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T Fukai

Publications and source records attributed to T Fukai.

At least 55 records · Page 3Linked to original sources
PubMed1995

Switching dynamics and the transient memory storage in a model enzyme network involving Ca2+/calmodulin-dependent protein kinase II in synapses.

The signal processing through a chain of phosphorylation-dephosphorylations mediated by a pair of enzymes, Ca2+/calmodulin-dependent protein kinase II and the associated phosphatase, is formulated as a nonautonomous dynamical system in the framework of nonautocatalytic, intraholoenzyme reaction dynamics. A classification of switching characteristics of the system is made in the parameter space comprising the three controllable system parameters: an input-pulse intensity and initial concentrations of the two associated enzymes. It is found that a region of parameter space exists termed the transition zone, that exhibits a quasi-switching behaviour characterized by a signal storage time being prolonged by more than several orders of magnitude (10(4) times in certain cases) for the increase of two orders of magnitude in the input signal intensity. The effect of alterations of certain rate constants on the quasi-switching property is explored. It is numerically demonstrated that the Ca2+/calmodulin-dependent kinase II-related phosphatase is the most important key enzyme for regulating the signal storage time.

Calcium-Calmodulin-Dependent Protein Kinase Type 2↗
PubMed1995

Detection of angina-provoking coronary stenosis by resting iodine 123 metaiodobenzylguanidine scintigraphy in patients with unstable angina pectoris.

Resting iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy was performed in 19 patients with unstable angina to determine if it can detect myocardial ischemia and identify the angina-provoking coronary artery. Visual assessment of 123I-MIBG single-photon-emission computed tomograms was related to coronary vessel stenoses revealed by arteriography at each vascular territory. Fourteen (74%) of 19 patients had regional 123I-MIBG-identified defects at areas with preserved thallium-201 perfusion. 123I-MIBG defects were highly positive at areas supplied by angina-provoking coronary arteries. The sensitivity and specificity of 123I-MIBG defects for identifying the angina-provoking coronary vessel were 71% and 78%, respectively. The interval between the most recent angina attack and imaging was shorter and the angina occurred more commonly after admission in patients with 123I-MIBG defects than in those without defects. These data suggest that repetitive myocardial ischemia impairs regional 123I-MIBG uptake and that this impairment persists for several days after perfusion has been restored. Thus resting 123I-MIBG scintigraphy is a useful noninvasive method to detect coronary stenoses provoking repetitive ischemia in patients with unstable angina in its acute phase.

3-Iodobenzylguanidine↗
PubMed1995

Structure of new cyclic depsipeptides, Bu-2841-08 and -10.

The structures of new antibiotics, Bu-2841-08 and -10, have been determined. They are cyclic depsipeptides and the sequence of amino acid residues was established by mass spectral analysis of the hydrolyzed linear peptide and NMR spectral analysis of the parent cyclic peptides.

Amino Acid Sequence↗
PubMed1995

Vasoreactivity and restenosis after coronary angioplasty in the atherosclerotic pig model.

BACKGROUND: The effect of coronary angioplasty on coronary spasm remains unknown. We examined the effects of balloon angioplasty, using an oversized balloon, on coronary hypercontraction and eventual restenosis in a pig model of coronary spasm. METHODS: We performed balloon angioplasty, using an oversized balloon at the site of coronary spasm superimposed on atherosclerosis with 6 (group A, n = 14) or 1 (group B, n = 14) atmospheres of inflation pressure in miniature pigs. Using coronary angiography we assessed the coronary basal diameter and diameter change in response to histamine and serotonin before, immediately after, and 4 weeks after angioplasty. Histological examinations were performed immediately after and 4 weeks after the angioplasty. RESULTS: Before angioplasty, histamine- and serotonin-induced hypercontraction was reproducibly noted at the atherosclerotic site. Immediately after angioplasty, the coronary diameter became larger (P < 0.01) than before angioplasty in group A, but there was no significant difference in group B. The hypercontraction in group A was abolished immediately after and 4 weeks after angioplasty, whereas the hypercontraction in group B was unchanged. Histological examination revealed medial necrosis immediately after and medial fibrosis 4 weeks after angioplasty, which were more prominent in group A. Four weeks after angioplasty, the magnitude of restenosis was greater in group A than in group B. CONCLUSIONS: Angioplasty using an oversized balloon with the higher atmosphere of inflation pressure abolished coronary hypercontraction immediately after and 4 weeks after angioplasty, which probably resulted from the irreversible damage to medial smooth muscles; however, this did not prevent restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1995

Endothelin-1 is not involved in serotonin-induced coronary spasm in a swine model.

