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Ikuo Fukuda

Publications and source records attributed to Ikuo Fukuda.

At least 37 records · Page 2Linked to original sources
PubMed2004

The state of platelets preserved in extracorporeal circulation with a glycoprotein IIb/IIIa inhibitor.

INTRODUCTION: Temporary inhibition of platelet function during extracorporeal circulation (platelet anesthesia) can preserve platelet count. We hypothesized that platelet anesthesia with a glycoprotein IIb/IIIa inhibitor could preserve activated platelets. MATERIALS AND METHODS: Fresh human blood from donors was recirculated for 120 min in a simulated extracorporeal circuit. Heparin and FK633, a short-acting platelet glycoprotein IIb/IIIa inhibitor, were added to recirculated blood in one group (group F, n=5) whereas only heparin was used in controls (group C, n=5). Blood samples were obtained from the donors, and at 0, 5, 15, 30, 60, and 120 min of recirculation. Platelet counts, beta-thromboglobulin, thrombin-antithrombin complex, and aggregation to adenosine diphosphate were measured. Flow cytometry was performed for measurement of fibrinogen binding, platelet surface expression of P-selectin, and microparticles. RESULTS AND CONCLUSIONS: In the FK633 group, platelet counts were preserved and beta-thromboglobulin levels remained unchanged, whereas in group C, platelet counts decreased significantly and beta-thromboglobulin increased significantly from 30 and 60 min, respectively. FK633 inhibited platelet aggregation and fibrinogen binding to platelets throughout recirculation. A significant difference between groups with respect to microparticle parameters and thrombin-antithrombin complex levels was evident by 120 min. P-selectin expression increased at 0 min in both groups, and was preserved significantly at 5 min and reduced at 120 min in group F. Platelet counts were preserved by platelet anesthesia during recirculation without platelet activation. These results suggest that FK633 inhibits the amplification loop by reducing the binding of fibrinogen to glycoprotein IIb/IIIa and platelet aggregation.

Adenosine Diphosphate↗
PubMed2004

Asymptomatic intracardiac metastasis from a low-grade endometrial stromal sarcoma with successful surgical resection.

BACKGROUND: The endometrial stromal sarcoma (ESS) is a rare neoplasm of the uterine origin. Intracardiac metastasis from the low-grade ESS is an extremely rare event. A case of a patient who successfully underwent surgical extraction of metastatic tumors of the low-grade ESS in the right ventricle is described in the present report. CASE: A 48-year-old woman was considered recurrence of the low-grade ESS 4 years after the initial operation for this disease. The CT scanning and magnetic resonance imaging demonstrated solid masses in the pelvis, the lungs, the inferior vena cava, and the right ventricle. The chemotherapy was effective against the recurrent tumors except for intracardiac site. Although she had no symptoms of right-sided heart failure, surgical resection of the intracardiac masses was successfully performed. Pathological examination confirmed intracardiac recurrent low-grade ESS. CONCLUSION: Surgical approach to intracardiac metastasis of the low-grade ESS is considered viable because of an excellent long-term prognosis in this disease and the likelihood of fatal heart failure or sudden death in untreated cases.

Endometrial Neoplasms↗
PubMed2004

Heparin inhibits IFN-gamma-induced fractalkine/CX3CL1 expression in human endothelial cells.

Heparin is primarily used as an anticoagulant but has many biological functions as well. It binds with high affinity to a range of cytokines including interferon-gamma (IFN-gamma) and members of chemokine superfamily. IFN-gamma is a proinflammatory cytokine that plays a pivotal role in immune and inflammatory responses; and in endothelial cells, it regulates the expression of fractalkine/CX3CL1 that is a potent agonist for the chemotaxis and adhesion of monocytes and lymphocytes. We have investigated the effect of heparin on the fractalkine expression in human umbilical vein endothelial cells (HUVEC) in culture. HUVEC were treated with approximately 100 mg/mL heparin and the expression of the IFN-gamma-induced fractalkine mRNA and protein were measured by reverse transcription-PCR and western blotting. The IFN-gamma-induced expressions of fractalkine mRNA and protein were inhibited by heparin in a concentration-dependent manner. Heparin also inhibited adhesion of mononuclear cells (MNC) to HUVEC monolayers stimulated with IFN-gamma, but it did not inhibit the MNC adhesion to the monolayers stimulated with interleukin-1beta. Electrophoretic analysis demonstrated direct binding of heparin to IFN-gamma and heparin was found to partially block the binding of IFN-gamma to IFN-gamma receptor (IFN-gamma R). Heparin may play a regulatory role in inflammatory and immune responses by modulating the interaction between leukocytes and the vascular endothelium.

