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Biomedical subjects

S Kihara

Publications and source records attributed to S Kihara.

At least 37 records · Page 2Linked to original sources
PubMed2001

Immunohistochemical localization of Betacellulin, a member of epidermal growth factor family, in atherosclerotic plaques of human aorta.

Betacellulin (BTC), a new member of the EGF family, has been reported to be a potent mitogen for rat vascular smooth muscle cells (SMCs). BTC mRNA is known to be expressed in several human organs. However, the localization of BTC in human vascular tissues has not yet been clarified. We investigated whether or not BTC protein is involved in the pathogenesis of human atherosclerosis. Recombinant human BTC showed a mitogenic activity on cultured human aortic SMCs by measuring [3H]thymidine incorporation. The immunohistochemical localization of BTC, SMCs, macrophages, EGF receptors and ErbB4 was examined in autopsied human aortas. BTC was detected in both intimal and medial SMCs of the aortic wall. The percentage of BTC-positive medial SMCs in early types of atherosclerotic lesions decreased with age, but in adult, it was significantly higher in advanced types than in early types of atherosclerotic lesions. BTC-positive SMCs were predominantly localized in the medial side of the intima. Furthermore, numerous BTC-positive SMCs and macrophages were observed around the core lesion of atherosclerotic plaques. Receptors for BTC, EGF receptor and ErbB4, were expressed on SMCs, suggesting that BTC is associated with EGF receptor family-mediated signaling. BTC is produced in human aortic tissue and might play important roles in atherogenesis.

Adolescent↗
PubMed2001

Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation--double-blind placebo-controlled trial.

BACKGROUND: It has been clarified that visceral fat accumulation leads to atherosclerosis through multiple risk factors such as insulin resistance, glucose intolerance, hyperlipidemia and hypertension. So far, it has been reported that a thaizolidinedione derivative, troglitazone, improves the insulin resistance in subjects with diabetes, glucose intolerance and obesity. However, it has not been reported yet that troglitazone affects fat distribution in subjects concomitant with visceral fat accumulation and multiple risk factors. METHODS: Twenty-nine subjects with visceral fat accumulation who had at least two risk factors including glucose intolerance, hyperlipidemia and hypertension were investigated. They were randomly assigned to receive either 200 or 400 mg per day of troglitazone or placebo for 12 weeks. A 75 g oral glucose tolerance test (OGTT) was performed before and after the treatment for 12 weeks. Fasting plasma glucose, insulin, HbA(1c), total serum cholesterol (T-chol), triglyceride (TG), HDL-cholesterol (HDL-C), and blood pressure, as well as the number of risk factors were measured periodically during the treatment. The change of the abdominal fat distribution was evaluated using computed tomographic scanning (CT scan) at the umbilicus level. RESULTS: After the treatment for 12 weeks, the area under the curve (AUC) of plasma glucose from a 75 g OGTT decreased dose-dependently. HbA(1c) and TG decreased significantly in the high-dose troglitazone group (400 mg per day) compared with the placebo group (P<0.05). Systolic blood pressure was significantly lower in subjects with hypertension in the pooled troglitazone group than in the placebo group (P<0.05). Therefore, the number of risk factors decreased with the troglitazone treatment. The ratio of visceral fat area (VFA) to subcutaneous fat area (SFA) (V/S ratio) decreased in the troglitazone groups due to decreased VFA and increased SFA. CONCLUSION: These results suggest that thiazolidinedione derivative may be a useful drug to improve multiple risk factors by changing the fat distribution in subjects with visceral fat accumulation.

Adipose Tissue↗
PubMed2001

The expression of SPARC in adipose tissue and its increased plasma concentration in patients with coronary artery disease.

