[Digital filling system for medical image data].
Explore the source record for details and available documents.
Cross Infection↗
Biomedical subjects
S Ohmori
Publications and source records attributed to S Ohmori.
Changes in calcium, PTH and 1,25(OH)2 vitamin D3 during tail-suspension in ovariectomized rats: effects of estrogen administration.
It is well known that estrogen deficiency results in osteoporosis in human and experimental animals. However, how its deficiency affects the development of disuse atrophy is not well understood. We thus investigated how estrogen deficiency caused by ovariectomy and estrogen supplements affect serum levels of calcium, parathyroid hormone (PTH), and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in tail-suspended rats. Five-week-old female Wistar rats were ovariectomized and divided into two groups. One group received an intramuscular injection of estradiol dipropionate once a week (OVX-E2 group), and the other received the vehicle alone (OVX group). After the third injection, the rats were subjected to tail-suspension in metabolic cages for 1, 3, 5 or 7 days. In the OVX group, urinary excretion of deoxypyridinoline (D-Pyr) tended to increase on day 1 after tail-suspension. In the OVX-E2 group, basal excretion was lower than that in the OVX group, and no increase was observed after the suspension. Serum concentrations of ionized calcium significantly increased on day 1 after the suspension in both groups. However, in the OVX-E2 group, the level tended to be higher than those in the OVX group from day 0 to day 3. Serum PTH tended to decrease on day 1 after suspension in the OVX group. In the OVX-E2 group, it did not change during the suspension, but the levels were higher than those in the OVX group during the experiment. Serum 1,25(OH)2D3 transiently and significantly increased on day 1 after suspension in both groups. However, in the OVX group, the level was significantly higher than that in the OVX-E2 group. These data indicate that estrogen treatment of ovariectomized rats modifies the changes in calcium metabolism induced by tail-suspension.
Amino Acids↗
Effect of estrogen and tail-suspension on expression of osteocalcin mRNA in femur of ovariectomized rats.
We investigated the effect of estrogen (E2) and tail-suspension on expression of osteocalcin (OC) mRNA in the femur of ovariectomized rats. Five-week-old female Wistar rats were ovariectomized and divided into two groups: one group received estradiol dipropionate (OVX-E2), and the other received the vehicle (OVX). Each group was further divided into two subgroups, tail-suspended (S) and non-suspended (N), giving a total of four groups: OVX-E2-S, OVX-E2-N, OVX-S and OVX-N. After a 7-day suspension, femurs were excised, and OC mRNA levels were determined by Northern blot analysis. A significant decrease of OC mRNA in OVX-E2-N was observed when compared with that of OVX-N, indicating that E2 decreases the OC expression. Interestingly, tail-suspension further decreased the mRNA levels in both OVX-S and OVX-E2-S when compared with the levels of OVX-N and OVX-E2-N, respectively. Since glucocorticoids have been shown to decrease OC expression, we also measured the urinary excretion of corticosterone during the suspension period that reflects the serum levels of corticosterone, and found that it was increased by E2 and further increased by tail-suspension. These results indicate that estrogen and glucocorticoids exert additive effects in inhibiting OC expression in the rat femur.
Animals↗
Expression of E16/CD98LC/hLAT1 is responsive to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
We employed cDNA representational difference analysis to identify new genes that are upregulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a human hepatoblastoma cell line HepG2. We isolated several TCDD-responsive cDNAs. Sequence analysis revealed that one of them encodes E16/CD98LC/hLAT1, an integral membrane protein involved in multiple cellular functions including cellular transport of L-type amino acids. Northern blot analysis confirmed the TCDD-dependent upregulation of the mRNA. Induction of E16/CD98LC/hLAT1 mRNA by TCDD did not require de novo protein synthesis as revealed by the experiment using cycloheximide. Consistent with the changes at mRNA level, the transport of 3H-leucine into HepG2 cells was significantly increased by TCDD treatment. These findings provide a novel aspect of biological effects of TCDD on human hepatocytes.
Amino Acid Transport Systems↗
Saccharomyces cerevisiae cultured under aerobic and anaerobic conditions: air-level oxygen stress and protection against stress.
Cells of Saccharomyces cerevisiae were grown aerobically and anaerobically, and levels of the protective compounds, cysteine and glutathione, and activities of defensive enzymes, catalase and superoxide dismutase, against an oxygen stress were determined and compared in both cells. Aerobiosis increased both the compounds and enzyme activities. The elevated synthesis of glutathione could be associated with the increased levels of cysteine which in its turn was found to be controlled by the oxygen-dependent activation of cystathionine beta-synthase.
Aerobiosis↗
Localization of the human nuclear receptor corepressor (hN-CoR) gene between the CMT1A and the SMS critical regions of chromosome 17p11.2.
