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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 379 records · Page 21Linked to original sources

The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on ethanol-induced sleep time and ethanol elimination in inbred strains of mice with different alcohol preference.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases. Male C57BL/6J and DBA/2J mice were given 6R-BH4 (0, 12.5, 25.0 and 50.0 mg/kg of body weight, i.v.) or saline, and then 4 h later, all animals were injected with ethanol (EtOH) (4.0 g/kg, i.p.), which causes them to lose the righting reflex, to investigate the differences in EtOH-induced sleeping time. 6R-BH4 pretreatment reduced EtOH-induced sleep time in DBA/2J mice with lower alcohol preference (p < 0.05), which showed no changes in the pharmacokinetics of blood EtOH. No changes in EtOH-induced sleep time were observed in C57BL/6J mice with higher alcohol preference. These results indicate that the sensitivity to EtOH in mice with lower alcohol preference was associated with 6R-BH4 activity in the CNS.

Alcohol Drinking↗

Mature CD4 single positive thymocytes in human Thymoma: T cells may differentiate in the thymic epithelial cell tumor.

Human thymoma, which is occasionally associated with autoimmune disease, is a thymic epithelial cell tumor and often contains a large number of lymphocytes. In a previous study, we have shown that a proportion of CD4 single positive T cells in human thymomas lack CD3, suggesting immaturity. In this study, we focused on the rest of the CD4 single positive T cells in thymomas that expressed CD3/TcR alpha beta and investigated the maturity of single positive T cells by analyzing lymphocyte surface antigens and the cells' proliferative response to a mitogen. CD4 single positive cells that expressed CD3 or TcR alpha beta also expressed CD69 and had probably undergone positive selection in the tumor. Further, isolated CD4 or CD8 single positive cells from the thymomas responsed to a mitogen although at lower levels than the corresponding single positive cells in the peripheral blood. These results indicate that thymomas contain single positive T cells which have mature phenotype and proliferative ability, and suggest that T cells may differentiate in thymoma.

Adult↗

Enantioselective fluorination of organic molecules. I. Synthetic studies of the agents for electrophilic, enantioselective fluorination of carbanions.

In order to develop novel methods for electrophilic and enantioselective fluorination of active methine compounds, preliminary experiments were carried out. The N-tosyl derivative 5 obtained from D-phenylglycine was fluorinated with FClO3 or diluted F2 gas to give the N-fluoro-N-tosyl derivative 6. N-tosyl- or N-mesyl-(S)-alpha-phenethylamine 7 or 8 was subjected to FClO3 fluorination to produce the corresponding N-fluoro derivative, 10 or 11, respectively. Enantioselective fluorination of some methine compounds was attempted employing the above N-fluoro agents. Best result was obtained when 2-benzyl-1-tetralone/KHMDS was treated with 10 to produce the fluorinated tetralone 17 in 53% yield with enantiomeric excess (ee) of 48%.

Anions↗

Syntheses and antifungal activity of dl-griseofulvin and its congeners. III.

Several congeners (1b-g), with novel substituents on the benzene ring of griseofulvin, were prepared by the application of a synthetic method developed by us. Antifungal activity of these congeners decreased in order of dl-griseofulvin (1a) = 1d > 1b, c >> 1e-f (inactive). The relationship between the antifungal activity and the position or kind of substituents on the benzene ring of griseofulvin is discussed.

Antifungal Agents↗

Synthesis and antitumor activity of fused quinoline derivatives. V. Methylindolo[3,2-b]quinolines.

Indolo[3,2-b]quinoline derivatives (1b-i) with a methyl group at each possible position have been synthesized. The 1-methyl (1b) and 9-methyl (1i) derivatives were inactive, but the 3-methyl (1d), 4-methyl (1e), and 6-methyl (1f) derivatives exhibited high treatment/control (T/C) value and cure rates against leukemia P388 in mice. These results indicated that modification of indolo[3,2-b]quinoline derivatives at 3, 4, and 6 positions may be useful approach for lead optimization.

Animals↗

Syntheses and antifungal activity of dl-griseofulvin and its congeners. II.

Griseofulvin derivatives, dl-6'-demethyl-6'-ethylgriseofulvin (dl-5) and dl-6'demethyl-6'phenylgriseofulvin (dl-6) were prepared by application of a synthetic method developed by us. Antifungal activity of these derivatives decreased in the order of dl-griseofulvin (dl-1) >> dl-6(inactive). The reaction of these derivatives with ethanethiol gave two types of compounds, 2'-(ethylthio)griseofulvin (15) and 4'-(ethylthio)isogriseofulvin (16). The relationship between the ratios of isolated yield of 15 and 16 and antifungal the activity of griseofulvin derivatives is discussed.

Antifungal Agents↗

Synthesis and antitumor activity of fused quinoline derivatives. IV. Novel 11-aminoindolo[3,2-b]quinolines.

