Jinsuke Yasuda

IL-15 Expression at Human Endometrium and Decidua

Abstract A large number of natural killer (NK) cells appear in human uterine mucosa during the secretory phase and first trimester pregnancy. We investigated the expression of interleukin (IL)-15, a possible stimulator for these NK cells, in human endometrium and first trimester decidua. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that IL-15 mRNA expression was stronger during the secretory phase and first trimester pregnancy than during the proliferative phase. Immunohistochemistry revealed that immunoreactivity for anti-IL-15 was higher during the secretory phase than it was during the proliferative phase. This was prominent in the perivascular stromal cells around invading spiral arteries during the mid- to late-secretory phase. In first trimester decidua, endothelial cells were also stained as strongly as stromal cells. A membrane-bound IL-15 molecule was detected on the surface of first trimester decidual cells by flow cytometry. Progesterone stimulated the release of soluble IL-15 in the supernatant of cultured decidual cells. These results suggest that IL-15 expression in human uterine mucosa corresponds to the fluctuation of uterine NK cells and that its production is hormonally controlled, especially by progesterone.

Effect of female sex steroids on human endometrial CD16neg CD56bright natural killer cells

OBJECTIVE To clarify whether female sex steroids directly affect the bioactivity of the human endometrial CD16neg CD56bright natural killer (NK) cells. DESIGN In vitro study. SETTING University obstetrics and gynecology department. PATIENT(S) Thirteen women with histologically normal endometrium who were undergoing hysterectomy and seven women during the first trimester of pregnancy who were undergoing selective termination. INTERVENTION(S) Endometrium or decidua was obtained. MAIN OUTCOME MEASURE(S) The effects of 17beta-estradiol or progesterone (10(-6), 10(-7), and 10(-8) M) on the proliferation, cytolytic activity, and cytokine secretion of the isolated endometrial CD16neg CD56bright NK cells were examined using a 3H-thymidine incorporation assay, 51Cr-releasing assay, and enzyme-linked immunosorbent assay, respectively. RESULT(S) Neither 17beta-estradiol nor progesterone had significant effects on the proliferation, cytolytic activity, and cytokine secretion of endometrial CD16neg CD56bright NK cells. CONCLUSION(S) Female sex steroids do not directly affect the bioactivity of the human endometrial CD16neg CD56bright NK cells.

Serum and urinary estrone sulfate during the menstrual cycle, measured by a direct radioimmunoassay, and fate of exogenously injected estrone sulfate

Serum and early-morning urinary levels of estrone sulfate during the menstrual cycle were measured by a direct radioimmunoassay without hydrolysis. These levels were high and showed prominent peaks [serum, 2.67 +/- 0.37 ng/ml (mean +/- SE); urine, 5.82 +/- 2.3 micrograms/l] around the day of the preovulatory estradiol-17 beta peak, and increased again during the luteal phase. Following intravenous injection of estrone sulfate, serum estrone sulfate, estrone and estradiol-17 beta were measured. The conversion of estrone sulfate to estrone and/or estradiol-17 beta was very small during their transit in the general circulation.

A pilot study of docetaxel-carboplatin versus paclitaxel-carboplatin in Japanese patients with epithelial ovarian cancer

BackgroundIt has been reported that a docetaxel-carboplatin combination as first-line chemotherapy for ovarian cancer showed a level of progression-free survival similar to that of paclitaxel-carboplatin while reducing neurotoxicity and improving quality of life. We investigated the recommended doses of docetaxel-carboplatin in Japanese patients with ovarian cancer and conducted a comparative study of docetaxel-carboplatin versus paclitaxel-carboplatin.MethodsThirty-nine patients with ovarian cancer were enrolled in this study and 38 patients were evaluated. We conducted a dose-escalation study using a docetaxel dose of 70 mg/m2 and carboplatin AUC 5 and 6. In the comparative study, patients received either docetaxel 70 mg/m2 and carboplatin AUC 5 or paclitaxel 175 mg/m2 and carboplatin AUC 5. Progression-free survival, survival rate at 2 years, response rate, toxicity, and quality of life were investigated.ResultsIn the dose-finding study, we determined the recommended doses as docetaxel 70 mg/m2 and carboplatin AUC 5. In the comparative study, the two arms showed similar progression-free survival. Grade 4 neutropenia occurred more frequently in the docetaxel-carboplatin group (84.6%) than in the paclitaxel-carboplatin group (43.8%), while sensory neurotoxicity was less frequent in the docetaxel-carboplatin group (53.8%) than in the paclitaxel-carboplatin (68.8%) group. There were significant differences in the quality-of-life data in favor of docetaxel-carboplatin.ConclusionWe determined the recommended doses of docetaxel-carboplatin for Japanese patients with ovarian cancer to be docetaxel 70 mg/m2 and carboplatin AUC 5. In the comparative study, we suggest that the docetaxel-carboplatin combination is effective and well tolerated as first-line chemotherapy for Japanese patients with ovarian cancer.

