Management of patients with carcinoma of the cervix with anuric renal failure.
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Adenocarcinoma↗
Biomedical subjects
I Miyakawa
Publications and source records attributed to I Miyakawa.
A 22 kDa protein specific for yeast mitochondrial nucleoids is an unidentified putative ribosomal protein encoded in open reading frame YGL068W.
Mitochondrial-nucleoid (mt-nucleoid) proteins of the yeast Saccharomyces cerevisiae were separated by two-dimensional gel electrophoresis. Analysis of the N-terminal amino acid sequence showed that a 22 kDa protein which is unique in the mt-nucleoid fraction is an unidentified protein encoded in the open reading frame YGL068W and shows a homology with the ribosomal protein L7/L12 of bacteria. We named this protein Mnp1p (for the mitochondrial-nucleoid protein 1). Immunoblotting of each fraction with an anti-Mnp1p antibody during the mt-nucleoid isolation showed that Mnp1p is highly concentrated in the mt-nucleoid fraction. Immunofluorescence microscopy suggested that Mnp1p is localized to mitochondria in vivo, and a significant amount of Mnp1p is associated with the mt-nucleoids. On the other hand, Northern blotting showed that a large amount of large and small mitochondrial ribosomal RNAs was not associated with the mt-nucleoids and remained in the supernatant after the isolation of mt-nucleoids. The null mutation of MNP1 led to a respiratory-deficient phenotype, but the morphology of the mt-nucleoids in the transformants carrying the null mutation was normal. These results suggest that a significant amount of Mnp1p plays a role as a major component of the mt-nucleoids.
Amino Acid Sequence↗
The clinical role of interleukin-6 and interleukin-6 soluble receptor in human follicular fluids.
In order to investigate the role of interleukin-6 (IL-6) and interleukin-6 soluble receptor (sR) in human ovulation, we evaluated the concentrations in human follicular fluid and analyzed the correlation of IL-6 and IL-6 sR with oocyte maturation. The oocytes were obtained from the follicular fluid of 45 women undergoing in vitro fertilization and embryo transfer. The concentrations of IL-6 and IL-6 sR in follicular fluid were measured by ELISA. In addition, granulosa cells obtained from the follicular fluid were cultured and treated with forskolin and 12- o-tetradecanoylphorbol 13-acetate for 24-48 h. The concentration of IL-6 was significantly higher in the follicular fluid than in the serum (P<0.01). In contrast, the concentration of IL-6 sR was significantly lower in the follicular fluid than in the serum (P<0.001). The concentrations of IL-6 and IL-6 sR were significantly higher in the follicular fluid containing mature oocytes than in fluid containing immature oocytes (P<0.05). The production of IL-6 was markedly increased over the basal level after 24 h of treatment with forskolin (P<0.001) and 48 h of treatment (P<0.01) with cultured granulosa cells. Our data suggest that IL-6 and IL-6 sR may play an important role in follicular growth and development in human preovulatory processes. It is possible that IL-6 in particular may be regulated by cAMP. IL-6 and IL-6 sR might also be valuable biochemical markers in the evaluation of oocyte maturation.
Cells, Cultured↗
Complete response to radiation therapy in a patient with chemotherapy-resistant ovarian clear cell adenocarcinoma.
Recurrent ovarian cancer after front-line chemotherapy is incurable. In most institutions, chemotherapy is continued as salvage therapy after primary chemotherapy failure and despite the fact that long-term survival and complete responses are infrequent. Radiation therapy for patients with recurrent ovarian cancer has often been done with palliative intent. A patient with ovarian clear cell adenocarcinoma received irradiation with palliative intent to the whole pelvis after chemotherapy (paclitaxel, carboplatin, and irinotecan) produced no effect. Although she developed a rectovaginal fistula due to cancer invasion during radiation therapy. One year and half after the therapy, she is still alive with no evidence of disease. In an effort to maximize salvage potential and quality of life while minimizing toxicity, selected patients with ovarian cancer should be treated with radiation therapy directed to residual or recurrent sites.
