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Biomedical subjects

N Terakawa

Publications and source records attributed to N Terakawa.

At least 19 recordsLinked to original sources

Platinum concentrations in uterus and serum after internal iliac arterial infusion of platinum compounds in rabbits.

OBJECTIVE: To compare three platinum compounds, and study the pharmacokinetics of these compounds after systemic and intra-arterial infusion. METHODS: Adult female rabbits received infusions of 1.7 mg/kg cisplatin, 10 mg/kg carboplatin, or 6 mg/kg cisdiammine(glycolato)platinum (254-S) via the internal iliac artery or jugular vein. The doses were equitoxic. Platinum tissue concentration in uterus and platinum serum levels were measured after internal iliac arterial or intravenous (i.v.) infusion with these platinum compounds. RESULTS: Platinum uterine concentration after intra-arterial infusion was significantly higher than that after i.v. infusion for each drug (P < .05). The ratios of platinum uterine concentration after intra-arterial infusion to those after i.v. infusion were 2.24 for cisplatin, 1.83 for carboplatin, and 1.67 for 254-S measured 20 minutes after drug administration. The area under the curve of filtrated platinum (micrograms/mL.hours) was significantly lower for cisplatin compared with carboplatin and 254-S in both infusion methods (1.5 for cisplatin, 32.1 for carboplatin, and 16.0 for 254-S after i.v. administration, and 0.8, 30.9, and 15.2 after intra-arterial administration, respectively). CONCLUSION: Cisplatin produced the highest ratio of uterine to serum concentration of platinum after intra-arterial infusion.

Animals

Reduced implantation rate associated with a subtle rise in serum progesterone concentration during the follicular phase of cycles stimulated with a combination of a gonadotrophin-releasing hormone agonist and gonadotrophin.

Our objective was to assess the effects of subtle increases in serum progesterone concentration (1.0-2.0 ng/ml) on the outcome of in-vitro fertilization (IVF), particularly on the quality of embryos, during the follicular phase of cycles stimulated with gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG). A total of 97 patients underwent 116 cycles of IVF and were stimulated with a combination of HMG and GnRHa. They were divided into two groups: those with a subtle progesterone rise and those with no progesterone rise. The two groups were compared with respect to serum oestradiol, progesterone, immunoreactive luteinizing hormone (I-LH), bioactive LH (B-LH), and results of IVF. The groups did not differ significantly in mean age or in total dose of HMG received. On the day that human chorionic gonadotrophin was administered, concentrations of oestradiol and progesterone were significantly higher in the subtle progesterone rise cycles than in the no progesterone rise cycles. In the no progesterone rise cycles, the percentages for embryos beyond the 4-cell stage, grade 1 embryos, and implantation rates were significantly higher than those in subtle progesterone rise cycles. The combination of GnRHa and HMG eliminated any significant rise in serum I-LH or B-LH concentration during the follicular phase, but did not suppress the subtle rise in progesterone. These results confirm our previous finding that a subtle progesterone rise adversely affects the outcome of IVF. It is also suggested that a reduction in embryo quality may influence the lower rate of implantation in subtle progesterone rise cycles.

Adult

Growth inhibition of uterine cervical cancer cells by a sequential administration of anticancer drugs and irradiation.

We investigated the growth-inhibitory effects of anticancer drugs and irradiation in relation to the cell cycle of cervical cancer. Irradiation 0 and 24 h after cisplatin administration significantly decreased cell growth. The number of cells in the G0G1 phase decreased 0-24 h and recovered 48 h after cisplatin or bleomycin administration. The present study suggests that irradiation for cervical cancer is preferable when the cancer cells accumulate during the proliferation phase after administration of cisplatin combined with bleomycin.

Adult

Quantitative analysis of endometrial stromal cells including behavioral changes related to the menstrual cycle in smear specimens.

