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Biomedical subjects

N Suganuma

Publications and source records attributed to N Suganuma.

107 records · Page 6Linked to original sources

Conservative surgery of infertile patients with pelvic endometriosis--factors affecting the pregnancy rate and expectancy.

Conservative surgery was used in the treatment of 95 infertile patients with endometriosis who desired to have a child; of these 95 patients, 44 (46.3%) became pregnant after treatment. We studied the postoperative pregnancy rate and the expectancy value for pregnancy and the factors affecting them. The postoperative pregnancy rate was significantly lower in the patients with an infertility period of more than 5 years. As the age of the patients at the time of operation increased, the pregnancy rate decreased; the expectancy value was also significantly lower in patients over 30 years of age. Endometriotic lesions were, in the ovary (77.9%), in the peritoneum (42.1%), and in the uterosacral ligament (42.1%). The rates of pregnancy in patients in Beecham's stages II (43.2%) and III (53.3%) were not statistically significant. The rate was significantly lower in stage IV. Intrapelvic complications were usually myoma of the uterus and cystoma of the ovary. Both pregnancy rate and expectancy value were significantly lower in the patients with pelvic complications. Hormonal therapy combined with conservative surgery gave a higher rate of pregnancy and expectancy value than surgery alone. Thus, the duration of infertility, the age of the patient at the time of operation, intrapelvic complications, and the mode of treatment were key factors affecting the postoperative rate of pregnancy and expectancy.

Adult↗

Plastic unification of a double uterus and the outcome of pregnancy.

Habitual abortion and premature delivery are occasionally associated with a bicornuate or septate type of uterus when the abnormality is severe. A considerable improvement of reproductive performance was seen in patients who underwent plastic operation of the uterus. The procedures introduced by Strassman, Jones and Tompkins were used. Although it is still difficult to compare the postoperative reproductive history of these three surgical procedures, the procedure used by Tompkins may be technically more simple and provides for an easier entrance into the endometrial cavities in order to incise the common lower uterine segment. Primary sterility still remains a controversial indication for metroplasty and the postoperative reproductive history for this is poor.

Abortion, Habitual↗

Relationship between maternal prolactin levels during pregnancy and lactation in women with pituitary adenoma.

To evaluate the relationship between maternal prolactin (PRL) levels and post puerperal lactation, serum PRL levels in patients with pituitary adenoma were serially measured throughout pregnancy. The patients were divided into two groups. In patients in group 1 with complete resection of the adenoma by transsphenoidal surgery, the serum PRL level did not show a sharp rise with the onset of pregnancy as can be seen in normal pregnancy, but continued at low levels of 30ng/ml or lower until the term. In patients in group 2 who had successful pregnancies following incomplete resection of pituitary adenoma in combination with bromocriptine or bromocriptine therapy alone, high PRL levels were maintained from early in gestation until term. One out of 3 patients in group 1 showed good lactation despite low PRL levels during pregnancy. Conversely, in 22 patients in group 2 with high PRL levels during pregnancy, there were 3 patients with insufficient lactation. After suckling stimuli, the maternal PRL level did not rise in either group. These results suggest that the PRL level in maternal blood during pregnancy might not influence the amount of lactation in puerperium. In addition, an abnormally high or low PRL level during pregnancy did not affect the PRL level in cord blood or amniotic fluid or the growth of neonates.

Adenoma↗

Binding capacity of sex-hormone-binding globulin and free testosterone determination in evaluation of hirsute women.