Adenocarcinoma, Clear Cell↗
Identification of the YMN-1 antigen protein and biochemical analyses of protein components in the mitochondrial nucleoid fraction of the yeast Saccharomyces cerevisiae.
We analyzed the protein components contained in the mitochondrial nucleoid (mt-nucleoid) fraction of the yeast Saccharomyces cerevisiae. Immunoblotting with anti-Abf2p antibody demonstrated the association of Abf2p, a major mitochondrial DNA-binding protein, with the mt-nucleoids. In contrast, porin and cytochrome c oxidase subunit III (CoxIIIp) were not detected by immunoblotting in the mt-nucleoid fraction. The YMN-1 monoclonal antibody recognized a 48 kDa protein of the mt-nucleoid fraction. The N-terminal amino acid sequence of the protein and immunological evidence showed that the YMN-1 monoclonal antibody recognizes dihydrolipoyl transsuccinylase (KE2), which is one of the constituents of the alpha-ketoglutarate dehydrogenase complex (KGDC). alpha-Ketoglutarate dehydrogenase (KE1) and dihydrolipoyl dehydrogenase (E3), which are other subunits of KGDC, were also detected in the mt-nucleoid fraction. An enzyme assay of the mt-nucleoid fraction showed that cytochrome c oxidase and fumarase activity were barely detected in the fraction, but the specific activity of KGDC in the mt-nucleoid fraction was relatively high and was approximately 60% of the specific activity in the mitochondrial fraction. Three components of KGDC were detected in the DNA-binding protein fractions after DNA-cellulose column chromatography of mt-nucleoid proteins. These results suggested that a part of KGDC in the mitochondrial matrix is associated with mt-nucleoids in vivo.
Acyltransferases↗
The effect of epidermal growth factor on vascular endothelial growth factor secretion by endometrial stromal cells.
Endometrial stromal cells undergo morphological and functional changes to facilitate oocyte implantation under regulation of various hormones and growth factors. We studied physiological induction by epidermal growth factor (EGF) of vascular endothelial growth factor (VEGF) in these cells. In human endometrial stromal cells, the effect of EGF, genistein, tryphostin AG1478 (a tyrosine kinase inhibitor), and wortmannin (a phosphatidylinositol 3-kinase inhibitor) on production of VEGF was examined. Total RNA was extracted and VEGF mRNA expression was quantified by Northern analysis. EGF induced production of VEGF by stromal cells in a time-dependent manner; the effect became significant after 12 h and increased further between 24 and 48 h (P<0.05). Dose dependency was also significant (P<0.01). Genistein, tryphostin AG1478, and wortmannin partially suppressed the increase in production induced by EGF (P<0.01, P<0.01, P<0.01), respectively. Production of EGF by fertilized oocytes and trophoblasts has been reported in early pregnancy. VEGF is believed to be induced by EGF through mechanisms involving tyrosine kinase and phosphatidylinositol 3-kinase. The increase in VEGF may contribute to neovascularization that promotes proliferation of endometrium and placentation.
Cells, Cultured↗
c-Ets1 is a promising marker in epithelial ovarian cancer.
c-Ets1 controls the expression of some genes involved in extracellular matrix remodeling. To elucidate the involvement of c-Ets1 in epithelial ovarian carcinogenesis, we investigated the role of the proto-oncogene c-ets1 in the regulation of physiological processes such as cell proliferation, differentiation, and tumor invasion. Using fluorescent immunohistochemistry, we analyzed serial frozen sections for c-Ets1 protein expression in 26 patients with ovarian epithelial carcinoma, 10 patients with benign cystadenoma of the ovary, and 10 premenopausal patients with normal ovaries. We analyzed the relationship between the percentage of c-Ets1 stained cells in a patient and characteristics of the patient including histological classification, clinical stage, histological grade, and clinical outcome. c-Ets1 was not detected in any cases of benign ovarian cystadenoma. Most of the c-Ets1 proteins were found in the cytoplasm and some in the nucleus of epithelial ovarian cancer tissues. Moreover, c-Ets1 was strongly expressed in the head portion of papillary cancer tissues that had invaded the stroma. c-Ets1 expression was significantly associated with clinical stage (p<0.01), histological grade (p<0.01), and clinical outcome (p<0.01). Survival data were available for all patients and univariate Cox regression analysis showed that c-Ets1 expression was significantly associated with a poor prognosis (p<0.05). Our results demonstrate that c-Ets1 expression in epithelial ovarian cancer correlates to the malignant potential of the tumor.
