Isao Miyakawa

Human ovarian carcinoma cells: histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosis.

Histone deacetylase inhibitors (HDACIs) can inhibit proliferation, stimulate apoptosis, and induce cell cycle arrest in malignant cells.

The clinical role of interleukin-6 and interleukin-6 soluble receptor in human follicular fluids.

Abstract. 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.

Production of vascular endothelial growth factor and angiogenic factor in human follicular fluid

The aim of this study was to quantitate of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and angiogenin in follicular fluid (FF) and to correlate the levels of these substances with oocyte maturation. FF were aspirated from women undergoing in vitro fertilization and embryo transfer. Sera were collected from women with normal menstrual cycles. VEGF in FFs and sera were measured by enzyme linked immunosorbent assay. VEGF, HGF, and angiogenin mRNA expression aspirated folliculars cell was analyzed by reverse transcription and polymerase chain reaction (RT-PCR). The concentrations of VEGF, HGF, and angiogenin in FF were significantly higher than those in serum (P<0.001). VEGF, HGF, and angiogenin mRNA in the aspirated follicles cell was detected by RT-PCR. HGF levels were higher in FF containing mature oocyte. The levels of VEGF in FF containing mature oocytes in women under 39 years of age were significantly lower than those in FF from women more than 40 years old (P<0.01). Our data suggest that VEGF, HGF, and angiogenin may play an important role in follicular growth and development, that VEGF levels in FF appear to be age-dependent; and that VEGF and HGF levels might be valuable biochemical markers of oocyte maturation.

The effect of inflammatory cytokines on secretion of macrophage colony-stimulating factor and monocyte chemoattractant protein-1 in human granulosa cells.

Problem:u2002 In order to investigate the role of macrophage colony‐stimulating factor (M‐CSF) and monocyte chemoattractant protein ‐1 (MCP‐1) in human ovulation, we studied the regulation of M‐CSF and MCP‐1 in cultured human granulosa cells.

Placenta percreta invading the urinary bladder.

IntroductionPlacenta percreta is a rare obstetric complication causing life-threatening hemorrhage.Case report The case of a woman with a placenta percreta invading the urinary bladder treated by cesarean hysterectomy and partial bladder resection is presented. Overall estimated blood loss was 11,130xa0ml, and 59 units of various blood products were transfused.ConclusionObstetricians and urologists should be aware of this rare condition.

Ureteral and Sigmoid Obstruction Caused by Pelvic Actinomycosis in an Intrauterine Contraceptive Device User

We report herein a rare case of ureteral and sigmoid obstruction caused by pelvic actinomycosis in a patient fitted with an intrauterine contraceptive device (IUCD). A 63-year-old Japanese woman was admitted complaining of lower abdominal pain and slight fever continuing for a month. She had a history of IUCD insertion 30 years previously and had been menopausal for the past 10 years. Ultrasonography and CT scan revealed a solid pelvic mass involving the uterus, sigmoid colon, urinary bladder, and right ureter. The IUCD was detected in the uterine cavity. Right hydronephrosis and hydroureter due to an obstruction of the distal ureter and the extensive stenosis of the sigmoid colon were also observed. Blood analysis showed leukocytosis, thrombocytosis, and elevated C-reactive protein levels. Although pathological and microbiological analysis of the removed IUCD showed negative results for Actinomyces infection, these findings suggested a pelvic abscess caused by actinomycosis. Benzyl penicillin administration was started immediately. Total hysterectomy, bilateral salpingo-oophorectomy, and lysis of adhesion around the ureter were performed. Actinomycosis was diagnosed based on histologic examination. The patient’s postoperative course was uneventful except for persistent mild hydroureter and hydronephrosis. The patient is now healthy without evidence of recurrent Actinomyces infection 1 year after treatment. As shown in the present case, pelvic actinomycosis should be considered as a cause of pelvic inflammatory disease in IUCD users, even though Actinomyces was not detected on the IUCD.

Effects of leptin on the production of cytokines by cultured human endometrial stromal and epithelial cells

