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Congenital heart defects are the most common fetal structural anomalies of which a significant number remain unrecognized during postnatal life. Fetal electrocardiography (FECG) is an ideal clinical tool to complement ultrasonography for the screening and management of these cases where early and accurate diagnoses would allow definite rather than palliative treatment. The objective of this report was to correlate the particular FECG results found with the different types of congenital heart defects involved and to further demonstrate the usefulness of FECG in clinical settings. This is a report of four cases of prenatally diagnosed congenital heart defects seen at a university hospital in Sendai, Japan. Their complete and thorough evaluation included, among other tests, abdominal FECG analysis. The presence of premature ventricular contractions, a prolonged pre-ejection period (PEP > 75 msec), and prolonged QTc intervals (QTc > 440 msec) served as markers of hemodynamic alteration but were unlikely determinants of disease severity precluding further investigation. In practice, similar findings found on FECG should raise the index of suspicion for the presence of congenital heart disease and prompt a targeted ultrasound scan. [ABSTRACT FROM AUTHOR]

The article presents guidelines on the determination and treatment of intrapartum fetal heart rate (FHR) patterns. The authors adopted a five-tier system to classify the FHR patterns and modified the color-coded classification. They propose a standardized management protocol according to FHR pattern, level for both doctors and midwives.

We examined the expression of the steroid and xenobiotic receptor (SXR) and evaluated its clinical significance in human epithelial ovarian carcinoma. One hundred forty-one cases were examined using immunohistochemistry for SXR with archival specimens. All cases were scored using a semi-quantitative histological scoring (HSCORE) method. Specimens with an HSCORE > 60 were regarded as SXR-positive. Various clinicopathologic variables were examined. SXR showed significant differences in age, histology, grade, ERα and PR. SXR was detected in 35 of 141 (24.8%) ovarian cancer tissues. There was a statistically significant negative correlation between SXR-positive status and both disease-free survival and overall survival ( P= 0.0415 and 0.0316, respectively), independent of stage ( P= 0.0167 and 0.021, respectively). In multivariate analysis, SXR was a statistically independent risk factor for both disease-free survival and overall survival ( P= 0.049 and 0.0354). Our results support an association of SXR between ERα and PR in epithelial ovarian cancers. Our data suggest that SXR is a prognostic factor in epithelial ovarian cancer and may represent a useful marker to identify patients at risk of recurrence or death. [ABSTRACT FROM AUTHOR]

Problem Transplantation of human ovarian cortex into host mice may permit various kinds of challenges in reproductive medicine. A novel immunodeficient mouse strain (NOD/SCID/γcnull: NOG) has been developed as a host of transplantation of human tissue. Method of study Human ovarian cortex was transplanted into various sites of NOG mice and human follicular development was examined by immunohistochemistry. Results Transplantation of human ovarian tissue into NOG mice resulted in approximately similar tissue survival and follicle growth as did transplantation into non-obese diabetic-severe combined immunodeficient mice. The human Graafian follicule from NOG mouse expressed the same steroidogenic enzymes as observed in human Graafian follicles, which developed in the human body. The NOG mice’s ovarian bursa was better placed for transplantation than the back skin or kidney capsule. Conclusion These results represent the successful generation and biological confirmation of the human Graafian follicles from the human ovarian cortex in the NOG mice. [ABSTRACT FROM AUTHOR]

Endometriotic nodules in the lower genital tract often cause dysmenorrhea and dyspareunia. We report here a case of posterior vaginal fornix endometriosis that was overlooked for several years. We performed a trans-vaginal resection after the associated pain was not relieved by repetitive gonadotropin-releasing hormone agonist (GnRHa) therapy or abdominal surgery. After the resection, the patient's symptoms disappeared. The patient subsequently conceived and proceeded to a full-term delivery. The pathological diagnosis was ‘endometriosis of the vagina.’ Immunohistochemical staining revealed that the progesterone receptor-positive cells outnumbered the estrogen receptor-positive cells. We emphasize that the existence of vaginal lesions should be considered in cases in which pain has not improved despite long-term GnRHa administration, or in cases involving dyspareunia. To provide appropriate treatment, attentive evaluation and careful examination of the disease are necessary for a patient with prolonged unsatisfactory progress. [ABSTRACT FROM AUTHOR]

