Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 181 records · Page 10Linked to original sources

PubMed1999

Serum hepatocyte growth factor levels in patients with renal diseases.

The serum levels of hepatocyte growth factor (HGF) were determined in patients with various renal diseases. In patients with acute-phase acute renal failure (ARF) and chronic tubulointerstitial nephritis (chronic TIN), the serum HGF levels were 0.55 +/- 0.24 and 0.44 +/- 0.37 ng/ml (mean +/- SD), respectively, and were significantly higher than that in the control group (0.12 +/- 0.12 ng/ml). The serum HGF level tended to be high also in patients with active-phase steroid-sensitive nephrotic syndrome (SSNS). The serum levels of HGF were not elevated in patients with IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), membranoproliferative glomerulonephritis (MPGN), poststreptococcal acute glomerulonephritis (PSAGN), unilateral renal atrophy, unilateral nephrectomy, or proximal tubular dysfunction. These observations suggest that glomerular disorders cause no apparent elevation of the serum HGF level, and that elevation of the serum HGF level may be associated with tubulointerstitial damage in renal diseases.

Adolescent↗

PubMed1999

Increased vitreous concentrations of human hepatocyte growth factor in proliferative diabetic retinopathy.

Human hepatocyte GF (hHGF) has strong neoangiogenesis activity. The present study was designed to investigate the possible involvement of hHGF in neovascularization in proliferative diabetic retinopathy (PDR) by measuring vitreous hHGF concentrations. The mean vitreous hHGF concentration was higher in subjects with PDR (5.70 +/- 0.68 ng/mL, n = 33) than in nondiabetic control subjects (1.50 +/- 0.20 ng/mL, n = 18, P < 0.01), nondiabetic subjects with proliferative vitreoretinopathy (3.31 +/- 0.57 ng//mL, n = 10, P < 0.05), or diabetic subjects without PDR (1.29 +/- 0.28 ng/mL, n = 8, P < 0.01). PDR subjects with neovascularization of iris, which suggests advanced retinal ischemia, showed a higher mean vitreous hHGF concentration than those without iridal neovascularization [7.33 +/- 1.16 ng/mL (n = 14) vs. 4.49 +/- 0.72 ng/mL (n = 19), P < 0.05]. The mean vitreous hHGF concentration was higher in PDR subjects with retinal neovascularization at the optic disc than in those with neovascularization elsewhere [7.3 +/- 1.1 ng/mL (n = 15) vs. 4.4 +/- 0.7 ng/mL (n = 18), P < 0.05]. Our results indicate that vitreous hHGF may play a role in retinal neovascularization in PDR.

Aged↗

PubMed1999

Serum hepatocyte growth factor as a possible indicator of vascular lesions.

To investigate the role of human hepatocyte growth factor (hHGF) in vascular lesions associated with endothelial injury, we measured serum hHGF concentrations in subjects with retinal arteriosclerosis, coronary atherosclerosis, or arteriolitis due to Henoch-Schönlein purpura. Individuals with more advanced grades of retinal arteriosclerosis showed higher serum hHGF concentrations [grade 0, 0.053+/-0.005 ng/mL (n = 68); grade 1, 0.144+/-0.022 ng/mL (n = 21; P<0.01 vs. grade 0); grade 2, 0.338+/-0.036 ng/mL (n = 20; P<0.01 vs. grade 0 or 1); grade 3, 0.526+/-0.051 ng/mL (n = 9; P<0.01 vs. grade 0, 1, or 2)]. Patients with active arteriolitis due to Henoch-Schönlein purpura showed higher (P<0.01) serum hHGF concentrations (0.347+/-0.038 ng/mL; n = 14) than those in the remission phase (0.097+/-0.017 ng/mL; n = 19). Mean serum hHGF concentrations were higher in subjects with coronary atherosclerosis than in those without, but a significant overlap in serum hHGF concentrations was found between subjects with and those without coronary atherosclerosis. Serum hHGF may be an indicator of the presence or development of arteriolar lesions.

Aged↗

PubMed1999

Effects of the central pair apparatus on microtubule sliding velocity in sea urchin sperm flagella.

