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Kunihiro Okamura

Publications and source records attributed to Kunihiro Okamura.

At least 73 records · Page 4Linked to original sources
PubMed2003

Increased production of tumor necrosis factor-alpha by peritoneal fluid mononuclear cells induced by 60-kDa heat shock protein in women with minimal to mild endometriosis.

PROBLEM: We sought to examine the role of Hsp60, a 60-kDa stress-responsive protein (hsp60) with potent immunostimulatory properties, in the pathophysiology of endometriosis. We investigated the response of peritoneal fluid mononuclear cells (PFMCs) to hsp60 to identify differences in PFMCs between women with and without endometriosis. METHOD OF STUDY: PFMCs from women with or without endometriosis were incubated with hsp60 in vitro. The release of tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The rapid secretion of TNF-alpha was observed following the exposure of PFMCs to hsp60. PFMCs from women with minimal to mild endometriosis produced greater amounts of TNF-alpha in response to hsp60 stimulation than levels seen in cells from women without endometriosis. CONCLUSION: Hsp60 may play a role in the activation of peritoneal immunity in patients with minimal to mild endometriosis.

Adult↗
PubMed2003

The correlation between the response to progestogen treatment and the expression of progesterone receptor B and 17beta-hydroxysteroid dehydrogenase type 2 in human endometrial carcinoma.

OBJECTIVE: In situ metabolism and synthesis of oestrogens are considered to play important roles in the pathogenesis and development of human endometrial endometrioid adenocarcinoma. Approximately 3-5% of patients with these neoplasms are under age 40, some of whom have been treated with progestogen alone as a primary therapy for both atypical endometrial hyperplasia and adenocarcinoma in order to preserve their fertility. Medroxyprogesterone acetate (MPA) has been used extensively in the treatment of both breast and endometrial disorders as an endocrine therapy. However, details of the alterations of in situ oestrogen metabolism following progestogen treatment have yet to be fully elucidated. DESIGN, PATIENTS AND MEASUREMENTS: In this study we examined the immunolocalization of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) types 1 and 2, oestrogen receptor (ER), progesterone receptor (PR)A + PRB, PRB, and Ki67 in progestogen-treated endometrial endometrioid adenocarcinoma (16 cases). We compared our findings both prior to and following treatment. These findings were then correlated with the treatment outcome of individual patients in order to elucidate factors associated with the response to treatment. RESULTS: 17beta-HSD type 2 immunoreactivity was detected in 8/16 cases examined, whereas 17beta-HSD type 1 immunoreactivity was undetected in all cases examined. 17beta-HSD type 2 positive immunostaining, PRA + PRB labelling index (LI), and PRB/PRA + PRB ratio were all significantly higher in cases responding to the treatment than in those not responding. There were no significant correlations between responsive and nonresponsive cases for positive 17beta-HSD type 1 immunostaining, Ki67 LI, ER LI and age. There were no significant differences in the positive immunostaining for 17beta-HSD types 1 and 2, Ki67 LI, ER LI, PRA + PRB LI, age and PRB/PRA + PRB ratio between specimens taken prior to and following progestogen treatment. CONCLUSION: These results suggest that in situ abundance of 17beta-HSD type 2 and PR, especially PRB, can predict the possible response of patients with endometrial carcinoma to progestogen treatment.

17-Hydroxysteroid Dehydrogenases↗
PubMed2003

A simple controlled-rate freezing method without a rate-controlled programmed freezer provides optimal conditions for both large-scale and small-scale cryopreservation of umbilical cord blood cells.

BACKGROUND: Umbilical cord blood (CB) is being used as a source of alternative HPCs for transplantation with increasing frequency. The goal of CB banks for unrelated transplantation is to provide good quality-controlled CB units that can be transplanted for HPCs into the largest possible number of patients. STUDY DESIGN AND METHODS: Large CB samples in freezing bags wrapped with insulators and small samples in cryotubes placed into double styrene-foam boxes were cryopreserved at -85 degrees C without a rate-controlled freezing machine, followed by storage in the liquid phase of nitrogen. After thawing these cells, the viability and recovery of cells, as well as the recovery rate of HPCs such as CD34+ cells, CFU-GM, and total CFU were evaluated. RESULTS: Measurement of the freezing rate in CB bags and cryotubes demonstrated that this simple method for cryopreservation of CB cells provided optimal conditions for both large-scale and small-scale cryopreservation. Recovery of CB progenitor cells after cryopreservation was also shown to be potentially acceptable when evaluated with CD34+ cells, CFU-GM, and total CFU. These results were comparable to the method using a rate-controlled programmed freezer. CONCLUSIONS: A simple method for cryopreservation of CB cells without a rate-controlled programmed freezer could provide a sufficient-enough potential for the transplantability of HPCs after thawing.

