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Biomedical subjects

Yuji Murata

Publications and source records attributed to Yuji Murata.

At least 37 records · Page 2Linked to original sources

Mid-second trimester measurement of fetal nasal bone length in the Japanese population.

AIM: We carried out a preliminary study to compare the nasal bone length (NBL) and biparietal diameter/NBL (BPD/NBL) ratio between the Japanese and white populations. METHODS: Three hundred and fifty nine (359) singleton fetuses of healthy Japanese couples were examined from June 2004 to October 2005. NBL was measured by the strict midsagittal section. The reference range of NBL was established from cross-sectional data between 15 and 25 weeks' gestation. RESULTS: The success rate of obtaining reliable NBL was 93% (333/356). There were 330 fetuses (93%) available for constructing a reference range from the population. The median NBL increased from 3.2 mm at 15 weeks' to 7.6 mm at 25 weeks' gestation. The median of BPD/NBL ratio was 9.01. CONCLUSIONS: We demonstrated that NBL was significantly shorter and BPD/NBL was significantly greater in the Japanese population than those in the white and black populations.

Adolescent↗

Spontaneous rupture of uterine surface varicose veins in pregnancy: a case report.

BACKGROUND: Spontaneous rupture of uterine surface varicose veins is rare but may become a serious complication of pregnancy. CASE: A 40-year-old woman, gravida 2, para 0-0-1-0, presented with worsening generalized abdominal pain after occasional nausea, vomiting and diarrhea over the previous 2 days. After a 4-hour observation period, sudden onset of severe, prolonged fetal heart rate decelerations was recognized along with frequent uterine contractions. Emergency cesarean section was performed under a tentative diagnosis of placental abruption. A live, female infant weighing 1,730 g was delivered and had Apgar scores of 5 and 9 at 1 and 5 minutes, respectively. Intraoperatively, approximately 500 mL of hemoperitoneum was present, and multiple bleeding sites from varicose veins on the posterior uterine surface were detected. Because the maternal vital signs became unstable and hemostasis was difficult, hysterectomy was performed and blood transfusion administered. CONCLUSION: Although very rare, hemoperitoneum should be included in the differential diagnosis when a pregnant woman experiences acute-onset, severe abdominal pain, even without an episode of abdominal trauma.

Adult↗

Secretory leukocyte protease inhibitor levels in cervicovaginal secretion of elderly women.

OBJECTIVE: Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. The aim of the present study was to examine whether there is an association between the SLPI concentration in the cervicovaginal secretion (CS) and vaginal complaints of post-menopausal women. METHODS: Uterine cervix tissues and CS of peri- or post-menopausal women were obtained. SLPI was assayed by ELISA. To determine the level of SLPI mRNA and the localization of SLPI protein in the uterine cervix, we performed RT-PCR and immunochemical staining, respectively. RESULTS: The levels of SLPI in the CS of post-menopausal women with vaginal complaints were significantly lower that those of post-menopausal women without vaginal complaints. The levels of SLPI in the CS of post-menopausal women were lower that those of peri-menopausal women and post-menopausal women treated with hormone replacement therapy. Positive staining was observed in epithelial cells of the cervix of elderly women, however, the intensity was weaker than that in peri-menopausal women. Positive staining was also observed in gland cells of the cervix of peri-menopausal women, but not in those of post-menopausal women. SLPI transcripts were detected in the cervix of post-menopausal women. The treatment of post-menopausal women with vaginal estrogen increased the concentrations of SLPI in CS of post-menopausal women. CONCLUSIONS: The present findings suggest that the decreased amount of SLPI in the CS of post-menopausal women might be one of the causes of the symptoms of post-menopausal women and contribute to the immunodefense mechanisms of the elderly women.

Aged↗

Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer.

LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2, were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis. To clarify the metastatic potential of LAMP3 in cervical cancers, we transfected a LAMP3 expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS cell-injected mice and in only 1 of 11 control mice. Histologic study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space. In clinical samples, quantitative real-time reverse transcription-PCR (RT-PCR) analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias, compared with a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers. These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential and may be a prognostic factor for cervical cancer.

Animals↗

Gestational change of K+ channel opener effect is correlated with the expression of uterine KATP channel subunits.