To produce oscillatory bending movement in cilia and flagella, the activity of dynein arms must be regulated. The central-pair microtubules, located at the centre of the axoneme, are often thought to be involved in the regulation, but this has not been demonstrated definitively. In order to determine whether the central-pair apparatus are directly involved in the regulation of the dynein arm activity, we analyzed the movement of singlet microtubules that were brought into contact with dynein arms on bundles of doublets obtained by sliding disintegration of elastase-treated flagellar axonemes. An advantage of this new assay system was that we could distinguish the bundles that contained the central pair apparatus from those that did not, the former being clearly thicker than the latter. We found that microtubule sliding occurred along both the thinner and the thicker bundles, but its velocity differed between the two kinds of bundles in an ATP concentration dependent manner. At high ATP concentrations, such as 0.1 and 1 mM, the sliding velocity on the thinner bundles was significantly higher than that on the thicker bundles, while at lower ATP concentrations the sliding velocity did not change between the thinner and the thicker bundles. We observed similar bundle width-related differences in sliding velocity after removal of the outer arms. These results provide first evidence suggesting that the central pair and its associated structures may directly regulate the activity of the inner (and probably also the outer) arm dynein.

Adenosine Triphosphate↗

PubMed1999

Significance of exercise QT dispersion in patients with coronary artery disease who do not have exercise-induced ischemic ST-segment changes.

The poor sensitivity and the poor predictive value of ST-segment depression have limited the usefulness of the exercise electrocardiogram (ECG) in the diagnosis and evaluation of coronary artery disease (CAD). The QT dispersion (QTD), recorded as the difference between maximal and minimal QT intervals on a 12-lead exercise ECG, is sensitive to myocardial ischemia and may improve the accuracy of exercise testing in patients with CAD who do not show an ST-segment depression. Exercise ECGs were analyzed in 50 subjects who had undergone coronary angiography for clinical indications. None of them showed an ST-segment depression during or after exercise: There were 25 patients with significant coronary artery stenosis and 25 without significant stenosis. The QTD measured before, immediately after, and 1 min after exercise was similar in the 2 groups. The QTD at 3 and 5 min after exercise was significantly greater in patients with CAD than in the controls, and the most marked difference in QTD was observed at 3 min after exercise. A QTD at 3 min after exercise of >60 ms had a sensitivity of 80% and specificity of 88% regarding the diagnosis of CAD. When a deltaQTD (post-exercise QTD minus QTD at rest) at 3 min after exercise of >0 ms was added to a QTD of >60 ms as a condition for positivity, the specificity increased to 96%. QTD measured at 3 min after exercise increases the accuracy of exercise testing in patients with CAD who do not show an ST-segment depression.

Adult↗

PubMed1999

Influence of exercise on QT dispersion in hypertensive patients with left ventricular hypertrophy without coronary artery disease.

In hypertensive patients with left ventricular hypertrophy (LVH), the influence of exercise on the regional variations in ventricular repolarization is not well understood. The present study compared dispersions of QT and QT apex (QTD and QTaD), which are indices of regional variations in ventricular repolarization, between hypertensive patients with echocardiographic evidence of LVH and those without LVH. Seventy essential hypertensive patients underwent a modified Bruce protocol exercise test, and QTD and QTaD were measured at rest and at peak exercise level. All subjects had undergone coronary angiography and did not have coronary artery disease. None of them showed ST-segment depression during or after exercise. There were 20 patients with LVH and 50 patients without LVH. The QTD and QTaD at rest were not different between the patients with LVH and those without LVH (56+/-32 vs 57+/-28 ms, 52+/-20 vs 49+/-23 ms). At peak exercise level, QTaD was significantly decreased compared with the baseline in hypertensive patients without LVH (49+/-23 to 42+/-16ms, p<0.05), whereas in patients with LVH QTaD increased (52+/-20 to 67+/-17ms, p<0.05). QTaD at peak exercise level was positively correlated with the left ventricular mass index (r=0.357, p=0.0024). These data were unchanged after correction for heart rate using Bazett's equation. In conclusion, QTaD increased after exercise in hypertensive patients with LVH. Inhomogeneity of repolarization is induced by exercise stress in hypertensives with LVH.

Adult↗

PubMed1999

[A case of atypical polypoid adenomyoma with intramural myoma-like growth].

We encountered a case of a large atypical polypoid adenomyoma (APA) which showed characteristic intramural appearance. As many cases of APA of the uterus have been reported in recent years, macro- and microscopic findings of the lesion and its clinical characteristics have been investigated. However the pathogenesis and the natural history of the lesion remained to be solved owing to still limited number of the cases. We report this case to discuss the macroscopic findings and clinicopathologic characteristics of the lesion.

Adenomyoma↗

PubMed1999

[Creatinine].

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Adult↗

PubMed1999

Ethanol's actions on cAMP-mediated signaling in cells transfected with type VII adenylyl cyclase.

BACKGROUND: Adenylyl cyclase (AC) activity is increased in the presence of ethanol. The magnitude of ethanol's action on AC depends on the isoform of AC expressed in a particular cell type. Type VII AC demonstrates the greatest potentiation of activity in the presence of ethanol, but questions have arisen regarding the effects of pharmacologically relevant (approximately 50 mM) concentrations of ethanol on type VII AC activity. Questions also remain as to whether the potentiation of AC activity by ethanol initiates downstream effects on protein kinase A activity. METHODS: HEK293 (human embryonic kidney 293) cells overexpressing type VII AC were used to study the dose-dependent actions of ethanol on cyclic adenosine monophosphate (cAMP) production. Studies were performed in the presence and absence of phosphodiesterase inhibitors. Protein kinase A activity was assessed under conditions similar to those used to measure ethanol's actions on AC. RESULTS: A significantly greater percent stimulation of prostaglandin E1-mediated cAMP accumulation was evident in the absence of the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine and Ro 20-1724 than in the presence of the phosphodiesterase inhibitors. We also showed that ethanol was not, itself, acting as a phosphodiesterase inhibitor. The calculated percent stimulation of AC activity by ethanol depended on the baseline levels of cAMP production in the absence of ethanol. In the absence of 3-isobutyl-1-methylxanthine (or other phosphodiesterase inhibitors), a 50 mM concentration of ethanol produced a 56% increase in prostaglandin E1-stimulated cAMP production in the type VII AC transfected HEK293 cells. This concentration of ethanol also produced a significant activation of protein kinase A beyond that produced by prostaglandin E1 alone. CONCLUSIONS: The present study indicates that, in the presence of a particular isoform of AC, moderately intoxicating concentrations of ethanol will significantly potentiate the transmitter-mediated activation of the cAMP signaling cascade. Activation of this signaling cascade may have important implications for the mechanisms by which ethanol produces intoxication and/or in the mechanisms of neuroadaptation leading to tolerance to, and physical dependence on, ethanol.

Adenylyl Cyclases↗

PubMed1999

[Dopamine].

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Dopamine↗

PubMed1998

Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina.

OBJECTIVES: We examined the effects of oral administration of vitamin E, an antioxidant, on endothelium-dependent vasodilation in patients with coronary spastic angina. BACKGROUND: We have recently reported that endothelium-dependent vasodilation is impaired in patients with coronary spastic angina (CSA). Furthermore, it is known that oxidative stress may play an important role in the impairment of endothelium-dependent vasodilation in cardiovascular diseases. METHODS: With the ultrasound technique, flow-dependent vasodilation of the brachial arteries during reactive hyperemia was examined before and after treatment for a month with either oral administration of vitamin E (alpha-tocopherol acetate, 300 mg/day) or placebo, which is randomly assigned, in patients with CSA (n=60). RESULTS: Before treatment, patients with CSA had impaired flow-dependent vasodilation, lower plasma levels of alpha-tocopherol and higher plasma levels of thiobarbituric acid reactive substances (TBARS), as compared with age- and sex-matched control subjects (n=60) (flow-dependent vasodilation: 3.1+/-1.8 vs. 7.1+/-2.5%, p < 0.001; alpha-tocopherol levels: 8.9+/-1.8 vs. 10.8+/-1.8 microg/ml, p < 0.001). In patients with CSA, treatment with vitamin E restored flow-dependent vasodilation (3.1+/-1.7 vs. 8.3+/-2.0%, p < 0.001), and this improvement was associated with the decreases in plasma TBARS levels and anginal attacks. CONCLUSIONS: The results indicate that vitamin E treatment improved endothelium-dependent vasodilation and decreased plasma TBARS levels in patients with CSA. Thus, increased oxidative stress may contribute to endothelial dysfunction and anginal attacks in patients with CSA.

Adult↗

PubMed1998

Capsaicin facilitates excitatory but not inhibitory synaptic transmission in substantia gelatinosa of the rat spinal cord.