Cells, Cultured↗
PubMed2003

Effect of MG132, a proteasome inhibitor, on the expression of growth related oncogene protein-alpha in human umbilical vein endothelial cells.

Growth related oncogene protein-alpha (GRO-alpha) is a member of C-X-C chemokine and plays an important role in inflammatory responses. Expression of GRO gene family is regulated by a number of factors at both transcriptional and posttranscriptional levels. In the present study, we have addressed the possible regulation of GRO-alpha expression by ubiquitin-proteasome system. Cultures of human umbilical vein endothelial cells were treated with a proteasome inhibitor, MG132, and the levels of GRO-alpha mRNA were analyzed by reverse transcription-polymerase chain reaction or northern blotting. Levels of GRO-alpha protein in the cell-conditioned medium were determined by enzyme-linked immunosorbent assay. MG132 alone increased the levels of GRO-alpha mRNA and protein; however, it did not affect the GRO-alpha mRNA induced by lipopolysaccharide (LPS) and inhibited the LPS-induced decrease in IkappaB levels. Other proteasome inhibitors, MG115 and lactacystin, also induced the expression of GRO-alpha mRNA. MG132 induced the phosphorylation of p38 MAPK, MEK and JNK. Pretreatment of the cells with SB203580, an inhibitor of p38 MAPK, suppressed the MG132-induced GRO-alpha expression, but pretreatment of the cells with U0126, PD98059 or SP600125, inhibitors of MEK1/2 or JNK, did not influence the effect of MG132. We conclude that MG132 upregulates GRO-alpha expression in vascular endothelial cells, at least in part, through the activation of p38 MAPK.

Acetylcysteine↗
PubMed2003

Left thoracotomy approach in reoperative off-pump coronary revascularization: bypass grafting from the left axillary artery or descending thoracic aorta.

OBJECTIVE: Reoperative coronary bypass grafting is at high risk. Particularly in redo cases where the patent graft is running near the midline of the sternum, the graft may be exposed to injury by a median sternotomy and subsequent dissection. Whereas, off-pump bypass grafting from the left axillary artery or descending thoracic artery by a left thoracotomy approach is safe for preventing graft damage. METHODS: From March 1998 to February 2002, we performed off-pump coronary artery bypass grafting by a left thoracotomy approach in 9 patients. The left axillary artery was used as the inflow vessel in 4 cases, and the descending thoracic aorta in 5. RESULTS: The radial artery was anastomosed proximally to the axillary artery in 4 cases and the descending thoracic aorta in one case. The saphenous vein graft was anastomosed proximally to the descending thoracic aorta in 4 cases. Transdiaphragmatic minimally invasive bypass grafting for the right coronary artery was simultaneously performed in 3 cases. Postoperative cardiac events were ventricular arrhythmia in 6 cases and supraventricular arrhythmia in 3 cases. There was no damage to the patent grafts. Postoperative coronary angiography performed in 8 cases revealed all the grafts to be patent without stenosis. Cardiac symptoms were not found after the operation in any of the cases. CONCLUSIONS: These procedures can prevent the injury to patent grafts caused by a median sternotomy, and will be one of the useful strategies for reoperative off-pump coronary artery bypass grafting.

Aged↗
PubMed2003

Correlation of oxidative stress with activity of matrix metalloproteinase in patients with coronary artery disease. Possible role for left ventricular remodelling.

AIMS: Oxidative stress is implicated in the progression of heart failure, and matrix metalloproteinase (MMP) activity is increased in patients with congestive heart failure. We examined the role of oxidative stress on MMP activity in humans. METHODS AND RESULTS: We measured the MMP activity and the level of 8-iso-prostagandin F2alpha (8-iso-PGF2alpha), a specific and quantitative maker of oxidant stress, in the pericardial fluid (PF) in 47 consecutive patients with coronary artery disease who underwent coronary artery bypass surgery. Zymography of PF showed bands at 92-85kDa (MMP-9) and 72-65kDa (MMP-2). The MMP activity was expressed as the ratio to MMP-2 standard. MMP-2, MMP-9 and total gelatinolysis activities were positively correlated with left ventricular end-diastolic volume index (LVEDVI), and MMP-2 and total gelatinolysis activities were also positively correlated with LV end-systolic volume index. Moreover, MMP-2, MMP-9 and total gelatinolysis activities were all positively correlated with pericardial level of 8-iso-PGF2alpha. Also, LVDEVI was positively correlated with pericardial level of 8-iso-PGF2alpha. CONCLUSIONS: Oxidative stress may play an important role in the regulation of MMP activity. Augmented MMP activity may be involved in the development of ventricular remodelling in patients with coronary artery disease.

