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Ichinomiya, Japan

Goto M.,Aichi Medical University | Miwa H.,Aichi Medical University | Suganuma K.,Aichi Medical University | Tsunekawa-Imai N.,Aichi Medical University | And 5 more authors.
BMC Cancer | Year: 2014

Background: Like normal hematopoietic stem cells, leukemia cells proliferate in bone marrow, where oxygen supply is limited. However, the growth and energy metabolism of leukemia cells under hypoxia have not been well understood. Although it has been known that reactive oxygen species (ROS) is generated under hypoxic conditions, normal and leukemia stem cells were characterized by relatively low levels of ROS. Roles of ROS on leukemia cells under hypoxia also have not been well understood.Methods: Four Leukemia cell lines were cultured under normoxia (21% O2) or hypoxia (1% O2), where NB4 and THP-1 were most extensively studied. To evaluate energy metabolism, we estimated whole cell number or apoptotic cells with or without a glycolysis inhibitor or an oxidative phosphorylation (OXPHOS) inhibitor. Glucose consumption and lactate production were also measured. To evaluate oxidative stress in hypoxic condition, the ROS level and GSH (reduced glutathione) / GSSG (oxidized glutathione) ratio was measured. In addition, pyruvate dehydrogenase kinase 1 (PDK1) and cytochrome c oxidase subunit 4 (COX4) were examined by western blotting or RT-PCR.Results: NB4, which grows well under normoxia depending on glycolysis, demonstrated prominent apoptosis and growth suppression after 48 hours culture under hypoxia. NB4 cells cultured under hypoxia showed significantly increased ROS. Culture with a ROS scavenger resulted in decrease of apoptotic cell death of NB4 under hypoxia. NB4 cells cultured for longer period (7 days) under hypoxia did not come to extinction, but grew slowly by upregulating GSH synthesis to protect from ROS generated in hypoxic condition. By contrast, THP-1, which largely depends on OXPHOS in mitochondria under normoxia, demonstrated more growth under hypoxia by changing metabolism from OXPHOS to glycolysis through upregulating PDK1. Moreover, THP-1 avoided ROS generation by substituting COX 4 subunit (from COX 4-1 to COX 4-2) through upregulation of LON, a mitochondrial protease under hypoxia.Conclusions: We showed that leukemia cells survive and adapt to the hypoxic condition through various pathways. Our results will help understanding energy metabolism of leukemia cells and creating novel therapeutics. © 2014 Goto et al.; licensee BioMed Central Ltd. Source

Akamatsu S.,Matsunami General Hospital | Kondo Y.,Fujifilm Co. | Ueda N.,Chuno Kousei Hospital | Kojima A.,Matsunami General Hospital | And 4 more authors.
Anesthesia and Analgesia | Year: 2011

Background: We developed a Doppler-equipped pulmonary artery catheter that provides continuous measurement of the true main pulmonary blood flow velocity independent of the angle of incidence formed by the pulmonary artery catheter and the main pulmonary artery blood flow. This device uses 2 orthogonally positioned Doppler transducers that allow trigonometric correction for differences in the angle of blood flow between each transducer. We tested the accuracy of the Doppler-equipped pulmonary artery catheter by comparing its cardiac output measurements with those done by conventional techniques in animals. Methods: The Doppler-equipped pulmonary artery catheter was evaluated in dogs. A pair of ultrasound Doppler transducers positioned at a fixed angle (90°) was mounted on the distal part of the thermodilution pulmonary artery catheter. The Doppler shifts (Δf1, Δf2) were detected by the 2 transducers sampling at 2 closely spaced points in the main pulmonary artery. The values of Δf1 and Δf2 were used to compute 2 velocity measurements. The true flow velocity of the main pulmonary artery was calculated with the following equation: Vpulm = {(Vtransducer1) + (Vtransducer2)} (Vpulm = true main pulmonary artery velocity; Vtransducer1 and Vtransducer2 = velocity detected by transducers 1 and 2, respectively). The flow velocities were calculated by using a phase differential technique. Cardiac output was calculated as Vpulm multiplied by a coefficient value. The coefficient value was calculated by dividing cardiac output, derived from conventional techniques, by Vpulm at the beginning of each experiment. After thoracotomy, an electromagnetic flowprobe was placed around the main pulmonary artery in dogs. Cardiac output was simultaneously measured by the Doppler-equipped pulmonary artery catheter (CO-Doppler), and the electromagnetic flowmeter (CO-EMF) or the thermodilution technique (CO-Thermo). Cardiac output was manipulated by dobutamine and propranolol. Results: CO-Doppler was highly correlated with CO-EMF (y = 1.16 × -0.26, r = 0.99, P < 0.001) and CO-Thermo (y = 1.24 × -0.90, r = 0.85, n = 48, P < 0.001). The bias between CO-EMF and CO-Doppler was -0.02 L/min; 95% limits of agreement were -0.32 to 0.28 L/min. The percentage error was 16%. The bias between CO-Thermo and CO-Doppler was 0.18 L/min; 95% limits of agreement were -0.62 to 0.98 L/min. Conclusions: The newly developed Doppler-equipped pulmonary artery catheter with 2 orthogonally positioned Doppler transducers allowed accurate and continuous measurements of cardiac output independent of the angle of incidence formed by the pulmonary artery catheter and the main pulmonary artery blood flow. Copyright © 2011 International Anesthesia Research Society. Source

