Biomedical subjects

Satoshi Fujii

Publications and source records attributed to Satoshi Fujii.

69 records · Page 4Linked to original sources

PubMed2002

Changes in [Ca2+](i) during adenosine triphosphate-induced synaptic plasticity in hippocampal CA1 neurons of the guinea pig.

The perfusion of adenosine triphosphate (ATP) induces long-term potentiation (LTP) in CA1 synapses of hippocampal slices, whereas the perfusion of ATP plus ,-2-amino-5-phosphonovaleric acid (AP5) can result in the formation of long-term depression (LTD). To clarify the difference in change of intracellular calcium concentration ([Ca2+]i) corresponding to induction of LTP or LTD, we measured [Ca2+]i during the perfusion of ATP or ATP+AP5, while simultaneously recording evoked field potentials. In both cases, ATP (or ATP+AP5) perfusion transiently increased [Ca2+]i but the extent of increase of [Ca2+]i by ATP was larger than that caused by ATP+AP5. Thus, the larger rise in [Ca2+]i induces LTP but the smaller rise induces LTD. These results are consistent with the Ca2+ hypothesis as proposed by Lisman (Trends Neurosci. 17 (1994) 406).

2-Amino-5-phosphonovalerate↗

PubMed2002

Induction of plasminogen activator inhibitor-1 in endothelial cells by basic fibroblast growth factor and its modulation by fibric acid.

Plasminogen activator inhibitor-1 (PAI-1) inhibits fibrinolysis and proteolysis. Basic fibroblast growth factor (bFGF) stimulates angiogenesis, which requires regional proteolysis. Because modulation of vasculopathy requires tight control of proteolysis, effects of bFGF on PAI-1 expression in endothelial cells (ECs) were characterized. bFGF increased PAI-1 mRNA and accumulation of PAI-1 protein in conditioned media in human umbilical vein ECs. The bFGF-mediated increase in PAI-1 mRNA was attenuated by inhibition of extracellular signal-regulated kinase kinase in human ECV304 cells. The rate of decrease in PAI-1 mRNA after actinomycin D treatment was not affected by bFGF. Transient transfection assays of the human PAI-1 promoter-luciferase construct demonstrated that bFGF-induced PAI-1 transcription was dependent on the elements within the -313 to -260 bp relative to the transcription start site. This region contains an E26 transformation specific 1 (Ets-1)-like site. Electrophoretic mobility shift assay showed that bFGF increased nuclear translocation or DNA binding of the Ets-1-like transcription factor to the PAI-1 promoter. Nucleotide substitution to disrupt the Ets-1-like site reduced bFGF-stimulated promoter activity. Fenofibric acid, an agonist ligand for the peroxisome proliferator-activated receptor-alpha, inhibited basal and bFGF-stimulated PAI-1 expression. By inducing PAI-1 expression from ECs, bFGF may control proteolysis and fibrinolysis in vessel walls.

5' Flanking Region↗

PubMed2002

In vivo nitric oxide transfer of a physiological NO carrier, dinitrosyl dithiolato iron complex, to target complex.

Dinitrosyl dithiolato iron complex (DNIC) has been identified as an endogenous NO carrier, yet in vivo mechanisms of NO donation remain undefined. Transnitrosylation, in which a coordinated NO group is transferred to another metal complex, has been observed in transition-metal-nitrosyl chemistry. In this study, we used three kinds of iron dithiocarbamate complexes (Fe-DTCs) as NO acceptors to elucidate in vivo transnitrosylation of diglutathionyl dinitrosyl iron complex [DNIC-(GS)(2)]. Fe-DTCs were administered to mice after the injection of DNIC-(GS)(2) and electron paramagnetic resonance (EPR) spectra were measured both in the resected organs and in the upper abdomen of living mice. The spectral feature gradually changed from an initial DNIC-(GS)(2) signal to mononitrosyl iron dithiocarbamate one, suggesting that NO-Fe-DTC was formed through in vivo reaction of DNIC-(GS)(2) with Fe-DTC. The spectral results in in vitro and in vivo systems indicate that NO-Fe-DTCs can be formed not only by the transfer of coordinated NO-group(s) in DNIC-(GS)(2) but also by the abstraction of Fe-NO group in DNIC-(GS)(2) by free DTC ligands. Transnitrosylation proceeded more rapidly in blood than in liver and kidney; and more efficiently in kidney than in liver. Further, the ability to accept NO from DNIC was dependent on water-solubility of Fe-DTCs. Thus, in vivo transnitrosylation from DNIC to exogenous iron complex could be observed and this reaction was influenced by biological constituents and properties of iron complex. These results demonstrate that the transnitrosylation from DNIC to intrinsic NO acceptors like metalloproteins has a probable significance in in vivo NO transfer process.

Animals↗

PubMed2002

Temperature dependence of synaptic responses in guinea pig hippocampal CA1 neurons in vitro.

1. Temperature-dependent properties of synaptic transmission were studied by recording orthodromic responses of the population spike and excitatory postsynaptic potential in CA1 pyramidal neurons of guinea pig hippocampal slices. 2. Increasing the temperature of the perfusing medium from 30 to 43 degrees C resulted in a decrease in the amplitude of the population spike (A-PS) and a reduced slope of the excitatory postsynaptic potential (S-EPSP). Bath application of the gamma-aminobutyric acid receptor antagonist, picrotoxin, or a change in the calcium concentration of the perfusate did not affect the A-PS during heating. 3. Increasing the strength of the synaptic input to that eliciting a PS with an amplitude 50, 75, or 100% of maximal at 30 degrees C resulted in a significant increase in the A-PS during the middle phase of hyperthermia (35-39 degrees C). 4. The long-term potentiation (LTP) induced at either 30 or 37 degrees C showed the same percentage increase in both the amplitude of the population spike and the S-EPSP after delivery of a tetanus (100 Hz. 100 pulses) to CA1 synapses. 5. The results of the present study, therefore, indicate that the decrease in CA1 field potential was linearly related to the temperature of the slice preparation, while LTP was induced in these responses during heating from 30 to 37 degrees C.

Action Potentials↗

PubMed2002

Effects of the mono- and tetrasialogangliosides GM1 and GQ1b on ATP-induced long-term potentiation in hippocampal CA1 neurons.

The effects of the mono- and tetrasialogangliosides, GM1 and GQ1b, on ATP-induced long-term potentiation (LTP) were studied in CA1 neurons of guinea pig hippocampal slices. Application of 5 or 10 microM ATP for 10 min resulted in a transient depression followed by a slow augmentation of synaptic transmission, leading to LTP. LTP induced by treatment with 5 microM ATP was facilitated in hippocampal slices prepared from animals treated for 6 days with a ceramide analog, L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol, which stimulates ganglioside biosynthesis. In addition, LTP induced by 5 microM ATP was significantly enhanced when naive slices were incubated with GQ1b but not with GM1. These results suggest that a cooperative effect between extracellular ATP and GQ1b enhances ATP-induced LTP in hippocampal CA1 neurons. In addition, the LTP induced by 10 microM ATP was blocked by coapplication of the NMDA antagonist AP5 (5 microM or 50 microM), and this effect was partially inhibited by GQ1b pretreatment of the slices, suggesting that in hippocampal CA1 neurons, the enhancing effect of GQ1b on ATP-induced LTP is mediated by modulation of NMDA receptors/Ca(2+) channels.

Adenosine Triphosphate↗

PubMed2002

Molecular dynamics investigation of the double stranded oligonucleotide d(AT)6d(AT)6.

Molecular dynamics simulation of double stranded 12-meric oligonucleotide carrying an A and T alternating sequence, d(AT)6d(AT)6, over 1 ns was carried out under low NaCl conditions by using AMBER 6. It was found that the d(AT)6d(AT)6 was stabilized in the D-type structure which is an intermediate structure between A- and B-type ones and this result was in agreement with the previous report.

Nucleic Acid Conformation↗

PubMed2002

RNA motif database catalogued by kink parameters.