Aged↗
PubMed2003

Thrombolytic therapy for delayed, in-hospital stroke after cardiac surgery.

Five patients who had delayed stroke after cardiac surgery underwent intraarterial administration of a fibrinolytic agent for thromboembolism (n = 4) or thrombosis (n = 1) of the cerebral artery. Complete recanalization of the occluded artery was obtained in 3 patients and partial recanalization in 2. Additional angioplasty for basilar artery stenosis was performed in 1 patient. No patients exhibited rebleeding into the pericardial space or wound bleeding. All patients survived with moderate or full functional recovery. Immediate cerebral angiography and local thrombolysis may improve functional outcome and survival in patients with postcardiotomy cerebral thromboembolism.

Aged↗
PubMed2003

Restoration of sarcoplasmic reticulum protein level by thyroid hormone contributes to partial improvement of myocardial function, but not to glucose metabolism in an early failing heart.

OBJECTIVE: In heart failure, sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) activity is decreased, resulting in abnormal Ca(2+) handling and contractile dysfunction. We have previously reported that impaired glucose transporter (GLUT4) activity was an early indicator of progression of heart failure in pressure overload hypertrophied heart. This study was aimed to examine the contribution of both SERCA2 and glucose metabolism in pressure overload hypertrophied heart. Thyroid hormone, which is known to restore GLUT4 and/or SERCA2 function, was also tested. METHODS: Hypertrophied rat heart was created by abdominal aortic banding for 16 and 26 weeks. Then 20-40 microg/kg of 3,5,3'-triiodo-L-thyronine (T3) was administered subcutaneously daily for the last 4 weeks. Hypertrophied myocytes were created by the stimulation of H9c2(2-1) rat heart myoblasts with 2 micromol/L of isoproterenol for 3, 7 and 10 days. Left ventricle function of the hypertrophied rat hearts were measured in Langendorff perfusion. Myocardial protein levels of GLUT4 and SERCA2 in two models were analyzed by Western immunoblotting. Glucose and lactate concentration of cultured medium of myocytes were measured enzymatically to determine the efficacy of glycolysis. RESULTS: Diastolic function (tau) was significantly deteriorated in 16-week heart with significantly lower SERCA2 protein (89.3%) than control. In 26-week heart, both systolic and diastolic function (+dP/dt max, -dP/dt max and tau) was significantly deteriorated. This was associated with significant decrease in both GLUT4 and SERCA2 protein (84.8 and 91.6%, respectively). In cultured hypertrophied myocytes, glycolysis was shifted from aerobic to anaerobic during progression of hypertrophy. GLUT4 protein was significantly decreased at day 7 (45.6% of control). This led to a down-regulation of SERCA2 protein at day 10 (51.8% of control). Although there was no impact of T3 treatment on GLUT4, SERCA2 protein level was almost reversed with partial improvement of myocardial function. CONCLUSIONS: We conclude that impairment of both glucose metabolism and SERCA2 function were seen in an early heart failure. Thyroid hormone partially improved myocardial function with successful improvement of SERCA2 protein but no impact on GLUT4 protein expression in hypertrophied rat heart. Restoration of glucose metabolism is a critical step to avoid further progression of heart failure.

Animals↗
PubMed2003

Risk factors and treatment of deep sternal wound infection after cardiac operation.

OBJECTIVE: Although deep sternal wound infection (DSWI) after cardiac surgery is infrequent, its consequences are serious. The purposes of this study were to define the risk factors, and to establish the best surgical treatment for DSWI. METHODS: Retrospective analysis for 863 patients who underwent cardiac surgery was performed. The patients were divided into the DSWI group (n=17) and the non-infection group (n=846). Preoperative, perioperative, and postoperative variables were compared between the two groups using univariate and multivariate logistic regression analysis. The modality of treatment for DSWI was also analyzed. RESULTS: The incidence of DSWI was 1.97%. Independent predictors for DSWI were concomitant coronary artery bypass grafting (CABG) with valve or aortic surgery [odds ratio, 4.1; 95% confidence interval, (1.1, 15.1)] and postoperative use of intraaortic balloon pumping [4.4, (1.6, 12.3)]. An independent predictor in isolated CABG patients was emergency operation [10.9, (2.7, 44.7)]. Four of 17 patients died. Methicillin-resistant Staphylococcus aureus (MRSA) was cultured from 10 (58.8%) patients, and all four of the deceased subjects died of its infection. Seventeen patients were treated by debridement, primary closure, and the addition of an omentum or muscle flap if necessary. CONCLUSIONS: Patients in poor perioperative condition are at high risk for the development of this infection. It was difficult to establish the best treatment, owing to the small series of this study. Mortality and morbidity of DSWI due to MRSA was high.

