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Biomedical subjects

N Suganuma

Publications and source records attributed to N Suganuma.

At least 37 records · Page 2Linked to original sources

Risk analysis of the exposure to GB virus C/hepatitis G virus among populations of intravenous drug users, commercial sex workers and male outpatients at STD clinic in Chiang Mai, Thailand: a cross-sectional case-control study.

An exposure to GB virus C/hepatitis G virus (GBV-C/HGV) was studied among populations at risk for blood and sexual exposure to analyze risk factor of the transmission of the virus. Blood samples were drawn from 98 intravenous drug users (IVDU), 100 female high-class commercial sex workers (CSW) and 50 male outpatients (MOP) at a sexually transmitted diseases (STD) clinic in Chiang Mai, Thailand. These blood samples were analyzed for GBV-C/HGV RNA; antibodies against second envelope protein of GBV-C/HGV (anti-E2); anti-hepatitis C virus antibody (HCV-Ab); hepatitis B core antibody (HBcAb); and antibodies against human immunodeficiency virus (HIV-Ab). Prevalences of GBV-C/HGV RNA, anti-E2, HCV-Ab, HBcAb and HIV-Ab were 27.6%, 16.3%, 84.7%, 76.5% and 45.0% in IVDU; 0%, 21.5%, 2.0%, 72.0% and 11.0% in CSW; 6.0%, 13.6%, 0%, 64.0% and 14.0% in MOP. While the prevalence of GBV-C/HGV RNA was higher in IVDU than in CSW and MOP, comparable prevalences of anti-E2 among the three populations were found. Intravenous drug injection showed association with GBV-C/HGV RNA, while history of STD associated with anti-E2. In conclusion, intravenous drug injection and STD were found to be risk factors for the previous exposure to GBV-C/HGV, but STD did not increase the risk of the GBV-C/HGV viraemia.

Adolescent↗

Reduced serum levels of ALT and GGT and high carbohydrate intake among workers exposed to toluene below the threshold limit values.

We have found decreased serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) levels in human males exposed to toluene at low levels, suggesting that toluene exposure or related factors in lifestyles were likely to have lowering effects on serum ALT and GGT activities between toluene-exposed and the control subjects. The present study was attempted to investigate whether there is any difference in nutrient intakes between the two groups. Biochemical results were also analysed together with nutrient intakes. In agreement with our previous reports, the present data also provided significant evidence of lowered serum ALT and GGT activities in toluene-exposed males after age matching (p < 0.05). Energy intakes from carbohydrate, fat and protein were 64.6%, 22.5% and 12.9% in the toluene-exposed group and 62.0% (p < 0.05), 24.8% (p < 0.05) and 13.2%, respectively, in the controls. Multiple regression analysis indicated that carbohydrate, protein and energy intakes are significantly associated with toluene exposure. No significant differences in alcohol consumption, tobacco use, work intensities and physical activities were found between the two groups. The present results suggest that the toluene exposure at levels generally considered to be safe, probably have some biological effects on the liver and related organs.

Adult↗

Fibronectin secretion from human peritoneal tissue induces Mr 92,000 type IV collagenase expression and invasion in ovarian cancer cell lines.

Our previous study showed that human peritoneal conditioned medium (CM) increased the matrix metalloproteinase-9 (MMP-9) secretion and invasiveness of ovarian cancer cells (NOM1). In an effort to identify this MMP-9-stimulating factor, we examined the effects of extracellular matrix components, such as type IV collagen, laminin, and fibronectin, on ovarian cancer cells. We found that fibronectin increased the MMP-9 activity of NOM1 cell CM in a concentration-dependent manner and that the peritoneal CM contained high level of fibronectin. An increase of MMP-9 activity in NOM1 cell CM by the peritoneal CM was almost completely blocked by 20 microg/ml of anti-integrin alpha5/FnR antibody and RGD polypeptides. Furthermore, after immunoprecipitation by antifibronectin antibody supernatant of the peritoneal CM did not increase MMP-9 activity in NOM1 cells. Fibronectin and the peritoneal CM also increased MMP-9 activity and expression in NOM1 cell lysate, and these effects were blocked by anti-integrin alpha5/FnR antibody. Invasiveness of NOM1 cells was enhanced by fibronectin and the peritoneal CM in a concentration-dependent manner, and anti-integrin alpha5/FnR antibody blocked these effects. These results suggested that fibronectin secreted from peritoneum increased MMP-9 activity and expression, and, in turn, invasiveness of ovarian cancer cells.

