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Biomedical subjects

Y Okamoto

Publications and source records attributed to Y Okamoto.

At least 55 records · Page 3Linked to original sources

Characterization of Ca(2+) channels involved in endothelin-1-induced mitogenic responses in vascular smooth muscle cells.

Ca(2+) channels involved in the endothelin-1-induced mitogenic response of cultured rat thoracic aorta smooth muscle cells, A7r5 cells, were characterized using the Ca(2+) channel blockers, LOE 908 and SK&F 96365. Stimulation of A7r5 cells with endothelin-1 induced a mitogenic response as well as a biphasic increase in the intracellular-free Ca(2+) concentration. Based on the sensitivity to nifedipine, a specific blocker of L-type voltage-operated Ca(2+) channel (VOCC), Ca(2+) influx through VOCC has a minor role in endothelin-1-induced mitogenic responses. On the other hand, Ca(2+) influx through voltage-independent Ca(2+) channels (VICCs) plays an important part in endothelin-1-induced mitogenesis. Moreover, based on their sensitivity to SK&F 96365 and LOE 908, VICCs consist of two types of Ca(2+)-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca(2+) channel (SOCC). Ca(2+) influx through NSCC-1, NSCC-2 and SOCC contributes to 35%, 30% and 35%, respectively, to the nifedipine-resistant component of the endothelin-1 mitogenic response.

Acetamides↗

Diastereoselective inter- and intramolecular pinacol coupling of aldehydes promoted by monomeric titanocene(II) complex Cp(2)TiPh.

A monomeric titanocene(III) derivative, Cp(2)TiPh, effectively promoted the pinacol coupling of both an aromatic aldehyde, benzaldehyde, and an aliphatic aldehyde, 3-phenylpropionaldehyde. The same reactive complex was successfully generated by a catalytic amount of a precursor, Cp(2)Ti(Ph)Cl, and its stoichiometric amount of Zn. The Cp(2)TiPh-catalyzed pinacol coupling of benzaldehyde derivatives and aliphatic aldehydes afforded the corresponding 1,2-diols in high yields with moderate to good threo-selectivity. On the other hand, Cp(2)TiPh-catalyzed pinacol cyclization of dials gave cyclic 1,2-diols with excellent diastereoselectivity. The extension of this protocol to chiral dials demonstrated that the phenyltitanium complex catalytically transmitted an axial chirality or a central chirality of the starting dials to the central chirality of the resultant 1,2-diols.

Journal Article↗

Comparison of source localization of interictal epileptic spike potentials in patients estimated by the dipole tracing method with the focus directly recorded by the depth electrodes.

The purpose of the study was to investigate the accuracy of location of equivalent current dipoles estimated by the dipole tracing method (DT) utilizing a realistic 3-shell (scalp-skull-brain) head model (SSB-DT). Three patients with intractable complex partial seizures, diagnosed as having typical temporal seizures were investigated. We recorded the interictal spike potentials with surface electrodes (International 10/20 system) and with intracerebral depth electrodes simultaneously. We compared the location of dipoles of the spikes estimated by the SSB-DT with the focus of the spikes determined by the recording from the depth electrodes. We found that the location of the dipoles estimated by SSB-DT corresponded to the location of the depth electrodes, which could record the epileptic spikes. This finding proved that SSB-DT is reliable and valid for estimating neural activity in deep locations such as the limbic system.

Action Potentials↗

Characterization of the active site structure of Pd and Pd-promoted Mo sulfide catalysts by means of XAFS.

Recently, noble metal catalysts are noted as promising candidates for new super-deep-hydrodesulfurization (HDS) catalysts. In this study, we investigated the structure of Pd particles supported on zeolite and Al2O3 under a sulfidation or reduction condition. From EXAFS analysis, it was found for sulfided Pd catalysts that small Pd sulfide clusters are formed without sintering. It was also revealed that no extensive growth of metal Pd particles occurs in Pd/NaY sulfide catalysts even after a treatment with H2 at 673 K. The dispersion of Pd metal particles is improved by H2/H2S treatment. These results indicate that in the presence of H2S, Pd shows high resistance against particle growth. A comparison of the Mo and Pd K-edge EXAFS spectra for MoS(x)/Pd-NaY and Pd-NaY catalysts revealed the existence of Mo-Pd bondings by the addition of Mo sulfide, indicating a direct interaction between Mo and Pd sulfides.

