Management of spontaneous isolated dissection of the superior mesenteric artery: Case report and literature review

<p>Abstract</p> <p>Background and method</p> <p>The aim of this study was to assess retrospectively the clinical presentation, management and outcome of three patients with isolated SMA dissection encountered at Okinawa Prefectural Chubu Hospital, Japan from 2005 to 2006, along with a review of the literature. We follow up the patient's clinical symptoms and the image by using enhanced dynamic CT at 1 week, 1 or 2 months, 6 months, and yearly after onset.</p> <p>Case presentation</p> <p>We present three patients with acute abdominal pain due to spontaneous dissection of the superior mesenteric artery (SMA), who were treated by surgical revascularization or conservative management. Two patients underwent surgery because of signs or symptoms of intestinal ischemia and one patient elected conservative management. The SMA was repaired by bypass graft in two cases, and in one of these, the graft was occluded because of prominent native flow from the SMA. All patients were symptom free and there was no evidence of disease recurrence after a median follow-up of 4.3 years.</p> <p>Conclusion</p> <p>Although the indications for surgery are still controversial, we should proceed with exploratory laparotomy if the patient has acute symptoms with suspicion of mesenteric ischemia. A non-operative approach for SMA dissection requires close follow-up abdominal CT, with a focus on the clinical signs of mesenteric ischemia and the vascular supply of the SMA, including collateral flow from the celiac artery and inferior mesenteric artery.</p

インフルエンザウイルスに対する宿主応答の解析とワクチン開発への応用

学位の種別:課程博士University of Tokyo(東京大学

Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models

Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors

A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness

Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy

Clinical background factors as predictors of the efficacy of 5-aminosalicylic acid suppositories in patients with ulcerative colitis

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulceratve colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Discussion/Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation

Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses

Influenza viruses resistant to antiviral drugs emerge frequently. Not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza A (H1N1) viruses with the neuraminidase (NA) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains resistant to these drugs. Sporadic cases of pandemic influenza have been associated with mutant viruses possessing a histidine-to-tyrosine substitution at position 274 (H274Y) in the NA, a mutation known to be responsible for oseltamivir resistance. Here, we characterized in vitro and in vivo properties of two pairs of oseltaimivir-sensitive and -resistant (possessing the NA H274Y substitution) 2009 H1N1 pandemic viruses isolated in different parts of the world. An in vitro NA inhibition assay confirmed that the NA H274Y substitution confers oseltamivir resistance to 2009 H1N1 pandemic viruses. In mouse lungs, we found no significant difference in replication between oseltamivir-sensitive and -resistant viruses. In the lungs of mice treated with oseltamivir or even zanamivir, 2009 H1N1 pandemic viruses with the NA H274Y substitution replicated efficiently. Pathological analysis revealed that the pathogenicities of the oseltamivir-resistant viruses were comparable to those of their oseltamivir-sensitive counterparts in ferrets. Further, the oseltamivir-resistant viruses transmitted between ferrets as efficiently as their oseltamivir-sensitive counterparts. Collectively, these data indicate that oseltamivir-resistant 2009 H1N1 pandemic viruses with the NA H274Y substitution were comparable to their oseltamivir-sensitive counterparts in their pathogenicity and transmissibility in animal models. Our findings highlight the possibility that NA H274Y-possessing oseltamivir-resistant 2009 H1N1 pandemic viruses could supersede oseltamivir-sensitive viruses, as occurred with seasonal H1N1 viruses

高知県産無毛型ネジバナ(ラン科) の系統的背景について

Spiranthes sinensis, a terrestrial orchid, has morphological and ecological variations such as plant size, flowering season, floral colour, and hair density on the inflorescence stems and ovaries. Spiranthes sinensis var. amoena has been described as having puberulous inflorescence stems and ovaries, while these in S. sinensisvar. sinensis are considered to be glabrous. In Japan, S. sinensis var. amoena grows on a wide area of the mainland (the Northern Ryukyus and northward). By contrast, the distribution of S. sinensis var. sinensis is limited to the Central and Southern Ryukyus. We found a glabrous individual of S. sinensis in Kochi Prefecture, Japan, which has identical DNA sequences of internal transcribed spacer (ITS) region of nuclear DNA and trnL-F intergenic spacer region of chloroplast DNA to S. sinensis var. amoena. Thus, this glabrous individual should be included in S. sinensis var. amoena.ネジバナ（Spiranthes sinensis var. amoena）には，個体サイズ，花色，開花期，花の形態，花序の毛の多寡など多くの変異が報告されているが，日本本土（トカラ海峡以北）において花序に毛のないネジバナが稀に発見されている。花序の毛の有無に関して，日本本土に産する有毛花序を持つものがネジバナ，奄美大島以南に産する無毛花序を持つものがナンゴクネジバナ（S. sinensis var. sinensis）として識別される。近年の遺伝的解析により，本土産のネジバナと沖縄産のナンゴクネジバナは遺伝的に異なることが示されているが，本土産の無毛型ネジバナ（ナンゴクネジバナ）の遺伝的解析は行われておらず，系統的位置が不明なままである。そこで，高知県南国市で発見した無毛型ネジバナの遺伝的解析を行うことによって，本土産の無毛型ネジバナが，ナンゴクネジバナの隔離分布であるのか，ネジバナの形態変異であるのかを明らかにすることを目的とした。その結果，高知県産の無毛型ネジバナはネジバナと核遺伝子ITS領域および葉緑体遺伝子trnL-F領域において同一の塩基配列を持っていたため，本土に稀産する無毛型ネジバナはネジバナの形態変異である可能性が高いことがわかった。したがって，両変種の同定形質である毛の有無のみではネジバナとナンゴクネジバナを完全には識別できないため，形態的，生理的，生態的，遺伝的調査を改めて行う必要がある

Infection of XC Cells by MLVs and Ebola Virus Is Endosome-Dependent but Acidification-Independent

Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells