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Biomedical subjects

Y Murata

Publications and source records attributed to Y Murata.

At least 55 records · Page 3Linked to original sources
PubMed2003

Bestatin results in pathophysiological changes similar to preeclampsia in rats via induction of placental apoptosis.

OBJECTIVE: To establish a rat preeclampsia model with fetoplacental growth restriction caused by bestatin via induction of placental apoptosis. STUDY DESIGN: 200 mg/kg/day of bestatin or saline as a control were infused intraperitoneally into pregnant Wistar rats from 15 days' gestation. In the first experiment, maternal blood pressure and proteinuria were examined during the pre- and postpartum periods. In the second experiment, cesarean sections were performed at 20 days' gestation and the weights of pups and placentas, and levels of proteinuria and placental apoptosis were examined. RESULTS: Physiological decrease of blood pressure in late pregnancy was not detected in the bestatin group but proteinuria level at 20 days' gestation was elevated. The weights of pups and placentas in the bestatin group were significantly lower than those in the controls, bestatin strongly inducing apoptosis in the placenta. CONCLUSION: Bestatin may cause a preeclampsia-like condition through induction of placental apoptosis.

Animals↗
PubMed2003

The influence of early ambulation and other factors on headache after lumbar myelography.

In order to determine the influence of early ambulation and other factors on headaches occurring after lumbar myelography we randomised 207 patients (127 men and 80 women) into two groups. Following the investigation, we allowed the 101 patients (65 men and 36 women) in group A to sit or stand freely, while we confined the 106 patients (62 men and 44 women) in group B to bed for 20 hours. The nine patients in group B who could not maintain bed rest were excluded. There was no significant difference between the two groups as regards the prevalence of spinal headache (8.9% in group A v 14.4% in group B). Patients who reported headaches, however, were significantly more likely to be women (18.7%) than men (73%), be younger (mean age 45 years v 56 years), have a higher cerebrospinal pressure before removal of fluid (mean values 172 v 137 mm H2O) and a lower systolic (mean values 120 v 134 mmHg) and diastolic blood pressure. We conclude that, although other factors may be associated with headaches, late ambulation is not effective in preventing spinal headaches after lumbar myelography.

Adult↗
PubMed2003

Molecular regulation of the oxytocin receptor in peripheral organs.

The oxytocin receptor belongs to the G-protein-coupled seven transmembrane receptor superfamily. Its main physiological role is regulating the contraction of uterine smooth muscle at parturition and the ejection of milk from the lactating breast. Oxytocin receptor expression is observed not only in the myometrium and mammary gland but also in the endometrium, decidua, ovary, testis, epididymis, vas deferens, thymus, heart and kidney, as well as in the brain. The expression profile shows a tissue-specific as well as a stage-specific pattern. The oxytocin receptor gene is a single-copy gene consisting of four exons and three introns, localized at 3p25-3p26.2 in the human chromosome. In transfection studies using a fusion construct containing the promoter region of the oxytocin receptor gene inserted in a reporter plasmid, neither proinflammatory cytokines nor oestrogen directly activate the gene. The nuclear fractions from up-regulated (term myometrium) and down-regulated (non-pregnant myometrium) tIssues show differential patterns of protein binding to the 5'-flanking region, and a human homologue of chicken MafF has been cloned as a term-myometrium-specific oxytocin receptor modulator. The oxytocin receptor gene appears to be highly methylated. Methylation around intron 1 and in intron 3 might contribute to tIssue-specific suppression of the gene. The oxytocin receptor is also regulated by desensitization, whose mechanism appears to involve loss of ligand-binding activity of the protein as well as suppression of the oxytocin receptor mRNA transcription. These findings taken together indicate that the oxytocin receptor is regulated in a very complicated manner, and the transcriptional regulatory elements critical for this regulation should be investigated further.

Animals↗
PubMed2003

Both estrogen and raloxifene cause G1 arrest of vascular smooth muscle cells.

