Biomedical subjects
Madoka Furuhashi
Publications and source records attributed to Madoka Furuhashi.
Amniotic fluid neutrophil elastase and lactate dehydrogenase: association with histologic chorioamnionitis.
BACKGROUND: Chorioamnionitis (CAM) is considered to be one of the main causes of preterm labor and has been associated with an adverse perinatal outcome in preterm infants. The diagnosis of acute histologic CAM requires delivery and examination of the placenta. Although numbers of markers have been reported to predict histologic CAM before birth, it is unknown whether the levels of neutrophil elastase and lactate dehydrogenase (LDH) in amniotic fluid are associated with histologic CAM. METHODS: Sixty women at gestational age of 16-35 weeks underwent transabdominal amniocentesis within 48 hr before delivery. Amniotic fluid was analyzed for white blood cell count, glucose level, LDH level, and neutrophil elastase level. The levels of neutrophil elastase were measured by latex immunoassay. Following delivery, tissue samples were obtained from umbilical cord, chorionic plate, and placental membranes. Histologic CAM was diagnosed based on Blanc's criteria. RESULTS: Receiver-operator characteristic curve analysis showed that the amniotic fluid neutrophil elastase had the best screening efficiency in predicting histologic CAM. Using amniotic fluid cut-off levels of 0.15 microg/ml for neutrophil elastase and 250 IU/l for LDH, the sensitivity, specificity, and positive and negative predictive values for predicting histologic CAM were 88.9% versus 84.1%, 73.3% versus 66.7%, 90.9% versus 88.1%, and 68.8% versus 58.8%, respectively. CONCLUSION: Amniotic neutrophil elastase and LDH are useful markers in predicting histologic CAM.
Maternal excessive vomiting: association with periventricular leukomalacia.
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[Medicines of human gonadotropins].
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[Neoadjuvant chemotherapy with intra-arterial infusion in the treatment of advanced cervical cancer].
Neoadjuvant chemotherapy (NAC) with intra-arterial infusion was performed in the treatment for 53 patients with advanced cervical squamous cell carcinoma. After NAC with intra-arterial infusion of the anticancer agents including cisplatin via internal iliac artery or uterine artery, 42 patients received radical hysterectomy. The response to therapy was observed in 45 of all patients (84.9%) clinically, and 36 of 42 patients (85.7%) pathologically. Cancer cells disappeared in 11.9% of patients with cervical invasion, 69.2% with vaginal wall invasion and 39.4% with parametrium invasion after NAG. Five-year survival rates were 100% in stage I, 71.5% in stage II, 52.2% in stage II and 0% in stage IV. The group of patients without cancer in the parametrium after NAC showed a significantly better 5-year survival rate than the group with residual cancer in the parametrium. According to the results, the elimination of cancer invasion to the parametrium by NAC is thought to be important for improvement of the prognosis in advanced cervical cancer.
Embryo evaluation by analysing blastomere nuclei.
BACKGROUND: To create a more effective selection standard for early embryos, we developed a new grading system consisting of conventional morphological evaluation in combination with analysis of blastomere nuclei. METHODS: A total of 744 embryos used during 459 cycles of embryo transfer on day 2 and blastocyst transfer were subjected to retrospective analysis. The overall implantation rate was 15.5% (115/744). Morphological evaluation of the embryos was performed on day 2 by referring to both the size of blastomere and fragmentation (conventional method) and the nucleic features of the blastomeres--either multinucleated or anucleic (nuclei counting method). The implantation rate for every transferred embryo and blastocyst was examined. RESULTS: Although a high implantation rate was observed with the highest quality embryos as judged by either the conventional method (24.1%; 57/237) or the nuclei counting method (26.1%; 104/399), the nuclei counting method predicted implantation rate better than the conventional method. The embryos that were considered to be high quality according to the conventional method, but low quality according to the nuclei counting method, had a limited implantation success rate of 6.3% (4/66). Also, after blastocyst transfer, implantation occurred most often when high quality embryos evaluated by the nuclei counting method were used (25.5%; 25/98), while the blastocysts from low quality embryos seldom implanted (3.2%; 2/63). CONCLUSIONS: When choosing which embryo to transfer, the normality of blastomere nuclei may be a more important index of quality than standard fragmentation features and/or blastomere uniformity analysis. When choosing among embryos, if nucleic status is identical, then embryos with the least fragmentation should be chosen. Moreover, in blastocyst transfer, a blastocyst whose nuclei were judged normal on day 2 should be selected on day 5 over any other blastocysts.
