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Yuji Taketani

Publications and source records attributed to Yuji Taketani.

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

FRL-1, a member of the EGF-CFC family, is essential for neural differentiation in Xenopus early development.

Recent studies indicate an essential role for the EGF-CFC family in vertebrate development, particularly in the regulation of nodal signaling. Biochemical evidence suggests that EGF-CFC genes can also activate certain cellular responses independently of nodal signaling. Here, we show that FRL-1, a Xenopus EGF-CFC gene, suppresses BMP signaling to regulate an early step in neural induction. Overexpression of FRL-1 in animal caps induced the early neural markers zic3, soxD and Xngnr-1, but not the pan-mesodermal marker Xbra or the dorsal mesodermal marker chordin. Furthermore, overexpression of FRL-1 suppressed the expression of the BMP-responsive genes, Xvent-1 and Xmsx-1, which are expressed in animal caps and induced by overexpressed BMP-4. Conversely, loss of function analysis using morpholino-antisense oligonucleotides against FRL-1 (FRL-1MO) showed that FRL-1 is required for neural development. FRL-1MO-injected embryos lacked neural structures but contained mesodermal tissue. It was suggested previously that expression of early neural genes that mark the start of neuralization is activated in the presumptive neuroectoderm of gastrulae. FRL-1MO also inhibited the expression of these genes in dorsal ectoderm, but did not affect the expression of chordin, which acts as a neural inducer from dorsal mesoderm. FRL-1MO also inhibited the expression of neural markers that were induced by chordin in animal caps, suggesting that FRL-1 enables the response to neural inducing signals in ectoderm. Furthermore, we showed that the activation of mitogen-activated protein kinase by FRL-1 is required for neural induction and BMP inhibition. Together, these results suggest that FRL-1 is essential in the establishment of the neural induction response.

Animals↗
PubMed2003

Genome-wide cDNA microarray analysis of gene-expression profiles involved in ovarian endometriosis.

Using a cDNA microarray consisting of 23,040 genes, we analyzed gene-expression profiles of ovarian endometrial cysts from 23 patients in order to identify genes involved in endometriosis. By comparing expression patterns between endometriotic tissues and corresponding eutopic endometria, we identified 15 genes that were commonly up-regulated in the endometrial cysts during both proliferative and secretory phases of the menstrual cycle, 42 that were up-regulated only in the proliferative phase, and 40 that were up-regulated only in the secretory phase. The up-regulated elements included genes encoding some HLA antigens, complement factors, ribosomal proteins, and TGFBI. On the other hand, 337 genes were commonly down-regulated throughout the menstrual cycle, 144 only in the proliferative phase, and 835 only in the secretory phase. The down-regulated elements included the tumor suppressor TP53, genes related to apoptosis such as GADD34, GADD45A, GADD45B and PIG11, and the gene encoding OVGP1, a protein involved in maintenance of early pregnancy. Semi-quantitative RT-PCR experiments supported the results of our microarray analysis. These data should provide useful information for finding candidate genes whose products might serve as molecular targets for diagnosis or treatment of endometriosis.

Adult↗
PubMed2002

SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin.

DNA topoisomerase I (Topo1) manages the topological state of DNA. Cleavable complexes, the covalent Topo1-DNA intermediates, become DNA damaged when the catalytic cycles are inhibited by the anti-tumor drug camptothecin (CPT). Intriguingly, Topo1 is modified rapidly and extensively with SUMO-1, a ubiquitin-like protein, in response to CPT. This study shows that the sumoylation enhances the cleavable complex formation and apoptosis induced by CPT. Indeed, substitutions of Lys117 and Lys153, identified as Topo1 sumoylation sites, reduced the CPT-induced cleavable complexes without influencing its in vitro catalytic activity. Consistent with this observation, CPT-induced cleavable complexes of wild-type Topo1 increased in a sumoylation-dependent manner. We also found that Topo1 sumoylation occurred independently of CPT when Topo1 was inactivated by mutation of the catalytic Tyr723. These findings suggested that Topo1 inactivation by CPT treatment can trigger Topo1 sumoylation, leading to enhanced cleavable complex formation.