Blood Banks↗
PubMed2003

Expression of erythropoietin and erythropoietin receptor in peritoneal endometriosis.

BACKGROUND: Recent studies have indicated new physiological roles for erythropoietin (Epo) unrelated to erythropoiesis. We previously demonstrated that the Epo concentrations in peritoneal fluid from patients with stage I endometriosis were significantly higher than those with stages II, III and IV of the disease. Therefore, we hypothesized that Epo may play a role in the pathogenesis of endometriosis, particularly during the early stages of the disease. METHOD: We investigated the localization of Epo and the Epo receptor (Epo-R) in peritoneal endometriosis and eutopic endometrium, using immunohistochemistry. RESULTS: We detected Epo and Epo-R localized within glandular epithelial cells in both peritoneal endometriosis and eutopic endometrium. There was no significant difference in Epo expression between red and black peritoneal lesions, whereas Epo-R expression was significantly lower in black peritoneal lesions when compared to red lesions. Epo and Epo-R expression levels within red peritoneal lesions were comparable to those of eutopic endometrium from patients with endometriosis. CONCLUSION: The present findings suggest that Epo may play a role in the pathophysiology of endometriosis.

Adult↗
PubMed2003

Carboplatin-based chemotherapy in patients with gynecological malignancies on long-term hemodialysis.

We report on three cases of long-term dialysis patients with gynecological malignancies who were successfully treated with chemotherapy. Two epithelial ovarian carcinoma patients were treated with a single agent, carboplatin (100-200 mg/m2). One recurrent endometrial carcinoma patient was treated with carboplatin (200 mg/m2) and paclitaxel (135 mg/m2). Hemodialysis was started 2 h after the carboplatin infusion and lasted 4 h in all three cases. All patients tolerated these therapies without significant myelosuppression or severe side-effects. Our findings suggest these regimens are feasible, and the combination of paclitaxel and carboplatin is effective chemotherapy when administered to long-term hemodialysis patients with recurrent endometrial carcinoma.

Adult↗
PubMed2003

Mirimostim (macrophage colony-stimulating factor; M-CSF) improves chemotherapy-induced impaired natural killer cell activity, Th1/Th2 balance, and granulocyte function.

The purpose of this study was to clarify the effects of mirimostim (macrophage colony-stimulating factor; M-CSF) on immunological functions after chemotherapy. The percentage of natural killer (NK) cells in peripheral blood mononuclear cells (PBMCs), NK cell activity, T-helper cell 1/T-helper cell 2 (Th1/Th2) ratio, and superoxide anion production by granulocytes (granulocyte function) were measured as immunological parameters before and after chemotherapy in 44 patients with primary ovarian cancer who received at least three consecutive courses of postoperative chemotherapy. Patients were observed during the first course of chemotherapy, and 39 patients who presented grade III or IV neutropenia were entered into this study and randomly allocated to an M-CSF-administered group (group 1; 19 patients) and a non-M-CSF-administered group (group 2; 20 patients) for the second course. For the third course, a crossover trial was conducted. In the observation period, chemotherapy significantly impaired the immunological parameters. In particular, those parameters were significantly decreased at day 14 compared to the level before chemotherapy. The values of the parameters of group 1 were significantly higher than those of group 2. In the course of chemotherapy during which M-CSF was administered, 19 of the 39 patients presented grade IV neutropenia, and received granulocyte colony-stimulating factor (G-CSF) between days 7 and 14. We compared the changes of those immunological parameters in the M-CSF alone group and the M-CSF + G-CSF group, and found that the concomitant use of G-CSF did not further improve the parameters. These results indicate that chemotherapy markedly impaired the immunological functions, and that the administration of M-CSF significantly improved the impaired immunological functions.

Adolescent↗
PubMed2003

Contribution of the fetal baroreceptor reflex to the low frequency component of fetal heart rate fluctuations.

