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Biomedical subjects

Hiroshi Takano

Publications and source records attributed to Hiroshi Takano.

At least 19 recordsLinked to original sources
PubMed2006

Neuroprotective effects of activated protein C through induction of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, and its downstream signal phosphorylated serine-threonine kinase after spinal cord ischemia in rabbits.

BACKGROUND AND PURPOSE: Activated protein C (APC) has beneficial effects on ischemia reperfusion injury in neuron. However, the possible mechanism of such beneficial effects is not fully understood. The aim of this study was to investigate the effects and possible mechanisms of APC on ischemic spinal cord damage. METHODS: After induction of spinal cord ischemia, APC (group A) or vehicle (group I) was injected intravenously. Severity of ischemic damage was analyzed by counting the number of motor neurons. To investigate the mechanisms by which APC prevents ischemic spinal cord damage, we performed immunoreactivity and Western blotting of insulin-like growth factor 1 (IGF-1), IGF-1 receptor, and phosphorylated serine-threonine kinase (p-Akt). RESULTS: APC eased the functional deficits and increased the number of motor neurons after ischemia. Immunoreactivity of IGF-1 in group A was stronger than in group I at 8 hours after reperfusion but was at the same level at 1 day. Induction of IGF-1 receptor and the downstream factor p-Akt was stronger and more prolonged in group A. CONCLUSIONS: These results indicate that induction of IGF-1, IGF-1 receptor, and p-Akt might partially explain the neuroprotective effects of APC after transient spinal cord ischemia in rabbit.

Animals↗
PubMed2006

Effect of a polymorphonuclear elastase inhibitor (sivelestat sodium) on acute lung injury after cardiopulmonary bypass: findings of a double-blind randomized study.

PURPOSE: We evaluated the effect of sivelestat sodium (SiV), a novel synthesized polymorphonuclear (PMN) elastase inhibitor, on acute lung injury (ALI) caused by cardiopulmonary bypass (CPB). METHODS: Fourteen patients who underwent cardiopulmonary surgery using CPB, followed by the development of both systemic inflammatory response syndrome (SIRS) and ALI, were treated with either 0.2 mg/kg per hour SiV (SiV group, n = 7) or saline (control group, n = 7) for 4 days from the time of arrival in the intensive care unit. RESULTS: The SiV group had a significantly lower ratio of serum PMN elastase and interleukin (IL)-8, a significantly lower ratio of the respiratory index, and a significantly higher ratio of PaO(2)/FiO(2) after 24 h of treatment than the control group. CONCLUSION: Sivelestat sodium suppressed the production of PMN elastase and IL-8, resulting in improved respiratory function in patients with ALI caused by CPB.

Acute Disease↗
PubMed2006

Large vessel - sternum adhesion after cardiac surgery; a risk-factor analysis.

PURPOSE: To study the clinical results of resternotomy in patients with dense and direct adhesion between the large vessels and the sternum, and define the morphologic features of the adhesion. METHODS: Between 2000 and 2003, 67 patients with a history of cardiac surgery underwent median resternotomy. We studied each patient's profile and the measurements taken from preoperative computed tomography scans. We then conducted multivariate logistic regression analysis to determine the predictive morphologic features of adhesion between the large vessels and the sternum in these 67 patients. RESULTS: Twenty (29.9%) of the 67 patients had direct adhesion between the large vessels and the sternum. Sternal re-entry was performed without injury to the large vessels in 18 (90%) but the aorta was injured in 2 (10%) patients, resulting in catastrophic hemodynamic disorder and operative death in one. Multivariate logistic regression analysis revealed that an extracardiac conduit and a high occupying rate of the aorta and pulmonary artery in the mediastinal space were significant morphologic factors. CONCLUSION: The morphologic features of large vessels to sternal dense adhesion as possible risk factors for injury to the large vessels are the presence of an extracardiac conduit and a large ascending aorta or pulmonary artery in relation to the mediastinal space.

Adult↗
PubMed2006

Inhaled particle deposition in unsteady-state respiratory flow at a numerically constructed model of the human larynx.

To evaluate the clinical effectiveness of aerosol therapy for the lower and upper respiratory airways, particle deposition at the human laryngeal region has been analyzed with various unsteady-state respiratory flow-patterns. The flow profiles and trajectory of aerosol particles were calculated by 3-D thermo-fluid analysis of a finite volume method (FVM) with 8-CPUs parallel computational system. A reconstructed physical model of the real laryngeal airways was modified from 3-D CAM modeling function of Rhinoceros based on the images of Magnetic Resonance Imaging (MRI). By using 104 MRI images taken vertically and horizontally at intervals of 2 mm on the oral cavity and the pharynx-larynx respectively, 3-D physical model of the laryngeal airways was obtained. The numerical results of flow profile analyzed by the unsteady-state respiration model showed that vortex flow was occurred with time at near larynx, showing uniform flow profile in both the oral cavity and upper side of pharynx. The vortex was appeared at the anterior part of the epiglottis and downward of the vocal cord. However, it was confirmed that few particles deposit in the vocal cord. In these cases, the particle deposition was taken place mostly at the oral cavity and the oropharynx. On the other hand, the relationship between the particle deposition efficiency and the impaction in the laryngeal region was well agreement with the data sets of ICRP task group (1993) for the larynx deposition.

