Search PubMed⌕ Search

Biomedical subjects

S Kihara

Publications and source records attributed to S Kihara.

At least 73 records · Page 4Linked to original sources

Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity.

Obesity which is defined as accumulation of excess body fat, is a major cause of atherosclerotic vascular disease in industrial countries. Recent advances in the biology of adipose tissue have revealed that adipose tissue is not simply an energy storage organ but it also secretes a variety of molecules which affect the metabolism of the whole body. Through a systematic search of active genes in adipose tissue, we found that adipose tissue, especially visceral fat expressed numerous genes for secretory proteins (about 30% of total genes analyzed). Among them, plasminogen activator-1 (PAI-1), which is a regulator of the fibrinolytic system, was overexpressed in the visceral fat in an animal model of obesity. Plasma levels of PAI-1 were closely correlated with visceral fat adiposity. Thus, PAI-1 secreted from visceral fat may play some role in thrombotic vascular disease in visceral obesity. Adiponectin, a novel adipose-specific gene product, which has a matrix-like structure, is abundantly present in the bloodstream. Dysregulated secretion of adiponectin may be related to vascular disease in obesity. Biologically active molecules secreted from adipose tissue (adipocytokines) may have important roles in the development of atherosclerotic disease in obesity.

Adiponectin↗

[Reoperative off-pump subclavian-coronary artery bypass grafting in an elderly patient with left internal thoracic artery stenosis].

A 80-year-old Japanese female was diagnosed to have angina pectoris and admitted to our hospital. She had been operated on with mitral valve replacement and coronary artery bypass grafting to right and circumflex coronary artery 4 years before. The coronary angiogram showed significant stenosis with severe calcification in the left anterior descending coronary artery, and it was unsuitable for catheter intervention. The patient also had stenotic left internal thoracic artery and multiple cerebral infarction, but successful off-pump subclavian-coronary artery bypass grafting using saphenous vein graft through small thoracotomy was performed without new neurological deficit. This procedure is useful for patients with left internal thoracic artery unsuitable for MIDCABG, due to quality, size, or injury during preparation.

Aged↗

[Management of patient with acute myocardial infarction due to left main trunk obstruction].

Between April 1995 and March 1998, we experienced 13 cases of Acute Myocardial Infarction due to Left Main Trunk Obstruction (LMT-AMI). Two cases died before emergent intervention. Eight cases underwent emergent intervention (Plain Old Balloon Angioplasty (POBA) in five cases, Stenting in 3 cases); 2 cases died of acute occlusion of POBA site, 1 case survived by only POBA, and the other 5 cases underwent following Coronary Artery Bypass Grafting (CABG). 3 cases underwent only CABG with stable hemodynamics condition by Intraaortic balloon pumping (IABP) support. In a result, seven of eight CABG cases survived. Emergent stenting made the hemodynamics before CABG stable, and six-month's follow up angiogram showed occluded bypass grafts and patent stented sites in two of three cases. The combination therapy of emergent stenting and CABG will have to be evaluated in future.

Adult↗

Two new drainage tubes for minimally invasive cardiac surgery.

BACKGROUND: The limited exposure typical of new minimally invasive surgical approaches to cardiac surgery makes it difficult to utilize traditional equipment such as temporary pacing electrodes or the placement of drainage tubes into the lateral pleural space. To overcome these difficulties, we have developed specialized drainage tubes just for limited access cardiac surgery. METHODS: The first device is a drainage tube with temporary pacing function. It has three fixed electrodes and one free pacing wire incorporated into an elliptical, angled 28 Fr silicone drainage tube. This tube is placed in the space between the heart and the diaphragm. The two fixed electrodes provide epicardial contact for ventricular pacing. The third fixed electrode and one free pacing wire are for the purpose of atrial pacing (Japanese patent #2,701,135). The second device is a Y-shaped drainage tube. Frequently, the pleural space is opened during harvesting of an internal mammary graft and then insertion of a chest tube in the thoracic cavity becomes necessary. We developed a new Y-shaped tube where one segment is placed in the retrosternal space and one segment is placed in the pleural cavity. (Japanese Association of Intellectual Copyright #130,591) RESULTS: The drainage-pacing device was used in 48 coronary artery bypass grafting (CABG) patients. Drainage function and pacing function were excellent in all patients. The bifurcated drainage device was used in 34 patients achieving effective drainage of both cavities without complication during or after removal. CONCLUSIONS: Due to the limited surgical exposure provided by the newer minimally invasive procedures in cardiac surgery, specialized equipment that can be inserted through small incisions needs to be developed. We report the development of a new drainage-pacing device as well as a bifurcated drain for simultaneous drainage of the mediastinal and pleural cavities. These devices have facilitated minimally invasive cases and were free of complications.

