Yoshiyuki Kinoshita

Expression of sex steroid hormone receptors in human cornea

Purpose. Previously we reported the occurrence of estrogen receptor a (ERa), estrogen receptor ß (ERß) and androgen receptor (AR) in mouse corneas. The present study was designed to investigate the occurrence of various sex steroid hormone receptors, including ERa, progesterone receptor (PR) and AR, in human corneas. Methods. We used reverse transcription-polymerase chain reaction (RT-PCR) to look for sex hormone receptor mRNAs (ERa, PR and AR) in human corneal epithelial cells obtained at autopsy. Next, using an immunocytochemical technique, we localized these receptors in donor human corneas. Results. mRNAs encoding all receptors tested for were found in corneal epithelial cells obtained from male and female donor eyes. Immunocytochemical examination revealed that the receptors were located in the nuclei of corneal epithelial, stromal, and endothelial cells. Conclusions. Since receptors for both male and female sex hormones are present in human corneas of both genders, we postulate that the receptors may influence the biological functions of corneal cells through direct interaction with specific hormones.

Alzheimer's disease and estrogen

The preventive effect of estrogen on Alzheimers disease (AD) has become clear with epidemiological data. Therapeutic effects of estrogen have not yet been established. In this presentation, we report our new basic and clinical data. The estrogen receptor, (ER)alpha, and ERbeta mRNA were investigated in rat brain. Estradiol-17beta (E(2)) treatment following OVX reduced the levels of ERalpha mRNA in the hypothalamus. In the substantia innominata (SI), the number of choline acetyltransferase immunoreacive cells increased significantly in the estrogen treatment rat. The neurons in SI projecting to the forebrain cortex contained ERalpha. Increasing amounts of intracellular calcium, peroxidation, and apoptosis with amyloid beta were suppressed in neuronal cells from rat pheochromocytoma (PC12) cells with E(2). ERalpha cDNA transfected PC 12 cells elaborated more neurite-like processes with E(2). In clinics, we are currently preparing vaginal progesterone tablets, which essentially may concentrate in the endometrium to prevent endometrial cancer, with few general circulation of progesterone inviting less depression. The therapeutic effects of cyclic estrogen, such as its preventive effect, are suggested in these studies, at least on mild AD.

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.

Expression of Nuclear Factor of Activated T Cells mRNA in Maternal Peripheral Blood Cells

PROBLEM:  In T lymphocytes, nuclear factor of activated T cells (NF‐AT) regulates the induction of cytokine genes upon antigenic stimulation. This study was designed to analyse the relationship between NF‐AT and pregnancy.

Expression of IL-4, IL-8 and IL-18 Messenger RNAs in Maternal Peripheral Blood and Relationships with the HbF-γ chain mRNA in it

Problem:  This study was designed to examine immunological changes in maternal peripheral blood and the relationship of these changes with the amount of fetal cells in the blood.