We aimed to obtain quantitative data regarding certain characteristics of stromal cells in smear specimens of normal endometrium, including the cytological changes associated with progression through the menstrual cycle. Eleven histological and 25 cytological specimens of normal endometrium were examined immunochemically using monoclonal antibodies to vimentin and keratin by streptavidin-biotin method. As a result, we decided to use the antibody to vimentin for the differential staining of endometrial smears: cells showing positive staining to vimentin were considered stromal cells. The quantitative nuclear measurements in the smear specimens revealed that the nuclei of endometrial stromal cells were more elongated and had a more dispersed distribution than the glandular cells in the proliferative phase. Although a part of the nuclei of stromal cells became rounder in shape in the secretory phase, they were larger in size than those of glandular cells.

Adolescent

Lipoadenofibroma of the uterine corpus. Report of a new variant of adenofibroma (benign müllerian mixed tumor).

This report documents an uncommon case of uterine adenofibroma with a fatty component, for which the term lipoadenofibroma is proposed. Abdominal computed tomography and echography revealed a cystic submucosal lesion in the uterine corpus of a 67-year-old woman. Microscopically, the tumor was composed of benign epithelial cells of a proliferative-endometrial type and nonepithelial stromal cells. The latter mesenchymal elements contained scattered foci of mature adipose cells. The present case is considered to be a new variant of adenofibroma (benign müllerian mixed tumor) of the uterine corpus.

Adenofibroma

Murine fibroblast growth factor receptor 1 gene generates multiple messenger RNAs containing two open reading frames via alternative splicing.

The arrangement of exons and introns encoding 5'-side of murine fibroblast growth factor (FGF) receptor 1 (FGFR-1) gene was mapped. A large intron with a size of 14 kb was identified between exon 1 and exon 2. In addition, all FGFR-1 subtypes including a unique variant form with 12 amino acids insertion and two amino acids deletion were observed to be able to be generated through alternative splicing. Furthermore, complete sequencing of the 5'-region of FGFR-1 mRNA revealed that a relatively large open reading frame precedes the major open reading frame encoding FGFR-1. These results indicate that FGFR-1 mRNAs are uniquely translated from an internal translation start site.

3T3 Cells

The hypothalamic-pituitary-ovarian axis in patients with endometriosis is suppressed by leuprolide acetate but not by danazol.

OBJECTIVE: To investigate the effects of leuprolide acetate (LA), a GnRH agonist (GnRH-a), and of danazol on the hypothalamic-pituitary-ovarian axis in patients with endometriosis. DESIGN: Ten patients were divided into LA and danazol treatment groups. MEASURES: Serum levels of E2, immunoreactive and bioactive LH, pulsatility of LH, and gonadotropins release by GnRH. Changes in serum E2 levels by hMG administration during LA treatment. RESULTS: Serum E2 level decreased to near castrated levels during the LA treatment, while it remained unchanged during the danazol treatment. Leuprolide acetate administration resulted in a significant suppression of the serum level of bioactive LH, of the pulsatility of LH release, of the pituitary response to GnRH injection, and of the elevation in the serum E2 level by hMG administration, but danazol treatment did not show these suppressive effects. CONCLUSION: Our results suggest that the hormonal actions of LA and danazol on endometriosis are different from each other, especially in the suppression of serum E2 level.

Adult

Confocal scanning laser microscopy of morphometric human sperm parameters: correlation with acrosin profiles and fertilizing capacity.