OBJECTIVE: The objective of this study was to examine whether the fetal baroreceptor reflex contributed to the low frequency component (LF: 0.025-0.125 cycles/beat) of fetal heart rate fluctuations. METHODS: Sheep fetuses in late gestation with normoxemia were used. The baroreceptor function was expressed as the baroreceptor reflex sensitivity (BRS) based on the change of the R-R interval in response to the elevation of blood pressure by noradrenaline (Nor-Ad). A frequency analysis was conducted by the autoregression method on heart rate fluctuations and blood pressure fluctuations in 300 stable heart beats immediately before the Nor-Ad test. The gain and the coherence from blood pressure LF to heart rate LF were calculated. The correlations between the BRS and the power values of heart rate LF, blood pressure LF, and the gain or the coherence were examined. RESULTS: The BRS and the gain showed a positive correlation (p < 0.01). There was a negative correlation between the heart rate LF and the BRS, and between the blood pressure LF and the BRS (p < 0.01, p < 0.005). CONCLUSIONS: This study showed that fetal BRS was involved in the change of LF in fetal heart rate fluctuation. Baroreceptor function should be considered when examining the change of LF domain in fetal heart beat fluctuation.

Animals↗
PubMed2003

Successful pregnancy after myomectomy using preoperative adjuvant uterine artery embolization.

A 30-year-old-woman presented with uterine leiomyoma and primary sterility. Abdominal myomectomy was performed; however, one cervical leiomyoma was not resected because of a risk of excessive blood loss. Two years after the procedure, a secondary myomectomy using preoperative adjuvant uterine artery embolization (UAE) was performed because of pronounced menorrhagia and her hope for bearing children. The patient's dysmenorrhea disappeared postoperatively and she conceived spontaneously 3 years after the secondary myomectomy. This case suggests that myomectomy using preadjuvant UAE may be an another approach for the treatment of leiomyoma in patients who wish bear children in the future.

Adult↗
PubMed2002

Expression of androgen receptor and 5alpha-reductases in the human normal endometrium and its disorders.

Androgen metabolism and actions are considered to play a very important role in the development and progression of the normal human endometrium and its disorders. Details regarding androgen actions in these tissues, however, have not been well studied. We first immunolocalized the androgen receptor (AR) and 5alpha-reductases, which catalyze the conversion of testosterone to the bioactive and potent androgen, 5alpha-dihydrotestesterone (DHT), in 18 normal cycling human endometria, 27 endometrial hyperplasia and 46 endometrioid endometrial adenocarcinomas. We also examined the mRNA expression of AR and 5alpha-reductases in 7 cases of endometrioid endometrial adenocarcinomas using reverse transcription polymerase chain reaction (RT-PCR). In the normal human endometrium, AR was immunolocalized predominantly in stromal cells of the proliferative phase of the menstrual cycle and in epithelial cells of the secretory phase, whereas 5alpha-reductase types 1 and 2 immunoreactivities were detected in the cytoplasm of epithelial cells but not in stromal cells throughout all phases of the menstrual cycle. In endometrial hyperplasia, the median labeling index (LI) for AR was 48.1%, whereas positive immunostaining for 5alpha-reductase Type 1 and Type 2 was detected in only 1 case. In endometrial carcinoma, AR immunoreactivity was detected in the nuclei of carcinoma cells and the number of positive cases was 39/44 (88.6%). Median LI for AR was 36.1%. Immunoreactivity for 5alpha-reductase Type 1 and Type 2 was detected in the cytoplasm of carcinoma cells and the number of positive cases was 37/44 cases (84.1%) and 34/44 (77.3%) for 5alpha-reductase Types 1 and 2, respectively. A significant positive correlation was detected between 5alpha-reductase Type 1 and Type 2 immunoreactivity (p < 0.001). AR LI was not correlated with the presence or absence of Type 1 and Type 2 5alpha-reductases. Results from our RT-PCR studies were consistent with those of immunohistochemistry. These results suggest that DHT may play more important roles than testosterone in the regulation of androgen action in endometrial cancer and normal human endometrium, especially in the secretory phase, in which both AR and 5alpha-reductase are increased. Androgenic actions may be also regulated predominantly by serum testosterone and not by DHT in endometrial hyperplasia because of the absence of 5alpha-reductases in the site of its actions.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

Up-regulation of cyclooxygenase-2 expression and prostaglandin synthesis in endometrial stromal cells by malignant endometrial epithelial cells. A paracrine effect mediated by prostaglandin E2 and nuclear factor-kappa B.

