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101.
Rena Nishizawa Toshihiko Nishiyama Katsuya Hisaichi Keisuke Hirai Hiromu Habashita Yoshikazu Takaoka Hideaki Tada Kenji Sagawa Shiro Shibayama Kenji Maeda Hiroaki Mitsuya Hisao Nakai Daikichi Fukushima Masaaki Toda 《Bioorganic & medicinal chemistry letters》2010,20(2):763-766
Spirodiketopiperazine-based CCR5 antagonists, showing improved pharmacokinetic profiles without reduction in antagonist activity, were designed and synthesized. We also demonstrate the anti-HIV activity of a representative compound 12, as measured in a p24 assay. 相似文献
102.
103.
Ferry G Ubeaud C Dauly C Mozo J Guillard S Berger S Jimenez S Scoul C Leclerc G Yous S Delagrange P Boutin JA 《Protein expression and purification》2004,38(1):84-98
Melatonin is synthesized by a series of enzymes, the penultimate one, serotonin N-acetyltransferase, catalyzing the limiting reaction. In the present study, we compared the recombinant serotonin N-acetyltransferases from rat, ovine, and human. The human protein is particularly difficult to purify because it interacts strongly with a putative chaperone protein from bacteria whereas the rat and sheep enzymes, which interact less strongly with this protein, have been purified close to homogeneity. We identified the contaminating protein as GroEL, the bacterial equivalent of Hsp60. We present numerous catalytic activities (substrate and cosubstrate specificities as well as inhibitor specificities) measured on the three species enzymes from which we deduced that the presence of the chaperone might partly explain the differences between the various species enzyme characteristics, beside the inter-species ones resulting from sequence differences. Despite several trials reported in the literature, a purification to homogeneity of the human (recombinant) enzyme has never been described. We present a new purification method, by using an original denaturation/renaturation process in which the enzyme is immobilized on an affinity chromatography column. The enzyme is then eluted in an active and pure form (i.e., absence of chaperone). The up-scaled system permitted us to perform the necessary experiments for the measurement of more accurate affinities of human serotonin N-acetyltransferase towards its main natural substrates, showing that only the activity of the enzyme towards phenylethylamine was modified. 相似文献
104.
Role of premature leptin surge in obesity resulting from intrauterine undernutrition 总被引:10,自引:0,他引:10
Yura S Itoh H Sagawa N Yamamoto H Masuzaki H Nakao K Kawamura M Takemura M Kakui K Ogawa Y Fujii S 《Cell metabolism》2005,1(6):371-378
Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to “developmental origins of health and disease.” 相似文献
105.
Tani K Naganawa A Ishida A Egashira H Sagawa K Harada H Ogawa M Maruyama T Ohuchida S Nakai H Kondo K Toda M 《Bioorganic & medicinal chemistry》2002,10(4):1107-1114
Further chemical modification of 1a and 2 was undertaken to identify a more chemically stable selective EP2-receptor agonist for development as a clinical candidate. 9beta-chloro PG analogues 4a-e and 5a, c-e were found to be potent and selective EP2-receptor agonists. Among them, the compound 4aLy, which is a chemically stabilized lysine salt of 4a, exhibited an excellent profile both in biological activities and physicochemical properties. The agonist 4aLy was found to suppress uterine motility in anesthetized pregnant rats, while PGE2 stimulated uterine motility. Structure-activity relationships (SARs) are discussed. 相似文献
106.
Shiraki K.; Sagawa S.; Konda N.; Park Y. S.; Komatsu T.; Hong S. K. 《Journal of applied physiology》1986,61(4):1475-1480
The present study was undertaken to investigate energy balance in professional male breath-hold divers in Tsushima Island, Japan. In 4 divers, rectal (Tre) and mean skin (Tsk) temperatures and rate of O2 consumption (VO2) were measured during diving work in summer (27 degrees C water) and winter (14 degrees C water). Thermal insulation and energy costs of diving work were estimated. In summer, comparisons were made of subjects clad either in wet suits (protected) or in swimming trunks (unprotected), and in winter, they wore wet suits. The average Tre in unprotected divers decreased to 36.4 +/- 0.2 degrees C at the end of 1-h diving work, but in protected divers it decreased to 37.2 +/- 0.3 degrees C in 2 h in summer and to 36.9 +/- 0.1 degree C in 1.5 h in winter. The average Tsk of unprotected divers decreased to 28.0 +/- 0.6 degrees C in summer and that of protected divers decreased to 32.9 +/- 0.5 degrees C in summer and 28.0 +/- 0.3 degrees C in winter. Average VO2 increased 190% (from 370 ml/min before diving to 1,070 ml/min) in unprotected divers in summer, but in protected divers it rose 120% (from 360 to 780 ml/min) in summer and 110% (from 330 to 690 ml/min) in winter. Overall thermal insulation (tissue and wet suit) calculated for protected divers was 0.065 +/- 0.006 degree C X kcal-1 X m-2 X h-1 in summer and 0.135 +/- 0.019 degree C X kcal-1 X m-2 X h-1 in winter.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
107.