To investigate the relation between free testosterone (T) and binding capacity of sex-hormone-binding globulin (SHBG-BC) and a degree of hirsutism, 34 women were classified into 3 groups according to the criteria of Ferriman and Gallway on the degree of the hirsutism; 11 patients with a total score of 1 to 3 (group 1), 8 patients with a total score of 4 to 10 (group 2), and 15 patients with a total score of 11 or more (group 3). Total plasma T, SHBG-BC, and free plasma T were measured in each group, and they were compared with those of controls. In groups 1 and 2, mean levels of total T were slightly higher than in controls but the differences were not significant. Total T levels were extremely elevated in group 3. Mean level of SHBG-BC in group 1 was slightly lower than in controls but was not statistically significant. SHBG-BC was drastically reduced in groups 2 and 3. The percent free T levels and free T concentrations were significantly higher than those of controls in groups 2 and 3, but not in group 1. The results suggested that decreased SHBG-BC and increased free T might be the cause of hirsutism in women with normal total T levels.

Amenorrhea↗

Successful pregnancies in patients with hyperprolactinemia--clinical and endocrinological studies on mothers and babies.

To study the effect of pregnancy and lactation on the clinical course of patients with pituitary adenoma and the influence of maternal hyperprolactinemia and bromocriptine treatment on fetal and neonatal development, prolactin levels were serially determined and abnormalities of newborn babies were examined. Ninety-nine patients with hyperprolactinemic amenorrhea were treated by surgery, bromocriptine therapy, and a combination of them; thus 34 patients conceived and gave birth to 43 babies. Almost all patients progressed uneventfully except for 2 cases who manifested diabetes insipidus and acute visual impairment. After the end of lactation, prolactin levels declined to lower values than before attempting pregnancy, except in 3 patients. Furthermore, those diagnosed as functional hyperprolactinemia before pregnancy were not found to have developed microadenoma. These results suggest that there is little influence on growth and activity of tumor throughout pregnancy and lactation. All of the newborns were normal and their growth up to 2 years after birth showed no special abnormalities. It was therefore concluded that maternal hyperprolactinemia or bromocriptine therapy in early pregnancy do not cause any deleterious effect on fetal and neonatal development.

Adenoma↗

Poly (adenosine diphosphate-ribose) synthesis in the anterior pituitary of the female rat throughout the estrous cycle: study of possible relation to cell proliferation and prolactin gene expression.

To investigate whether cell proliferation and PRL gene expression in female rat pituitary during estrous cycle were mediated by the poly (ADP)-ribosylation of chromatin proteins, anterior pituitaries at different estrous cycle were obtained from female Wistar rats, and poly (ADP-ribose) synthesis, DNA synthesis, PRL and GH messenger RNAs and PRL content in the pituitary, and serum concentrations of PRL and estradiol were analyzed. From diestrus to proestrus, poly (ADP-ribose) synthesis, the contents of PRL messenger RNA and PRL in the pituitary increased significantly, and decreased at estrus. However, DNA synthesis and serum concentration of PRL showed a significant increase from proestrus to estrus. Serum estradiol concentration increased from diestrus to proestrus. No significant change was observed in the pituitary GH messenger RNA content during estrous cycle. The increase of PRL messenger RNA from diestrus to proestrus was abolished completely by the administration of nicotinamide, an inhibitor of poly (ADP-ribose) synthesis, to rats at diestrus. These results indicate that poly (ADP)-ribosylation of chromatin proteins may play some role in cell proliferation and transcription of PRL gene during rat estrous cycle.

Animals↗

Positive correlation between cytochrome P450 2E1 mRNA level and serum estradiol level in human uterine endometrium.

Most carcinogens are bioactivated by cytochrome P450s (CYPs) and these enzymes within target cells are closely related to susceptibility to cancer. Since extrahepatic CYPs occur typically at much lower levels, the existence and the role of CYP in extrahepatic tissues have been difficult to assess. In this study, we modified the reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the relative quantities of CYP 2E1 mRNA in human endometrium. Total RNA from human endometrium was reverse-transcribed and co-amplified by PCR in the same tube containing both primer pairs of CYP 2E1 and beta-actin. The CYP 2E1 and beta-actin PCR products were 298 and 600 bp, respectively. The restriction enzyme MboI digested these two products to the predicted size for DNA fragments, demonstrating that both PCR products were specific and CYP 2E1 mRNA exists in human endometrium. CYP 1A1 mRNA was also examined, but could not be detected clearly. Adding [alpha-32P]dCTP to the reaction mixture made it possible to quantify the relative yield of the CYP 2E1 PCR product in comparison with the beta-actin product. The ratio of the yield of the CYP 2E1 PCR product to the beta-actin PCR product could be calculated at a point of 25 cycles of amplification. This ratio and serum estradiol levels were correlated positively (r = 0.654; p < 0.05), but no relationship to serum progesterone levels was observed.