We investigated the regulation of prostaglandin production in normal endometrial stromal cells (ESC) by malignant endometrial epithelial cells. We found that cyclooxygenase (COX)-2 mRNA and protein levels and prostaglandin (PG)E(2) production in ESC were significantly increased by Ishikawa malignant endometrial epithelial cell conditioned medium (MECM). By using transient transfection assays, we found that the -360/-218-bp region of the COX-2 promoter gene was critical for MECM induction of promoter activity. This MECM-responsive region contained a variant nuclear factor (NF)-kappa B site at -222 to -213 that, when mutated, completely abolished COX-2 promoter activation by MECM. Employing electrophoretic mobility shift assays, we further demonstrated that binding of NF-kappa B p65 to this NF-kappa B-binding site is, in part, responsible for the COX-2 promoter activation by MECM. To investigate further the potential effects of MECM on COX-2 mRNA stability, ESC were treated with MECM in the absence or presence of actinomycin D, a general transcription inhibitor. We found that MECM significantly increased COX-2 mRNA stability. Intriguingly, we found that PGE(2) was one of the major factors in MECM, which was responsible for up-regulating COX-2 expression in ESC. ECC-1 and HEC-1A malignant endometrial epithelial cell lines also produced significantly increased quantities of PGE(2). In conclusion, malignant endometrial epithelial cells secrete PGE(2) that induces COX-2 expression in normal endometrial stromal cells in a paracrine fashion through activation of transcription and stabilization of COX-2 mRNA.

Cyclooxygenase 2↗
PubMed2002

Erythropoietin and erythropoietin receptor expression in human endometrium throughout the menstrual cycle.

Erythropoietin (Epo) is an important regulator of erythropoiesis. Recent studies have demonstrated non-classical sites of Epo and Epo-receptor (Epo-R) expression, suggesting new physiological roles unrelated to erythropoiesis. Other studies have shown that the mouse uterus expresses Epo and its receptor, and produces Epo protein in an estrogen-dependent manner. We therefore hypothesized that Epo is one of the growth factors involved in cyclic endometrial changes. We determined Epo and Epo-R mRNA expression in isolated endometrial epithelial and stromal cells using RT-PCR. While both Epo and Epo-R were detected in all samples of isolated epithelial cells analysed throughout the menstrual cycle, neither one was detected in isolated stromal cells. In addition, using quantitative real-time RT-PCR with the TaqMan detection system, we showed that isolated epithelial cells had higher Epo mRNA levels in the secretory phase than in the proliferative phase. Immunohistochemical analyses revealed that Epo and Epo-R protein expression in glandular epithelial cells was increased during the mid-proliferative phase and was maintained during the late proliferative and the early, mid- and late secretory phases. These findings suggest that Epo may be involved in cyclic proliferation and differentiation of endometrial glandular epithelial cells, acting in an autocrine manner. In addition, we also hypothesize that ovarian steroids may stimulate Epo production in human endometrial glandular epithelial cells.

Adult↗
PubMed2002

A transgenic mouse model for non-immune hydrops fetalis induced by the NS1 gene of human parvovirus B19.

Human parvovirus B19 (B19) infection during pregnancy is associated with the adverse foetal outcome known as non-immune hydrops fetalis (NIHF). Although B19 is known to infect erythroid-lineage cells in vivo as well as in vitro, the mechanism leading to the occurrence of NIHF is not clear. To investigate the possible involvement of the B19 non-structural protein NS1 in NIHF, three independent lines of transgenic mice were generated that expressed NS1 under the control of the Cre-loxP system and the GATA1 promoter. Two of the three lines expressed NS1 in erythroid-lineage cells. Most of the transgenic mice died at the embryonic stage, some of which developed hydropic changes caused by severe anaemia at embryonic day 15.5 (E15.5). Histological examination of embryos at E15.5 showed significantly fewer erythropoietic islands in the liver parenchyma, whereas their hearts showed no abnormal signs, such as cardiomegaly and apoptotic cells. The NS1-transgenic mouse lines established here provide an animal model for human NIHF and suggest that NS1 plays a crucial role in the adverse outcome associated with intrauterine B19 infection in humans.

Animals↗
PubMed2002

Differential expression of progesterone receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors.

