Biomedical subjects

Y Yokoyama

Publications and source records attributed to Y Yokoyama.

At least 19 recordsLinked to original sources

PubMed2003

Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma.

We assessed the presence of vascular endothelial growth factor (VEGF)-C, VEGF-D and their receptor VEGFR-3 by immunohistochemistry in 59 epithelial ovarian carcinomas, 11 borderline tumours and 20 benign cystadenomas. VEGF-C and VEGF-D were generally expressed in tumour cells and also in endothelia adjacent to tumour nests which showed a strong staining for them. VEGFR-3 was expressed in lymphatic and vascular endothelial cells adjacent to tumour nests. Immunoreactivity was significantly more frequent as lesions progressed from a benign tumour to advanced carcinoma. A strong correlation was found between VEGF-C and VEGF-D detected in carcinoma and VEGFR-3 detected in neighbouring endothelial cells. Increased expression of VEGF-C, VEGF-D and VEGFR-3 was significantly associated with lymph node metastasis and peritoneal metastasis outside the pelvis. There was a significant correlation between the high levels of VEGF-C and VEGF-D proteins, and poor survival. The presence of VEGF-D was an independent prognostic indicator by multivariate analysis. We conclude that VEGF-C, VEGF-D and VEGFR-3 play an important role in lymphatic spread and intraperitoneal tumour development in ovarian carcinoma. Since VEGF-D was found to be an independent predictor of poor outcome, its measurement, together with other prognostic markers may improve prospective identification of patients with a poor prognosis.

Adenocarcinoma, Clear Cell↗

PubMed2003

Cell death induced by the phenolic antioxidant tert-butylhydroquinone and its metabolite tert-butylquinone in human monocytic leukemia U937 cells.

2-tert-Butyl-4-hydroquinone (TBHQ), a phenolic antioxidant used as a food additive, and its metabolite 2-tert-butyl-1,4-benzoquinone (TBQ) were both cytotoxic in human monocytic leukemia U937 cells, TBQ being the more strongly cytotoxic. Both compounds induced caspase activity towards DEVD-MCA as a substrate and the cleavage of poly(ADP-ribose) polymerase in cells. Enzyme activities of caspase-3,-7,-6 and -9 seemed to be induced, and procaspases-3 and-7 were processed to active forms in cells treated with TBHQ and TBQ. They induced nuclear condensation and fragmentation in some cells. Electron microscopic examination revealed severe disruption of mitochondrial structure and the formation of intracellular vacuoles. Morphological changes were more marked in the cells treated with TBHQ than TBQ. Mitochondrial transmembrane potential was disrupted. Cytochrome c was released from mitochondria to cytosol and ATP level was moderately decreased by the treatment of cells with these chemicals. Cellular glutathione (GSH) appeared to contribute to defense against cell death induced by TBQ, but its contribution was not marked in the case of TBHQ. TBHQ and TBQ exhibited the apoptotic features in various assays, but the mode of cell death may not be defined as a typical apoptosis or necrosis.

Adenosine Triphosphate↗

PubMed2003

The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells.

BACKGROUND: Barrier function in gastric epithelial cells is essential for the gastric defence mechanism against acid back-diffusion into the mucosal layer. Our previous study indicated that trans-epithelial resistance (TER) of rat gastric epithelial cells was rapidly increased when the cells were exposed to acid. This response to acid was diminished by indometacin. AIM: Evaluate the effects of a mucoprotective agent, rebamipide, on the nonsteroidal anti-inflammatory drug (NSAID)-induced increase of gastric epithelial permeability. METHODS: Rat gastric epithelial cells were plated on tissue culture inserts. Cells were exposed to a NSAID (indometacin, 10-7 M). Trans-epithelial permeability was measured by TER and diffusion rate of 14C-mannitol. The effect of rebamipide was evaluated by measuring TER. Endogenous prostaglandin E2 (PGE2) production in culture medium was also measured. RESULTS: Indometacin gradually and significantly decreased TER and increased 14C-manitol permeability. Rebamipide reversed the indometacin-induced changes in epithelial permeability and induced PGE2 synthesis. This induction was blocked by either indometacin or a Cyclooxygenase (COX)-2 specific inhibitor. CONCLUSIONS: COX inhibitors such as indometacin inhibit regulation of epithelial permeability by reducing PGE2. COX-1 has an important role in the gastric defense mechanism. Rebamipide suppressed an indometacin-induced increase in gastric epithelial permeability by increasing PGE2 levels in a COX-2 dependent manner.