Actions of capsaicin were examined on synaptic transmissions in the substantia gelatinosa (SG) of adult rat spinal cord slices using the whole-cell patch-recording technique. Bath-applied capsaicin at a concentration of 2 microM activated a slow inward current (having an amplitude of 33 pA at -70 mV), which was accompanied by an increase in the frequency of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs; by 234%); these actions were blocked by a capsaicin-receptor antagonist, capsazepine (10 microM). The capsaicin-induced increase in sEPSC frequency was resistant to tetrodotoxin (0.5-1 microM). On the other hand, capsaicin (2 microM) did not affect either glycine- or gamma-aminobutyric acid-mediated spontaneous synaptic transmission. The results indicate that capsaicin enhances excitatory but not inhibitory synaptic transmission, possibly through a direct action on primary afferent terminals in the SG. As the SG has been thought to participate in nociceptive pathway, it is suggested that such a presynaptic action of capsaicin contributes to nociceptive transmissions.

Animals↗

PubMed1998

Quantitative measurements for type 1 deiodinase messenger ribonucleic acid in human peripheral blood mononuclear cells: mechanism of the preferential increase of T3 in hyperthyroid Graves' disease.

To evaluate the regulatory mechanism of human Type 1 iodothyronine deiodinase (D1) gene expression, we measured the D1 mRNA levels in peripheral blood mononuclear cells (PBMC) in normal control subjects and in patients with Graves' disease. We used competitive reverse transcriptase-polymerase chain reaction with the deleted complimentary RNA of D1 as the standard for quantification. The D1 mRNA levels in PBMC were increased significantly in patients with Graves' disease compared with that in normal controls. There was a significant (p < 0.01) positive correlation (r=0.698) between D1 mRNA level and serum T3 concentration. When PBMC from the normal volunteers were cultured with various doses of T3, the quantity of D1 mRNA increased significantly in a dose-dependent manner. These findings indicate that PBMC D1 mRNA is actually up-regulated by T3 in vivo, and we postulate that a vicious spiral of increasing T3 and D1 is responsible for the exacerbation of thyrotoxicosis in hyperthyroid Graves' disease.

Gene Expression Regulation↗

PubMed1998

Modulation by chloramine-T of 4-aminopyridine-sensitive transient outward current in rabbit atrial cells.

The effects of an oxidizing agent, chloramine-T, on the 4-aminopyridine-sensitive transient outward current (ITO) were investigated in rabbit atrial myocytes by using patch-clamp techniques. Extracellular application of chloramine-T at 20 microM irreversibly slowed the time course of inactivation of the whole-cell ITO, and increased the peak by 19.3% (n = 19) at +40 mV. At 100 microM, chloramine-T decreased the peak by 22.5% (n = 9) of the control, and subsequently induced a glibenclamide-sensitive time-independent outward K+ current. Under superfusion with dithiothreitol (3 mM), chloramine-T (100 microM) produced no change in ITO. The chloramine-T-induced slowing of ITO inactivation was partially reversed by subsequent application of 3 mM dithiothreitol. In single-channel recordings with the cell-attached patch configuration, chloramine-T (20 microM) increased the open probability of the ITO channel from 0.15 to 0.46 at a potential 100 mV positive to the resting potential, and the mean open lifetime from 5.1 ms to 7.0 ms (n = 5). The unitary current amplitude was not affected. As a result, chloramine-T increased the ensemble current in amplitude and slowed its decay. These results indicated that: (1) inactivation of the native A-type channels of rabbit heart is susceptible to oxidation; and (2) oxidation of ITO channels may contribute to the genesis of arrhythmias.

4-Aminopyridine↗

PubMed1998

Agonist stimulation of B1 and B2 kinin receptors causes activation of the MAP kinase signaling pathway, resulting in the translocation of AP-1 in HEK 293 cells.

In response to bradykinin, phosphorylated MAP kinases (ERK-1 and ERK-2) were abundantly increased in HEK 293 cells, which overexpress the rat B2 kinin receptor. In a similar way des-Arg9-bradykinin stimulation of B1 kinin receptor-overexpressing HEK 293 cells caused activation of the same species of MAP kinase. Furthermore, nuclear translocation of transcription factor AP-1 was also found in the cells after stimulation with either agonist. PD98059, a MAP kinase kinase (MEK-1) inhibitor, blocked the agonist-induced AP-1 translocation as well as the phosphorylation of the MAP kinases. This communication provides the first evidence for both B1 and B2 kinin receptors mediating the MAP kinase signaling pathway to activate AP-1.