OBJECTIVES: The role of endothelin-1 (ET-1) in the pathogenesis of coronary artery spasm is not well understood. We aimed to determine if ET-1 is involved in serotonin-induced coronary spasm in the swine model. METHODS: In 10 miniature pigs, a segment of the left anterior descending coronary artery was denuded and irradiated with X-ray. Three months after endothelial denudation, coronary vasomotion was assessed in vivo by quantitative arteriography. RESULTS: Intracoronary serotonin at 10 micrograms/kg provoked coronary spasm (augmented narrowing of the luminal diameter) at the denuded site (diameter reduction 93 +/- 4%) but not at the non-denuded control site (19 +/- 4%, P < 0.01) associated with ST segment elevation in the region perfused by the denuded artery. Intracoronary administration of ET-1 at 25 ng/kg caused mild vasoconstriction of the denuded (26 +/- 4) and non-denuded site (16 +/- 3%, n.s.), but provoked ST segment elevation in the regions perfused by both the denuded and non-denuded arteries. The treatment with an endothelin antagonist (BQ123 0.1 mg/kg) significantly attenuated coronary vasoconstriction and ST segment elevation evoked with ET-1, but did not alter serotonin-induced vasoconstriction either at the denuded or control site. CONCLUSIONS: The results of this study suggest that endogenous ET-1 may not be involved in the pathogenesis of serotonin-induced coronary spasm in our swine model.

Animals↗
PubMed1995

Adenosine triphosphate stress echocardiography in the detection of myocardial ischemia.

The purpose of this study was to assess feasibility and safety in the diagnosis of coronary artery in the diagnosis of coronary artery disease and myocardial ischemia using adenosine triphosphate (ATP) stress echocardiography. ATP, a product of human myocardial tissue, is more potent than adenosine in increasing coronary blood flow. Like adenosine, ATP also has a short half-life (<10 s). Left ventricular echocardiograms were recorded during step-wise infusions of ATP in 86 patients who underwent coronary angiography and stress thallium 201 scintigraphy. No serious complications occurred with ATP infusion and most of the side effects were mild and transient. Significant coronary artery disease (>75% diameter stenosis) was present in 34 of 48 patients who had normal echocardiograms at rest. The sensitivity and specificity of ATP-induced wall motion abnormalities for coronary artery disease was 65% (22 of 34) and 100% (14 of 14), respectively. The sensitivity was 50% (10 of 20) in those with one-vessel disease and 86% (12 of 14) in those with multivessel disease (P < .05). In patients with normal echocardiograms at rest and without prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of myocardial ischemia assessed by 201Tl single proton emission computed tomography was 58%, with a specificity of 76%, and a diagnostic accuracy of 66%. The sensitivity was 43% in those with one-vessel disease, and 86% in those with multivessel disease (P = .05). In patients with prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of viable but jeopardized myocardium was 81%, with a specificity of 91%. The patients with well-developed collateral circulation had a higher incidence of developing wall motion abnormality than those without collaterals (70% v 40%, P < .01). ATP stress echocardiography is valuable for the assessment of coronary artery disease in patients with multivessel disease, coronary collaterals, and with prior myocardial infarction.

Adenosine Triphosphate↗
PubMed1994

Synchronization of neural activity is a promising mechanism of memory information processing in networks of columns.

