IMMUNOLOGIC PROPERTIES OF MOUSE THYMUS CELLS : IDENTIFICATION OF T CELL FUNCTIONS WITHIN A MINOR, LOW-DENSITY SUBPOPULATION

The functional attributes of minor subpopulations of mouse thymus cells derived by bovine serum albumin density gradient centrifugation, cortisone treatment, or selective depletion by anti-TL or anti-θ treatment have been examined. A subpopulation derived in each fashion contains the cells required to evoke graft-versus-host reactions in neonatal F1 hybrid recipients and to be stimulated by alloantigens in vitro in one-way mixed lymphocyte cultures and by phytohemagglutinin. The functions of this subpopulation are abrogated by treatment with anti-H-2 plus complement and by high concentrations of anti-θ. A tentative ordering of the various thymus cell subpopulations, on the basis of these and other data, is described

CLONAL CHARACTER OF F1 HYBRID LYMPHOCYTE SUBSET RECOGNITION OF PARENTAL CELLS IN ONE-WAY MIXED LYMPHOCYTE CULTURES

Proliferation of F1 hybrid lymphocytes in mixed lymphocyte cultures is stimulated by mitomycin-blocked parental cells. The demonstration of this phenomenon using F1 hybrids derived from congenic lines of mice establishes that the stimulation is controlled by genes in or closely linked to the major histocompatibility locus chromosome region. In agreement with the finding that tumor-bearing mice have an increased capacity for primary alloantigen recognition, it was observed that the F1 hybrid response to parent was also augmented by tumor bearing. Chromosomal analysis of dividing cells in one-way mixed cultures confirms that F1 cells, and not the blocked parental cells, enter mitosis. Stimulation of F1 cells by a soluble mediator liberated by the parental cells was not observed and mitomycin blocking of parental cells seems to be a completely effective blocking agent ensuring that parental cells can not enter DNA synthesis. The specificity and clonal nature of F1 recognition of parent was demonstrated using a 5-bromodeoxyuridine-suicide procedure. Distinct clones of lymphocytes in F1 spleen cell populations seem to recognize one or the other parent, but not both, in such experiments. These observations and others in tumor systems suggest that most or all heterozygous organisms may possess potentially self-reactive clones of lymphocytes

Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: A matched-pair analysis

Acute myeloid leukemia (AML) with t(6;9)(p23;q34) is well known to have a poor prognosis treated with chemotherapy and autotransplantation. The presence of this karyotype is an indicator for allogeneic hematopoietic stem cell transplantation (HSCT); however, the impact of t(6;9)(p23;q34) on the HSCT outcome remains unclear. We conducted a matched-pair analysis of de novo AML patients with and without t(6;9)(p23;q34) using data obtained from the Japanese HSCT data registry. A total of 57 patients with t(6;9)(p23;q34) received transplants between 1996 and 2007, and 171 of 2056 normal karyotype patients matched for age, disease status at HSCT and graft source were selected. The overall survival, disease-free survival, cumulative incidence of relapse and the non-relapse mortality in t(6;9)(p23;q34) patients were comparable to those for normal karyotype patients. A univariate analysis showed that t(6;9)(p23;q34) had no significant impact on the overall survival. These findings suggest that allogeneic HSCT may overcome the unfavorable impact of t(6;9)(p23;q34) as an independent prognostic factor. © 2012 Macmillan Publishers Limited All rights reserved

Prognostic factors for acute myeloid leukemia patients with t(6;9)(p23;q34) who underwent an allogeneic hematopoietic stem cell transplant

We have recently reported that the outcome of acute myeloid leukemia (AML) patients with t(6;9)(p23;q34) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) was comparable to that of patients with a normal karyotype. We performed a further analysis regarding the prognostic factors for t(6;9)(p23;q34) AML patients who underwent a HSCT. Seven pediatric patients and 57 adult patients, transplanted between 1996 and 2007, were assessed in this study. The overall survival (OS) of the pediatric patients tended to be better than the OS of the adults, although there were no statistically significant differences. The present study focused on the adult patients revealed that the disease status at HSCT was the sole prognostic factor affecting the OS identified in the univariate analysis. A multivariate analysis showed that the disease status at HSCT and M2 in the FAB classification were extracted as the significant variables affecting the OS. The patients who were not in remission at HSCT and had non-FAB-M2 showed a poorer outcome; 6 deaths in the 9 patients were due to a relapse of the AML. These findings suggest that novel therapeutic approaches might be needed for patients with these poor prognostic factors.発行後6か月より全文公開