Antibodies, Monoclonal↗

Positive correlation between inhibitors of matrix metalloproteinase 1 and matrix metalloproteinases in malignant ovarian tumor tissues.

To investigate the relation between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in malignant ovarian tumor, MMP and TIMP activities in conditioned media of 16 malignant ovarian tumor tissues and six normal ovaries were detected by zymography and reverse zymography, respectively and were quantitated with a densitometer. TIMP-1 and TIMP-2 were detected in all normal and malignant ovarian tumor tissues by reverse zymography. In normal ovaries, the intensity of TIMP-2 bands was stronger than TIMP-1, but in malignant tumor tissues those of TIMP-1 were stronger. The ratios of TIMP-1 to TIMP-2 and MMP-9 to MMP-2 were significantly higher in malignant tumor tissues than in normal ovaries (P < 0.001). TIMP activity consisting of TIMP-1 and TIMP-2 correlated significantly to MMP activity of MMP-2 and MMP-9 (r = 0.67, P < 0.005). There was a significant correlation between TIMP-1 activity and MMP activity (r = 0.72, P < 0.001), but no correlation was observed between TIMP-2 activity and MMP activity. The high level of TIMP-1 appeared to be related to malignant phenotype in ovaries as well as the high level of MMP-9.

Adolescent↗

The biologic action of single-chain choriogonadotropin is not dependent on the individual disulfide bonds of the beta subunit.

Disrupting disulfide loops in the human chorionic gonadotropin beta subunit (CGbeta) inhibits combination with the alpha subunit. Because the bioactivity requires a heterodimer, studies on the role of disulfide bonds on receptor binding/signal transduction have previously been precluded. To address this problem, we bypassed the assembly step and genetically fused CGbeta subunits bearing paired cysteine mutations to a wild-type alpha (WTalpha) subunit. The changes altered secretion of the single-chain mutants which parallel that seen for the CGbeta monomeric subunit. Despite conformational changes in CG disulfide bond mutants (assayed by gel electrophoresis and conformationally sensitive monoclonal antibodies), the variants bind to the lutropin/CG receptor and activated adenylate cyclase in vitro. The data show that the structural requirements for secretion and bioactivity are not the same. The results also suggest that the extensive native subunit interactions determined by the cystine bonds are not required for signal transduction. Moreover, these studies demonstrate that the single-chain model is an effective approach to structure-activity relationships of residues and structural domains associated with assembly of multisubunit ligands.

Chorionic Gonadotropin↗

Clinical behavior of borderline ovarian tumors: a study of 150 cases.

BACKGROUND: We evaluated the clinical features, treatment, and survival status of the patients with borderline ovarian tumors. METHODS: A retrospective review of the charts of 150 patients with borderline ovarian tumor registered at the Tokai Ovarian Tumor Study Group from January 1, 1980, to December 31, 1994, was conducted to obtain clinical and pathological information. RESULTS: In stage II and III disease, the numbers of patients with no residual tumor, residual tumor of <2 cm, 2-5 cm, and >5 cm were 9, 10, 3, and 3, respectively. The sizes of residual tumors and corresponding clinical response to chemotherapy were as follows: residual tumor of <2 cm, complete response (CR), 6 patients; no change (NC), 2; progressive disease (PD), 2; tumors 2-5 cm, NC, 1 patient, PD, 2; tumors >5 cm, PD, 3 patients. The survival for patients with residual tumor <2 cm was significantly better than for those with residual tumor from 2-5 cm and of >5 cm (P < 0.05). The survival for patients with stage II and III serous tumor was significantly longer than that for patients with stage II and III mucinous tumor (P < 0.05). CONCLUSION: In advanced borderline ovarian tumor, the prognosis of patients with gross residual tumor after initial surgery, and especially with mucinous tumor, was poor.

Adolescent↗

Squamous cell carcinoma arising from mature cystic teratoma of the ovary: a clinicopathologic analysis.

