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.
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.
Anda T.,Shunan Memorial Hospital |
Honda M.,Shunan Memorial Hospital |
Ishihara T.,Tokuyama Medical Association Hospital |
Kamei T.,Yamaguchi Grand Medical Center
Neurologia Medico-Chirurgica | Year: 2014
The authors describe a male patient who developed a large intracranial meningioma during the hormone therapy for pre-existing prostate cancer. A 70-year-old man received a brain check-up, and no intracranial abnormality was detected. Five months later, prostate cancer was diagnosed, and he underwent prostatectomy. Leuprorelin acetate, a luteinizing hormone-releasing hormone (LH-RH) agonist, was subsequently administered to the patient once a month for 3 years. After that he presented with a large parasagittal mass, which was excised. The tumor was histologically diagnosed as meningothelial menin-gioma, and LH-RH receptors were verified immunohistochemically in the cytoplasm of the tumor cells. Leuprorelin acetate may accelerate the rapid growth of meningioma in this patient.
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.
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.
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.
Okayama M.,Jichi Medical University |
Takeshima T.,Jichi Medical University |
Ae R.,Jichi Medical University |
Harada M.,Yamaguchi Grand Medical Center |
Kajii E.,Jichi Medical University
BMC Family Practice | Year: 2013
Background: The current research into single nucleotide polymorphisms has extended the role of genetic testing to the identification of increased risk for common medical conditions. Advances in genetic research may soon necessitate preparation for the role of genetic testing in primary care medicine. This study attempts to determine what proportion of patients would be willing to undergo genetic testing for salt-sensitive hypertension in a primary care setting, and what factors are related to this willingness. Methods. A cross-sectional study using a self-report questionnaire was conducted among outpatients in primary care clinics and hospitals in Japan. The main characteristics measured were education level, family medical history, personal medical history, concern about hypertension, salt preference, reducing salt intake, and willingness to undergo genetic testing for salt-sensitive hypertension. Results: Of 1,932 potential participants, 1,457 (75%) responded to the survey. Of the respondents, 726 (50%) indicated a willingness to undergo genetic testing. Factors related to this willingness were being over 50 years old (adjusted odds ratio [ad-OR] = 1.42, 95% Confidence interval = 1.09 - 1.85), having a high level of education (ad-OR: 1.83, 1.38 - 2.42), having a family history of hypertension (ad-OR: 1.36, 1.09 - 1.71), and worrying about hypertension (ad-OR: 2.06, 1.59 - 2.68). Conclusions: Half of the primary care outpatients surveyed in this study wanted to know their genetic risk for salt-sensitive hypertension. Those who were worried about hypertension or had a family history of hypertension were more likely to be interested in getting tested. These findings suggest that primary care physicians should provide patients with advice on genetic testing, as well as address their anxieties and concerns related to developing hypertension. © 2013 Okayama et al.; licensee BioMed Central Ltd.
Yoshihara S.,Hyogo College of Medicine |
Ando T.,Yamaguchi Grand Medical Center |
Ogawa H.,Hyogo College of Medicine
Biology of Blood and Marrow Transplantation | Year: 2012
Acute myeloid leukemia may manifest as myeloid sarcoma in a variety of extramedullary (EM) tissues at diagnosis or at relapse. Although EM relapse after allogeneic hematopoietic stem cell transplantation (alloSCT) has been considered to be rare, recent studies have suggested that it occurs in 5% to 12% of patients who receive alloSCT, accounting for 7% to 46% of total relapses. The incidence of EM relapse after immunomodulation (eg, donor lymphocyte infusion) or a second SCT is even higher. Moreover, patients with EM relapse are more likely to have had preceding acute graft-versus-host disease or chronic graft-versus-host disease relative to those with bone marrow relapse. Collectively, these observations suggest that the preferential occurrence of the graft-versus-leukemia effect underlies the pathogenesis of EM relapse. Establishing an early diagnosis of EM relapse has been challenging because of the immense diversity in the relapse sites; however, recent studies have suggested the usefulness of 18F-fluorodeoxyglucose positron emission tomography scans in the detection of EM relapse. As a treatment for EM relapse, a combination of local and systemic therapy should be considered, because local therapy alone often results in subsequent systemic relapse. The prognosis for patients who develop EM relapse after SCT remains poor but is slightly better than that after bone marrow relapse. In addition to an early diagnosis with new modalities, clinical studies using new agents that may offer systemic activity while preserving the graft-versus-leukemia effect are warranted as part of an effort to improve the clinical outcome. © 2012 American Society for Blood and Marrow Transplantation.
Murakami R.,Yamaguchi Grand Medical Center |
Tanaka K.,Nagasaki University
Japanese Journal of Plastic Surgery | Year: 2016
The reverse flow flap is defined as a flap that relies on retrograde arterial flow through the artery of the pedicle and requires venous drainage to occur against the anatomic obstruction of the valves. In 1976, Bostwick and colleagues introduced the reverse flow temporal island flap to enable the distal transposition of a proximally located tissue. Since 1983, many reverse flow flaps such as the reverse forearm flap, the distally based sural flap, and the reverse vascular pedicle digital island flap have been used for the reconstruction of defects in the distal limb. The reverse flow flaps are easier to raise and less time-consuming to perform. They can offer one-stage reconstruction. The major advantage of these flaps is obviating the need for microsurgical skills in the reconstruction of limb defects. The clinical survival of reverse flow flaps indicates that venous drainage occurs through the venous system of the pedicle despite the retrograde direction of the valves of the venae comitantes. The venous valves must become regurgitant or be bypassed by collaterals, since most flaps survive without infarction. Many anatomical studies have been performed in order to elucidate the mechanism of the reverse flow.
Shigeoka T.,Yamaguchi Grand Medical Center
[Rinshō ketsueki] The Japanese journal of clinical hematology | Year: 2013
An 89-year-old woman presented to our hospital with hemolytic anemia and a high titer of cold agglutinins. Red cell agglutination was observed on a blood smear. Agglutination visibly decreased after warming the blood; therefore, the patient was diagnosed with cold agglutinin disease (CAD). Bone marrow aspiration revealed no infiltration of malignant cells. Computed tomography indicated moderate splenomegaly. The patient had neither an infection nor autoimmune disease. Initial steroid therapy was ineffective and hemolysis worsened. Meanwhile, thrombocytopenia, delirium, fever, and schistocytes in the blood were observed. The progression of hemolysis was attributed not only to CAD but also to coexisting thrombotic thrombocytopenic purpura (TTP) because of the decreased ADAMTS 13 level. Autopsy revealed mild paraaortic lymphadenopathy and splenomegaly. Microscopic examination revealed lymphoma cell infiltration in the spleen, liver, bone marrow, and paraaortic lymph nodes. These observations suggested that TTP and CAD were both secondary complications. This case highlights the importance of an autopsy for the detection of latent lymphoma, which can be difficult to diagnose before the patient's death. Careful examination to exclude lymphomas is important in patients with CAD at the time of diagnosis.