Immune thrombocytopenic purpura （ITP） is characterized by inhibition/destruction of megakaryocytes in bone marrow （BM） and/or platelets in the spleen and liver. Interleukin-（IL-）17-mediated cells contribute to the imbalance of cellular immunity in the pathogenesis of ITP. Therefore, we examined samples of BM clots to observe the morphological change of megakaryocytes and to test whether IL-17-mediated immunological changes occur in the BM of patients with ITP.　We enrolled 33 patients who were diagnosed with chronic ITP. BM clots were obtained before treatment and stained with hematoxylin and eosin stains for morphological examination and the following markers: CD3, CD4, CD8, CD20, CD25, CD68, CD163, and IL-17. Pathological findings were compared between the ITP patient samples and 11 control samples from patients with malignant lymphoma without infiltration of lymphoma cells. Univariate analysis revealed that patients with ITP had increased numbers of cells expressing CD68, CD163, and IL-17 compared with the control subjects （P ＜0.05）. There were significant correlations between CD68 and CD163 expression levels, and these markers also showed correlations with IL-17 expression．IL-17 expression showed the same distribution as these cells’ expression in immunohistochemical （IHC） staining. Our results indicate that macrophages and monocytes may be involved in deregulated expression of IL-17 in BM of ITP. We suggest that BM examination and IHC staining in patients with ITP may lead to a better understanding of the mechanism of ITP and the pathological diagnosis.

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A disintegrin and metalloprotease 15 （ADAM-15） is expressed in several malignancies. However, the relationship between ADAM-15 and rheumatoid arthritis （RA） is still unclear. In this study, we investigated the role of ADAM-15 in RA angiogenesis. RA and normal （NL） serum, and in the same way, RA and osteoarthritis （OA） synovial fluids were obtained from RA patients and control patients. ADAM-15 expression was determined in serum and synovial fluid from RA and NL using ELISA. To determine ADAM-15 expression in RA synovial tissues, immunohistochemistry was performed. To determine the role of ADAM-15 in RA, cytokines in ADAM-15 siRNA-treated human umbilical vein endothelial cell （HUVEC） was measured. Then, in order to confirm the role of angiogenesis, we did Matrigel assays in vitro. Finally, to determine whether ADAM-15 mediates adhesion to ECs, we performed in vitro adhesion assays. ADAM-15 in RA serum was significantly higher compared with NL and it was significantly higher in RA compared with OA synovial fluids. ADAM-15 is expressed on the endothelial cell in RA synovial tissues. ENA-78/CXCL5 and ICAM-1 in TNF-α-stimulated ADAM-15 siRNA-transfected HUVEC conditioned medium were decreased compared with in TNF-α-stimulated control siRNA-transfected HUVEC conditioned medium. ADAM-15 siRNA-treated HUVECs had a decreased EC line and tube formed in response to RA synovial fluids compared with non-treated HUVECs. Adhesion index of ADAM-15 siRNA transfected HUVECs was significantly decreased compared with adhesion index of control siRNA transfected HUVECs. These data show ADAM-15 plays a role in RA angiogenesis, suggesting that ADAM-15 may be a potential target in inflammatory diseases such as RA.

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The “A disintegrin and metalloprotease” （ADAM） family is thought to play an important role in tissue destruction and inflammatory reactions. ADAM-17 was first described as the protease responsible for tumor necrosis factor （TNF）-α shedding. Here, we show the expression of ADAM-17 in inflammatory myopathy and demonstrate the role of inflammation in interstitial lung disease （ILD）. ADAM-17, in inflammatory myopathy sera ［polymyositis （n＝26）, dermatomyositis （n＝34） and clinically amyopathic dermatomyositis （n＝10）］ and in the sera of healthy controls （n＝19）, was measured using enzyme-linked immunosorbent assay. The relationship between ADAM-17 and clinical data was examined. We performed immunohistological analysis to investigate the expression of ADAM-17 on the muscles of the inflammatory myopathy patients. ADAM-17 in inflammatory myopathy was significantly higher than in healthy controls （mean±SEM; 1,048±312pg/ml and 36±18 pg/ml, respectively, p＜0.05）. ADAM-17 in post-treatment with corticosteroid and/or immunosuppressant serum was significantly decreased compared with that in pre-treatment serum （1,465±562pg/ml and 1,059±503pg/ml, respectively, p＜0.01）. ADAM-17 was significantly positively correlated with fractalkine/CX3CL1 and CXCL16. In addition, ADAM-17 in ILD patients （n＝46） with inflammatory myopathy was significantly higher than in non-ILD patients （n＝24） （1,379±454pg/ml and 413±226 pg/ml, respectively, p＜0.05）. We uncovered the expression of ADAM-17 on muscle biopsy tissue. ADAM-17 is expressed in inflammatory myopathies, particularly in ILD, suggesting that ADAM-17 plays a role in lung fibrosis. ADAM-17 may be a potential therapeutic target in inflammatory myopathies with ILD.