OBJECTIVE: There have been few studies concerning the clinical pathology of squamous cell carcinoma arising from ovarian mature cystic teratoma. Thus, the objective of this study is to determine clinicopathologic factors affecting survival in this rare tumor. METHODS: From September 1979 to June 1996, 37 patients with squamous cell carcinoma arising from ovarian mature cystic teratoma were treated by the Tokai Ovarian Tumor Study Group. A retrospective clinicopathologic and survival analysis of these patients was performed. The mode of infiltration was classified into expansive, moderately diffused, and diffused patterns. RESULTS: Although the 5-year survival rate was 94.7% and 80.0% for stage I and II patients, respectively, 12 of 13 patients with stage III died within 20 months (P = .0001). A significant difference was also observed between the survival of the groups with and without residual tumor at surgery (P = .0001). Pathologic features, grade, mode of infiltration, and vascular involvement were significant factors by univariate analysis. Multivariate analysis showed significant differences in survival related to grade (P = .0154) and mode of infiltration (P = .0053). The preoperative squamous cell carcinoma antigen level was significantly higher in the patients with squamous cell carcinoma arising from mature cystic teratoma than in patients with mature cystic teratoma (P < .0001). CONCLUSION: This study suggests that pathologic factors, grade, and mode of infiltration can provide valuable information for predicting the survival of patients with squamous cell carcinoma arising from mature cystic teratoma. In addition, squamous cell carcinoma antigen may be a useful marker to detect this disease preoperatively.

Adult↗

Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue.

Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4 mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M(r) 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.

Collagenases↗

Alteration of N-linked oligosaccharide structures of human chorionic gonadotropin beta-subunit by disruption of disulfide bonds.

The human chorionic gonadotropin beta-subunit (hCGbeta) is a glycoprotein in which 12 cysteine residues pair to form six intramolecular disulfide bonds. In order to elucidate the effect of each disulfide bond on glycosylation of the molecule, we analysed structures of asparagine-linked oligosaccharides of various recombinant hCGbeta produced in Chinese hamster ovary (CHO) cells: wild-type hCGbeta (betaWT) and mutants in which any one of the six intramolecular disulfide bonds had been disrupted by site-directed mutagenesis. SDS-PAGE analysis of betaWT and these mutants before and after digestion with endoglycosidase F and H revealed structural changes in the oligosaccharide moieties of some mutants. In addition, structural analysis of oligosaccharides obtained from metabolically labeled betaWT and a mutant showed that the mutant contained additional high mannose type oligosaccharides. These results suggest that elimination of a specific disulfide bond, resulting in a change in the protein conformation, disturbs the normal assembly of the mature complex type oligosaccharides in the hCGbeta molecule.

Acetylglucosamine↗

Hyaluronidase activity in gynaecological cancer tissues with different metastatic forms.

We investigated hyaluronidase activity in gynaecological normal and malignant tissues. Hyaluronidase activity in culture medium of tissue specimens was detected by hyaluronic acid zymography and quantified by densitometry. Hyaluronidase activity was shown as one dominant band (molecular weight 65 kDa) at pH 3.5. Hyaluronidase activity was significantly higher in normal ovary (P < 0.05) and normal endometrium (P< 0.05) than in normal cervix. One dominant 65-kDa hyaluronidase was expressed in 100% (14 out of 14) of ovarian cancer tissues and in 91% (10 out of 11) of endometrial cancer tissues. However, hyaluronidase activity was not observed in cervical cancer tissues. Hyaluronidase activity was significantly higher in ovarian (P < 0.001) and endometrial (P < 0.01) cancer tissues than in cervical cancer tissue and was significantly higher in ovarian cancer tissue than in endometrial cancer tissue (P < 0.05). These facts suggest that the cancer cells make use of the original characteristic of the organ to invade and metastasize. Moreover, these results reflect the difference in metastatic forms and are suggestive of a strong relationship between hyaluronidase activity and invasion and metastasis of ovarian and endometrial cancers compared with cervical cancer.

Adult↗

Effects of gonadotropin, estrogen, and progesterone on c-mos gene expression in mouse oocytes in vivo and in vitro.

