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Biomedical subjects

H Tomoda

Publications and source records attributed to H Tomoda.

At least 37 records · Page 2Linked to original sources

The effect of spatial frequency on chromatic and achromatic steady-state visual evoked potentials.

OBJECTIVE: Little is known about the physiological properties of the major components of steady-state visual evoked potentials (VEPs). Based on the hypothesis that isoluminant color and high contrast pattern differentially activate the parvo- and magnocellular pathways, we studied difference in spatial frequency function between chromatic and achromatic VEPs to sinusoidal gratings. METHODS: Steady-state VEPs to isoluminant chromatic (red-green) and high contrast (90%) achromatic (black-white) sinusoidal gratings with nine spatial frequencies (0.5 to 8.0 cycles/degrees (cpd)) at 4 Hz (8 reversals/s) were recorded in 13 normal subjects. VEPs were Fourier analyzed to obtain phase and amplitude of the second (2F) and fourth (4F) harmonic responses. RESULTS: The 2F amplitude of chromatic VEPs decreased above 4.0 cpd in a low-pass function while that of achromatic VEPs showed a band-pass function with a peak at 4.0 cpd. The 4F amplitude of chromatic VEPs was not affected significantly by spatial frequency whereas that of achromatic VEPs exhibited a high-pass function. The phases of 2F and 4F showed a non-monotonic function of spatial frequency in both chromatic and achromatic stimuli with peaks at middle spatial frequencies. CONCLUSION: Chromatic and achromatic visual stimuli differently affected 2F and 4F components, which thus suggests that 2F and 4F components are generated from different neuronal subgroups largely in the parvocellular pathway.

Adolescent↗

Complete inhibition of mouse macrophage-derived foam cell formation by triacsin C.

Primary mouse peritoneal macrophages effectively take up and metabolize phosphatidylcholine/cholesterol liposomes containing a small amount of phosphatidylserine, which results in the massive accumulation in the cytoplasm of oil red O positive lipid droplets consisting of cholesteryl ester (CE) and triacylglycerol (TG) [Nishikawa et al. (1990) J. Biol. Chem. 265, 5226-5231]. A number of inhibitors of CE synthesis have been reported, but their effects on the lipid droplet formation have not been fully examined. Furthermore, the contribution of TG synthesis to lipid droplet formation has been poorly investigated. We have investigated the relationship between CE and TG syntheses and cytosolic lipid droplet formation in macrophages cultured in the presence of inhibitors with different modes of action. When macrophages were cultured with liposomes and [14C]oleic acid in the presence of triacsin C, a potent inhibitor of long chain acyl-CoA synthetase, both [14C]CE and [14C]TG syntheses were inhibited to similar extents with IC50 values of 0.19 and 0.10 microM, respectively. On the other hand, pregnenolone, a well-known inhibitor of cellular cholesterol transport, and CL-283,546, a potent inhibitor of acyl-CoA:cholesterol acyltransferase, inhibited [14C]CE synthesis specifically with IC50 values of 5.0 and 0.038 microM, respectively. Microscopic observation revealed that the inhibitors of cholesterol metabolism produce only a partial decrease in cytosolic lipid droplets even at the highest doses which cause almost complete inhibition of [14C]CE synthesis. However, the triacsin C-dose dependent inhibition of lipid droplet formation was almost complete at 0.59 microM, a concentration that inhibits [14C]CE and [14C]TG syntheses by about 90%. These results show that inhibiton of acyl-CoA synthetase by triacsin C causes a decrease in the cellular levels of acyl-CoA, the common substrate for CE and TG syntheses, leading to an inhibiton of neutral lipid synthesis and eventually to the complete disappearance of cytosolic lipid droplets from macrophages. These findings suggest that TG synthesis, as well as CE synthesis, is responsible for macrophage-derived foam cell formation, and is therefore a potential target for new antiatherosclerotic agents.

Animals↗

Prediction of coronary artery lesions in unstable angina by iodine 123 beta-methyl iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, single photon emission computed tomography at rest.

