Biomedical subjects

Yuji Taketani

Publications and source records attributed to Yuji Taketani.

At least 19 recordsLinked to original sources

PubMed2004

Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia.

Sufficient cytotrophoblast (CT) invasion into the uterine wall and subsequent remodeling of maternal uterine vasculature is critical to establish uteroplacental circulation. The production of vascular endothelial growth factor (VEGF) family molecules is confirmed in placental cells including CTs, but it is not elucidated how the VEGF system in CTs is controlled by oxygen tension and how it is involved in the development of placental circulation. To address this, we explored the effect of oxygen tension on the expression of VEGF, placenta growth factor (PlGF), and their antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1) using ELISA and real-time PCR in a primary CT cell culture. For comparison, the same was conducted in parallel using other cells comprising placenta, such as human umbilical vein endothelial cells (HUVECs) and villous fibroblasts (VFs). Reduced oxygen resulted in a pronounced increase in sFlt-1 mRNA amount and sFlt-1 release into the culture media in CTs, whereas this was not the case with HUVECs and VFs. Free (not bound to sFlt-1) VEGF was not detected in CT culture media regardless of oxygen concentration, even though VEGF expression was stimulated by reduced oxygen in CTs, which was similar to the stimulation in HUVECs and VFs. Free PlGF was also diminished in CT culture media by reduced oxygen. These results implicate that CTs possess a unique property to enhance sFlt-1 production under reduced oxygen, which could consequently antagonize angiogenic activity of VEGF and PlGF. The presented findings might provide a framework with which to understand the mechanism of uterine vascular remodeling and its perturbations as exemplified in preeclampsia.

Cell Line, Tumor↗

PubMed2004

Association of PTEN mutation with HPV-negative adenocarcinoma of the uterine cervix.

Serous, mucinous, endometrioid, and clear cell adenocarcinomas arise from reproductive organs of mullerian origin. Although the mutation of PTEN, a tumor suppressor, is known to be involved in tumorigenesis of endometrioid adenocarcinomas of the endometrium and ovary, the role of PTEN alteration in endometrioid adenocarcinoma of the cervix remains to be investigated. To elucidate the molecular pathogenesis of cervical adenocarcinoma and adenosquamous carcinoma, and in particular to examine the potential role of PTEN mutation in endometrioid-type cancer of the cervix, we analyzed 32 cervical adeno- or adenosquamous carcinomas (8 endometrioid adenocarcinomas, 14 mucinous adenocarcinomas and 10 adenosquamous carcinomas) for PTEN mutations and HPV infections. PTEN mutation was detected in 2 of 8 (25.0%) endometrioid cases, 2 of 14 (14.3%) mucinous cases, and none of 10 (0%) adenosquamous cases. HPV DNA was detected in 11 out of 18 (61.1%) PTEN wild-type adenocarcinomas and 8 out of 10 (80.0%) adenosquamous carcinomas. Among 11 HPV-negative adenocarcinomas, 40.0% (2/5) endometrioid cases and 33.3% (2/6) mucinous cases were shown to be PTEN mutated, while no cases (0/21) were PTEN-mutant in the remainder (i.e. adenosquamous carcinomas and HPV-positive adenocarcinomas). The current observations suggest that PTEN mutation is frequently detected in HPV-negative adenocarcinomas of the cervix and the most prevalent occurrence of PTEN mutation in endometrioid subtype is keeping with endometrial and ovarian carcinomas.

Adenocarcinoma, Mucinous↗

PubMed2004

Concentration of osteoprotegerin (OPG) in peritoneal fluid is increased in women with endometriosis.

