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Biomedical subjects

T Isshiki

Publications and source records attributed to T Isshiki.

At least 37 records · Page 2Linked to original sources

Quantitative intensity measurement of equal thickness fringes in Si and MgO crystal images with an energy-filtering transmission electron microscope using an imaging plate.

Quantitative measurement of intensity profiles of equal thickness fringes has been carried out in Si and MgO crystal images with an energy-filtering transmission electron microscope using an imaging plate. The crystals have a 90 degrees wedge-shape with [110] surfaces for Si and with [100] surfaces for MgO, and are observed under the exact axial incidence of a 200 keV electron beam along the [100] axis for Si and along the [110] axis for MgO. The intensities are measured in bright field and 022 and 040 dark field images for Si, and in bright field and 111, 002, 220, 113, 222, and 004 dark field images for MgO, with and without an energy slit having +/- 5 eV energy width for incident electrons. The intensity profiles obtained from the images are presented as standard experimental data for calculation of electron diffraction intensities. A few simulation programs for high-resolution transmission electron microscopy are checked by comparing the calculated diffraction intensities with the experimental data. The complex potential suitable for matching the data is discussed.

Journal Article↗

Comprehensive analysis of the renin-angiotensin gene polymorphisms with relation to hypertension in the Japanese.

BACKGROUND: Components of the renin-angiotensin (R-A) system have been repeatedly investigated as candidate genes for essential hypertension. In particular, suggestive or significant association has been detected in some studies for the angiotensinogen M235T, angiotensin I-converting enzyme I/D, angiotensin II type 1 receptor A1166C, and aldosterone synthase C-344T polymorphisms, although the results remain inconclusive. OBJECTIVE AND METHODS: To evaluate the importance of these candidate genes for hypertension, we undertook an extensive association study in the Japanese. This case-control study was conducted in a total of 1476 individuals using the four R-A gene polymorphisms. In the assessment of genotyping data, 843 hypertensive subjects were divided into three case subgroups according to severity of hypertension, while 633 normotensive subjects divided into two control subgroups by the age of enrollment. Each subgroup was further divided by sex. Subsequently, the presence of synergy (or gene-gene interaction) was evaluated among four R-A gene polymorphisms. RESULTS: No significant association was observed between the individual R-A gene polymorphisms and hypertension status in our case-control study. The results were almost unchanged when severity of hypertension, sex-specificity, and synergy were taken into account CONCLUSIONS: Despite a relatively large number of subjects, we did not find significant evidence for disease association in the Japanese population. Given confounding factors in the case-control strategy, the lack of association does not exclude the relevance of the R-A genes to hypertension. Further investigation needs to be performed in large-scale populations, where the use of not only hypertension status, but also 'intermediate' phenotypes would be useful.

Angiotensin II↗

[Therapeutic strategy and long-term prognosis of acute coronary syndrome].

The relation between initial therapeutic strategy and long-term prognosis was reviewed in patients with acute coronary syndrome. In the Q wave infarction, the effectiveness of reperfusion therapy has been established. The earlier ischemic myocardium is reperfused, the better is its prognosis. The long-term prognosis becomes better when TIMI 3 flow is obtained after the reperfusion therapy. Direct PTCA, which can obtain TIMI 3 flow in more than 90% of the patients, has showed lower mortality, lower rate of reocclusion and lower rate of cerebrovascular accident than thrombolytic therapy. As for the long-term efficacy of stent implantation, several more years are needed although early outcomes of primary stenting are impressive. The lesions in patients with non-Q wave myocardial infarction or unstable angina frequently show severe stenosis with platelet-rich thrombi. This type of lesion is thought to be unstable and the chance of cardiac events are high when percutaneous intervention or bypass surgery is performed during this period. Thus, the conservative strategy with waiting for 1 to 2 weeks to stabilize the plaque has been recommended. However, in the long span, the prognosis of unstable angina seems not bad after the complicated early course. The long-term prognosis of unstable angina could be affected by the early outcome.

Angina, Unstable↗

[Different inhibiting effects of abciximab and tirofiban on platelet thrombus formation on a collagen surface under flow conditions].