Iodine 123 beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP), a beta-methyl-branched fatty acid analogue, has been proven by experimental studies to reveal abnormalities in fatty-acid-related metabolism. This study was undertaken to validate the accuracy and limitations of 123I-BMIPP imaging at rest in detecting myocardial metabolic abnormalities and predicting coronary lesions in unstable angina (UA). One hundred UA patients without prior myocardial infarction were studied. 123I-BMIPP and thallium 201 chloride (201TlCl) imaging with single photon emission computed tomography (SPECT) and coronary and left ventricular cineangiography (LVC) were performed 1 week after the last episode of angina. There was reduced uptake of 123I-BMIPP imaging in 70 patients, reduced uptake of 201TlCl in 41, and abnormal LVC contraction in 49 patients. There were significant increases in severity scores of 123I-BMIPP imaging along with increases in the number of stenosed coronary arteries and the severity of stenosis in individual coronary arteries. There was a significant reduction in 123I-BMIPP severity scores 1 month after percutaneous transluminal coronary angioplasty (p < 0.01) and a significant correlation between the severity scores of 123I-BMIPP and LVC (r=0. 579, p<0.001). Overall rates of sensitivity and specificity in detecting significant coronary stenosis by 123I-BMIPP imaging were 74% and 86%, respectively, whereas rates of sensitivity and specificity in detecting significant coronary stenosis by 201TlCl were 31% and 91%, respectively. 123I-BMIPP sensitivity increases to 86% if only advanced coronary stenosis of >90% is included. In conclusion, 123I-BMIPP myocardial imaging is an effective method of predicting coronary artery lesions of UA patients without provocative test.

Adult↗

Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979.

Beauveria sp. FO-6979, a soil isolate, was found to produce inhibitors of lipid droplet formation in mouse peritoneal macrophages. A new compound beauveriolide III was isolated along with a known compound beauveriolide I from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Beauveriolides I and III caused a reduction in the number and size of cytosolic lipid droplets in macrophages at 10 microM without any cytotoxic effect on macrophages.

Animals↗

Ferroverdins, inhibitors of cholesteryl ester transfer protein produced by Streptomyces sp. WK-5344. I. Production, isolation and biological properties.

Streptomyces sp. WK-5344, a soil isolate, was found to produce structurally related inhibitors of cholesteryl ester transfer protein (CETP). New active compounds, designated ferroverdins B and C, were isolated along with known ferroverdin A from the fermentation broth by solvent extraction, ODS column chromatography and silica gel column chromatography. All ferroverdins showed a dose-dependent inhibitory activity against human CETP. The IC50 values were 21, 0.62 and 2.2 microM for ferroverdins A, B and C, respectively, indicating that ferroverdin B is one of the most potent CETP inhibitors of microbial origin.

Bacteria↗

Ferroverdins, inhibitors of cholesteryl ester transfer protein produced by Streptomyces sp. WK-5344. II. Structure elucidation.

The structures of ferroverdins B and C, novel inhibitors of cholesteryl ester transfer protein, were elucidated by spectroscopic studies including various NMR measurements. They are the complex between one Fe2+ and three ligands, that is, two common p-vinylphenyl-3-nitroso-4-hydroxybenzoates and one hydroxy p-vinylphenyl-3-nitroso-4-hydroxybenzoate for ferroverdin B and one carboxylic acid p-vinylphenyl-3-nitroso-4-hydroxybenzoate for ferroverdin C.

Carrier Proteins↗

Structure-specific inhibition of cholesteryl ester transfer protein by azaphilones.

The effect of thirteen different fungal azaphilones, which have a common 6-iso-chromane-like ring, was tested on cholesteryl ester transfer protein (CETP) activity in vitro. Chaetoviridin B showed the most potent inhibitory activity with an IC50 value of < 6.2 microM, followed by sclerotiorin with an IC50 value of 19.4 microM. Rotiorin, chaetoviridin A and rubrorotiorin had moderate inhibitory activity (IC50 ; 30 approximately 40 microM), but others showed very weak or no inhibitory activity. The relationship between the structures and their inhibitory activity indicated that the presence of an electrophilic ketone(s) and/or enone(s) at both C-6 and C-8 positions in the isochromane-like ring is essential for eliciting CETP inhibitory activity. The transfer activity of both CE and TG was inhibited by sclerotiorin to approximately the same extent (IC50: 14.4 and 10.3 microM, respectively). A model of the reaction suggested that sclerotiorin reacts with a primary amine of amino acids such as lysine in the protein to form a covalent bond.