OBJECTIVE: Adipocytes secrete various cytokines and matrix proteins. Several of them precipitate in obesity-associated diseases, including atherosclerosis. In the current study, we have examined the expression of secreted protein, acidic and rich in cysteine (SPARC) in adipose tissue and its significance in obesity and coronary artery disease (CAD). RESEARCH METHODS AND PROCEDURES: The SPARC mRNA expressions both in vivo and in vitro were detected by Northern blot analysis. Plasma SPARC concentrations were measured by enzyme immunosorbent assay. First, we investigated the plasma SPARC levels of 88 unrelated adult Japanese subjects (62 men and 26 women; average age: [+/- SD] 50 +/- 12 years; body mass index [BMI]: 16 to 46 kg/m(2)). Additionally 31 subjects with CAD diagnosed by coronary angiography (20 men and 11 women) were also investigated. RESULTS: Human adipose tissues expressed abundant SPARC mRNA. SPARC expression in adipose tissues was upregulated in obese db/db mice. Markedly enhanced expression of SPARC mRNA was observed in 3T3-L1 fibroblasts during adipocyte differentiation. Consistent with these results, plasma SPARC levels proved a positive correlation with BMI in humans (r = 0.27; p < 0.01). Interestingly, plasma SPARC concentrations were significantly elevated in age- and BMI-matched subjects with CAD (p < 0.05). DISCUSSION: SPARC was expressed in adipose tissues and its expression was enhanced in obese mice. In human, plasma SPARC levels were elevated in obesity and CAD patients. This elevated SPARC may be involved in the progression of CAD.

Adipose Tissue↗
PubMed2001

Repeated administration of protamine does not attenuate circulatory changes caused by protamine reversal of heparin in dogs.

OBJECTIVE: To determine whether repeated administration of protamine attenuates circulatory changes caused by protamine reversal of heparin and to evaluate the significance of nitric oxide generation. DESIGN: Prospective, randomized, controlled, animal study. SETTING: University research laboratory. PARTICIPANTS: Twenty-seven adult mongrel dogs. INTERVENTIONS: The animals were randomly assigned to 3 groups (n = 9 in each) according to the pretreatment. The control group was pretreated with normal saline, and the 2 other groups were given 2 different doses of protamine: protamine 0.1 (protamine, 0.1 mg/kg) and protamine 1.0 (protamine, 1.0 mg/kg). Under general anesthesia, all animals were anticoagulated with intravenous heparin, 200 IU/kg. Five minutes after heparin injection, preadministered saline (control) or protamine in saline was infused during 60 seconds. Five minutes after the pretreatment, protamine, 2.0 mg/kg in control, 1.9 mg/kg in protamine 0.1, or 1.0 mg/kg in protamine 1.0, was administered intravenously during 10 seconds. MEASUREMENTS AND MAIN RESULTS: Percent changes in mean arterial blood pressure among the 3 groups at each period were not significantly different except 60 minutes after protamine infusion. Mean pulmonary arterial pressure in the protamine 1.0 group at 5, 15, 20, and 60 minutes was higher than in the control group. Serum nitrate concentration was not significantly different among the 3 groups at baseline and 10 minutes after protamine injection. CONCLUSION: Repeated administration of protamine does not attenuate circulatory changes caused by protamine reversal of heparin in dogs. Nitric oxide generation does not appear to be responsible for the phenomenon.

Animals↗
PubMed2001

Staged coronary artery bypass grafting after percutaneous angioplasty for intracranial vascular stenosis.

OBJECTIVE: Cerebrovascular disease is commonly associated with coronary artery disease and is a major risk factor for cardiac surgery. Concomitant coronary artery bypass grafting and carotid endarterectomy may reduce the risk of stroke; however, this staged operation is effective only for extracranial lesions. The strategy for on-pump coronary artery bypass grafting for patients with intracranial vascular stenosis is still controversial. METHODS: The subjects were 157 consecutive candidates for coronary artery bypass grafting who underwent computed tomography and digital subtraction cerebral angiography preoperatively to check for cerebrovascular disease. Additional single-photon emission computed tomography was performed to evaluate cerebral ischemia, according to the neurologist's request. Patients with diffuse intracranial vascular stenosis impossible to treat with percutaneous transluminal angioplasty underwent off-pump coronary artery bypass grafting. Patients with a circumflex coronary artery lesion first underwent percutaneous transluminal angioplasty for cerebral vascular stenosis followed by secondary on-pump coronary artery bypass grafting. RESULTS: Three patients were selected for staged operations. Percutaneous transluminal angioplasty was performed for 4 intracranial stenotic lesions. All lesions were dilated successfully, and no complications developed during or after the procedure. All patients tolerated staged coronary artery bypass grafting and were extubated within 1 day without any mental disturbance. No further neurologic complication occurred, and computed tomography performed postoperatively revealed no significant changes. CONCLUSION: Staged on-pump coronary bypass after percutaneous transluminal angioplasty for cerebrovascular disease may reduce the risk of stroke during cardiopulmonary bypass, and it is useful especially in patients with intracranial cerebrovascular disease.