OBJECTIVES: Recently developed anti-GPIIb/IIIa agents effectively inhibit acute thrombotic occlusion of coronary arteries after interventional treatment, and have similar inhibiting effects on plasma ligand binding to GPIIb/IIIa. Clinical investigation has revealed that abciximab, the chimeric monoclonal antibody against GPIIb/IIIa, has superior in vivo antithrombotic effects to other agents. The inhibiting effects of abciximab and another anti-GPIIb/IIIa agent, tirofiban, were investigated on platelet thrombus formation on a collagen surface under flow conditions. METHODS: Blood was drawn from 6 normal volunteers and anticoagulated with a specific inhibitor of thrombin, argatroban, at a final concentration of 100 microM. Platelets were rendered fluorescent by addition of mepacrine to a final concentration of 10 microM. Mepacrine is concentrated in the dense granules of platelets and leukocytes, but does not accumulate in red blood cells, so platelet thrombi can be detected by fluorescence microscopy even in the presence of red blood cells. Horizontal glass slips covered with fibrillar type I collagen were assembled in a Hele-Shaw type flow chamber. RESULTS: Platelet thrombi were developed on the collagen surface even in the absence of platelet activating agents. Both abciximab and tirofiban inhibited the platelet thrombus formation. Single platelet adhesion on the collagen surface was inhibited only by abciximab and not by tirofiban. CONCLUSIONS: The superior in vivo antithrombotic effects of abciximab may be partially explained by its inhibiting effects on the platelet adhesion on exposed subendothelial matrix.

Abciximab↗

Efficacy of a new hemostatic device, Adapty , after transradial coronary angiography and intervention.

A novel hemostatic device, Adapty (Medikit, Tokyo, Japan), was developed to achieve effective and comfortable hemostasis following transradial procedures. The device consists of a pad fixed to a transparent plastic plate and a self-adhesive strap. The catheter sheath is removed from the radial artery after the pad has been positioned precisely over the puncture site, with the strap attached to the plate. Compression pressure then is adjusted with the self-adhesive strap, as is required with occlusive clamps. Patients do not need to maintain hyperextension of the wrist after the procedure. The wrist can be mobilized immediately after application. The efficacy of Adapty was evaluated in prospective observations of 200 patients. The device was successfully applied in all patients immediately after sheath removal. No patient required interruption of compression because of pain, congestion or ischemia. Complete hemostasis was obtained in 199 patients (99.5%), and the device caused no vascular complications. This study demonstrates that Adapty is highly effective for achieving hemostasis after transradial procedures.

Aged↗

Impact of cilostazol on clinical and angiographic outcome after primary stenting for acute myocardial infarction.

Cilostazol, an antiplatelet drug that also may inhibit smooth muscle proliferation, was given together with aspirin after primary stenting to treat patients with acute myocardial infarction. In a randomized controlled trials of 50 patients, clinical and angiographic outcome at 6 months was significantly improved with cilostazol, depicting a significantly smaller late loss and/or loss index.

Adult↗

Efficacy of transradial primary stenting in patients with acute myocardial infarction.

We conducted a prospective observational study to assess the effectiveness of "transradial primary stenting" in 33 patients with acute myocardial infarction, along with acute risk stratification and accelerated patient care. With use of adequate inclusion and exclusion criteria, the radial artery can be used as an access site for catheterization, and transradial primary stenting can be performed rapidly and successfully by trained coronary interventionalists.

Aged↗

AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation induced by high shear stress in platelet-rich plasma from patients with acute coronary syndromes.

The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesis that occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm2) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 microgram/mL AJvW-2. Under low-shear conditions (12 dyne/cm2), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries.

Acute Disease↗

[Aggressive diagnostic and therapeutic approach for acute coronary syndrome].