Coronary Artery Bypass↗

Lipoprotein(a) enhances the expression of intercellular adhesion molecule-1 in cultured human umbilical vein endothelial cells.

BACKGROUND: We reported an increase in serum lipoprotein(a) [Lp(a)] levels in patients with thromboangiitis obliterans, suggesting that Lp(a) could also contribute to the pathogenesis of cardiovascular diseases by a mechanism different from atherosclerosis. Adhesion molecules were shown to contribute to the development of not only atherosclerotic but also inflammatory vascular diseases. METHODS AND RESULTS: We evaluated the effect of Lp(a) on the expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in human umbilical vein endothelial cells by a cell ELISA. Lp(a) dramatically enhanced the levels of ICAM-1 in a dose-dependent manner. A discernible increase in ICAM-1 expression was observed at a physiological concentration of 0.26 mmol cholesterol/L Lp(a) after 48-hour incubation. A 1.8-fold increase in ICAM-1 expression was observed 48 hours after the addition of Lp(a) (1.04 mmol cholesterol/L). Northern blot analysis demonstrated that the amount of ICAM-1 mRNA was increased after treatment with Lp(a). In contrast to ICAM-1, the expression of VCAM-1 and E-selectin was not significantly affected by Lp(a). Lp(a-) [apolipoprotein(a)- removed Lp(a) by reduction with dithiothreitol] and LDL had no significant effect on the expression of ICAM-1. In contrast, recombinant apolipoprotein(a) protein alone significantly enhanced ICAM-1 expression. Lp(a) decreased the level of active transforming growth factor (TGF)-beta in the conditioned medium. Furthermore, recombinant TGF-beta significantly decreased the Lp(a)-induced ICAM-1 expression. These findings suggested that Lp(a) may enhance the ICAM-1 expression by decreasing active TGF-beta level. CONCLUSIONS: Lp(a) could contribute to the development of cardiovascular diseases by enhancing the expression of ICAM-1 in endothelial cells.

Antibodies↗

Calcium channel blockers attenuate cardiovascular responses to tracheal extubation in hypertensive patients.

PURPOSE: Hypertensive patients exhibit exaggerated cardiovascular responses to tracheal extubation. This study was undertaken to examine the inhibitory effects of calcium channel blockers, nicardipine and diltiazem, on haemodynamic changes after tracheal extubation. METHODS: Sixty hypertensive patients (ASA physical status II) undergoing elective orthopaedic (upper and lower extremity) surgery received, in a randomized, double-blind manner, 30 micrograms.kg-1 nicardipine, 0.2 mg.kg-1 diltiazem or saline (as a control) (n = 20 of each) i.v. before tracheal extubation. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and after tracheal extubation. RESULTS: The HR, MAP and RPP increased after tracheal extubation in the control group (P < 0.05). The increases in these haemodynamic variables were attenuated with nicardipine or diltiazem. The inhibitory effects of diltiazem on these cardiovascular responses to tracheal extubation were greater than those of nicardipine (HR; 86 +/- 7 vs 101 +/- 10, RPP; 11,437 +/- 1,575 vs 14,675 +/- 2,874, mean +/- SD, P < 0.05). CONCLUSION: Compared with nicardipine, administration of diltiazem produced greater attenuating the circulatory responses to tracheal extubation in hypertensive patients.

Adult↗

[Coronary artery bypass grafting for cases which were not amenable to preoperative left ventriculogram].

We evaluated the coronary artery bypass grafting (CABG) for the cases which were not amenable to preoperative left ventriculograms (LVG). Between June 1970 and March 1996, we had 2045 cases of isolated CABG, and 52 cases of which were not amenable to preoperative LVG. The reasons of no preoperative LVG were during cardiopulmonary resuscitation (CPR) in 4 cases, shock state in 14, NYHA class IV or CCS class IV in 26, angina attack after coronary angiography in 3 and so on. Preoperative diagnoses were acute myocardial infarction in 28, angina after infarction in 13, unstable angina in 9 and effort angina in 2. Preoperative conditions were reoperation in 6, insertion of intra-aortic balloon pumping in 46, chronic renal failure in 15 (hemodialysis in 4) and arrhythmia (VT or Vf) in 12. Concerning the coronary lesions, left main trunk and triple vessel diseases occupied 75% of all. Surgical deaths were 5 cases (9.6%) and hospital deaths were 4 cases (7.7%). The all cases which needed preoperative CPR were died with brain injury. The result of the cases which were not amenable to preoperative LVG were worse than the cases with ischemic cardiomyopathies. In conclusion, no preoperative LVG is one of the highest risk factors of all.