Binding Sites↗
PubMed2002

Neutralizing antibodies against oncogenic human papillomavirus as a possible determinant of the fate of low-grade cervical intraepithelial neoplasia.

To determine whether neutralizing antibodies (NAs) against HPV16 is responsible for a higher regression rate of low-grade cervical intraepithelial neoplasia (CIN1), we investigated an association between the presence of the NAs and the fate of the HPV16-related CIN1. All the women examined in this study had HPV16 positive cervix. The women were allocated into four groups by their cervical pathology, i.e., non-pathological (n:7), CIN1 (n:37), CIN2/3 (n:19), and cervical cancer (n:13). Their sera were tested for the presence of NAs against HPV16 by an in vitro assay using HPV16-pseudovirions. As for the CIN1 cases, clinical regression of the lesions were compared between NA-positive and NA-negative groups. Copy number of HPV16-DNA in smear samples was measured by quantitative PCR. The incidence of the presence of the NAs in the women with a non-pathological cervix (85.7%) was significantly higher than in the CIN1 cases (21.5%), the CIN2/3 cases (15.7%), and the cervical cancer cases (0%) (p<0.0001). The regression of the CIN1 lesion was closely associated with the presence of the N As (p=0.0002). The presence of the NAs was associated with low-level copy number of the viral DNA relative to the NA-negative group (p=0.05). The presence of the NAs against HPV16 was associated with a higher regression rate of HPV-related CIN1 lesions. The NAs seem to have a role in deterring HPV-related cervical lesions from progressing to CIN2/3 by inhibiting the infection with de novo replicated HPV. This study further suggests that HPV vaccine to induce the NAs may be effective in eliminating CIN lesions, especially in the NA-negative cases.

Antibodies, Viral↗
PubMed2002

Distinct lymphatic spread of endometrial carcinoma in comparison with cervical and ovarian carcinomas.

The distribution of metastatic pelvic lymph nodes (PLNs) and aortic lymph nodes (ALNs) in 27 node-positive endometrial carcinomas (ECs) was analyzed in comparison with that in 25 node-positive cervical carcinomas (CCs) and 58 node-positive ovarian carcinomas (OCs). All patients underwent systematic pelvic and aortic lymphadenectomy. Lymph nodes were classified into the five subgroups: ALN above the inferior mesenteric artery (IMA; A1), ALN below the IMA (A2), the common iliac and sacral LNs (P1), the internal and external iliac LNs and obturator LNs (P2) and the suprainguinal LNs (P3). EC was similar to CC in that metastases to P2 were more frequent compared to A1 or A2, whereas EC and OC shared a common feature in that A1, A2 and P2 were involved at high rates. ALN metastases were significantly associated with P1 positivity in both EC and CC (P<0.05), but not in OC. However, the incidence of both ALN and PLN metastases in EC (67%) was similar to that in OC (61%), being much higher than that in CC (36%). ALN involvement alone was observed in 7% for EC, 0% for CC and 21% for OC. Based on the distribution of LN metastases, it appears that CC metastasizes primarily to PLN, whereas OC metastasizes almost equally to both PLN and ALN. Interestingly, EC can directly metastasize to both PLN and ALN with PLN metastases being dominant, a distinct lymphatic spread pattern better viewed as being somewhere between CC and OC.

Adult↗
PubMed2002

Soluble FLT-1 expression suppresses carcinomatous ascites in nude mice bearing ovarian cancer.

