Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer

Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL

びまん性血管損傷 磁化率強調画像を用いた重症頭部外傷での収束性出血

INTRODUCTION:Susceptibility-weighted image (SWI) is one of the most sensitive methods for detect microbleeding and useful for evaluation of traumatic brain damage. The purpose of this study is to delineate the characteristics and importance of supratentorial deep white matter hemorrhages detected by SWI in cases of traumatic brain damage. METHODS:Twenty-one consecutive cases with severe traumatic head injury were included in the current study. MRI examinations were made within 1 month after injury. We evaluated the degree and distribution of the supratentorial hemorrhages on SWI retrospectively. We classified the degree of bleeding into four grades: "small hemorrhage," "single bead-like hemorrhage," "convergent-type hemorrhage," and "massive hemorrhage." We then correlated the degree and distribution of the hemorrhage to clinical outcomes. We also evaluated the apparent diffusion coefficient (ADC) image of lobes with "convergent-type hemorrhage." RESULTS:Existence of "massive hemorrhage" correlated with a poor outcome, that is, worse than "severely disabled" on the Glasgow Outcome Scale. The number of lobes affected by "convergent-type hemorrhage" also correlated with poor outcome. There were 45 lobes with "convergent-type hemorrhage" and 27 of them showed increased diffusivity on ADC images. CONCLUSION:Supratentorial massive hemorrhages and supratentorial convergent-type multiple hemorrhages were associated with poor prognosis after traumatic brain injury. The increased diffusivity in lobes with convergent-type hemorrhages may indicate that congestion of the proximal medullary vein may play some role for these hemorrhages.博士（医学）・甲第594号・平成25年3月15日© Springer International Publishing AG,201

Diagnostic Utility of SOX4 Expression in Adult T-Cell Leukemia/Lymphoma

Differentiation between adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is often challenging based on pathological findings alone. Although serum anti-HTLV-1 antibody positivity is required for ATLL diagnosis, this information is often not available at the time of pathological diagnosis. Therefore, we examined whether the expression of SOX4 and p16 would be helpful for differentiating the two disease entities. We immunohistochemically examined SOX4 and p16 expression (which have been implicated in ATLL carcinogenesis) in 11 ATLL patients and 20 PTCL-NOS patients and classified them into four stages according to the percentage of positive cells. Among the ATLL cases, 8/11 (73%) were SOX4-positive, while only 2/20 (10%) PTCL-NOS cases expressed SOX4. The mean total score was 4.2 (standard deviation (SD): 0.61) in the ATLL group and 0.50 (SD: 0.46) in the PTCL-NOS group (p < 0.001). Positive expression of p16 was noted in 4/11 (36%) patients with ATLL and 3/20 (15%) patients with PTCL-NOS, with mean total scores of 1.9 (SD: 0.64) and 0.70 (SD: 0.48) in the ATLL and PTCL-NOS groups, respectively (p = 0.141). These results suggest that SOX4 may be strongly expressed in ATLL compared to PTCL-NOS cases. Therefore, it may be helpful to perform immunohistochemical staining of SOX4 when pathologists face challenges discriminating between ATLL and PTCL-NOS

PD-L1 expression is associated with the spontaneous regression of patients with methotrexate-associated lymphoproliferative disorders

Background Most patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) show diffuse large B-cell lymphoma (DLBCL) or classic Hodgkin lymphoma (CHL) types. Patients with MTX-LPD often have spontaneous remission after MTX discontinuation, but chemotherapeutic intervention is frequently required in patients with CHL-type MTX-LPD. In this study, we examined whether programmed cell death-ligand 1 (PD-L1) expression levels were associated with the prognosis of MTX-LPD after MTX discontinuation. Methods A total of 72 Japanese patients diagnosed with MTX-LPD were clinicopathologically analyzed, and immunohistochemical staining of PD-L1 was performed in 20 DLBCL-type and 24 CHL-type MTX-LPD cases to compare with the clinical course. Results PD-L1 was expressed in 5.0% (1/20) of patients with DLBCL-type MTX-LPD, whereas it was expressed in 66.7% (16/24) of the patients with CHL-type MTX-LPD in more than 51% of tumor cells. Most CHL-type MTX-LPD patients with high PD-L1 expression required chemotherapy owing to exacerbations or relapses after MTX discontinuation. However, no significant differences in clinicopathologic findings at diagnosis were observed between PD-L1 high- and low-expression CHL-type MTX-LPD. Conclusion PD-L1 expression was significantly higher in patients with CHL-type than DLBCL-type MTX-LPD, suggesting the need for chemotherapy in addition to MTX discontinuation in CHL-type MTX-LPD patients to achieve complete remission. No association was observed between PD-L1 expression levels and clinical findings at diagnosis, suggesting that PD-L1 expression in tumor cells influences the pathogenesis of CHL-type MTX-LPD after MTX discontinuation

