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Biomedical subjects

T Egawa

Publications and source records attributed to T Egawa.

At least 37 records · Page 2Linked to original sources
PubMed1997

Rolipram and its optical isomers, phosphodiesterase 4 inhibitors, attenuated the scopolamine-induced impairments of learning and memory in rats.

We investigated the effects of (+/-)-rolipram, a phosphodiesterase (PDE) 4 inhibitor, and its isomers on scopolamine-induced deficits of learning and memory in rats using an 8-arm radial maze task and a passive avoidance task. 1) In the 8-arm radial maze task, (+/-)-rolipram (0.02-0.2 mg/kg, p.o.), (-)-rolipram (0.01-0.02 and 0.2-0.5 mg/kg, p.o.) and (+)-rolipram (20-50 mg/kg, p.o.) attenuated the scopolamine-induced deficits of spatial cognition. As for the minimum effective dose of each drug, (-)-rolipram was 2 and 2000 times as potent as (+/-)-rolipram and (+)-rolipram, respectively. (-)-Rolipram produced a biphasic dose-response and (+/-)-rolipram produced a broad dose-response. 2) (+/-)-Rolipram and its isomers also attenuated the scopolamine-induced deficits in the passive avoidance response. Also for the minimum effective dose, (-)-rolipram (0.01-0.02 mg/kg) was 2 and 200 times as potent as (+/-)-rolipram (0.02-0.1 mg/kg) and (+)-rolipram (2mg/kg). 3) The behaviorally effective doses of (+/-)-rolipram and its isomers also enhanced the oxotremorine-induced tremors in mice. Comparing these racemic isomers, (-)- and (+/-)-rolipram have more potent effects than (+)-rolipram on scopolamine-induced deficits in the 8-arm radial maze task and passive avoidance task. Especially (+/-)-rolipram has a wide dose range in these behavioral study. These results suggest that the ameliorating effects of rolipram might result from the indirect potentiation of various transmitters including cholinergic and noradrenergic systems by an increase in cAMP with the inhibition of PDE4.

Animals↗
PubMed1995

Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver.

Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min per gram of liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 microM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity. The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cell which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 microM) or a cGMP analogue 8-bromo-cGMP (1 microM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.

Animals↗
PubMed1995

5-HT1A-receptor subtype mediates the effect of fluvoxamine, a selective serotonin reuptake inhibitor, on marble-burying behavior in mice.

The effect of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, was studied in a model of anxiety and/or obsessive compulsive disorder (OCD) in mice. In the anxiety/OCD model, marble-burying behavior, marble-burying was significantly suppressed by fluvoxamine at 30 and 60 mg/kg, p.o. and the monoamine reuptake inhibitor clomipramine, at 60 mg/kg, p.o. No suppressive effect, however, was observed by the selective norepinephrine reuptake inhibitor desipramine at doses from 15 to 60 mg/kg, p.o. Suppressive effects were obtained by the serotonergic anxiolytic buspirone at 30 and 60 mg/kg, p.o. and the benzodiazepine anxiolytic diazepam at 10 mg/kg, p.o. The effect of fluvoxamine on marble-burying was slightly attenuated after repeated administration. On the other hand, both the effects of buspirone and diazepam completely disappeared after repeated administration. Effect of fluvoxamine on the marble-burying was unaffected by the 5-HT2 antagonist ritanserin. However, the 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine) inhibited the suppressive effect of fluvoxamine on the marble-burying. From these results, the 5-HT1A-receptor subtype may be involved in the suppressive effect of fluvoxamine on the marble-burying, but the 5-HT2-receptor subtype is not involved in this effect.

Analysis of Variance↗
PubMed1995

Neither the 5-HT1A- nor the 5-HT2-receptor subtype mediates the effect of fluvoxamine, a selective serotonin reuptake inhibitor, on forced-swimming-induced immobility in mice.

