遺残胎盤組織：診断と臨床的取り扱いにおけるMRI所見の役割

OBJECTIVE:To assess the role of MRI in diagnosis and predicting clinical outcome in women with retained placental tissue. PATIENTS AND METHODS:Eleven patients with pathologically proven RPT were retrospectively studied. All underwent MRI. The following MRI parameters of RPT were studied: size, signal intensity on T1- and T2-weighted images, enhancement pattern on dynamic study, extent of attachment to the uterine myometrium, and myometrial thickness at the attachment site. Clinical reports were reviewed and MRI findings were compared with respect to outcome. RESULTS:RPT diameter varied from 30 to 102 mm. On T2-weighted images, 10 cases showed high intensity, while on T1-weighted images, seven cases showed high intensity. Nine cases were hypervascular. The myometrium was thinner at the attachment side than at the opposite side. All five cases in which RPT was delivered spontaneously showed an attachment area of less than a semicircle, hence broad attachment appears to impede detachment and necessitate additional therapy. After uterine arterial embolization, two patients showed complete infarction of RPT on enhanced MRI. CONCLUSION:MRI is useful for diagnosis and follow-up of RPT. The evaluation of extent of RPT attachment to the myometrium and vascularity on MRI can help the clinical assessment.博士（医学）・乙第1351号・平成26年12月3日© Springer Verlag. The definitive version is available at " http://dx.doi.org/10.1007/s00261-010-9604-x

超常磁性体酸化鉄造影MRIを用いた大動脈ステントグラフ治療後のエドリークの検出 : 造影CTとの比較検討

OBJECTIVE: Contrast-enhanced computed tomography (CE-CT) has been commonly used for follow-up imaging after endovascular aneurysm repair (EVAR), but it is difficult to use on patients with renal insufficiency. Superparamagnetic iron oxide (SPIO) particles, contrast medium for magnetic resonance imaging (MRI) that has been widely used for detection of the liver tumor, rarely affects renal function. The present study examined SPIO-enhanced dynamic MRI as a potential alternative to CE-CT for detection of endoleaks after EVAR. METHODS: Institutional review board approval was obtained for this prospective study. Twenty-three consecutive patients with normal renal function were evaluated using both CE-CT and SPIO-enhanced MRI within 2 weeks after EVAR. The median interval between the two modalities was 2 days. SPIO-enhanced MRI was performed at 1.5 T with T1-weighted, SPIO-enhanced dynamic, and postcontrast T1-weighted gradient echo sequences. The CE-CT protocol consisted of triple scans. Two experienced, blinded observers evaluated all images. Consensus reading of CE-CT and SPIO-MRI was defined as the reference standard. Interobserver, intraobserver, and intermodality agreement for endoleak detection was assessed by κ statistics. RESULTS: A total of 11 type II endoleaks originating from either the lumbar or inferior mesenteric artery were detected. Eight were able to be detected by CE-CT (8/11:73%) and 10 (10/11:91%) by SPIO-enhanced MRI. Interobserver (κ = 0.91; 95% CI, 0.74-1.00) and intraobserver agreement for MRI (κ = 1.00) were excellent. Intermodality agreement for endoleak detection was moderate (κ = 0.63; 95% CI, 0.32-0.94; and κ = 0.62; 95% CI, 0.29-0.95 for observers A and B, respectively). CONCLUSIONS: SPIO-enhanced MRI could represent a useful alternative to CE-CT, as it offers excellent interobserver, intraobserver agreement, and could detect more endoleaks than CE-CT.博士（医学）・乙第1379号・平成28年7月8日Copyright © 2013 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved

Effect of anticomplement agent K-76 COOH in hamster-to-rat and guinea pig- to-rat xenotransplantation

In normal rats, the xenobiotic K76 inhibited the C5 and probably the C2 and C3 steps of complement and effectively depressed classical complement pathway activity, alternative complement pathway activity, and the C3 complement component during and well beyond the drug's 3-hr half-life. It was tested alone and with intramuscular tacrolimus (TAC) and/or intragastric cyclophosphamide (CP) in rat recipients of heterotopic hearts from guinea pig (discordant) and hamster (concordant) donors. Single prevascularization doses of 100 and 200 mg/kg increased the median survival time of guinea pig hearts from 0.17 hr in untreated controls to 1.7 hr and 10.2 hr, respectively; with repeated injections of the 200-mg dose every 9-12 hr, graft survival time was increased to 18.1 hr. Pretreatment of guinea pig heart recipients for 10 days with TAC and CP, with or without perioperative splenectomy or infusion of donor bone marrow, further increased median graft survival time to 24 hr. Among the guinea pig recipients, the majority of treated animals died with a beating heart from respiratory failure that was ascribed to anaphylatoxins. Hamster heart survival also was increased with monotherapy using 200 mg/kg b.i.d.i.v. K76 (limited by protocol to 6 days), but only from 3 to 4 days. Survival was prolonged to 7 days with the addition to K76 of intragastric CP at 5 mg/kg per day begun 1 day before operation (to a limit of 9 days); it was prolonged to 4.5 days with the addition of intramuscular TAC at 2 mg/kg per day beginning on the day of transplantation and continued indefinitely. In contrast to the limited efficacy of the single drugs, or any two drugs in combination, the three drugs together (K76, CP, and TAC) in the same dose schedules increased median graft survival time to 61 days. Antihamster antibodies rapidly increased during the first 5 days after transplantation, and plateaued at an abnormal level in animals with long graft survival times without immediate humoral rejection. However, rejection could not be reliably prevented, and was present even in most of the xenografts recovered from most of the animals dying (usually from infection) with a beating heart. Thus, although effective complement inhibition with K76 was achieved in both guinea pig- and hamster-to-rat heart transplant models, the results suggest that effective interruption of the complement cascade will have a limited role, if any, in the induction of xenograft acceptance

