモーター,Cre/lox P系を用いた組換アデノウイルスベクター二重感染による肝癌遺伝子治療

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    取得学位:博士(医学),学位授与番号:医博甲第1443号,学位授与年月日:平成12年10月31日,学位授与年:200

    Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations

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    Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations.BackgroundWe previously reported three aquaporin-2 (AQP2) gene mutations known to cause autosomal-dominant nephrogenic diabetes insipidus (NDI) (Am J Hum Genet 69:738, 2001). The mutations were found in the C-terminus of AQP2 (721delG, 763 to 772del, and 812 to 818del). The wild-type AQP2 is a 271 amino acid protein, whereas these mutant genes were predicted to encode 330 to 333 amino acid proteins due to the frameshift mutations leading to the creation of a new stop codon 180 nucleotides downstream. The Xenopus oocyte expression study suggested that the trafficking of the mutant AQP2s was impaired.MethodsTo determine the cellular pathogenesis of these NDI-causing mutations in mammalian epithelial cells, Madin-Darby canine kidney (MDCK) cells were stably transfected with the wild-type AQP2, or the 763 to 772del mutant AQP2, or both. Cells were grown on the membrane support to examine the localization of AQP2 proteins by immunofluorescence microscopy.ResultsConfocal immunofluorescence microscopy showed that the wild-type AQP2 was expressed in the apical region, whereas the mutant AQP2 was apparently located at the basolateral region. Furthermore, the wild-type and mutant AQP2s were colocalized at the basolateral region when they were cotransfected, suggesting the formation of mixed oligomers and thereby mistargeting.ConclusionMixed oligomers of the wild-type and the 763 to 772del mutant AQP2s are mistargeted to the basolateral membrane due to the dominant-negative effect of the mutant. This defect is very likely to explain the pathogenesis of autosomal-dominant NDI. The mistargeting of the apical membrane protein to the basolateral membrane is a novel molecular pathogenesis of congenital NDI

    Perpendicular magnetic anisotropy at Fe/Au(111) interface studied by M\"{o}ssbauer, x-ray absorption, and photoemission spectroscopies

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    The origin of the interfacial perpendicular magnetic anisotropy (PMA) induced in the ultrathin Fe layer on the Au(111) surface was examined using synchrotron-radiation-based M\"{o}ssbauer spectroscopy (MS), X-ray magnetic circular dichroism (XMCD), and angle-resolved photoemission spectroscopy (ARPES). To probe the detailed interfacial electronic structure of orbital hybridization between the Fe 3dd and Au 6pp bands, we detected the interfacial proximity effect, which modulates the valence-band electronic structure of Fe, resulting in PMA. MS and XMCD measurements were used to detect the interfacial magnetic structure and anisotropy in orbital magnetic moments, respectively. InIn-situsitu ARPES also confirms the initial growth of Fe on large spin-orbit coupled surface Shockley states under Au(111) modulated electronic states in the vicinity of the Fermi level. This suggests that PMA in the Fe/Au(111) interface originates from the cooperation effects among the spin, orbital magnetic moments in Fe, and large spin-orbit coupling in Au. These findings pave the way to develop interfacial PMA using pp-dd hybridization with a large spin-orbit interaction
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