Biomedical subjects

S Okazaki

Publications and source records attributed to S Okazaki.

At least 55 records · Page 3Linked to original sources

PubMed1996

Positive inotropic and chronotropic effects of beraprost sodium, a stable analogue of prostacyclin, in isolated guinea pig myocardium.

1. Inotropic and chronotropic effects of beraprost sodium (beraprost), a chemically stable prostacyclin analogue, were examined in isolated myocardial preparations of guinea pigs. 2. In the left atria, 10(-9) - 10(-7) M beraprost had no significant effect on the contractile force, but 10(-6) and 10(-5) M produced a concentration-dependent positive inotropic response. This effect was antagonized by S-145, a potent and selective thromboxane A2 (TXA2) receptor antagonist, but not by propranolol. 3. Beraprost, from 10(-9) to 10(-5) M, had no significant inotropic effect in the right ventricular papillary muscles. 4. In the right atria, 10(-9) and 10(-8) M beraprost had no significant effect, but 10(-7) - 10(-5) M caused an increase in beating rate; this effect was not affected by S-145. 5. The present study demonstrates that beraprost has positive inotropic and chronotropic effects at high doses on isolated guinea pig atria. The inotropic effect may be mediated by the TXA2 receptor, but some mechanism other than the TXA2 receptor is responsible for the chronotropic effect.

Adrenergic beta-Antagonists↗

PubMed1996

Effects of calcitonin gene-related peptide and interleukin 6 on myoblast differentiation.

Effects of calcitonin gene-related peptide (CGRP) and interleukin 6 (IL-6) on muscle cell differentiation were studied using cultured rat myoblasts (L6 cells). Cell morphology and the amounts of the messenger RNAs (mRNAs) of myogenin and Myf-5, DNA content, creatine kinase (CK) activity, and myoglobin (Mb) content in the cultured cells were examined serially over 10 days of culture. In the presence of CGRP or IL-6, the mRNAs of myogenin and Myf-5 were expressed earlier and at a higher concentration in the treated cells than in the control cells. The ratios of CK activity to DNA content (CK/DNA) and of Mb content to DNA content (Mb/DNA) on day 10 of culture also were greater than in the control cells. Furthermore, the mRNAs of myogenin and Myf-5 in cultured cells incubated with both CGRP and IL-6 increased more rapidly than in cells cultured with CGRP or IL-6 alone, and the ratios of CK/DNA and Mb/DNA on day 10 were more than twice those in the presence of CGRP or IL-6. These findings indicate that both CGRP and IL-6 facilitate the differentiation of myoblasts and may have an additive effect.

Animals↗

PubMed1995

Biodegradation of toluene diamine (TDA) in activated sludge acclimated with aniline and TDA.

The biodegradability of toluene diamine (TDA) which has been regarded as a "recalcitrant compound" was examined in activated sludges. In this study, a microorganic-enzyme system which metabolized TDA was obtained by acclimating the activated sludge with aniline and TDA. In the sludge subject to be 200 days' acclimation, the considerable increase in respiration rate with the addition of TDA, accompanied the sharp decrease in its concentration. This indicated that TDA was metabolized fortuitously. The rate of biodegradation of TDA in the absence of aniline was first order with respect to its concentration when the initial TDA concentration was less than about 5 mg/l. The rate constant in this relation was proportional to mixed liquor suspended solid (MLSS). However, when the initial TDA concentration exceeded 5 mg/l, the plots were deviated from a first order rate equation.

Aniline Compounds↗

PubMed1995

Inhibition of restenosis by beraprost sodium (a prostaglandin I2 analogue) in the atherosclerotic rabbit artery after angioplasty.

We examined the effect of beraprost sodium (BPS), a stable prostaglandin I2 (PGI2) analogue, on restenosis after balloon angioplasty in the atherosclerotic artery in rabbits. Regional atherosclerosis was induced in the femoral artery of New Zealand white rabbits by balloon deendothelialization and 2% cholesterol diet. After establishment of atheroma in the femoral artery, angioplasty was performed. In all, 65 rabbits were assigned to the following six subcutaneous drug treatment groups: control group (n = 13, saline 0.25 ml/kg); BPS low-dose group (n = 11, BPS 50 micrograms/kg twice daily); BPS high-dose group (n = 12, BPS 100 micrograms/kg twice daily); 2-day BPS high-dose group (n = 11, BPS 100 micrograms/kg twice daily for 2 days after angioplasty); aspirin (ASA) group (n = 10, ASA 30 mg once daily); and BPS+ASA group (n = 8, BPS 50 micrograms/kg twice daily plus ASA 30 mg once daily). Administration of each drug was started 30 min before balloon angioplasty and was continued until 4 weeks thereafter, except in the 2-day BPS high-dose group. Re-examination 4 weeks after the angioplasty showed significant (p < 0.05) preservation of the luminal diameter in the BPS high-dose and 2-day BPS high-dose groups (1.30 +/- 0.15 and 1.25 +/- 0.09 mm, respectively) as compared with that in the control group (0.83 +/- 0.10 mm); however, the luminal diameter in the BPS low-dose, ASA, and BPS+ASA groups (0.94 +/- 0.18, 1.06 +/- 0.11, and 1.05 +/- 0.15 mm, respectively) was not significantly different from that in the control group.