Journal Article↗

Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages.

BACKGROUND: Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. METHODS AND RESULTS: Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. CONCLUSIONS: The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.

Adipocytes↗

Progressive change of optical coherence tomography scans in retinal degeneration slow mice.

OBJECTIVE: To study whether optical coherence tomography (OCT) scans correlate retinal histologic findings with the progression of retinal degeneration in retinal degeneration slow (rds) mice. METHODS: Sensory retinal thickness (SRT) and outer retinal thickness (ORT), representing photoreceptor cell layer, in temporal retina at a distance 1 to 2 disc diameters from the optic disc were measured using scan profile in OCT from 6 healthy mice (16 weeks old) and 2-week-old (n = 6), 6-week-old (n = 4), and 60-week-old (n = 2) rds mice. Histologic sections were obtained from Epon-embedded retinas from the corresponding location. RESULTS: Cross-sectional OCT images correlated to the corresponding histologic sections in each mouse. Both SRT and ORT of 2-week-old rds mice (150 +/- 4 microm and 28 +/- 4 microm, respectively) lacking photoreceptor outer segments were already shorter than those of healthy mice (174 +/- 5 microm and 37 +/- 6 microm, respectively) (P<.001). In 6-week-old mice, microscopic findings revealed a decreased number of nuclei in the outer nuclear layer, and SRT and ORT (136 +/- 2 microm and 20 +/- 1 microm, respectively) were shorter than those of 2-week-old rds mice (P<.001). The SRT of 60-week-old rds mice without a photoreceptor layer was remarkably reduced (120 +/- 7 microm), and no ORT could be measured. CONCLUSION: Our findings suggest a possible relationship between SRT and ORT, as measured by OCT, and histologic change in retinal degenerative diseases. CLINICAL RELEVANCE: The quantitative analysis obtained by OCT scans may have potential to detect progressive change in degenerative retina and may be used in studying human retinal degeneration.

Animals↗

Generalized-ensemble algorithms for molecular simulations of biopolymers.

In complex systems with many degrees of freedom such as peptides and proteins, there exists a huge number of local-minimum-energy states. Conventional simulations in the canonical ensemble are of little use, because they tend to get trapped in states of these energy local minima. A simulation in generalized ensemble performs a random walk in potential energy space and can overcome this difficulty. From only one simulation run, one can obtain canonical-ensemble averages of physical quantities as functions of temperature by the single-histogram and/or multiple-histogram reweighting techniques. In this article we review uses of the generalized-ensemble algorithms in biomolecular systems. Three well-known methods, namely, multicanonical algorithm, simulated tempering, and replica-exchange method, are described first. Both Monte Carlo and molecular dynamics versions of the algorithms are given. We then present three new generalized-ensemble algorithms that combine the merits of the above methods. The effectiveness of the methods for molecular simulations in the protein folding problem is tested with short peptide systems.

Algorithms↗

Effect of organic solvent, electrolyte salt and a loading of cellulose tris (3,5-dichlorophenyl-carbamate) on silica gel on enantioseparation characteristics in capillary electrochromatography.

The effect of the amount of the chiral selector, cellulose tris(3,5-dichlorophenylcarbamate) (CDCPC) on the separation characteristics of enantiomers of some charged and neutral analytes was studied in capillary electrochromatography (CEC). For better understanding of the effect of the loading of the chiral selector on the particles and pore size of the packing material, laser-beam particle size analyzer and scanning electron microscopy (SEM) were used. As shown in this study, CDCPC can be used for CEC enantioseparations of a wide range of chiral charged and neutral analytes with high efficiency. The loading of the polysaccharide derivative on the surface of silica materials even in high amounts does not markedly affect the particle size and porous structure of the packing material. The separation characteristics are strongly affected by the loading of CDCPC onto silica gel in both CEC and capillary liquid chromatography (CLC).