Explore the source record for details and available documents.
Animals↗
Chaos and spectral analyses of heart rate variability during head-up tilting in essential hypertension.
To investigate nonlinear and linear components of heart rate variability (HRV) in essential hypertension (EHT), we analyzed HRV by chaos and spectral analyses in patients with EHT (n = 18) and normotensives (n = 10) during head-up tilting. We used the correlation dimension (CD) and Lyapunov exponents as the parameters of chaos. The CD, an index of complexity, was lower at rest in EHT group than in normotensives, and did not change in EHT group in response to head-up tilting, but decreased in normotensives. Head-up tilting did not change the Lyapunov exponents, an index of sensitive dependence on initial condition, a hallmark of chaos, in both groups. In the spectral analysis, the normalized high-frequency component (%HF) was decreased in EHT group at rest, and head-up tilting increased the low- to high-frequency ratio (L/H) and reduced the %HF in both groups. The CD and Lyapunov exponents at rest were correlated with the %HF and L/H. These results suggest that chaos analysis can assess the different aspect of HRV from spectral analysis and that nonlinear components of HRV may be associated with hypertension through an impaired dynamic regulation of HRV.
Adult↗
Enantioselectivity of bunitrolol 4-hydroxylation is reversed by the change of an amino acid residue from valine to methionine at position 374 of cytochrome P450-2D6.
The enantioselectivity of 4-hydroxylation of bunitrolol (BTL), a beta-adrenoceptor blocking drug, was studied in microsomes from human liver, human hepatoma (Hep G2) cells expressing CYP2D6, and lymphoblastoid cells expressing CYP2D6. Kinetics in human liver microsomes showed that the Vmax value for (+)-BTL was 2.1-fold that of (-)-BTL, and that the Km value for (+)-BTL was lower than that for the (-)-antipode, resulting in the intrinsic clearance (Vmax/Km) of (+)-BTL being 2.1-fold over its (-)-antipode. CYP2D6 (CYP2D6-met) expressed in Hep G2 cells had a methionine residue at position 373 of the amino acid sequence and a rat-type N-terminal peptide (MELLNGTGLWSM) instead of the human-type (MGLEALVPLAVIV), and showed enantioselectivity of [(+)-BTL < (-)-BTL] for the rate of BTL 4-hydroxylation. In contrast, enantioselectivity [(+)-BTL > (-)-BTL] for Hep G2-CYP2D6 (CYP2D6-val) with a human-type N-terminal peptide that had a valine residue at 374, which corresponds to the methionine of the CYP2D6-met variant, was the same as that for human liver microsomes. We further confirmed that CYP2D6-met and CYP2D6-val expressed in human lymphoblastoid cells, both of which have methionine and valine, respectively, at position 374 and a human-type N-terminal peptide, exhibited the same enantioselectivities as those obtained from CYP2D6-met and CYP2D6-val expressed in the Hep G2 cell system. These results indicate that the amino acid at 374 of CYP2D6 is one of the key factors influencing the enantioselectivity of BTL 4-hydroxylation.
Adrenergic beta-Antagonists↗
A Japanese family with autosomal dominant growth hormone deficiency.
UNLABELLED: We report a 1-year-old Japanese boy and his father with isolated growth hormone deficiency II. In both cases, a G-->A transition of the first base of the donor splice site of intron 3 of the growth hormone-1 gene was detected. All unaffected family members were homozygous normal. CONCLUSION: This is the fourth reported case of autosomal isolated growth hormone deficiency II with a G-->A transition. The CG dinucleotide at the exon 3-intron 3 junction of the growth hormone-1 gene appears to be a hot spot for point mutations.
Adult↗
Blood and urinary levels of ethanol, acetaldehyde, and C4 compounds such as diacetyl, acetoin, and 2,3-butanediol in normal male students after ethanol ingestion.
Aldehyde dehydrogenase (ALDH) isozyme 2 genes were determined in 15 students. Of these subjects, five healthy male students were administered 0.4 kg/kg ethanol. One subject was defective in aldehyde dehydrogenase 2 (ALDH2), two had normal ALDH2, and the other two were hetero type. After the intake of alcohol, the concentration of ethanol, acetaldehyde, and C4 compounds in blood and urine were determined. The student with the inactive form of ALDH2 was flushed and his levels of 2,3-butanediol and acetaldehyde in blood and urine were found to be the highest.
Acetaldehyde↗
Effects of interferon on circadian changes in blood pressure and heart rate variability in patients with chronic hepatitis.