Adult↗

Mucinous carcinoma of the ovary. Clinicopathologic analysis.

Since the incidence of mucinous carcinoma of the ovary is relatively low, with only small numbers of cases at any institution, detailed clinicopathologic studies on the prognosis and the care of patients with mucinous carcinoma are missing. Forty-four patients with mucinous carcinoma were histopathologically subclassified into endocervical (n = 8) and intestinal types (n = 36), and studied for clinical manifestations. All tumors of the endocervical type were stage I, whereas 14 intestinal-type tumors were stage II or higher (p < 0.05). Stromal invasion was not observed in 14 of 44 tumors, 13 of which were stage I. Analysis of prognostic factors disclosed that the clinical stage, maximum residual tumor diameter, volume of ascites, stromal invasion, and preoperative CA125 and CA19-9 levels significantly affected prognosis. However, multivariate analysis (stepwise regression) showed that the only significant factor was clinical stage (p < 0.004). In conclusion it is believed that, pathologically, the endocervical-type mucinous carcinoma is not as aggressive as the intestinal-type cancer. The clinical stage was found to be a significant prognostic factor even by multivariate analysis, and the prognosis at stages III and IV was unfavorable compared to stages I and II.

Adenocarcinoma, Mucinous↗

Transfection of human cytochrome P-450 reductase cDNA and its effect on the sensitivity to toxins.

NADPH-cytochrome P-450 reductase (CYPR; EC 1.6.2.4) is an essential enzyme for the catalytic function of cytochromes and is also regarded as being implicated in drug activation. To examine whether CYPR is directly involved in the drug metabolism, a cDNA encoding human CYPR was stably transfected into Chinese hamster ovary cells. Three clonal cell lines were identified which expressed increased levels of CYPR activity (9.3- to 11.2-fold). Western blot analysis indicated that CYPR-transfectant cells contained markedly elevated levels of CYPR protein, while wild-type Chinese hamster ovary cells contained low levels. They showed 1.8- to 3.3-fold higher sensitivity to Adriamycin, 2.1- to 3.0-fold higher sensitivity to mitomycin C, and 2.9- to 4.3-fold higher sensitivity to paraquat than wild-type cells. We also studied other common-use anticancer agents: vinblastine, vincristine, VP-16, and cisplatin, but there were no differences observed in the sensitivity. This report provides the first evidence that transfection of human CYPR into mammalian cells is concerned in the sensitivity to some drugs.

Animals↗

A randomized trial of cisplatin, vinblastine, and bleomycin versus cyclophosphamide, aclacinomycin, and cisplatin in epithelial ovarian cancer.

After primary cytoreductive surgery, a randomized clinical trial was conducted in women with epithelial ovarian cancer to compare the impact on survival between PVB chemotherapy, consisting of cisplatin, vinblastine and bleomycin, and CAP chemotherapy, consisting of cyclophosphamide, aclacinomycin and cisplatin. There were 148 evaluable patients. One hundred and five patients with stage II, III and IV were analyzed in this study, 49 of them received PVB chemotherapy while the remaining 56 patients received CAP chemotherapy. Sixty-four patients fulfilled the criteria for clinical remission set by the Tokai Ovarian Tumor Study Group [Gynecol Oncol 1993;48:342-348]. The remission rate was 73 and 50% in the PVB and CAP groups, respectively, and showed a significant advantage for the PVB group (p = 0.0139). Moreover, the recurrence rate was 44% in the PVB group and 61% in the CAP group after clinical remission, although there was no significant difference between the two groups. The final survival rate was 32% in the PVB group and 24% in the CAP group. There was a significant difference of survival rate between both groups at 24 months (p = 0.0378) and 48 months (p = 0.0450), but finally no significant difference was found at 96 months (p = 0.0660). Compared to the CAP regimen, the PVB combination has a significantly higher efficacy in remission, but there was no significant difference in the long-term survival rate. Furthermore, multivariate analysis demonstrated that the PVB chemotherapy improved the survival, but it was not significant. The authors conclude that PVB chemotherapy may be more effective than CAP chemotherapy for epithelial ovarian cancer.