The proliferation of vascular smooth muscle cells (VSMC) is a crucial pathophysiological process in the development of atherosclerosis. Although estrogen is known to inhibit the proliferation of VSMC, the mechanism responsible for this effect remains to be elucidated. In addition, the effect of raloxifene on VSMC remains unknown. We have shown here that 17beta-estradiol (E(2)) and raloxifene significantly inhibited the platelet-derived growth factor (PDGF)-stimulated proliferation of cultured human VSMC. Flow cytometry demonstrated that PDGF-stimulated S-phase progression of the cell cycle in VSMC was also suppressed by E(2) or raloxifene. We found that PDGF-induced phosphorylation of retinoblastoma protein (pRb), whose hyperphosphorylation is a hallmark of the G1-S transition in the cell cycle, was significantly inhibited by E(2) and raloxifene. These effects were associated with a decrease in cyclin D1 expression, without a change in cyclin-dependent kinase 4 or cyclin-dependent kinase inhibitor, p27(kip1) expression. ICI 182,780 abolished the inhibitory effects of E(2) and raloxifene on PDGF-induced pRb phosphorylation. Next, we examined which estrogen receptor (ER) is necessary for these effects of E(2) and raloxifene. Since VSMC express both ERalpha and ERbeta, A10, a rat aortic smooth muscle cell line that expresses ERbeta but not ERalpha, was used. The dose-dependent stimulation of A10 cell proliferation by PDGF was not inhibited by E(2) or raloxifene in contrast to the results obtained in VSMC. Moreover, E(2) and raloxifene significantly inhibited the PDGF-induced cyclin D1 promoter activity in A10 cells transfected with cDNA for ERalpha but not in the parental cells. These results suggested that E(2) and raloxifene exert an antiproliferative effect in VSMC treated with PDGF, at least in part through inhibition of pRb phosphorylation, and that the inhibitory effects of E(2) and raloxifene may be mainly mediated by ERalpha.

Animals↗
PubMed2003

Concurrent chemoradiotherapy with daily low dose intra-arterial cisplatin plus 5-fluorouracil for stage IV nasopharyngeal cancer.

This study aims to treat locally-advanced nasopharyngeal cancer by concurrent conventional irradiation at 2.0 Gy/day five days per week up to a total dose of 68 Gy, and daily intra-arterial infusion of cisplatin 3 mg/m2 plus 24 hours intravenous drip infusion of 5-fluorouracil 150 mg/m2 per day, five days per week. All of five enrolled patients completed the schedule, and treatment compliance was considered to be identical. Of the five patients evaluable for response, four with complete response (80%) and one with partial response (20%), with an overall response rate of 100% was achieved. The median survival time was 26 months. Two-year survival of the patients was 80%. This regimen showed marginal mucositis but well tolerated. We concluded that this treatment option is safe and effective for the locally-advanced nasopharyngeal cancer.

Adult↗
PubMed2002

Relationship of the fistulas to the rectum and genitourinary tract in mouse fetuses with high anorectal malformations induced by all-trans retinoic acid.

Since high anorectal malformations with fistulae in human embryos and fetuses of successive developmental stages have not been reported, the embryologic relationship between the rectal fistula (RF) and the genitourinary tract (GUT) in high anorectal agenesis (ARA) remains to be elucidated. This study investigates the developmental relationship between the RF and the GUT in male and female fetuses with high ARA using our established model for high ARA with fistula in mice. Pregnant mice received all-trans retinoic acid suspended in corn oil (5 mg/ml) 100 mg/kg i.p. on day 9 of pregnancy. All fetuses were removed from the uterus on a single day from days 12 to 18 of pregnancy. The caudal regions were analyzed histologically with hematoxylin and eosin staining. All fetuses examined had high ARA with fistula. On day 12 of pregnancy, an anomalous communication was seen between the urogenital sinus (UGS) and the rectum. In the affected female fetuses, on day 14 of pregnancy the paramesonephric (müllerian) ducts and müllerian tubercle were located above the rectocloacal fistula (RCF), and on day 18 of pregnancy the uterovaginal canal was located between the cloaca and the RCF. In the male fetuses, on day 14 of pregnancy the junction between the mesonephric (wolffian) duct and the UGS was located away from the junction between the rectum and the UGS. On day 18 of pregnancy the ejaculatory duct was located between the urinary bladder and the rectourethral fistula. The results of our experiment clearly show the embryologic relationship between the RF and the GUT with high ARA. The anomalous communication between the UGS and the rectum may interfere with normal caudal migration along the dorsal wall of the UGS at the junction between the UGS and the mesonephric or paramesonephric duct.

Anal Canal↗
PubMed2002

Effect of estrogen deficiency in the male: the ArKO mouse model.