BACKGROUND: Failure of apoptosis of refluxed endometrial cells within the peritoneal cavity is a possible etiologic factor for development of endometriosis. Osteoprotegerin (OPG) is a survival factor that exerts its effect by binding to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thus preventing TRAIL from binding to the apoptosis receptors DR4 and DR5. In the present study, we addressed the possibility that the TRAIL/OPG system is involved in the pathogenesis of endometriosis. METHODS: Concentrations of OPG and TRAIL in the peritoneal fluid (PF) of women with or without endometriosis were measured using specific enzyme-linked immunoabsorbent assay. The expression of DR4 and DR5 in the endometriotic tissue was examined by reverse transcription-polymerase chain reaction. RESULTS: OPG concentrations in PF of women with endometriosis were significantly higher than those of women without endometriosis (P=0.006). With respect to the stages of the disease, the concentrations of OPG in women with stage III/IV endometriosis were significantly higher than in those without endometriosis and those with stage I/II endometriosis. On the other hand, the ratios of TRAIL/OPG concentrations were significantly lower in stage III/IV endometriosis compared to those in non-endometriosis and stage I/II endometriosis. DR5 mRNA expression was clearly detected in all the endometriotic tissues studied. CONCLUSIONS: These findings suggest that the TRAIL/OPG system is involved in the pathophysiology of endometriosis, possibly affecting the apoptosis of endometriotic cells.

Adult↗

PubMed2004

Fractal analysis of surface growth patterns in endometrioid endometrial adenocarcinoma.

OBJECTIVE: A fractal is a shape made of parts similar to the whole in some way. The objective of this study was to determine whether surface growth patterns in endometrioid endometrial adenocarcinoma are fractal, and the mean fractal dimension differs according to histologic grades and depth of myometrial invasion. METHODS: After the images of photographs of 120 resected uteri with endometrial cancers were digitized, the fractal dimensions of surface of tumors were measured using a fractal analysis software. RESULTS: The mean fractal dimensions of surface growth patterns in G1, G2, and G3 adenocarcinoma were 2.318, 2.303, and 2.383, respectively. These values were significantly greater than the topological dimension of a surface (= 2). The value was significantly higher in G3 than in G2 (p = 0.03). And although not statistically significant, the value of G3 was greater than G1 (p = 0.10) and than (G1 and G2) group (p = 0.06). No significant difference nor tendency was found in the fractal dimension of the surface of the tumor according to depth of invasion. CONCLUSION: This study shows that the surface of endometrioid endometrial adenocarcinoma has a fractal structure, and the mean fractal dimension may differ according to histologic grades. Our report proposes a new way of looking at endometrial cancer pathology. We believe that fractal geometry gives insights into tumor morphology and becomes a useful tool for analyzing complex and irregular tumor growth patterns mathematically.

Adult↗

PubMed2004

A case of laryngeal atresia (congenital high airway obstruction syndrome) with chromosome 5p deletion syndrome rescued by ex utero intrapartum treatment.

The authors report a case of laryngeal atresia (congenital high airway obstruction syndrome [CHAOS]) that was diagnosed prenatally. The patient underwent successfully tracheostomy by ex utero intrapartum treatment (EXIT). The fetal ultrasonography and magnetic resonance imaging MRI showed a typical CHAOS pattern with expanded hyperechogenic lungs, inverted diaphragms, and a dilated trachea. Recently, 3 cases of prenatally diagnosed CHAOS were reported to be treated successfully by EXIT. The clinical manifestation and course of this case was not similar to these 3 cases. The 3 previous patients did not fare as well during gestation and were delivered earlier than that in our case. In our case, fetal hydrops was seen at 23 gestational weeks, but it gradually subsided and disappeared at 30 gestational weeks. The fetus was stable and well. After delivery at 39 weeks, the baby received respiratory assistance by ventilator assistance. After 3 days, she could breath well on her own. The patient also had chromosome 5p deletion syndrome and perineal groove. More experience in treating CHAOS cases with EXIT to fully estimate its clinical course and prognosis is needed.

Abnormalities, Multiple↗

PubMed2004

Hypoxia does not reduce HLA-G expression on extravillous cytotrophoblasts.