Aged↗
PubMed2001

The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome.

Here we present the first genetic analysis of adiponectin levels, a newly identified adipocyte-derived protein. Recent work has suggested that adiponectin may play a role in mediating the effects of body weight as a risk factor for coronary artery disease. For this analysis we assayed serum levels of adiponectin in 1100 adults of predominantly northern European ancestry distributed across 170 families. Quantitative genetic analysis of adiponectin levels detected an additive genetic heritability of 46%. The maximum LOD score detected in a genome wide scan for adiponectin levels was 4.06 (P = 7.7 x 10(-6)), 35 cM from pter on chromosome 5. The second largest LOD score (LOD = 3.2; P = 6.2 x 10(-5)) was detected on chromosome 14, 29 cM from pter. The detection of a significant linkage with a quantitative trait locus on chromosome 5 provides strong evidence for a replication of a previously reported quantitative trait locus for obesity-related phenotypes. In addition, several secondary signals offer potential evidence of replications for additional previously reported obesity-related quantitative trait loci on chromosomes 2 and 10. Not only do these results identify quantitative trait loci with significant effects on a newly described, and potentially very important, adipocyte-derived protein, they also reveal the emergence of a consistent pattern of linkage results for obesity-related traits across a number of human populations.

Adiponectin↗
PubMed2001

PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.

Insulin resistance and its dreaded consequence, type 2 diabetes, are major causes of atherosclerosis. Adiponectin is an adipose-specific plasma protein that possesses anti-atherogenic properties, such as the suppression of adhesion molecule expression in vascular endothelial cells and cytokine production from macrophages. Plasma adiponectin concentrations are decreased in obese and type 2 diabetic subjects with insulin resistance. A regimen that normalizes or increases the plasma adiponectin might prevent atherosclerosis in patients with insulin resistance. In this study, we demonstrate the inducing effects of thiazolidinediones (TZDs), which are synthetic PPARgamma ligands, on the expression and secretion of adiponectin in humans and rodents in vivo and in vitro. The administration of TZDs significantly increased the plasma adiponectin concentrations in insulin resistant humans and rodents without affecting their body weight. Adiponectin mRNA expression was normalized or increased by TZDs in the adipose tissues of obese mice. In cultured 3T3-L1 adipocytes, TZD derivatives enhanced the mRNA expression and secretion of adiponectin in a dose- and time-dependent manner. Furthermore, these effects were mediated through the activation of the promoter by the TZDs. On the other hand, TNF-alpha, which is produced more in an insulin-resistant condition, dose-dependently reduced the expression of adiponectin in adipocytes by suppressing its promoter activity. TZDs restored this inhibitory effect by TNF-alpha. TZDs might prevent atherosclerotic vascular disease in insulin-resistant patients by inducing the production of adiponectin through direct effect on its promoter and antagonizing the effect of TNF-alpha on the adiponectin promoter.

3T3 Cells↗
PubMed2001

Coronary artery bypass grafting in 105 patients with hemodialysis-dependent renal failure.