Pterygoid Muscle Necrosis Caused by Radiation and Intra-Arterial Cisplatin Infusion Chemotherapy (RADPLAT): A Case Report

Introduction: Radiation and intra-arterial cisplatin infusion chemotherapy (RADPLAT) for advanced maxillary sinus cancer has accumulated evidence as a treatment with fewer complications and better 5-year survival rates. In this study, we report a case in which pterygoid muscle necrosis occurred 6 months following RADPLAT treatment for maxillary sinus cancer. Case Presentation: The 45-year-old woman had a long history of taking immunosuppressants against rheumatoid arthritis (RA) prior to treatment. Although achieving complete response (CR) to RADPLAT, the patient developed trismus (1 fingerbreadth or less) 6 months following treatment. Abscess formation and recurrence were suspected from the imaging findings; however, the biopsy with endoscopy indicated necrotic tissue. Currently, 18 months have passed without cancer recurrence. Although trismus temporarily improved with rehabilitation, the width of the mouth opening is currently a few millimeters, so the patient can only take liquid food. Conclusion: Pterygoid muscle necrosis should be recognized as a new major complication

A Case of Granulocyte-Colony Stimulating Factor-Producing Hepatocellular Carcinoma Confirmed by Immunohistochemistry

Granulocyte-colony stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation and maturation of precursor cells in the bone marrow into fully differentiated neutrophils. Several reports of G-CSF-producing malignant tumors have been published, but scarcely any in the hepatobiliary system, such as in hepatocellular carcinoma (HCC). Here, we encountered a 69-yr-old man with a hepatic tumor who had received right hepatic resection. He showed leukocytosis of 25,450/µL along with elevated serum G-CSF. Histological examination of surgical samples demonstrated immunohistochemical staining for G-CSF, but not for G-CSF receptor. The patient survived without recurrence for four years, but ultimately passed away with multiple bone metastases. In light of the above, clinicians may consider G-CSF-producing HCC when encountering patients with leukocytosis and a hepatic tumor. More cases are needed to clarify the clinical picture of G-CSF-producing HCC

Amplified EPOR/JAK2 Genes Define a Unique Subtype of Acute Erythroid Leukemia

ゲノム解析から急性赤白血病の変異プロファイルと治療標的を解明 --特定の遺伝子変異群の組み合わせと、特徴となる遺伝子の増幅が鍵--. 京都大学プレスリリース. 2022-08-05.Acute erythroid leukemia (AEL) is a unique subtype of acute myeloid leukemia characterized by prominent erythroid proliferation whose molecular basis is poorly understood. To elucidate the underlying mechanism of erythroid proliferation, we analyzed 121 AEL using whole-genome/exome and/or targeted-capture sequencing, together with transcriptome analysis of 21 AEL samples. Combining publicly available sequencing data, we found a high frequency of gains/amplifications involving EPOR/JAK2 in TP53-mutated cases, particularly those having >80% erythroblasts designated as pure erythroid leukemia (10/13). These cases were frequently accompanied by gains/amplifications of ERG/ETS2 and associated with a very poor prognosis, even compared with other TP53-mutated AEL. In addition to activation of the STAT5 pathway, a common feature across all AEL cases, these AEL cases exhibited enhanced cell proliferation and heme metabolism and often showed high sensitivity to ruxolitinib in vitro and in xenograft models, highlighting a potential role of JAK2 inhibition in therapeutics of AEL

Phosphoproteomics-Based Modeling Defines the Regulatory Mechanism Underlying Aberrant EGFR Signaling

BACKGROUND: Mutation of the epidermal growth factor receptor (EGFR) results in a discordant cell signaling, leading to the development of various diseases. However, the mechanism underlying the alteration of downstream signaling due to such mutation has not yet been completely understood at the system level. Here, we report a phosphoproteomics-based methodology for characterizing the regulatory mechanism underlying aberrant EGFR signaling using computational network modeling. METHODOLOGY/PRINCIPAL FINDINGS: Our phosphoproteomic analysis of the mutation at tyrosine 992 (Y992), one of the multifunctional docking sites of EGFR, revealed network-wide effects of the mutation on EGF signaling in a time-resolved manner. Computational modeling based on the temporal activation profiles enabled us to not only rediscover already-known protein interactions with Y992 and internalization property of mutated EGFR but also further gain model-driven insights into the effect of cellular content and the regulation of EGFR degradation. Our kinetic model also suggested critical reactions facilitating the reconstruction of the diverse effects of the mutation on phosphoproteome dynamics. CONCLUSIONS/SIGNIFICANCE: Our integrative approach provided a mechanistic description of the disorders of mutated EGFR signaling networks, which could facilitate the development of a systematic strategy toward controlling disease-related cell signaling