Alanine↗

PubMed2002

Alopecia related to low dose oral contraceptive.

We present a patient with diffuse baldness related to low dose oral contraceptive (LD-OC). Although LD-OC scarcely induce troublesome side effects if prescribed in accordance with Managing Contraceptive Pill Patients Guideline, this trouble might become a source of poor compliance to LD-OCs.

Adult↗

PubMed2002

PTEN augments staurosporine-induced apoptosis in PTEN-null Ishikawa cells by downregulating PI3K/Akt signaling pathway.

Staurosporine is a potent apoptosis inducer, but its mechanism remains to be clarified. We investigated the involvement of PTEN in staurosporine-induced apoptosis. Ishikawa cells, from an endometrial carcinoma cell line, expressed a high amount of PTEN mRNA but did not express the PTEN protein because of protein truncations. We isolated clones expressing the steady-state level of the PTEN protein from PTEN-null Ishikawa cells by transfection. The obtained clones showed reduced proliferative activity and reduced anchorage-independent cell growth with the augmented p27(Kip1). These cell lines were sensitized to apoptosis by staurosporine. A low concentration of UCN-01 did not affect apoptosis, but a high concentration augmented apoptosis in the PTEN-expressing clone. Alpha-sphingosine and H-7 did not affect apoptosis in these cell lines. PI3K inhibition augmented staurosporine-induced apoptosis in the parental cell line, but not in the PTEN-expressing clone. In the clone, phosho-Akt/PKB and phospho-Bad (Ser-136) were downregulated. Staurosporine reduced the levels of phospho-Akt/PKB and phospho-Bad (Ser-136) in all the cell lines, but the reduction was most significant in the PTEN-expressing clone. These results suggest that inhibition of the PI3K/Akt/PKB signaling pathway might be associated with staurosporine-induced apoptosis in Ishikawa cells.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed2002

Mechanism of action of Tripterygium Wilfordii polyglycoside on experimental endometriosis.

PURPOSE OF INVESTIGATION: This study was designed to examine the therapeutic effectiveness and mechanism of action of Tripterygium Wilfordii polyglycoside (TWP) in the treatment of endometriosis. METHODS: An experimental endometriosis model was developed using New Zealand White rabbits where endometrial tissue was autotransplanted into the peritoneum. Six weeks after transplantation, a total of 22 rabbits were randomly placed into two groups: Group I (n=17) was treated with TWP (10 mg/kg/day) and Group 2 (n=5) served as the water-fed control for three successive months. The volume of endometrial implants was measured before and after administration of TWP and water. Immune and endocrine systems were investigated in the normal phase, six weeks after induction of endometriosis, and three months after TWP treatment and water administration. RESULTS: After treatment with TWP, the average volume of endometrial implants significantly decreased (p < 0.0001), and the antiendometrial antibody (EmAb) level decreased (p < 0.05) to near normal levels, but it did not decrease in the untreated controls. Serum FSH and LH levels also decreased after TWP treatment. Furthermore, electron microscopic examination of the pituitary ultrastructure revealed morphological changes in gonadotropic cells (G-cell) after treatment with TWP, and changes gradually disappeared four weeks after withdrawal of TWP. CONCLUSION: This study indicates that TWP has both hormonal and immune system action that is effective as a medical treatment for experimental endometriosis by modulating both reproductive endocrine functions and immunosuppression that results in remission of the disease.

Animals↗

PubMed2001

Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation.