Animals↗

Zelkovamycin, a new cyclic peptide antibiotic from Streptomyces sp. K96-0670. II. Structure elucidation.

The structure of antibiotic zelkovamycin was elucidated as a cyclic peptide comprising glycyl, 2-aminobutanoyl, 2-amino-2-butenoyl, N-methyl glycyl, alanyl, 1,3-thiazoyl, 7-methoxytryptophanyl and 2-methyldehydrothreonyl residues. The sequence of the amino acids was established by spectroscopic studies including 1H-1H COSY, 13C-1H COSY, 13C-1H HMQC, 13C-1H HMBC, 15N-1H HMQC and 15N-1H HMBC NMR experiments.

Anti-Bacterial Agents↗

Roselipins, inhibitors of diacylglycerol acyltransferase, produced by Gliocladium roseum KF-1040.

Gliocladium roseum KF-1040, a marine isolate, was found to produce a series of new inhibitors of diacylglycerol acyltransferase (DGAT). Four active compounds, designated roselipins 1A, 1B, 2A and 2B, were isolated from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography and preparative HPLC. The highest production of roselipins was observed when cultured in the medium containing natural sea water. Roselipins inhibit DGAT activity with IC50 values of 15 approximately 22 microM in an enzyme assay system using rat liver microsomes.

Acyltransferases↗

Structure elucidation of roselipins, inhibitors of diacylglycerol acyltransferase produced by Gliocladium roseum KF-1040.

The structures of roselipins 1A, 1B, 2A and 2B were elucidated by spectroscopic studies including 1H-1H COSY, 13C-1H COSY, 13C-1H HMQC and 13C-1H HMBC NMR experiments, and degradation experiments. They have the common skeleton of 2,4,6,8,10,12,14,16,18-nonamethyl-5,9,13-trihydroxy-2E,6E, 10E-icosenoic acid modified with a D-mannose and a D-arabinitol. Roselipin A and B groups were stereoisomers at the arabinitol moiety, which esterified the fatty acid from the different terminal hydroxy residue. Roselipin 2 group was 6"-O-acetyl roselipin 1 group.

Acyltransferases↗

Phenochalasins, inhibitors of lipid droplet formation in mouse macrophages, produced by Phomopsis sp. FT-0211.

Phomopsis sp. FT-0211, a soil isolate, was found to produce inhibitors of lipid droplet formation in mouse peritoneal macrophages. Structurally related new compounds designated phenochalasins A and B were isolated from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography and preparative HPLC. Phenochalasin A caused a dose-dependent reduction in the number and size of lipid droplets in macrophages without any cytotoxic effect at least up to 20 microm. On the other hand, phenochalasin B showed inhibition of lipid droplet formation with a severe cytotoxic effect on macrophages.

Animals↗

Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma.

BACKGROUND: Smoking and alcoholic beverage drinking habits as well as a family history of cancer are well known risk factors for the multifocal occurrence of squamous cell carcinoma of the esophagus and the head and neck region. However, the role of these risk factors in multiple gastric carcinoma remains to be clarified. The purpose of this study was to examine the risk factors for multiple gastric carcinoma. METHODS: The smoking and drinking habits as well as the family history of 157 patients with synchronous multiple gastric carcinoma and 157 patients with solitary gastric carcinoma who were similar with regard to gender, age, stage of the tumor, and year of admission were investigated. The risk of a multiple occurrence of gastric carcinoma also was elevated using the odds ratio (OR). RESULTS: The ORs of a multifocal occurrence of gastric carcinoma in patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8, respectively, although the ORs were not related to the quantity of smoking or drinking. In patients with a close relative with gastric carcinoma the OR was 2.1 (95% confidence interval [CI], 1.3-3.7). In those patients with > or =2 close relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1). Conversely, no significant elevation in the ORs was recognized regarding a family history of other cancers. CONCLUSIONS: In this study, a family history of gastric carcinoma was found to be clearly associated with the multifocal occurrence of gastric carcinoma; however, no significant correlation between the multifocal occurrence of gastric carcinoma in these patients and their smoking and drinking habits was recognized.

Alcohol Drinking↗