Biomedical subjects

Osamu Ishiko

Publications and source records attributed to Osamu Ishiko.

At least 19 recordsLinked to original sources

PubMed2006

Insulin-lowering agents inhibit synthesis of testosterone in ovaries of DHEA-induced PCOS rats.

BACKGROUND: Insulin-lowering agents are reported to be useful in treating polycystic ovary syndrome (PCOS) anovulation. It has been suggested that lower insulin levels secondarily affect ovarian tissue, although the direct mechanism of action has not yet been verified. Here we investigated if these agents directly affect the ovary. METHODS: Thirty female Wister rats were studied. Six control rats were injected subcutaneously with 0.2 ml sesame oil, while 24 rats used as PCOS models were injected subcutaneously with dehydroepiandrosterone (DHEA) and divided into four groups. Six rats were injected with only DHEA, while the remaining 18 rats received metformin, pioglitazone or troglitazone. The ovaries were immunohistochemically stained with anti- testosterone and anti-17beta-HSD antibodies, and then evaluated for morphological changes. RESULTS: In the DHEA administration group, the number of atretic follicles significantly increased compared to that of control rats. The insulin-lowering agents did not improve the multicystic appearance. Serum testosterone concentrations significantly increased with DHEA administration, but the increase was inhibited by oral administration of insulin-lowering agents. Testosterone deposits in ovarian tissue were also reduced by feeding rats insulin-lowering agents. CONCLUSION: Insulin-lowering agents affected ovarian tissue by inhibiting testosterone biosynthesis in vivo.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

Effects of different sampling points on evaluation of fetal descending aortic flow.

BACKGROUND: Widespread use of fetal aortic blood flow velocity measurements for assessment of fetal circulatory status has been precluded by difficulties in achieving an adequate Doppler insonation angle at particular sampling points. The goal of this study was to evaluate the differences in resistance index (RI) and systolic peak velocity (Vmax) of fetal aortic blood flow velocity waveforms throughout gestation among various Doppler sampling points. METHODS: A total of 551 normal women between 18-41 weeks of pregnancy participated in this study. Pulsed Doppler flow velocity waveforms were acquired from three different aortic sampling points (thoracic portion, beneath the diaphragm, and abdominal portion) of the fetal descending aorta. The Vmax and RI were calculated at the respective sampling points. RESULTS: The Vmax were significantly lower in abdominal portion than those in thoracic portion at every time point (from 69 +/- 11 cm/second in thoracic to 49 +/- 8 cm/second in abdominal portion at 18-19 gestational weeks, p<0.0001), and RI were also lower (from 0.84 +/- 0.05 in thoracic portion to 0.76 +/- 0.05 in abdominal portion at 18-19 gestational weeks, p<0.0001). Significant increase in the Vmax was seen until third trimester (from 58+/-10 cm/second at 18-19 gestational weeks to 113 +/- 13 cm/second at 38-39 gestational weeks beneath the diaphragm, p<0.0001), while the RI remained stable (0.79 +/- 0.04 at 18-19 gestational weeks; 0.80 +/- 0.05 at 38-39 gestational weeks beneath the diaphragm). CONCLUSIONS: In measuring the fetal circulatory status, these data demonstrate that the sampling point should be considered when evaluating the maximum systolic velocity and the resistance index of the fetal descending aorta.

Aorta, Thoracic↗

PubMed2005

Microwave power and duration without extrauterine thermal damage in microwave endomyometrial ablation at 2.45 GHz.