Aromatase, the enzyme responsible for the conversion of androgens to estrogens, is present in the mouse gonads, brain, adipose tissue and bone. Depletion of endogenous estrogens in the aromatase deficient mouse (ArKO) caused by the targeted disruption of the Cyp19 gene resulted in an impairment of sexual behaviour and an age-dependent disruption of spermatogenesis. This disruption occurred during early spermiogenesis, due possibly to increased number of apoptotic round spermatids. Development of obesity was associated with ageing, decrease in lean mass, hypercholesterolemia, hyperleptinemia, and insulin resistance and hepatic steatosis. However, it was not correlated with hyperphagia but to decreased physically-active behaviour. ArKO mice also developed osteoporosis. Thus, studies using the ArKO mice model has led to several insights into the multiple roles played by estrogens in the development and maintenance of fertility, sexual behaviour, lipid metabolism and bone remodelling.

Animals↗
PubMed2002

Young's interference of electrons in field emission patterns.

We have observed interference fringes of electrons in field emission patterns from multiwalled carbon nanotubes at 60 K. The observed fringe pattern is reproduced by calculations based on the formula of Young's interference of two beams. Three-beam interference has also been detected over short time periods. We discuss the reason why Young's interference appears in the electron emission pattern in accelerating fields.

Journal Article↗
PubMed2002

Characteristic MRI findings in multiple system atrophy: comparison of the three subtypes.

We reviewed MRI findings in 29 patients with probable multiple system atrophy (MSA) to see whether there were common and or less common neuroradiological findings in the various clinical subtypes. We divided the patients into three clinical subtypes according to initial and predominant symptoms: 14 with olivopontocerebellar atrophy (OPCA), eight with the Shy-Drager syndrome (SDS) and seven with striatonigral degeneration (SND). The patients showed atrophy of the brain stem and cerebellum, high signal on T2-weighted images of the base of the pons and middle cerebellar peduncles, high and low signal on T2-weighted images of the putamen and atrophy of frontal and parietal lobes. The degree of atrophy of the middle cerebellar peduncle and cerebellum was greater in OPCA patients and a high-signal lateral rim to the putamen more frequent in SND. However, all findings were observed in all subtypes, and the degrees of atrophy of the putamen and pons and the frequency of high signal in the base of the pons were similar in the subtypes. We also found atrophy of the cerebral hemispheres, especially the frontal and parietal lobes, but its degree was not significantly different in the various subtypes. Our findings suggest that, although MSA can be divided clinically into three subtypes, most of the features on MRI are common and overlap in the subtypes, independently of the clinical presentation.

Brain↗
PubMed2002

Endoscopic fluorescence observation of gastric mucosa after indomethacin treatment in rats.

BACKGROUND AND STUDY AIMS: The present authors have already reported that mucosal autofluorescence intensity was increased in gastric lesions induced by nonsteroidal anti-inflammatory drugs. The aim of this study was to clarify whether the observation of mucosal autofluorescence with a newly established endoscopic fluorescence analyzing system could help us to recognize indomethacin-induced gastric lesion formation in vivo. MATERIALS AND METHODS: Gastric mucosal fluorescence intensity was measured time-sequentially after indomethacin treatment in rats, using a fluorescence endoscope system. The concentration of thiobarbituric acid-reactive substances in gastric mucosa was measured as an indicator of tissue lipid peroxidation. Fluorescent substances from rat stomachs were analyzed using high performance liquid chromatography. RESULTS: Treatment with indomethacin induced a time-dependent increase of fluorescence intensity. The concentration of thiobarbituric acid-reactive substances was also increased after the treatment. Pretreatment with radical scavenging reagent constrained the increase of both the fluorescence intensity and the concentration of thiobarbituric acid-reactive substances. The fluorescence products were coproporphyrin, protoporphyrin and mesoporphyrin. CONCLUSIONS: These findings indicate that the intensity of porphyrin fluorescence increased in gastric mucosal lesions induced by oxygen radicals. Endoscopic observation of mucosal fluorescence was shown to aid the sensitive and objective diagnosis of gastric injuries.

Animals↗
PubMed2002

A new method for measuring dynamic change of tracer distribution using dynamic single photon emission tomography with a slip-ring rotational gamma camera.