Fusions of the ETV6/TEL gene to receptor or protein tyrosine kinases (TKs), such as PDGFRbeta, JAK2, ABL, ABL2, TRKC, and Syk, have been reported in various hematological malignancies. Expression of the resultant chimeric proteins is believed to lead to constitutive TK activity through activation by the helix-loop-helix (HLH) domain of ETV6. We identified a novel ETV6 partner gene, fibroblast growth factor receptor 3 (FGFR3), in a patient with peripheral T-cell lymphoma (PTCL) with a t(4;12)(p16;p13) translocation. The ETV6-FGFR3 transcript showed a fusion of exon 5 of ETV6 to exon 10 of FGFR3, resulting in an open reading frame for a chimeric protein consisting of the HLH domain of ETV6 and the TK domains of FGFR3. This is the first report of ETV6 and FGFR3 involvement in PTCL.

Amino Acid Sequence↗

PubMed2001

Complement plays an important role in gastric mucosal damage induced by ischemia-reperfusion in rats.

Ischemia-reperfusion (I/R) of stomach causes gastric mucosal injury. Complement can also cause tissue damage, however its role in gastric I/R injury has not been thoroughly investigated. We evaluated the effect of complement suppression in reducing damage to the gastric epithelium caused by local I/R. Local gastric ischemia was induced by clamping the left gastric artery. The blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. 51Cr-EDTA clearance increased shortly after reperfusion with peak values at 10 min. Intraperitoneal administration of cobra venom factor (CVF; 50 units) prior to I/R, which reduced the serum complement value (CH50) to an undetectable level, remarkably suppressed the 51Cr-EDTA clearance following reperfusion. A monocarboxylic acid derivative of K-76 (K-76 COOH) reduced the CH50 by more than 30% (100 mg/kg) and 60% (200 mg/kg). Rats pretreated with K-76 significantly attenuated the increase in 51Cr-EDTA clearance produced by I/R. These results suggest that complement inhibitor could be used to protect gastric mucosal injury induced by local I/R stress.

Animals↗

PubMed2001

Carbonyl reductase as a significant predictor of survival and lymph node metastasis in epithelial ovarian cancer.

We have recently reported a novel function for carbonyl reductase (CR), namely, its ability to modulate the metastatic potential of malignant mouse cells. Because there are currently no data addressing a similar function for CR in human cancers, the aim of this study was to assess a correlation between survival and metastasis, and CR level in epithelial ovarian cancer. Using anti-CR antibody, immunohistochemical staining was performed on 73 epithelial ovarian cancers, 13 borderline malignant tumours, and 25 benign ovarian tumours for a total of 111 specimens. The combined rate for strongly and weakly positive reactions for CR was 32.0% for benign tumours, 38.5% for borderline malignant tumours, and 61.6% for ovarian cancers. The CR-positive rate was 35.7% (weakly positive alone) for ovarian cancers with retroperitoneal lymph node (RLN) metastasis and 67.8% for those without RLN metastasis (P< 0.05). The 5-year survival rate was 62.7% for the patients with CR-negative cancer and 86.1% for those with CR-positive cancer (P< 0.05). The present results indicate that decreased CR expression in epithelial ovarian cancer is associated with RLN metastasis and poor survival.

Adult↗

PubMed2001

Maternal origin of a unique extra chromosome, der(9)(pter-->q13::q13-->q12:) in a girl with typical trisomy 9p syndrome.

We report on a girl with the typical trisomy 9p syndrome who had an additional E-sized metacentric chromosome. On the basis of GTG- and CBG-banding, her karyotype was considered to be 47,XX,+der(9)(pter-->q13::q13-->q12:) de novo. Results of a fluorescence in situ hybridization study using a chromosome 9-specific painting probe were compatible with this cytogenetic interpretation. Molecular analyses of six highly polymorphic dinucleotide repeat loci on the short arm and the proximal long arm of chromosome 9 demonstrated that the girl inherited one allele from her father and two identical or different alleles from the mother. We speculated that the extra chromosome may have resulted from either nondisjunction of chromosome 9 followed by a U-type exchange and a crossing-over between different sister chromatids during maternal meiosis I and subsequent breakage and malsegregation during meiosis II, or nondisjunction during meiosis II followed by isochromosome formation in one of the two maternal chromosomes 9 and subsequent breakage.