Vascular endothelial growth factor (VEGF), a bifunctional protein enhancing vascular permeability and stimulating endothelial growth, is thought to be responsible for fluid accumulation and angiogenesis in ascites tumors. To investigate the effects of stable expression of the soluble form of Flt-1 VEGF receptor (sFlt-1), a known endogenous inhibitor of VEGF, on the malignant ascites tumors, we cotransduced RMG-1 human ovarian cancer cells with adeno-associated virus vectors carrying the sFlt-1 cDNA and Neo gene or Neo gene alone and isolated both the sFlt-1-expressing clone and the Neo-expressing clone. In vitro growth characteristics were essentially the same. As expected, conditioned medium collected from the sFlt-1-expressing cells significantly inhibited the human umbilical vein endothelial cell proliferation in the presence of recombinant VEGF. Expression of sFlt-1 significantly suppressed RMG-1 cell-induced angiogenesis in vivo in the mouse dorsal air sac assay model. We then inoculated sFlt-1- or Neo alone-expressing cells i.p. into female BALB/c nude mice. The average volume of ascites fluid, number of leaked RBCs, and number of cancer cells were significantly lower in mice injected with sFlt-1-expressing cells than in the controls. Survival time was significantly prolonged in mice injected with sFlt-1-expressing cells. These results suggest that inhibition of VEGF activity by sFlt-1 expression may provide a means to control carcinomatous ascites and angiogenesis of malignant ascites tumors.

Animals↗
PubMed2002

Bisphenol A induces apoptosis and G2-to-M arrest of ovarian granulosa cells.

We investigated the impact of bisphenol A (BPA) on murine ovarian granulosa cells. Ovarian granulosa cells were cultured with 100 fM to 100 microM BPA for 24 h to 72 h. BPA decreased granulosa cell viability in a dose- and time-dependent manner. The lowest concentration that induced a significant decrease was 100 pM (89.2 +/- 4.0% of the control). TUNEL analysis demonstrated that treatment with BPA increased apoptosis of granulosa cells in a dose- and time-dependent manner. In addition, flow cytometry analyses revealed that treatment with BPA resulted in G2-to-M arrest, which was most prominent at 48 h. BPA increased the expression of Bax and concomitantly decreased the expression of Bcl2 at both protein and mRNA levels of granulosa cells. These findings suggest that low, presumably environmentally relevant doses of BPA, decrease the viability of granulosa cells by inducing apoptosis and G2-to-M arrest. Up-regulation of Bax and down-regulation of Bcl2 were suggested to be involved in this apoptotic effect.

Animals↗
PubMed2002

The evaluation of the sentinel node successfully conducted in a case of malignant melanoma of the vagina.

BACKGROUND: The sentinel node biopsy has been established as a standard procedure in many types of cancer. To date, only one case was reported for successful detection of the sentinel node using a radiopharmaceutical-directed mapping technique in malignant melanoma of the vagina. CASE: An 81-year-old woman developed malignant melanoma arising from the lower third of the vagina. She underwent local resection of the tumor and exploration of the sentinel node using blue dye. The sentinel node was detected successfully in the groin, and was negative for metastasis. Intra-cavity irradiation was given as an adjuvant therapy. CONCLUSION: In view of relative ease and minimal trauma, sentinel node mapping could be a routine procedure in malignant melanoma arising from the vagina or vulva.

Aged↗
PubMed2002

Fractal tumor growth of ovarian cancer: sonographic evaluation.

OBJECTIVE: The objective of this study was to determine whether sonographically depicted ovarian tumor growth is fractal, and the mean fractal dimension differs according to stages of the disease and histologic types. METHODS: The fractal dimensions of outlines of sonographically depicted solid components in 160 ovarian tumors were measured using a box-counting method. RESULTS: The mean fractal dimensions of the surface of intracystic solid components in serous, mucinous, endometrioid, and clear cell adenocarcinoma were 1.259, 1.243, 1.238, and 1.182, respectively. These values were significantly greater than the topological dimension of a line (=1). The value was significantly higher in stage I or II (1.381) than stage III or IV (1.205) in serous carcinoma (P = 0.02), but not significantly different in clear cell carcinoma (1.187 and 1.172, respectively). In stage I or II, the value of serous carcinoma (1.381) was significantly higher than that of clear cell carcinoma (1.187) (P = 0.03). The value of mucinous cystadenoma of low malignant potential was 1.337, which was also significantly greater than 1. The mean fractal dimensions of outlines of solid tumors in cases with dysgerminoma and thecoma-fibroma were 1.036 and 1.023, respectively. These values were not significantly different from 1. CONCLUSION: This study shows that the surface of solid components in cystic epithelial ovarian cancers has a fractal structure, and the mean fractal dimension may differ according to stages of the disease and histologic types. Fractal geometry, a vocabulary of irregular shapes, can be useful for describing the pathological architecture of ovarian tumors and for yielding insights into the mechanisms of tumor growth.