The effect of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, was studied in the forced-swimming test, a model of depression, in mice. Fluvoxamine at 60 mg/kg, p.o. significantly decreased the immobility time in the forced-swimming test. A similar effect was observed by the selective norepinephrine reuptake inhibitor desipramine at the same dose. Furthermore, the suppression of immobility time was slightly potentiated by repeated administration of fluvoxamine, and a significant effect was observed at 30 mg/kg, p.o. The effect of fluvoxamine on forced-swimming was unaffected by the 5-HT2 antagonist ritanserin. On the other hand, the 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine) potentiated the effect of fluvoxamine on forced-swimming. It is expected, however, that a 5-HT1A antagonist should antagonize the effect of fluvoxamine when 5-HT1A mediates the suppressive effect of fluvoxamine on the immobility time in forced-swimming. From these results, neither the 5-HT1A- nor the 5-HT2-receptor subtype is involved in the suppressive effect of fluvoxamine on the immobility associated with forced-swimming.

Analysis of Variance↗
PubMed1994

Evidence for compound I formation in the reaction of cytochrome P450cam with m-chloroperbenzoic acid.

During the reaction of m-chloroperbenzoate with low spin ferric form of cytochrome P450cam, the formation of at least four transient intermediates was detected by employing rapid scan absorption spectrometry. Among them, the first one which appeared within 10 msec after the start of reaction gave an absorption spectrum indistinguishable from that of compound I of chloroperoxidase, another thiolate-heme protein. The intermediate exhibited the major absorption maxima at 367 and 694 nm, while chloroperoxidase compound I is known to have the maxima at 367 and 688 nm. The shapes of the bands at 367 nm were very similar to each other. Based on these spectral similarities, we suggest that the intermediate found in this study is the compound I of cytochrome P450cam.

Camphor 5-Monooxygenase↗
PubMed1993

Roles of proximal ligand in heme proteins: replacement of proximal histidine of human myoglobin with cysteine and tyrosine by site-directed mutagenesis as models for P-450, chloroperoxidase, and catalase.

Histidine-93(F8) in human myoglobin (Mb), which is the proximal ligand of the heme iron, has been replaced with cysteine or tyrosine by site-directed mutagenesis. The resultant proximal cysteine and tyrosine mutant Mbs (H93C and H93Y Mbs, respectively) exhibit the altered axial ligation analogous to P-450, chloroperoxidase, and catalase. Coordination of cysteine or tyrosine to the ferric heme iron is confirmed by spectroscopic measurements including electronic absorption, hyperfine-shifted 1H-NMR, EPR, resonance Raman spectroscopies, and redox potential measurements of ferric/ferrous couple. H93C Mb is five-coordinate ferric high-spin with the proximal cysteine. H93Y Mb bearing the proximal tyrosine ligated to the iron is also in a ferric high-spin, five-coordinate state. The reactions of the mutants with cumene hydroperoxide show that the thiolate ligand enhances heterolytic O-O bond cleavage of the oxidant, while the phenolate ligand hardly affects the heterolysis/homolysis ratio for O-O bond scission in comparison with wild-type Mb. Monooxygenase activities such as epoxidation of styrene and N-demethylation of N,N-dimethylaniline, and catalase activity (dismutation of hydrogen peroxide) by wild-type Mb and the mutants, are examined by using H2O2. The increase of the catalytic activities by the mutation was, at most, 5-fold in the epoxidation reaction.

Benzene Derivatives↗
PubMed1992

Observation of the FeIV=O stretching Raman band for a thiolate-ligated heme protein. Compound I of chloroperoxidase.

The FeIV=O stretching vibration has never been identified for a cysteine-coordinated heme enzyme. In this study, resonance Raman and visible absorption spectra were observed simultaneously for transient species in the catalytic reaction of chloroperoxidase with hydrogen peroxide by using our original apparatus for mixed-flow and Raman/absorption simultaneous measurements. For the first intermediate, the FeIV=O stretching Raman band was observed at 790 cm-1, which shifted to 756 cm-1 with the 18O derivative, but the v4 band was too weak to be identified. This suggested the formation of an oxoferryl porphyrin pi cation radical. The second intermediate gave an intense v4 band at 1,372 cm-1 but no oxygen isotope-sensitive Raman band, suggesting oxygen exchange with bulk water.