OBJECTIVES: To develop quantitative criteria for assessing sperm morphology and to determine the correlation between the percentage of morphologically normal spermatozoa and the outcome of the sperm hypo-osmotic swelling test, sperm acrosin profile, and sperm capacity for fertilization. DESIGN: The maximal length and width of the sperm head, the length of the midpiece and principal piece of the sperm tail, and the ratio of the surface of the acrosomal region to the total surface of the head were determined in specimens obtained from a group of infertile men and a group of fertile men using a confocal scanning laser microscope. Group A consisted of 53 infertile men who were participating in an IVF program, and group B consisted of 98 fertile men. The mean +/- 2 SD of the morphometric parameters in group B was established as representing the lowest and highest normal values in both groups. A normal spermatozoon was defined as one with morphometric parameters within normal levels. The lowest percentage of morphologically normal spermatozoa, hypo-osmotic swelling test result, and acrosin activity in group B were also taken as the lowest normal values in group A. SETTING: In vitro fertilization program at the Tottori University School of Medicine, Yonago, Japan. MAIN OUTCOME MEASURES: Sperm morphometric parameters, percentage of morphologically normal spermatozoa, hypo-osmotic swelling test, and acrosin activity. RESULTS: The length of the midpiece, ratio (x 100) of the surface of the acrosomal region to the total surface of the sperm head, percentage of morphologically normal spermatozoa, outcome of hypo-osmotic swelling test, and acrosin activity were significantly higher in group B than in group A. The maximal width of the head was significantly lower in group B than in group A. Strongly positive correlations were observed between percentage of morphologically normal spermatozoa or length of midpiece and the proportion of fertilized oocytes in group A and between ratio (x 100) of the surface of the acrosomal region to the total surface of the head and acrosin activity in groups A and B. Sperm morphology showed high positive and negative predictive values for acrosin activity (normal/abnormal) and fertility potential (present/absent). CONCLUSIONS: Using quantitative strict criteria, we found that sperm morphology was an important predictor of sperm fertilizing capacity. The confocal scanning laser microscope provided useful information about the sperm cytoskeleton and its importance in fertilization.

Acrosin

Assessment of functional integrity of frozen-thawed mouse embryos by albumin and leucine uptake.

To assess the effects of freezing-thawing on metabolic functions of embryos prior to implantation, we measured the uptake of [125I]bovine serum albumin (BSA) and [3H]leucine in 2-cell mouse embryos, that were freshly collected (control), exposed to cryoprotectants (non-frozen), and frozen-thawed, and in morulae and blastocysts cultured from these 2-cell embryos. No significant difference in [125I]BSA uptake by 2-cell embryos was observed among the three groups. However, [125I]BSA uptake by blastocysts in the frozen-thawed group was significantly reduced compared with the control and non-frozen groups. [3H]leucine uptake by 2-cell embryos in the frozen-thawed and non-frozen groups was significantly less than in the control group. Fluorescein diacetate staining was performed in the control and frozen-thawed 2-cell embryos. The intensity of fluorescence after fluorescein diacetate exposure did not differ between the control and frozen-thawed embryos. The present study with mouse embryos suggests that freezing-thawing procedures impair the metabolic functions, in particular the membrane transport system, of embryos. Measurements of BSA and leucine uptake in embryos may be useful for evaluating the quality of frozen-thawed embryos.

Animals

Laparoscopic unwinding of adnexal torsion caused by ovarian hyperstimulation.

A case of laparoscopic unwinding of a twisted enlarged ovary and Fallopian tube caused by ovarian hyperstimulation is presented. The laparoscopic unwinding was simple and was carried out in a short time. The patient's post-operative course was uneventful. Complications such as thromboembolism were not observed and the post-operative ovarian function was well preserved after such procedures. Preservation of the ovary is highly important in young infertile women. Prompt diagnosis with an immediate unwinding of the twisted adnexa by a laparoscopic technique can produce a valuable outcome.

Adnexal Diseases

Retroperitoneal lymphadenectomy, including the para-aortic nodes in patients with stage III ovarian cancer.

