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Biomedical subjects

Yuji Murata

Publications and source records attributed to Yuji Murata.

At least 91 records · Page 5Linked to original sources
PubMed2003

Tamoxifen inhibits cell proliferation via mitogen-activated protein kinase cascades in human ovarian cancer cell lines in a manner not dependent on the expression of estrogen receptor or the sensitivity to cisplatin.

Although tamoxifen (TAM), which is widely used in the treatment of breast cancer, also has a beneficial effect on cisplatin-refractory ovarian cancer, the biological mechanism of this effect has remained obscure. TAM, besides its action as an antiestrogen, also inhibits cell proliferation of estrogen receptor (ER)-negative cells by an unknown mechanism. Therefore, we examined the roles of the MAPK family in the antiproliferative effect of TAM on cisplatin-resistant Caov-3, which expresses ER and cisplatin-sensitive A2780, which does not express ER. The number of viable cells was reduced by TAM dose-dependently. TAM induced the activation of ERK, c-Jun N-terminal protein kinase (JNK), and p38 with different time courses. PD98059 canceled the reduction of the number of viable cells by 1 microM TAM and inhibited the TAM-induced cell-cycle arrest at the G(1) phase and dephosphorylation of the retinoblastoma protein. Either expression of dominant-negative JNK or pretreatment with SB203580 canceled the reduction of the number of viable cells by 5 microM TAM and inhibited the apoptotic nuclear changes and the cleavage of poly (ADP-ribose) polymerase induced by TAM. These results provide evidence that whereas the ERK cascade is involved in the induction of cell-cycle arrest at the G(1) phase by lower concentrations of TAM, the JNK or p38 cascade is involved in the induction of apoptosis by higher concentrations of TAM in both types of cells.

Adenocarcinoma, Papillary↗
PubMed2003

Estrogen inhibits paclitaxel-induced apoptosis via the phosphorylation of apoptosis signal-regulating kinase 1 in human ovarian cancer cell lines.

The influence of postoperative estrogen replacement therapy on the sensitivity of ovarian cancer to paclitaxel remains elusive. We examined whether estrogen affects paclitaxel-induced apoptosis in the Caov-3 human ovarian cancer cell line, which expresses estrogen receptor. 17beta-Estradiol (E2) significantly reversed the paclitaxel-induced apoptosis and reduction of cell viability, and a highly selective estrogen receptor antagonist, ICI182,780, and a phosphatidylinositol 3-kinase inhibitor, LY294002, attenuated the reversal effect of E2 on paclitaxel-induced apoptosis and reduction of cell viability. E2 significantly induced the phosphorylation of Akt. Akt and apoptosis signal-regulating kinase 1 (ASK1) were physically associated, and E2 induced the phosphorylation of ASK1 at serine-83, which is a consensus Akt phosphorylation site. We confirmed a previous report showing that paclitaxel induces cell damage via the ASK1-c-Jun N-terminal protein kinase (JNK) cascade. E2 inhibited the paclitaxel-induced JNK activation, and the E2-induced inhibition of the paclitaxel-induced JNK activation was attenuated in cells treated with either ICI182,780 or LY294002 or transfected with ASK1S83A, in which a consensus Akt phosphorylation site at serine-83 was converted to alanine. The inhibitory effect of E2 on the paclitaxel-induced reduction of cell viability and apoptosis was diminished in cells transfected with ASK1S83A. These results indicate that E2 inhibits paclitaxel-induced cell damage by inhibiting JNK activity via phosphorylation of Akt-ASK1. Thus, treatment of ovarian cancer with paclitaxel might be less effective in the setting of postoperative estrogen replacement therapy.

Adenocarcinoma, Papillary↗
PubMed2003

Anticarcinogenic activity of natural sweeteners, cucurbitane glycosides, from Momordica grosvenori.