Gene silencing associated with aberrant DNA methylation of promoter CpG islands is one mechanism through which several genes may be inactivated in human cancers. Cyclin D2, a member of the D-type cyclins, implicated in cell cycle regulation, differentiation and malignant transformation, is inactivated due to aberrant DNA methylation in several human cancers. In the present study, we examined the promoter methylation status and expression of Cyclin D2 in human epithelial ovarian cancer, and then determined the relationship between methylation status and various clinicopathological variables. Twelve ovarian cancer cell lines and 71 surgical specimens were examined by methylation-specific polymerase chain reaction and quantitative reverse transcription–polymerase chain reaction to evaluate the methylation status and expression of the Cyclin D2 gene. The relationship between methylation status and various clinicopathological variables was evaluated using statistical analysis. Aberrant methylation of Cyclin D2 was present in five of 12 ovarian cancer cell lines and 16 of 71 primary ovarian cancer tissues. In five cell lines with methylation, expression of the Cyclin D2 gene tended to be lower than in cell lines without methylation. In ovarian cancer tissues, methylation bands were detected in 16 of 71 cases. The methylation status of Cyclin D2 was associated with advanced stage and a residual tumor size (>2 cm) ( P = 0.027 and P = 0.031, respectively). Based on univariate analysis, patients with aberrant methylation of the Cyclin D2 promoter had a significantly worse chance of disease-free survival than those without methylation ( P = 0.021). Our results suggest that aberrant promoter methylation of the Cyclin D2 gene is significantly associated with patient prognosis in epithelial ovarian cancer. ( Cancer Sci 2007; 98: 380 –386) [ABSTRACT FROM AUTHOR]

The possible role of specific progesterone receptor (PR) isoforms (PRA and PRB) as predictive factors in endometrial carcinoma is unclear. The present study was undertaken to evaluate the clinical significance of intratumoral PR isoform status in patients with endometrioid endometrial carcinoma. We studied 103 cases of endometrioid endometrial carcinoma using immunohistochemistry. We correlated the findings with various clinicopathological parameters of the patients. PRA and PRB immunoreactivity was detected in 51/103 (48.5%) and 79/103 (76.7%) of carcinoma cases, respectively. A significant positive correlation was detected between the status of PRB immunoreactivity and the amount of PRB mRNA by real-time reverse transcription–polymerase chain reaction ( P = 0.012). PR isoform expression was significantly lower in the cases with higher histological grade ( P = 0.0001 and P = 0.002, for PRA and PRB, respectively). Cases that were negative for either one or both PR isoforms were significantly associated with shorter disease-free and overall survival of the patients. The absence of either one or both of these two PR isoforms was detected in all nine patients who died (100.0%), whereas the absence of these immunoreactivities was detected only in 43 of 94 (45.7%) patients who had lived during the same period. In addition, multivariate analysis demonstrated that an absence of PRA immunoreactivity was an independent risk factor in disease-free survival of the patients ( P = 0.0258). The results of our study demonstrated that loss or absence of PR isoform expression determined by immunohistochemistry could become an important prognostic indicator in patients with endometrioid endometrial carcinoma. ( Cancer Sci 2006; 97: 1308–1314) [ABSTRACT FROM AUTHOR]

The article discusses the mechanisms of birth at term and preterm. The article suggests that the role of intraplacental prostaglandin E-2 in sheep as intermediate between the fetal and maternal events of parturition may be mimicked in human gestation by placental corticotrophin-releasing hormone. The importance of both cytokine and glucocorticoid pathways of increased prostaglandin production at the time of parturition is also discussed.

DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1) is a recently characterized member of the orphan nuclear receptor family. DAX-1 functions as a global negative regulator of steroid hormone production. It inhibits adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1 (SF-1) pathway-dependent P450arom expression in cultured human endometriotic stromal cells and acts as a corepressor for estrogen receptors (ER). In this study we first examined the localization of DAX-1 in 46 normal cycling endometria, 36 cases of endometrial hyperplasia and 103 cases of endometrial carcinoma by using immunohistochemistry to elucidate the possible involvement of DAX-1 and its correlation to the status of Ad4BP/SF-1, a universal transcription factor of steroidogenesis. We then evaluated DAX-1 mRNA expression, using quantitative reverse transcription–polymerase chain reaction for DAX-1 in 33 cases of endometrial carcinoma for further characterization. We subsequently correlated these findings with various clinicopathological parameters of the cases. Ad4BP/SF-1 immunoreactivity was not detected in any human endometria examined. A significant inverse correlation was detected between the status of DAX-1 immunoreactivity and histological grade ( P = 0.0003) in endometrial carcinoma. The labeling index (LI) values of DAX-1 in normal endometrium during the secretory phase ( P < 0.0001) and hyperplasia ( P < 0.0001) were significantly higher than that of carcinoma. No significant correlations were detected between DAX-1 immunoreactivity and amounts of aromatase mRNA. There was a statistically significant positive correlation between DAX-1 and ERα ( P = 0.006) and ERβ LI ( P < 0.001). These findings suggest that DAX-1 may inhibit the proliferation and progression of endometrial carcinoma through inhibition of estrogenic actions, possibly by interacting with ER present in carcinoma cells, rather than regulating in situ steroidogenesis. ( Cancer Sci 2005; 96: 645 – 652) [ABSTRACT FROM AUTHOR]