This study was proposed to define early and long-term results of coronary artery bypass grafting (CABG) in dialysis-dependent renal failure (RF) patients, and preoperative patient characteristics. This study included 105 patients (87 males and 18 females; mean age 60.0 +/- 9.0 years, range 39-79) with RF on maintenance dialysis (hemodialysis 100, peritoneal dialysis 5) who underwent isolated CABG between August 1985 and April 2000. Postoperative follow-up was completed in 100% and averaged 3.1 years. There were 22 emergency and 2 re-CABG cases. Previous myocardial infarction (MI) was found in 55 patients (52%), and unstable angina was noted in 53 patients (50%). Diabetes mellitus was the cause of RF in 50 patients (48%; 24 patients required insulin). There was 1 case of single vessel disease, 31 cases of double vessel disease, 54 cases of triple vessel disease, and 19 cases of left main disease. Preoperative left ventriculography was performed in 92 patients (88%). Left ventricular ejection fraction (LVEF) was 48.3 +/- 15.8% (range 11-74%) and was 40% or less in 25 patients (27%). The mean number of distal anastomoses was 2.5 (range 1-5). Three patients received only vein grafts, but all were cases of emergency CABG. The remaining 102 patients (97%) received at least 1 arterial conduit. Among them, 64 patients received only arterial conduits, and 72 patients received 2 or more distal anastomoses with arterial conduits. Five patients (4.8%) died within 30 days after CABG (2 cardiac deaths and 3 noncardiac deaths), and 8 patients (7.6%) died beyond 30 days after CABG before discharge (all noncardiac deaths). The cause of 2 cardiac deaths was abrupt circulatory collapse during or after hemodialysis in patients with severe left ventricular dysfunction (LVEF; 11% and 28%) in the early postoperative period. The causes of 8 noncardiac deaths included infection in 4 and rupture of aortic aneurysm, stroke, sleep apnea syndrome, and mesenteric infarction. During the follow-up period, there were 29 late deaths (8 cardiac, 13 noncardiac, and 8 sudden death), 6 MIs, 13 percutaneous transluminal coronary angioplasty, and 1 re-CABG. The 5-year actuarial survival rate was 59.8%, the cardiac death-free rate was 83.0%, and the cardiac event-free rate was 62.4%. Although CABG in patients on hemodialysis is associated with high early and long-term mortality in terms of both cardiac and noncardiac deaths in proportion to the severity of the preoperative condition, long-term survival was still better than that of general dialysis patients. Meticulous perioperative management may be the key factor in the improvement of early results.

Adult↗
PubMed2001

[The intubating laryngeal mask: its advantages and limitations].

It has been hypothesized that the intubating laryngeal mask (ILM) has some advantages: (1) tracheal intubation is achieved with a neutral head-neck position and limited mouth opening, (2) intubation is not interfered with blood and secretion in the mouth, (3) ventilation via the device is possible, and (4) it is easy to use. Many studies have brought evidences for these points. Actually, cervical spine movement is unavoidable to a small extent although tracheal intubation is possible with a neutral head-neck position. Degree of hemodynamic changes and incidences of postoperative airway complications are similar between the ILM and the laryngoscope. ILM-users should pay attention to these limitations when they use the ILM.

Evaluation Studies as Topic↗
PubMed2001

[Early and mid-term results of elephant trunk method using stent graft during total arch replacement].

Combined therapy of stent graft implantation and open surgery is an alternative method for aortic aneurysm. Seven patients with aortic aneurysm [annulo aortic ectasia (AAE) + Marfan syndrome (4), AAE + arch aneurysm + s/o Behçet disease (1), acute dissected aneurysm (type A) (1), thoracic aortic true aneurysm (1)] were successfully treated by means of elephant trunk method using a stent graft during total arch replacement. There was no complication related to the stent graft during the perioperative period. Postoperative computed tomographic scans were performed 1 and 6 months later. There was no endleak and no migration, and the aortic diameter around the stent graft was not changed in six patients. However, one patient showed thrombus around the stent graft, because of endleak 2 months after the operation. Such patients should therefore have careful long-term follow-up.

Adult↗
PubMed2001

[A re-operative case of bentall operation and aortic arch replacement using a stent graft for a Marfan syndrome, post sternum turnover and post mitral valve replacement].