Administration, Oral↗

PubMed1995

The prevalence of obsessive-compulsive disorder in Japan: a study of students using the Maudsley Obsessional-Compulsive Inventory and DSM-III-R.

The prevalence of obsessive-compulsive disorder (OCD) was measured in 424 Japanese students using a Japanese version of the Maudsley Obsession-Compulsive Inventory (MOCI-J). Six students (1.7%) of 350 interviewed students were diagnosed as OCD according to DSM-III-R. When the cut-off point of the MOCI-J was 12, the sensitivity was 100% and the specificity was 96%. Our results suggest that individuals with OCD are not rare among the young Japanese population and that the MOCI-J is a useful tool for screening OCD.

Adolescent↗

PubMed1995

Structural analysis of TRAS1, a novel family of telomeric repeat-associated retrotransposons in the silkworm, Bombyx mori.

We characterized TRAS1, a retrotransposable element which was inserted into the telomeric repetitive sequence (CCTAA)n of the silkworm, Bombyx mori. The complete sequence of TRAS1, a stretch of 7.8 kb with a poly(A) tract at the 3' end, was determined. No long terminal repeat (LTR) was found at the termini of the element. TRAS1 contains gag- and pol-like open reading frames (ORFs) which are similar to those of non-LTR retrotransposons. The two ORFs overlap but are one nucleotide out of frame (+1 frameshift). Most of the approximately 250 copies of TRAS1 elements in the genome were highly conserved in the structure. Chromosomal in situ hybridization showed that TRAS1 elements are clustered at the telomeres of Bombyx chromosomes. A phylogenetic analysis using the amino acid sequence of the reverse transcriptase domain within the pol-like ORF revealed that TRAS1 falls into one lineage with R1, which is a family of non-LTR retrotransposons inserted into the same site within the 28S ribosomal DNA unit in most insects. TRAS1 may have been derived from R1 and changed the target specificity so that TRAS1 inserts into the telomeric repetitive sequence (CCTAA)n. Southern hybridization and Bal 31 exonuclease analyses showed that TRAS1 elements are clustered proximal to the terminal long tract of (CCTAA)n. TRAS1 is a novel family of non-LTR retrotransposons which are inserted into the telomeric repetitive sequences as target sites.

Amino Acid Sequence↗

PubMed1995

Disruption of the mouse RBP-J kappa gene results in early embryonic death.

The RBP-J kappa protein is a transcription factor that recognizes the sequence C(T)GTGGGGA. The RBP-J kappa gene is highly conserved in a wide variety of species and the Drosophila homologue has been shown to be identical to Suppressor of Hairless [Su(H)] which plays important roles in the development of the peripheral nervous system. To explore the function of the RBP-J kappa gene in mouse embryogenesis, a mutation was introduced into the functional RBP-J kappa gene in embryonic stem (ES) cells by homologous recombination. Null mutant ES cells survived but null mutant mice showed embryonic lethality before 10.5 days of gestation. The mutant mice showed severe growth retardation as early as 8.5 days of gestation. Developmental abnormalities, including incomplete turning of the body axis, microencephaly, abnormal placental development, anterior neuropore opening and defective somitogenesis, were observed in the mutant mice at 9.5 days of gestation. RBP-J kappa mutant embryos expressed a posterior mesodermal marker FGFR1. Their irregularly shaped somites expressed a somite marker gene Mox 1 but failed to express myogenin. The RBP-J kappa gene was revealed to be essential for postimplantation development of mice.

Animals↗

PubMed1995

[Smoking habits in chronic schizophrenics].

