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Biomedical subjects

I Sakuma

Publications and source records attributed to I Sakuma.

At least 19 recordsLinked to original sources
PubMed2002

Long-acting calcium channel blocker benidipine suppresses expression of angiogenic growth factors and prevents cardiac remodelling in a Type II diabetic rat model.

AIMS/HYPOTHESIS: Calcium channel blockers, widely used for the treatment of hypertension and angina, could prevent cardiovascular complications in patients with diabetes. They can improve cardiac remodelling in animal models of a variety of cardiovascular diseases. Here, we examined the therapeutic effect of benidipine, a long-acting calcium channel blocker, on cardiac remodelling in Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a Type II (non-insulin-dependent) diabetes mellitus model. METHODS: The methods for morphometric analysis included double staining for coronary capillaries, dye-binding staining for collagen content and Masson's trichrome staining for perivascular fibrosis. Immunohistochemical and in situ hybridization techniques were used for detecting protein and mRNA expressions for vascular endothelial growth factors (VEGF), basic fibroblast growth factors (bFGF) and TGF-beta(1), endothelial nitric oxide synthase (eNOS), and anti- and pro-apoptotic markers. RESULTS: OLETF rats showed an increased coronary capillary density, a reduced venular capillary proportion, an increased cardiac collagen content and prominent cardiac perivascular fibrosis. In OLETF rat hearts, significant increases in vascular expressions for VEGF, bFGF and TGF- beta(1) were found. Furthermore, the apoptosis signalling pathways, involving eNOS and apoptotic markers, were markedly altered, and coronary endothelial cell apoptosis was lower. These alterations with the exception of eNOS expression were significantly blocked by benidipine treatment. CONCLUSION/INTERPRETATION: The suppressive effect of benidipine on overproduction of angiogenic growth factors could prevent cardiac angiogenesis and fibrosis, resulting in an improvement of cardiac remodelling in diabetes. As VEGF and bFGF potently block endothelial cell apoptosis execution, physiological apoptosis revived by benidipine treatment could also contribute to coronary vessel regression.

Animals↗
PubMed2001

Angiotensin-converting enzyme inhibition attenuates hypofibrinolysis and reduces cardiac perivascular fibrosis in genetically obese diabetic mice.

BACKGROUND: Obesity and insulin resistance are associated with accelerated macrovascular and microvascular coronary disease, cardiomyopathic phenomena, and increased concentrations and activity in blood of plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of fibrinolysis. METHODS AND RESULTS: To determine whether hypofibrinolysis in blood and tissues and its potential sequelae could be attenuated pharmacologically, we studied genetically modified obese mice. By 10 weeks of age, obese mice exhibited increases in left ventricular weight and glucose and immunoreactive insulin in blood. PAI-1 activity in blood measured spectrophotometrically was significantly elevated as well. The difference compared with values in lean controls widened by 20 weeks of age. Perivascular fibrosis in coronary arterioles and small coronary arteries was evident in obese mice 10 and 20 weeks of age, paralleling increases in PAI-1 and tissue factor expression evident by immunohistochemical image analysis, in situ hybridization, and reverse transcription-polymerase chain reaction. Inhibition of ACE activity initiated in obese mice 10 weeks of age and continued for 20 weeks arrested the increase in PAI-1 activity in blood and in cardiac PAI-1 and tissue factor mRNA as well as coronary perivascular fibrosis. CONCLUSIONS: Thus, inhibition of proteo(fibrino)lysis and augmented tissue factor expression in the heart precede and may contribute to the coronary perivascular fibrosis seen with obesity and insulin resistance. Furthermore, inhibition of ACE activity can attenuate all 3 phenomena.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

System for robotically assisted percutaneous procedures with computed tomography guidance.