To search for cancer chemopreventive agents from natural resources, many phytochemicals and food additives have been screened. Consequently, two natural sweeteners, mogroside V and 11-oxo-mogroside V isolated from the fruits of Momordica grosvenori, exhibited strong inhibitory effect on the primary screening test indicated by the induction of Epstein-Barr virus early antigen (EBV-EA) by a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). These sweet glycosides, having cucurbitane triterpenoid aglycon, exhibited the significant inhibitory effects on the two-stage carcinogenesis test of mouse skin tumors induced by peroxynitrite (ONOO-) as an initiator and TPA as a promoter. Further, 11-oxo-mogroside V also exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2003

Genetic alterations in ovarian carcinoma: with specific reference to histological subtypes.

Multiple genetic changes including activation of proto-oncogenes and inactivation of tumor suppressor gene are involved in the development of human ovarian cancer. We describe such genetic alterations with specific reference to histological subtypes. K-ras activation is specific for mucinous tumors including adenomas. Borderline tumors and carcinomas, suggesting that K-ras activation may be associated with the mucinous differentiation rather than malignant transformation. Inactivation of p53 is detected in 30-40% of ovarian carcinoma. Mutations are more frequently observed in serous carcinomas, but not found in adenomas or rarely found in borderline tumors, suggesting that p53 mutations may be directly involved in malignant transformation. TGFbeta-2 mutations are found in 50% of endometrioid carcinoma, but rarely in other type. Loss of DCC mRNA expression is found in 50% of serous carcinomas but less frequently in other type. Loss of DCC expression is rare in borderline tumors and adenomas, suggesting that inactivation of DCC may be directly involved in malignant transformation. Microsatellite instability (MI) is found in 17% of ovarian carcinomas, and is frequently found in endometrioid carcinomas. Although inactivation of p16 by point mutation or deletion is rare, p16 inactivation by loss of expression is relatively common.

Acid Anhydride Hydrolases↗
PubMed2003

Rapid changes of flow-mediated dilatation after surgical menopause.

OBJECTIVES: Estrogen acts directly on endothelial nitric oxide synthase through a non-genomic mechanism, resulting in rapid dilatation of blood vessels. In this study, we examined the change of endothelial function after surgical menopause. METHODS: In 20 subjects who underwent gynecological operations (ovariectomy (OVX) 12, sham (SHAM) operation 8), postoperative changes of flow-mediated dilatation (FMD) of the brachial artery were examined using ultrasonography. Postoperative changes of the response to nitroglycerin (NTG) were also studied in these patients. RESULTS: In the OVX group, significant decreases of FMD were observed 1 week after the operation, although no changes were observed in the response to NTG. In the SHAM group, no remarkable changes of FMD or the response to NTG were observed after the operation. CONCLUSIONS: OVX influences endothelium-dependent vasodilatation within as little as 1 week. Therefore, it may be important to address the rapid changes of circulation after surgical menopause in order to prevent cardiovascular disease.

Adult↗
PubMed2003

Regional cerebral blood flow in depressed patients with white matter magnetic resonance hyperintensity.

BACKGROUND: Functional neuroimaging studies have consistently demonstrated decreased regional cerebral blood flow (rCBF) or metabolism in the frontal lobe, temporal lobe, or anterior cingulate gyrus of depressed patients. On the other hand, white matter hyperintensity as defined by magnetic resonance imaging (MRI) has been the most consistently replicated finding in structural neuroimaging studies on depression; however, these functional and structural neuroimaging findings of depression have not been well integrated. We aimed to clarify the possible associations of MRI-defined subcortical hyperintensities with rCBF changes in depressed patients. METHODS: Twelve depressed patients with subcortical hyperintensities defined by MRI, 11 depressed patients without MRI hyperintensities, and 25 healthy volunteers underwent 99mTc ECD SPECT. Group comparisons of their rCBF and correlation analysis between MRI hyperintensity and rCBF in patients were performed with a voxel-based analysis using statistical parametric mapping (SPM) software. RESULTS: Depressed patients showed decreased rCBF compared with control subjects in the frontal lobe, temporal lobe, and anterior cingulate gyrus whether subcortical hyperintensity existed or not; however, the patients with MRI hyperintensity showed decreased rCBF in the thalamus, basal ganglia, and brainstem in addition to cortical areas. Further, the score for white matter hyperintensity correlated negatively with rCBF in subcortical brain structures, including the thalamus and right basal ganglia. CONCLUSION: Our study indicates that depressed patients with MRI hyperintensities may have dysfunction in subcortical brain structures in addition to dysfunction in the fronto-temporal cortical structures.