Processing of O-linked glycosylation in the chimera consisting of alpha-subunit and carboxyl-terminal peptide of the human chorionic gonadotropin beta-subunit is affected by dimer formation with follicle-stimulating hormone beta-subunit.
hCG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit, but differ in their hormone-specific beta-subunits. hCGbeta is unique among beta-subunits due to a carboxyl-terminal peptide (CTP) bearing four O-linked oligosaccharides. We previously reported that there were differences in O-glycosylation between two chimeras consisting of alpha-subunit and CTP, i.e. a variant with CTP at the N-terminal region (Calpha) and another analog with CTP at the C-terminus (alphaC) of the alpha-subunit. To address whether O-glycosylation is influenced by the heterodimer formation, Calpha and alphaC were expressed alone or with FSHbeta-subunit in Chinese hamster ovary cells. The O-linked glycosylation was assessed by continuous labeling with [(35)S]methionine/cysteine, immunoprecipitation with anti-alpha or anti-FSH serum, serial digestion with endoglycosidase-F and neuraminidase, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The decrease in molecular weight of dimeric chimeras digested with endoglycosidase-F was greater in Calpha than that in alphaC after treatment with neuraminidase, revealing that both chimeras have different numbers of sialic acids on O-linked carbohydrates. By treating with endoglycosidase-F, the dimeric alphaC migrated faster than its free form, whereas the mobility difference between assembled and unassembled forms of Calpha was very little. These data indicate that processing of O-glycosylation is affected by the backbone polypeptide chain(s).
Primary adenocarcinoma of the vulva with an unusual histological pattern.
CASE REPORT: The authors present a case report of primary adenocarcinoma of the vulva. An ulcerated tumor on the left side of the vulva in a 59-year-old woman was presented. The tumor was excised, and histological examination revealed both papillary and tubulocystic patterns of adenocarcinoma. In some areas, the tumor was composed of cells with a clear cytoplasm. Lymph nodes showed positive in bilateral superficial inguinal nodes but negative in pelvic nodes, showing FIGO stage IVa. Following the operation, both chemotherapy and irradiation therapy were undergone to her. She has been without evidence of disease for more than 5 years following the completion of the treatment. CONCLUSION: Because primary adenocarcinoma of the vulva is very rare, therapeutic modality to date is individually selected.
Serum follicle-stimulating hormone level is a predictor of bone mineral density in patients with hormone replacement therapy.
METHODS: A retrospective study regarding the relationship between serum hormonal levels and bone mineral density (BMD) was performed in 125 women with hormone replacement therapy (HRT). Serum estradiol (E(2)), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and BMD were evaluated before and at 12 and 24 months of HRT. RESULTS: There was a significant increase in E(2) and decrease in FSH at both 12 (E(2), 39.3+/-76.6 pg/ml to 71.0+/-67.9 pg/ml; FSH, 67.9+/-36.3 mIU/ml to 47.9+/-29.0 mIU/ml) and 24 months (E(2), 68.3+/-54.5 pg/ml; FSH, 45.3+/-24.4 mIU/ml). LH level was high at baseline (26.5+/-16.1 mIU/ml) and decreased at 12 months (22.9+/-14.0 mIU/ml). On the contrary, it increased from 12 to 24 months (27.4+/-14.9 mIU/ml). In the lumbar spine BMD, a significant rise was seen only in the first 12 months (0.933+/-0.157 g/cm(2) to 0.938+/-0.152 g/cm(2)). When percentage change was analyzed, a significant positive correlation was found between E(2) and BMD and a negative correlation between gonadotropin levels and BMD. CONCLUSION: These data demonstrate that serum gonadotropin levels, especially FSH, are a good marker to predict BMD in women with HRT.