OBJECTIVE: We analyzed the gestational changes of pharmacological activity and molecular levels of KATP channels in rat myometrium. STUDY DESIGN: Using rat myometrium, the effects of K+ channel openers (KCOs) were examined in an isometric tension study of oxytocin-induced contraction. We also examined the effects of KCOs on the intracellular Ca2+ levels of cultured myometrial cells. The expression of myometrial KATP channels was assessed by RT-PCR and Northern blot analysis. RESULTS: The effect of KCOs were altered during pregnancy, with a significant increase of their potency at day 18 of pregnancy followed by a decline towards the non-pregnant level at the day of delivery. KCOs suppressed the Ca2+ influx across the cell membrane. The mRNAs encoding each component of myometrial KATP channels, Kir6.1 and SUR2B, exhibited gestational stage-dependent alterations similar to those of the effects of KCOs. CONCLUSION: These findings suggest that KCOs inhibit uterine myometrial contraction more effectively during pregnancy than in the non-pregnant state due to gestation-enhanced expression of KATP channels, implying that KCOs might be useful for preventing premature delivery.

Animals↗

In vivo gene transfer into the mouse uterus: a powerful tool for investigating implantation physiology.

In vivo transient transfection of cDNA into uterine endometrium during the implantation period provides great opportunities to analyse the physiology/pathophysiology of implantation at the molecular level. We review here methodologies which have been applied for this purpose. Viral vectors are widely used for in vivo gene therapy models; however, there is no successful example of gene transfer into the uterus using such vectors. Cationic liposome-based technologies have produced some successful results, causing alterations in implantation physiology. We applied a haemagglutinating virus of Japan envelope (HVJ-E) vector system and showed that the transfection efficiency was much higher than that of methods based on cationic liposome. Commercial HVJ-E vector (GenomONE-Neo) is now also available. Several successful examples of in vivo gene transfer revealed that calcitonin, Hoxa 10 and NF kappaB play important roles in determining the efficiency or timing of implantation. Based on this knowledge, we should further analyse the pathophysiology of human implantation failure using human materials.

Abortion, Spontaneous↗

Up-regulation of c-met protooncogene product expression through hypoxia-inducible factor-1alpha is involved in trophoblast invasion under low-oxygen tension.

During early pregnancy, the invasion of trophoblast cells into the decidua of the uterus is one of the essential steps in appropriate placentation. In this period, trophoblast cells are exposed to a relatively low-oxygen environment. The c-met protooncogene product (Met), which is a high-affinity receptor for hepatocyte growth factor, plays an important role in controlling the invasion of many types of cells. The present study was designed to investigate the effect of low-oxygen tension on Met expression and the invasiveness of trophoblast cells isolated from early-stage human placenta and trophoblast-derived BeWo cells and JEG-3 cells. RT-PCR and immunoblot analyses demonstrated that low-oxygen tension (1% O2) stimulated the expression of Met mRNA and protein, respectively. Hepatocyte growth factor production in the cells was not affected by oxygen tension. Transient transfection of BeWo cells with a hypoxia-inducible factor (HIF)-1alpha expression vector to induce exogenous expression of HIF-1alpha significantly increased the level of Met mRNA and protein, compared with transfection of a control vector. To examine whether this up-regulation of Met was directly induced by HIF-1alpha, we performed the chromatin immunoprecipitation assay, which revealed that HIF-1alpha binds to the promoter region of the Met gene under low-oxygen tension. JEG-3 cells cultured under 1% O2 showed a more invasive character than those cultured under 20% O2, whereas inhibition of Met expression by small interfering RNAs prevented the low-oxygen, tension-induced invasiveness. These results suggest that the induction of Met expression by low-oxygen tension may play an important role in the physiology of early pregnancy by promoting the invasion of trophoblast cells into the decidua of the uterus.

Cell Movement↗

Expression of nectin-2 in mouse granulosa cells.