Adenocarcinoma↗
PubMed2002

Human chorionic gonadotropin combined with progesterone for luteal support improves pregnancy rate in patients with low late-midluteal estradiol levels in IVF cycles.

PURPOSE: To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles, and to assess whether human chorionic gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels. METHODS: The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed. Unsuccessful women with low late-midluteal estradiol levels (< 100 pg/mL) proceeded with the exploratory second IVF cycles where they were randomly given with either progesterone alone (P protocol) or hCG +progesterone (P+hCG protocol) for luteal support. RESULTS: Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium (100-500 pg/mL) and high (> 500 pg/mL) levels (13.3, 26.8, and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate (31.7%) than P protocol (13.7%). CONCLUSIONS: hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels.

Adult↗
PubMed2002

Studies on fetal forelimb movements by using a wrist actigraph in sheep.

The purpose of this study was to investigate whether an actigraph can be a tool for measuring fetal movements in sheep. Actiwatches were placed on a fetal forelimb and the maternal uterine wall in near-term pregnant sheep. No significant correlation was found between fetal and maternal activity counts for periods of 1 min. The patterns of fetal activity counts were characterized by ultradian rhythms, with bursts of activity every 20-30 min; however, there was no evidence of diurnal changes in fetal activity counts. The results suggest that fetal movements can be measured by using an actigraph in chronically prepared fetal sheep.

Animals↗
PubMed2002

Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure.

BACKGROUND: There is broad human exposure to bisphenol A (BPA), an estrogenic endocrine-disrupting chemical widely used for the production of plastic products. BPA is reported to affect preimplantation embryos or fetuses and alter their postnatal development at doses typically found in the environment. We measured contamination of BPA in various kinds of human biological fluids by a novel enzyme-linked immunosorbent assay. METHODS: Blood samples were obtained from healthy premenopausal women, women with early and full-term pregnancy, and umbilical cord at full-term delivery. Ovarian follicular fluids obtained during IVF procedures and amniotic fluids obtained at mid-term and full-term pregnancy were also subject to BPA measurements. RESULTS: BPA was present in serum and follicular fluid at approximately 1-2 ng/ml, as well as in fetal serum and full-term amniotic fluid, confirming passage through the placenta. Surprisingly, an approximately 5-fold higher concentration, 8.3 +/- 8.7 ng/ml, was revealed in amniotic fluid at 15-18 weeks gestation, compared with other fluids. CONCLUSION: These results suggest accumulation of BPA in early fetuses and significant exposure during the prenatal period, which must be considered in evaluating the potential for human exposure to endocrine-disrupting chemicals.

Air Pollutants, Occupational↗
PubMed2002

Ovarian hyperstimulation syndrome complicated by peritonitis due to perforated appendicitis.

We describe a case of ovarian hyperstimulation syndrome (OHSS) complicated by peritonitis due to perforated appendicitis. A 29-year-old woman presented with abdominal distension after ovarian stimulation with HMG followed by ovulation induction with HCG. Massive ascites with swollen ovaries was observed on ultrasound, and she was admitted on the diagnosis of OHSS. Daily infusion of serum albumin and low dose dopamine failed to increase her urine output and her abdominal symptoms became increasingly deteriorated after her urine pregnancy test turned out to be positive. Paracentesis performed for alleviation of her abdominal distension revealed infected, foul-smelling fluid. An emergency laparotomy was performed, and the definite diagnosis was made as panperitonitis due to perforated appendicitis with right tubal pregnancy. Appendectomy, right tubectomy and vigorous irrigation with drainage were performed. The case implies that OHSS might not only mask typical manifestations of appendicitis, but could also compromise concurrent intraperitoneal infection.

