女児尿道ポリープの1例

Urethral polyps are rarely found in young girls. A total of 12 urethral polyps have been described in young girls in the English literature to date. Here we present a case of urethral polyp that was detected in the distal urethra of a 12-year-girl. Her chief complaint was a sudden blood discharge. On examination, a 15 x 9 mm polypoid mass with a 7 mm pedicle was seen protruding from the urethral meatus. The mass was excised under general anesthesia. Histopathologically, the polyp was covered with urothelium and squamous epithelium, and was composed of congested blood vessels and inflammatory infiltrates. These findings were similar to those of urethral caruncles in postmenopausal female. She has been free from recurrence and has had no complications, as of 12 months after excision.症例は12歳, 女児。生来健康。約1年前より外尿道口から脱出する腫瘤に気付くも症状なく放置していた。2005年10月に外陰部より突然の出血を認めたため, 近医を受診。外尿道口より脱出する小指頭大のポリープを認め, 同年10月31日, 精査加療目的に当院紹介となった。受診時, 他に理学所見上, 特に異常認めず, また尿沈渣, 血液学的検査, エコー, IVPなどにおいても異常所見を認めなかった。同年11月10日全身麻酔下, 尿道膀胱鏡および尿道ポリープ切除術を施行した。尿道鏡にて前部尿道の6時にポリープの起始部を認めた。膀胱内に特に異常所見は認めなかった。起始部からポリープを鋭的に切除し, 欠損部を5-0 PDSにて縫合した。術後経過は良好で術後1日目に尿道カテーテル抜去, 2日目に退院となった。病理組織学的検査にて尿道ポリープは移行上皮および扁平上皮に覆われ, 上皮下組織に小血管の増生と著明な炎症細胞の浸潤を認め, 尿道カルンクラに非常に類似していた。腫瘍性変化や異型細胞の増殖は認めなかった。現在, 術後1年が経過しているが, 再発, 合併症など認めていない。小児における尿道ポリープは稀な疾患であるが, 男児に比べ女児における報告はさらに少ない。われわれが調べうる限り12例の女児尿道ポリープが報告されている。またBen-Meirらは思春期前の女児尿道ポリープの5症例を検討し, 病理組織学的に尿道カルンクラとの類似性を指摘している。今回, われわれは女児尿道ポリープの1例を経験したので若干の文献的考察を加え, ここに報告する。(著者抄録

Data-driven normalization strategies for high-throughput quantitative RT-PCR

Background: High-throughput real-time quantitative reverse transcriptase polymerase chain reaction (qPCR) is a widely used technique in experiments where expression patterns of genes are to be profiled. Current stage technology allows the acquisition of profiles for a moderate number of genes (50 to a few thousand), and this number continues to grow. The use of appropriate normalization algorithms for qPCR-based data is therefore a highly important aspect of the data preprocessing pipeline

A novel approach for the endothelialization of xenogeneic decellularized vascular tissues by human cells utilizing surface modification and dynamic culture

Decellularized xenogeneic vascular grafts can be used in revascularization surgeries. We have developed decellularization methods using high hydrostatic pressure (HHP), which preserves the extracellular structure. Here, we attempted ex vivo endothelialization of HHP-decellularized xenogeneic tissues using human endothelial cells (ECs) to prevent clot formation against human blood. Slices of porcine aortic endothelium were decellularized using HHP and coated with gelatin. Human umbilical vein ECs were directly seeded and cultured under dynamic flow or static conditions for 14 days. Dynamic flow cultures tend to demonstrate higher cell coverage. We then coated the tissues with the E8 fragment of human laminin-411 (hL411), which has high affinity for ECs, and found that Dynamic/hL411showed high area coverage, almost reaching 100% (Dynamic/Gelatin vs Dynamic/hL411; 58.7 ± 11.4 vs 97.5 ± 1.9%, P = 0.0017). Immunostaining revealed sufficient endothelial cell coverage as a single cell layer in Dynamic/hL411. A clot formation assay using human whole blood showed low clot formation in Dynamic/hL411, almost similar to that in the negative control, polytetrafluoroethylene. Surface modification of HHP-decellularized xenogeneic endothelial tissues combined with dynamic culture achieved sufficient ex vivo endothelialization along with prevention of clot formation, indicating their potential for clinical use as vascular grafts in the future