Indolo[3,2-b]quinoline derivatives (1) having various amine moieties were prepared and their antitumor activities against P388 leukemia in mice were evaluated, for the purpose of gaining an insight into the role of the amine moiety in the antitumor activity and searching for an effective amine moiety. Introduction of a methylene group between the phenyl group and amino or methanesulfonamido group resulted in decrease or loss of activity.

Animals↗

[Induction of passive cutaneous anaphylaxis by oral administration of antigen].

Passive cutaneous anaphylaxis (PCA) reaction was developed by Ovary et al. as an animal model of mainly human type I allergic inflammation reaction. This is the most sensitive reaction for the detection of cutaneously sensitizing antibodies and provides a very effective means by which to investigate immunological reactions concerning the mechanisms of development and inhibition of allergic reactions, levels and specificity of antibodies, and the structure of antigens. These cutaneous inflammations mimic atopic dermatitis. Food ingestion has been pointed out as one of the worsened factors of atopic dermatitis. However, the body is generally protected against the invasion of high molecular substances such as non-ingested food by several barriers including digestive enzymes that break down complex food molecules into simpler substances and gastrointestinal mucosae. Accordingly, oral ingestion of food antigen seems to be physiologically and immunologically in conflict with the occurrence of dermatitis. With a view to determining whether allergic dermatitis occurs after oral ingestion of food, the present study was carried out on animals, utilizing the PCA reaction. C 57 BL/6 Ncr j mice were immunized with immunogen derived from commercially obtained eggs. Wistar rats were used as a model of PCA reaction. The results of the present investigation are summarized as follows. 1) Blue spots of 10 mm diameter were observed as a PCA reaction 50 min or more after oral administration of antigen, and the blue spots reached maximum size (20-21 mm, 1.8-1.7 micrograms) after 90-120 min. The PCA reaction was induced 20 min or more after intravenous administration of antigen. When the maximum reaction was compared between the oral and the intravenous routes after 50 min (29.5 micrograms) and 90 min (1.8 micrograms) respectively, there was about a 16-fold difference in the capacity to induce inflammations. 2) The maximum PCA reaction values were 100 and 1,600 for the oral and intravenous routes, respectively, there being a 16-fold difference between the two routes. 3) The minimum antigen concentration required to induce the PCA reaction was 10 mg/ ml for the oral route and 0.01 mg/ml for the intravenous, there being a 1,000-fold difference between the two routes. 4) Reactions with anti-egg mixture antibody and main egg constituents were specific. The PCA inhibition test results confirmed that the undigested structural portion of antigen was associated with the induction of PCA. The present investigation demonstrated that there existed a mechanism by which type I allergy is induced via the gastro-intestinal tract. This fact indicates that part of the food ingested undergoes no change in its molecular structure when transferred to the blood, thus acting as a PCA inducing antigen. This phenomenon suggests that this animal model of human type I allergic dermatitis is a useful system that strongly suggests the association of food antigen with the development of allergic dermatitis.

Administration, Oral↗

Pathophysiological changes evoked by lipopolysaccharide administration in goats.

To establish an adequate experimental model for the study of immuno-neuroendocrine mechanisms underlying the behavioral changes during the acute infection, temporal relationship of various physiological responses to endotoxin administration was examined in ovariectomized goats. Immediately after intravenous injection of 200 ng/kg of lipopolysaccharide, there were an abrupt decrease of white blood cell number and a gradual increase of rectal temperature, which were followed by elevation of plasma levels of adrenocorticotropic hormone, cortisol, glucose, free fatty acids, and then later by an increase of heart rate. The results suggest that the endotoxin administration would evoke a stereotyped cascade of, febrile, neuroendocrine and metabolic as well as autonomic response to the activation of immune systems in the ruminant species.

Acute Disease↗

Immunohistochemical localization of corticotropin-releasing factor, [arginine8]-vasopressin and oxytocin neurons in the goat hypothalamus.

Distribution patterns of corticotropin-releasing factor (CRF), [arginine8]-vasopressin (AVP) and oxytocin (OXY) neurons were examined immunohistochemically in the female goat hypothalamus. The majority of the CRF immunoreactive (-IR) cells were located in the parvocellular part of the paraventricular nucleus (PVN) with smaller population found in the magnocellular part of the PVN. CRF-IR cells were also found in the suprachiasmatic nucleus, the preoptic area and around the fornix in the caudal part of the hypothalamus. AVP- and OXY-IR cells were similarly distributed in the hypothalamus. The majority of AVP- and OXY-IR cells were observed in the magnocellular part of PVN and the supraoptic nucleus. Smaller numbers of AVP- and OXY-IR cells were found in the parvocellular part of the PVN and lateral hypothalamic area. AVP-IR but not OXY-IR cells were located in the suprachiasmatic nucleus. CRF-IR fibers were concentrated in the external palisade zone of the median eminence (ME) with a few fibers found in the internal palisade zone of the ME, whereas AVP- and OXY-IR fibers were concentrated in the internal palisade zone of the ME with a few fibers found in the external zone. These results support the view that not only CRF but also AVP and OXY are released into the hypophysial portal blood and involved in the control of pituitary endocrine function in ruminant species.