The smoking habits of 48 chronic schizophrenics who were inpatients of private psychiatric were examined. Subjects were divided into three groups; non-smokers, moderate smokers and heavy smokers, and tested by Fagerstrom's Tolerance Questionnaire (FTQ) as a tobacco dependence evaluation, and Bender Gestalt Test (BGT) and Benton Visual Retention Test (BVRT) as a neuropsychological battery. In addition, we used the Scales for the Assessment of Negative Symptoms (SANS) to evaluate the degree of schizophrenic negative symptoms, confirming the correlation between SANS score and the amount of nicotine intake or FTQ item. From the results of FTQ scores and their correlation with SANS scores, the amount of nicotine intake was significantly related to the severity of schizophrenic negative symptoms including affective blunting, poverty of thinking and attention impairment. BGT and BVRT showed disturbances in visual-motor gestalt function, and attention and memory, in chronic schizophrenics who smoked, especially in heavy smokers. These results suggest that smoking behavior in chronic schizophrenics might increase the individual vigilance against negative symptoms, from the perspective of self-medication.

Adult↗

PubMed1994

A novel nuclear protein with zinc fingers down-regulated during early mammalian cell differentiation.

We introduced a promoter trap vector carrying a neo gene as a selectable marker into F9 cells and established several cell lines in which the expression of neo gene is under the control of an endogenous host gene that is active only in the undifferentiated F9 cells. Using one of these cell lines, G19, we isolated the integrated neo construct and its flanking host sequences by the plasmid rescue method, identified the host gene which contributes to the expression of neo gene, and named it the Zfp-57 gene. Two different Zfp-57 transcripts (1.8 and 3.2 kilobases) were identified in the undifferentiated F9 cells, and the levels of these transcripts were decreased significantly within a short time after induction of differentiation. We examined mouse organs for the presence of the Zfp-57 RNAs and found that the 1.8-kilobase RNA was detected only in the testis. The Zfp-57 cDNAs corresponding to the two different RNAs were isolated, and a comparison of the nucleotide sequences revealed that their coding regions were completely identical, but they differed both in length and in sequence of the 3'-untranslated region. The Zfp-57 cDNA encoded a protein consisting of 421 amino acids with an extremely high content of basic amino acid residues and multiple zinc finger motifs. Immunocytochemical analysis revealed that this protein is localized in the nucleus. These findings suggest that the Zfp-57 protein is a DNA-binding protein.

Amino Acid Sequence↗

PubMed1994

Effect of chylomicron remnants on apolipoprotein E synthesis in HepG2 cells.

The effect of chylomicron remnants (CM-R) on apolipoprotein (apo) E synthesis by HepG2 cells was studied. The accumulation rate of apo E in the medium was increased in cells incubated with CM-R (chylo-cells) compared with that in the control cells. However, the abundance of apo E mRNA was not greater in chylo-cells than in control cells. The time course of apo E accumulation in the medium showed that apo E increased in the chylo-cells linearly up to 24 hours, whereas it increased in the control cells linearly only up to 6 hours, when it reached a plateau. The results suggest that the secretion rate of apo E was not affected by incubation with CM-R, but that uptake of the newly secreted apo E by the cells may be depressed by incubation with CM-R. Autoradiography of newly synthesized apo E showed that chylo-cells produced much more "larger" apo E than did the control cells. Two-dimensional electrophoresis of the apo E newly synthesized by the chylo-cells showed that the larger apo E was slightly acidic even after treatment with neuraminidase. Pulse-chase labeling of apo E showed that the larger apo E was secreted by both control and chylo-cells equally and that the larger apo E was converted to regular apo E in the medium more effectively in control cells than in chylo-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins E↗

PubMed1994

Effect of starving and refeeding on lipid metabolism in suncus.

We have previously reported that fatty liver is easily induced in a novel experimental animal, Suncus murinus (suncus) by withholding food, and that apolipoprotein B (apo B) is not actively synthesized in the liver. In the present paper we describe the effect of starving and refeeding on lipid and lipoprotein metabolism in suncus, in order to explore the mechanisms of induction of fatty liver by starving and of its improvement by refeeding. Starvation induced increase in triglyceride content and decrease in glycogen content of the liver. Although the glycogen content returned to the level before starvation at 12 h after refeeding, the triglyceride content decreased gradually but did not reach the prestarvation level even at 24 h after refeeding in suncus. Plasma lipids, glucose, and insulin levels were decreased by starvation and returned to the levels before starvation between 8 and 24 h after refeeding. On the other hand, the plasma levels of free fatty acid and ketone bodies were elevated significantly by starvation and decreased rapidly by refeeding. These responses to starvation and refeeding, except for the change in hepatic triglyceride, are in common with other experimental animals, suggesting that there are no abnormalities in glucose metabolism or in fatty acid metabolism in suncus. In conclusion, the fatty liver induced by starvation in suncus may be caused by impaired triglyceride transport out of the liver, for which apolipoprotein B is mostly responsible, as reported previously.

