Monocyte/macrophage response to β2-microglobulin modified with advanced glycation end products

Monocyte/macrophage response to β2-microglobulin modified with advanced glycation end products. We recently found that acidic β2-microglobulin (β2m), a major isoform of β2m in amyloid fibrils of patients with dialysis-related amyloidosis (DRA), contained early Amadori products and advanced glycation end products (AGEs) formed nonenzymatically between sugar and protein. Further analysis revealed that acidic β2m induces monocyte chemotaxis and macrophage secretion of bone-resorbing cytokines, suggesting the involvement of acidic β2m in the pathogenesis of DRA. Acidic β2m, however, is a mixture of heterogeneous molecular adducts due to various types of modification. In the present study, we investigated the modification responsible for the biological activity of acidic β2m toward monocytes/macrophages. The presence of a fair amount of β2m species with deamidation was detected in acidic β2m isolated from urine of non-diabetic long-term hemodialysis patients, but deamidated β2m had no biological activity. In contrast, normal β2m acquired the activity upon incubation with glucose in vitro. Among the glycated β2m, the pigmented and fluorescent β2m that formed after a long incubation period, that is, AGE-modified β2m, exhibited biological activity, whereas β2m modified with Amadori products, major Maillard products in acidic β2m, had no such activity. These findings suggest that AGEs, although only a minor constituent of acidic β2m, are responsible for monocyte chemotaxis and macrophage secretion of cytokines, implicating the contribution of AGEs to bone and joint destruction in DRA

R-mini CHP in ≥80-year-old Patients with Diffuse Large B-cell Lymphoma: A Multicenter, Open-label, Single-arm Phase II Trial Protocol

In very-elderly diffuse large B-cell lymphoma (DLBCL) patients, treatment intensities must be lowered due to the risks of comorbidities and organ function deterioration, and treatment outcomes are worse compared to younger patients. Very-elderly patients are often excluded from DLBCL clinical trials, and optimal treatments and dosages are not established. In this clinical trial, we examined the efficacy and safety of 6 courses of R-mini CHP therapy (cf., CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]) in which vincristine is omitted to avoid the peripheral neuropathy that reduces elderly patients’ quality of life, as remission induction therapy in DLBCL patients aged≥80 years

Esophageal Adenocarcinoma Developing after Eradication of Helicobacter pylori

A 75-year-old man underwent endoscopic hemostatic therapy for hemorrhagic gastric ulcer in September 2002. After healing of the gastric ulcer, he underwent Helicobacter pylori eradication therapy in February 2003. In August 2007, an irregular tumor was detected in the lower esophagus at annual checkup for gastric cancer screening using X-ray. Endoscopic examination showed that the lower margin of the tumor almost coincided with the esophagogastric junction and that a short segment of Barrett's epithelium existed near the tumor. Biopsies of the tumor showed moderately to poorly differentiated adenocarcinoma. Mild reflux esophagitis and minor hiatal hernia was also observed, and the previously treated gastric ulcer was not recurrent. Absence of H. pylori was confirmed by serum antibody and urea breath test. Surgical resection of the lower esophagus and proximal stomach was performed. The tumor invaded into the muscularis propria of the esophageal wall but had no evidence of lymph node metastasis. Based on macroscopic and pathological findings, the tumor was recognized as esophageal adenocarcinoma. Previous endoscopic examination did not detect any apparent signs of tumor in the esophagogastric junction. As far as we know, this is the first report documenting a newly developed esophageal adenocarcinoma after the successful eradication of H. pylori

Treatment responses and their predictors in patients with rheumatoid arthritis treated with biological agents

Biological agents represent an important advancement in for the treatment of rheumatoid arthritis (RA), but there is a subset of patients who do not improve despite therapy. This study aimed to determine the efficacy of biological agents for RA and to identify clinical factors that are associated with their response. We studied 98 patients with RA who started an initiating biological agent which was selected from infliximab, etanercept, adalimumab and tociliximab at 4 medical institutions. Etanercept was the most frequently used biological agent followed by infliximab although there was a difference in the selection of the biological agents among medical institutions. We found that etanercept achieved the highest treatment response, remission rate and drug survival rate. A high disease activity in the baseline disease activity score-c-reactive protein (CRP) was shown to be a negative predictor of the treatment response, and high patient global assessment was significantly less likely to achieve a good response. At week 4, decreases in 28 swollen joint counts and CRP were useful as predictors for sustaining the efficacy up to week 48. These data demonstrate that assessments of the disease activity at baseline and the early treatment response may be useful in predicting the efficacy and drug survival rate of biological agents

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

トウキョウ ノウギョウ ダイガク ガクセイ ガ ガクガイ ノウギョウ ケンキュウ ニ タイシテ キタイスル ヨウソ ノ トウケイガクテキ チュウシュツ

東京農業大学農学部にて開講されている，農業ビジネスデザインの受講学生を対象に，学生が学外農業研修で感じた「良かった点」の特徴を明らかにすることを目的として，自由記述によるアンケートを実施した。データ化した自由記述回答にテキストマイニングを施し，抽出した名詞の出現件数のデータに数量化Ⅲ類解析を施した。その結果，研修を主催する個人農家・企業，自治体，大学，の3属性によって，良かった点の内容が異なる1軸を含む3つの有効軸が算出された。本研究により，研修を受けた学生が現地に対して感じた良かった点は，‘人’および‘農家’の要素によって説明できると考えられた。これらの要素は同時に，農業志向の高い若者が農業研修に対して期待するものとして解釈することができると考えられ，今後，研修先との情報共有，意思疎通および研修内容の改善を通して，研修生と受け入れ先とのマッチングに役立てるなど，日本農業の担い手育成のためのPDCAサイクル化に大いに役立つと考えられた。A questionnaire based on free description was conducted with the aim of clarifying the features of “positive characteristics of the agricultural training course” that students felt through participating in agricultural training held outside the campus as part of “Studies for agricultural career design”, held at the Faculty of Agriculture, Tokyo University of Agriculture. The obtained responses were typed up and analyzed by text-mining method and multivariate analysis of the quantification theory type 3 was demonstrated on converted category (1/0) data based on the appearance of extracted nouns in answerers’ responses. As results, 3 axes including 1 axis where the mean value of the score according to the classification of the promoter mediating agricultural training courses significantly differed, were calculated. According to these results, the “positive characteristics of the agricultural training courses” that students felt, were might be summarized as the experience of “person” and “farmer”. It was also thought that these components could be interpreted as what expected of an agricultural experience program by the agriculture-minded young. In conclusion, findings in this study could be utilized as information sharing and communication tools in the training place for improvements in training contents, and would be useful for PDCA cycling, such as helping the match between students and training places, in developing agricultural human resources