The clinical applicability of dynamic single photon emission tomograpy (SPET) using a dual-head gamma camera equipped with a slip-ring rotational mechanism, referred to as serial SPET, was examined in the present investigation. Serial SPET enables the production of tomographic images for any arbitrary time frame from an arbitrary range of data to 360 degrees. In a pre-clinical evaluation, a correlation between radioactivity concentration and serial SPET counts was evaluated in a phantom with continuous changes in 99mTc concentration. A differential value was obtained from each pair of SPET images; moreover, moving average approximation processing was investigated with respect to the elimination of noise in the data. In 11 and one patient presenting with cerebrovascular disease and meningioma, respectively, changes in SPET counts were evaluated when 99mTc ethyl cysteinate dimer (99mTc-ECD) was continuously administered at a constant rate in the resting state. Furthermore, in six of 11 subjects with cerebrovascular disease, changes occurring in SPET counts were examined by using acetazolamide loading while continuously administering 99mTc-ECD at a constant rate. Consequently, serial SPET enabled the evaluation of changes in radioactivity concentration over time in both the phantom and preliminary clinical studies. Data analysis by differential processing utilizing moving average approximation processing enabled the detection of minor changes in radioactivity concentration. An increase of 15.1+/-5.4% was observed in SPET counts of the unaffected cerebral hemisphere with acetazolamide loading. The response of the affected hemisphere was less prominent. These findings suggest that serial SPET would be an effective technique for the pharmacokinetic analysis of radiopharmaceuticals.

Acetazolamide↗
PubMed2002

Increase in focal concentration of deoxyhaemoglobin during neuronal activity in cerebral ischaemic patients.

BACKGROUND AND PURPOSE: Blood oxygenation level dependent contrast functional magnetic resonance imaging (BOLD-fMRI) has been applied to functional mapping in brain disorders, based on the assumption that normal adults and patients with brain disorders exhibit similar evoked cerebral blood oxygenation (CBO) changes. This study compared evoked CBO changes measured by near infrared spectroscopy (NIRS) with the activation mapping obtained by BOLD-fMRI in patients with cerebral ischaemia. METHODS: The study involved six normal adults and six patients with cerebral ischaemia. Hand grasping was performed as a motor task. All patients could perform the task similarly to the controls at the time of examination, but single photon emission computed tomography demonstrated low baseline cerebral blood flow and a decreased haemodynamic reserve in the primary sensorimotor cortex on the lesion side. Using NIRS, concentration changes of deoxyhaemoglobin (Deoxy-Hb), oxyhaemoglobin (Oxy-Hb), and total haemoglobin (Total-Hb) were measured in the primary sensorimotor cortex contralateral to the task. BOLD-fMRI signals were measured by 1.5 T magnetic resonance imaging using an echo-planar technique. Activation maps were calculated by statistical parametric mapping. RESULTS: In the controls, Deoxy-Hb decreased in association with increases of Oxy-Hb and Total-Hb in the primary sensorimotor cortex during the task. However, in the patients, Deoxy-Hb increased significantly from baseline, while Oxy-Hb and Total-Hb also increased, indicating the presence of rCBF increases in response to neuronal activation. BOLD-fMRI demonstrated only limited activation areas in the primary sensorimotor cortex on the lesion side. CONCLUSION: The CBO changes in patients with cerebral ischaemia differed from those of normal adults; Deoxy-Hb was increased in activation areas of the patients. This implies that BOLD-fMRI may overlook activation areas in the patients unless both increases and decreases of signal are taken into consideration.

Adult↗
PubMed2001

DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression.

In the human oxytocin receptor (OTR) gene, there is a CpG island from 140 bp upstream to 2338 bp downstream of the transcription start site (TSS). We investigated whether the methylation state of this region affects the transcription of the OTR gene. HepG2 derived from human hepatoblastoma, in which OTR gene transcription was suppressed, was treated with a demethylating agent, 5-azacytidine (Aza-C) for 2 days. Semiquantitative RT-PCR indicated that OTR mRNA was significantly increased by Aza-C treatment in a dose-dependent manner. We estimated the level of methylation within the CpG islands of the OTR gene in peripheral blood leukocytes, nonpregnant uterine myometrium, term uterine myometrium and liver. A 1.5-kb region located 5' upstream of the translation start site was divided into four fragments. Each was amplified by PCR after complete digestion with methylation-sensitive restriction enzyme HpaII. The amount of PCR products was largest in the liver, suggesting that this CpG island in the OTR gene is most highly methylated in liver, where the gene is always inactivated. We compared the effect of in vivo methylation of the CpG island on transcriptional activity of an OTR-reporter plasmid. The reporter gene activity of expression plasmid -2860/+1342-GL3, containing the CpG island, in HepG2 cells was suppressed to 30.6% of the control level after methylation with SssI methylase, while that of -2840/+144-GL3, without the CpG island was suppressed only to 81.4%. The deletion of the segment (MT2) where the level of methylation was most different between liver and uterus (-2860/+1342(del)MT2-GL3) rescued the suppression rate to 68.0%. These results indicate that the methylation of the CpG island in the human OTR gene promoter suppressed its transcription at least in liver and may regulate tissue specific gene expression among organs.