OBJECTIVE: To analyze the effects of gonadotropin and ovarian steroid hormones on the gene expression of c-mos in mouse oocytes. METHODS: The changes of c-mos messenger RNA (mRNA) levels in oocytes were examined after the administration of pregnant mare's serum gonadotropin (PMSG) in vivo, or after incubation with estrogen and/or progesterone in vitro. Five IU PMSG was injected intraperitoneally to female immature mice, and human chorionic gonadotropin was also injected intraperitoneally 48 hours after the PMSG injection, with or without mating with male mice. The oocytes were collected from follicles or oviducts at 24, 30, 36, 42, 48, 60, 72, and 84 hours after the injection. The RNAs were extracted from 5 oocytes at each time point, and a reverse-transcription polymerase chain reaction using specific primers to c-mos DNA was performed to measure the relative amount of c-mos mRNA. RESULTS: The c-mos mRNA in oocytes at 36 hours after the injection was 2.7 times higher than that at 24 hours. The c-mos mRNA level gradually decreased thereafter, and after ovulation the level was only 1/10 of the peak level. When the oocytes that were retrieved 24 hours after PMSG injection were incubated with 800 ng/ml estradiol 17-beta or 600 ng/ml progesterone for 120 minutes, the c-mos gene expression was significantly suppressed or stimulated, respectively, in comparison with the absence of these substances. CONCLUSION: Although the regulatory mechanism of c-mos gene expression in oocytes is still unclear because the result obtained from the in vitro study, that estrogen suppressed the c-mos gene expression directly, was inconsistent with the result of the in vivo study, that increases of both c-mos mRNA and estrogen occurred simultaneously with PMSG stimulation in the early phase of preovulatory oocytes, our present study revealed that gonadotropin and steroid hormones might affect c-mos gene expression in mouse oocytes indirectly and/or directly.

Animals↗

Apoptosis in human endometrial and endometriotic tissues.

Apoptosis has recently been proposed to represent programmed cell death. Several investigations have revealed that uterine endometrium in mammals can be regulated by apoptosis. However, apoptosis may be less likely to occur in human eutopic endometrium. On the other hand, immunoreactivity of Bcl-2 that may serve a regulatory function in protecting from undergoing apoptosis was observed in uterine endometrial glandular cells in the proliferative phase through to the early secretory phase. In endometriotic tissues, although apoptosis was detected in all the samples from ovarian endometriosis, it was indicated in only a few tissues from adenomyosis. Bcl-2 was negative in almost all samples from ovarian endometriosis, whereas it was positive in all adenomyotic tissues from cases in the proliferative phase, but in none of tissues from cases in the secretory phase. Thus, ovarian endometriosis can be discriminated from adenomyosis based on the existence of apoptosis though both represent a type of ectopic endometrial tissue, and the pathogenesis or condition of the cells may be different between ovarian endometriosis and adenomyosis.

Apoptosis↗

Epididymal sperm retrieval by epididymal micropuncture combined with intracytoplasmic sperm injection: difference between acquired and congenital irreparable obstructive azoospermia.

To evaluate the differences in fertilization and pregnancy rates following intracytoplasmic sperm injection (ICSI) of retrieved epididymal sperm between congenital (group 1) and acquired (group 2) unreconstructable obstructive azoospermic patients, we compared the outcome of the ICSI procedure between these two groups. Thirty-six patients with obstructive azoospermia received epididymal sperm retrieval by the micropuncture method for the ICSI procedure. Main parameters evaluated were epididymal fluid volume, sperm concentration, sperm-motility; fertilization rate and clinical pregnancy rate. There were no significant differences in epididymal fluid and sperm concentration between the two groups. However, the sperm motility in group 1 was significantly higher than that in group 2. The fertilization rates per couple in groups 1 and 2 were 78.2 and 82% (nonsignificant). The pregnancy rate per couple in group 1 was 37.5% (6/16), while that in group 2 was only 5% (1/20); this difference was statistically significant (p < 0.05). Using epididymal sperm for the ICSI procedure, the chances of pregnancy for couples with congenital absence of the vas deferens were significantly higher compared with couples with acquired unreconstructable obstructive male infertility.

Adult↗

Distribution of platinum in human gynecologic tissues and pelvic lymph nodes after administration of cisplatin.