In the large RNA molecules, the helical stems close to each other with specific arrangement. These specific interactions are mostly identified by the similar mode and can be classified to the several patterns. Several motifs are well characterized at an atomic resolution. The database, structural information about the assemblage and the space distribution of base moieties, can be a useful tool. Kink parameter affords the structural description between the adjacent groups in any irregular geometry. The relative rotational and positional features may be a preferable information to cite the curved or bend phenomenon in not only the successive strand but also the inter strands. The geometrical parameters about hydrogen bond and base stacking would provide the tolerant aspect for multiple strand packing. The tentative database including these geometrical parameters has been constructed. The user can obtain the selected list with the several descriptors for the structure definition and sequence properties. In addition to this nucleic acid system, RNA-protein system would be included.

Databases, Nucleic Acid↗

PubMed2002

Structural equation modeling of determinants of planning.

A model is proposed that implies that planning evoked by the formation of an implementation intention is related to behavioral intention and perceived behavioral control, whereas in accordance with the theory of planned behavior, behavioral intention is related to attitude and perceived behavioral control. Measures of attitude toward the behavior, perceived behavioral control, behavioral intention, and planning were constructed from 192 undergraduates' ratings of descriptions of two fictitious situations in which a target behavior was varied with respect to benefit and actual behavioral control. Structural equation modeling yielded an acceptable fit of the proposed model.

Adult↗

PubMed2002

In vivo echocardiographic detection of cardiovascular lesions in apolipoprotein E-knockout mice using a novel high-frequency high-speed echocardiography technique.

Apolipoprotein E-knockout (apoE-KO) mice have been used for studying atherogenesis, but the in vivo features including cardiovascular function have not yet been reported. This study aimed to noninvasively evaluate cardiovascular lesions in 6 apoE-KO mice and 6 control (C57BL/6) mice using transthoracic echocardiography performed using an originally developed linear scanner that permits a high-speed scan with wideband high-frequency ultrasound. Two independent observers evaluated and scored the degree of atherosclerotic changes in the aortic root from 2-dimensional long-axis and short-axis images. M-mode measurements included left ventricular end-diastolic dimension (LVDd), posterior wall thickness (LVPWT), fractional shortening, aortic root dimension and rate of systolic expansion of the aorta (%SEAo). The wall thickness of the aortic root was measured from the serial histological sections. Significant differences between apoE-KO and C57BL/6 mice were found in the atherosclerotic score, %SEAo, LVDd and LVPWT. The atherosclerotic score and %SEAo were significantly correlated with the aortic wall thickness. Transthoracic echocardiography with a high-frequency ultrasound system can detect atherosclerotic lesions and the decreased distensibility of the ascending aorta, as well as secondary changes in left ventricular geometry, in apoE-KO mice.

Animals↗

PubMed2002

Comparison of nitric oxide production in response to carbachol between macrovascular and microvascular cardiac endothelial cells.

Cardiac microvascular endothelial cells (EC) play an important role in the physiological regulation of coronary blood flow, but their function has not been rigorously examined, because suitable in vitro models have not been available. Cardiac macrovascular and microvascular EC were isolated and cultured from 14-16-week-old Sprague-Dawley rats to examine the pharmacological responses of carbachol-induced nitric oxide (NO) production using a Griess method. Carbachol-induced NO production was only detected in cardiac macrovascular EC, which suggests that endothelial production of NO differs between macrovascular and microvascular EC. Next, cardiac microvascular EC was treated with either vehicle, angiotensin-converting enzyme (ACE) inhibitor (captopril, 10 micromol/L) or angiotensin II type 1 (AT1) receptor antagonist (CV11974, 10 micromol/L) for 4 days. Carbachol-induced NO production was improved by captopril (136+/-45nmol, p<0.01 vs vehicle) and CV11974 (146+/-30nmol, p<0.01 vs vehicle). Angiotensin II concentration in the culture medium and protein expressions of endothelial nitric oxide synthase and AT1 receptor in the EC were similar among the 3 groups. Interestingly, the level of muscarinic subtype 3 (M3) receptor was significantly increased in the EC treated with captopril (214%, p<0.01) and CV11974 (296%, p<0.01). When cardiac microvascular EC were treated with neomycin (non-selective phospholipase C inhibitor), carbachol-induced NO production was also improved (146+/-35nmol, p<0.01, neomycin I mmol/L) together with increased expression of M3 receptor (p<0.01). These data suggest that the upregulation of the M3 receptor by captopril or CV11974 occurs via a phospholipase C-dependent pathway. Cardiac microvascular EC also produced NO constitutively, as did the macrovascular EC, but carbachol-induced NO production was decreased. The present data suggest that the upregulation of the M3 receptor by the ACE inhibitor and AT1 receptor antagonist is a new beneficial effect of these drugs on microvascular endothelial function.