Aclarubicin↗

Microsurgical epididymal sperm aspiration versus epididymal micropuncture with perivascular nerve stimulation for intracytoplasmic sperm injection to treat unreconstructable obstructive azoospermia.

A novel sperm collection method by epididymal micropuncture combined with perivascular nerve stimulation has been developed to obtain as many clean sperm as possible for IVF for patients with surgically irreparable vasal obstruction. To assess whether the new technique could improve the fertilization and pregnancy rates obtained when attempting microsurgical epididymal sperm aspiration (MESA) to retrieve epididymal sperm from such patients, a prospective randomized comparative study was conducted. Twenty-nine cycles of conventional MESA with ICSI were performed on 25 couples with congenital bilateral absence of the vas deferens (CBAVD) and four failed vasovasostomy cases (group 1). Thirty cycles of epididymal micropuncture with nerve stimulation with ICSI were performed on 28 couples with CBAVD and two failed epididymovasostomy cases (group 2). The mean volume of epididymal fluid and sperm motility in group 2 was significantly higher than that in group 1 (p < .001). Both fertilization and pregnancy rates in group 2 were significantly higher than those in group 1 (p < .001 and p < .03). This novel epididymal sperm collection method for ICSI can provide significantly higher fertilization and pregnancy rates than conventional MESA for ICSI.

Cytoplasm↗

Glutathione related enzymes in cis-diamminedichloroplatinum (II)-sensitive and-resistant human ovarian carcinoma cells.

A cis-diamminedichloroplatinum (II) (CDDP)-resistant cell line (NOS2CR) demonstrated 7.4-fold greater resistance to CDDP compared with the parental cell line (NOS2) established from a patient with serous cystadenocarcinoma of the ovary. We investigated the role of enzyme systems associated with glutathione (GSH) in these cell lines. The GSH content was almost identical in both cell lines. Preincubation with 50 microM DL-buthionine-S, R-sulfoximine (BSO), an inhibitor of gamma-glutamyl cysteine synthetase, for 24 hr reduced the IC50 in both NOS2 and NOS2CR cells. Glutathione-S-transferase pi (GST-pi) activity and mRNA level in NOS2CR cells were higher than in NOS2 cells. However, gamma-glutamyltranspeptidase (GGT) activity in NOS2CR cells was 2.4-fold less than in NOS2 cells. The GST activity and mRNA level in both cell lines were constant when the cells were exposed to CDDP. Exposure to CDDP for 48 hr increased the GGT mRNA level 4.4 and 1.8 times in NOS2 and NOS2CR cells, respectively, compared with no exposure. By exposure to CDDP for 48 hr, the GGT activities in NOS2 and NOS2CR cells were increased 1.6-and 2.5-fold, respectively, compared with no exposure. The above data provide the first evidence that GGT activity and GGT mRNA are induced by CDDP in human carcinoma cell lines.

Blotting, Western↗

Potentiating effect of amphotericin B on five platinum anticancer drugs in human cis-diamminedichloroplatinum (II) sensitive and resistant ovarian carcinoma cells.