OBJECTIVE: The development and maturation of the ovarian follicles are characterized by structural changes that require components involved in cell-cell adhesion systems. Recently a novel group of cell adhesion molecules named nectins has been identified. The present study examined expression and cell-specific localization of nectins during mouse follicular development. STUDY DESIGN: Expression of nectins in mouse ovary was investigated by immnuoblot analysis and immunohistochemistry. More precise localization was determined by electron microscopy. RESULTS: Immunoblot analysis revealed expression of nectin-2 and nectin-3 but not nectin-1 in ovarian granulosa cells. Immunohistochemistry demonstrated expression of nectin-2 at cell-cell adhesion sites of granulosa cell layer in the primary and preantral follicles. Especially, intense immunoreactivity of nectin-2 accumulated around the zona pellucida. In antral follicles, the intensity of nectin-2 expression on granulosa cells was decreased. By electron microscopy nectin-2 was detected not only on thin extensions of granulosa cells penetrating the zona pellucida, but also on the attachment sites between thin extensions of granulosa cells and oocyte surface. CONCLUSION: The restricted expression of nectin-2 in the granulosa cells of primary and preantral follicles might reflect some of the molecular changes in cell-cell adhesion during early follicular development.

Animals↗

Elevated expression of N-acetylglucosaminyltransferase V in first trimester human placenta.

In early pregnancy, placental trophoblast cells rapidly grow and invade into maternal uterine tissue. N-Acetylglucosaminyltransferase V (GnT-V) and its product, beta1-6-GlcNAc branching glycan, are known to correlate with tumor invasion and metastasis. Since the placentation process resembles invasion of cancer cells, we examined the expression of beta1-6-GlcNAc branching glycan and GnT-V in human placenta. Placentas derived from the first trimester contained a larger amount of beta1-6-GlcNAc branching glycan, detected by leukoagglutinating phytohemagglutinin lectin blotting, than those at term. Immunohistochemical study revealed that beta1-6-GlcNAc branching glycans and GnT-V protein were localized in the trophoblast layer. Both protein expression and the enzyme activity of GnT-V in first trimester placentas were higher than those at term. These results suggest that GnT-V would contribute to placentation in the early phase of pregnancy, possibly regulating the process of invasion of trophoblast cells.

Agglutinins↗

Triterpene glycosides of Siraitia grosvenori inhibit rat intestinal maltase and suppress the rise in blood glucose level after a single oral administration of maltose in rats.

The effect of the crude extract from Siraitia grosvenori Swingle (SG-ex) on the postprandial rise in blood glucose level was investigated. The increase in plasma glucose level in response to the oral administration of maltose was significantly suppressed in rats when SG-ex was given orally 3 min before the maltose administration. There was, however, no effect when glucose was administered instead, suggesting that the antihyperglycemic effect of SG-ex is elicited by inhibition of maltase in the small intestinal epithelium. In vitro, SG-ex inhibited rat small intestinal maltase. Similar effects were also observed both in vivo and in vitro when the concentrate of the sweet elements (triterpene glycosides) prepared from SG-ex was used. Furthermore, the main sweet element of SG-ex, mogroside V, and some minor elements such as mogroside IV, siamenoside I, and mogroside III also exhibited maltase inhibitory effect with IC50 values of 14, 12, 10, and 1.6 mM, respectively. These results suggest that SG-ex exerts anti-hyperglycemic effects in rats by inhibiting maltase activity and that these effects are at least partially exerted by its sweet elements, triterpene glycosides.

Animals↗

Geranylgeranylacetone inhibits lysophosphatidic acid-induced invasion of human ovarian carcinoma cells in vitro.

BACKGROUND: Lysophosphatidic acid (LPA) induced a dose-dependent increase of cancer cell invasion by promoting Rho/Rho-associated kinase signaling. Prenylation of Rho is essential for regulating cell growth, motility, and invasion. Geranylgeranylacetone (GGA), an isoprenoid compound, is used clinically as an antiulcer drug. Recent findings suggested that GGA might inhibit the small GTPase activation by suppressing prenylation. The authors hypothesized that the anticancer effects of GGA result from the inhibition of Rho activation. METHODS: The authors examined the effect of GGA using an in vitro invasion assay in human ovarian carcinoma cells, and analyzed the mechanism of the GGA effect on Rho activation, stress fiber formation and focal adhesion assembly, which are essential processes for cell invasion. RESULTS: The induction of ovarian carcinoma cell invasion by LPA was inhibited by the addition of GGA in a dose-dependent manner. Treatment of cancer cells with GGA resulted in inactivation of Rho, changes in cell morphology, loss of stress fiber formation and focal adhesion assembly, and the suppression of tyrosine phosphorylation of focal adhesion proteins. The effect of GGA on cancer cells was partially prevented by the addition of geranylgeraniol, which is an intermediate of geranylgeranyl pyrophosphate and compensates geranylgeranylation of Rho. CONCLUSIONS: The inhibition of LPA-induced invasion by GGA was, at least in part, derived from suppressed Rho activation by preventing geranylgeranylation.