A 36-year-old male with Marfan syndrome succesfully underwent Bentall operation and aortic arch replacement using a stent graft as an elephant trunk. He had received MVR with sternum turn over 14 years previously. Median sternotomy was performed. Under circulatory arrest with rertograde cerebral perfusion we performed Bentall operation and aortic arch replacement using a stent graft. The sternum was cured well. Retractive breathing was not detected. This surgical procedure was effective for cardiovascular disease with Marfan syndrome.

Adult↗
PubMed2001

[Cardiovascular effects of colforsin daropate hydrochloride for acute heart failure after open heart surgery].

Colforsin daropate hydrochloride (COL) is a novel drug for the treatment of acute heart failure. COL stimulates adenylate cyclase directly and produces positive inotropic and vasodilator effects accompanied by the increase in cellular cAMP. We investigated its cardiovascular effects for 9 patients who showed low cardiac index (< 3.0 l/min/m2) after open-heart surgery in ICU. After 2 or 3 hours from administration of COL, heart rate and cardiac index increased, and pulmonary artery pressure and central venous pressure decreased significantly, but blood pressure and systemic venous oxygen saturation did not show significant change. In conclusion, COL improved hemodynamics through positive inotropic and vasodilator effects without hypotension. We should investigate more proper usage of this drug to avoid such side effects as tachycardia and arrhythmia, which occurred in some cases.

Acute Disease↗
PubMed2001

[A case report of extended thoracoabdominal graft repair for dissecting aneurysm (DeBakey Type IIIb) with visceral ischemia].

A 62-year-old man diagnosed as dissecting aneurysm (DeBakey type IIIb) with visceral is chemia was transferred to our hospital. He had suffered from abdominal pain and the absence of right femoral pulse. Emergent laparotomy revealed no evidence of visceral infarction. Right axillo-femoral bypass was performed. However, visceral ischemia gradually progressed. Enhanced CT and angiography showed that celiac artery and supramesenteric artery (SMA) were collapsed. He underwent graft replacement of thoracoabdominal aorta involving visceral arteries with femoro-femoral bypass with a centrifugal pump as an ajunct. The visceral arteries were reconstructed. Postoperative CT revealed sufficient flow of branch arteries. He recovered well without complication and then discharged.

Aortic Dissection↗
PubMed2000

Voltammetric measurement in supercritical CO2 utilizing a water-in-CO2 microemulsion

A novel method for voltammetric measurement in supercritical CO2 is described. In this method a water-in-supercritical CO2 microemulsion is utilized to raise the conductivity of the fluid phase. Well-defined voltammograms for the redox reactions of ferrocene and tetramethyl-p-phenylenediamine were obtained in supercritical CO2 in the presence of the microemulsion. The electrolysis product is stabilized in the water core of the microemulsion. This implies a wide range of electrochemical synthesis involving ionic or radical species in supercritical CO2 may be possible utilizing the microemulsion. The electrochemical results obtained from the water-in-supercritical CO2 microemulsion system are different from that obtained from a supercritical CO2-ethanol mixture system.

Journal Article↗
PubMed2000

Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway.

BACKGROUND: Among the many adipocyte-derived endocrine factors, we found an adipocyte-derived plasma protein, adiponectin, that was decreased in obesity. We recently demonstrated that adiponectin inhibited tumor necrosis factor-alpha (TNF-alpha)-induced expression of endothelial adhesion molecules and that plasma adiponectin level was reduced in patients with coronary artery disease (CIRCULATION: 1999;100:2473-2476). However, the intracellular signal by which adiponectin suppressed adhesion molecule expression was not elucidated. The present study investigated the mechanism of modulation for endothelial function by adiponectin. METHODS AND RESULTS: The interaction between adiponectin and human aortic endothelial cells (HAECs) was estimated by cell ELISA using biotinylated adiponectin. HAECs were preincubated for 18 hours with 50 microg/mL of adiponectin, then exposed to TNF-alpha (10 U/mL) or vehicle for the times indicated. NF-kappaB-DNA binding activity was determined by electrophoretic mobility shift assays. TNF-alpha-inducible phosphorylation signals were detected by immunoblotting. Adiponectin specifically bound to HAECs in a saturable manner and inhibited TNF-alpha-induced mRNA expression of monocyte adhesion molecules without affecting the interaction between TNF-alpha and its receptors. Adiponectin suppressed TNF-alpha-induced IkappaB-alpha phosphorylation and subsequent NF-kappaB activation without affecting other TNF-alpha-mediated phosphorylation signals, including Jun N-terminal kinase, p38 kinase, and Akt kinase. This inhibitory effect of adiponectin is accompanied by cAMP accumulation and is blocked by either adenylate cyclase inhibitor or protein kinase A (PKA) inhibitor. CONCLUSIONS: These observations raise the possibility that adiponectin, which is naturally present in the blood stream, modulates the inflammatory response of endothelial cells through cross talk between cAMP-PKA and NF-kappaB signaling pathways.