Localization of interferon regulatory factor-1 in human endometrium throughout the menstrual cycle

OBJECTIVE To determine the expression and localization of IRF-1 in human endometrium throughout the menstrual cycle. DESIGN A comparative study. SETTING Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine. PATIENTS Thirty-eight women aged 33 to 46 years, with regular menstrual cycles and nonpathological endometrium, undergoing hysterectomy. INTERVENTION(S) Endometrial tissues were obtained from operative samples. MAIN OUTCOME MEASURE(S) Expression of IRF-1 mRNA throughout the menstrual cycle was investigated using semiquantitative reverse transcription-polymerase chain reaction. Localization of IRF-1 protein was determined using immunohistochemistry. RESULT(S) IRF-1 mRNA was expressed in the human endometrium at each phase of the menstrual cycle. The immunoreactivity for IRF-1 was observed in the extranuclear compartment of the surface and glandular epithelial cells, both during the proliferative and secretory phases, as well as in the gland secretion during the secretory phase. In contrast, stromal cells were nearly unstained. CONCLUSION(S) IRF-1 was localized in the human endometrium, implying that this nuclear protein plays some role other than as a transcription factor.

A Novel Pharmacokinetic Method for Analysis of Placental Transfer of Latamoxef in Humans

SummaryA novel pharmacokinetic method was developed for analysing the behaviour of a drug in tissues. The absolute transfer ratio of a drug to a tissue was defined using the pharmacokinetic parameters obtained by this method. Composite data of latamoxef (moxalactam) concentration in maternal blood, umbilical cord blood and amniotic fluid following a 2g intravenous injection to pregnant women at delivery were analysed by this method to study the drug behaviour in pregnant women, fetuses and amniotic fluid.Latamoxef kinetics in pregnant women at full term were generally similar to that in previously reported healthy subjects. The concentration of latamoxef in umbilical cord blood peaked about 2 hours after dosing then decreased in parallel with the maternal blood concentration. The amniotic fluid concentration peaked about 7 hours after administration, then decreased slowly. The absolute transfer ratios to fetus and amniotic fluid were calculated to be about 2.5 and 0.37% respectively.

A questionnaire survey on the theory of postoperative infection prophylaxis in gynecology

A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among gynecologists in Japan in the period from April to July 2000. Fifty-six of the 83 gynecologists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., Escherichia coli and Bacteroides fragilis group. Use an AMP agent that archives a bactericidal concentrations in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. The newer agents should be considered as a therapeutics for postoperative infections. The therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for clean operations are cefazolin (CEZ), followed by cefotiam (CTM) and cefmetazole (CMZ). The most commonly used agent for clean-contaminated operations where low grade level of bacterial invasion expected is CTM, followed by CEZ and CMZ, where as operations where mild grade level of bacterial invasion expected is flomxef (FMOX), followed by CTM and other cephalosporins.

Uptake of estrone and estrone-3-sulfate by lung of macaca fuscata.

An equimolar mixture of 3H-E1-S2 and 14C-E1 was injected in one shot into the inferior vena cava near the heart of female Japanese monkey. Following the injection, blood was collected from the aortic arch at intervals of 15 s over a period of 10 min. The concentration of radioactivities in the whole blood and serum was measured. The metabolites were analyzed by DEAE-Sephadex A-25 column chromatography, enzyme hydrolysis, thin layerchromatography and paperchroma-tography. Both radioactivities of 3H-E1-S and 14-E1 rapidly decreased in the first 90-s serum sample. The 3H/14C ratio in the 0-15-s serum sample was 5 times higher than the initial ratio of injected compounds. The radioactivities in the serum gradually decreased after 90 s of injection. The 3H/14C ratio in the pulmonary tissue was very low after collecting the final blood sample. This result shows that the most of 3H-E1-S passed through the lung and the larger part of 14C-E1 remained in the lung following injection of these materials. So, it is probable that E1-S is in a form to be carried in the general circulation.