BACKGROUND: Defining tissue accumulation of platinum may be of importance, since it may provide a pharmacological explanation for organ-specific cisplatin activity. This study was conducted to evaluate the efficacy of cisplatin at the tissue level in different gynecologic organs. The doses administered were equivalent to those used in neoadjuvant chemotherapy regimens. STUDY DESIGN: Cisplatin was administered intravenously to patients with cervical or endometrial cancer 1 h before operation, and platinum accumulations in tissues were assayed by the atomic absorption method. RESULTS: Platinum accumulation was highest in the cervix and next highest in the myometrium in both cancers. Platinum accumulation in ovary and lymph node was only 0.58 and 0.57 times that in the myometrium, respectively. In patients with cervical cancer, the platinum accumulations in the myometrium and cervix were significantly higher than in the ovary and lymph node. Platinum accumulation in cervical cancer tissue was lower than in the myometrium and cervix, suggesting that delivery of cisplatin to a cervical cancer is somewhat more difficult than to the normal cervix. In patients with endometrial cancer, there was significantly more accumulation in the cervix than in the ovary and lymph node. CONCLUSIONS: These data indicated that cisplatin was easily distributed to the cervix and myometrium, but not to the ovary, lymph node, and cancer tissues.

Adult↗

A live birth from intracytoplasmic injection of a testicular spermatozoon.

Testicular sperm was retrieved from a man with complete epididymal obstruction, and intracytoplasmic sperm injection was performed on his wife's oocytes. In four mature treated, two fertilized eggs were obtained, and a clinical pregnancy was established with embryo transfers. One healthy girl (2715 g) was delivered by cesarean section at 38 weeks' gestation. Our case shows that the use of testicular sperm can result in a normal live birth.

Adult↗

Conservative handling of the uterus in a 10-week cervical pregnancy case.

A patient with a living 10-week old cervical pregnancy who desired to preserve fertility was successfully treated with methotrexate, intraamniotic KCI injection and endocervical curettage. In the case of living cervical pregnancy even after 10 weeks, conservative treatment remains an option, although intensive management and care should be given.

Adult↗

Selective fallopian tube catheterisation in female infertility: clinical results and absorbed radiation dose.

Clinical results of fluoroscopic fallopian tube catheterisation and absorbed radiation doses during the procedure were evaluated in 30 infertility patients with unilateral or bilateral tubal obstruction documented on hysterosalpingography. The staged technique consisted of contrast injection through an intrauterine catheter with a vacuum cup device, ostial salpingography with the wedged catheter, and selective salpingography with a coaxial microcatheter. Of 45 fallopian tubes examined, 35 (78%) were demonstrated by the procedure, and at least one tube was newly demonstrated in 26 patients (87%). Six of these patients conceived spontaneously in the follow-up period of 1-11 months. Four pregnancies were intrauterine and 2 were ectopic. This technique provided accurate and detailed information in the diagnosis and treatment of tubal obstruction in infertility patients. The absorbed radiation dose to the ovary in the average standardised procedure was estimated to be 0.9 cGy. Further improvement in the X-ray equipment and technique is required to reduce the radiation dose.

Adult↗

Clinical factors for successful cryopreserved-thawed embryo transfer.

PURPOSE: To study how clinical factors such as embryo quality, cell stage of embryo at cryopreservation, and synchronization of developmental stages between embryo and endometrium at thawing affect the implantation rate after cryopreserved-thawed embryo transfer (ET), these factors were examined in 106 cryopreserved-thawed ETs including 204 embryos. RESULTS: In 86 embryos graded as high quality before transfer by morphological evaluation, 31 implantations were successful, while the other, low-quality embryos did not implant at all. High-quality embryos received less cryoinjury during cryopreservation compared to the injuries sustained by embryos in moderate and poor quality. When cyopreservation was performed at the 1-, 2-, and 3-day cell stages, pregnancies were similiarly achieved among most of the embryos at all cell stages. At thawed ETs in natural ovulation cycles, there were some differences among the developmental stages between thawed embryo and endometrium that received the thawed transferred embryos. Although the transfer timelag ranged a day or more, asynchronism of endometrium growth to the cell stage did not reduce pregnancy rates. CONCLUSIONS: These results indicated that embryo quality evaluated morphologically was the most important clinical factor for successful implantation of cryopreserved-thawed ET.

Blastocyst↗