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Fukutomi M.,Yamaguchi Grand Medical Center | Kario K.,Jichi Medical University
Expert Review of Cardiovascular Therapy | Year: 2010

Aging is known to be a dominant risk factor in the progression of hypertension. Thus, accompanied by an increasing mean age of the population in developed countries, prevention and management of hypertension in the elderly is a task of pressing urgency. Age-associated blood pressure elevation is a result of the aging process in organ systems, which play a key role in the regulation of blood pressure. In addition, advanced aging of the cardiovascular system contributes to the presence of a varied phenotype in elderly hypertension, such as nocturnal hypertension and morning hypertension. Therefore, in order to detect and treat age-associated hypertension appropriately, it is important to assess ambulatory blood pressure monitoring throughout the 24-h period. © 2010 Expert Reviews Ltd. Source

Tanaka H.,Yamaguchi Grand Medical Center | Tanaka H.,U.S. National Institute on Aging | Mine T.,Yamaguchi University | Ogasa H.,U.S. National Institute on Aging | And 4 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

The interaction between receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation.Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen α1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The expression of bone formation markers was activated in the bone formation phase, followed by the stimulation of RANKL/OPG expression in the bone resorption phase, which confirmed that these molecules are key factors linking bone formation to resorption during bone remodeling. © 2011 Elsevier Inc. Source

Suzuki K.,Yamaguchi Grand Medical Center
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2013

A 34-year-old man experienced lower limb ischemia due to tumor emboli as an initial symptom. Histopathologic examination of the embolic material revealed undifferentiated sarcoma. By echocardiography the original tumor was arising from the posterior mitral leaflet, and therefore, excision of the mitral valve resulted in complete resection of the sarcoma. Mitral valve replacement was performed, and his postoperative course was uneventful. He did not receive postoperative adjuvant therapy. The patient has been undergoing positron emission tomography and electrocardiography on an outpatient basis to check for signs of recurrence. However, no signs of recurrence have been detected for 7 years postoperatively, and the patient leads an active life. Source

Nishimura J.-I.,Osaka University | Yamamoto M.,Osaka University | Hayashi S.,Tokyo Medical and Dental University | Ohyashiki K.,Tokyo Medical University | And 19 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: Eculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement-mediated hemolysis associated with paroxysmal nocturnal hemoglobinuria (PNH). The molecular basis for the poor response to eculizumab in a small population of Japanese patients is unclear. METHODS: We assessed the sequences of the gene encoding C5 in patients with PNH who had either a good or poor response to eculizumab. We also evaluated the functional properties of C5 as it was encoded in these patients. RESULTS: Of 345 Japanese patients with PNH who received eculizumab, 11 patients had a poor response. All 11 had a single missense C5 heterozygous mutation, c.2654G→A, which predicts the polymorphism p.Arg885His. The prevalence of this mutation among the patients with PNH (3.2%) was similar to that among healthy Japanese persons (3.5%). This polymorphism was also identified in a Han Chinese population. A patient in Argentina of Asian ancestry who had a poor response had a very similar mutation, c.2653C→T, which predicts p.Arg885Cys. Nonmutant and mutant C5 both caused hemolysis in vitro, but only nonmutant C5 bound to and was blocked by eculizumab. In vitro hemolysis due to nonmutant and mutant C5 was completely blocked with the use of N19-8, a monoclonal antibody that binds to a different site on C5 than does eculizumab. CONCLUSIONS: The functional capacity of C5 variants with mutations at Arg885, together with their failure to undergo blockade by eculizumab, account for the poor response to this agent in patients who carry these mutations. (Funded by Alexion Pharmaceuticals and the Ministry of Health, Labor, and Welfare of Japan.) Copyright © 2014 Massachusetts Medical Society. Source

Takahashi T.,Yamaguchi Grand Medical Center
[Rinshō ketsueki] The Japanese journal of clinical hematology | Year: 2013

Herein, we report the case of a 28-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). The patient received induction chemotherapy, including imatinib (IM) therapy, which required early cessation because of a severe infection. After the resolution of the infection, general flaccid paralysis was observed, which was diagnosed as critical illness myopathy (CIM). Ph(+)ALL showed molecular remission (MR) on day 42. We intended to maintain MR with only IM therapy for several months until the improvement of CIM; however, owing to the patient's intolerance to IM, therapy was changed to dasatinib. Because the symptoms of myopathy gradually improved and disappeared completely, the patient was able to undergo one course of intensive chemotherapy and allogeneic stem cell transplantation from an HLA-matched sibling donor, 8 months after admission (7 months after the re-administration of IM). Thus, this case report suggests that a tyrosine kinase inhibitor is an alternative therapy for maintaining the response of Ph(+)ALL patients who refrain from conventional chemotherapy. Source

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