We have determined the effects of interferon therapy on circadian changes in blood pressure and heart rate variability in normotensive hospitalized patients with chronic active hepatitis. Body temperature and pulse rate increased for the initial few days of interferon therapy without significant change in casual or ambulatory blood pressure. Interferon therapy failed to elicit any significant changes in the power spectrum of R-R intervals. In addition, urinary excretion of norepinephrine did not differ between before and during the therapy. These results suggest that interferon therapy caused transient increases in body temperature and pulse rate, but that it did not change either sympathetic or parasympathetic outflow, or the circadian rhythm of blood pressure and heart rate variability, in normotensive subjects.
Antiviral Agents↗
Comparison of urinary 6beta-hydroxycortisol/cortisol ratio between neonates and their mothers.
AIMS: To assess CYP3A enzyme activity in human neonates by measuring the urinary 6beta-hydroxycortisol/cortisol (6beta-OHF/C) ratio. METHODS: Fifty-six mature male neonates with normal delivery, seventeen of their mothers and twenty-four healthy non-pregnant young women participated in this study. Urinary 6beta-OHF/C ratio was determined on the day of birth in neonates and their mothers. In addition, changes in the ratio after birth were determined in neonates. RESULTS: On the day of birth, the urinary 6beta-OHF/C ratio of neonates was significantly higher than that of their mothers (20.5 vs 6.9). In contrast, no significant difference was observed in the mean ratio of urinary 6beta-OHF/C between women with and without pregnancy (6.9 vs 9.0). The urinary 6beta-OHF/C ratio after birth was decreased day by day in neonates. CONCLUSION: These results indicate that the high urinary 6beta-OHF/C ratio in mature neonates on the day of birth is independent of the activity of CYP3A enzyme in their mothers.
Aryl Hydrocarbon Hydroxylases↗
A novel mutation at the donor splice site of intron 3 of the GH-I gene in a patient with isolated growth hormone deficiency.
A G - C transversion at the fifth nucleotide of intron 3 of GH-I gene was identified in a sporadic case of isolated growth hormone deficiency (IGHD). The mutation was absent in both of the parents, indicating that the mutation occurred de novo. An abnormal hGH mRNA lacking a region encoded by exon 3 was spliced when the mutant GH-I gene was expressed in cultured cells. Since skipping of exon 3 is a common feature for four different mutant GH-I genes identified in patients with autosomal dominantly inherited IGHD, we conclude that the mutation causes IGHD in this case.
Cell Line↗
Responsiveness to thyroid hormone is enhanced in rat hepatocytes cultured as spheroids compared with that in monolayers: altered responsiveness to thyroid hormone possibly involves complex formed on thyroid hormone response elements.
We previously reported that the expression of type I iodothyronine 5'-deiodinase (5'DI) gene was increased by 3,3,',5-triiodothyronine (T3) in isolated rat hepatocytes when cultured as spherical aggregates (spheroids), whereas this effect was greatly attenuated in conventional monolayer cultures. In the current study, we examined whether the enhanced T3 responsiveness in spheroid cultures extends to other T3-responsive genes. As observed for 5'DI, T3 increased spot 14, malic enzyme and fibronectin messenger RNAs (mRNAs) by fourfold to fivefold in spheroid cultures, while the effect in monolayer cultures was blunted. This difference in T3 responsiveness was also observed when T3-responsive reporters consisting of the luciferase gene under the control of triiodothyronine response element (TRE) were introduced into hepatocytes using a replication-defective adenovirus vector. These results suggest that the factors required for T3-dependent transcriptional activation are preserved in spheroid cultures and that they must exert their effect by interacting with TRE. Maximal binding capacity of nuclear T3 receptor was not different between monolayer and spheroid cultures while the expression of retinoid X receptor-alpha (RXR alpha) mRNA was higher in spheroid cultures compared with that in monolayers. The difference in RXR alpha mRNA expression, together with enhanced proteolytic cleavage in monolayers that we demonstrated recently, may account for the difference in T3 responsiveness between the two hepatocyte culture systems.
Animals↗
Inhibition of growth hormone (GH) secretion by a mutant GH-I gene product in neuroendocrine cells containing secretory granules: an implication for isolated GH deficiency inherited in an autosomal dominant manner.
Isolated GH deficiency (IGHD) type II is a disease inherited in an autosomal dominant manner. Although point mutations at the donor splice site of intron 3 of the GH-I gene have been identified in patients, the mechanism of how such mutations result in severe GH deficiency is unclear. Recently, we identified two mutations in Japanese patients with IGHD type II, G to A substitutions at the first (mutA) and fifth (mutE) nucleotides of intron 3. Messenger ribonucleic acids skipping exon 3 were transcribed from both mutant GH-I genes. We studied in this report the synthesis and secretion of GH encoded by the mutant GH-I genes and tested whether inhibition of wild-type GH secretion by mutant products could be demonstrated in cultured cell lines. A metabolic labeling study in COS-1 cells revealed that a mutant GH with a reduced molecular mass was synthesized from the mutant messenger ribonucleic acid and retained in the cells for at least 6 h. On the other hand, the wild-type GH was rapidly secreted into the medium. Coexpression of mutant and wild-type GH did not result in any inhibition of wild-type GH secretion in COS-1 or HepG2 cells. However, coexpression of mutant GH resulted in significant inhibition of wild-type GH secretion in somatotroph-derived MtT/S cells as well as in adrenocorticotroph-derived AtT-20 cells, without affecting cell viability. We conclude that the dominant negative effect of mutant GH on the secretion of wild-type GH is at least in part responsible for the pathogenesis of IGHD type II. Our results also suggest that neuroendocrine cell type-specific mechanisms, including intracellular storage of the secretory proteins, are involved in the inhibition.