We present the prototype of an image-guided robotic system for accurate and consistent placement of percutaneous needles in soft-tissue targets under CT guidance inside the gantry of a CT scanner. The couch-mounted system consists of a seven-degrees-of-freedom passive mounting arm, a remote center-of-motion robot, and a motorized needle-insertion device. Single-image-based coregistration of the robot and image space is achieved by stereotactic localization using a miniature version of the BRW head frame built into the radiolucent needle driver. The surgeon plans and controls the intervention in the scanner room on a desktop computer that receives DICOM images from the scanner. The system does not need calibration, employs pure image-based registration, and does not utilize any vendor-specific hardware or software features. In the open air, where there is no needle-tissue interaction, we systematically achieved an accuracy better than 1 mm in hitting targets at 5-8 cm from the fulcrum point. In the phantom, the orientation accuracy was 0.6 degrees, and the distance between the needle tip and the target was 1.04 mm. Experiments indicated that this robotic system is suitable for a variety of percutaneous clinical applications.

Biopsy, Needle↗
PubMed2001

Alterations in EDHF-mediated hyperpolarization and relaxation in mesenteric arteries of female rats in long-term deficiency of oestrogen and during oestrus cycle.

This study was undertaken to determine whether endothelium-dependent relaxations are altered in mesenteric arteries from young female rats during oestrus cycle and after castration. The contractile response to phenylephrine (Phe) was significantly enhanced in arteries from rats subjected to ovariectomy than in those from sham-operated (control) rats. Treatment of ovariectomized rats with 17beta-oestradiol returned the Phe response to the control level. Arteries from rats at the diestrus stage also exhibited greater contraction in response to Phe. In the presence of 100 microM N(G)-nitro-L-arginine (L-NOARG), the enhancement of the Phe contractile response associated with oestrogen deficiency was not observed. Endothelium-dependent relaxations elicited by acetylcholine (ACh) in arteries precontracted with Phe were significantly reduced in ovariectomized and diestrus rats regardless of whether endothelium-derived nitric oxide (NO) was blocked with L-NOARG. Treatment with 17beta-oestradiol prevented the reduced vascular relaxant response to ACh in ovariectomized rats. The reduction in the ACh responses observed in ovariectomized and diestrus rats was eliminated when 500 nM apamin and 100 nM charybdotoxin were present. ACh-induced endothelium-dependent hyperpolarizations were depressed in arteries from ovariectomized and diestrus rats. The hyperpolarizing response to ACh was significantly improved when ovariectomized rats were treated with 17beta-oestradiol. The resting membrane potentials and pinacidil-induced hyperpolarizations were unaffected by ovariectomy or the diestrus stage. These results suggest that oestrogen-deficient states of both short and long duration reduce the basal release of NO from the endothelium and specifically attenuate endothelium-dependent hyperpolarization and relaxation transduced by endothelium-derived hyperpolarizing factor.

Acetylcholine↗
PubMed2001

Assessment of newly developed perfluorocarbon emulsion: oxygen carrying capacity as the blood substitute in vivo.

This study provides the evaluation of oxygen carrying capacity of the novel perfluorocarbon emulsion (Neo-PFC) produced by the new emulsifying technology named High Pressure Process. For the performance comparison of oxygen carrying abilities of Neo-PFC and a representative PFC emulsion, the oxidation states of cerebral tissues in substituted animals were measured by near-infrared spectrometry. After the 70% exchange transfusion of whole blood of rats by Neo-PFC and Fluosol-DA, fractional inspired oxygen (FiO2) was gradually decreased from 100% to 0%. As the control experiments, the blood was substituted by Krebs Ringer bicarbonate buffer containing 3% BSA. When the blood of rats was substituted by Neo-PFC, Cyt. ox., a terminal enzyme in mitochondrial respiratory chain maintained fully oxidized state with FiO2 values between 100 to 40%. By contrast, in the models substituted by Fluosol-DA and BSA-buffer. Cyt. ox. was gradually reduced with FiO2 values below 60% and 80%, respectively. This specific advantage of Neo-PFC was explained by its higher oxygen solubility in arterial blood. The novel PFC emulsion prepared by the new emulsifying technology is a potential basis for blood substitutes.

Animals↗
PubMed2001

Role of endothelial Ni(2+)-sensitive Ca(2+) entry pathway in regulation of EDHF in porcine coronary artery.

Elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) in endothelial cells is proposed to be required for generation of vascular actions of endothelium-derived hyperpolarizing factor (EDHF). This study was designed to determine the endothelial Ca(2+) source that is important in development of EDHF-mediated vascular actions. In porcine coronary artery precontracted with U-46619, bradykinin (BK) and cyclopiazonic acid (CPA) caused endothelium-dependent relaxations in the presence of N(G)-nitro-L-arginine (L-NNA). The L-NNA-resistant relaxant responses were inhibited by high K(+), indicating an involvement of EDHF. In the presence of Ni(2+), which inhibits Ca(2+) influx through nonselective cation channels, the BK-induced EDHF relaxant response was greatly diminished and the CPA-induced response was abolished. BK and CPA elicited membrane hyperpolarization of smooth muscle cells of porcine coronary artery. Ni(2+) suppressed the hyperpolarizing responses in a manner analogous to removal of extracellular Ca(2+). EDHF-mediated relaxations and hyperpolarizations evoked by BK and CPA in porcine coronary artery showed a temporal correlation with the increases in [Ca(2+)](i) in porcine aortic endothelial cells. The extracellular Ca(2+)-dependent rises in [Ca(2+)](i) in endothelial cells stimulated with BK and CPA were completely blocked by Ni(2+). These results suggest that Ca(2+) influx into endothelial cells through nonselective cation channels plays a crucial role in the regulation of EDHF.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Preparation and characterization of SNO-PEG-hemoglobin as a candidate for oxygen transporting material.

Acellular hemoglobin (Hb) derivates developed as oxygen carriers are known to cause hypertensive reactions due to their nitric oxide (NO) scavenging action. To modulate this undesired activity, we have developed a new Hb derivative, s-nitrosylated polyethylene glycol (PEG)-modified hemoglobin (SNO-PEG-Hb), which can deliver oxygen and NO. After human Hb was modified with PEG to increase its molecular weight, the free sulfhydryl groups of Hb were s-nitrosylated with s-nitrosoglutathione. Administration of unmodified Hb into anesthetized rats caused a hypertensive reaction, while s-nitrosylated Hb derivatives such as SNO-Hb and SNO-PEG-Hb did not raise blood pressure. The plasma half-lives of heme and NO bound to SNO-PEG-Hb were 11.5 and 2.4 hours respectively, indicating that the s-nitrosylated Hb derivative may act as a slow-releasing agent for NO. Based on these findings, SNO-PEG-Hb is a useful candidate for a blood substitute and tool for oxygen therapeutics.

Analysis of Variance↗
PubMed2000

Attenuation of hypothermia-induced platelet activation and platelet adhesion to artificial surfaces in vitro by modification of hemoglobin to carry S-nitric oxide and polyethylene glycol.

Hypothermic cardiopulmonary bypass alters platelet function and hypothermia is associated with postoperative myocardial ischemia. Thrombogenic surfaces such as extracorporeal circuits, vascular graft materials, and components of atherosclerotic plaque induce activation of platelets. The effects of human hemoglobin (Hb) covalently modified to carry S-nitric oxide (NO) functional groups (SNO-Hb), polyethylene glycol (PEG-Hb), and SNO-PEG-Hb on platelet activation were studied. Platelet activation was assessed by cytometric analysis of GPIIb-IIIa activation and P-selectin expression at hypothermic condition (22 degrees C) after stimulation with Hb derivatives. Platelet adhesion and aggregation were measured in a parallel glass plate chamber coated with unmodified Hb, SNO-Hb, PEG-Hb, SNO-PEG-Hb, and collagen. Platelet binding of antibodies to GPIIb-IIIa and P-selectin was significantly enhanced by hypothermic condition and by unmodified Hb. There was significantly less platelet binding of antibodies to GPIIb-IIIa and P-selectin with SNO-Hb, PEG-Hb, and SNO-PEG-Hb compared with unmodified Hb. There was significantly less platelet attachment, adhesion, and aggregation on the SNO-Hb, PEG-Hb and SNO-PEG-Hb coated surfaces compared with unmodified Hb-coated and -uncoated surfaces. SNO-Hb, PEG-Hb, and SNO-PEG-Hb induced less platelet activation at hypothermic temperature, and induced less platelet adhesion and aggregation on thrombogenic surfaces compared with unmodified Hb. The inhibitory effect may be derived from antiadhesive properties of Hb, antiplatelet actions of NO, and molecular barrier action of PEG.

