141 research outputs found
Detection of AR-V7 mRNA in whole blood may not predict the effectiveness of novel endocrine drugs for castration-resistant prostate cancer
No full textTakumi Takeuchi, Yumiko Okuno, Mami Hattori-Kato, Masayoshi Zaitsu, Koji MikamiDepartment of Urology, Kanto Rosai Hospital, Kawasaki, JapanAbstract: A splice variant of androgen receptor (AR), AR-V7, lacks in androgen-binding portion and leads to aggressive cancer characteristics. Reverse transcription-polymerase chain reactions (PCRs) and subsequent nested PCRs for the amplification of AR-V7 and prostate-specific antigen (PSA) transcripts were done for whole blood of patients with prostate cancer and male controls. With primary reverse transcription PCRs, AR-V7 and PSA were detected in 4.5% and 4.7% of prostate cancer, respectively. With nested PCRs, AR-V7 messenger RNA (mRNA) was positive in 43.8% of castration-sensitive prostate cancer and 48.1% of castration-resistant prostate cancer (CRPC), while PSA mRNA was positive in 6.3% of castration-sensitive prostate cancer and 18.5% of CRPC. Whole-blood samples of controls showed AR-V7 mRNA expression by nested PCR. Based on multivariate analysis, expression of AR-V7 mRNA in whole blood was not significantly correlated with clinical parameters and PSA mRNA in blood, while univariate analysis showed a correlation between AR-V7 mRNA and metastasis at initial diagnosis. Detection of AR-V7 mRNA did not predict the reduction of serum PSA in patients with CRPC following abiraterone and enzalutamide administration. In conclusion, AR-V7 mRNA expression in normal hematopoietic cells may have annihilated the manifestation of aggressiveness of prostate cancer and the prediction of the effectiveness of abiraterone and enzalutamide by the assessment of AR-V7 mRNA in blood.Keywords: AR-V7, prostate cancer, castration-resistan
Deeper ‘GO’ Phase in Rat Fibroblasts Affects the Lag Time Required for T Antigen Induced DNA Synthesis, but not the Lag Time Required for SV40 T Antigen Expression
No full textDetection of Brain Metastases by 3-Dimensional Magnetic Resonance Imaging at 3 T: Comparison Between T1-Weighted Volume Isotropic Turbo Spin Echo Acquisition and 3-Dimensional T1-Weighted Fluid-Attenuated Inversion Recovery Imaging
Get PDFObjective: To compare the diagnostic performance in detection of brain metastases between contrast-enhanced T1-weighted-Volume ISotropic Turbo-spin-echo Acquisition (T1-VISTA) and 3-dimensional T1-weighted fluid-attenuated inversion recovery (3D-T1-FLAIR) imaging at 3T. Methods: Two neuroradiologists selected 129 true (metastases) and 70 false (vessels and artifacts) lesions on the contrast-enhanced T1-VISTA and 3D-T1-FLAIR images of 14 cancer patients with hyperintense brain lesions. Four blinded neuroradiologists distinguished between the true and false lesions, using a five-point confidence rating scale. The receiver operating characteristic analysis was performed to compare the diagnostic performance. Contrast-to-noise ratio (CNR) of the true lesions was also compared between the two sequences by using paired t-tests. Results: For lesions < 3 mm, the area under curve and sensitivity achieved by T1-VISTA imaging were significantly greater than 3D-T1-FLAIR imaging. The CNR was also significantly greater with T1-VISTA imaging. Conclusion: The contrast-enhanced T1-VISTA imaging is better suited than 3D-T1-FLAIR imaging, for detection of small metastases
Novel immunological approach to asses donor reactivity of transplant recipients using a humanized mouse model
Get PDFIn organ transplantation, a reproducible and robust immune-monitoring assay has not been established to determine individually tailored immunosuppressants (IS). We applied humanized mice reconstituted with human (hu-) peripheral blood mononuclear cells (PBMCs) obtained from living donor liver transplant recipients to evaluate their immune status. Engraftment of 2.5 x 10(6) hu-PBMCs from healthy volunteers and recipients in the NSG mice was achieved successfully. The reconstituted lymphocytes consisted mainly of hu-CD3(+) lymphocytes with predominant CD45RA(-)CD62L(lo) T-EM and CCR6(-)CXCR3(+)CD4(+) Th1 cells in hu-PBMC-NSG mice. Interestingly, T cell allo-reactivity of hu-PBMC-NSG mice was amplified significantly compared with that of freshly isolated PBMCs (p < 0.05). Furthermore, magnified hu-T cell responses to donor antigens (Ag) were observed in 2/10 immunosuppressed recipients with multiple acute rejection (AR) experiences, suggesting that the immunological assay in hu-PBMC-NSG mice revealed hidden risks of allograft rejection by IS. Furthermore, donor Ag-specific hyporesponsiveness was maintained in recipients who had been completely weaned off IS (n = 4), despite homeostatic proliferation of hu-T cells in the hu-PBMC-NSG mice. The immunological assay in humanized mice provides a new tool to assess recipient immunity in the absence of IS and explore the underlying mechanisms to maintaining operational tolerance