Actins↗

Altered protein expression in endometrial carcinogenesis.

We have discovered several protein biomarkers that are altered during carcinogenesis of the human uterine endometrium. Proteins prepared from 19 endometrial carcinomas (Group A), and 20 normal endometria obtained from benign gynecological conditions (Group B), were investigated by Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). Two proteins, EC1 and EC2, were consistently expressed differentially. EC1 had an increased level of expression in carcinomas (P<0.001), while EC2 was expressed at a lower level (P=0.004). The isoelectric points of EC1 and EC2 were approximately pH 5.0 and 7.0, respectively. These proteins are thus potential biomarkers for detection of endometrial carcinoma.

Adult↗

Alendronate inhibits intraperitoneal dissemination in in vivo ovarian cancer model.

Ovarian cancer is characterized by diffuse peritoneal carcinomatosis and often by large volumes of ascites. We previously reported that alendronate, a nitrogen-containing bisphosphonate, inhibited ovarian cancer cell migration by attenuating the activation of Rho through inhibiting the mevalonate pathway. However, questions remain about the ability of alendronate to inhibit the invasiveness of cancer cells to the adherent tissues and the growth of disseminated ovarian cancer in vivo. We established an in vivo ovarian cancer model with i.p. carcinomatosis in athymic immunodeficient mice. In the prevention model, in which alendronate administration started from the day after tumor inoculation, alendronate prevented the stromal invasion, reduced the tumor burden, and inhibited ascites accumulation. Histologic observation revealed that alendronate treatment decreased the stromal invasion of the i.p. tumor while inhibiting the metalloproteinase-2 activity in ascites. This antitumor effect might result from the inhibition of cancer cell migration and proteolytic activity. In the treatment model, in which alendronate was given from 10 days after tumor inoculation when macroscopic tumors are already implanted in the peritoneum, the antitumor effect was weaker but still significant. Furthermore, alendronate administration decreased the serum CA-125 levels of mice bearing disseminated ovarian cancer compared with those of nontreated mice. The potent effects of alendronate in reducing stromal invasion, tumor burden, and ascites suggest that it will be of value in regimens for treatment of women with ovarian cancer.

Alendronate↗

Contrast-enhanced power Doppler sonography of malignant ovarian tumors using harmonic flash-echo imaging: preliminary experience.

To investigate the potential usefulness of contrast-enhanced intermittent harmonic sonography in the diagnosis of ovarian cancer, we evaluated 4 patients with complex adnexal masses suspected of malignancy using intermittent harmonic sonography after injection of a contrast agent. Tumor and/or mural nodule tissue enhancement was detected in all cases of ovarian malignancy. Contrast-enhanced, intermittent harmonic sonography provides a satisfactory visualization of blood flow in the solid portion of the tumor tissue and may support a diagnosis of ovarian malignancy. Depiction of blood vessels using low MI techniques may be possible with other vascular ultrasonographic contrast agents.

Contrast Media↗

Tocolytic effect of a Rho-kinase inhibitor in a mouse model of lipopolysaccharide-induced preterm delivery.

OBJECTIVE: The small guanosine triphosphatase RhoA/Rho-kinase cascade has been implicated in uterine contraction. Our purpose was to evaluate the tocolytic effect of a Rho-kinase inhibitor, Y-27632, in lipopolysaccharide-induced preterm delivery in mice. STUDY DESIGN: We used an animal model of lipopolysaccharide-induced preterm delivery in C3H/HeN x B6D2F1 pregnant mice. Y-27632 was delivered continuously through an osmotic pump that was implanted into the peritoneal cavity 6 hours before lipopolysaccharide treatment. The primary outcome was the preterm delivery rate. To further study the possible involvement of this cascade in lipopolysaccharide-induced preterm delivery, we determined the effect of lipopolysaccharide and prostaglandin F2alpha on RhoA activation in mouse myometrial cells and uterine smooth muscle tissues. RESULTS: The rate of preterm delivery for lipopolysaccharide-treated animals was 94.4%. The administration of Y-27632 (1 or 10 mg/kg/d) significantly reduced the preterm delivery rate to 61.1% or 15.8%, respectively. The level of guanosine triphosphate-bound RhoA was increased after the addition of lipopolysaccharide or prostaglandin F2alpha. CONCLUSION: The RhoA/Rho-kinase cascade is involved in lipopolysaccharide-induced preterm delivery, which suggests that Rho-kinase could be used as a new therapeutic target for the prevention of preterm labor.