AIM: We investigated microwave power and duration of use, which does not affect extrauterine organs, in order to treat organic menorrhagia caused by myomas or adenomyosis. METHODS: Electric fields around a microwave applicator at a frequency of 2.45 GHz were calculated using the finite element method with commercially available software for analysis of electromagnetic fields. Transient temperature distributions around the applicator were obtained by numerically solving the bioheat transfer equation during microwave irradiation for 120 s in the human uterus and swine liver. We compared areas enclosed by the 60 degrees C isotherm obtained using numerical simulations and necrosis areas after microwave irradiation. Postoperative avascular areas in a Gd-enhanced MRI of a uterus enlarged by adenomyosis after clinical microwave endomyometrial ablation were compared with numerical simulations. RESULTS: There was good agreement between the calculated results and the experiments. At 40 W of output power for 50 s of duration and 64.5 W for 100 s, the depth of the necrotized uterine wall did not increase beyond 7 mm and 11 mm, respectively, either in the calculations or the experiments. Generally, the 50 degrees C isotherm was located approximately 2 mm external to the 60 degrees C isotherm in temperature distributions. The Gd-enhanced MRI after the operation depicted avascular areas, which agreed with the results of numerical simulations. CONCLUSIONS: The myometrial portion of a uterine wall > or = 13 mm throughout the uterus irradiated for < or = 64.5 W for 100 s is sufficient to avoid thermal damage of the extrauterine organs during microwave endomyometrial ablation.

Animals↗

PubMed2005

Microwave endometrial ablation for menorrhagia caused by large submucous myomas.

AIM: To examine the feasibility of microwave endometrial ablation (MEA), using a curved microwave applicator, in patients with menorrhagia caused by a submucous myoma greater than 3 cm in diameter, which is among the contraindications for conventional endometrial ablation. METHODS: Patients included were refractory to medication, more than 45 years of age, and due to undergo hysterectomy to treat menorrhagia as a result of submucous myomas, although they hoped to avoid hysterectomy. Three patients underwent MEA at 2.45 GHz using a curved microwave applicator and microwave tissue coagulator to treat menorrhagia. Patients 1, 2 and 3 had submucous myoma nodes 4.5, 5.0 and 13 cm in diameter respectively. The applicator was guided under transabdominal ultrasonography to microwave irradiation sites arranged to cover the entire uterine lining based on preoperative magnetic resonance images. MEA was performed under general anesthesia or spinal anesthesia. Microwaves were irradiated at 40 W for 50 s for single irradiation sites. RESULTS: Patient 1 became amenorrheic after the second MEA, which was performed 2 months after the first operation. Patients 2 and 3 became amenorrheic after the first MEA. Postoperative abdominal pain was controllable by a suppository of non-steroidal anti-inflammatory drugs. The patients were discharged the day after the operation. No remarkable complications were encountered during or after surgery. CONCLUSION: Microwave endometrial ablation improves menorrhagia caused by large submucous myomas when the microwave applicator reaches all parts of the uterine cavity.

Endometrial Neoplasms↗

PubMed2005

Expression of apoptosis-related proteins in advanced uterine cervical cancer after balloon-occluded arterial infusion chemotherapy as an indicator of the efficiency of this therapy.

We previously reported satisfactory therapeutic results of cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy (BOAI) as neoadjuvant chemotherapy, which enabled treatment by hysterectomy in patients with advanced cervical cancer. We also reported expression of apoptosis among these patients and determined that the bax gene is related to this apoptosis. In the present study, we investigated the relationship between the effectiveness of BOAI therapy and expression of apoptosis regulatory genes and proteins in these cases. The subjects were 27 women with advanced cervical cancer classified as FIGO (International Federation of Gynecology and Obstetrics) stage III or higher who were admitted to the Department of Gynecology, Osaka City University Medical School Hospital between 2000 and 2003. All patients were treated by BOAI, and expression of cancer cell apoptosis was examined by the TUNEL method, expression of bax, bcl-2 and bcl-xL proteins were examined by immunohistochemistry, and expression of bax, bcl-2 and bcl-xL mRNA was examined by quantitative RT-PCR before and 3 days after BOAI. The effectiveness of BOAI therapy was thus determined. The 20 patients in whom BOAI was effective showed significantly higher expression of the bax protein and gene after BOAI, and cancer cell apoptosis was accelerated. On the other hand, the 7 patients in whom BOAI was ineffective showed significantly higher expression of the bcl-xL protein and gene after BOAI. These results suggest that bax/bcl-xL expression can be used as an indicator of the effectiveness of BOAI therapy.