Adult↗
PubMed2003

Apoptosis and related proteins in placenta of intrauterine fetal death in prostaglandin f receptor-deficient mice.

The present study investigated whether the increase of apoptosis in the placenta is associated with intrauterine fetal death in prostaglandin F receptor-deficient mice. Apoptosis was demonstrated within placental and decidual tissue by the TUNEL method. The majority of apoptosis was found in syncytiotrophoblast tissues. Enhanced TUNEL-positive staining in the syncytiotrophoblast layer was scattered in the placental tissues in clusters of apoptotic cells in the death group. Marked TUNEL-positive cells were identified in decidua of both groups. The rate of apoptosis in the placenta and decidua in the death group was higher than that in the survival group (P < 0.05). Immunohistochemical analysis showed that the level of active caspase-3 protein expression in the placenta in the death group was much higher than that in the survival group. The level of Bcl-2 protein expression in the placenta in the death group was much lower than that in the survival group. Western blot analysis demonstrated that increased expression of the active form of caspase-3 was detected in the placenta and decidua in the death group compared with that in the survival group. In contrast, a decrease in the expression of Bcl-2 was detected in the placenta and decidua in the death group compared with that in the survival group. Enhanced expression of Bax:Bcl-2 ratio was detected in placenta and decidua in the death group compared with that in the survival group. Thus, significantly increased apoptosis in the mouse placenta and decidua might be involved in the pathophysiologic mechanism of intrauterine fetal death.

Animals↗
PubMed2003

MR imaging of the thyroid: correlation between apparent diffusion coefficient and thyroid gland scintigraphy.

PURPOSE: To evaluate the usefulness of echo-planar MR imaging for assessing the thyroid function and confirm the clinical use of MR imaging for thyroid diseases. MATERIALS AND METHODS: Thirty-four patients with a variety of thyroid disorders (24 Graves disease; five subacute thyroiditis; five Hashimoto thyroiditis) were examined using T1-, T2-, and diffusion-weighted magnetic resonance (MR) imaging and thyroid scintigraphy with Tc-99m pertechnetate. RESULTS: The ADC values obtained from the diffusion-weighted images of the patients with Graves disease were significantly higher than those of patients with subacute hyroiditis and Hashimoto thyroiditis, though no difference among those disorders was observed on T1- and T2-weighted images. Based on the ADC value, anisotropy was not observed in the thyroid gland. An ADC value of 1.82 x 10(-3) mm(2)/second or higher indicated the presence of Graves disease (sensitivity 75%, specificity 80%). CONCLUSION: Diffusion-weighted MR images may be of value for the diagnosis of thyroid diseases and could be clinically important in the evaluation of thyroid function.

Diffusion Magnetic Resonance Imaging↗
PubMed2003

Brain perfusion SPECT in patients with corticobasal degeneration: analysis using statistical parametric mapping.

We sought to determine the characteristics of brain perfusion in patients with corticobasal degeneration (CBD) using single photon emission computed tomography (SPECT) and statistical parametric mapping (SPM). Thirteen patients with CBD and 10 age-matched healthy volunteers were examined using brain perfusion SPECT and (99m)Tc-ethyl cysteinate dimer (ECD). Regional cerebral blood flow (rCBF) measurements were performed noninvasively using a graphic analysis method. Both the absolute rCBF data (raw data) and the adjusted rCBF data (global CBF normalized to 50 ml/100 g/min) were used in the SPM analysis. A significant decrease in the absolute rCBF was observed in extended areas of the brain in CBD patients compared to the control group. These areas included the frontal, parietal, and temporal cortices; basal ganglia; thalamus; and pontocerebellar regions. Our results suggest that the extent of the reduced rCBF region in CBD patients is more widespread than previously reported.