Administration, Inhalation↗
PubMed2006

Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene.

Brain-type fatty acid-binding protein (B-FABP) belongs to a family of intracellular lipid-binding proteins. B-FABP exhibits a binding affinity to long-chain fatty acids (FAs) whose effects on brain functions including development, emotion, learning and memory have been proposed. B-FABP is localized in the ventricular germinal cells in embryonic brain and astrocytes in developing and mature brain of rodents. In the present study we generated the mouse harboring a null mutation in the B-FABP gene and studied its phenotype. B-FABP mutant mice exhibited the enhanced anxiety and increased fear memory as well as the decreased content of docosahexaenoic acid (DHA) in their brain during the neonatal period without detection of any histological changes in the brain. In the adult brain, B-FABP was localized more numerously to the astrocytes in the amygdala and septal area than to those in the hippocampal area. Analysis of FA content in the amygdala of adult brain revealed that arachidonic and palmitic acids increased significantly in the mutant mice compared with wild-type. Furthermore, the response of N-methyl-d-aspartate receptor-mediated current to DHA in isolated neurons from B-FABP mutant brain was significantly decreased compared with that of wild-type, while no significant differences were detected in behavioral responses related to the spatial learning/memory or in the hippocampal long-term potentiation. These data indicate that B-FABP is crucially involved in the fear memory and anxiety through its binding with FAs and/or its own direct effects on pertinent metabolism/signaling of FAs.

Animals↗
PubMed2006

Graft replacement and muscle wrap for infected aneurysm of thoracic aorta.

A 68-year-old man was admitted with high fever and enlargement of the distal aortic arch on chest radiography. Computed tomography showed a huge proximal descending thoracic aortic aneurysm. Graft replacement of the proximal descending thoracic aorta was performed on an emergency basis, and a pectoralis major muscle flap was wrapped around the graft. Salmonella enteritidis was detected in the resected tissue. The patient recovered well, with no signs of infection.

Aged↗
PubMed2006

E2F decoy oligodeoxynucleotide ameliorates cartilage invasion by infiltrating synovium derived from rheumatoid arthritis.

This study examined the ability of E2F decoy oligodeoxynucleotides (ODN) to inhibit proliferation of synovial fibroblasts derived from patients with rheumatoid arthritis (RA). The effect of E2F decoy ODN on cartilage invasion by RA synovium in a murine model of human RA was also investigated. E2F decoy ODN were introduced into synovial tissue and synovial fibroblasts derived from patients with RA using hemagglutinating virus of Japan (HVJ)-liposomes. The effect of E2F decoy ODN on synovial fibroblast proliferation was evaluated by MTT assay and by RT-PCR for the cell cycle regulatory genes proliferating-cell nuclear antigen (PCNA) and cyclin-dependent kinase 2 (cdk2). Changes in production of inflammatory mediators by RA synovial tissue following transfection with E2F decoy ODN were assessed by ELISA. Human cartilage and RA synovial tissue transfected with E2F decoy ODN were co-transplanted in severe combined immunodeficient (SCID) mice. After 4 weeks, the mice were sacrificed and the implants histologically examined for inhibition of cartilage damage by E2F decoy ODN. E2F decoy ODN resulted in significant inhibition of synovial fibroblast proliferation, corresponding with reduced expression of PCNA and cdk2 mRNA in synovial fibroblasts. The production of interleukin-1beta (IL-1beta), IL-6 and matrix metalloproteinase (MMP)-1 by synovial tissue was also significantly inhibited by the introduction of E2F decoy ODN. Further, in an in vivo model, cartilage that was co-implanted with RA synovial tissue transfected with E2F decoy ODN exhibited no invasive and progressive cartilage degradation. These data demonstrate that transfection of E2F decoy ODN prevents cartilage destruction by inhibition of synovial cell proliferation, and suggest that transfection of E2F decoy ODN may provide a useful therapeutic approach for the treatment of joint destruction in arthritis.

Animals↗
PubMed2006

Paraplegia and paraparesis after descending thoracic aortic aneurysm repair: a risk factor analysis.