Adult↗

[A combination of reoperation for pseudoaneurysm following the Cabrol procedure and total aortic arch replacement in a patient with Marfan syndrome--a case with an aberrant right subclavian artery].

A 44-year-old male with Marfan's syndrome had undergone an initial operation for DeBakey type I acute aortic dissection with annulo-aortic ectasia. He had undergone replacement of the ascending aorta and aortic valve with a composite graft and reconstruction of the coronary artery by the Cabrol procedure. At 5 years after the initial surgery he experienced chest pain and was subsequently examined. Computed tomography revealed a pseudoaneurysm in the ascending aorta and the residual aortic dissection. The maximum diameter of the pseudoaneurysm was 85 mm and the maximum diameter of the aortic arch was 55 mm. The aortic arch was associated with an aberrant right subclavian artery. Angiography revealed that the pseudoaneurysm was caused by leakage at the coronary ostium-graft anastomoses. We repaired the anastomoses and performed total aortic arch replacement with reconstruction of four arch branches. The postoperative course was uneventful without any complications. We report this case because there have been few reports regarding arch replacement in cases with an aberrant right subclavian artery.

Aortic Dissection↗

Troglitazone enhances glucose uptake and inhibits mitogen-activated protein kinase in human aortic smooth muscle cells.

The thiazolidinedione analogue troglitazone is an antidiabetic agent that improves insulin resistance in rodents and humans. Although coronary artery disease is common in patients with the insulin resistance syndrome, the effects of troglitazone on smooth muscle cells (SMC) have not been fully elucidated. We therefore examined the effects of troglitazone on cell growth and glucose uptake in human aortic SMC. Mitogen-activated protein (MAP) kinase activity and glucose transporter (Glut) 1 mRNA levels were also studied. In the absence of troglitazone, insulin (10(-7) M) caused a 2-fold increase of DNA synthesis in SMC and troglitazone suppressed the increase of DNA synthesis in a dose-dependent manner. This growth suppression was accompanied by inhibition of MAP kinase activity. On the other hand, troglitazone significantly increased Glut 1 mRNA and enhanced glucose uptake in SMC. These results suggest that troglitazone affects the insulin signaling pathways in SMC and suppresses growth while promoting glucose uptake. Our findings support the application of troglitazone as an inhibitor of SMC proliferation in patients with insulin resistance.

Aorta↗

Troglitazone suppresses intimal formation following balloon injury in insulin-resistant Zucker fatty rats.

Troglitazone, a thiazolidinedione derivative, overcomes insulin resistance through promoting insulin receptor function. However, the effect of the resultant enhancement of insulin action on the regulation of cellular proliferation remains unknown. We investigated the effect of troglitazone on intimal proliferation after balloon injury in insulin-resistant Zucker fatty rats. Troglitazone markedly decreased blood glucose and triglyceride levels at the therapeutic dosage. The area of neointima significantly decreased in treated animals 2 weeks after operation, as compared with the untreated control animals (0.0526 +/- 0.0292 and 0.115 +/- 0.0354 mm2, respectively). The ratio of neointimal to medial area in treated rats (0.75 +/- 0.26) decreased by as much as 53% compared with untreated rats (1.40 +/- 0.05). We next examined DNA synthesis in cultured smooth muscle cells (SMCs) derived from non-insulin-resistant rats, to assess whether troglitazone suppresses the proliferation of vascular SMCs independent of metabolic effects. The result showed that troglitazone decreased [methyl-3H]thymidine incorporation into DNA. In conclusion, treatment with troglitazone in Zucker fatty rats resulted in a reduction in neointima formation after balloon injury, and also corrected hypertriglyceridemia and hyperglycemia. In addition, in vitro studies revealed that the anti-proliferative effect of troglitazone stems from its direct action on DNA synthesis rather than any accompanying metabolic changes. Therefore, troglitazone seems to be applicable in preventing atherosclerosis in patients with insulin resistance.

Animals↗

High concentration of glucose induces the expression of intercellular adhesion molecule-1 in human umbilical vein endothelial cells.