Alleles↗

PubMed2001

Structures of mutagens produced by the co-mutagen norharman with o- and m-toluidine isomers.

Norharman, abundantly present in cigarette smoke and cooked foods, is not mutagenic to Salmonella typhimurium strains. However, norharman shows mutagenicity to S. typhimurium TA98 and YG1024 in the presence of S9 mix when coexisting with aromatic amines, including aniline, o- and m-toluidines. We previously reported that the mutagenicity from norharman and aniline in the presence of S9 mix was due to the formation of a mutagenic compound, 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorharman). In the present study, we analyzed the mutagens produced by norharman with o- or m-toluidine in the presence of S9 mix. When norharman and o-toluidine were reacted at 37 degrees C for 20 min, two mutagenic compounds, which were mutagenic with and without S9 mix, respectively, were produced, and these were isolated by HPLC. The former mutagen was deduced to be 9-(4'-amino-3'-methylphenyl)-9H-pyrido[3,4-b]indole (amino-3'-methylphenylnorharman) on the basis of various spectral data, and this new heterocyclic amine was confirmed by its chemical synthesis. The latter mutagen was identified to be the hydroxyamino derivative. Amino-3'-methylphenylnorharman induced 41,000 revertants of TA98, and 698,000 revertants of YG1024 per microg with S9 mix. Formation of the same DNA adducts was observed in YG1024 when amino-3'-methylphenylnorharman or a mixture of norharman plus o-toluidine was incubated with S9 mix. These observations suggest that norharman reacts with o-toluidine in the presence of S9 mix to produce amino-3'-methylphenylnorharman, and this compound is metabolically activated to yield its hydroxyamino derivative. After activation by O-acetyltransferase, it might bind to DNA and exert mutagenicity in S. typhimurium TA98 and YG1024. When norharman and m-toluidine were reacted in the presence of S9 mix, 9-(4'-amino-2'-methylphenyl)-9H-pyrido[3,4-b]indole (amino-2'-methylphenylnorharman) was identified as a mutagen. Thus, the mutagenicity of norharman with m-toluidine may follow a mechanism similar to that with o-toluidine.

Animals↗

PubMed2001

XAFS study on the sulfidation mechanisms of Co-Mo catalysts supported on activated carbon and alumina: effect of complexing agent.

The effect of nitrilotriacetic acid (NTA) as a complexing agent on the sulfidation mechanisms of Co-Mo catalysts supported on activated carbon and alumina was examined by the XAFS technique. The XAFS results revealed that NTA interacted with Co atoms and formed the Co-NTA interaction, while it showed almost no influence on the local structures around Mo atoms. The Co-NTA interaction suppressed the aggregation of cobalt atoms and the interaction between cobalt and alumina during sulfiding, and consequently promoted the formation of the Co-Mo-S phase.

Journal Article↗

PubMed2001

Structure of a full-length cDNA clone for the pro-alpha1(V/XI) collagen chain of red seabream.

The cDNA of type V/XI collagen alpha1 (rsCOL) chain has been isolated from cells established from eyed-period eggs of red seabream, Pagrus major, and sequenced. The amino acid sequence deduced from red seabream alpha1(V/XI) chain resembles that of type XI collagen alpha1 chain. On the other hand, tissue distribution of rsCOL resembles that of type V collagen based on RT-PCR analysis. This is the first report of the cloning of the full-length cDNA of type V/XI collagen alpha1 chain from fish.

Amino Acid Sequence↗

PubMed2001

Visualization of blood flow in hepatic vessels and hepatocellular carcinoma using B-flow sonography.