Synchronization of the oscillatory discharge of cortical neurons could be a part of the mechanism that is involved in cortical information processing. On the assumption that the basic functional unit is the column composed of local excitatory and inhibitory cells and generating oscillatory neural activity, a network model that attains associative memory function is proposed. The synchronization of oscillation in the model is studied analytically using a sublattice analysis. In particular, the retrieval of a single memory pattern can be studied in the system, which can be derived from the original network model of interacting columns and is formally equivalent to a system of an isolated column. The network model simulated numerically shows a remarkable performance in which retrieval is achieved simultaneously for more than one memory pattern. The manifestations of this simultaneous retrieval in the network dynamics are successive transitions of the network state from a synchronized oscillation for a memory pattern to that for another memory pattern.

Cerebral Cortex↗
PubMed1994

A model of cortical memory processing based on columnar organization.

Recent neurophysiological experiments using mammalian brains indicated that some cortical neurons exhibit oscillatory activities which can be of functional importance in visual perception. These findings suggest that the oscillation is an ubiquitous feature of cortical information processing carried out by columns which are receiving growing attention as functional subdivisions of cortical circuitry. On the assumption that a basic functional unit is a column comprising excitatory and inhibitory neurons, a network model of cortical memory processing which can account for these oscillations is proposed. Numerical simulations revealed that for appropriately determined parameters the network can attain memory-pattern retrieval resulting from fixed-point behaviour despite the fact that columns have the characteristic of oscillators.

Animals↗
PubMed1994

Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm in a swine model.

BACKGROUND: The intracellular mechanism of coronary artery spasm is still unknown. The pathway mediated by protein kinase C (PKC) is an important intracellular process of various cellular responses, including vascular smooth muscle contraction. Thus, we examined the role of the PKC-mediated pathway in the pathogenesis of coronary artery spasm in our in vivo swine model. METHODS AND RESULTS: Seven Göttingen miniature pigs underwent coronary balloon injury and x-ray irradiation to induce atherosclerotic lesion. After 6 to 18 months, intracoronary serotonin (3 micrograms/kg) or histamine (3 micrograms/kg) repeatedly induced coronary artery spasm at the atherosclerotic site. At the spastic site, intracoronary administration of phorbol-12,13-dibutyrate (PDBu) (10(-9) mol/kg), a PKC-activating phorbol ester, also induced coronary artery spasm, which was completely blocked by pretreatment with intracoronary staurosporine (10 micrograms/kg), a PKC inhibitor. Intracoronary administration of an inactive phorbol ester, phorbol-12,13-didecanoate (10(-9) mol/kg), did not induce coronary vasoconstriction. Coronary artery spasm induced by the autacoids was significantly augmented by pretreatment with intracoronary PDBu and partially inhibited by staurosporine. Intracoronary administration of Bay K 8644 (10 micrograms/kg), a dihydropyridine-sensitive L-type calcium channel agonist, also induced coronary artery spasm at the spastic site, which was significantly inhibited by pretreatment with intracoronary staurosporine or nifedipine (0.1 mg/kg). CONCLUSIONS: These results suggest (1) the PKC-mediated pathway is importantly involved in the pathogenesis of coronary artery spasm, (2) activation of the PKC-mediated pathway partially accounts for serotonin- and histamine-induced coronary artery spasm, and (3) at the spastic site, calcium influx through dihydropyridine-sensitive L-type calcium channel and/or calcium sensitivity of the contractile proteins may be augmented by the PKC-mediated pathway.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Effects of a new calcium antagonist, CD-832, on experimental coronary artery spasm in miniature pigs.

The effects of a new calcium antagonist, CD-832, on experimental coronary artery spasms were studied in Göttingen miniature pigs. Pigs underwent endothelial denudation at the left anterior descending coronary artery using a balloon catheter. Changes in the diameter of the denuded and nondenuded site in response to an intracoronary administration of serotonin (10 micrograms/kg) or histamine (10 micrograms/kg) were assessed quantitatively by selective coronary arteriography 1 week after endothelial denudation. Percent reductions of the coronary artery diameter induced by serotonin or histamine in the denuded site were significantly greater than those in the nondenuded site (p < 0.01). Coronary artery spasm induced by serotonin or histamine in the denuded site was attenuated in a dose-dependent manner by intravenous infusion of CD-832 (10 and 30 micrograms/kg/min) or nifedipine (1 and 3 micrograms/kg/min). The degrees of inhibition of coronary artery spasm by CD-832 were similar to those produced by nifedipine. CD-832 and nifedipine at the high dose caused comparable increases in the basal coronary artery diameter. These results suggest that CD-832 may be a useful drug for the treatment of coronary artery spasm.