Placental hypoxia following the immature remodeling of spiral arteries by extravillous cytotrophoblasts (CTs) is focused on the pathogenesis of pre-eclampsia. At the same time, the expression of human leukocyte antigen (HLA)-G is decreased at the protein and mRNA levels in the pre-eclamptic placenta. In view of the potential function of HLA-G in immunological tolerance in the feto-maternal interface, we were much concerned to find whether the lowered expression of HLA-G in the pre-eclamptic placenta is a precursor or the result of placental hypoxia. The effect of oxygen on the expression of membrane-bound (mb) and soluble (s) HLA-G was investigated in primary cultures of extravillous CTs. The undifferentiated CTs isolated from the first-trimester placenta were cultured with different concentrations of oxygen (20%, 8% and 2%). The protein expression of mbHLA-G and of sHLA-G was assessed using flow cytometry, and mRNA expression was analyzed using real-time PCR. Expression of mbHLA-G and of sHLA-G protein was intensified with time in culture regardless of the oxygen concentration, and the expression intensities were synchronized between the 20% and the 2% oxygen concentrations at each time point. The mRNA expressions of mbHLA-G1 and sHLA-G1 at 2% oxygen were increased to twice those with 20% oxygen. Our findings demonstrate that no reduction of HLA-G was induced in CTs by short-term exposure to hypoxia, although further study may be required to find the effect of chronic hypoxia.

Cells, Cultured↗

PubMed2004

A novel method of preoperative autologous blood donation with a large volume of plasma for surgery in gynecologic malignancies.

The objective of this study was to establish a novel method of preoperative autologous blood donation (PAD) for surgery of gynecologic malignancies, which requires considerable amounts of plasma relative to the red blood cell component. To collect a double volume of plasma over the amount obtained from whole blood without using an aphaeresis system, we first collected 500 ml of whole blood (2.5 units), and centrifuged it. We gave back the resultant red cell component alone, and retained the plasma component. We further collected an additional 500 ml of whole blood, and centrifuged it. The red cell component (2.5 units) was stored in the refrigerator (as a concentrated red cell, CRC). The resultant plasma together with the plasma collected first (5 units) was frozen and stored in the freezer (fresh frozen plasma, FFP), We repeated this procedure at most three times at intervals of 1 week. Erythropoietin was injected once a week and iron tablets were prescribed. Ninety-nine patients undergoing surgery for a gynecological malignancy were subjected to this method and 86 patients without PAD served as a control. We conducted the procedure for PAD without any noticeable side effects. The amount of actual use of allogeneic CRC and FFP were significantly reduced in the PAD group compared with the control group. In particular, 93.6% of the PAD cases who gave 10 or less units of FFP could go without allogeneic FFP. Postoperative serum albumin levels were higher in the PAD group compared with the control. We have established a novel PAD method which can yield a greater volume of FFP relative to CRC, thus meeting requirements for surgery for gynecological malignancies.

Blood Loss, Surgical↗

PubMed2004

Differential clinical manifestations of congenital cytomegalovirus infection between dizygotic twins: a case report.

To understand a mechanism for the difference in clinical manifestations of congenital cytomegalovirus (CMV) infection between dizygotic twins, the placentas of the dizygotic twins were evaluated for the number of the cells infected with CMV by immunohistochemical and in situ hybridization studies. A Japanese woman with dizygotic twin pregnancy had immunoglobulin M antibodies to CMV at 15 weeks gestation. Intrauterine growth retardation was noted only in the first twin. At birth, CMV was isolated from urine culture in both twins. Clinical manifestations for CMV, such as petechiae, jaundice, hepatosplenomegaly, and deafness were more pronounced in the first twin than in the second twin. Immunohistochemical and in situ hybridization studies showed CMV-positive cells two or three times more densely distributed in the placenta of the first twin compared with the second twin. These data suggest the severity of CMV manifestations of dizygotic twins may be in accord with the number of CMV-positive cells in the placenta.

Adult↗

PubMed2004

Methylation-associated silencing of the Wnt antagonist SFRP1 gene in human ovarian cancers.

The SFRP1 gene on chromosome 8p11.2 encodes a Wnt signaling antagonist, and was recently demonstrated to be a new tumor suppressor that is inactivated by promoter methylation in human colon cancers. Here, we analyzed promoter methylation of the SFRP1 gene in human ovarian cancers, in which loss of heterozygosity in 8p is frequently observed and involvement of the Wnt signaling pathway has been suggested. Methylation-specific PCR (MSP) analysis showed that four of 13 ovarian cancer cell lines and two of 17 primary ovarian cancers had methylated SFRP1, while an immortalized ovarian epithelial cell line, HOSE, and seven ovarian endometrial cyst samples did not. In the four ovarian cancer cell lines with the methylation, SFRP1 was not expressed at all as determined by quantitative RT-PCR analysis. A cell line with SFRP1 methylation, MCAS, was treated with a demethylating agent, 5-aza-2'-deoxycytidine, and demethylation of the promoter and re-expression of SFRP1 were observed. These results show that SFRP1 is inactivated by promoter methylation in human ovarian cancers, as well as colon cancers.