Chloride Peroxidase↗
PubMed1992

Hormonal regulation of vitamin D-binding protein production by a human hepatoma cell line.

Regulation of vitamin D-binding protein production by various hormones was studied in an established human hepatoma cell line, HuH-7. Among all the hormones studied, the maximal production of the binding protein was obtained by an extra-cellular addition of triamcinolone or epidermal growth factor. Cell numbers were not so changed except for the addition of insulin or glucagon. Our data indicate that the protein production may be regulated by insulin, estradiol, triamcinolone, dihydrotestosterone or epidermal growth factor.

Carcinoma, Hepatocellular↗
PubMed1991

Observation of the O-O stretching Raman band for cytochrome P-450cam under catalytic conditions.

Dioxygen stretching (voo) Raman band was observed for the oxy form of Pseudomonas putida cytochrome P-450 (P-450cam) generated at room temperature under catalytic conditions, that is, in the presence of D-camphor, beta-NADH, putidaredoxin, and putidaredoxin reductase, by using the mixed flow transient Raman apparatus. At the same time the visible absorption spectra were monitored for the transient species. It was found that the voo frequency is little altered by binding of putidaredoxin to P-450cam, although the reduction rate of the oxy form becomes faster. Another intermediate with an oxygen isotope-sensitive band was not found in a time region until 2 s after mixing of the reduced enzyme with oxygen.

Camphor 5-Monooxygenase↗
PubMed1991

Interaction of vitamin D-binding protein with immobilized cibacron blue F3-GA.

An interaction of vitamin D-binding protein to immobilized Cibacron Blue F3-GA was studied under urea containing buffers. In these buffers, this protein was adsorbed to the immobilized dye and was eluted with salt gradients as in the same buffer without urea. The protein was also adsorbed to immobilized diethylaminoethyl but not to immobilized carboxymethyl. It is implicated that a combination of pseudo-ligand affinity and/or hydrogen bonding interaction plays a large role whereas ionic, hydrophobic and lipophilic interactions act little between the protein and the immobilized blue dye.

Buffers↗
PubMed1991

Macular lesions predisposing to senile disciform macular degeneration.

Senile disciform macular degeneration (SMD) is a neovascular/exudative form of age-related macular degeneration (AMD). In this study 340 eyes were followed up to assess the progression of SMD. The 340 eyes consisted of two groups. Group 1 was composed of 157 eyes with age-related macular changes other than choroidal neovascular membrane. Group 2 was made up of the contralateral eyes of 183 unilateral SMD eyes. Average ages were 61 and 64 in groups 1 and 2, respectively, and respective follow-up periods were 44 and 52 months. Choroidal neovascular membrane developed in 12 eyes in group 1 (7.6%) and in 19 eyes in group 2 (10.4%), a total of 31 eyes (9.1%). Retinal pigment epithelium (RPE) detachment was found as a predisposing lesion in 25 of these 31 eyes. Choroidal neovascular membrane developed in 12 of the 24 eyes with large RPE detachments. In 3 eyes neovascular membrane developed from an RPE detachment which had evolved from soft drusen. There were 3 eyes among the 62 eyes with soft drusen in which neovascular membrane developed directly from soft drusen. Based on these results, we classified AMD into 3 types; 1) atrophic, 2) predisciform, which includes RPE detachment and soft drusen, and 3) SMD.

Aged↗
PubMed1991

Leiomyoma of the duodenum--a case report.

A 36-year-old man with anemia due to gastrointestinal bleeding, diagnosed to have a leiomyoma of the duodenum, is described. The conventional barium meal study and gastroendoscopy were useful for diagnosing the lesion. More invasive radiological methods, such as abdominal angiography and technetium-99m scintigraphy failed to detect the tumor. Early diagnosis and resection of the tumor would result in a good prognosis.

Adult↗
PubMed1990

Resonance Raman study on mutant cytochrome P-450 obtained by site-directed mutagenesis.