PURPOSE: A B-flow sonographic technique was recently developed to provide direct visualization of blood flow with gray-scale sonography. Compared with color Doppler sonography, B-flow imaging has wideband resolution and a high frame rate. The purpose of this study was to evaluate the usefulness of B-flow sonography for visualizing blood flow in hepatic vessels and tumor vascularity in patients with liver cirrhosis or hepatocellular carcinoma (HCC). METHODS: Twenty-five patients with liver cirrhosis, including 15 with HCC, were studied by B-flow and color Doppler sonography. Blood-flow detection rates in portal veins and hepatic arteries and tumor vascularity in HCC were analyzed, and the 2 methods were compared. RESULTS: Using B-flow, blood flow was visualized in the portal vein in 23 (92%) of 25 patients and was visualized in the hepatic artery separately from the portal vein in 9 (36%) of 25 patients. The blood-flow signals were visualized only within vessels, never "bleeding" outside the vessel's lumen. Blood flow in the portal vein was observed with color Doppler sonography in all 25 patients, but the hepatic artery was never clearly separated from the portal vein. Vascularity within the HCC tumor was detected in 9 (60%) of 15 nodules with B-flow imaging, and fine arteries flowing into the tumor were observed in 6 nodules. Color Doppler sonography detected blood flow in 13 (87%) of the 15 HCC nodules. CONCLUSIONS: Blood flow in hepatic vessels and tumor vessels of HCC were visualized with B-flow sonography. B-flow sonography is a potentially useful technique for the evaluation of liver vascularity and intratumoral vessels.

Aged↗

PubMed2001

Characterization of the gene EPAC2: structure, chromosomal localization, tissue expression, and identification of the liver-specific isoform.

The liver-specific protein cAMP-GEFII (also known as Epac2) belongs to a family of cyclic adenosine monophosphate (cAMP) binding proteins having guanine nucleotide exchange factor (GEF) activity (the cAMP-GEF family). Here we clone the gene EPAC2, encoding cAMP-GEFII, from a human liver cDNA library. Human EPAC2 has at least 31 exons and is mapped to human chromosome 2q31. Analyses by primer extension, reverse transcriptase-polymerase chain reaction, and in situ hybridization revealed the presence of three transcription start sites of liver-specific Epac2: two major sites located in exon 10 and a minor site in intron 9. The same translation start site is used in all three transcripts. Liver-specific cAMP-GEFII protein, which lacks the first cAMP-binding domain and the Dishevelled/Egl-10/Pleckstrin domain, was detected at 79 kDa by immunoblot analysis, confirming the presence of the short form of cAMP-GEFII in the liver. Liver-specific cAMP-GEFII also has GEF activity toward Rap1. These results demonstrate the presence of liver-specific cAMP-GEFII. Together with the previous finding that cAMP-GEFII is responsible for cAMP-dependent exocytosis in secretory cells, our study suggests that cAMP-GEFII may have a distinct role in liver.

Amino Acid Sequence↗

PubMed2001

High sensitivity of PCR in situ hybridization for the detection of human papillomavirus infection in uterine cervical neoplasias.

OBJECTIVE: This study was designed in order to examine whether the sensitivity of PCR in situ hybridization (PISH) is superior to that of fluorescence in situ hybridization (FISH) and immunocytochemical staining (ICS) in detecting the presence of human papillomavirus (HPV) infection in uterine cervical neoplasias. METHODS: Three cell specimens were obtained from every 54 patients who had been histologically and cytologically diagnosed as severe dysplasia of the uterine cervix (SD), carcinoma in situ of the uterine cervix (CIS), or microinvasive carcinoma of the uterine cervix (MIC). All of them were first stained by the Papanicolaou (pap) method before the experiments. After specimens were classified into SD (n = 17) and CIS/MIC groups (n = 37), the sensitivities of detection for HPV infection were compared among PISH, FISH, and ICS methods which had been carried out after decolorization of the pap stain. RESULTS: In the SD group, PISH demonstrated a 58.8% positive incidence of HPV, which was significantly higher than that (23.5%) shown by FISH (P < 0.05). There was no significant difference in the positivities of HPV between the PISH and ICS (47.1%) methods. In the CIS/MIC group, PISH, FISH, and ICS showed 73.0, 43.2, and 54.1% positive incidences of HPV, respectively. There was significant difference in HPV positivities between PISH and FISH as well as ICS (P < 0.01, P < 0.05). The total frequency of the detection of HPV infection by PISH was significantly higher than that by FISH (P < 0.01) and high with a marginal significance compared to that by ICS (P = 0.051). Moreover, the morphologic change of a single cell and the HPV-positive signals could be observed simultaneously by the PISH technique. CONCLUSION: Because PISH possesses high sensitivity for the detection of HPV infection in morphologically intact cells from uterine cervical neoplasia, the PISH technique might have promising potential for application to the detection of HPV presence in situ in screening.