Biomarkers, Tumor↗
Polo-like kinase (PLK) expression in endometrial carcinoma.
Polo-like kinase (PLK) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase. Recent reports have shown a critical role for PLK during tumorigenesis. To explore whether PLK plays a general role as a tumor marker of endometrial carcinomas, we examined the expression of PLK mRNA and protein in endometrial carcinomas and normal endometrium, and analyzed the relationship between PLK protein expression and malignant potential. We found that PLK mRNA was expressed in all specimens from endometrial carcinoma patients using RT-PCR methods, although some specimens from normal endometria were negative. Immunohistochemically, most of the PLK was found in the cytoplasm (around the nucleus), and partly in the nucleus of endometrial carcinoma glands and also secreted tissues from endometrial carcinoma glands. PLK was expressed at the basement membrane of carcinoma glands and partly expressed in the head portion of papillary carcinoma tissues. There was a significant correlation between percentages of PLK-positive cells and histological grade of endometrial carcinoma (P<0.0001). However, the expression of proliferating cell nuclear antigen and Ki-67 was independent of PLK expression. Moreover, we noted that PLK is strongly expressed in invading carcinoma cells. PLK expression could reflect the degree of malignancy and proliferation in endometrial carcinoma. Thus, in addition to being of diagnostic value, modulation of PLK activity in the tumors by chemotherapeutic agents or gene therapy may prove to be of therapeutic value.
Adult↗
Id1 expression is associated with histological grade and invasive behavior in endometrial carcinoma.
Basic helix-loop-helix (bHLH) DNA-binding proteins have been reported to regulate tissue-specific transcription of cellular differentiation within multiple cell lineages. The Id family of helix-loop-helix proteins does not possess a basic DNA-binding domain and functions as a negative regulator of bHLH proteins by forming high-affinity heterodimers with bHLH proteins. Id proteins were originally characterized as inhibitors of DNA binding and cell differentiation. Thus, overexpression of Id proteins correlates with cell proliferation and arrested differentiation in many cell lineages. To elucidate the involvement of Id1 in endometrial carcinogenesis, we analyzed serial frozen sections for Id1 protein expression in 20 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of Id1-stained cells and the patient's characteristics, including histological grade, clinical stage, presence of invasion to >1/2 myometrium, and clinical outcome. In normal endometria, Id1 was not detected in either the proliferative or the secretory phase. There was, however, abundant Id1 immunoreactivity in the endometrial carcinoma cells. Moreover, Id1 was strongly expressed in the inflammatory cells. Scoring on the basis of the percentage of positive cells indicated that Id1 expression is significantly associated with histological grade (P<0.05) and the presence of invasion to >1/2 myometrium (P<0.05). Our results demonstrate that increased Id1 expression in endometrial carcinoma correlates with the malignant potential of this tumor.
Adult↗
Expression of polo-like kinase in ovarian cancer is associated with histological grade and clinical stage.