Atherosclerosis is known to be accelerated in patients with diabetes mellitus. We have examined the effect of glucose on the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human umbilical vein endothelial cells (HUVEC) and the adhesion of cells of monocyte-like cell line, THP-1, to HUVEC. HUVEC exposed to a high glucose concentration (16.7 mM) showed a 1.4-fold increase in the adhesion of THP-1 cells and a 1.3-fold increase in cell surface expression of ICAM-1 after 6 h exposure compared with those cultured in medium with a low glucose concentration (5.6 mM). ICAM-1 expression began to increase after 3 h exposure, was maximal at 6 h and gradually decreased afterwards. At 16.7 mM, raffinose stimulation produced a significantly lower expression of ICAM-1 on HUVEC than glucose, furthermore it caused a significantly lower expression than low glucose stimulation (5.6 mM). We conclude that a high concentration of glucose can induce ICAM-1 in endothelial cells and that this effect may play an important role in atherogenesis in patients with diabetes mellitus.

Cell Adhesion↗

[Central venous access via the distal femoral vein using ultrasound-guidance].

We used a new method for central venous (CV) access via the distal femoral vein using ultrasound guidance in two cases. In the first case, because of multiple catheter punctures for hemodialysis previously, femoral catheter placement was impossible using a standard landmark technique. In the second case of laryngoplasty, it was also impossible to place a CV catheter at usual groin sites because of extensive mycosis. In these two cases, we attempted CV catheterization via the distal femoral vein at the femur (10 cm from the inguinal ligament) by using ultrasound guidance. In both cases the catheter placement was easy and took a short time. No complication due to puncture and catheterization was observed. CV access via the femoral vein in the groin has been the first-choice for the patients undergoing neuro- or neck-surgery. However, the femoral CV catheters at inguinal site has been associated with higher incidence of catheter infection than the subclavian or internal jugular vein. These methods have a potential for decrease in catheter infection rate. These two case reports suggest that the CV catheterization at distal femoral site by ultrasound-guidance is useful as a new method of CV access.

Aged↗

Role of membrane-anchored heparin-binding epidermal growth factor-like growth factor and CD9 on macrophages.

Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) is a potent mitogen for smooth-muscle cells (SMCs) belonging to the EGF family. We have previously determined that HB-EGF is expressed in macrophages and SMCs of human atherosclerotic lesions and that its membrane-anchored precursor, proHB-EGF, also has a juxtacrine mitogenic activity which is markedly enhanced by CD9, a surface marker of lymphohaemopoietic cells. Therefore, when both proHB-EGF and CD9 are expressed on macrophages, they may strongly promote the development of atherosclerosis. In the present study we have investigated the changes in proHB-EGF and CD9 in THP-1 cells during differentiation into macrophages and by the addition of oxidized low-density lipoproteins (OxLDL) and assessed juxtacrine growth activity of THP-1 macrophages for human aortic SMCs. HB-EGF and CD9 at both the mRNA and the protein level were up-regulated after differentiation into macrophages, and further expression of HB-EGF was induced by the addition of OxLDL or lysophosphatidylcholine. Juxtacrine induction by formalin-fixed growth was suppressed to control levels by an inhibitor of HB-EGF and was partially decreased by anti-CD9 antibodies. These results suggest that co-expression of proHB-EGF and CD9 on macrophages plays an important role in the development of atherosclerosis by a juxtacrine mechanism.

Antigens, CD↗

Characteristics of coronary artery disease and lipoprotein abnormalities in patients with heterozygous familial hypercholesterolemia associated with diabetes mellitus or impaired glucose tolerance.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of serum low density lipoprotein (LDL) cholesterol and premature coronary atherosclerosis. In order to elucidate the influence of abnormal glucose metabolism on the development of coronary artery disease (CAD) in FH patients, we examined the prevalence of CAD and characteristics of lipoprotein abnormalities in patients with heterozygous FH who were accompanied by diabetes mellitus (DM) or impaired glucose tolerance (IGT). The subjects of the present study were 150 patients with heterozygous FH, all over 40 years of age. Oral glucose tolerance tests demonstrated that 15 patients had DM and 27 had IGT. The combination of DM or IGT with FH was associated with a further increase in the prevalence of CAD (DM:IGT:normal glucose tolerance (N), 87:59:43%). Furthermore, the prevalence of the stenoses in the distal coronary arteries was significantly higher in the DM group than in the N group, while there was no significant difference in the prevalence of proximal and middle lesions. Serum triglyceride levels were significantly higher in the DM and IGT groups than in the N group (P < 0.01, DM versus N group; P < 0.01, IGT versus N group), while total cholesterol levels were not significantly different. When lipoproteins were analyzed by polyacrylamide gel electrophoresis, the frequency of midband appearance, which implies an increase in remnant lipoproteins, was significantly higher in the DM and IGT groups than in the N group (DM:IGT:N, 87:72:29%, P < 0.01, DM versus N group; P < 0.01, IGT versus N group). Ultracentrifugation analysis of lipoproteins revealed that intermediate density lipoprotein cholesterol was increased in DM and IGT groups compared with the N group. These data suggest that abnormal glucose metabolism may accelerate the development of CAD in FH patients due to an increase in atherogenic remnant lipoproteins in addition to high concentration of LDL. Special attention should be paid in the treatment of FH patients with impaired glucose metabolism, to avoid the advancement of coronary atherosclerosis.