Human epithelial ovarian neoplasm is well-known to be sex steroid-related, but the possible biological significance of progesterone actions in these tumors remains controversial. In this study, we examined the differential expression patterns of the two progesterone receptor (PR) isoforms, PRA and PRB, using immunohistochemistry and real-time quantitative RT-PCR in normal and neoplastic ovarian tissues, and in cell lines derived from a normal ovarian surface epithelium and an ovarian epithelial carcinoma in order to further elucidate the possible involvement of progesterone in the development of ovarian neoplasms. The median H scores for PR isoforms in normal (n = 8), benign (n = 10), borderline (n = 8) and malignant (n = 24) ovarian tissues were as follows; PRA: 194.0, 171.0, 49.5, 0 (P < 0.05), and PRB: 175.0, 180.5, 251.5, 168.5, respectively. In ovarian cancer cell lines (OVCAR-3 and Caov-3), the PRB / PRAB mRNA ratio was increased by 17beta-estradiol, both time- and dose-dependently. However, this ratio was unaltered following the addition of 17beta-estradiol in a normal ovarian epithelial cell line (NOV-31). Immunoblotting analysis demonstrated that PRB protein expression was markedly up-regulated in OVCAR-3, whereas the PRA and PRB isoforms both appeared to be increased in NOV-31. These results suggest that down-regulation of PRA is associated with the development of ovarian epithelial carcinoma.

Dose-Response Relationship, Drug↗
PubMed2002

Prediction of pregnancy in infertile women with endometriosis.

To estimate the probability of pregnancy in infertile women with endometriosis, two series of multivariate analyses were performed in Tohoku University Hospital. In the first series, from 1993 to 1997, 103 patients participated. The Cox proportional hazard regression model revealed a hazard ratio of 2.43 in patients with high ovarian adhesion scores. Bilateral ovarian adhesion was an important variable in anatomical factors, probably second only to bilateral tubal adhesion. In the next series, from 1998 to 1999, 23 patients were included, and the preoperative serum concentrations of cytokines, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha were analyzed. Only TNF-alpha was selected with a forward stepwise analysis after forcing age and infertile duration. In the logistic regression model, the serum TNF-alpha level had a significant and negative impact on the likelihood of pregnancy.

Adult↗
PubMed2002

V-shaped deceleration differs in the pattern of carotid blood flow from variable deceleration provoked by cord compression.

OBJECTIVE: To investigate whether V-shaped decelerations in fetal heart rate tracing are a physiologic response to fetal movements or secondary to cord compression. STUDY DESIGN: Six pregnant sheep and their fetuses (115-125 days of gestation) were surgically instrumented and studied. Fetal electrocardiogram, carotid blood flow, arterial blood pressure and fetal movement were continuously monitored for 24 hours. Following the undisturbed 24 hour recording, these parameters were monitored during umbilical cord compression (n = 6). Differences in these parameters between V-shaped decelerations and decelerations provoked by cord compressions were examined. RESULTS: Elevation of blood pressure and decreased carotid blood flow were observed coincidentally with the initiation of V-shaped decelerations. In cord compression, elevation of both blood pressure and carotid blood flow were followed by a decreased heart rate. V-shaped decelerations exhibited a different alteration of carotid blood flow compared to decelerations caused by umbilical cord compression. CONCLUSION: V-shaped deceleration is a physiologic response secondary mainly to fetal movements and is not caused by cord compression.

Animals↗
PubMed2002

The cul-de-sac packing method with a metreurynter in gynecologic gasless laparoscopy.

Laparoscopic surgery has inherent restrictions with respect to the operative field of view and the range of surgical manipulation. Of the two procedures which secure sufficient operative space, the operative view of the gasless method is inferior to that of a pneumoperitoneum. In order to gain greater surgical visualization in gynecological gasless laparoscopy, the authors devised the cul-de-sac packing method employing a metreurynter, an instrument familiar to obstetricians in Japan. A metreurynter was lead into the cul-de-sac, and was inflated with saline, which resulted in the adnexae being raised up. This method was performed in three patients whose preoperative diagnoses were unknown infertility, ovarian cyst, and ectopic pregnancy, respectively. In all cases this method was able to keep the bowels out of the cul-de-sac space. In the first case, we were able to perform a tubal patency test under tension-free conditions, while at the same time bilateral tubal information could be obtained in a single view. In the latter two cases the adnexal lesions were maintained at an inspectional position throughout the operation without the necessity of being held by forceps to prevent them from falling down into the cul-de-sac space. No complications occurred in our three cases. This method will not be useful for patients whose cul-de-sac space is closed due to adhesions. However, except in such cases, this technique supplies a good operative view while being simple, safe, and inexpensive. Furthermore, this method supports gentler and less traumatic manipulation throughout the operation.

Adult↗