Biomedical subjects

Takuya Ozawa

Publications and source records attributed to Takuya Ozawa.

9 recordsLinked to original sources

PubMed2006

Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.

Bone marrow cell implantation (BMI) has been utilized to treat patients with limb and heart ischemia. BMI provides angiogenic precursors and angiogenic cytokine-producing cells, especially erythroid cells. In this study, we induced in vitro angiogenesis cultures and in vivo BMI simulation using a murine limb ischemia model to examine the role of erythroid cells and the effect of erythropoietin (EPO). Human erythroid colonies (BFU-e) induced capillary networks around the colonies in vitro. Erythroid cells in human bone marrow produced vascular endothelial growth factor and placental growth factor. The angiogenic effects of erythroid cells were further amplified in the presence of EPO. Limb-ischemic mice were treated with BMI +/- EPO, and limb survival, blood flow recovery, and muscle histology were analyzed. Treatment with whole bone marrow cells + EPO significantly improved limb survival and blood flow. The cumulative effects of EPO on BMI induced and increase in capillary number and artery enlargement. Erythroid cells were essential for the in vivo effects of BMI, and CD14-positive cells supported the biological effects. In addition to the direct effect of EPO on angiogenesis, EPO showed indirect effect on angiogenesis through amplifying the angiogenic effects by erythroid cells supported by CD14-positive cells.

Adult↗

PubMed2005

Relationship between serum lipoprotein(a) concentrations and coronary vasomotion in coronary spastic angina.

BACKGROUND: Elevated lipoprotein(a) (Lp(a)) concentrations are reported to impair endothelium-dependent vasodilatation of the epicardial coronary artery. However, the effects on vasomotor abnormalities in coronary spastic angina (CSA) have not been thoroughly investigated. METHODS AND RESULTS: In the present study 80 sites of spasm (spastic sites) without significant organic stenosis (% diameter stenosis <50%) were assessed in 80 patients with CSA diagnosed by intracoronary ergonovine (EM) test. Spastic sites were divided into 2 groups: Group 1 included 30 sites provoked by the full dose (=50 microg) of EM, and Group 2 included 50 sites provoked with less than 50 microg (34.7+/-8.2 microg). Control subjects (n=22) did not show coronary spasm with the EM test. Serum Lp(a) concentrations were measured in all patients. Group 2 had a significantly greater basal coronary artery tone in the spastic sites than Group 1 (p<0.001). Lp(a) level in Group 2 was significantly higher compared with both the control group and Group 1 (p<0.05 by analysis of variance). Multivariate analysis confirmed that only serum Lp(a) concentration was associated with low-dose EM spasm provocation. CONCLUSIONS: Serum Lp(a) concentration could be a marker for high disease activity in CSA.

Adult↗

PubMed2004

Clinical application of bone marrow implantation in patients with arteriosclerosis obliterans, and the association between efficacy and the number of implanted bone marrow cells.

BACKGROUND: There have been a number of recent reports on the use of autologous bone marrow implantation (BMI) in the treatment of peripheral arterial disease, with a clinical response rate of approximately 70%. However, the factors that influence efficacy have not yet been clarified. We have analyzed the relationship between the number of implanted bone marrow cells and the clinical efficacy of BMI. METHODS AND RESULTS: Eight patients with arteriosclerosis obliterans were treated with BMI. Bone marrow was aspirated from the ilium (500-1,000 ml), the mononuclear cells were separated and then were implanted. The clinical effectiveness of BMI was evaluated by assessing changes in the ankle-brachial pressure index (ABI) and the transcutaneous oxygen pressure (TcO2) between the pre-treatment baseline, with follow-up testing at 4 weeks. These changes were defined as DeltaABI and DeltaTcO2. The mean number of CD34-positive cells was 1.04+/-0.60 x10(6) /kg body weight. There was a strong correlation between the number of CD34-positive cells and DeltaABI (r=0.754, p=0.028). CONCLUSIONS: It is likely that the number of implanted CD34-positive cells is one of the primary factors that influence the clinical efficacy of BMI.