The purpose of this article is to propose an "aggressive strategy" in the treatment of patients with acute coronary syndrome (ACS), especially unstable angina. The indication and timing of emergent coronary angiography in patients with ACS remains to be validated. The results of TIMI III B trial, a randomized, controlled trial about this issue, show that an early invasive strategy reduced the average length of initial hospitalization and the incidence of rehospitalization within 6 weeks. However, the same kind of clinical trial named VANQWISH reported that no benefit was obtained from such an aggressive strategy. It is of paramount importance to note that these 2 studies were performed in the era of plain old balloon angioplasty. Now we can use many kinds of coronary stent which impart both excellent radial strength and flexibility. Recent studies have demonstrated that culprit lesions of ACS can be treated at the same success rate as those of stable effort angina. In our hospital, use of coronary stents in patients with ACS dramatically reduced the recurrence of ACS and the incidence of angiographic restenosis with the same initial procedure success rate. Since the mid-nineties, the radial artery has been used as a vascular access site of coronary intervention. The major advantage of this technique is lesser access site-related complications and increased patient comfort, which reduced hospital stay and cost. Recently it was demonstrated that ad-hoc transradial intervention can be applied in patients with unstable angina or even those with acute myocardial infarction by trained angioplasters. Thus, we would like to conclude that the best strategy in the management of ACS is to perform emergent coronary angiography from the radial artery as soon as possible after admission, and to do ad-hoc intervention using coronary stents suitable for the lesion anatomy.

Aged↗

Dorsoventral patterning in the Drosophila central nervous system: the vnd homeobox gene specifies ventral column identity.

The Drosophila CNS develops from three columns of neuroectodermal cells along the dorsoventral (DV) axis: ventral, intermediate, and dorsal. In this and the accompanying paper, we investigate the role of two homeobox genes, vnd and ind, in establishing ventral and intermediate cell fates within the Drosophila CNS. During early neurogenesis, Vnd protein is restricted to ventral column neuroectoderm and neuroblasts; later it is detected in a complex pattern of neurons. We use molecular markers that distinguish ventral, intermediate, and dorsal column neuroectoderm and neuroblasts, and a cell lineage marker for selected neuroblasts, to show that loss of vnd transforms ventral into intermediate column identity and that specific ventral neuroblasts fail to form. Conversely, ectopic vnd produces an intermediate to ventral column transformation. Thus, vnd is necessary and sufficient to induce ventral fates and repress intermediate fates within the Drosophila CNS. Vertebrate homologs of vnd (Nkx2.1 and 2.2) are similarly expressed in the ventral CNS, raising the possibility that DV patterning within the CNS is evolutionarily conserved.

Animals↗

Endothelium-dependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia.

BACKGROUND: Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. In vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered after VEGF treatment. METHODS AND RESULTS: Ischemia was induced in the hindlimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 microg of a plasmid encoding VEGF or ss-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radiation microangiography, with a spatial resolution of 30 microm, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound dilation of collaterals was observed after acetylcholine in VEGF-treated animals. This response was evident in vessels with a linear appearance but not in those with an undulating appearance. The resulting blood flow in the ischemic limb after administration of acetylcholine in the control animals was only 64.6+/-17.0% of that of the contralateral normal limb, whereas blood flow was augmented to 106.1+/-8.4% in VEGF-treated animals (P<0.05). CONCLUSIONS: These results demonstrate in vivo that the use of VEGF restores impaired vasomotor responses in some types of collateral microvessels, which may help to provide a basis for understanding the microcirculation after therapeutic angiogenesis with VEGF.

Acetylcholine↗

Significance of development of late potentials after anterior wall acute myocardial infarction despite successful primary angioplasty of the left anterior descending coronary artery.

We classified 33 patients with a first anterior infarction and single-vessel disease who had undergone successful primary angioplasty and had a patent infarct-related artery into groups based on the development of late potentials. Left ventricular function improved between 1 and 3 months after angioplasty only in patients without late potentials; the development of late potentials after acute anterior infarction was associated with prolonged left ventricular dysfunction despite successful revascularization with primary angioplasty.

Aged↗

Novel guide catheter for left coronary intervention via a right upper limb approach.

We designed a novel guide catheter specifically for interventions to the left coronary artery via a right upper limb approach. The catheter has a novel first loop design which utilizes the angle between the right subclavian and innominate arteries for support. The first loop introduces the catheter into the correct position and generates powerful and coaxial back-up power. We report successful implantation of Palmaz-Schatz stents in five cases using this 6 Fr. catheter.

Aged↗

Platelet aggregation in acute coronary syndromes: use of a new aggregometer with laser light scattering to assess platelet aggregability.