Changes in oligosaccharide expression on plasma membrane of the mouse oocyte during fertilisation and early cleavage.
It has been reported that various structural and functional changes occur on the surface of the plasma membrane of the ovum and embryo during fertilisation and cleavage in preparation for implantation. Glycoproteins are thought to be one of the factors in cell attachment. Thus, we investigated the changes in glycoprotein expression on the cell surface membrane of the mouse embryo by using lectins. Among seven types of lectin (ConA, WGA, UEA-I, MPA, LCA, DBA and PNA), the fluorescent intensities of ConA and WGA markedly increased from unfertilised ova to blastocysts. By quantitative analysis using immuno-scanning electron microscopy, the numbers of ConA-gold particles were small until 4-cell cleavage, but increased significantly at the blastocyst stage. In contrast, an increased number of WGA-gold particles was detected even at the 4-cell stage, and this increase continued to the blastocyst stage. From the above observations, we conclude that the numbers of sugar chains bound to both ConA andWGA increases with blastocyst formation and earlier expression is observed with WGA. The present study dearly shows that glycoproteins on the cell membrane surface of the mouse embryo quantitatively increase at the time of implantation, and the possibility has been indicated that glycoproteins are involved in intercellular recognition and adhesion between the embryo and endometrial epithelium.
Effect of additional N-glycosylation signal in the N-terminal region on intracellular function of the human gonadotropin alpha-subunit.
hCG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit, but differ in their hormone-specific beta-subunits. The alpha-subunit has two N-glycosylation sites at Asn52 and Asn78. To obtain more information on the relationship between the structure and function of the alpha-subunit, we introduced a novel N-glycosylation site in the N-terminal region by mutating Asp3 and Gln5 into Asn and Thr, respectively. Glycosylation mutants were expressed alone or with hCGbeta-subunit in Chinese hamster ovary cells. New N-linked oligosaccharides were efficiently added to the wild-type and mutant alpha-subunits lacking N-glycan at Asn52 (alpha deltaAsn1), Asn78 (alpha deltaAsn2), and both (alpha deltaAsn(1 + 2)). The new sugar chain did not affect secretion and assembly except that 1) it increased the intracellular degradation of alpha deltaAsn(1 + 2), and 2) it augmented the assembly of alpha deltaAsn1 with hCGbeta-subunit. Amino acid changes generated the attachment of O-glycosylation in free alpha-subunit but not in assembled form. These data indicate that the newly introduced N-glycosylation consensus sequence is functional, and that the N-terminal region of the alpha-subunit is flexible and can be modified without affecting the intracellular function. Furthermore, amino acid sequences in the N-terminus are involved in the O-glycosylation in free alpha-subunit.
Bone mineral density in adult patients with Turner's syndrome: analyses of the effectiveness of GH and ovarian steroid hormone replacement therapies.
To analyze the effects of treatments with GH and cyclic estrogen/progesterone (E/P) replacement on bone mineralization in patients with Turner's syndrome (TS), bone mineral density (BMD) was measured longitudinally. BMDs of the whole body and the lumbar spine in 16 adult female patients with TS (17-38 year old; 0-20 years by length of E/P treatment) were assessed using dual energy X-ray absorptiometry one to 5 times over a treatment period of up to 7 years maximum. GH treatment was performed in 9 cases (GH group), but not in the remaining 7 (non-GH group). E/P replacement therapy was initiated in all patients after they finished GH administration. The BMDs of both the whole body and the lumbar spine in the patients with TS were significantly less than those in age-matched normal subjects, and did not improve with E/P treatment. Although there were no differences in final body height and age at the beginning of E/P administration between the GH and non-GH groups, whole body BMD in the GH group was significantly lower than that in the non-GH group. These results indicate that GH administration in childhood and adolescence and E/P treatment in adulthood did not increase bone mineralization in the TS patients. Therefore, we can conclude that the optimal protocol of hormonal replacement therapy with GH and E/P during childhood and adolescence should be established as soon as possible.