Aged↗
PubMed2003

Pneumoretroperitoneum, pneumomediastinum, pneumopericardium, and subcutaneous emphysema complicating sigmoidoscopy: report of a case.

An 80-year-old woman presented to our outpatient center with abdominal pain and blood-stained stools. She underwent a colonoscopy, which showed a 4-cm type II tumor in the rectum. About 2 h after the colonoscopy, mild facial edema and subcutaneous emphysema developed around her neck. A chest X-ray showed pneumopericardium, pneumomediastinum, and subcutaneous emphysema, and an abdominal X-ray demonstrated retroperitoneal air. An exploratory laparotomy was performed on the second day after the colonoscopy, which showed air in the subserosal space of the sigmoid colon. The air seemed to have leaked from a 2-cm inflamed diverticulum in the sigmoid colon. The mesosigmoid was also expanded by air. We discuss the anatomical mechanism of the various clinical presentations of extraluminal air following colonoscopy.

Adenocarcinoma↗
PubMed2003

Bladder tumor found by tension-free vaginal tape procedure.

BACKGROUND: Tension-free vaginal tape (TVT) is thought to be a most effective therapy against stress urinary incontinence. It is rare to find a bladder tumor by the TVT procedure. CASE: A 76-year-old woman with stress urinary incontinence underwent a TVT procedure. Cystoscopy performed in conjunction with the TVT procedure detected a papillary tumor. Transurethral resection of the bladder tumor was performed after the TVT procedure. CONCLUSION: Taking the possible presence of bladder tumors into consideration, TVT-related cystoscopy procedures should be performed carefully. Moreover, the case reported here suggests, at least in the short term, not only that the TVT device does not adversely affect the operability of transurethral resection of the bladder tumor, but also that the transurethral resection of the bladder tumor procedure does not lead to increased levels of urinary incontinence.

Aged↗
PubMed2003

Fetal hemorrhage associated with congenital intestinal atresia.

We encountered two cases of severe intrauterine hemorrhage associated with congenital intestinal atresia. In both cases, the first sign that necessitated immediate clinical management was the abnormal fetal heart rate patterns, represented by prolonged bradycardias and late decelerations. This occurred immediately after the onset of labor. An emergency cesarean section was performed on both patients and, despite being born with severe anemia, the condition of the infants was excellent. We found that continuous fetal heart rate monitoring should be performed if polyhydramniosis suspected, when the fetus is diagnosed with congenital intestinal atresia and when changes in intrauterine pressure are clinically expected, such as at the onset of labor or after amniocentesis.

Adult↗
PubMed2003

Effects of hyperthermia on hypoxic-ischemic brain damage in the immature rat: its influence on caspase-3-like protease.

OBJECTIVE: Recent clinical studies suggested that intrapartum maternal fever is a strong independent risk factor for neonatal encephalopathy. With use of a well-studied rat model of neonatal hypoxic-ischemic encepalopathy, this study investigated the hypothesis that intraischemic hyperthermia accelerates and worsens brain injury in immature animals and examined whether apoptotic cell death machinery is involved in the underlying mechanisms. STUDY DESIGN: Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% oxygen for 15 minutes (n = 32 rats). During the 15-minute hypoxic insult, body temperature was elevated to 40 degrees C in 16 animals (hyperthermic hypoxic insult group), and was maintained at 37 degrees C in 16 animals (normothermic hypoxic insult group). Then both groups were placed in the same chamber in a water bath at 37 degrees C for 24 hours and finally returned to the mothers. Caspase-3-like activity was assessed 36 hours after the hypoxic-ischemic insult. One week later, microtubule-associated protein-2 immunostaining was used to examine neuronal damage. RESULTS: Intraischemic hyperthermia was shown to activate the caspase-3 activity 36 hours after hypoxia-ischemia while caspase-3 was activated insignificantly in the normothermic hypoxic insult group at that time. The hyperthermic hypoxic insult group also showed a reduced microtubule-associated protein-2-positive area 7 days after hypoxia-ischemia compared with that in the normothermia group. CONCLUSION: Hyperthermia during hypoxia-ischemia makes the immature brain inordinately susceptible to hypoxic-ischemic insult and causes brain injury, even if hypoxic-ischemic insult is so mild that it causes no or little injury by itself. This effect may be mediated by the escalation of the apoptotic cell death pathway in the immature animal.