Anions↗

Stereocontrol in radical polymerization.

The stereospecific radical polymerization of vinyl esters, methacrylates, and alpha-substituted acrylates was studied. Fluoroalcohols, as a solvent, have remarkable effects on the stereoregularity of the radical polymerizations of vinyl acetate, vinyl pivalate, and vinyl benzoate, affording polymers rich in syndiotacticity, heterotacticity, and isotacticity, respectively. This method was successfully applied to the polymerization of methacrylates to give syndiotactic polymers. The steric repulsion between the entering monomer and the chain-end monomeric unit bound by the solvent through hydrogen bonding is important for the stereochemical control in these systems. Lewis acid catalysts, such as lanthanide trifluoromethanesulfonates and zinc salts, were also effective for the stereocontrol during the radical polymerization of methyl methacrylate, to reduce the syndiotacticity and alpha-(alkoxymethyl)acrylates to synthesize isotactic and syndiotactic polymers. Radical polymerization of the methacrylates bearing a bulky ester group, such as the triphenylmethyl methacrylate derivatives, gave highly isotactic polymers, as in the case of anionic polymerization. In addition, the control of one-handed helical conformation was attained in the radical polymerization of 1-phenyldibenzosuberyl methacrylate using chiral neomenthanethiol or cobalt(II) complexes as an additive.

Journal Article↗

A novel missense mutation in human lactate dehydrogenase B-subunit gene.

Reduced activity of serum lactate dehydrogenase (LDH; EC 1.1.1.27) was found in a male medical student during practical examinations of his own blood. Serum LDH isoenzyme pattern showed reductions in activities of the isoenzymes with lower subunit A/B ratios such as LDH1 and LDH2. These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting. Polymerase chain reaction (PCR)-based DNA sequence analysis of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B subunit gene that resulted in a glycine to glutamic acid substitution (G69E). The mutation was confirmed by PCR-restriction fragment length polymorphism (RFLP) analysis using a mismatched primer to introduce a new NcoI restriction site. The same heterozygous mutation was found in his mother but not in other family members. This mutation involves a residue belonging to alphaC helix in LDH-B subunit protein molecule that functions as an interface for other subunits.

Adult↗

A case of adenoid cystic carcinoma (ACC) of the breast and review of the utility of preoperative imaging diagnose.

A case of adenoid cystic carcinoma (ACC) of the breast in a 66-year-old woman is reported herein. ACC accounts for about 0.1% of all breast cancers. Our patient presented with a small, elastic and hard mass, measuring 2.0x2.0 cm, between both outer quadrants of the right breast. Although physical examination, ultrasonography and magnetic resonance (MR) mammography suggested a benign tumor, aspiration biopsy cytology (ABC) was performed twice, and the second ABC specimen was evaluated as suspicious for breast carcinoma. Breast conserving surgery with a level II lymph node dissection was subsequently performed. There was no lymph node metastases and estrogen receptor (ER) status was negative. Light microscopy revealed various growth patterns, with the cells showing biphasic cellularity. According to immunohistochemical analyses, CEA, actin and vimentin were positive, S-100 protein was negative, and the cytokeratin reaction was partially positive. Therefore, ACC of the breast was diagnosed. Although ACC of the breast is a rare neoplasm, it should be considered in the differential diagnosis even if various diagnostic imaging studies suggest a benign tumor of the breast. Awareness of this tumor will help prevent misdiagnosis.

Actins↗

Failure of endothelin-1 to activate store-operated Ca2+ channels by lack of mobilization from intracellular Ca2+ stores in cultured bovine adrenal chromaffin cells.