Aged↗

PubMed2004

Plasma concentrations of cytokines and neurohumoral factors in a case of fulminant myocarditis successfully treated with intravenous immunoglobulin and percutaneous cardiopulmonary support.

A 53-year-old Japanese man with fulminant myocarditis was referred. Percutaneous cardiopulmonary support (PCPS) was introduced immediately and intravenous immunoglobulin (IVIG) therapy followed for 2 days. Cardiac function showed signs of recovery on the 4th hospital day and the patient was weaned from PCPS on the 7th hospital day. Creatine kinase-MB peaked at 12 h after admission and was 176 ng/ml. Endomyocardial biopsy showed active myocarditis. A marked increase of the neutralizing antibody titer suggested coxsackievirus B3 infection. Plasma concentrations of cytokines and neurohumoral factors were analyzed. Proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF-alpha), and anti-inflammatory cytokines, such as IL-1 receptor antagonist, soluble TNF receptor-1 and IL-10, were elevated on admission and all had decreased on the 7th hospital day. Brain natriuretic peptide and noradrenaline were already elevated upon admission (1,940 pg/ml and 4.6 ng/ml, respectively) and decreased thereafter. Although IVIG therapy under PCPS is a common treatment for fulminant myocarditis, the immunological response in vivo remains unclear. This case demonstrated suppression of serum cytokines after IVIG and PCPS treatment. Immunological parameters in those who have been treated with IVIG and PCPS and survived without complications are of great value for evaluation of the therapy. Further analysis with more cases in a multicenter study is necessary.

Cardiology↗

PubMed2003

Spatiotemporal changes of coxsackievirus and adenovirus receptor in rat hearts during postnatal development and in cultured cardiomyocytes of neonatal rat.

Coxsackievirus B is the most common cause of viral myocarditis and is particularly virulent in neonates and children. Adenovirus is also a leading cause of the disease. The determinant of tropism for both viruses is considered to be the expression of coxsackievirus and adenovirus receptor (CAR) in target organs. However, developmental change and physiological localization of CAR in the heart are unknown. We examined expression levels of CAR in rat hearts by quantitative real-time polymerase chain reaction and Western blot analysis and found that CAR decreased gradually during postnatal development, although CAR was detectable, even in adults. Immunohistochemistry revealed CAR on the whole surface of cardiomyocytes in immature rat hearts. In contrast, CAR was detected predominantly on intercalated disks in the adult heart and was accumulated especially at the contact point between the cultured cardiomyocytes, even though they were prepared from the neonatal rat heart. In conclusion, CAR was expressed abundantly on the whole surface of cardiomyocytes in immature rat hearts. Both the expression level and the localization of CAR are possible determinants of the susceptibility to viral myocarditis of neonates and children.

Animals↗

PubMed2003

Masked MLL gene rearrangement was disclosed in the clinical course and sequential development of chromosome abnormality in a patient with therapy related acute myelogenous leukemia.

Therapy related acute myelogenous leukemia in a 55-year-old Japanese woman is described. She had been treated for a diagnosis of non-Hodgkin's lymphoma 2 years before the onset of the secondary leukemia. She was diagnosed as AML (FAB: M2) with monosomy 7, and successfully treated by an intensive combination chemotherapy followed by an autologous peripheral blood stem cell transplantation. The disease relapsed shortly after the treatment, and the karyotype analysis revealed a complex abnormality accompanied with t(9;11)(p22;q23), however, monosomy 7 was absent. Southern blotting analysis was performed, and MLL rearrangement was evident in both the bone marrow samples obtained at that time and the cryopreserved marrow cells obtained at the onset of the disease. The bone marrow sample stored in a Carnoy solution at the onset was further analyzed, and three karyotype panels showing 45,XX, -7, t(9;11)(p22;q23) were found. Like this situation, a masked MLL rearrangement may have existed in some cases with hematopoietic malignancies, and appear to be disclosed in the clinical course.