Tomita N.,Aichi Cancer Center Hospital | Nakajima K.,Ichinomiya Municipal Hospital | Kodaira T.,Aichi Cancer Center Hospital | Murao T.,Ichinomiya Municipal Hospital | And 2 more authors.
Japanese Journal of Radiology | Year: 2012

Castleman disease (CD) is a rare lymphoproliferative disorder. Two clinical entities are described: a unicentric form with disease confined to a single lymph node region and a multicentric form characterized by generalized lymphadenopathy and systemic symptoms. Although surgery is regarded as standard therapy for the unicentric form, no consensus has been reached concerning the standard treatment for multicentric CD. We report here a case of cervical multicentric CD treated with intensity-modulated radiation therapy (IMRT), using helical tomotherapy to minimize xerostomia in comparison with conventional radiotherapy. A 29-year-old woman complained of neck swelling. Computed tomography showed lymphadenopathy in both sides of the neck. The patient was diagnosed with the plasma cell subtype of CD on biopsy. After initial treatment with prednisone, IMRT was planned to avoid normal structures, for example the parotid gland. The cervical lymphadenopathy shrank gradually during IMRT with 44 Gy in 22 fractions. Four years and 3 months after IMRT, regrowth of cervical lymph nodes has not been detected. The parotid function improved dramatically on quantitative salivary scintigraphy between 3 and 12 months after IMRT. Radiotherapy could be an option for multicentric CD, and IMRT is an effective means of minimizing xerostomia in head and neck lesions. © 2012 Japan Radiological Society. Source

Tajima Y.,Gifu Prefectural General Medical Center | Suzuki E.,Gifu Prefectural General Medical Center | Saito J.,Gifu Prefectural General Medical Center | Murase H.,Daiyukai General Hospital | And 2 more authors.
Endocrine Journal | Year: 2015

Blood flow in lower extremity arteries is frequently impaired in diabetic patients even though they have a normal ankle-brachial index (ABI 1.0-1.4). Risk factors contributing to this lower extremity arterial disease have not been fully elucidated. We enrolled 52 type 2 diabetic patients with normal ABI and 30 age-matched nondiabetic subjects consecutively admitted to our hospital. Plasma B-type natriuretic peptide (BNP) concentrations were measured. Distensibility in ascending thoracic and abdominal aortas as well as total flow volume and resistive index at popliteal artery were evaluated by gated magnetic resonance imaging. An automatic device was used to measure ABI and brachial-ankle pulse-wave velocity (baPWV). Diabetic patients showed lower distensibility in ascending thoracic aorta (p<0.001) and total flow volume (p<0.001) and higher baPWV (p<0.001) and resistive index (p=0.005) and similar BNP and distensibility in abdominal aorta compared to nondiabetic subjects. Simple linear regression analyses revealed that distensibility in ascending thoracic (p=0.019) and abdominal (p=0.030) aortas positively as well as baPWV (p=0.020), resistive index (p<0.001) and BNP (p<0.001) negatively correlated with total flow volume. Stepwise multiple regression analysis demonstrated that increased BNP and resistive index were independent risk factors for total flow volume in diabetic patients (r2=0.639, p<0.001). These results indicate that increased plasma BNP levels and peripheral vascular resistance, but not decreased aortic distensibility, associate with impaired blood flow in lower extremity arteries in diabetic patients. © The Japan Endocrine Society. Source

A 63-year-old woman was referred to our hospital because of bilateral infiltrations and nodular opacities in her chest radiograph taken in the mass radiography screening in September 2010. The chest computed tomography showed patchy infiltrations with bronchiectasis in the lower lung fields on both sides. She was diagnosed with pulmonary Mycobacterium avium complex (MAC) disease based on the bacteria recovered from the sputum and the bronchoalveolar lavage fluid. To elucidate an environmental MAC source, we investigated her home, and isolated M.avium and M.gordonae from the bathtub and shower tap, respectively, in her residential bathroom. Analysis of the hsp65- PR A variants digested with Bam HI and some insertion sequences showed that the clinical strains recovered from sputum and strains from the bathtub were M.avium subsp. kominissuis. A dendrogram of the Mycobacterium avium tandem repeat loci variable-number tandem- repeat (MATR-VNTR) analysis of the MAC strains showed that the bathtub strains formed a polyclonal colonization, and that 1 of the 5 MATR-VNTR patterns was identical to the corresponding pattern of the sputum strain from the patient. In conclusion, we believe that the residential bathroom of the patient was the environmental source of her pulmonary MAC disease, as has been previously reported. Source

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