Carcinoma↗

PubMed2001

Cytoplasmic/nuclear expression without mutation of exon 3 of the beta-catenin gene is frequent in the development of the neoplasm of the uterine cervix.

OBJECTIVE: The dual function of beta-catenin (e.g., as an intermediate protein between adherence junctions and the microfilaments, and as a mediator of the Wnt signaling pathway) is currently known. Stabilization of beta-catenin and subsequent activation of the Wnt signaling pathway are involved in the development of some malignancies. We analyzed the immunohistochemical localization of beta-catenin and the somatic mutation of exon 3 of the beta-catenin gene in the malignant phenotype of the uterine cervix. METHODS: Immunohistochemical localization of beta-catenin and mutation of exon 3 of the beta-catenin gene were analyzed in 38 precancerous lesions and 43 cancerous lesions. RESULTS: In normal cervix, beta-catenin was observed around the plasma membrane of the cells in the basal and parabasal layers of the epithelium. The frequency of cytoplasmic/nuclear beta-catenin expression correlated with a high histological grade of cervical intraepithelial neoplasia. Among invasive carcinomas, 11 (73%) of 15 samples showed cytoplasmic/nuclear localization to variable extents. A mutational analysis showed that mutation occurred in 7 of 68 specimens. Six cases with mutations revealed cytoplasmic/nuclear beta-catenin expression, though 32 (84%) of the 38 samples showing cytoplasmic/nuclear beta-catenin expression were not associated with the mutation. CONCLUSION: These results indicate that cytoplasmic/nuclear expression of beta-catenin is associated with the malignant phenotype of the cervix, but the contribution of mutation of the beta-catenin gene is limited.

Adult↗

PubMed2001

Effects of melatonin on the proliferation and cis-diamminedichloroplatinum (CDDP) sensitivity of cultured human ovarian cancer cells.

OBJECTIVES: In this study, we investigated the antiproliferative effect and telomerase activity of melatonin with or without cis-diamminedichloroplatinum (CDDP) on CDDP-sensitive HTOA cells and CDDP-resistant OVCAR-3 cells of cultured human ovarian cancer. METHODS: HTOA cells and OVCAR-3 cells were cultured in RPMI-1640 at 37 degrees C with 5% CO(2) for 132 h. To examine the antiproliferative effect of melatonin, cells were cultured with or without melatonin (10(-12)-10(-6) M) and thereafter counted in a 96-well microplate using the alamarBlue assay. To examine the effect of melatonin and CDDP, cells were divided into group A (intermittent CDDP, 0.5 microg/ml), group B (intermittent CDDP + melatonin), and group C (sequential (12-h interval) CDDP/melatonin) and thereafter counted in a 96-well microplate using the alamarBlue assay. In different series, cells were cultured and treated with either ethanol, melatonin, CDDP, or CDDP + melatonin. After harvest, telomerase activity was semiquantified with a fluorescence-based telomeric repeat amplification protocol (F-TRAP). RESULTS: (1) Melatonin produced no antiproliferative effect on both types of ovarian cancer cells. (2) Melatonin 10(-6) M induced the antiproliferative effect in groups B and C compared with group A in the HTOA cell line. (3) Melatonin 10(-9) M produced the antiproliferative effect in groups B and C compared with group A in the OVCAR-3 cell line. (4) Telomerase activity in the HTOA cell line did not change but, in the OVCAR-3 cell line, was significantly lower in the CDDP + melatonin group compared with the ethanol and CDDP groups. CONCLUSIONS: Melatonin enhanced CDDP sensitivity in two ovarian cancer cell lines. Thus, melatonin may improve ovarian cancer chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