The role of lymphadenectomy in patients with advanced ovarian cancer is controversial. To evaluate the effect of lymphadenectomy, we retrospectively assessed the outcome of 53 patients with stage III epithelial ovarian cancer who were divided into two groups, which were matched for age distribution and postoperative chemotherapy, but received different surgical procedures. A total of 29 patients (group A) underwent hysterectomy, bilateral salpingoophorectomy, omentectomy, and retroperitoneal lymphadenectomy, including resection of the para-aortic nodes. The remaining 24 patients (group B) received hysterectomy, bilateral salpingoophorectomy, and omentectomy without retroperitoneal lymphadenectomy. Postoperative chemotherapy consisted of a combination of cisplatin, Adriamycin, and cyclophosphamide in both groups. The 2-year survival rate for group A was significantly greater than that for group B, but there was no significant difference between the groups with regard to the estimated 5-year survival rate. The 2-year survival rate of patients with positive nodes who underwent lymphadenectomy was similar to that of patients with negative nodes. Multivariate analysis indicated that lymph node involvement did not relate to prognosis of the patients undergoing lymphadenectomy. While a defined randomized trial is required to reach substantive conclusion, it is suggested that lymphadenectomy may be useful for improvement of the prognosis of patients with advanced ovarian cancer.

Adult

Synergistic enhancement of cisplatin cytotoxicity by SN-38, an active metabolite of CPT-11, for cisplatin-resistant HeLa cells.

A cisplatin (cis-diamminedichloroplatinum(II); CDDP)-resistant HeLa cell line (HeLa/CDDP cells), which showed more than 8-fold resistance to CDDP compared to the parent cells, was newly established for this study. HeLa/CDDP cells accumulated 50% less platinum than the parent cells. There was no difference in intracellular glutathione (GSH) content between the parent and HeLa/CDDP cells. The dose modification factor by DL-buthionine-S,R-sulfoximine (BSO) pretreatment was similar in both cell lines. HeLa/CDDP cells had cross-resistance to diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA), (cis-diammine(glycolato)platinum (254-S), but not to (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) (DWA2114R), adriamycin, or VP-16. HeLa/CDDP cells showed a collateral sensitivity to 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11). Furthermore, isobologram analysis indicated synergistic interaction of CDDP and SN-38 only for HeLa/CDDP cells. The present study suggests that combination therapy with CDDP and CPT-11 may be potentially useful in the treatment of some patients with CDDP-resistant cancer.

Camptothecin

Differentiation between physiologic and pathologic sinusoidal FHR pattern by fetal actocardiogram.

Two cases of physiologic sinusoidal FHR pattern and one case of pathologic sinusoidal FHR pattern recorded on fetal actocardiograms are reported. The physiologic sinusoidal FHR patterns were recorded during periodic fetal respiratory movements and sucking movements. The physiologic sinusoidal FHR patterns were accompanied and synchronized with periodic fetal movement bursts. The pathologic sinusoidal FHR pattern observed in a case of severe fetal anemia due to massive fetal-to-maternal hemorrhage was not accompanied by any fetal movement bursts. It is suggested that with the use of fetal actocardiogram physiologic sinusoidal FHR pattern can be distinguished from pathologic sinusoidal FHR pattern.

Adult

Transvaginal ultrasonographic diagnosis of bladder-wall invasion in patients with cervical cancer.

OBJECTIVE: To evaluate the use of transvaginal ultrasonography for diagnosing invasion of the bladder by cervical cancer. METHODS: Twenty-one women with stages Ib-IIIb cervical cancer underwent radical hysterectomy or staging laparotomy. All had computed tomography (CT) scans and cystoscopic examinations, and five also underwent magnetic resonance imaging (MRI). During transvaginal ultrasonography, a transvaginal transducer was inserted into the anterior fornix of the vagina and the bladder wall was studied in the sagittal plane. The moveability of the bladder wall was assessed by the ability of the bladder to slide along the uterine cervix when the probe was pushed up against the bladder from the anterior fornix. Moveability was considered to indicate an intact bladder wall. RESULTS: The accuracy of transvaginal ultrasonography was superior to that of the other methods for detecting bladder-wall invasion by cervical cancer. The accuracy was 95% for transvaginal ultrasonography, 76% for CT, 86% for cystoscopy, and 80% for MRI. CONCLUSION: Transvaginal ultrasonographic examination is useful for detecting invasion of the bladder wall by cervical cancer.