Azacitidine↗
PubMed2001

The reaction of fullerene C(60) with 4,6-dimethyl-1,2,3-triazine: formation of an open-cage fullerene derivative.

A thermal reaction of fullerene C(60) with 4,6-dimethyl-1,2,3-triazine (4) in o-dichlorobenzene gave azacyclohexadiene-fused fullerene derivative 5, by the reaction with intermediate azete 11, and then, after flash chromatography over SiO(2), open-cage fullerene derivative 6 having an eight-membered ring orifice on the C(60) cage. Compound 6 is assumed to be formed via addition of diradical intermediate 13 to C(60). Compound 6 underwent a further photochemical reaction with singlet oxygen with the cleavage of one of the double bonds at the rim of the orifice to afford triketone derivative 8 having a 12-membered ring orifice.

Carbon↗
PubMed2001

Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a member of the scavenger receptor family, and is known to be expressed in monocytes/macrophages. We investigated the effect of histamine on the expression of LOX-1 in cells of the human monocytic leukemia cell line THP-1. Histamine as well as forskolin and dibutyryl cyclic AMP (Bt2-cAMP) stimulated the THP-1 monocytes to express the LOX-1 gene at the transcription level. This histamine effect on LOX-1 gene expression, via the histamine H2 receptor-mediated cAMP signal transduction pathway, was reduced after differentiation of the cells into macrophages, even though forskolin and Bt2-cAMP still enhanced the gene expression. The alteration of the responsiveness of LOX-1 expression to histamine was related to suppressed expression of the H2 receptor in THP-1 macrophages. The switch of the predominant class of histamine receptors between H1 and H2 would modulate the effects of histamine on LOX-1 gene expression in monocytes and macrophages, and therefore, would play a certain role in the inflammatory aspects of atherogenesis.

Bucladesine↗
PubMed2001

Involvement of nuclear transcription factor Sp1 in regulating glucose transporter-1 gene expression during rat trophoblast differentiation.

Glucose transporter-1 (GLUT1) is important in placental glucose transport. However, the mechanism of regulation of placental GLUT1 expression remains to be elucidated. We show here that the level of GLUT1 protein in rat choriocarcinoma cells (Rcho-1) decreased during differentiation. To analyze the regulatory mechanism of rat GLUT1 (rGLUT1) gene expression, we transfected rGLUT1 promoter-chloramphenicol acetyltransferase constructs into Rcho-1 cells. Deletion analysis of the rGLUT1 promoter suggested that the region -76/-53 bp was essential for basal transcriptional activity. Electrophoretic mobility shift assays showed that transcription factors Sp1 and Sp3 bound two GC boxes in the region -99/-33 bp of the rGLUT1 promoter. Mutation analysis of the Sp1 binding sites revealed that the promoter-proximal site located between -76 and -53 bp was essential for basal rGLUT1 promoter activity. Furthermore, the decreased level of GLUT1 may result from a decreased level of Sp1 during differentiation. These findings suggest that Sp1 is involved in the regulation of rGLUT1 gene expression during rat trophoblast differentiation.

Animals↗
PubMed2001

The reaction of fullerene C(60) with phthalazine: the mechanochemical solid-state reaction yielding a new C(60) dimer versus the liquid-phase reaction affording an open-cage fullerene.

The reaction of fullerene C(60) with phthalazine was studied both in solution and in the solid state using the high-speed vibration-milling technique. The reaction in solution gave open-cage fullerene derivative 1 in 44% yield by a one-pot reaction. In contrast, the solid-state reaction afforded dimeric derivative 2 as the sole product. Dimeric derivative 2 was found to undergo intramolecular [2 + 2] cycloaddtion between the two C(60) cages located in close proximity to give a new C(60) dimer 6 in quantitative yield. The structures of these new derivatives of C(60) were determined by spectroscopic methods, and the electrochemical behavior of 2 and 6 was also studied.

Journal Article↗