PETREL: Platform for Extra and Terrestrial Remote Examination with LCTF

A small satellite ”PETREL” for UV astronomy and remote sensing with ”tunable” multi-spectral cameras conducted by an academia-industrial collaboration is presented. This project was originally proposed by an astronomer who desired a satellite for exploration of explosive objects in ultraviolet. To avoid the earthshine the astronomical observations are scheduled only in the nighttime. To utilize the daytime more electively we conceived a plan of ”satellite sharing” with the industrial collaborators, that can also reduce the developing cost drastically. The daytime mission is spectroscopy that is one of the potential fields in terms of data business, because that can provide chemical and biological information on the surface of the earth. We employ multi-spectral cameras making use of liquid crystal tunable filters (LCTFs) that enable adaptive observations at the optimized wave-bands for each targets. In 2020, this remote-sensing project and ultraviolet astronomy mission were accepted as a small satellite project of JAXA’s Innovative Satellite Technology Demonstration program and as an ISAS/JAXA’s small-scale program, respectively. This satellit

RUNX1 transactivates BCR-ABL1 expression in Philadelphia chromosome positive acute lymphoblastic leukemia

The emergence of tyrosine kinase inhibitors as part of a front-line treatment has greatly improved the clinical outcome of the patients with Ph⁺ acute lymphoblastic leukemia (ALL). However, a portion of them still become refractory to the therapy mainly through acquiring mutations in the BCR-ABL1 gene, necessitating a novel strategy to treat tyrosine kinase inhibitor (TKI)-resistant Ph⁺ ALL cases. In this report, we show evidence that RUNX1 transcription factor stringently controls the expression of BCR-ABL1, which can strategically be targeted by our novel RUNX inhibitor, Chb-M'. Through a series of in vitro experiments, we identified that RUNX1 binds to the promoter of BCR and directly transactivates BCR-ABL1 expression in Ph⁺ ALL cell lines. These cells showed significantly reduced expression of BCR-ABL1 with suppressed proliferation upon RUNX1 knockdown. Moreover, treatment with Chb-M' consistently downregulated the expression of BCR-ABL1 in these cells and this drug was highly effective even in an imatinib-resistant Ph⁺ ALL cell line. In good agreement with these findings, forced expression of BCR-ABL1 in these cells conferred relative resistance to Chb-M'. In addition, in vivo experiments with the Ph⁺ ALL patient-derived xenograft cells showed similar results. In summary, targeting RUNX1 therapeutically in Ph⁺ ALL cells may lead to overcoming TKI resistance through the transcriptional regulation of BCR-ABL1. Chb-M' could be a novel drug for patients with TKI-resistant refractory Ph⁺ ALL

Adalimumab Dose-Escalation Therapy Is Effective in Refractory Crohn’s Disease Patients with Loss of Response to Adalimumab, Especially in Cases without Previous Infliximab Treatment

Background/Aims: Adalimumab dose escalation is one of the most important options in refractory Crohn’s disease patients with loss of response to adalimumab. The goal of this study was to evaluate the effectiveness of adalimumab dose escalation in Crohn’s disease patients with loss of response to adalimumab, since there are few reports of adalimumab dose escalation, especially in East Asia. Methods: The clinical response to adalimumab dose escalation in Crohn’s disease patients with loss of response to adalimumab was evaluated retrospectively, using the Crohn’s disease activity index score, serum C-reactive protein levels, and endoscopic analyses. Results: Of the 203 Crohn’s disease patients treated with anti-tumor necrosis factor, 14 refractory Crohn’s disease patients with loss of response to adalimumab received adalimumab dose-escalation therapy. The C-reactive protein level was significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in the whole group, although there were no significant reductions of Crohn’s disease activity index scores. Both Crohn’s disease activity index scores and C-reactive protein levels were significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in patients without previous infliximab treatment, although C-reactive protein levels were positive in all cases with previous infliximab exposure at weeks 12 and 52. Endoscopic mucosal healing was achieved with adalimumab dose escalation in 2 cases without previous infliximab treatment. Conclusions: Adalimumab dose-escalation therapy is effective in refractory Crohn’s disease patients with loss of response to adalimumab, especially in cases without previous infliximab treatment

Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi

Transcriptional regulation by transcriptional regulatory factors (TRFs) of their target TRF genes is central to the control of gene expression. To study a static multi-tiered inter-TRF regulatory network in the human hepatoma cells, we have applied a Matrix RNAi approach in which siRNA knockdown and quantitative RT-PCR are used in combination on the same set of TRFs to determine their interdependencies. This approach focusing on several liver-enriched TRF families, each of which consists of structurally homologous members, revealed many significant regulatory relationships. These include the cross-talks between hepatocyte nuclear factors (HNFs) and the other TRF groups such as CCAAT/enhancer-binding proteins (CEBPs), retinoic acid receptors (RARs), retinoid receptors (RXRs) and RAR-related orphan receptors (RORs), which play key regulatory functions in human hepatocytes and liver. In addition, various multi-component regulatory motifs, which make up the complex inter-TRF regulatory network, were identified. A large part of the regulatory edges identified by the Matrix RNAi approach could be confirmed by chromatin immunoprecipitation. The resultant significant edges enabled us to depict the inter-TRF TRN forming an apparent regulatory hierarchy of (FOXA1, RXRA) → TCF1 → (HNF4A, ONECUT1) → (RORC, CEBPA) as the main streamline

One-Step Detection of the 2009 Pandemic Influenza A(H1N1) Virus by the RT-SmartAmp Assay and Its Clinical Validation

<div><h3>Background</h3><p>In 2009, a pandemic (pdm) influenza A(H1N1) virus infection quickly circulated globally resulting in about 18,000 deaths around the world. In Japan, infected patients accounted for 16% of the total population. The possibility of human-to-human transmission of highly pathogenic novel influenza viruses is becoming a fear for human health and society.</p> <h3>Methodology</h3><p>To address the clinical need for rapid diagnosis, we have developed a new method, the “RT-SmartAmp assay”, to rapidly detect the 2009 pandemic influenza A(H1N1) virus from patient swab samples. The RT-SmartAmp assay comprises both reverse transcriptase (RT) and isothermal DNA amplification reactions in one step, where RNA extraction and PCR reaction are not required. We used an exciton-controlled hybridization-sensitive fluorescent primer to specifically detect the HA segment of the 2009 pdm influenza A(H1N1) virus within 40 minutes without cross-reacting with the seasonal A(H1N1), A(H3N2), or B-type (Victoria) viruses.</p> <h3>Results and Conclusions</h3><p>We evaluated the RT-SmartAmp method in clinical research carried out in Japan during a pandemic period of October 2009 to January 2010. A total of 255 swab samples were collected from outpatients with influenza-like illness at three hospitals and eleven clinics located in the Tokyo and Chiba areas in Japan. The 2009 pdm influenza A(H1N1) virus was detected by the RT-SmartAmp assay, and the detection results were subsequently compared with data of current influenza diagnostic tests (lateral flow immuno-chromatographic tests) and viral genome sequence analysis. In conclusion, by the RT-SmartAmp assay we could detect the 2009 pdm influenza A(H1N1) virus in patients' swab samples even in early stages after the initial onset of influenza symptoms. Thus, the RT-SmartAmp assay is considered to provide a simple and practical tool to rapidly detect the 2009 pdm influenza A(H1N1) virus.</p> </div