Adult↗

PubMed2004

Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction.

This study was performed to investigate the serum levels of bisphenol A (BPA), an endocrine disruptor, in women with ovarian dysfunction and obesity. Fasting serum samples were obtained from 19 non-obese and 7 obese women with normal menstrual cycles: 7 patients with hyperprolactinemia, 21 patients with hypothalamic amenorrhea, and 13 non-obese and 6 obese patients with polycystic ovary syndrome (PCOS). BPA was measured by an enzyme-linked immunosorbent assay. BPA was detected in all human sera. Serum BPA concentrations were significantly higher in both non-obese and obese women with polycystic ovary syndrome (1.05 +/- 0.10 ng/ml, 1.17 +/- 0.16 ng/ml; p<0.05, respectively) and obese normal women (1.04 +/- 0.09 ng/ml, p<0.05) compared with those in non-obese normal women (0.71 +/- 0.09 ng/ml). There was no difference among women with hyperprolactinemia, women with hypothalamic amenorrhea, and non-obese normal women. There were significant positive correlations between serum BPA and total testosterone (r = 0.391, p<0.001), free testosterone (r = 0.504, p<0.001), androstenedione (r = 0.684, p<0.001), and DHEAS (r = 0.514, p<0.001) concentrations in all subjects. These findings show that there is a strong relationship between serum BPA and androgen concentrations, speculatively due to the effect of androgen on the metabolism of BPA.

Androgen Antagonists↗

PubMed2004

Changes in the size of maternal inferior vena cava during pregnancy.

AIMS: To investigate the changes in the size of maternal inferior vena cava (IVC) during normal pregnancy. METHODS: The diameter and the area of IVC were measured in 32 non-pregnant and 214 pregnant women by ultrasonography. They were measured not only in the supine but also in the complete left lateral position when gestation was over 16 weeks. RESULTS: IVC in the 4-7 weeks pregnant group was larger than that in the non-pregnant group, and it decreased as gestation progressed during an early stage of pregnancy. After 16 weeks gestation, it demonstrated no change, at least for depending on the periods when the mother was in the supine position. On the contrary, they increased with the gestational progress as for the maternal left lateral position. CONCLUSIONS: The size of IVC at an early stage of pregnancy is enlarged, suggesting an underfilling state of arterial circulation. In the second and third trimesters, it is stationary when the mother is supine. In the left lateral position, it increases as the gestation progresses, reflecting blood volume expansion during pregnancy.

Adult↗

PubMed2003

Human papillomavirus type 16 E6 variants and HLA class II alleles among Japanese women with cervical cancer.

The enhanced oncogenicity of particular human papillomavirus type 16 (HPV16) E6 variants is population-dependent, implying the involvement of additional genetic cofactors. This study was designed to investigate the association between E6 variants and human leukocyte antigen (HLA) polymorphism within a Japanese population. Fifty-seven women with HPV16-positive cervical cancer were analyzed for E6 sequence variation and its relationship to HLA class II alleles. Compared with local controls (n = 138) and published controls (n = 916), DRB1*1501 and DQB1*0602 frequencies were significantly increased among patients with HPV16 E6 prototype (n = 11). Additionally, DRB1*1502 was positively associated with a particular E6 variant designated D25E (n = 25), although we could not find a significant association between HLA class II alleles and L83V variants (n = 16). Our observations suggest that a specific match between E6 variant proteins and HLA types may contribute to HPV16-related cervical carcinogenesis.

Carcinoma in Situ↗

PubMed2003

Safety and immunogenicity of a peptide containing the cross-neutralization epitope of HPV16 L2 administered nasally in healthy volunteers.