Angiotensin II↗

PubMed2002

Association of cardiovascular risk factors and endothelial dysfunction in japanese hypertensive patients: implications for early atherosclerosis.

Although hypertension, hyperlipidemia, diabetes and smoking are known risk factors of atherosclerosis in Caucasians, their relative contributions to early atherosclerosis among Japanese are unknown. Decrease in flow-mediated dilation (FMD) of the brachial artery is a useful marker of endothelial dysfunction and early atherosclerosis. To evaluate the relative contribution of hypertension to early atherogenesis, we determined FMD, as well as plasma levels of tissue-type plasminogen activator (t-PA; a sensitive index of endothelial damage) and tumor necrosis factor (TNF)-a and interleukin (IL)-6 (established markers of inflammation) in normotensive and hypertensive patients under treatment. FMD was significantly reduced as the number of risk factors increased, suggesting that accumulations of risk factors were related to endothelial dysfunction. FMD was reduced in hypertensives (9.9 +/- 5.8 (SD) %) compared to normotensives (14.6 +/- 7.6, p<0.01) despite good blood pressure control (139 +/- 20/80 +/- 14 mmHg in hypertensives). Nitroglycerine-induced endothelium-independent vasodilation was not altered in hypertensives (16.0 +/- 6.3%) as compared to normotensives (16.7 +/- 5.8). Plasma t-PA, TNF-alpha, and IL-6 levels were increased in hypertensives despite good blood pressure control. Thus, hypertension alone is a high risk for early atherosclerosis. Persistent endothelial damage and moderate inflammation may increase the risk of early atherosclerosis synergistically under the presence of hypertension in Japanese.

Adult↗

PubMed2002

Prevalence and predictors of renal artery stenosis in patients undergoing cardiac catheterization.

Renal artery stenosis (RAS) is recognized as a major co-morbid condition for patients with cardiovascular disease. Although the prevalence of RAS in Western countries has been reported as 13.5-18% in patients with suspected coronary artery disease (CAD) undergoing coronary angiography, there is little information available about the prevalence of RAS in Asian populations, which are less susceptible to atherosclerosis. To evaluate the prevalence of RAS in Japanese patients suspected of cardiovascular disease and the relationships among RAS and vascular risk factors, especially hypertension, renal artery angiography was performed in a total of 289 consecutive patients receiving diagnostic cardiac catheterization. RAS with a stenosis diameter greater than 50% was considered significant. The prevalence of RAS was 21/289 (7%) including 18 (6%) cases of unilateral stenosis and 3 (1%) of bilateral stenosis. RAS accompanied 14/220 (6%) cases of CAD, 4/34 (12%) cases of valvular heart disease and 1/14 (7%) cases of cardiomyopathy. In the subgroups of CAD, the prevalence of RAS was 5%, 10%, 9%, and 19% in cases of 0, 1, 2 and 3-vessel disease, respectively. Hypertension was more frequent among patients with than among those without RAS (86% vs. 45%, p=0.0003). The prevalence of RAS was 13% in hypertensives and 2% in normotensives (p = 0.004). Thus RAS was frequent in patients with established CAD, and particularly in those with 3-vessel disease. Together, the results showed that hypertension was closely associated with RAS, appearing as both a risk factor and a possible clinical manifestation of the disease. We conclude that more attention should be paid to RAS in Japanese patients with hypertension and cardiovascular disease.

Aged↗

PubMed2002

Relationships between brachial artery flow mediated dilation and carotid artery intima-media thickness in patients with suspected coronary artery disease.