Adult↗

PubMed2005

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in uterine endometrial carcinoma and a correlation between expression of matrix metalloproteinase-7 and prognosis.

Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several human malignant tumors, in particular MMP-7, which is mainly produced by the cancer cell itself. We examined the expression of MMP-2, 7 and 9, and tissue inhibitors of metalloproteinase (TIMP)-1 and 2 in uterine endometrial carcinoma, and compared the expression with clinicopathological characteristics in uterine endometrial carcinoma (UEC). A group of 256 patients with UEC received surgery at the Osaka City University Medical School Hospital, and 196 tumor samples were immunohistochemically stained to examine the expression of MMP-2, 7 and 9, and TIMP-1 and 2. Additionally, the invasion ability of cell stain established from UEC was examined using an in vitro invasion assay. The expression of MMP-2, 7 and 9, and TIMP-1 and 2 was observed in the cytoplasm, and the expression of MMP-2 and 7, and TIMP-1 and 2 was observed in stromal cells around the tumor cells. The expression of MMP-7 was significantly stronger in higher-grade than lower-grade tumors (P<0.05). The invasion assay showed that the invasion of cells derived from UECs was significantly inhibited by TIMP-1 and 2. The disease-free interval was significantly shorter when MMP-7 expression was intense. This increased expression of MMP-7 in high grade UECs may be associated with tumor invasion and metastasis, and MMP-7 could serve as a prognostic maker in UEC.

Adult↗

PubMed2005

[A case of complex endometrial hyperplasia with atypia treated by microwave endometrial ablation].

Complex endometrial hyperplasia with atypia (CEHA) often precedes an endometrial carcinoma. A nulli-gradiva woman at high risk due to various complications underwent microwave endometrial ablation (MEA) at a frequency of 2.45 GHz for treatment of CEHA as an alternative to hysterectomy. The endometrium near the internal orifice was conserved to avoid hematometra. Endometrial biopsy specimen from the neighborhood of the internal orifice did not show any signs of endometrial hyperplasia postoperatively. Two years after the operation, endometrial biopsy revealed recurrence. The second MEA was performed. MRI one month after the second operation revealed that the uterine lining was completely replaced by avascular area without signs of regrowing endometrium or endocevix. Eighteen months have passed without recurrence.

Catheter Ablation↗

PubMed2004

Disease associations and altered immune function in CD45 138G variant carriers.

The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance.

Alternative Splicing↗

PubMed2004

The importance of studying pressure-flow for predicting postoperative voiding difficulties in women with stress urinary incontinence: a preliminary study that correlates low Pdet x Qave with postoperative residual urine.

We evaluated the parameters of preoperative pressure-flow for predicting the postoperative voiding difficulties in women with stress urinary incontinence. The preoperative urodynamic study records of 14 women treated using the tension-free vaginal tape (TVT) procedure were retrospectively analyzed. Of the patients treated with the TVT procedure, urinary retention occurred in one patient, and three had a residual urine volume of more than 30 ml. All patients became completely free of stress urinary incontinence postoperatively. The lowest Pdet max (5 cmH(2)O) in the preoperative pressure-flow study was found in a patient with a remarkable postoperative residual urine volume of more than 50 ml. The second lowest Pdet max value (8 cmH(2)O) was seen in a patient with postoperative urinary retention, whose residual urine volume, however, decreased to almost zero 1 year after the operation. The preoperative Pdet max x Qave values were remarkably low for these three patients, including the one with the lowest Pdet max, with a post-void residual urine volume of more than 30 ml. The plots of Pdet max x Qave versus the age of patients show that the Pdet max x Qave values tend to decrease with aging. The preoperative Pdet max x Qave value can be an important parameter for predicting increased residual urine after TVT sling surgery.