BACKGROUND: The risk factors of paraplegia and paraparesis (P/P) after surgical repair of descending thoracic aortic aneurysm (TAA) are controversial. PATIENTS AND METHODS: Seventy five patients underwent surgical repair of descending TAA from 2001 through 2002. The mean age was 64.2+/-5.2 years old (range; 26-81) and 58 patients (77.3%) are male. There were 47 patients (62.7%) with nondissecting aortic aneurysm and 28 patients (37.3%) with chronic dissecting aortic aneurysm. Emergent operation was performed in 13 cases (17.3%). Retrospective analysis based on data of these 75 patients was performed to determine the risk factors of P/P. RESULTS: 30-days hospital mortality was 2.7%. The overall incidence of P/P was 12.0% (9/75) overall (immediate paraplegia; 4 (5.3%), delayed paraplegia; 1 (1.3%), immediate paraparesis; 3 (4.0%), delayed paraparesis; 1 (1.3%)). Logistic regression analysis revealed that predictive factors of the development of P/P were; cases in which the distal part (below Th9) of the descending thoracic aorta was included in the extent of graft replacement (P=0.020; odds ratio (OR), 7.981) and nondissecting aneurysm (P=0.029; OR, 12.109). CONCLUSION: There was an increased risk of P/P after descending TAA repair in cases in which the extent of graft replacement included below the Th9 or in cases with nondissecting aortic aneurysm.

Adult↗
PubMed2005

The RNA-binding protein HuD regulates neuronal cell identity and maturation.

Neural Hu proteins (HuB/C/D) are RNA-binding proteins that have been shown to induce neuronal differentiation activity when overexpressed in immature neural progenitor cells or undifferentiated neuronal tumors. Newly generated HuD-deficient mice exhibited a transient impaired-cranial-nerve-development phenotype at an early embryonic stage. Adult HuD-deficient mice exhibited an abnormal hind-limb reflex and poor rotarod performance. Analysis of neurosphere formation revealed that the number and self-renewal capacity of the neural stem/progenitor cells were increased in HuD-deficient mice. HuD-deficient primary neurospheres also generated a smaller number of neurons. Cohort analysis of the cellular proliferative activity by using BrdUrd and iododeoxuridine labeling revealed that the number of differentiating quiescent cells in the embryonic cerebral wall was decreased. Long-term administration of BrdUrd revealed that the number of slowly dividing stem cells in the adult subventricular zone was increased in the HuD-deficient mice. Taken together, the results suggest that HuD is required at multiple points during neuronal development, including negative regulation of proliferative activity and neuronal cell-fate acquisition of neural stem/progenitor cells.

Animals↗
PubMed2005

Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid.

Hyaluronic acid (HA) is a component of the extracellular matrix that has been shown to play an important role in bone formation, resorption, and mineralization both in vivo and in vitro. We examined the effects of HA at several molecular weights on osteoclast formation and function induced by RANKL (receptor activator of NF-kappa B ligand) in a mouse monocyte cell line (RAW 264.7). HA at M(r) < 8,000 (low molecular weight HA (LMW-HA)) enhanced tartrate-resistant acid phosphatase-positive multinucleated cell formation and tartrate-resistant acid phosphatase activity induced by RANKL in a dose-dependent manner, whereas HA at M(r) > 900,000 (high molecular weight HA (HMW-HA)) showed no effect on osteoclast differentiation. LMW-HA enhanced pit formation induced by RAW 264.7 cells, whereas HMW-HA did not, and LMW-HA stimulated the expression of RANK (receptor activator of NF-kappa B) protein in RAW 264.7 cells. In addition, we found that LMW-HA enhanced the levels of c-Src protein and phosphorylation of ERKs and p38 MAPK in RAW 264.7 cells stimulated with RANKL, whereas the p38 MAPK inhibitor SB203580 inhibited RANKL-induced osteoclast differentiation. This enhancement of c-Src and RANK proteins induced by LMW-HA was inhibited by CD44 function-blocking monoclonal antibody. These results indicate that LMW-HA plays an important role in osteoclast differentiation and function through the interaction of RANKL and RANK.

Acid Phosphatase↗
PubMed2005

Neuropeptide substance P stimulates the formation of osteoclasts via synovial fibroblastic cells.

The present study was designed to evaluate the effects of neuropeptide substance P (SP) on the formation of osteoclasts via synovial fibroblastic cells. Synovial fibroblastic cells derived from rat knee joint expressed the SP receptor, neurokinin-1 receptor (NK(1)-R). The addition of SP stimulated the proliferation of synovial fibroblastic cells and this effect was inhibited by SP or NK(1)-R antagonists. Increased expression of the receptor activator of nuclear factor kappaB ligand (RANKL) in synovial fibroblastic cells after the addition of SP was demonstrated by reverse transcriptase-polymerase chain reaction and immunofluorescence staining. Osteoprotegerin expression in synovial fibroblastic cells was decreased after incubation with SP. In co-cultures of synovial fibroblastic cells and rat peripheral blood monocytes, SP stimulated osteoclastogenesis. These results suggest that SP in the joint cavity may cause both hypertrophy of the synovium and induction of increased osteoclast formation through the increased expression of RANKL in the synovium.