Adult↗
PubMed2000

Regional differences in arrhythmogenic aftereffects of high intensity DC stimulation in the ventricles.

Regional differences of the aftereffects of high intensity DC stimulation were investigated in isolated rabbit hearts stained with a voltage-sensitive dye (di-4-ANEPPS). Optical action potential signals were recorded from the epicardial surface of the right and left ventricular free wall (RVep, LVep) and from the right endocardial surface of the interventricular septum (IVS). Ten-millisecond monophasic DC stimulation (S2, 20-120 V) was applied to the signal recording spots during the early plateau phase of the action potential induced by basic stimuli (S1, 2.5 Hz). There was a linear relationship between S2 voltage and the S2 field intensity (FI). S2 caused postshock additional depolarization, giving rise to a prolongation of the shocked action potential. With S2 > or = 40 V (FI > or = approximately 20 V/cm), terminal repolarization of action potential was inhibited, and subsequent postshock S1 action potentials for 1-5 minutes were characterized by a decrease in the maximum diastolic potential and a decrease in the amplitude and a slowing of their upstroke phase. The higher the S2 voltage, the larger the aftereffects. The changes in postshock action potential configuration in RVep were significantly greater than those observed in LVep and IVS when compared at the same levels of S2 intensity. In RVep, 12 of 20 shocks of 120 V resulted in a prolonged refractoriness to S1 (> 1 s), and the arrest was often followed by oscillation of membrane potential. Ventricular tachycardia or fibrillation ensued from the oscillation in five cases. No such long arrest or serious arrhythmias were elicited in LVep and IVS. These results suggest that RVep is more susceptible than LVep and IVS for arrhythmogenic aftereffects of high intensity DC stimulation.

Animals↗
PubMed2000

Heat shock protein 72 expression in the right ventricle of patients undergoing congenital cardiac surgery.

While heat shock protein (HSP) 72 is known as a stress protein, there have been no reports of HSP 72 expression in patients who have undergone surgery for congenital heart disease. Fourteen patients (7 males and 7 females) who had undergone surgery for congenital heart disease were studied. The ages of the patients ranged from 2 months to 43 years old (mean 6.5 +/- 10.8 years old; median 3.0 years old). The diagnoses were Tetralogy of Fallot in seven, pulmonary atresia with ventricular septal defect (VSD) in three, complex anomalies in three, and VSD in one patient. Histological study and HSP analysis using Western blots and immunostaining with anti-HSP 72 monoclonal antibody were performed for right ventricular muscle samples resected during the surgery. The histological findings showed hypertrophic changes of ventricular cardiomyocytes in all samples studied. Western blots detected HSP 72 expression of various degrees in all specimens. Immunostaining using monoclonal antibody against HSP 72 showed that the protein was present in the nuclei and cytoplasm of cardiomyocytes. In conclusion, although it is difficult to determine the cause of the "stress" that triggers HSP 72 expression in cardiomyocytes, low O2 saturation and pressure overload might act as a "stress", and the only common factor that induced HSP 72 in every sample was hypertrophy.

Adult↗
PubMed1999

A new safe laparoscopic manipulator system with a five-bar linkage mechanism and an optical zoom.

This paper describes a new type of laparoscopic manipulator system designed with regard to its safety and sterilization in medical settings. It consists of a laparoscope manipulator using a five-bar linkage mechanism, an optical zoom called the automatic microzoom laparoscope, and a man-machine interface called the Head-Mouse system. The movement of the laparoscope manipulator in the X-Y plane determines the angle of the laparoscope, and the optical zoom substitutes for back-and-forth movements. This system achieves intrinsic safety and ease of sterilization due to limitations in the range of movement. The system achieves high reliability because of the simplicity of both its mechanism and its software. The newly developed optical zoom avoids the possibility of contact with organs by eliminating the back-and-forth movements of the laparoscope required for close-up observation while preserving a high-quality laparoscopic image. The Head-Mouse system for man-machine interface was designed to avoid incorrect inputs by the surgeon. To evaluate the performance of this newly developed system, an experiment was conducted in which a surgeon used the system to perform an in vivo laparoscopic cholecystectomy on a pig.