Adult↗
PubMed2002

Expression of alpha-synuclein, the precursor of non-amyloid beta component of Alzheimer's disease amyloid, in human cerebral blood vessels.

The non-amyloid beta component of Alzheimer's disease amyloid (NAC) is detected in cerebral amyloid angiopathy; and the precursor of NAC is now known to be identical to alpha-synuclein (alpha-S), a major component of Lewy bodies in Parkinson's disease. We studied if cerebral vascular cells express alpha-S. Immunohistochemical studies of human cerebral tissues from control and cerebral amyloid angiopathy patients revealed the expression of alpha-S in vascular endothelial and smooth muscle cells. Then we studied the expression of alpha-S in vitro using cultures of vascular cells. Cultures of human umbilical vein endothelial cells and umbilical artery smooth muscle cells were found to constitutively express alpha-S messenger RNA and protein. alpha-S is normally expressed in vascular cells and may play some physiological role in the vascular wall.

Aged↗
PubMed2002

Tsallis dynamics using the Nosé-Hoover approach.

On the basis of the Nosé-Hoover method, we developed a deterministic algorithm that produces an arbitrary probability density. An ordinary differential equation in the algorithm can realize the Tsallis distribution density. The Tsallis distribution has been considered a candidate of a distribution that represents a physical system in a heat bath. The Tsallis distribution density employed in this algorithm is defined using a full energy function form E(x,p), along with the Tsallis index q > or = 1. Using the current equation, numerical simulations were performed for simple systems and the Tsallis distributions were observed.

Journal Article↗
PubMed2002

Relationship between postoperative recurrence and expression of cyclin E, p27, and Ki-67 in non-small cell lung cancer without lymph node metastases.

BACKGROUND: Cyclin E and p27 play pivotal roles in cancer development and progression. We investigated whether the prognosis in cases of non-small cell lung cancer without lymph node metastases that underwent complete resection could be associated with tissue expression of cyclin E, p27, and Ki-67. METHODS: Tumors from 62 patients at least 5 years after surgery were assessed by immunohistochemistry for expression of cyclin E, p27, and Ki-67. Disease-free survival (DFS) after surgery was used to evaluate disease prognosis. We also investigated the relationship between expression of these factors and postoperative recurrence. RESULTS: In non-small cell lung cancer, p27-negative expression and pT factor were significantly unfavorable prognostic factors in multivariate analysis. The DFS rate in cyclin E-positive expression was significantly lower than in cyclin E-negative expression. Similarly, p27-negative expression and high Ki-67 expression correlated with a shortened DFS rate. In combinations of expression of cyclin E and p27, the cyclin E-negative/p27-positive group had a significantly higher DFS rate than did the other groups. According to histological type, there were correlations between the risk of postoperative recurrence and expression of these three biological factors, especially in adenocarcinoma. CONCLUSION: By analyzing the expression of cyclin E, p27, and Ki-67 of tumor cells, it was possible to extract the patient group for whom closer follow-up and postoperative treatment is necessary to improve survival rate.

Adenocarcinoma↗
PubMed2002

Proteasome inhibitor MG-132 enhances the expression of interleukin-6 in human umbilical vein endothelial cells: Involvement of MAP/ERK kinase.

Interleukin-6 (IL-6) is a multifunctional cytokine that plays an important role in inflammatory reactions. We have addressed the possible regulation of IL-6 expression by the ubiquitin-protease system in human umbilical vein endothelial cells. Cultured endothelial cells were treated with MG-132, a protease inhibitor, and the levels of IL-6 mRNA and protein were measured by reverse transcription-PCR and ELISA. MG-132 increased the expression of IL-6 mRNA and protein;and this effect was abolished by the pretreatment of the cells with U0126, an inhibitor of MAP or ERK kinases (MEK 1/2). MG-132 treatment was also found to enhance the level of phosphorylated MEK 1/2. Treatment of the cells with actinomycin D inhibited IL-6 expression in response to MG-132, suggesting the transcriptional upregulation of IL-6 under proteasomal inhibition. We conclude that a protease inhibitor MG-132 upregulates IL-6 expression in vascular endothelial cells, at least in part, through the activation of MEK 1/2.

Butadienes↗