Animals↗
PubMed2003

Antenatal prediction of pulmonary hypoplasia by acceleration time/ejection time ratio of fetal pulmonary arteries by Doppler blood flow velocimetry.

OBJECTIVE: The purpose of this study was to develop a new method for the antenatal prediction of pulmonary hypoplasia by Doppler blood flow velocimetry. STUDY DESIGN: One hundred seventy-seven fetuses (160 normal fetuses and 17 fetuses with congenital anomalies that may affect fetal lung growth and/or development) were studied. Blood flow waveforms at the main branches of the pulmonary arteries were recorded by Doppler echocardiography from 20 to 39 weeks of gestation. The ratio of acceleration time to ejection time was calculated from the waveform as a parameter to predict pulmonary hypoplasia. RESULTS: Doppler waveform of normal fetal pulmonary artery showed a "spike-and-dome" pattern. The normal values of acceleration time/ejection time ratio from the right and left pulmonary arteries were 0.17 +/- 0.04 and 0.15 +/- 0.04, respectively. These values were not significantly altered through the gestational age observed in this study. The acceleration time/ejection time ratio of either right or left pulmonary artery was measured successfully in all cases of fetal congenital anomalies. In 8 of 17 fetuses, acceleration time/ejection time ratio was measured at both of the pulmonary arteries. Because of a congenital anomaly that affected the fetal lung or thorax asymmetrically (as in congenital diaphragmatic hernia or congenital cystic adenomatoid malformations of the lung), the acceleration time/ejection time ratio of both of the pulmonary arteries could be measured in only 5 of 13 fetuses. The technical difficulties for the measurement always existed in the affected side. Eleven of the 17 fetuses with congenital anomalies survived without signs of clinical pulmonary hypoplasia or persistent pulmonary hypertension of the newborn infant. The fetuses revealed normal acceleration time/ejection time ratio from at least one pulmonary artery. The remaining 6 fetuses died of pulmonary hypoplasia, and the diagnosis was confirmed by autopsy or clinical findings. Of those 6 fetuses, 5 fetuses demonstrated the acceleration time/ejection time ratio below normal in one side, and the ratio could not be obtained on the other side; 1 fetus showed the acceleration time/ejection time ratio below the normal range in both sides. CONCLUSION: The acceleration time/ejection time ratio by Doppler velocimetry that was obtained at the main branches of fetal pulmonary artery was consistent throughout gestational age from 20 to 39 weeks. This ratio appears to be an accurate parameter with which to predict the subsequent development of pulmonary hypoplasia and clinical outcomes of the newborn infants with high positive and negative predictive values (positive predictive value, 100%; negative predictive value, 100%).

Blood Flow Velocity↗
PubMed2003

Fractalkine (FRK) levels in amniotic fluid and its production during pregnancy.

Fractalkine is a new CX(3)C chemokine that has chemoattractant activity for T cells, monocytes and natural killer (NK) cells. Western blot analysis revealed that fractalkine protein was detected as a 95 kDa band in both the amniotic fluid and the amnion during the second and third trimesters. Immunohistochemistry using an anti-fractalkine polyclonal antibody revealed positive staining of epithelial cells in amnion and trophoblasts in both the second and third trimesters. Neonatal urine also contained detectable amounts of fractalkine. RT-PCR detected fractalkine mRNA transcripts in the amnion. To determine whether fractalkine receptor (CX(3)CR1)-positive cells were present in amniotic fluid and amnion, we performed RT-PCR using specific primers for CX(3)CR1. CX(3)CR1-positive cells had migrated into the amniotic fluid and the amnion. The present findings suggest that fractalkine found in amniotic fluid may contribute to the immunodefence mechanism during pregnancy.