Aged↗

PubMed2004

Activity of synthetic enzymes of tetrahydrobiopterin in the human placenta.

Tetrahydrobiopterin (BH4) is an essential co-factor for nitric oxide (NO) synthase (NOS) and regulates the production of NO, or endothelium-derived relaxation factor. Although NOS is highly expressed in the placenta and NO plays a critical role in the regulation of feto-placental circulation, the mechanism maintaining the level of BH4 is not known. To investigate the de novo synthesis of BH4 in the human placenta, the activity of guanosine triphosphate cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and sepiapterin reductase (SR) in the chorionic tissue during the first, second and third trimester of pregnancy was analyzed. GTPCH activity was the lowest of the three enzymes and became negligible after the second trimester. There was no significant change in PTPS activity throughout pregnancy. Although SR activity decreased significantly after the second trimester, the levels remained abundant throughout pregnancy. These results showed that GTPCH is a rate-limiting enzyme and the total activity of the de novo synthesis of BH4 is negligible in the mature placenta after the second trimester when fetal growth is accelerated. The present study suggests that the level of BH4 in the placenta depends principally on the system other than de novo synthesis. The salvage pathway is considered the most potent system, which is formed by the transfer of the substrates from the fetus and their enzymatic conversion to BH4 in the placenta.

Alcohol Oxidoreductases↗

PubMed2004

VEGF mRNA in adipocytes increase with rebound weight-gain after diet-restriction.

The mechanism of rebound body weight-gain after a restricted-diet state is unclear. We investigated the expression of angiogenic factors in human adipocytes with a changing nutritional state in culture medium, and attempted to ascertain the mechanisms involved in rebound weight-gain. Adipocytes were divided into three groups; the first group (control group) was cultured in medium with 10% fetal calf serum (FCS), the second (DR3% group) was cultured in medium with 3% FCS, and the third (DR6% group) was cultured in medium with 6% FCS. After being cultured for 48 h, each was next cultured with 12% FCS for a further 48 h. When made to change from a low nutrition state to a higher one, adipocytes changed from hypotrophic to hypertrophic. Simultaneously, vascular endothelial growth factor (VEGF) in the culture medium increased significantly. When investigated immunohistochemically, the expression of VEGF was similarly shown in the cytoplasm of adipocytes. The same tendency with the same quantity of mRNA was shown by RT-PCR. These results show that VEGF produced and secreted from adipocytes increases, when the cultivation state of adipocytes is changed from a low nutritional state to a higher one. VEGF produced and secreted from adipocytes may be related to rebound weight-gain.

Adipocytes↗

PubMed2004

Association of HPV infection with prognosis after neoadjuvant chemotherapy in advanced uterine cervical cancer.

Whether the human papillomavirus (HPV) status of the tumor affects the sensitivity to neoadjuvant chemotherapy, and the prognosis in advanced uterine cervical cancer (FIGO stage III or higher) remains unknown. We examined the HPV status of 43 patients who had received CDDP therapy by balloon-occluded arterial infusion (BOAI), as neoadjuvant chemotherapy for advanced uterine cervical cancer (squamous cell carcinoma) stage III or higher. DNA was extracted from formalin-fixed, paraffin-embedded tumor samples obtained by punch biopsy before the neoadjuvant chemotherapy. The detection of HPV and its typing were analyzed by a polymerase chain reaction (PCR)-based assay using consensus primers for the L1 consensus regions. HPV DNA was detected in all 43 patients (100%): 29 cases with HPV 16 (67.4%), 5 cases with HPV 33 (11.6%), 4 cases with HPV 31 (9.3%), 3 cases with HPV 35 (7.0%), 1 case with HPV 18 (2.3%) and 1 case with HPV 58 (2.3%). The HPV types were divided into 3 groups, HPV 16, HPV 33 and other HPV types (HPV 18, 31, 35, 58), and comparisons and examinations were performed among the 3 groups. Although the rates of tumor reduction and operation accomplishment after 3 courses of BOAI showed no significant differences among the 3 groups, there were significant differences in the survival rates. The survival rate of advanced uterine cervical cancer patients with HPV 33 infection was the highest, followed by that of patients with HPV 16 infection. The survival rates of patients with the other types of HPV infection were the worst among the 3 groups and significantly lower than those of patients with HPV 16 or HPV 33 infection. The differences in the curative effect after BOAI may depend on the different characters of the HPV types.