Diagnostic Imaging

Tumor DNA ploidy and prognosis of patients with serous cystadenocarcinoma of the ovary.

BACKGROUND: Although it is important to determine any relationship between tumor DNA ploidy and its biologic behavior, the correlation between DNA ploidy and the prognosis of patients with ovarian cancer is not conclusive. Accordingly, the authors evaluated the clinical application of DNA ploidy in ovarian cancer. METHODS: Flow cytometric measurements were performed in 45 selected patients with well-differentiated serous cystadenocarcinoma of the ovary, Stages Ic-IV. All of them had the same surgical procedure, with retroperitoneal lymphadenectomy including paraaortic nodes, followed by the same postoperative chemotherapeutic regimen. RESULTS: Of the 45 ovarian cancers, 28 were diploid and 17 were aneuploid. The 2-year survival rate and the estimated 5-year survival rate for patients with diploid tumors were significantly greater than those for patients with aneuploid tumors (73.2% versus 46.7% and 29.1% versus 22.4%, respectively). The 2-year survival rate in patients with advanced disease (Stage III or IV) was also significantly higher for those with diploid tumors (53.3% versus 37.4%, respectively), but the estimated 5-year survival rate was similar in both groups (8.9% versus 9.1%, respectively). Patients with advanced disease had aneuploid tumors more frequently than those with early-stage disease. A significantly higher incidence of retroperitoneal lymph node metastasis was observed in aneuploid tumors than in diploid tumors (43.8% in diploid tumors versus 86.7% in aneuploid tumors). The authors found no difference in the response to chemotherapy between diploid and aneuploid tumors. CONCLUSIONS: Although tumor DNA ploidy was not as reliable as conventional parameters such as surgical stage in establishing prognosis, it may provide an indicator of lymph node involvement.

Adult

Involvement of the local immune response in a case of advanced cervical cancer in a patient with systemic lupus erythematosus.

Although patients with systemic lupus erythematosus (SLE) have frequently accompanying malignancies, there are few documented cases in the literature of advanced cervical cancer patients with SLE. This report describes a case of advanced cervical cancer in a 39-year-old patient with a 20-year history of SLE (FIGO stage IIIb) and evaluates the immunological response of the tumor. The clinical course of this patient with SLE, with rapid growth of cervical cancer and a poor prognosis, may suggest that T cells play a key role in the growth of cancer.

Adult

Tumor cell kinetics in elderly patients with cervical cancer.

OBJECTIVE: To determine whether cell kinetics in cervical cancer differ by patient age. METHODS: We analyzed specimens from 118 women who had been treated for cervical squamous cell carcinoma. In a preliminary study, labeling indices were determined in 16 patients using bromodeoxyuridine in vitro. Adjacent portions of the same specimens were analyzed by flow cytometry. Proliferation indices were calculated and compared with labeling indices for 12 diploid tumors. For the remaining 102 tumors, paraffin-embedded specimens were analyzed by flow cytometry to determine DNA ploidy and proliferation index. Using these findings, we examined the relationship between tumor cell kinetics and age. RESULTS: There was a significant correlation between the labeling index and age (r = 0.86, P < .001) and a weak but statistically significant correlation between the proliferation index and the labeling index (r = 0.58, P < .05). The proportion of aneuploid tumors increased with age. The cutoff point of highest statistical significance was 65 years (P = .025). The proliferation index showed an age-dependent shift, and the cutoff point of highest statistical significance was also 65 years. Aneuploid tumors were more common in elderly patients aged 65 or more years. Proliferation indices were also significantly larger in the elderly patients (P < .005). Although stage III tumors were more common in the elderly, stage was not related to ploidy pattern or to proliferation index. CONCLUSION: Tumor cell kinetics of cervical squamous cell carcinomas differ between elderly and younger women.

Adult