Polo-like kinase (PLK), a cell cycle-regulated, cyclin-independent serine/threonine protein kinase, has been shown in recent reports to play a critical role during tumorigenesis. To investigate whether PLK plays a general role as a tumor marker of ovarian cancers, we examined the expression of PLK protein in ovarian cancers, and analyzed the relationship between PLK protein expression and histological grade. Immunohistochemically, the majority of PLK was found in the cytoplasm (around the nucleus), and a portion was found in the nucleus of ovarian cancer glands and also in the fluid secreted from these glands. PLK was expressed at the basement membrane of cancer glands and partly expressed in the head portion of papillary cancer tissues. A significant correlation was found between percentages of PLK-positive cells and histological grade of ovarian cancer (P<0.001). However, the expression of proliferating cell nuclear antigen, Ki-67, and cyclin B1 was independent of PLK expression. Taken together, these findings suggest that PLK expression may reflect the degree of malignancy rather than the degree of proliferation in ovarian cancer. Thus, in addition to being of diagnostic value, PLK activity in ovarian tumors may be modulated by chemotherapeutic agents or gene therapy to therapeutic effect.
Adenocarcinoma↗
FTIR spectroscopic analyses of human placental membranes.
We investigated the differences in the Fourier transform infrared (FTIR) spectra of normal and abnormal human placentas. Normal placentas, placentas with infant intrauterine growth restriction (IUGR), and placentas from mothers with diabetes mellitus (DM) were used, none of which had been treated before measurement. The tissues were divided into three parts: the upper one-third portion (P1), the middle portion (P2), and the lower one-third portion (P3). Placental tissues were also investigated histochemically. The differences of the main second-derivative FTIR spectra among P1, P2, and P3 in normal placentas were observed in bands appearing between 1080 and 1090 cm(-1). Bands in P2 were observed at 1083 cm(-1), which was significantly higher than that in P3 (p < 0.05). The spectrum of P2 tissue in placentas with infant IUGR had a peak at 1081 cm(-1), which was significantly different from those of P1 and P3 (p < 0.05). In placentas with DM, the P2 band was shifted to a peak at 1088 cm(-1). These data were well correlated with the histochemical sugar-chain staining pattern of the P2 portion of the placenta. Our data suggested that this IR technique is applicable to the clinical diagnosis of diseases in the gynecological field.
Adult↗
Effect of endotoxin-induced reactive oxygen species on sperm motility.
OBJECTIVE: To define the mechanism of infection-induced damage of sperm. DESIGN: The effect of lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) on sperm motility and its modification by scavengers were investigated. SETTING: Research laboratory of a university hospital. PATIENT(S): Normozoospermic semen samples were obtained from 37 healthy volunteers. INTERVENTION(S): The sperms were incubated in the presence of LPS with or without scavengers. MAIN OUTCOME MEASURE(S): Sperm motility was evaluated by a sperm quality analyzer (SQAIIB). ROS formation in semen samples was measured by a Berthold luminometer (LB953). RESULT(S): Motility of spermatozoa was decreased in the LPS-treated samples compared with that in the control groups. ROS was significantly higher in the LPS-treated groups than in the control groups. The addition of ROS scavengers restored the motility index and suppressed ROS production in the LPS-treated semen samples. CONCLUSION(S): These data suggest that endotoxin-induced excessive production of ROS is responsible for the decrease in sperm motility and that antioxidant therapy may be a therapeutic option for infertile men with bacterial genital tract infection.
Endotoxins↗
The effect of dexamethasone on expression of mitogen-induced cyclooxygenase-2 mRNA by amnion-derived (WISH) cells.
OBJECTIVES: It has been reported that prostaglandin E(2) (PGE(2)) is synthesized in the amnion and that this synthesis increases during labor. The purpose of this study was to clarify the mechanism for the expression of cyclooxygenase-2 (COX-2) mRNA and the PGE(2) synthesis of amnion-derived (WISH) cells. STUDY DESIGN: Cells were cultured and treated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and dexamethasone (DEX). PGE(2) in the culture medium was measured by ELISA. Total RNA was extracted from the cells, and COX-2 mRNA expression was analyzed by Northern blot analysis. RESULTS: During the time course of PGE(2) production in response to TPA stimulation, the PGE(2) production could not be detected until incubation had continued for 2h, but this production appeared to continue after 4h of incubation. PGE(2) production was significantly increased by TPA and suppressed by treatment with TPA and DEX. During the time course of COX-2 mRNA expression in response to treatment with TPA, the COX-2 mRNA band was detected after 1.5h. The strongest expression of COX-2 mRNA was observed at 2h incubation. After pre-treatment with TPA for 1h, the TPA-induced COX-2 mRNA was suppressed by treatment with DEX for 1 or 2h incubation in a dose-dependent manner. CONCLUSIONS: These results suggest that COX-2 mRNA is induced by TPA which activate protein kinase C, and suppressed by DEX in WISH cells.