Animals↗

PubMed1994

[Single dose toxicity studies of lactitol (NS-4) in mice and rats].

The single dose toxicity studies of lactitol, a hepatic encephalopathy drug, were performed in ddY mice and SD rats of both sexes by administering the drug orally, intravenously or subcutaneously. The drug was administered as a single dose followed by a 14-day observation. Oral LD50 values of lactitol were estimated to be between 23 and 30 g/kg in male mice, approximately 30 g/kg in female mice, and more than 30 g/kg in male and female rats. Lethal dose was more than 10 g/kg intravenously and subcutaneously in mice and rats of both sexes. The signs of toxicity in mice and rats observed following the administration of this drug included the following: decreased spontaneous movement [p.o., i.v., s.c.]; diarrhea, oligopnea or prone position, transient decreased body weight [p.o]. There were no treatment-related changes in gross examination. Based on these results, it was found that lactitol had a very low acute toxicity when administered by a single dose method in mice and rats.

Administration, Oral↗

PubMed1994

[52-week oral toxicity study of lactitol (NS-4) in rats followed by 9-week recovery test].

Twenty five male and 25 female Slc:SD rats were given orally lactitol, a hepatic encephalopathy drug, for 52 weeks at doses of 0, 0.4, 2 or 10 g/kg/day. A 9 week recovery test was conducted after the discontinuation of the drug treatment. Treatment related death, soft stool, diarrhea, decreased body weight gain and food intake and increased water consumption were observed in the 10 g/kg group. Urinalysis showed increased Ca excretion in the 2 and 10 g/kg groups. In the 10 g/kg group, there were increased Ca++ excretion and urine specific gravity and decreased K+ and Na+ excretion and urine volume. Hematologic examination showed decreased platelet count in the 10 g/kg group. Biochemical examination revealed higher A/G ratio in the 2 and 10 g/kg groups. In the 10 g/kg group, there were lowered level of total cholesterol, triglyceride, phospholipid, Na+, Cl- and total protein. Distention of the cecum with increased organ weight was seen pathologically in the 2 and 10 g/kg groups. In the 10 g/kg group, cecal mucosa was hyperplasic. The adrenal gland was hypertrophic in the zona glomerulosa in the 2 and 10 g/kg groups. In the 10 g/kg group, the adrenal weight was increased. Dilatation of renal tubules was also found in the 10 g/kg group. The above mentioned changes were satisfactorily reversible except for the increased cecum weight in the 10 g/kg group. Based on the results obtained, the NOAEL of this study was suggested to be 0.4 g/kg/day.

Administration, Oral↗

PubMed1994

[A resected case of esophageal leiomyoma with 15 cm in long diameter, diagnosed by transesophageal ultrasonic endoscopy].

A 28-year-old man whose chest X-ray film showed a mass on the right upper mediastinum was admitted. Preoperative examination, including CT, MRI, esophagogram, did not make it possible to determine clinically from which organ the tumor originated. On diagnosing with transesophageal ultrasonic endoscopy (TUE) the tumor was found to originate in the esophageal submucosa, with no involvement of the mediastinal organ apparent. Esophageal sub-mucosal tumor enucleation was performed. The resected tumor was 15 cm in long diameter and weighed 125 g. We therefore believe that TUE is clinically useful in diagnosing the tumor originating in the esophageal wall or adjoining esophageal wall.

Adult↗

PubMed1993

Nucleosides and nucleotides. 123. Synthesis of 1-(2-deoxy-2-isocyano-beta-D-arabinofuranosyl)cytosine and related nucleosides as potential antitumor agents.

2'-Deoxy-2'-isocyano-1-beta-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2'-azido-2'-deoxy-1-beta-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2'-deoxy-2'-isocyanocytidine (14b) failed due to the insertion of the 2'-alpha isocyano group into the 3'-OH group, affording the 2',3'-oxazoline derivative 15b. Stability of the isocyano derivative 6a and 2',3'-oxazoline derivative 15a under basic and acidic conditions were examined. The isocyano group in 6a was stable in basic conditions but unstable even in weakly acidic conditions to furnish the corresponding 2'-beta formamide derivative 17. Compound 15a was easily hydrolyzed the corresponding 2'-alpha formamide derivative 16 on treatment with H2O at room temperature. The cytotoxicity of 8, 6a, and 6b was examined in mouse and human tumor cells in vitro and compared with that of ara-C. Of these nucleosides, 8 was moderately cytotoxic to these cell lines. In vivo antitumor activity of 8 against Lewis lung carcinoma cells was also investigated and 8 showed only moderate tumor volume inhibition.