Antineoplastic Agents↗

PubMed2004

Successful microwave endometrial ablation in a uterus enlarged by adenomyosis.

Adenomyosis can cause severe menorrhagia, which is a common indicator of the need for hysterectomy. None of the ablative techniques developed over the last two decades are of use in treating menorrhagia in a uterus enlarged by deep adenomyosis. Using a curved microwave applicator specifically developed for enlarged uterine cavities, microwave endometrial ablation at a frequency of 2.45 GHz was successfully applied in the treatment of menorrhagia in a patient with adenomyosis and an enlarged uterine cavity 12 cm in length. Two weeks after the operation, the patient experienced a menstrual period of ten days with no flooding. Menstrual duration gradually decreased to six days over the following six months. The quality of life score recovered to within the normal range six months after the operation. The post-operative sub-endometrial low signal intensity zone on the T2-weighted magnetic resonance images, which corresponds to the region of necrotic tissue, vanished 12 months after the operation. Although microwave endometrial ablation using the curved applicator could not treat bleeding from deep adenomyosis lesions, it improved menorrhagia in the uterus, which would conventionally require a hysterectomy.

Catheter Ablation↗

PubMed2003

A high-frequency polymorphism in exon 6 of the CD45 tyrosine phosphatase gene (PTPRC) resulting in altered isoform expression.

CD45 (leukocyte common) antigen is a hemopoietic cell-specific tyrosine phosphatase essential for antigen receptor-mediated signaling in lymphocytes. The molecule undergoes complex alternative splicing in the extracellular domain, and different patterns of CD45 splicing are associated with distinct functions. Lack of CD45 leads to severe combined immunodeficiency, and alterations of CD45 splicing, because of a polymorphism in exon 4, have been associated with altered immune function. Here we describe a polymorphism in exon 6 (A138G) of the gene encoding CD45 that interferes with alternative splicing. The polymorphism results in an amino acid substitution of Thr-47 to Ala in exon 6, a potential O- and N-linked glycosylation site. This exon 6 A138G variant is present at a frequency of 23.7% in the Japanese population but is absent in Caucasoids. Peripheral blood T cells from individuals carrying the A138G variant show a significant decrease in the proportion of cells expressing the A, B, and C CD45 isoforms and a high frequency of CD45R0+ cells. These phenotypic alterations in the A138G carriers may lead to changes in ligand binding, homodimerization of CD45, and altered immune responses, suggesting the involvement of natural selection in controlling the A138G carrier frequency.

Adult↗

PubMed2003

Microwave endometrial ablation for an enlarged uterus.

INTRODUCTION: An enlarged uterus of more than 12 cm in cavum length with a distorted cavity is a contra-indication for conventional ablative techniques. It is difficult to perform satisfactory endometrial ablation in a large uterus with submucosal myomas using straight instruments. A new curved microwave applicator 4 mm in diameter was developed for microwave endometrial ablation (MEA) for uteri with an enlarged distorted uterine cavity. METHOD: For three patients of menorrhagia due to submucosal myomas with cavum lengths 13 to 15 cm, MEA was performed using the curved applicator. RESULTS: Menorrhagia was improved in each case. No complications were encountered. CONCLUSION: A large number of hysterectomies could be avoided using the new curved microwave applicator.

Adult↗

PubMed2003

Granulated metrial gland cells in the murine uterus: localization, kinetics, and the functional role in angiogenesis during pregnancy.