Amnion↗
Expression of cathepsin L in normal endometrium and endometrial cancer.
OBJECTIVE: To evaluate the expression of cathepsin L in normal endometrium and endometrial adenocarcinoma. STUDY DESIGN: Tissue from eight cases of G1 and eight of G2 endometrioid adenocarcinoma, and 15 normal endometrial specimens were examined by immunohistochemistry. RESULTS: In the normal endometrium, cathepsin L was expressed in a few cell layers of the apical part of the glandular epithelium throughout the menstrual cycle. In the carcinomas, there was an inverse correlation between the grade of tumor and the cathepsin L expression. CONCLUSION: Cathepsin L expression may cease during endometrial carcinogenesis and its expression may be less important in tumor progression than it is in tumors of other tissues.
Adenocarcinoma↗
Effect of ceramide analogs on interleukin-1alpha-induced production of prostaglandin E2 by amnion-derived (WISH) cells.
BACKGROUND: Prostaglandin E2 (PGE2) is reportedly synthesized in the amnion, and its levels are increased during labor. Our objective was to measure the level of PGE2 induced by interleukin (IL)-1alpha following treatment with ceramide analogs in amnion-derived cells. METHODS: Amnion-derived (WISH) cells were cultured and stimulated by IL-1alpha, IL-1 receptor antagonist (ra), C2-ceramide and C6-ceramide. The levels of PGE2 in the media were measured by ELISA. The induction of prostaglandin H synthase (PGHS)-2 mRNA was detected by reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: Following stimulation with IL-1alpha, the production of PGE2 could not be detected until incubation had continued for 2 h, but this production appeared to continue after 4 h of incubation. The production of PGE2 was significantly increased by IL-1alpha, and was suppressed by IL-1 ra, in a dose-dependent manner. PGE2 production was significantly increased by IL-1alpha and C2-ceramide as compared with IL-1alpha alone. However, PGE2 production was not significantly increased by IL-1alpha and C6-ceramide as compared with IL-1alpha alone. PGHS-2 mRNA were induced by treatment with IL-1alpha, and were strongly induced by treatment with IL-1alpha and C2-ceramide by RT-PCR. CONCLUSIONS: Results suggest that IL-1alpha induce the PGHS-2 mRNA and stimulate the production of PGE2 by a mechanism that involves the sphingomyelin-ceramide system. Ceramide may be important in increasing the production of PGE2 during parturition.
Amnion↗
Synergistic effect of interleukin-1alpha and ceramide analogue on production of prostaglandin E2 and F2alpha by endometrial stromal cells.
PROBLEM: Prostaglandins (PGs) are synthesized in the endometrium. Our objective was to evaluate interleukin (IL)-1alpha-induced production of PGE2 and PGF2alpha in endometrial stromal cells (ESC) following treatment with ceramide analogues. METHODS OF STUDY: ESC were obtained from human uterine endometrium by enzymic digestion and filtration. ESC were treated with IL-1alpha, IL-1 receptor antagonist (ra), C2-ceramide and C6-ceramide. The concentrations of PGE2 and PGF2alpha in media were determined using ELISA. The induction of prostaglandin H synthase (PGHS)-2 mRNA was also ascertained by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The production of PGE2 and PGF2alpha was significantly increased by IL-lalpha and suppressed by IL-1 ra, in a dose-dependent manner. PGF2alpha production was further increased by treatment with the combination of IL-1alpha and C2-ceramide as compared with IL-1alpha treatment alone. There was no significant difference in PGE2 production between cells treated with IL-1alpha and C2-ceramide and those treated with IL-1alpha alone. Both PGE2 and PGF2alpha production were significantly increased by treatment with IL-1alpha and C6-ceramide as compared with IL-1alpha treatment alone. Treatment of ESC with IL-1alpha stimulated PGHS-2 mRNA. PGHS-2 mRNA was decreased when IL-1 ra was added to the IL-1alpha-stimulated cells. CONCLUSIONS: These results suggest that IL-1alpha stimulates the production of PGE2 and PGF2alpha by a mechanism that involves the sphingomyelin-ceramide system, and thus that ceramide may be important in increasing the production of PGE2 and PGF2alpha in the human endometrium.