Amino acid (aa) 108-120 of L2 protein of human papillomavirus (HPV) type 16 contains a cross-neutralization epitope against genital HPV. We designed a placebo-controlled trial in healthy adults to evaluate the safety and immunogenicity of a synthetic peptide consisting of the aa 108-120 of HPV16 L2 (L2-108/120) region. A total of 13 volunteers were given nasal inoculations with 0.1 (n=5) or 0.5mg (n=5) doses of the peptides or placebo (n=3) without adjuvant at weeks 0, 4, and 12. Sera were collected before inoculation and at 6, 16 and 36 weeks. The inoculation caused no serious local and systemic complications. The inoculation generated anti-L2 antibodies binding to both HPV16 and 52 L1/L2-capsids in four of the five recipients in the 0.5mg group. Sera of the four recipients showed neutralizing activities against HPV16 and 52. Serological responses to the peptides were not found in the 0.1mg group and the placebo group recipients. This study suggests the L2-108/120 peptide is tolerable in humans and has the potential as a broad-spectrum prophylactic vaccine against genital HPV.

Administration, Intranasal↗

PubMed2003

IgG antibodies to human papillomavirus 16, 52, 58, and 6 L1 capsids: case-control study of cervical intraepithelial neoplasia in Japan.

In Japan, human papillomavirus (HPV) 16, 52, and 58 are most commonly associated with cervical intraepithelial neoplasia (CIN). By contrast, HPV6 is primarily associated with genital warts. This study was designed to evaluate the association between IgG antibody responses to common HPVs and the risk of CIN development within a Japanese population. CIN cases (n = 141) and controls (n = 109) were tested for cervical HPV DNA and serum IgG antibodies to L1 capsids of HPV16, 52, 58, and 6. Seropositivity to HPV16, 52, and 58 L1 capsids was significantly higher in CIN cases than in controls: 27%, 21%, and 31% versus 16%, 11%, and 11%, respectively (P < 0.05). HPV6 L1 seropositivity was not significantly associated with CIN lesions (P = 0.11). Presence of viral DNA for either HPV16, 52, or 58 correlated with a significant antibody response against the homologous L1 capsids but not heterologous L1 capsids. Furthermore, seropositivity to multiple types of HPV16, 52, and 58 was more strongly associated with an increased risk of CIN development than seropositivity to a single type (P for trend <0.001). These findings indicate that IgG antibodies to L1 capsids of HPV16, 52, and 58 represent an increased risk of CIN development, with antibodies to multiple types being indicative of a further increase in risk. The presence of CIN lesions in women with seropositivity to multiple types suggests that viral exposure to a given type may not be protective against infections by other types and subsequent CIN development.

Adult↗

PubMed2003

Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1 beta as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma.

Of all of the epithelial ovarian cancers, clear cell carcinoma (CCC) of the ovary has the worst prognosis. We applied the oligonucleotide array technique to identify genes generally involved in CCC. Of the approximately 12,600 genes that were analyzed, 28 were expressed significantly differently between four CCC and seven non-CCC cell lines. Among 16 up-regulated genes in CCC, we further investigated a transcription factor, hepatocyte nuclear factor-1 beta (HNF-1 beta). We validated up-regulation of HNF-1 beta in CCC in terms of both mRNA and protein level using real-time quantitative reverse transcriptase-polymerase chain reaction and immunoblotting. Immunohistochemical analysis of 83 surgically resected ovarian cancers showed that almost all CCC specimens (21 of 22 cases) had nuclear staining for HNF-1 beta, whereas most non-CCC specimens (60 of 61 cases) showed no immunostaining or only focal and faint staining in the nucleus. Furthermore, we investigated the significance of HNF-1 beta expression in CCC using RNA interference. The reduction of HNF-1 beta expression by RNA interference induced apoptotic cell death in ovarian CCC cells, which was confirmed by terminal dUTP nick-end labeling and fluorescence-activated cell-sorting analyses. Our results suggest that HNF-1 beta is not only an excellent CCC-specific molecular marker but also a molecular target for therapy of ovarian CCC.