カンイガタ ジキシキ ショクジ レキホウ シツモンヒョウ（BDHQ） オ モチイタ ガイライ トウニョウビョウ エイヨウ シドウ タイショウシャ チュウシュツホウ ニカンスル ケントウ

【背景】地域に開かれた無床診療所には、管理栄養士はほとんど常勤しておらず、栄養指導が必要な生活習慣 病患者に対する指導でさえも十分に実施できていない現状がある。また、糖尿病栄養指導対象者抽出については、医 師の主観（治療歴、患者背景、患者の性格等）や血液検査値等の客観的指標のみを参考にしており、必ずしも食事調 査結果に基づいた抽出をしている訳ではない。そのため、実際に食習慣が乱れており、糖尿病栄養指導の必要性が高 い患者に対して効率良く栄養指導ができているとは言い難い。 【目的】無床診療所における外来糖尿病患者の治療効果を向上させるため、BDHQ から得られた食事調査結果を活 用した新しい外来糖尿病栄養指導対象者抽出法を確立すること。 【方法】M 医院（大阪府阪南市）に通院している2 型糖尿病患者のうち、研究の趣旨に同意が得られた109 名（男 性77 名、女性32 名、平均年齢64.7±7.4 歳）にBDHQ を実施し、ある1 日の平均的な「栄養素摂取量」を算出し た。次いで当該患者カルテの検査値（HbA1c、クレアチニン等）を記録し、食事調査結果と組み合わせた栄養指導 対象者抽出基準を検討した。 【結果および考察】糖尿病食事療法のうち、栄養基準が大きく変化する糖尿病性腎症第3 期B に該当する患者は、 109 名中25 名であった。このうち、BDHQ から得られたたんぱく質摂取量が1.0g/kg 標準体重/日を上まっている 患者は17 名であり、特にこれらの患者は管理栄養士による詳細な栄養指導を受ける必要性が高いことが考えられる。 BDHQ は集団での妥当性はある程度証明されているが、個人での妥当性は証明されていない。そのため得られた結 果の解釈には慎重な配慮を要する。しかし、少なくとも今回のように、無床診療所において管理栄養士による詳細な 栄養指導を受ける必要性があるか否かを大雑把に判定するような目的には最適であろうと考えられた。Purpose: To improve therapeutic efficacy of ambulatory patients with diabetes in non-bed clinics and to establish a new method of identifying subjects at risk of diabetes related complications using a dietary survey obtained from a brief self administered diet history questionnaire（BDHQ）. Methods: Among patients with type 2 diabetes attending M clinic（Osaka, Japan）, 109 gave informed consent（male 77, female 32, mean age 64.7 ± 7.4 years）. A BDHQ was administered to calculate the average “nutrient intake” per day. The test results in the patients’ medical records（HbA1c, creatinine, etc.） were recorded. The criteria for identifying patients requiring nutritional guidance were also examined in conjunction with the dietary surveys. Results: For 25 of the participants, their nutritional standards put them at risk of third phase B diabetic nephropathy. Of these, the protein intake of 17, as calculated from the BDHQ, was >1.0 g/kg/day. It was considered essential that these patients receive detailed nutritional guidance from registered dietitians. Although the relevance of administering group BDHQ is to some extent proved, the benefit for the individual has not been demonstrated. The interpretation of the results must, therefore, be viewed with caution. However, there are indicators that suggest detailed nutritional guidance by registered dietitians at non bed clinics would be advisable. Keywords: Non bed Clinic, I

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI

BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed

The DBCLS BioHackathon: standardization and interoperability for bioinformatics web services and workflows. The DBCLS BioHackathon Consortium*

Web services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands for efficient systems without the need to transfer entire databases for every step of an analysis. However, various incompatibilities among database resources and analysis services make it difficult to connect and integrate these into interoperable workflows. To resolve this situation, we invited domain specialists from web service providers, client software developers, Open Bio* projects, the BioMoby project and researchers of emerging areas where a standard exchange data format is not well established, for an intensive collaboration entitled the BioHackathon 2008. The meeting was hosted by the Database Center for Life Science (DBCLS) and Computational Biology Research Center (CBRC) and was held in Tokyo from February 11th to 15th, 2008. In this report we highlight the work accomplished and the common issues arisen from this event, including the standardization of data exchange formats and services in the emerging fields of glycoinformatics, biological interaction networks, text mining, and phyloinformatics. In addition, common shared object development based on BioSQL, as well as technical challenges in large data management, asynchronous services, and security are discussed. Consequently, we improved interoperability of web services in several fields, however, further cooperation among major database centers and continued collaborative efforts between service providers and software developers are still necessary for an effective advance in bioinformatics web service technologies