Cells, Cultured↗
The effect of pregnancy on cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activities in humans.
OBJECTIVE: Our objective was to evaluate the activity of cytochrome P4501A2 (CYP1A2), xanthine oxidase (XO), and N-acetyltransferase 2 (NAT2) from early to late pregnancy and after delivery. METHODS: Twelve women were studied on three occasions during pregnancy (early, 8-16 weeks' gestation; middle, 20-28 weeks' gestation; and late, 32-39 weeks' gestation) and about 1 month after delivery. Caffeine was used as a metabolic probe. After the women ingested a can or a bottle of caffeine-containing soft drink, urine samples were collected for 12 hours. The caffeine metabolites measured were 5-acetylamino-6-amino-3-methyluracil (AAMU), 1-methylxanthine (1X), 1-methyl-uric acid (1U), 1,7-dimethyl-uric acid (17U), and 1,7-dimethylxanthine (17X). The hepatic enzyme activities were estimated by the urinary caffeine metabolic ratios as follows: CYP1A2 = (AAMU + 1X + 1U)/17U; XO = 1U/(1X + 1U); NAT2 = AAMU/(AAMU + 1X + 1U). RESULTS: Statistically significant differences were found in CYP1A2 (P < .0001) and NAT2 (P < .01). The mean metabolic ratios for CYP1A2 during pregnancy (6.80, 5.18, and 4.97 for the early phase, middle phase, and late phase, respectively) were significantly lower than the ratio after delivery (10.39). The mean metabolic ratio for NAT2 in the early phase (0.57) was significantly lower than after delivery (0.66). There was no significant difference in metabolic ratios for XO during pregnancy and after delivery. CONCLUSION: The data demonstrate that pregnancy influences CYP1A2 and NAT2 activity. CYP1A2 activity decreases not only in late pregnancy but also in early and middle pregnancy.
Adult↗
Effects of interleukin-4 on the in-vitro production of cytokines by human endometrial stromal cells.
A T helper (Th)1/Th2 model has been applied to as a system regulating the cytokine network during pregnancy. To evaluate the effects of interleukin (IL)-4, a Th2 cytokine, on the cytokine production by endometrial stromal cells (ESC), an enzyme-linked immunosorbent assay was used to measure the concentrations of IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and macrophage colony-stimulating factor (M-CSF) in the culture media of ESC and of an endometrial stromal sarcoma cell line, MaMi, following the addition of recombinant human IL-4. The expression of mRNAs for IL-6 and IL-8 in ESC after stimulation with IL-4 was also evaluated by Northern blot analysis. Increases in the concentrations of IL-6, IL-8, MCP-1, and M-CSF in the culture media of ESC and MaMi cells were observed on the addition of increasing amounts of IL-4. This cytokine also stimulated the transcription of IL-6 and IL-8 in ESC in a dose-dependent manner. It is suggested that IL-4 secreted by the maternal decidual tissue as well as by the developing embryo may stimulate the production of IL-6, IL-8, MCP-1, and M-CSF by ESC. The increased concentration of these cytokines in the local environment may contribute to the maintenance of early pregnancy by modulating the immune reaction at the feto-maternal interface.
Animals↗