Animals↗
PubMed1999

Arrhythmogenic changes in action potential configuration in the ventricle induced by DC shocks.

Failure of defibrillation by direct current (DC) shocks is the result in part of new ventricular tachyarrhythmias induced by the shocks. We investigated the arrhythmogenic substrate produced by the shocks. Fluorescent action potential (AP) signals were recorded from rabbit hearts perfused in vitro with the use of our original optical recording system. Localized application of 10-ms shocks (S2) during the plateau phase of APs by basic stimuli (S1) caused field intensity (FI)-dependent changes in APs: (a) S2 > 7 V/cm caused additional depolarization, giving rise to a prolongation of AP duration (APD); (b) With S2 > 20 V/cm, terminal repolarization was inhibited, and subsequent postshock S1 APs for 1 to 5 min were characterized by decreases in the maximum diastolic potential and amplitude of APs; and (c) S2 > 30 V/cm often resulted in a prolonged refractoriness, oscillation of membrane potential leading to ventricular tachycardia or fibrillation (VT/VF). The right ventricle was more susceptible than other regions for the aftereffects of high-intensity shocks. Using an 8-channel recording system, we compared the effect of 10-ms monophasic (M) and 5/5-ms biphasic (B) shocks applied to the whole ventricles with FI of 1 to 20 V/cm at the signal recording sites. B shocks were less potent than M shocks in the FI-dependent action potential duration (APD) prolongation, and in the shock-induced enhancement of APD dispersion. Incidence and duration of VT/VF induced by M shocks were significantly greater than those by B shocks. These findings suggest that DC shocks will cause two types of arrhythmogenic substrate: one induced at sites of high FI, and the other at sites with moderate FI. The former would produce local block or focal repetitive excitation due to prolonged depolarization and oscillation of membrane potential, and the latter circuitous movement of wavefronts through an enhancement of spatial inhomogeneity of repolarization.

Animals↗
PubMed1999

CD95 ligand is expressed in Reed-Sternberg cells of Hodgkin's disease.

Reed-Sternberg (RS) cells and their mononuclear variants, Hodgkin's (H) cells, are considered to be the neoplastic cells of Hodgkin's disease (HD). The cellular origin of H-RS cells remains the subject of considerable controversy, although most recent papers have claimed that H-RS cells are of B cell origin. Recently, however, it has been reported that some H-RS cells express granzyme B, as observed in cytotoxic T cells and/or natural killer cells, which also express CD95 ligand (FasL/APO-1L). In the present study, the expression of CD95L and granzyme B in H-RS cells of HD was investigated. CD95L was detected in H-RS cells in five of nine HD cases (one case of lymphocyte-rich classical HD, two of these cases of nodular sclerosis type, and two of four cases of mixed cellularity type). All three examined HD cell lines expressed CD95L in the cytoplasm, although cell surface expression was seen only in L428 cells. Three HD cases expressed both CD95L and granzyme B. It was concluded that CD95L is frequently expressed in H-RS cells, which is one of their notable characteristics; albeit it seems to be irrespective of cell lineage.

Adolescent↗
PubMed1999

Experimental study on hemolysis in centrifugal blood pumps: improvement of flow visualization method.

To evaluate rotary blood pumps, flow visualization is commonly applied to determine the flow patterns in a centrifugal blood pump, which have a relationship to its hemolytic performance. However, it is very troublesome to visualize the flow near the vanes due to the high rotational speed of the impeller. The rotational speed of the impeller in a centrifugal blood pump is usually several hundred revolutions per minute. In this study, we combined a high-speed video camera based imaging method and an optical system in which the image of the rotating impeller was kept stationary. In the optical system, a prism rotating at half the speed of the impeller reflected the image of the impeller. The resultant reflected image was observed by a high-speed video camera through a half mirror. With this optical setup, the image through the half mirror became stationary, and the path of a specific tracer particle could be traced for a longer duration. A longer duration of measurements and better quality of the obtained images were realized through this improvement. Movement of a specific tracer from the inlet portion to the outlet portion of the impeller could be examined using the developed method.