Animals↗
Estimation of chemical structure of notopterol metabolites.
Notopterol, 5[(2E)-5-hydroxy-3,7-dimethyl-2,6-octadienyloxy]psoralen showed an inhibitory effect on aminopyrine N-demethylase activity in liver microsomes. In addition, notopterol has been found to be metabolized by cytochrome P450, and two kinds of metabolites were formed from notopterol. Furthermore, specific cytochrome P450 3A4 inhibitors which were isolated from grapefruit juice had the same furocoumarin structure as notopterol. Two metabolites of notopterol were separated by HPLC, and the chemical structures of the hydroxylated metabolites were estimated by 1H-NMR spectra and liquid chromatography-mass spectrometry.
Animals↗
Effects of salt-loading on membrane potentials in mesenteric arteries of spontaneously hypertensive rats.
Although salt intake and blood pressure are correlated, with hypertensives tending to exhibit higher blood pressure sensitivity to salt than normotensives, the precise mechanisms underlying this relationship remain unclear. This study aimed to determine whether salt-loading affects arterial membrane properties of spontaneously hypertensive rats (SHR). SHR and age-matched Wistar Kyoto rats (WKY) received either an 8% high salt diet or standard rat chow from 6 to 16 wk of age. Systolic blood pressure was significantly higher in salt-loaded SHR than in control SHR (267+/-7 vs. 235 +/- 5 mmHg, p < 0.05). The membrane potential of isolated conduit and resistance arteries of the superior mesenteric vascular bed, measured with microelectrodes, was less negative in salt-loaded SHR than in control SHR or salt-loaded WKY (conduit arteries, -39.9 +/- 0.3 vs. -44.5 +/- 0.4 or -47.4 +/- 0.4 mV, respectively, p < 0.05 for each; resistance arteries, -55.5 +/- 0.5 vs. -62.5 +/- 0.5 or -67.0 +/- 0.5 mV, respectively, p < 0.05 for each). Furthermore, conduit arteries of salt-loaded SHR exhibited spontaneous electrical activity (4-13 mV, 1-3/min), which was sensitive to ONO-3708, a thromboxane A2/prostaglandin H2 receptor antagonist. These findings suggest that salt-loading in SHR leads to a membrane depolarization in both conduit and resistance arteries, as well as to spontaneous electrical activity, presumably mediated by eicosanoids, in conduit arteries. These alterations in membrane properties might contribute to the exacerbation of hypertension and/or the target organ damage after salt loading in SHR.
Animals↗
Polymorphism of homopolymeric glutamines in coactivators for nuclear hormone receptors.
Some of the recently identified coactivators which interact with members of nuclear hormone receptors contain a stretch of homopolymeric glutamines (poly-Q). Length of poly-Q in several genes are known to be polymorphic in healthy subjects, and extraordinary expansion of poly-Q in specific genes is known to cause neurodegenerative disorders. In the present study, we investigated whether such polymorphism can be observed in two coactivators, CBP (CREB [cyclic AMP responsive element binding protein]-binding protein) and AIB1/ACTR (amplified in breast cancer-1/ACTR, also called RAC3/TRAM-1). The genomic regions encoding the poly-Q were amplified by means of PCR using fluorescence labeled primer and analyzed by an automatic sequencer. While contiguous glutamine residues inAIB1/ACTR ranged from 26 to 32 with a heterozygosity of 54%, no polymorphism could be observed in poly-Q of CBP among 54 unrelated subjects. These results suggest that the residue in CBP may play a critical role in the function so that individuals with CBP containing different sizes of poly-Q might have been eliminated. It has been reported that AIB1/ACTR is overexpressed in some of the cell lines derived from breast cancer. If the length of poly-Q alters the stability of AIB1/ACTR and/or potency to enhance hormone action through nuclear receptors, the length of poly-Q is likely to be one of the genetic factors affecting not only susceptibility to breast cancers but also the sensitivity to hormones. This polymorphism should also be tested in patients with neurodegenerative disorders of unknown cause.
Acetyltransferases↗