We have recently shown that in addition to L-type voltage-operated Ca2+ channel (VOC), endothelin-1 (ET-1) stimulation opens two types of Ca2+-permeable nonselective cation channels [designated nonselective cation channel-1 (NSCC-1) and NSCC-2]. However, in this Ca2+ entry, the involvement of store-operated Ca2+ channel (SOCC), which is suggested to exist in chromaffin cells, was unclear. Those NSCCs as well as SOCC can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. To clarify whether SOCC should actually exist and play a role in Ca2+ entry in chromaffin cells stimulated with ET-1, we examined the effects of removal of extracellular Ca2+, thapsigargin (TG, an inhibitor of endoplasmic reticulum Ca2+-ATPase), LOE 908 and SK&F 96365 on cytosolic free Ca2+ concentrations ([Ca2+]i) in cultured bovine adrenal chromaffin cells. After the cells were exposed to Ca2+-free medium followed by exposure to TG to deplete Ca2+ from the intracellular Ca2+ store, restoration of extracellular Ca2+ caused a gradual increase in [Ca2+]i (to about 200% of control). The increase was unaffected by LOE 908, but completely abolished by SK&F 96365. In the Ca2+-free medium, no increase in [Ca2+]i by ET-1 was observed, but the subsequent restoration of extracellular Ca2+ induced a rapid increase in [Ca2+]i (to the same level of [Ca2+]i as that evoked by ET-1 in the normal medium (1.0 mM Ca2+)). Since SK&F 96365 is also a blocker of SOCC, these results indicate that in bovine adrenal chromaffin cells, Ca2+ entry through SOCC (Ca2+ influx through the capacitative Ca2+ entry system) occurs but is comparably weak, and that it virtually does not work on the stimulation of ET-1.

Acetamides↗

Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain.

RATIONALE: Lithium is the most widely prescribed mood stabilizer, but the precise mechanism of lithium is unresolved. OBJECTIVE: We examine the effects of the administration of therapeutically relevant concentrations of lithium on the expression of brain-derived neurotrophic factor (BDNF) and its receptor, Trk B, as well as glia-derived neurotrophic factor (GDNF) and its receptors, RET and GDNFR-alpha, in the rat brain. In addition, we also examined the effect of another well-prescribed mood stabilizer, valproate, on the expression of BDNF and GDNF. METHODS: Rats were kept on a 0.2% lithium carbonate-containing diet for 1, 7, 14, or 28 days or treated with valproate (400 mg/kg per day i.p.) for 1 or 14 days. After the brains were rapidly removed, the levels of BDNF, GDNF, and their receptors were measured by ELISA or western blot analysis. RESULTS: Chronic lithium treatment for 14 and 28 days significantly increased the expression of BDNF in the hippocampus and temporal cortex. In addition, chronic lithium treatment for 14 days significantly increased the expression of BDNF in the frontal cortex. In contrast, acute or chronic dietary lithium treatment did not alter GDNF expression in these brain regions. In addition, acute or chronic lithium treatments did not change the levels of Trk B, RET, or GDNFR-alpha immunoreactivity. As well as lithium, repeated administration of valproate also increased the expression of BDNF in the frontal cortex and hippocampus. CONCLUSIONS: Our results suggest that the chronic administration of mood stabilizers may produce a neurotrophic effect mediated by the upregulation of BDNF in the rat brain.

Administration, Oral↗

Ritodrine-induced skin rash.

A 32-year-old nulligravida was hospitalized because of preterm labor and treated with intravenous ritodrine hydrochloride. After 33 days of therapy, the patient developed a fine maculopapular rash.

Adrenergic beta-Agonists↗

Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction.

Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha-myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function.

Activating Transcription Factor 3↗

Progesterone inhibits transcriptional activation of human chorionic gonadotropin-alpha gene through protein kinase A pathway in trophoblast cells.