Granulated metrial gland (GMG) cells are a major immune cell population in the murine pregnant uterus, and contribute to the maintenance of pregnancy by functioning as uterus-specific natural killer (NK) cells. In order to reveal their kinetics, activation, and functional roles in pregnancy, we conducted quantitative and immunohistochemical analyses in normal and immuno-modulator-treated mice. Under a light microscope, GMG cells were identified by red cytoplasmic granules in periodic-acid-Schiff (PAS)-stained sections. They progressively increased in number and size with the peak at day 12-14 of pregnancy in the decidua and metrial gland. New vessel formation was most prominent around day 8, and the total vascular area reached the peak at day 13. GMG cells were often located near the blood vessels, and expressed vascular endothelial growth factor (VEGF), suggesting their possible inducing role in angiogenesis during the development of decidua/metrial gland. While blood vessels in the non-pregnant uterus were negative for vascular cell adhesion molecule (VCAM)-1, those in the pregnant one were positive. Treatment with neutralizing antibody against VCAM-1, however, did not decrease the number of GMG cells. On the other hand, mitosis of GMG cells was frequently observed. These data suggest that the increment of GMG cells during pregnancy may largely result from local proliferation in the uterus rather than an increased influx of precursor cells. Although we attempted to induce in vivo activation of GMG cells by administration of interleukin-12 (IL-12) or alpha-galactosylceramide, a potent activator for natural killer-T (NK-T) cells, the number of GMG cells did not appreciably increase. The present study has demonstrated that GMG cells locally proliferate in the pregnant uterus, not being related to VCAM-1 expression by the uterine vasculature or systemic activation of NK cells and NK-T cells, and seem to be involved in angiogenesis in the pregnant uterus through VEGF production.

Animals↗

PubMed2003

Leukemia inhibitory factor regulates cell survival of normal human endometrial stromal cells.

Leukemia inhibitory factor (LIF) is produced locally in decidual tissues, but its direct effects on endometrial stromal cells have not been well characterized. In this study, we examined the direct effects of LIF on normal human endometrial stromal cells using an in vitro decidualization assay system with 8-Br-cAMP, a decidualization inducer. We found no effects of LIF on cell viability and prolactin secretion of unstimulated endometrial stromal cells. LIF dose-dependently enhanced cell viability, but not prolactin secretion of 8-Br-cAMP-stimulated cells. LIF dose-dependently enhanced the viability of stromal cells co-stimulated with 8-Br-cAMP and LIF without any significant effect on PRL secretion from the cells. Further, the extracellular matrix did not affect these stimulatory effects of LIF on cell viability of 8-Br-cAMP-stimulated endometrial stromal cells. These results indicate that LIF enhances the cell viability of PRL-non-secreting 8-Br-cAMP-stimulated stromal cells, and that the cell survival signals generated by LIF are independent of those generated by the extracellular matrix. LIF produced locally in decidual tissues may enhance cell viability in certain activated endometrial stromal cells in an autocrine or paracrine manner, and possibly protect against cell damage during embryo implantation and trophoblastic invasion.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2003

Using a vortex mixer for testicular sperm collection.

OBJECTIVE: To evaluate 2 methods of processing testicular tissue for the retrieval of viable sperm from men with nonobstructive azoospermia. STUDY DESIGN: Fresh testicular tissue was obtained from nonobstructive azoospermia patients using a biopsy needle. The specimens were divided into 2 fractions. All specimens were minced and immersed in human tubal fluid (HTF). The first fraction was filtered through a nylon filter and incubated for 3 hours. The supernatant was centrifuged, resuspended in HTF and analyzed. The second fraction was immediately vortexed for 5 minutes and filtered through a nylon filter. The supernatant was centrifuged, resuspended in HTF and analyzed. RESULTS: Spermatozoa were obtained in 13 of 24 cases (54.2%) using the vortex method and in 5 of 24 cases (20.8%) with the nylon filter method. CONCLUSION: The vortex mixing method may be a better option than the conventional method for processing testicular tissue for sperm collection.

Adult↗