Acrylic Resins↗
PubMed1999

Differential effect of interferon on hepatitis C virus 1b quasispecies in the nonstructural protein 5A gene.

A close correlation was reported between amino acid mutations in the nonstructural protein 5A (interferon [IFN] sensitivity-determining region [ISDR]) of hepatitis C virus (HCV)-1b and the response to IFN therapy. The dynamic change of ISDR quasispecies during IFN treatment was investigated in 22 patients. In 18 nonresponders, the number of ISDR mutations in major quasispecies decreased after therapy (P=.039). In each nonresponder, the percentage of wild-type (no mutations in the ISDR) quasispecies increased after treatment (P=.008), whereas the percentages of intermediate- (1-3 mutations) and mutant-type (>/=4 mutations) quasispecies decreased (P=.037 and P=.043, respectively). No mutant-type quasispecies were detected after therapy. Four complete responders had only quasispecies with >/=3 mutations before therapy. Thus, HCVs have fewer mutations in the ISDR after IFN therapy than those before therapy. These IFN-resistant HCVs were already present before therapy as minor quasispecies and were selected by IFN in nonresponders.

Adult↗
PubMed1999

Effect of prolonged treatment with amlodipine on enhanced vascular contractility in cardiomyopathic hamsters.

This study examined the effects of prolonged treatment with amlodipine on the enhanced vascular contractions in dilated cardiomyopathic (CM) hamsters. From the ages of 5 to 20 weeks, CM hamsters (BIO 53.58) orally received amlodipine. Then we compared the contractile responses to vasoconstrictors in aortas and mesenteric arteries from CM hamsters with or without treatment with those in the arteries from controls (F1b). We also investigated the effect of amlodipine treatment on the Ca2+ sensitivity of tension in beta-escin-skinned smooth muscle of mesenteric artery. The contractile responses to phenylephrine, angiotensin II, and high K+ in both aorta and mesenteric artery were greatly enhanced in CM hamsters compared with controls. Amlodipine treatment slightly but significantly inhibited the enhanced responses in aorta but did not alter the responses in mesenteric arteries. The Ca2+ sensitivity of tension was significantly increased in CM hamster preparations, which was unaffected by amlodipine treatment. These data indicate that amlodipine treatment differentially affects the enhanced responses to vasoconstrictors between large and small blood vessels from CM hamsters. The lack of effect of amlodipine treatment on the responsiveness of CM mesenteric artery leads to the suggestion that the preventive effect of amlodipine on focal myocytolytic necrosis of cardiomyocytes, which was previously reported to be the main cause of cardiomyopathy, results from an action on cardiomyocytes.

Actin Cytoskeleton↗
PubMed1999

Efficacy of endoscopic clipping for bleeding gastroduodenal ulcer: comparison with topical ethanol injection.

OBJECTIVE: Although endoscopic clipping is used widely for the treatment of bleeding gastroduodenal ulcers, clinical trials on its efficacy are scarce. The aim of this study is to assess the efficacy and safety of endoscopic clipping for hemostasis from bleeding gastroduodenal ulcers. METHODS: The present study was designed as a retrospective study using historical controls. One hundred consecutive patients with bleeding gastroduodenal ulcers were treated by endoscopic clipping. The preceding 91 consecutive patients treated by endoscopic pure ethanol injection were regarded as controls. Forty-nine of the clipping group and 41 of the ethanol group had lesions at sites difficult to perform endoscopic manipulation. Hemostatic rates, rebleeding rates, amounts of blood transfusion, and durations of hospital stay were analyzed. RESULTS: The hemostatic rate was 96% in both clipping and ethanol groups, whereas the rebleeding rate was lower (15% vs 29%, p = 0.023) in the former than the latter. In technically difficult cases, the hemostatic rate was comparable (96 vs 90%). CONCLUSION: In patients with bleeding gastroduodenal ulcers, endoscopic clipping may be a choice of therapy because of a low rebleeding rate compared with pure ethanol injection.

Ethanol↗