We have determined an effect of amphotericin B (AMB), an antifungal drug, on the cytotoxicity of cis-diamminedichloro-platinum (II) (CDDP) and 4 CDDP analogues in a human ovarian carcinoma cell line (NOS2). Intracellular accumulation of CDDP was elevated significantly by treatment with AMB, and AMB significantly potentiated the cytotoxicity of CDDP by MTT assay. Intracellular accumulation of 4 CDDP analogues was also elevated by the treatment with AMB and the order of increasing accumulation rate of platinum drugs was consistent with that of dose modification factor (DMF). AMB also increased the intracellular CDDP accumulation in CDDP resistant cells (NOS2CR), derived from NOS2. The intracellular accumulations of 4 CDDP analogues were elevated slightly by the treatment with AMB in NOS2CR cells. DMFs of 5 platinum drugs in NOS2CR cells, however, were more than those in NOS2 cells. These results indicate that AMB sensitizes NOS2 and NOS2CR cells to platinum drugs, partially due to the increasing intracellular accumulation of these drugs. In addition, CDDP analogues are more effective in NOS2CR cells than CDDP, but the cytotoxicity of CDDP was most potentiated by AMB among the 5 platinum drugs under study.

Amphotericin B↗

Distribution of platinum in human gynecologic tissues and lymph nodes after intravenous and intraarterial neoadjuvant chemotherapy.

Fourteen patients with ovarian and cervical cancer were treated with platinum drug-based intravenous and intraarterial neoadjuvant chemotherapy, respectively, followed by reductive surgery. Platinum accumulation in tissues was assayed to compare the distribution of platinum in cancer tissues, myometrium, ovary, and pelvic lymph node following intravenous and intraarterial administration. Platinum accumulation was higher in the cancer tissue and in the myometrium than in the ovary and the lymph nodes after the intraarterial neoadjuvant chemotherapy. The level of platinum accumulation in tissues to that in the cancer tissues was calculated and compared between the two groups. The level of platinum accumulation in the lymph node to that in the cancer tissue was significantly higher in the intravenous than in the intraarterial group. Furthermore, the relative platinum accumulation was calculated from the total dosage of cisplatin administered. The relative platinum accumulation in the cancer tissue and the myometrium was significantly higher in the intraarterial than in the intravenous group. However, there were no significant differences in the lymph nodes. These findings suggest that intraarterial neoadjuvant chemotherapy should be effective on advanced cervical cancer.

Adult↗

A newly synthesized bifunctional inhibitor, CKA1083, enhances adriamycin activity against human ovarian carcinoma cells.

BACKGROUND: A newly synthesized drug, CKA1083 ((S)-N-[2-(4-benzyloxy-carbonylpiperazinyl)-1-(P-methoxybenzyl) ethyl]-N-methyl-N(5-isoquinolinesulfonamide)), has the same glutathione-S-transferase (GST)-binding site structure as W-77, a bifunctional inhibitor that enhances the cytotoxicity of Adriamycin for human ovarian carcinoma cells. We examined the effects of CKA1083 on the cytotoxicity of Adriamycin and the resistance of human ovarian carcinoma cells to this drug. MATERIALS AND METHODS: We used GST-pi transfected cells and Adriamycin-sensitive or -resistant cells of human ovarian carcinoma. GST-pi activity, the intracellular Adriamycin content, and the cytotoxicity of Adriamycin in these cell lines in the presence or absence of CKA1083 were measured and compared to the findings obtained with W-77 or verapamil. RESULTS: CKA1083 inhibited GST-pi activity in an uncompetitive manner and more strongly than W-77. It enhanced the cytotoxicity of Adriamycin for GST-pi transfected cells by about 3-times. Further, CKA1083 increased the intracellular Adriamycin content about 3-fold in two Adriamycin-resistant cell lines (NOS2AR and NOS3AR). CKA1083 (10 microM) reduced the IC50 of Adriamycin to 1/38 in NOS2AR cells and 1/21 in NOS3AR cells, and overcame Adriamycin resistance more effectively than both W-77 and verapamil. CONCLUSIONS: CKA1083 enhanced the antitumor effect of Adriamycin more than W-77 by inhibiting both GST activity and P-glycoprotein.

Antineoplastic Agents↗