Animals↗
PubMed1993

Role of coronary vasospasm in the pathogenesis of myocardial infarction: study in patients with no significant coronary stenosis.

The role of coronary vasospasm in the pathogenesis of myocardial infarction is unclarified. Among 212 patients with myocardial infarction in whom percutaneous transluminal coronary angioplasty (PTCA) or coronary thrombolysis was not performed at the acute stage, 21 patients (10%) showed no significant coronary stenosis (the degree of stenosis was less than 50% of the luminal diameter) by coronary angiography 4 weeks after myocardial infarction. Among them, 11 (52%) had preinfarction angina at rest, including two with variant angina, and nine (43%) had postinfarction angina at rest. Intracoronary ergonovine maleate induced coronary vasospasm in 12 (75%) of 16 patients examined. Coronary vasospasm occurred in the infarct-related coronary arteries in all patients, and importantly, multivessel coronary vasospasm occurred in 11 patients (69%). The infarct size was relatively small in these patients: (1) seven patients (33%) had Q wave myocardial infarction while 14 patients (67%) had non-Q wave myocardial infarction; (2) peak creatine phosphokinase (CPK) was lower than 1000 IU/ml in all patients; and (3) thallium-201 (Tl-201) scintigraphic study showed no perfusion defect in 8 of 18 patients. There was only one patient with congestive heart failure and no patient died. These results suggest that coronary vasospasm may play an important role in the pathogenesis of myocardial infarction in patients without significant coronary stenosis. The relatively small infarct size suggests that coronary reperfusion occurred in the early stages of myocardial infarction.

Adult↗
PubMed1993

The role of endothelium-derived nitric oxide in acetylcholine-induced coronary vasoconstriction in closed-chest pigs.

BACKGROUND: The effects of an inhibitor of endothelium-derived nitric oxide on acetylcholine (ACh)-induced coronary vasoconstriction were examined in 13 anesthetized closed-chest pigs. METHODS: Coronary blood flow was measured using a previously implanted ultrasonic transmit-time flow probe. The diameter of the large epicardial coronary arteries was assessed by coronary arteriography. RESULTS: Intracoronary infusions of ACh (0.1, 0.3, and 1.0 micrograms/kg/min) resulted in dose-dependent decreases in coronary blood flow. Arterial pressure and heart rate were minimally altered by ACh. The high dose of ACh decreased coronary blood flow by 67 +/- 11% and caused myocardial ischemia, demonstrated by ST-segment elevation. Coronary arteriograms revealed diffuse narrowing of peripheral coronary arteries and a filling delay of the contrast medium evoked with ACh. Vasospasm of the large epicardial coronary arteries was not observed. The decreases in coronary blood flow with ACh were inhibited by atropine (0.2 mg). Intracoronary administration of an inhibitor of endothelium-derived nitric oxide, NW-nitro-L-arginine (NNLA, 1.0 mg/kg), slightly increased arterial pressure but did not change baseline coronary blood flow. The percentage decreases in coronary blood flow induced by ACh were significantly augmented by NNLA administration, but those induced by prostaglandin F2 alpha (0.5 microgram/kg/min) were not affected by NNLA. The response of the large coronary arteries to ACh was not altered by NNLA. CONCLUSIONS: Our results suggest that, in pigs, ACh decreased coronary blood flow and caused myocardial ischemia as a result of the direct cholinergic vasoconstriction of peripheral small coronary arteries. The augmentation of ACh-induced coronary vasoconstriction by NNLA suggests that ACh facilitated the release of endothelium-derived nitric oxide, which attenuated the direct coronary vasoconstriction induced by ACh.