Animals↗

PubMed1993

Modification of hepato- and renal carcinogenesis by catechol and its isomers in rats pretreated with N-ethyl-N-hydroxyethylnitrosamine.

Modifying effects of catechol, resorcinol, and hydroquinone on second stage hepato- and renal carcinogenesis was investigated in rats pretreated with N-ethyl-N-hydroxyethyl-nitrosamine (EHEN). Groups of twenty 6-week-old Wistar/Crj male rats were treated with 0.1% EHEN in the drinking water for 3 weeks. Starting 1 week after the termination of EHEN treatment, they were given a diet containing 0.8% catechol, 0.8% resorcinol, or 0.8% hydroquinone or basal diet for 36 weeks. Further groups of 15 rats were each treated with the same doses of phenolic compounds or basal diet alone without EHEN pretreatment. All surviving animals were killed at the end of week 40 when histopathological assessment revealed significant reduction of the numbers per rat of hepatocellular adenomas and hepatocellular carcinomas by resorcinol, whereas hydroquinone significantly enhanced the numbers per rat of renal microadenomas and renal cell tumors. On the other hand, the number of alpha 2u-globulin positive tubules in the animals treated with hydroquinone was significantly lower than controls, without any alteration in bromodeoxyuridine (BrdU) incorporation. Lipid peroxidation, as evaluated by thiobarbituric acid reactive substance (TBARS), was at control levels in the kidneys of rats treated with hydroquinone throughout the experiment. The results showed that the known renal carcinogen hydroquinone potently enhances the second stage of EHEN-induced renal carcinogenesis, while its isomer resorcinol inhibited hepatocarcinogenesis. alpha 2u-Globulin and lipid peroxidation may not play roles in hydroquinone-associated promotion of renal carcinogenesis.

Adenoma↗

PubMed1993

Identification of a pentanucleotide telomeric sequence, (TTAGG)n, in the silkworm Bombyx mori and in other insects.

A pentanucleotide repetitive sequence, (TTAGG)n, has been isolated from a silkworm genomic library, using cross-hybridization with a (TTNGGG)5 sequence, which is conserved among most eukaryotic telomeres. Both fluorescent in situ hybridization and Bal 31 exonuclease experiments revealed major clusters of (TTAGG)n at the telomeres of all Bombyx chromosomes. To determine the evolutionary origin of this sequence, two types of telomeric sequence, (TTAGG)5 and a hexanucleotide repetitive sequence, (TTAGGG)4, which is conserved mainly among vertebrate and several invertebrate telomeres so far examined, were hybridized to DNAs from a wide variety of eukaryotic species under highly stringent hybridization conditions. The (TTAGGG)5 oligonucleotide hybridized to genomic DNAs from vertebrates and several nonvertebrate species, as has been reported so far, but not to any DNAs from insects. On the other hand, the Bombyx type of telomere sequence, (TTAGG)n, hybridized to DNAs from 8 of 11 orders of insect species tested but not to vertebrate DNAs, suggesting that this TTAGG repetitive sequence is conserved widely among insects.

Animals↗

PubMed1993

A monoclonal antibody which inhibits growth of T cell lines.

In an attempt to elucidate the intricate structure and possibly the signal transduction pathway of the interleukin-2 receptor (IL-2R) we tried to produce monoclonal antibodies against putative human IL-2R-associated molecules which precipitated from YT2C2 cells with a monoclonal antibody (Mik beta 3) against the human IL-2R beta chain. One of the antibodies obtained (7 x A10) recognizes a cell surface molecule of about 120 kDa (p120). Cross-linking of [125I]-IL-2 and immunoprecipitation with 7 x A10 suggest that the p120 protein may somehow associate physically with the IL-2R beta chain. Although p120 itself did not bind IL-2, and 7 x A10 did not inhibit IL-2 binding to the IL-2R, growth of the human IL-2-dependent cell lines ED40515 and Kit225 was completely inhibited by adding 7 x A10 to the culture at a relatively low concentration (0.2 micrograms/ml). At a higher concentration (2 micrograms/ml) 7 x A10 inhibited the growth of YTC3 and YT2C2 cells expressing IL-2Rs with high and intermediate affinities, respectively. The B cell line FLEB-14 and the erythroid cell line K562, which both express p120 as determined by flow cytometry, but no IL-2R alpha or beta chains showed only slight proliferation changes at high 7 x A10 concentrations. Out of 16 lymphocyte cell lines tested so far, only Molt-4, Raji and Daudi did not express p120, and therefore 7 x A10 did not influence their growth behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