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Pitching involves the combined motion of the entire body. Injury is common in the acceleration phase of the pitching motion. Previous studies have reported on factors like the load placed on joints during this phase. The complexity of the combined motions makes evaluating a single pattern challenging. In such a complex motion, the rotational angle of the shoulder joint is affected by the position of the elbows and forearms, rendering evaluation of the rotational angle during pitching motion difficult. In this study, we investigated the pitching motion of 6 right-handed individuals experienced in baseball, without a history of arm surgery. Five throws were analyzed per individual. Subjects wore marker bases and anchors that we developed for recording via a motion capture system. Changes in the humeral rotation angle were calculated based on spatial coordinates obtained using software that analyzes 3D motion over time. The mean rotation angle across all attempts was 113.13°; the maximum and minimum rotational angles of the humerus were 190.29±1.36° （p＜0.05） and 34.82±2.09° （p＜0.05）, respectively. The rotational angle of the shoulder joint of the 5 subjects immediately before ball release decreased to approximately 20°. However, this value for one individual was 129.37±5.53° （p＜0.05）, showing a significant difference （p＝0.00033）. The measurement of shoulder joint rotation, immediately before ball release, reflects the individualized pitching motions. Unlike previous reports, the possibility of mathematical analysis of pitching motion images （with the humerus as an index） indicates that this method can be used for clinical evaluation. We plan to conduct additional high-precision studies on shoulder joint rotation in a group of disabled individuals to advance the prevention and treatment of shoulder disorders due to pitching.

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During solid tumor development, tumor cells, known as circulating tumor cells （CTCs）, invade the peripheral blood. Although the mechanisms of invasive and metastatic behaviors of CTCs are not fully understood, CTCs are an important prognostic marker for cancer patients, providing information for the therapy and follow-up. We have challenged CTC analysis by flow cytometry. In this article, we focus on our recent development on the enumeration of intact CTCs.

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The management of pediatric bronchial asthma has improved drastically with the popularization of inhalable steroids. Because of this, the improvement of adherence in pharmacotherapy has become a new important clinical issue in asthma treatment. We attempted to improve adherence through asthma guidance and verified our evaluation using the new adherence evaluation questionnaire, “Pediatric Asthma Adherence Questionnaire （PAAQ）”. We delivered asthma guidance to our subjects: children participating in the district-hosted bronchial asthma health classes in Tokyo and their guardians. The subjects receiving the intervention were the Shinagawa District Swimming Class （guardian intervention）, the Shinagawa District Summer Health Class （patient intervention）, and the Edogawa District Swimming Class （no intervention）. The guardian intervention group received one 40-minute lecture, while the patient intervention group received five 40-minute lectures. We then analyzed the results, with the change in the PAAQ before and after the guidance being the main evaluation point, and evaluated 12 other adherence inquiries as well. The analysis targets were 9 members of the Shinagawa District Swimming Class, 15 members of the Edogawa District Swimming Class, and 14 members of the Shinagawa District Summer Health Class. We did not note any significant difference in the patient characteristics among the three groups. The PAAQ did not show any significant differences before and after the intervention in all three groups, although some of the other questions were answered negatively after intervention. We did not note any marked change in the PAAQ through asthma guidance intervention. We hope to develop a more efficient guidance method in order to improve adherence in the future.

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Given the current clinical situation, there is an increasing need for ethics education programs for medical professionals’ ethical sensitivity. We studied the issue of medical ethics education in terminal care by examining the difference in consciousness for euthanasia and dignity between medical students and liberal arts students. The data obtained were statistically analyzed with regard to the students’ field of specialty. When considering euthanasia, medical students held the opinion of “disagree” for their family and for themselves more frequently than liberal arts students. The medical students who were clinicians, held the opinion of “agree” for ‘dignity with meeting conditions’ more frequently than liberal arts students. Most medical students desired legislation for ‘death with dignity’ though the opinions of liberal arts students were divided between “desire” and “not desire” regarding dignity and euthanasia. From the results obtained there were definite differences between the 2 groups of students. The conclusion seems to be that medical students would not perform passive euthanasia or death with dignity, and their moral conscientiousness was shaken by the sense of resistance to ethical issues in terminal care. It is very important for not only medical students but also clinicians to develop their ethical sensitivity by medical ethics education. The present study seems to indicate that the upward and downward fluctuations between medical knowledge and the clinical issues regarding medical ethics education have become recently considered to be important even in terminal care.

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Japan is under a circumstance in that the number of deaths will continue to increase up to the year 2040. The aim of this study is to suggest the development of a new system of death diagnosis and the issuance of a death certificate under such circumstances. This study was to assess the recognition by medical students and non-medical students of the idea of a death diagnosis and the issuance of a death certificate by nurses. In the case of a terminally ill patient undergoing medical treatment who dies at home in the company of a nurse, 46.3％ of medical students and 61.5％ of non-medical students felt that the nurse may diagnose the patient’s death. In addition, under these circumstances, 32.2％ of medical students and 39.0％ of non-medical students felt that the nurse may issue a death certificate. Interestingly, at this time, Japan is undergoing a review process of how doctors work, including task shift; advanced medical treatment is becoming recognized as the work of a nurse according to the Act on Public Health Nurses, Midwives and Nurses. Further, a comprehensive community care system, which aims for the continuation of patients to live in a familiar area until the end of life, has been promoted. In addition, several western countries or states have legalized death diagnosis by nurses. On the basis of our results and consideration, we suggest revision of the law to allow nurses to make a death diagnosis, including the judgement of an abnormal death, in the case of terminally ill patients dying at home.

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