Adult↗
PubMed2002

Allelotype analysis of common epithelial ovarian cancers with special reference to comparison between clear cell adenocarcinoma with other histological types.

Determination of the histological type of epithelial ovarian cancer is clinically important to predict patient prognosis. To estimate accurately the chromosomal regions that frequently show loss of heterozygosity (LOH) in each histological type, LOH at 55 loci on 38 chromosomal arms was examined by means of laser capture microdissection and PCR-LOH analysis in 45 epithelial ovarian cancers composed of clear cell adenocarcinoma (CCA), serous adenocarcinoma (SEA), endometrioid adenocarcinoma (EMA) and mucinous adenocarcinoma (MUA). In addition, p53 (exons 5 - 8) gene mutations and the nuclear immunoreactivity of p53 proteins in these tumors were examined by PCR-SSCP and immunohistochemistry. In CCA, LOH was detected primarily on 1p (69%) followed by 19p (45%) and 11q (43%). On the other hand, in SEA, LOH was detected in at least 50% of cases on 1p, 4p, 5q, 6p, 8p, 9q, 12q, 13q, 15q, 16p, 17p, 17q, 18p, 18q, 19p, 20p and Xp. The incidences of LOH on 5q, 12q, 13q and 17p were significantly lower in CCA than in SEA (P = 0.019, 0.031, 0.0035 and 0.012). EMA showed a tendency for frequent LOH on 7p, whereas MUA showed significantly high occurrence of LOH at 17p13.1. The incidences of p53 mutation and p53 nuclear immunoreactivity also differed between CCA and SEA: 0% and 7% in the former and 64% and 45% in the latter (P = 0.0006 and 0.039). These findings clarify that there are differences in LOH distribution patterns among different histological subtypes of epithelial ovarian cancer. In CCA, p53 tumor-suppressor gene (TSG) is not involved in carcinogenesis and tumor-suppressor genes located on 1p are considered to play an important role in tumor development.

Adenocarcinoma, Clear Cell↗
PubMed2002

Role of laparoscopy in the treatment of endometriosis-associated infertility.

Endometriosis is assumed to be one of the causative factors of infertility, although the mechanism remains to be elucidated. Mechanical factors distorting the pelvic anatomy and/or changes in the biochemical and cellular environment in the peritoneal cavity are possible contributing factors impairing fertility. Laparoscopy is a widely used diagnostic and therapeutic means of treating endometriosis-associated infertility. However, pregnancy outcome after laparoscopy varies depending on preexisting tubal adhesions and endometriosis. Without tubal adhesions, the pregnancy rate is essentially the same irrespective of the presence or stages of endoemetriosis. Minimal/mild endometriosis benefited the most from laparoscopic manipulation when tubal adhesions were present. On the other hand, IVF-ET outcome of patients who previously underwent laparoscopy was not influenced by preexisiting tubal adhesions and endometriosis.

Adult↗
PubMed2002

A case of estrogen-producing Brenner tumor with a stromal component as a potential source for estrogen.

BACKGROUND: Although Brenner tumors with endocrine activities have been reported, the source or mechanisms for hormone production is poorly known at present. CASE REPORT: A 66-year-old Japanese woman presented with atypical vaginal bleeding. A left ovarian tumor was detected on ultrasonography and CT scanning. Her serum estradiol level was elevated (73.5 pg/ml). We performed total hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy. The ovarian tumor was diagnosed as a benign Brenner tumor associated with simple hyperplasia of the endometrium. Postoperatively, the serum estradiol level decreased. Immunoreactivity of cytochrome P-450 aromatase was detected in stromal cells. CONCLUSION: Stromal contribution to the secretion of estrogen was shown in this case. Considering the known source of estrogen production being tumor cells in certain cases of Brenner tumor, there seem to be two types of estrogen-producing Brenner tumors depending on the source of estrogen, i.e. tumor cells or stromal cells.

Aged↗