Animals↗

PubMed1998

Association of remnant lipoprotein levels with impairment of endothelium-dependent vasomotor function in human coronary arteries.

BACKGROUND: It remains undetermined whether triglyceride-rich lipoproteins are an independent risk factor for atherosclerosis. METHODS AND RESULTS: The correlation of responses of coronary arterial diameter (quantitative coronary angiography) and coronary blood flow (intracoronary flow wire technique) to intracoronary infusion of acetylcholine (10 and 50 microg/min) with coronary risk factors including remnant lipoprotein levels was statistically analyzed in 106 consecutive subjects with normal coronary angiograms. Remnant lipoproteins were isolated from fasting blood with an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. In multivariate stepwise regression analysis, remnant lipoprotein levels had the most significant correlation with abnormal epicardial coronary vasomotor responses to acetylcholine infusion, reflected by impaired dilation or constriction of the epicardial coronary arteries, and the levels also had an inverse and independent correlation with the coronary blood flow increase in response to acetylcholine. In a subgroup of 53 consecutive subjects, constrictor responses of epicardial coronary diameters to intracoronary infusion of NG-monomethyl-L-arginine (50 micromol/min for 4 minutes) at baseline, reflecting the presence of coronary nitric oxide bioactivity, had an inverse and independent correlation with remnant lipoprotein levels by use of multivariate analysis. CONCLUSIONS: Remnant lipoprotein levels were independently associated with abnormal endothelium-dependent vasomotor function in large and resistance coronary arteries in humans, indicating that remnant lipoproteins may impair endothelial vasomotor function in human coronary arteries. The decrease in coronary nitric oxide bioactivity may be responsible in part for the inhibitory effects of remnant lipoproteins.

Acetylcholine↗

PubMed1998

Dynein arms are oscillating force generators.

Eukaryotic flagella beat rhythmically. Dynein is a protein that powers flagellar motion, and oscillation may be inherent to this protein. Here we determine whether oscillation is a property of dynein arms themselves or whether oscillation requires an intact axoneme, which is the central core of the flagellum and consists of a regular array of microtubules. Using optical trapping nanometry, we measured the force generated by a few dynein arms on an isolated doublet microtubule. When the dynein arms on the doublet microtubule contact a singlet microtubule and are activated by photolysis of caged ATP8, they generate a peak force of approximately 6pN and move the singlet microtubule over the doublet microtubule in a processive manner. The force and displacement oscillate with a peak-to-peak force and amplitude of approximately 2 pN and approximately 30 nm, respectively. The geometry of the interaction indicates that very few (possibly one) dynein arms are needed to generate the oscillation. The maximum frequency of the oscillation at 0.75 mM ATP is approximately 70 Hz; this frequency decreases as the ATP concentration decreases. A similar oscillatory force is also generated by inner dynein arms alone on doublet microtubules that are depleted of outer dynein arms. The oscillation of the dynein arm may be a basic mechanism underlying flagellar beating.

Adenosine Triphosphate↗

PubMed1998

Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation.

BACKGROUND: Oxygen free radicals have been shown to cause endothelial vasomotor dysfunction. This study examined the effect of reduced glutathione (GSH), an antioxidant, on human coronary circulation. METHODS AND RESULTS: Responses of epicardial diameter and blood flow of the left anterior descending coronary artery to intracoronary infusion of acetylcholine (ACh, 50 microg/min) were measured by quantitative coronary angiography and Doppler flow-wire technique, respectively, before and during combined intracoronary infusion of GSH (50 mg/min) or saline in 26 subjects with no significant coronary stenosis. GSH infusion suppressed the constrictor response of epicardial diameter to ACh and enhanced the increase in blood flow response to ACh. Furthermore, GSH potentiated the coronary dilator effect of nitroglycerin. A beneficial effect of GSH on the epicardial diameter response to ACh was observed in a subgroup of subjects with > or = 1 coronary risk factors but not in a subgroup without risk factors. Saline infusion did not have any effects. CONCLUSIONS: The results indicate that GSH improved coronary endothelial vasomotor function, particularly in subjects with coronary risk factors, and it potentiated the vasodilator effect of nitroglycerin in human coronary arteries.

Acetylcholine↗