Selective blockade of CD28 on human T cells facilitates regulation of alloimmune responses
No full textInternational audienceT cells are central to the detrimental alloresponses that develop in autoimmunity and transplantation, with CD28 costimulatory signals being key to T cell activation and proliferation. CTLA4-Ig molecules that bind CD80/86 and inhibit CD28 costimulation offer an alternative immunosuppressive treatment, free from some of the chronic toxicities associated with calcineurin inhibition. However, CD80/86 blockade by CTLA4-Ig also results in the loss of coinhibitory CTLA4 signals that are critical to the regulation of T cell activation. Here, we show that a nonactivating monovalent anti-CD28 that spares CTLA4 signaling is an effective immunosuppressant in a clinically relevant humanized mouse transplant model. We demonstrate that selective CD28 blockade prolongs human skin allograft survival through a mechanism that includes a reduction in the cellular graft infiltrate. Critically, selective CD28 blockade promotes Treg function in vivo and synergizes with adoptive Treg therapy to promote transplant survival. In contrast to CTLA4-Ig treatment, selective CD28 blockade promotes regulation of alloimmune responses and facilitates Treg-based cellular therapy
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Why make sense of silence? The clausal syntax of a reduced why-question
Get PDFIn this paper, I investigate the syntax of a reduced why-question that I call Why-VP; these are clauses like "Why take Structure of Japanese?" These questions are reduced in a very particular way; they are missing an overt subject and the verb never shows tense marking as is typical in why-questions, such as "why was John taking Structure of Japanese?" Why-VP has received very little attention in the literature even though they are incredibly frequent in production. Over the course of the last year, several naturally occurring examples drawn together with their discourse context have accumulated, specifically from the New York Times portion of the Gigaword corpus. These were found completely by accident when, as part of the Santa Cruz Ellipsis Group, we began annotating root sluices. Despite the fact that they are reduced, and that they were accidentally captured by a parser as ellipsis, the corpus of naturally occurring examples lead me to conclude that these really do not fit the standard profile of ellipsis as they really do not rely on an antecedent. As such, I argue that Why-VP are free-standing and intact clauses, best understood as infinitival and as having a covert modal, thus contributing to our understanding of the clause-building mechanisms available in the language which make reduced clauses such as Why-VP possible. I present evidence that 'why' in Why-VP is best analyzed as a head, which selects for the covert modal hosted by a silent infinitival T, which hosts the structural subject and also selects the v/VP; so while Why-VP questions seem reduced, they actually carry elements typical of the extended projectio
脂肪滴はヒト肝細胞株におけるPorphyromonas gingivalisのオートファジー・リソソームシステムを介した排除機構に影響する
Get PDFRecent studies have shown that infection with Porphyromonas gingivalis, a major periodontal pathogen, hastens the progression of non-alcoholic fatty liver disease (NAFLD). However, the intracellular fate of P. gingivalis in hepatocytes remains unknown. Here, using oleic-acid-induced HepG2 cells as an in vitro model for NAFLD, we found that lipid droplets increased the existence of P. gingivalis in the cells at an early phase of infection. Confocal microscopic analysis revealed that lipid droplets affected the formation of autolysosomes in infected cells. Thus, lipid droplets affect the elimination of P. gingivalis in HepG2 cells by altering the autophagy-lysosome system.長崎大学学位論文 学位記番号:博(医歯薬)甲第916号 学位授与年月日:平成29年3月21日Author: Yumi Zaitsu, Mayumi Iwatake, Keiko Sato, Takayuki TsukubaCitation: Microbes and Infection, 18(9), pp.565-571;201
Cell mediated rejection.