Morphological analyses of interleukin-8 effects on rat ovarian follicles at ovulation and luteinization in vivo.
The aim of the present study was to elucidate functions of the interleukin (IL)-8 at ovulation and luteinization in vivo. To compare the morphological differences between human chorionic gonadotropin (hCG) and IL-8 stimulation, scanning electron microscopy was employed to study rat ovarian vascular corrosion casts. Follicular growth and increased capillary vessel densities around the follicles were seen in vascular corrosion casts after IL-8 injection, similar to the result of hCG administration. This result indicated that exogenous IL-8 could play a role in the neovascularization during follicular development as an angiogenetic factor. Many fenestrations were observed in the vascular endothelium by hCG administration. In contrast, no fenestrations were observed with IL-8 injection, indicating that IL-8 may not be sufficient to increase the vascular permeability directly. Although germinal vesicle breakdown (GVBD) occurred at rates of 82% after the hCG injection, only 20% GVBD was observed after the IL-8 injection. The present study indicated that IL-8 might have important effects on rat follicles at ovulation and luteinization via vascularization in a similar manner to hCG. However, IL-8 was not effective on vascular permeability and oocyte maturation, which were different from hCG. Thus, we can conclude that IL-8 can participate in follicular development in part and may play important roles in ovulation and luteinization as one of some mediators induced by endogenous luteinizing hormone.
Management of missed abortion in a patient with congenital cervical atresia.
OBJECTIVE: To describe a patient with congenital cervical atresia who became pregnant through IVF and thawed transmyometrial ET and then experienced a missed abortion. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A patient with congenital cervical atresia who underwent reconstructive surgery at 23 years of age and underwent IVF twice at 28 and 30 years of age. INTERVENTION(S): Abortion management. MAIN OUTCOME MEASURE(S): Medical follow-up of IVF-ET, resultant pregnancy, and abortion. RESULT(S): After the second cycle of IVF with frozen-thawed transmyometrial ET, the patient became pregnant but then experienced a missed abortion. Serum beta-hCG levels decreased, the two gestational sacs disappeared, and genital bleeding without signs of infection occurred 14 weeks after diagnosis of the abortion. The abortion was managed conservatively. CONCLUSION(S): When assisted reproductive techniques are used in patients with congenital cervical atresia, the risks (including those relating to the management of an abortion) should be explained in detail to the couple and sufficient informed consent should be obtained before starting IVF-ET procedures.
Pretreatment for ovarian endometrial cyst before in vitro fertilization.
Assisted reproductive technology is a widely accepted treatment for infertile women with endometriosis. The presence of an ovarian endometrial cyst reduces the quality of oocytes, while surgical resection of endometrioma may reduce the ovarian reserve for ovarian stimulation by exogenous gonadotropins. To determine what pretreatment should be performed for ovarian endometrial cyst before IVF-ET, we analyzed IVF outcomes with or without pretreatment in patients with endometrioma. Infertile women with endometrioma who underwent IVF-ET were divided into 3 groups, including patients who had received laparotomy or laparoscopy, patients for whom the endometrioma content had been aspirated and treated with or without alcohol fixation, and patients who did not undergo pretreatment. The number of retrieved oocytes, rate of mature oocytes, and fertilization rate were compared among groups. The results showed that pretreatment for endometrioma reduces the number of retrieved oocytes. Although oocyte quality as a rate of mature oocytes was not affected by the presence of an ovarian endometrial cyst, the fertilization rate was improved by cyst aspiration. We propose that surgical pretreatment is not necessary for ovarian endometrial cyst before IVF-ET, but cyst aspiration may be beneficial after several failed attempts of IVF.