The astrometric Gaia-FUN-SSO observation campaign of 99 942 Apophis

Astrometric observations performed by the Gaia Follow-Up Network for Solar System Objects (Gaia-FUN-SSO) play a key role in ensuring that moving objects first detected by ESA's Gaia mission remain recoverable after their discovery. An observation campaign on the potentially hazardous asteroid (99 942) Apophis was conducted during the asteroid's latest period of visibility, from 12/21/2012 to 5/2/2013, to test the coordination and evaluate the overall performance of the Gaia-FUN-SSO . The 2732 high quality astrometric observations acquired during the Gaia-FUN-SSO campaign were reduced with the Platform for Reduction of Astronomical Images Automatically (PRAIA), using the USNO CCD Astrograph Catalogue 4 (UCAC4) as a reference. The astrometric reduction process and the precision of the newly obtained measurements are discussed. We compare the residuals of astrometric observations that we obtained using this reduction process to data sets that were individually reduced by observers and accepted by the Minor Planet Center. We obtained 2103 previously unpublished astrometric positions and provide these to the scientific community. Using these data we show that our reduction of this astrometric campaign with a reliable stellar catalog substantially improves the quality of the astrometric results. We present evidence that the new data will help to reduce the orbit uncertainty of Apophis during its close approach in 2029. We show that uncertainties due to geolocations of observing stations, as well as rounding of astrometric data can introduce an unnecessary degradation in the quality of the resulting astrometric positions. Finally, we discuss the impact of our campaign reduction on the recovery process of newly discovered asteroids.Comment: Accepted for publication in A&

AUTS2 Governs Cerebellar Development, Purkinje Cell Maturation, Motor Function and Social Communication

Autism susceptibility candidate 2 (AUTS2), a risk gene for autism spectrum disorders (ASDs), is implicated in telencephalon development. Because AUTS2 is also expressed in the cerebellum where defects have been linked to ASDs, we investigated AUTS2 functions in the cerebellum. AUTS2 is specifically localized in Purkinje cells (PCs) and Golgi cells during postnatal development. Auts2 conditional knockout (cKO) mice exhibited smaller and deformed cerebella containing immature-shaped PCs with reduced expression of Cacna1a. Auts2 cKO and knock-down experiments implicated AUTS2 participation in elimination and translocation of climbing fiber synapses and restriction of parallel fiber synapse numbers. Auts2 cKO mice exhibited behavioral impairments in motor learning and vocal communications. Because Cacna1a is known to regulate synapse development in PCs, it suggests that AUTS2 is required for PC maturation to elicit normal development of PC synapses and thus the impairment of AUTS2 may cause cerebellar dysfunction related to psychiatric illnesses such as ASDs

A Report on Overseas Teaching Practicum by Graduate Students in Elementary/Secondary Schools in the United States (Ⅶ)

The present reports is on the 7th overseas teaching practicum in the United States by 15 graduate students of Hiroshima University, Japan, partly organized by Hiroshima University Global Partnership School Center since 2007. The group was comprised of 13 elementary school and 2 secondary school education major graduate students. They planned and conducted lessons in English in three local public schools in North Carolina. The expected outcomes of this project were: 1) to self-develop practical instructional competence by teaching pupils with diverse backgrounds in the U.S.; 2) to enhance the abilities in developing teaching materials through hands-on teaching experiences in English; and 3) to acquire the abilities to design, implement and evaluate programs for promoting global partnership. In addition, the teaching experience was followed by cross-cultural study visits to Raleigh, NC and Washington, D.C. It helped to boost our group motivation that the local media, newspaper and TV, and the city Board of Education covered our visit. It is hoped that this project will enhance the students’ teaching competence in designing quality materials/lessons and classroom communication skills in English

The astrometric Gaia-FUN-SSO observation campaign of 99942 Apophis

© 2015 ESO. Aims. Astrometric observations performed by the Gaia Follow-Up Network for Solar System Objects (Gaia-FUN-SSO) play a key role in ensuring that moving objects first detected by ESA's Gaia mission remain recoverable after their discovery. An observation campaign on the potentially hazardous asteroid (99 942) Apophis was conducted during the asteroid's latest period of visibility, from 12/21/2012 to 5/2/2013, to test the coordination and evaluate the overall performance of the Gaia-FUN-SSO. Methods. The 2732 high quality astrometric observations acquired during the Gaia-FUN-SSO campaign were reduced with the Platform for Reduction of Astronomical Images Automatically (PRAIA), using the USNO CCD Astrograph Catalogue 4 (UCAC4) as a reference. The astrometric reduction process and the precision of the newly obtained measurements are discussed. We compare the residuals of astrometric observations that we obtained using this reduction process to data sets that were individually reduced by observers and accepted by the Minor Planet Center. Results. We obtained 2103 previously unpublished astrometric positions and provide these to the scientific community. Using these data we show that our reduction of this astrometric campaign with a reliable stellar catalog substantially improves the quality of the astrometric results. We present evidence that the new data will help to reduce the orbit uncertainty of Apophis during its close approach in 2029. We show that uncertainties due to geolocations of observing stations, as well as rounding of astrometric data can introduce an unnecessary degradation in the quality of the resulting astrometric positions. Finally, we discuss the impact of our campaign reduction on the recovery process of newly discovered asteroids

経仙骨式到達法による膀胱直腸瘻閉鎖術

膀胱あるいは尿道直腸痩の閉鎖術式には各種の到達法がある。しかしいずれも一長一短があって絶対的なものはない。一般にはYoungおよびStoneのpull- through operation が推奨されているが，膀胱直腸痩では狭い視野の奥深い部位での操作が要求され，確実に修復することは必ずしも容易ではない。著者は，外傷によって膀胱頚部から前立腺左葉を貫通して直腸に至る痩孔を形成し，しかも数次にわたる開腹手術，経膀胱的手術の既往を有する21歳男子症例対し，経仙骨式到達法による痩孔閉鎖術を施行した。その結果，前立腺膀胱頚部付近を容易に露出でき，痩孔は直視下に確実に切除，縫合することが可能であった。経仙骨式到達法は，このアプローチによる前立腺摘出術を施行している一部の専門家を除けば，まだ一般化していないが，腹式あるいは会陰式到違法で操作図難と予想される後部尿道ないし膀胱頸部先頭部付近の手術には用いられてしかるべき方法であると考えられる