No full textRejection is the major barrier to successful transplantation and usually results from the integration of multiple mechanisms. Activation of elements of the innate immune system, triggered as a consequence of tissue injury sustained during cell isolation or organ retrieval as well as ischemia-reperfusion, will initiate and amplify the adaptive response. For cell mediated rejection, T cells require multiple signals for activation, the minimum being two signals; antigen recognition and costimulation. The majority of B cells require help from T cells to initiate alloantibody production. Antibodies reactive to donor HLA molecules, minor histocompatibility antigens, endothelial cells, red blood cells, or autoantigens can trigger or contribute to rejection early as well as late after transplantation
東インドと隣接諸王国における珍奇なものに関する略説」 ー ライプツィッヒの外科医兼商人カスパル・シャムベルゲルの生涯と業績に関する新発見 ー
No full textEinleitung / Abriss eines abenteuerlichen Lebens / Zurück aus Ostindien – Schamberger in Leipzig / Zum Druck der Schambergerschen Erläuterung/ Struktur und Besonderheiten der drei Schildereyen / Mitbringsel aus der Fremde / Frühe Ostindien-Fahrer und ihre Bildmaterialien / Caspar Schmalkalden / Zacharias Wagener / Heinrich Muche / Johann Wilhelm Vogel / Elias Hesse / Albrecht Herport / George Meister / Andreas Cleyer / Engelbert Kaempfer / Zum Inhalt der Schambergerschen »Erläuterung« / Handel und Wandel der Niederländer in Ostindien / Früchte, Wurzeln, Nüsse / Tiere / Münzen / Ethnische Abbildungen / Sprache und Schrift / Rückblick / Text: Dreier in Untertänigkeit offerierten Schildereien kurze Erläuterung / Quellen und Literatur / Handschriftliche Quellen / Gedruckte Quellen (16.-18. Jh.) / Sekundärliteratur / Allgemeine Nachschlagewerke / RegisterThis book presents a newly discovered text of which only one copy has survived in the Dresden State Art Collections (Staatliche Kunstsammlungen Dresden, Münzkabinett). It was dedicated to the Duke of Saxony Johann Georg III. and published in 1686 as a private print under the title \u22Short explanation of the most prominent rarities in East India and the neighbouring kingdoms\u22. The author Caspar Schamberger (1623-1706) had worked in Asia for twelve years as a surgeon on VOC ships and in Dutch trading posts. He is known as the \u22father\u22 of the first fully-fledged Western-style medical school in Japan. His text describes fruits, plants, animals, ethnic groups, coins etc. from Persia to Japan including the Khoikhoi (Khoisan) in Southern Africa. This is one of the earliest Western accounts of these matters based on observations made during the late 1640s and 1650s. The extensive commentary (126 pages) gives an outline of Schamberger\u27s life presenting numerous new information on his activities after his return to Leipzig in 1658. Schamberger\u27s descriptions are analysed in detail within the context of similar accounts of nine contemporary German travellers: Caspar Schmalkalden, Zacharias Wagener, Heinrich Muche, Johann Wilhelm Vogel, Elias Hesse, Albrecht Herport, George Meister, Andreas Cleyer, Engelbert Kaempfer. Forty-six illustrations selected from Western and Japanese sources proviede the iconographic background
Delayed Anti-CD3 Therapy Results in Depletion of Alloreactive T Cells and the Dominance of Foxp3+CD4+Graft Infiltrating Cells
No full textThe engineered Fc-nonbinding (crystallizable fragment-nonbinding) CD3 antibody has lower mitogenicity and a precise therapeutic window for disease remission in patients with type 1 diabetes. Before anti-CD3 can be considered for use in transplantation, the most effective timing of treatment relative to transplantation needs to be elucidated. In this study anti-CD3F(ab′) 2 fragments or saline were administered intravenously for 5 consecutive days (early: d1-3 or delayed: d3-7) to mice transplanted with a cardiac allograft (H2b-to-H2k; d0). Survival of allografts was prolonged in mice treated with the early protocol (MST = 48 days), but most were rejected by d100. In contrast, in mice treated with the delayed protocol allografts continued to survive long term. The delayed protocol significantly inhibited donor alloreactivity at d30 as compared to the early protocol. A marked increase in Foxp3+ T cells (50.3 ± 1.6%) infiltrating the allografts in mice treated with the delayed protocol was observed (p < 0.0001 vs. early (24.9 ± 2.1%)) at d10; a finding that was maintained in the accepted cardiac allografts at d100. We conclude that the timing of treatment with anti-CD3 therapy is critical for inducing long-term graft survival. Delaying administration effectively inhibits the alloreactivity and promotes the dominance of intragraft Foxp3+ T cells allowing long-term graft acceptance. © 2013 The Authors. American Journal of Transplantation Published by Wiley Periodicals Inc
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