OBJECTIVEnTo evaluate the effects of leptin on the production of interleukin (IL)-6 family cytokines and chemokines by human endometrial stromal cells (ESC) and epithelial cells.nnnDESIGNnThe effects of leptin on the production of IL-6, IL-11, leukemia inhibitory factor (LIF), IL-8, growth-regulated oncogene (GRO)-alpha, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-3alpha by ESC and the endometrial epithelial cell line HHUA were investigated.nnnSETTINGnResearch laboratory at a medical university.nnnPATIENT(S)nEight endometrial specimens in the late proliferative phase were used for the isolation of ESC.nnnINTERVENTION(S)nESC and HHUA were incubated for 24 hours with recombinant human leptin.nnnMAIN OUTCOME MEASURE(S)nThe concentration of IL-6, IL-11, LIF, IL-8, GRO-alpha, MCP-1, and MIP-3alpha were measured using ELISAs.nnnRESULT(S)nUnstimulated ESC and HHUA constitutively secreted IL-6, IL-11, LIF, IL-8, GRO-alpha, MCP-1, and MIP-3alpha. The increase in levels of IL-6, IL-8, GRO-alpha, MCP-1, and MIP-3alpha in the culture media of ESC and HHUA paralleled the addition of increasing amounts of leptin. In contrast, the levels of IL-11 and LIF were not affected by leptin administration.nnnCONCLUSION(S)nThe present findings suggest that leptin may be an additional modulator of IL-6 and chemokine expression in the endometrium. Leptin may contribute to the normal and pathological processes of human reproduction by the regulation of these cytokines in the local environment.

Secretion of granulocyte chemotactic protein-2 by cultured human endometrial stromal cells

OBJECTIVEnTo evaluate the expression of granulocyte chemotactic protein-2 (GCP-2) in human endometrial stromal cells.nnnDESIGNnThe effects of interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha, TNF-beta, interferon (IFN)-gamma, and lipopolysaccharide (LPS) on the production of GCP-2 by endometrial stromal cells were investigated.nnnSETTINGnResearch laboratory at a medical university.nnnPATIENT(S)nEight endometrial specimens in the late proliferative phase were used.nnnINTERVENTION(S)nEndometrial stromal cells were incubated for 24 hours with IL-1alpha, IL-1beta, TNF-alpha, TNF-beta, IFN-gamma, and LPS.The concentration of GCP-2 in the culture media was measured using an enzyme-linked immunosorbent assay (ELISA).nnnRESULT(S)nA small amount of GCP-2 was detected in the culture media of unstimulated endometrial stromal cells. The production of GCP-2 by endometrial stromal cells was stimulated with IL-1alpha, IL-1beta, TNF-alpha, TNF-beta, and LPS in a dose-dependent manner. Interferon-gamma did not affect GCP-2 production by these cells.nnnCONCLUSION(S)nThese results suggest that GCP-2 is an additional ELR(+)-CXC chemokine expressed in endometrial stromal cells. The modulation of GCP-2 concentrations in the local environment may contribute to the normal and pathological processes of human reproduction by regulating the neutrophil trafficking in the endometrium.

Expression of c-Ets1 protein in normal human placenta.

Background: The proto-oncogene product c-Ets1 is a transcriptional factor that controls the expression of a number of genes involved in extracellular matrix remodeling such as stromelysin-1 (matrix metalloproteinase-3; MMP-3), collagenase-1, and urokinase-type plasminogen activator (u-PA). To elucidate the involvement of c-Ets1 in the invasive pathway of the trophoblasts, we analyzed c-Ets1 protein expression in placentas by fluorescent immunohistochemistry and Western blot analysis. Methods: We analyzed serial frozen sections for c-Ets1 protein expression of the chorionic villi and cell column in the first trimester and the basal plate of placenta and amniotic membranes in the third trimester by fluorescent immunohistochemistry. Moreover, we examined the expression of c-Ets1 in the first and the third trimester by Western blot analysis. Results: In the first trimester, c-Ets1 was strongly expressed in the cytoplasm of cytotrophoblasts. Moreover, the cell column that invaded the endometrium had the strongest expression of c-Ets1. In the third trimester, c-Ets1 was detected in both cytoplasm and nucleus of the invading trophoblasts in the basal plate. Furthermore, c-Ets1 was expressed in both cytoplasm and nucleus of the trophoblasts in amniotic membrane. Western blotting revealed that c-Ets1 expressions in the first trimester were stronger than those in the third trimester. Conclusion: Our results demonstrate that c-Ets1 expression in normal human placenta correlates to the invasive behavior of the trophoblasts, probably by activating the transcription of matrix-degrading MMPs, including MMP-3, collagenase-1, and u-PA.

Adenoid cystic carcinoma of the uterine cervix

Adenoid cystic carcinoma of the uterine cervix is a rare and peculiar variant of adenocarcinoma. This tumor represents 3% of all primary cervical adenocarcinomas, and it is locally aggressive and capable of metastasis to other organs even in its early stage. We report a case of adenoid cystic carcinoma stage IIIb that was successfully treated with radiotherapy. The patient shows no evidence of recurrent tumor at 5 years after radiotherapy. Generally, radiotherapy and chemotherapy are chosen as the first treatment, because this cancer is seen most commonly in the elderly.