Amnion↗
PubMed2003

Highly efficient and minimally invasive in-vivo gene transfer to the mouse uterus using haemagglutinating virus of Japan (HVJ) envelope vector.

The uterus is obviously critical in implantation, development of the fetus and parturition. Endometrial cancer derived from endometrial epithelium is one of the common malignancies in the female reproductive tract. In order to clarify the local mechanisms of reproductive physiology and establish a non-systemic therapeutic strategy for reproductive failure as well as for endometrial cancer, we applied haemagglutinating virus of Japan envelope (HVJ-E) vector to in-vivo gene transfer into the uterine cavity of IVCS mice. Injection of HVJ-E vector into mouse uterine cavity on day 1.5 post coitum (p.c.) introduced a reporter gene approximately 120-fold more efficiently than introduction using the cationic liposome method. The expression of the introduced gene continued for at least 3 days. The plasmid vector was localized in the endometrial epithelium, whereas oligo deoxynucleotides were distributed throughout the epithelium, stromal cells and myometrium. HVJ-E vector did not affect the pregnancy rate, course of pregnancy, litter size, fetal growth in utero or parturition, and did not transfect the exogenous gene to the fetus. These results indicate that gene transfer into the uterus using HVJ-E vector is highly efficient and safe during pregnancy, and results in a well controlled distribution of the exogenous DNA. We believe that this procedure should be widely applicable for investigations of reproductive physiology as well as for methods of local gene therapy in the uterus.

Animals↗
PubMed2003

Mutations in the STK11 gene characterize minimal deviation adenocarcinoma of the uterine cervix.

Minimal deviation adenocarcinoma (MDA) is a well-differentiated variant of mucinous adenocarcinoma of the uterine cervix and is found relatively infrequently in the general population. However, MDA is strongly associated with Peutz-Jeghers syndrome (PJS), a rare hereditary autosomal disorder characterized by benign hamartomatous polyposis in the gastrointestinal tract and mucocutaneous pigmentation. A serine threonine kinase gene, STK11, has been identified as the tumor suppressor gene responsible for the PJS. In this study we investigated the possible direct role of STK11 in the development of MDA of the uterine cervix. Eleven rare cases of mucinous MDA, not known to be associated with PJS, were screened for the presence of mutations in the STK11 gene by single-strand conformation polymorphism analysis of PCR-amplified DNA fragments. Subsequently our findings were confirmed with cloning and sequencing. As a control, 24 cases of endocervical adenocarcinomas of other histologic subtypes, with no family history of PJS (19 mucinous adenocarcinomas, 4 endometrioid adenocarcinomas, and 1 clear cell adenocarcinoma), 15 cases of squamous cell carcinomas of the uterine cervix, 5 cases of endocervical glands with pyloric gland metaplasia, and 2 deeply situated nabothian cysts were investigated. Somatic mutations of the STK11 gene were confirmed in 6 (55%) of the 11 mucinous MDAs and 1 (5%) of the 19 mucinous adenocarcinomas, but not in the 5 nonmucinous adenocarcinomas, the 15 squamous cell carcinomas, nor the 5 endocervical glands with gastric metaplasia. MDAs with the STK11 mutation had a significantly poorer prognosis than MDAs without the STK11 mutation (p = 0.039). A germline mutation of STK11 was detected in one PJS patient with mucinous adenocarcinoma of the uterine cervix. These results suggest that mutations in the STK11 gene may play an important role in the etiology of MDA of the uterine cervix and may distinguish this rare tumor from other common types of adenocarcinoma of the uterine cervix.

AMP-Activated Protein Kinase Kinases↗