OBJECTIVE: Platelet aggregation has been implicated in the pathogenesis of acute coronary syndromes. Small aggregates consisting of < or = 100 platelets cannot be quantified with a conventional aggregometer employing optical density. Using a recently developed aggregometer based on laser light scattering, we studied platelet aggregability in patients with acute coronary syndromes. METHODS: Peripheral blood samples were obtained from 39 patients with acute myocardial infarction or unstable angina who had received no prior antiplatelet or anticoagulant therapy, to be assayed immediately using a PA-100 platelet aggregometer. Blood samples from 14 healthy volunteers were used as controls. RESULTS: Spontaneous formation of platelet aggregates was observed only in patients with acute coronary syndromes. The size of these aggregates was small, consisting of < or = 100 platelets (primary aggregation). Agonist-induced aggregation consisted of two phases. In the first few minutes, the number of small aggregates increased markedly (primary aggregation), followed by an increase in larger aggregates (secondary aggregation). The EC50 of epinephrine for primary aggregation was nearly 50 times lower in acute coronary patients than in controls (P < 0.001), while the EC50 for secondary aggregation was only 2 times lower (P < 0.001). CONCLUSIONS: Aggregometry using light scattering suggests that platelet hyperaggregability and hypersensitivity in acute coronary syndromes may occur in primary but not secondary aggregation.

Acute Disease↗

Regional specification of muscle progenitors in Drosophila: the role of the msh homeobox gene.

The somatic musculature in the abdominal hemisegments of Drosophila consists of 30 uniquely identifiable muscle fibers. Previous studies have suggested that the muscle diversity originates in a special class of myoblasts, called muscle founders, that are formed by the division of muscle progenitors. However, the mechanisms that locate and specify the muscle progenitors/founders are largely unknown. In this study, we first used a novel marker, rP298-LacZ, to chart the development of muscle progenitors/founders during the formation of distinct groups of mature muscles. We then determined the function of the muscle segment homeobox (msh) gene in myogenesis. msh encodes a homeobox-containing protein, vertebrate homologues of which are known as Msxs. We show that msh is expressed in the dorsal and lateral domains of muscle progenitors and is required for the specification of the progenitor cells. Ectopic expression of msh in the entire mesoderm inhibits the proper development of the normally msh-negative muscle progenitors in the dorsolateral domain. These results suggest that msh plays a role in regional specification of muscle progenitors/founders.

Animals↗

Relation of duration of ST reelevation at reperfusion and improvement of left ventricular function after successful primary angioplasty of the left anterior descending coronary artery in anterior wall acute myocardial infarction.

We conducted a prospective study to investigate the relation between ST reelevation during primary angioplasty and improvement in left ventricular function. The duration, not the occurrence, of ST reelevation at reperfusion was associated with improvement in left ventricular function in patients with anterior wall acute myocardial infarction successfully recanalized by primary angioplasty.

Aged↗

Use of cilostazol, a novel antiplatelet agent, in a post-Palmaz-Schatz stenting regimen.

We evaluated the therapeutic efficacy of cilostazol, a novel potent inhibitor of phosphodiesterase, for the prevention of stent thrombosis following implantation of a Palmaz-Schatz stent guided by angiographic visual estimation alone in 71 patients with 84 lesions. Patients received 81 mg of aspirin 3 times daily and 100 mg of cilostozol twice daily after angiographic confirmation of optimal Palmaz-Schatz stent implantation. Of the 84 vessels stented, 65 (77%) were classified as type B2 or C lesions according to the modified American Heart Association/American College of Cardiology classification, and 51 (61%) were <3.0 mm in diameter. Multiple stents were used in 26 patients (31%). The final balloon inflation pressure was 18.3 +/- 1.5 atm. The balloon-to-vessel ratio was 1.18 +/- 0.16. No patient received heparin or warfarin after the procedure. There were no deaths, Q-wave myocardial infarctions, in- or out-of-hospital stent thrombosis, coronary bypass surgery, or serious side effects such as neutropenia and/or liver dysfunction during the 1-month follow-up period. These results indicate that cilostazol was a safe and effective antiplatelet agent with minimum side effects after Palmaz-Schatz stent implantation.

Adult↗