The purpose of this study was to analyze the mechanism of transcriptional inhibition of human chorionic gonadotropin-alpha (hCGalpha) gene by progesterone in trophoblast cells. We stably transfected -290 bp hCGalpha promoter-CAT constructs (-290halphaCAT) into Rcho-1 cells and monitored the promoter activities. Differentiation-dependent activation of -290 bp hCGalpha promoter containing a tandem repeat of cAMP response element (CRE) was inhibited by progesterone in a dose-dependent manner. To further analyze the mechanism of the progesterone action, Rcho-1 cells stably transfected with -290halphaCAT were treated with forskolin in the presence of progesterone. Progesterone inhibited forskolin-induced transcriptional activation of hCGalpha gene. Moreover, progesterone inhibited forskolin-induced transcriptional activation of CRE-CRE-tk-CAT. These results suggest that progesterone may inhibit cAMP-induced transcriptional activation of hCGalpha gene through CRE. Although progesterone did not alter the amount of CRE-binding protein (CREB), which is a main transcriptional factor bound to CRE(s) on hCGalpha promoter, progesterone abolished forskolin-induced CREB phosphorylation. In addition, pretreatment with progesterone abolished forskolin-induced activation of nuclear protein kinase A (PKA). In conclusion, progesterone inhibits hCGalpha gene transcription, at least in part, via the CRE region by inhibiting CREB phosphorylation through PKA pathway in trophoblast cells.

Blotting, Western↗

Fosfomycin nebulizer therapy to chronic sinusitis.

OBJECTIVE: effects of Fosfomycin (FOM) nebulizer therapy were studied in patients with chronic sinusitis. METHODS: about 28 patients with chronic sinusitis were administered 2 ml of FOM sodium (3% w/v) by nebulizer three times per week for 4 weeks. Levels of IL-1 beta, IL-6, IL-8, and TNF-alpha in nasal lavage were also measured before and at the end of treatment. RESULTS: the overall efficacy of this treatment on the basis of both subjective and objective symptoms, was 'excellent' for 28.6%, 'good' for 10.7%, 'fair' for 39.4%, and yield 'no change' for 21.4% of the patients. Both IL-1 beta and IL-6 concentrations were significantly decreased after treatment. Although the IL-8 level did not significantly decrease, it seems to be related to the overall efficacy. TNF-alpha was not detected in all of the samples. CONCLUSION: FOM nebulization therapy is highly effective in treatment for chronic sinusitis, and efficacy may be due to an immunomodulatory mechanism, as well as its bactericidal effect.

Adolescent↗

Plasma levels of amino acids and hypermetabolism in patients with chronic obstructive pulmonary disease.

Plasma levels of amino acids were measured by ion-exchange, high-pressure liquid chromatography in 30 ambulatory patients with chronic obstructive pulmonary disease (COPD; mean +/- SD: age 64 +/- 13 y and forced expiratory volume in 1 s [FEV1] 0.85 +/- 0.25 L) and 30 age- and sex-matched healthy control subjects with regard to nutritional status, resting energy expenditure (REE), and pulmonary function. The ratio of branched-chain amino acids to aromatic amino acids was significantly (P < 0.001) decreased in COPD patients and was significantly correlated with percentage of ideal body weight (r = 0.403, P < 0.05), percentage of arm-muscle circumference (r = 0.492, P < 0.01), and %FEV1 (r = 0.467, P < 0.05). Plasma levels of alanine and cysteine were decreased, whereas levels of glutamine, aspartic acid, serine, and ornithine were elevated in COPD patients as opposed to control subjects. The ratio of resting energy expenditure to predicted resting energy expenditure was negatively correlated with the ratio of branched-chain to aromatic amino acids (r = -0.716, P < 0.01), percentage of arm-muscle circumference (r = -0.770, P < 0.05), %FEV1 (r = -0.839, P < 0.01), and the maximal inspiratory pressure (r = -0.803, P < 0.001). Underweight COPD patients also exhibited a greater degree of hyperinflation (percentage of residual volume = 205 +/- 15 for underweight patients and 156 +/- 8 for normal-weight patients). In conclusion, a decrease in plasma levels of branched-chain amino acids in relation to hypermetabolism, possibly resulting from the severity of COPD and respiratory muscle weakness, and various disturbances in plasma amino-acid levels were found in underweight COPD patients.

Aged↗