Animals↗
PubMed2005

Successful mitral valve replacement in a patient with Ehlers-Danlos syndrome type VI.

A 40-year-old patient with Ehlers-Danlos syndrome type VI (ocular type) had mitral regurgitation due to mitral valve prolapse. Because the patient's tissue was fragile, we replaced the mitral valve with a reinforced prosthetic valve to prevent paravalvular leakage. The excised mitral leaflet showed significant myxomatous change and decrease in collagen fibers. We believe this is the first report of cardiac surgery in a patient with Ehlers-Danlos syndrome type VI.

Adult↗
PubMed2005

Surgical resection for lung cancer with infiltration of the thoracic aorta.

OBJECTIVE: The purpose of this study was to evaluate the results of a combined resection of the thoracic aorta and primary lung cancer. METHODS: Sixteen patients underwent thoracic aorta resection along with a left pneumonectomy (n = 6), left upper lobectomy (n = 9), or partial lung resection (n = 1), of whom 10 also received preoperative induction therapy. Cardiopulmonary bypass was used in 10 patients, and a passive shunt between the ascending aorta and the descending aorta was used in 4 patients. RESULTS: Six postoperative major complications occurred in 5 patients, including postoperative bleeding (n = 3), intraoperative bleeding (n = 1), chylothorax (n = 1), and respiratory failure (n = 1). The postoperative morbidity rate was 31%, and the mortality rate was 12.5% (2/16). Furthermore, 4 patients died of systemic tumor relapse, and 1 patient died of intrapleural recurrence. Nine patients were alive after a median follow-up of 54 months (range, 12-199 months). The median survival time of patients with postoperative pathologic N0 disease was 31 months, whereas it was 10 months for those with pathologic N2 or N3 disease. Five-year survivals were 70% for patients with N0 disease and 16.7% for patients with N2 or N3 disease ( P = .0070). CONCLUSIONS: Although pulmonary resection with the involved aorta might cause high surgical morbidity and mortality rates, encouraging long-term survivals were obtained in patients without mediastinal nodal involvement.

Adenocarcinoma↗
PubMed2005

Three-dimensional identification of hemangiomas and feeding arteries in the head and neck region using combined phase-contrast MR angiography and fast asymmetric spin-echo sequences.

OBJECTIVE: To evaluate a proposed technique for the 3-dimensional (3D) detection of hemangiomas, including vascular malformation and their feeding arteries, in the head and neck. The new technique combines phase-contrast magnetic resonance angiography (PCMRA) without contrast medium and 3D fast asymmetric spin-echo (FASE) sequences. METHODS: The technique was applied to 3 patients having hemangiomas in the head and neck region. In 1 patient the image obtained with the proposed technique was compared to that obtained by standard contrast angiography. RESULTS: In all 3 patients, the 3D presence of the hemangiomas and the feeding arteries were well defined in images created by the proposed technique. Additionally, the characterization of the hemangioma's 3D structure and distribution of the feeding arteries coincided with those observed using contrast angiography in the case for which contrast angiography was also performed. CONCLUSIONS: Preliminary experience shows that the proposed technique combining 3D-FASE and 3D-PCMRA is useful to visualize both the 3D structure of hemangiomas and to identify the 3D distribution of the feeding arteries without using contrast medium.

Adult↗
PubMed2004

Human parvovirus B19 transgenic mice become susceptible to polyarthritis.

Human parvovirus B19 (B19) often causes acute polyarthritis in adults. In this paper, we analyzed nucleotide sequences of the B19 genome of patients with rheumatoid arthritis (RA), and then introduced the nonstructural protein 1 (NS1) gene of B19 into C57BL/6 mice that had a genetic origin not susceptible to arthritis. The transgenic mice developed no lesions spontaneously, but were susceptible to type II collagen (CII)-induced arthritis. B19 NS1 was expressed in synovial cells on the articular lesions that were histologically characteristic of granulomatous synovitis and pannus formation in cartilage and bone. Serum levels of anti-CII Abs and TNF-alpha increased in NS1 transgenic mice to the same levels as those of DBA/1 mice, which were susceptible to polyarthritis. Stimulation with CII increased secretion of Th1-type- and Th2-type cytokines in NS1 transgenic mice, indicating that a nonpermissive H-2(b) haplotype in the wild type of C57BL/6 mice can be made susceptible to polyarthritis through the expression of NS1. This study is the first to show that a viral agent from the joints in humans can cause CII-induced arthritis resembling RA.

Animals↗