Adult↗

Interferon alpha induces disorder of lipid metabolism by lowering postheparin lipases and cholesteryl ester transfer protein activities in patients with chronic hepatitis C.

The effect of recombinant interferon alpha 2a (rIFN-alpha2a) on serum lipoprotein metabolism was assessed in 39 patients with chronic viral hepatitis C. rIFN-alpha2a was administered intramuscularly at a dose of 9 x 10(6) U/d for 2 weeks and then for 3 times a week over 6 months. The serum cholesterol concentration significantly decreased one week after rIFN-alpha2a administration. Approximately 67% of this decrease was attributed to the reduction of high-density lipoprotein (HDL)-cholesterol; a decrease in HDL2-cholesterol was more evident. By contrast, serum triglyceride levels, largely derived from very-low density lipoprotein (VLDL), significantly increased following rIFN-alpha2a treatment. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities in the postheparin plasma were reduced by 75.7% and by 79.4%, respectively, and decreases in plasma cholesteryl ester transfer protein (CETP) activity and its protein mass were also observed. However, prothrombin time was ameliorated by rIFN-alpha2a, suggesting that the decrease in LPL, HTGL, and CETP activities may not be due to a reduction in protein synthesis by the liver. Simple correlation analysis demonstrated that the changes in LPL activity before and after 2 weeks of treatment with rIFN-alpha2a showed a significant negative correlation with changes in serum triglyceride and VLDL-triglyceride and a positive correlation with changes in HDL-cholesterol and HDL2-cholesterol. These results suggest a major contribution of reduced LPL activity with regard to the lipoprotein disorders. In conclusion, rIFN-alpha2a treatment on patients with chronic hepatitis C causes marked changes in serum lipoprotein metabolism associated with decreases in LPL, HTGL, and CETP activities.

Adult↗

Increased serum remnant lipoproteins in patients with apolipoprotein E7 (apo E Suita).

Apolipoprotein (apo) E7 was originally identified by Yamamura et al. in subjects with atherosclerotic cardiovascular diseases (J. Clin. Invest. 1984;74:1229). However, the lipoprotein abnormalities associated with apo E7 phenotype have not been elucidated. In the current study, to clarify the physiological roles of apo E7, lipoprotein abnormalities were studied in 12 apo E7 heterozygotes. A total of seven subjects were hyperlipidemic and five subjects were normolipidemic. The apo E phenotype was apo E7/3 in 11 subjects and apo E7/4 in one subject. Polymerase chain reaction revealed that all of the subjects with apo E7 phenotype had the same mutation as that of apo E(Suita) as reported previously (J. Biochem. 1989;105:249). All the hyperlipidemic subjects were over 40 years of age and two of them also had and severe coronary heart disease. Ultracentrifugal analysis revealed that the cholesterol level both in very low density lipoprotein and in intermediate density lipoprotein (IDL) was substantially higher in hyperlipidemic apo E7 heterozygotes, compared with control subjects and that the IDL cholesterol was also increased even in normolipidemic apo E7 heterozygotes. Polyacrylamide gel electrophoresis of lipoproteins showed a midband, which implies the increase of remnant lipoproteins, in 11 subjects out of 12, irrespective of the presence or absence of hyperlipoproteinemia. In two cases, a broad beta pattern was observed similar to that seen in type III hyperlipoproteinemia. Dietary therapy was dramatically effective for the treatment of hyperlipidemia in patients with apo E7. These findings confirm that apo E is crucial for remnant lipoprotein metabolism and that apo E7 is related to the increase in serum remnant lipoproteins, which leads to hyperlipoproteinemia in association with obesity, aging and impaired glucose metabolism.

Adult↗