Animals↗

Lipopolysaccharide-induced suppression of the hypothalamic gonadotropin-releasing hormone pulse generator in ovariectomized goats.

Ovariectomized goats were implanted with the electrode arrays for monitoring the electrophysiological manifestation of the activity of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, namely multiple-unit activity (MUA) volleys associated with pulsatile luteinizing hormone secretion. They were then subjected to i.v. challenges of lipopolysaccharide (LPS) at the dose of 200 or 400 ng/kg. The interval between the MUA volleys was significantly prolonged by higher dose of LPS whereas neither amplitude nor duration of the MUA volleys was altered. These results suggest that immunological disturbance as evoked by LPS administration directly affects the hypothalamic GnRH pulse generator by slowing down the pulse frequency, and thereby lowers gonadotropin secretion from the anterior pituitary gland, which would culminate in gonadal suppression.

Animals↗

Role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors in rat preosteoblastic RCT-1 cells.

Retinoic acid induces differentiation of preosteoblastic cells. We have demonstrated that osteoblastic differentiation and down-regulation of transforming growth factor (TGF)-beta receptors requires the interaction of type I collagen with alpha 2 beta 1 integrin (J Biol Chem 271: 3938-3944, 1996). The purpose of this study was to clarify the role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors using preosteoblastic RCT-1 cells. Retinoic acid enhanced the expression of alkaline phosphatase and type I collagen, and reduced TGF-beta receptors in these cells. Inhibiting collagen synthesis abolished these changes. Because TGF-beta inhibits osteoblastic differentiation, the changes described here may contribute to the osteoblastic differentiation by retinoic acid.

Alkaline Phosphatase↗

Cancer cachexia and depressive states: a neuro-endocrine-immunological disease?

Plasma 5-hydroxytryptamine (serotonin), tryptophan, neopterin and cortisol levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-gamma) production, and cortisol values, but decreased serotonin and tryptophan levels. Much work has been done to elucidate the possible role of serotonin in depressive states. IFN-gamma induces a high level of indoleamine dioxygenase (IDO), a tryptophan degrading enzyme, and high cortisol levels induce high tryptophan oxygenase activity, which in turn increases metabolism along the tryptophan-nicotinic acid pathway. These results suggest that persistent immune activation and intense adrenal activity occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism followed by depression in cancer cachexia.

Adult↗

Drinking habit as a base for blood pressure elevation--difference in epidemiological significance by beverage type.

To investigate whether blood pressure differs by taking preferred alcoholic beverage among habitual drinkers, systolic and diastolic blood pressure (SBP, DBP) were compared among groups with different beverage types in 563 middle-aged Japanese males using data from a cross-sectional health survey conducted from February, 1989 through March, 1991 in five areas of Japan. Mean values of SBP and DBP, adjusted for residence, age and body mass index (BMI), were significantly greater in 'exclusively sake' drinkers (adjusted SBP: 127.2 mmHg, adjusted DBP: 83.0 mmHg) and in 'exclusively shochu' drinkers (adjusted SBP: 127.5 mmHg, adjusted DBP: 84.2 mmHg) than in non-drinkers (adjusted SBP: 120.9 mmHg, adjusted DBP: 77.3 mmHg). Adjusted SBP and DBP of 'exclusively beer' drinkers (adjusted SBP: 121.9 mmHg, adjusted DBP: 79.1 mmHg) were significantly (for SBP: p = 0.016, for DBP: p = 0.008) lower than those of 'exclusively sake' drinkers. Similar patterns of blood pressure differences between five beverage types of habitual drinkers were found especially in the group with less than 150 g of weekly ethyl-alcohol consumption. Even after adding ethyl-alcohol consumption as a covariate among 479 habitual drinkers, the significant differences in adjusted SBP and DBP between 'exclusively beer' drinkers and 'exclusively sake' drinkers (for SBP: p = 0.032, for DBP: p = 0.044) were noted. These results may suggest that the effects of drinking on blood pressure differ by beverage type in middle-aged Japanese males.

Adult↗

Low back pain among cooks in nursery schools.

A cross-sectional questionnaire study was conducted on cooks working for nursery schools in N city in order to verify epidemiological evidence of the work-relatedness of low back pain among them. After female workers aged 30 or more were selected from a study base of 2,799 workers in social welfare facilities, low back pain prevalence of cooks (n = 240) was compared with nursery school teachers (n = 955). Age-standardized prevalence ratios (PRs) of low back pain were 1.9 (95% CI: 1.5-2.5) in cooks compared with nursery school teachers. Among cooks, relative risks of low back pain increased with the increase in the number of lunches to be prepared and decreased with the increase in the number of cooks making lunches in a logistic regression model controlling age and body length. Low back pain was also found to be associated with self-estimated job stressors/ work load by logistic regression models. Multifactorial effects from ergonomic and psychosocial factors, and individual factors on the low back were suggested. From the viewpoint of epidemiological criteria for work-relatedness, it was concluded that the work-relatedness of low back pain among cooks in nursery schools was partially supported.

Adult↗