Resonance Raman spectra were observed for the threonine-301 to serine or valine mutant as well as the wild type of rabbit liver microsomal cytochrome P-450 [laurate(omega-1)-hydroxylase] (P-450(omega-1], which were prepared through site-directed mutagenesis. The high-spin marker resonance Raman (RR) bands became similarly stronger for all the P-450s examined in the oxidized form upon addition of laurate, and the RR spectra in the higher frequency region of the oxidized, reduced and CO-adduct forms did not distinctly differ among the P-450s examined. Nevertheless, the Fe-CO stretching mode (vFe-CO) of the CO adduct exhibited an upshift for the valine mutant, suggesting positional proximity of Thr-301 to bound CO like Thr-252 of P-450cam, in agreement with the expectation from the sequence analysis. The vFe-CO band was shifted to higher frequency upon binding of normal alkyl fatty acids with C10 or longer alkyl chain but little affected by binding of shorter fatty acids.

Animals↗
PubMed1990

Human pulmonary infection with Corynebacterium equi.

A 28 year old man with no underlying disease developed a cavity and multiple nodules in the lung from which Corynebacterium equi was isolated. He experimented with organic solvents and microorganisms including Corynebacterium species for several years. Computed tomography of his pulmonary lesions revealed that these nodules were related to the bronchial tree. Histologically, the lesions were compatible with nonspecific inflammatory changes. The clinician must suspect the pulmonary infections with Corynebacterium species even if the patient has no underlying disease.

Actinomycetales Infections↗
PubMed1989

Partial purification and characterization of human hepatoma-derived growth factor.

A human hepatoma cell line, HuH-7, which was established from a hepatoma tissue removed at surgical operation from an adult Japanese male, grows autonomously in a serum-free chemically defined medium. A human hepatoma-derived growth factor with potent growth-promoting activity, was partially purified from the conditioned medium of HuH-7 cells, using ion-exchange, heparin affinity chromatography and gel filtration. The partially purified growth factor (HuHGF) is acid- and heat-labile, and sensitive to reduction and trypsin digestion. HuHGF, which is of relatively high molecular weight (about 64 kDa) examined by gel filtration, stimulates not only the DNA synthesis of Swiss mouse 3T3 fibroblasts, but also the growth of HuH-7 cells in serum-free chemically defined medium, suggesting that it is produced by and acts on HuH-7 cells as an autocrine growth factor. This putative growth factor may play an important role in the autonomous growth of hepatoma and may lead to useful diagnostic or therapeutic approaches to human hepatoma.

Carcinoma, Hepatocellular↗
PubMed1989

Electric charge distribution in proteins and ionic strength dependence of reaction rate.

The ionic strength dependence of the reaction rate between protein and dichloride anion radical has been investigated by flash photolysis of aqueous chloride-containing lysozyme, ribonuclease A, or insulin. The rate constant for the reaction of lysozyme or ribonuclease A with dichloride anion radicals decreases with increasing ionic strength, while it increases for insulin. The dependence was found to obey an equation derived from the theory of Debye and Hückel or the equation of Wherland and Gray for lysozyme within experimental errors. For ribonuclease A, however, it deviates largely from these equations. In the case of insulin a moderate deviation was observed. The different behavior in the ionic strength dependence is discussed in terms of the electric charge distribution in the protein molecules.

Amino Acid Sequence↗
PubMed1989

Affinity separation of human plasma gelsolin on Affi-Gel Blue.

Human plasma gelsolin was specifically eluted with 1 mM adenosine 5'-triphosphate from an Affi-Gel Blue column. Since the ionic strength of sodium chloride required to elute the protein from the dye column was much higher than that of 1 mM adenosine 5'-triphosphate, the binding of plasma gelsolin with the dye-ligand appeared to be biospecific. Taking advantage of this affinity interaction, we have developed a revised purification method of human plasma gelsolin. The purification included ammonium sulfate precipitation, diethylaminoethyl-Sepharose chromatography, Affi-Gel Blue chromatography, and Phenyl-Sepharose chromatography. The method allowed a reproducible purification of the protein to apparent homogeneity, producing a 331-fold purification with a yield of 6%.

Actins↗