Cell Transformation, Neoplastic↗

PubMed2003

Analysis of postextrasystolic relaxation response in the human heart.

Postextrasystolic potentiation is the phenomenon in which ventricular contractile force is strengthened by a preceding premature beat. However, the response of diastolic function after an extrasystole is unknown. We studied 58 patients with chronic heart failure (CHF) and two control subjects to evaluate the response of relaxation following extrasystole. At cardiac catheterization, from the derivative of the left ventricular (LV) pressure, the ratio of LV peak negative dP/dt (-dP/dt) of a postextrasystole to a basal beat was calculated and defined as the postextrasystolic relaxation response (PRR). PRR was compared with parameters of left ventriculography: LV end-diastolic volume index (EDVI), LV end-systolic volume index (ESVI), and LV ejection fraction (EF). The PRRs of the two control subjects were 0.80 and 0.84. The mean PRR of the CHF patients was 0.99 +/- 0.15. In all subjects, including patients and controls, correlation analysis between (EDVI, ESVI, and EF) and PRR yielded the following: (a) EDVI vs. PRR: R = 0.273, p = 0.036; (b) ESVI vs. PRR: R = 0.446, p < 0.001; and (c) EF vs. PRR: R = -0.520, p < 0.001. Thus, normal or non-failing human hearts showed a decline of -dP/dt in postextrasystole compared with the basal beats, but failing hearts had potentiated relaxation following an extrasystole.

Adult↗

PubMedDate not supplied

Expression of coxsackievirus and adenovirus receptor in neointima of the rat carotid artery.

Our previous study revealed that the coxsackievirus and adenovirus receptor (CAR) is a homophilic cell adhesion molecule and may function as a sensor of cell-cell interactions in the brain and damaged heart. In this study, we investigated if CAR expression is involved in the formation of neointimal hyperplasia using a balloon injury model of rat carotid artery. Cultured vascular smooth muscle cells (SMCs) from rat aorta were also studied. CAR antigen was constitutively detected in the endothelial cells (ECs) but not in SMCs before injury. On Day 5 after balloon injury, CAR was expressed strongly in the first layer of medial SMCs. Neointimal hyperplasia was observed on Day 7, and strong expressions of CAR concomitantly with proliferating cell nuclear antigen (PCNA) were obvious in the neointimal SMCs, while CAR in medial SMCs disappeared. The expression of CAR mRNA reached a peak on Day 7 and declined gradually to the basal levels. When the ECs regenerated on Day 14, CAR antigen was observed in the ECs but disappeared in the neointima. CAR together with PCNA was expressed abundantly in the proliferating SMCs in vitro and diminished in cells grown to a confluent state. The abundant expression of CAR in the neointima may facilitate an adenoviral gene therapy.

Animals↗

PubMedDate not supplied

Marked decrease of plasma VEGF after implantation of autologous bone marrow mononuclear cells in a patient with critical limb ischemia--a case report.

The authors performed autologous bone marrow mononuclear cells implantation (BMI) in a 79-year-old man with critical limb ischemia. After BMI, the resting pain of the ischemic leg improved gradually. They measured the plasma concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and serum hepatocyte growth factor (HGF) in the blood from bilateral femoral veins. Before BMI, the plasma VEGF and bFGF concentrations were much greater in the ischemic leg than in the other lower limb, but decreased to the same concentrations as those in the contralateral lower extremity after BMI. The large concentrations of the angiogenic factors VEGF and bFGF in plasma indicate the severity and extent of the leg ischemia. BMI resulted in lower levels of VEGF and bFGF, and this fall is the hallmark of the effectiveness of BMI in the treatment of peripheral artery disease.

Aged↗