The correlation of peripheral endothelial dysfunction and intima-media thickness (IMT) in patients with suspected coronary artery disease (CAD) has been unclear. Inflammation and thrombosis may play a role at early stages of atherosclerosis. Thus, early atherosclerosis was noninvasively examined morphologically by IMT of carotid arteries, and functionally by flow mediated dilation (FMD) of brachial arteries in patients who were suspected of CAD and had undergone coronary angiography. Plasma antigen levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, representative atherogenic cytokines, tissue factor (TF) and tissue factor pathway inhibitor (TFPI), markers of coagulation, and plasma activity level of plasminogen activator inhibitor type-1 (PAI-1), a marker of defective fibrinolysis, were measured. Patients with coronary atherosclerosis in one or more vessels with lesion > or = 50% had significantly reduced FMD compared with those with angiographically normal coronary arteries. Carotid artery IMT increased significantly only in patients with advanced coronary atherosclerosis in one or more vessels with lesion > or = 90%. Plasma antigen levels of IL-6 were significantly increased in patients with reduced FMD (< 5%) compared to those in patients with FMD between 10 and 15%. Plasma antigen levels of TF, total and free TFPI, and PAI-1 activity tended to increase with a reduction in FMD. Thus, (1) FMD was reduced at early stages of CAD while IMT was increased in advanced CAD, and (2) inflammation and thrombosis may play a role in the early stages of the atherosclerotic process.

Aged↗

PubMed2001

Effects of temperature on adenosine A1 receptor activation in guinea pig hippocampus in vitro.

The effects of temperature on adenosine A1 receptor activation were studied both by electrophysiological analysis of synaptically evoked responses in CA1 neurons in guinea pig hippocampal slices, and by measuring the binding of adenosine analogues to adenosine A1 receptors in crude synaptosomes from guinea pig hippocampal neurons. Increasing the temperature of the perfusing medium from 30 degrees C to 45 degrees C attenuated the amplitude of the synaptically and the non-synaptically evoked CA1 population spikes. Bath application of 1 microM 8-cyclopentyltheophylline, an adenosine A1 receptor antagonist, did not affect non-synaptically evoked CA1 population spikes, but significantly increased the amplitude of synaptically evoked population spikes in the upper range of hyperthermia (37-43 degrees C). In contrast, application of 5 microM L- N(6)-phenylisopropyladenosine, an adenosine A1 receptor agonist, did not affect non-synaptically evoked CA1 population spikes, but significantly decreased the amplitude of synaptically evoked population spikes in the upper range of hyperthermia. Binding assays using crude hippocampal synaptosomes showed that the affinity of adenosine A1 receptors for a radio-labeled adenosine analogue increased in response to a temperature increase. These results suggest that increased activation of adenosine A1 receptors in response to a temperature increase depresses excitatory synaptic responses in hippocampal CA1 neurons.

Adenosine↗

PubMedDate not supplied

Loss of heterozygosity and microsatellite instability in epithelial hyperplasia of the breast.

We evaluated loss of heterozygosity (LOH) and microsatellite instability (MSI) in epithelial hyperplasia of the breast by the PCR method using microsatellite markers. Seven loci of 16q, 17p, 17q, and 18q were examined in 35 lesions of epithelial hyperplasia observed in non-neoplastic breast tissue of eight breast carcinoma cases, and 29 lesions were observed within 19 fibroadenomas. These hyperplastic lesions were classified by standard criteria into three groups, namely, mild, moderate and atypical ductal hyperplasia (ADH). In the breast carcinoma cases, the frequency of loss of heterozygosity was 40% in mild, 50% in moderate, and 100% in ADH; while in the fibroadenoma cases, the frequency was 10% in mild, 27% in moderate, and 25% in ADH; total frequency of LOH was statistically higher in carcinoma cases than in fibroadenoma cases. On the other hand, the frequency of microsatellite instability was higher in fibroadenoma cases (28%) than in breast carcinoma cases (11%). Furthermore, we analyzed two cases of noninvasive ductal carcinoma arising in fibroadenoma, which had various types of hyperplasia along with carcinoma in situ, and many hyperplasias showed LOH at several of the same markers as carcinoma in situ. From those results, we speculated that LOH at these markers is an early event in mammary tumorigenesis, and some of the hyperplastic lesions with LOH have precancerous natures.

Adult↗