Acetylcholine↗
PubMed1993

Serotonin-induced coronary spasm in a swine model. A minor role of defective endothelium-derived relaxing factor.

BACKGROUND: Coronary spasm may be caused by endothelial dysfunction, vascular smooth muscle hyperreactivity, or both. We aimed to determine the relative role of endothelial dysfunction and vascular smooth muscle hyperreactivity in the pathogenesis of coronary artery spasm in the swine model in vivo. METHODS AND RESULTS: In Göttingen miniature pigs given a high cholesterol diet, a segment of the left coronary artery was denuded and irradiated with x-ray (total, 30 Gy). Three months after endothelial denudation and irradiation, vasomotor responses of the denuded and control sites to agonists were assessed by quantitative arteriography. Serotonin (10 micrograms/kg) provoked coronary spasm at the denuded site (diameter reduction, 79 +/- 6%) associated with ST elevation but not at the nondenuded control site (21 +/- 6%). Intracoronary infusion of N omega-nitro-L-arginine methyl ester (LNNA, an inhibitor of endothelium-derived nitric oxide) of 1 and 3 mg/kg potentiated constriction evoked with serotonin (1, 3, 10 micrograms/kg) at the control site but did not alter it at the denuded site. However, serotonin-induced constriction after LNNA was still less at the control site (31 +/- 3%) than at the denuded site (80 +/- 5%). Endothelium-dependent vasodilation with substance P (0.1, 1, 10 ng/kg), which was inhibited by LNNA, was less (P < .01) at the denuded site than at the control site, whereas vasodilation with the nitrovasodilator SIN-1 (0.1, 1, 10 ng/kg) was comparable between the two sites. Histological study revealed regenerated endothelial cells and intimal thickening at the denuded site. CONCLUSIONS: The results suggest that the denuded segment of the coronary artery with regenerated endothelium was associated with defective endothelium-dependent vasodilation mediated by nitric oxide and vascular smooth muscle hyperreactivity to serotonin. However, provocation of coronary spasm with serotonin resulted primarily from vascular smooth muscle hyperreactivity but not by defective nitric oxide production in this swine model.

Animals↗
PubMed1992

Nodular regenerative hyperplasia of the liver with portal vein thrombosis and hyperplasia of the adrenal gland.

Nodular regenerative hyperplasia (NRH) of the liver is an uncommon entity of unknown origin and pathogenesis. We report here a case of NRH of the liver which was associated with portal vein thrombosis and adrenal hyperplasia. A 48-year-old man who was admitted for further examination of portal hypertension and splenomegaly, died of acute myocardial infarction. Autopsy revealed an enlarged heart with occluded coronary arteries and fresh multiple necrosis in the myocardium. The spleen and the liver were enlarged. In the liver diffusely distributed nodules of regenerative hyperplasia were noted. Organized thrombi of the portal vein and adenomatous hyperplasia of the left adrenal gland were also noted. Antinuclear antibody was positive in the serum.

Adrenal Glands↗
PubMed1990

Cytotoxicity of asymmetric platinum complexes against L-1210 cells. Effect of bulky substituents.

The asymmetric platinum complexes cis-Pt(LL')Cl2 (L = NH3, L' = CH3NH2, (CH3)2NH, C2H5NH2 and (C2H5)2NH and LL' = N,N-dimethylethylenediamine),--one of the NH3 groups of cis-Pt(NH3)2Cl2 was substituted by alkylamine--, were synthesized and their cytotoxic effects have been measured using L-1210 cells. The IC50 values of the asymmetric platinum complexes,--being obtained after 24 h exposure of L-1210 cells to the platinum complexes--, are almost comparable to the corresponding value of cis-Pt(NH3)2Cl2. In 2 h exposure, however, the IC50 values of the platinum complexes were dramatically changed, i.e., a marked difference was observed between those of L' = RNH2 and L' = R2NH. On the other hand, the amounts of platinum taken into the L-1210 cells is little affected by the alkylamino substitution. The results suggest that the bifunctional platinum binding to the target molecule may be responsible for the cytotoxicity.

Animals↗