Adenylyl Cyclase Inhibitors↗
PubMed2000

Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.

We investigated the functions of adiponectin, an adipocyte-specific secretory protein and a new member of the family of soluble defense collagens, in hematopoiesis and immune responses. Adiponectin suppressed colony formation from colony-forming units (CFU)-granulocyte-macrophage, CFU-macrophage, and CFU-granulocyte, whereas it had no effect on that of burst-forming units-erythroid or mixed erythroid-myeloid CFU. In addition, adiponectin inhibited proliferation of 4 of 9 myeloid cell lines but did not suppress proliferation of erythroid or lymphoid cell lines except for one cell line. These results suggest that adiponectin predominantly inhibits proliferation of myelomonocytic lineage cells. At least one mechanism of the growth inhibition is induction of apoptosis because treatment of acute myelomonocytic leukemia lines with adiponectin induced the appearance of subdiploid peaks and oligonucleosomal DNA fragmentation. Aside from inhibiting growth of myelomonocytic progenitors, adiponectin suppressed mature macrophage functions. Treatment of cultured macrophages with adiponectin significantly inhibited their phagocytic activity and their lipopolysaccharide-induced production of tumor necrosis factor alpha. Suppression of phagocytosis by adiponectin is mediated by one of the complement C1q receptors, C1qRp, because this function was completely abrogated by the addition of an anti-C1qRp monoclonal antibody. These observations suggest that adiponectin is an important negative regulator in hematopoiesis and immune systems and raise the possibility that it may be involved in ending inflammatory responses through its inhibitory functions. (Blood. 2000;96:1723-1732)

Adiponectin↗
PubMed2000

Aquaporin adipose, a putative glycerol channel in adipocytes.

Adipose tissue is a major site of glycerol production in response to energy balance. However, molecular basis of glycerol release from adipocytes has not yet been elucidated. We recently cloned a novel member of the aquaporin family, aquaporin adipose (AQPap), which has glycerol permeability. The current study was designed to examine the hypothesis that AQPap serves as a glycerol channel in adipocytes. Adipose tissue expressed AQPap mRNA in high abundance, but not the mRNAs for the other aquaglyceroporins, AQP3 and AQP9, indicating that AQPap is the only known aquaglyceroporin expressed in adipose tissue. Glycerol release from 3T3-L1 cells was increased during differentiation in parallel with AQPap mRNA levels and suppressed by mercury ion, which inhibits the function of AQPs, supporting AQPap functions as a glycerol channel in adipocytes. Fasting increased and refeeding suppressed adipose AQPap mRNA levels in accordance with plasma glycerol levels and oppositely to plasma insulin levels in mice. Insulin dose-dependently suppressed AQPap mRNA expression in 3T3-L1 cells. AQPap mRNA levels and adipose glycerol concentrations measured by the microdialysis technique were increased in obese mice with insulin resistance. Accordingly, negative regulation of AQPap expression by insulin was impaired in the insulin-resistant state. Exposure of epinephrine translocated AQPap protein from perinuclear cytoplasm to the plasma membrane in 3T3-L1 adipocytes. These results strongly suggest that AQPap plays an important role in glycerol release from adipocytes.

3T3 Cells↗