Cardiorenal-endocrine responses to head-out immersion at night 总被引:1,自引:0,他引:1
Shiraki K.; Konda N.; Sagawa S.; Claybaugh J. R.; Hong S. K. 《Journal of applied physiology》1986,60(1):176-183
Cardiorenal-endocrine responses to 3-h head-out immersion (HOI) (water temperature = 34.5 +/- 0.5 degrees C) were studied during day (0900-1400 h) and night (2300-0400 h) in six hydropenic male human subjects. Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude during the day compared with night (P less than 0.05). Na excretion and osmolal clearance (Cosm) also followed the identical response pattern as urine flow, and in fact, the HOI-induced diuresis was entirely accounted for by the increased Cosm. Endogenous creatinine clearance was not different between the day and the night and remained unchanged during HOI. Both plasma renin activity and aldosterone concentration and urinary aldosterone excretion were nearly twofold greater during the day compared with night before HOI but decreased to the same level during HOI in both daytime and the nighttime series (P less than 0.05). There was no correlation between the Na excretion rate and renin-aldosterone levels either before or during HOI. Plasma antidiuretic hormone (ADH) level was comparable between day and night before HOI and decreased to a similar level during HOI in both daytime and nighttime series (P less than 0.05 for nighttime HOI). Cardiac output increased from 3.3 1/min before HOI to 5-6 1/min during HOI without showing any significant circadian difference. Hematocrit, hemoglobin, and plasma concentrations remained unchanged under all conditions. It is concluded that the renal response to HOI is subject to nocturnal inhibition, which cannot be attributed to circadian differences in the degree of HOI-induced central blood pooling, renin-aldosterone, or ADH responses. 相似文献
108.
This study examined the thermal and metabolic responses of six men during exercise in water at critical temperature (Tcw, 31.2 +/- 0.5 degrees C), below Tcw (BTcw, 28.8 +/- 0.6 degrees C), at thermoneutrality (Ttn, 34 degrees C), and above Ttn (ATtn, 36 degrees C). At each water temperature (Tw) male volunteers wearing only swimming trunks completed four 1-h experiments while immersed up to the neck. During one experiment, subjects remained at rest (R), and the other three performed leg exercise (LE) at three different intensities (LE-1, 2 MET; LE-2, 3 MET; LE-3, 4 MET). In water warmer than Tcw, there was no difference in metabolic rate (M) during R. The M for each work load was independent of Tw. Esophageal temperature (Tes) remained unchanged during R in water of ATtn (36 degrees C). However, Tes significantly (P less than 0.05) declined over 1 h during R at Ttn (delta Tes = -0.39 degrees C), Tcw (delta Tes = -0.54 degrees C), and BTcw (delta Tes = -0.61 degrees C). All levels of underwater exercise elevated Tes and M compared with R at all Tw. In water colder than Tcw, the ratio of heat loss from limbs compared with the trunk became greater as LE intensity increased, indicating a preferential increase in heat loss from the limbs in cool water. Tissue insulation (Itissue) was lower during LE than at R and was inversely proportional to the increase in LE intensity. A linearly inverse relationship was established between Tw and M in maintaining thermal equilibrium.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
109.
A protocol for the micropropagation of Wikstroemia uva-ursi A. Gray ('Ãkia) was developed by the establishment of axenic shoot cultures from field-grown plants, induction of shoot proliferation, and rooting in vitro. The best shoot proliferation was obtained from the distal half of stem explants in 8.8 μM 6-benzyladenine. High frequencies of rooting were obtained. The best rooting occurred for shoots grown in half-strength MS plus 2.46 μM indole-3-butyric acid for two weeks. 相似文献
110.
The interactions of DNA with histone H4 and with its fragments N-H4 (1-84) and C-H4 (85-102) have been studied by using electrooptical techniques, viscosity and electron microscopy. Electron microscopy reveals that histone H4 induces a large folding of DNA molecules : this is in agreement with electrooptical measurements which indicate that, with the increase of their ratio, H4/DNA complexes undergo a gradual process of condensation. Viscosity measurements show that complexes at ratios up to 0.20-0.25 become more rigid as compared to DNA. It appears that C-H4, and not the N-H4 fragment, causes a great distorsion to the structure of DNA, accompanied by an increase of rigidity at ratios up to 0.20-0.25, as occurs for H4/DNA complexes. Electrooptical studies of C-H4/DNA complexes show, along a range of histone/DNA ratios, an important permanent dipole component. These effects reveal a particular mode of interaction of C-H4 with DNA, indicating that some charged residues of the peptide are kept distant enough from the DNA backbone. As no dipole character, in addition to that shown for DNA, has been detected for H4/DNA complexes, it is concluded that the conformation of the H4 molecule modifies to some extent the interaction of the C-terminal region. Our results show that this histone, and particularly its C-terminal region, is important as a determinant factor in the folding of DNA within artificial complexes. 相似文献