Adenocarcinoma, Clear Cell↗

PubMed2003

Ovarian choriocarcinoma arising from partial mole as evidenced by deoxyribonucleic acid microsatellite analysis.

BACKGROUND: Recent developments in genetic analysis allow determination of the origin of choriocarcinoma (ie, gestational or nongestational), which helps determine the strategy for clinical treatment of the disease. CASE: We present a case of ovarian choriocarcinoma forming a huge ovarian mass 40 days after the patient's last menstrual period. Deoxyribonucleic acid microsatellite analysis of the tumor revealed that it contained a single maternal and two paternal alleles at several independent loci, consistent with the tumor resulting from ovarian pregnancy of a partial hydatidiform mole. CONCLUSION: This is the first description of an ovarian pregnancy of a partial hydatidiform mole-derived ovarian choriocarcinoma.

Adult↗

PubMed2003

A subclass of soluble HLA-G1 modulates the release of cytokines from mononuclear cells present in the decidua additively to membrane-bound HLA-G1.

PROBLEM: Our previous studies have demonstrated that a subclass of soluble human leukocyte antigen-G1 protein (sub-sHLA-G1), that has alpha1 to alpha3 extra-cellular portion but lacks C-terminus of authentic soluble HLA-G1 secreted by trophoblasts, fine-tunes the release of cytokines from peripheral blood mononuclear cells (PBMCs) chiefly by counterbalancing membrane-bound HLA-G1 (mHLA-G1), and thereby may play a role in maintaining pregnancy. In this study, we investigated whether the presence of sHLA-G1 protein altered the release of cytokines from decidual mononuclear cells (DMCs) which are localized at the interface of feto-maternal interaction and whose cell population is completely different from PBMCs. METHOD OF STUDY: We cultured peripheral DMCs with either HLA-A and -B lacking B lymphoblast cell line (721.221 cells) or the cells transfected with mHLA-G1 (721.221-G1 cells) with or without sub-sHLA-G1. Cytokines concentrations in the culture media were determined by an enzyme-linked immunosorbent assay. RESULTS: Regardless of the presence of mHLA-G1 expressing cells, the addition of the recombinant sub-sHLA-G1 protein in the DMC culture media decreased the amounts of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, with the release of IL-4 from DMCs being unchanged. CONCLUSION: The sub-sHLA-G1 protein modulates the release of cytokines from DMCs additively to mHLA-G1 expressing cells. In view of the distinct fetomaternal interaction during implantation, it appears that sHLA-G1 might play a role in the establishment of pregnancy by regulating cytokine release in concert with mHLA-G1.

Cell Membrane↗

PubMed2003

Concentrations of interferon-gamma-induced protein-10 (IP-10), an antiangiogenic substance, are decreased in peritoneal fluid of women with advanced endometriosis.

PROBLEM: To assess whether interferon-gamma-induced protein-10 (IP-10), a chemokine that has antiangiogenic activities, may be involved in the pathogenesis of endometriosis. METHOD OF STUDY: A total of 120 patients undergoing laparoscopy for pain and/or infertility were recruited, and peritoneal fluid (PF) and bone marrow derived cells in PF were collected. Concentrations of IP-10 in PF were measured with a specific enzyme-linked immunosorbent assay. Expression of IP-10 and IP-10 receptor, CXCR3, in bone marrow derived cells in PF, peritoneum and endometriotic cells was analyzed by reverse transcription-polymerase chain reaction. RESULTS: All of the PF samples examined contained detectable concentrations of IP-10. In women with advanced stages of endometriosis, IP-10 concentrations in PF were significantly lower than those of women in early stages (P = 0.02). The IP-10 concentrations in women with advanced endometriosis also appeared to be lower than those without endometriosis although the difference was statistically marginal (P = 0.06). The expression of both IP-10 and CXCR3 was clearly detected in the bone marrow derived cells in PF, peritoneum and endometriotic stromal cells. CONCLUSIONS: Decreased concentrations of IP-10 in PF from women with advanced stages of endometriosis may imply that the peritoneal environment of these women is permissive to the development of the disease by enhancing angiogenesis and/or modulating inflammatory/immunological responses.

Adult↗