Amides↗

Mechanisms of platinum drug resistance.

Platinum-based drugs are among the most active anticancer agents available and are used widely for the treatment of a variety of human solid tumors. Although patients show high response rates to platinum drugs, most patients develop resistance to these drugs during treatment. Because the acquisition of resistance is a major obstacle to the clinical use of platinum drugs, the processes by which cells develop such resistance are of great interest and efforts have been made to overcome this problem. Both mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) cascades are involved in resistance to these drugs, and clinical trials of some small-molecule inhibitors of the MAPK and PI3K-Akt cascades to overcome resistance to platinum drugs are ongoing.

Animals↗

Prognostic value of brain perfusion single-photon emission computed tomography (SPECT) for language recovery in patients with aphasia.

AIM: To determine the prognostic value of brain perfusion single-photon emission computed tomography (SPECT) in patients with aphasia after a stroke. METHODS: Brain perfusion SPECT with 99mTc-ethyl cysteinate dimer (99mTc-ECD) was used in 16 right-handed patients with aphasia after a left-sided cerebrovascular accident (CVA) in the early chronic period after the onset of CVA. The region of interest (ROI) method was used to calculate the relative regional cerebral blood flow (rCBF) in each cerebral lobe, the thalamus, the putamen and the cerebellum as ratios to the count in the left cerebellar hemisphere. The Standard Language Test of Aphasia (SLTA) was performed twice, once at the same time as SPECT, a mean of 2.3 months after CVA onset (early SLTA), and again a mean of 17.0 months after CVA onset (late SLTA). In addition to the overall language function score, scores for taking dictation (Dictation), oral reading (Speaking) and comprehension (Comprehension) were calculated, and the correlations with each of the rCBF values were evaluated. RESULTS: Left temporal CBF correlated with the late Dictation score; bilateral frontal, bilateral temporal and right parietal CBF correlated with the late Speaking score; and right frontal, left temporal and left occipital CBF correlated with the late Comprehension score. CONCLUSION: Brain perfusion SPECT in the early chronic stage was shown to be useful for predicting recovery from aphasia, recovery of oral reading, ability to take dictation and comprehension.

Aged↗

Tension-free vaginal tape procedure with manual-tapping method: a potentially useful technique.

AIM: Stress urinary incontinence (SUI) is accompanied by pelvic organ prolapse (POP) in many cases. We investigate a procedure to adjust the level of suspension of the mid-urethra using tension-free vaginal tape (TVT) under general anesthesia at the time of POP repair surgery. METHODS: Preliminary examination carried out prior to this study showed that the pressure stress applied by a surgeon is less than half of that induced using the cough-stress method: the manual-tapping method (MTM) showed an average intravesical urinary leak point pressure (IULPP) of 21.4 mmHg (range 19-23 mmHg), when the cough-stress method demonstrated an average IULPP >52.4 mmHg (range 45-58 mmHg; n = 3). An attempt was made to predict postoperative SUI by packing sponge gauze into the manually replaced vagina preoperatively. If SUI appeared, TVT was added to the repair operation for POP in those patients (n = 11). Lastly, the MTM was used to decide the level of urethral suspension during the TVT procedure following POP repair surgery under general anesthesia (n = 11). RESULTS: Eleven patients underwent the TVT procedure combined with POP repair surgery. The mean postoperative follow-up period was 23.8 months (range 9-40 months). There was no case of post-surgical ischuria. One patient showed a cystocele during the postoperative course. However, all other patients were relieved from the symptoms of POP, and none complained of SUI following the procedure. CONCLUSION: The MTM seems to be a more appropriate indicator by which to adjust the level of urethral suspension during the TVT procedure than the conventional method, particularly under general anesthesia. To prevent and cure perioperative SUI, the MTM as a TVT procedure combined with POP repair surgery under general anesthesia is a useful procedure.

Aged↗