From gamete to neonate, human fertilization is a series of cell motilities (motion and morphological changes). Cytoskeletons play a role in cell motility as they work as a field worker in the cell. The present study is a review of dynamic motility of cytoskeletons (microfilaments and microtubules) during mammalian gamategenesis and fertilization. Dynamic and proper organization of cytoskeletons is crucial for the completion of oocyte maturation and spermatogenesis. By intracytoplasmic sperm injection, some difficulties in fertilization by sperm entry into the egg cytoplasm are overcome. However, the goal of fertilization is the union of the male and female genome, and sperm incorporation into an oocyte is nothing but the beginning of fertilization. Sperm centrosomal function, which introduces microtubule organization and promotes pronuclear apposition and first mitotic spindle formation, plays the leading role in the ‘motility’ of post-intracytoplasmic sperm injection events in fertilization. The present review introduces novel challenges in functional assessment of the human sperm centrosome. Furthermore, microtubule organization during development without the sperm centrosome (e.g. parthenogenesis) is mentioned. (Reprod Med Biol 2005; 4: 179–187) [ABSTRACT FROM AUTHOR]

Hysteroscopic myomectomy is regarded as the best treatment for patients with submucous myomata. However, this procedure has a number of associated complications, including uterine perforation, cervical laceration, hyponatremia and hemorrhage, especially in cases of sessile submucous myomata. To avoid these problems, it is important to make well-advised preparations and manipulations both pre- and intraoperatively. The main surgical considerations for safe hysteroscopic myomectomy are shortening the operating time and avoiding cutting too deeply into the myometrium. With these requirements in mind, a combination of techniques using vaporization and a powerful oxytocic agent, such as prostaglandin F-2α, appears to be the safest method of carrying out hysteroresectoscopy for unpedunculated sessile submucous myomata. [ABSTRACT FROM AUTHOR]

In most mammalian fertilization, the sperm introduces the centrosome, which acts as a microtubule organizing center (MTOC) and is essential for pronuclear movement. In rabbit fertilization, biparental centrosomal contribution in microtubule organization has been suggested.To reveal the function and inheritance of the centrosome during rabbit fertilization, we compared microtubule organization and early embryonal development following intracytoplasmic sperm injection (ICSI) with and without sperm centrosome. Sperm centrosome was removed by sonication, and the isolated sperm head was injected by a Piezo-driven micromanipulator. Samples were studied by light microscope after immunocytological stain.The sperm aster formation was observed 2–3 h after ICSI with intact sperm. In contrast, microtubules were organized between the male and female pronucleus without a nucleation site in the eggs after ICSI with an isolated sperm head. In the late pronuclear stage following ICSI with an isolated sperm head, microtubule organization was the same as in late pronuclear stage eggs after intact sperm injection. The first mitotic spindle was organized in eggs following ICSI with an isolated sperm head, as observed in eggs following ICSI with an intact sperm.These results indicate that the MTOC is in oocyte cytoplasm during fertilization and fulfils the function when the sperm centrosome is absent. (Reprod Med Biol 2005;4: 169–178) [ABSTRACT FROM AUTHOR]

Terada Y, Nakamura S, Morita J, Tachibana M, Morito Y, Ito K, Murakami T, Yaegashi N, Okamura K. Use of mammalian eggs for assessment of human sperm function: molecular and cellular analyses of fertilization by intracytoplasmic sperm injection. AJRI 2004; 51:290–293 © Blackwell Munksgaard, 2004 Intracytoplasmic sperm injection (ICSI ) has been described as the ‘cure’ for male sterility because a single sperm can now be directly introduced into an egg with some chance of pregnancy. While ICSI has revolutionized the practice of assisted reproductive techniques (ART), there are few molecular and cellular studies about its safety and efficacy. Even by using ICSI, fertilization in humans succeeds only if the sperm effectively accomplishes a number of tasks including ‘post-ICSI events’ in fertilization. To assess the function of human sperm after ICSI, we used heterologous ICSI with human sperm into animal eggs. Egg activation, sperm decondensation and sperm centorosomal function were examined in sperm from fertile men and infertile patients. Sperm from fertile men and infertile patients were injected into hamster, rabbit and bovine eggs by Piezo micromanipulator, and studied in decondensation of sperm nuclei, egg activation and microtubule organization. Decondensation human sperm head following ICSI into hamster eggs occurred initially form basal lesion, and apical portion of sperm nuclei which is surrounded by acrosome and perinuclear theca, still condensed in early pronuclear stage. Radial array of microtubules from sperm centrosome ‘sperm aster’ which is essential for pronuclear movement was observed in 30% rabbit eggs following ICSI with human sperm. By heterologous ICSI system with fertile human sperm and bovine eggs, 83.3% of eggs was activated and 60% eggs had sperm aster, indicating that bovine Piezo ICSI system is appropriate for assessing human sperm oocyte activation ability and human sperm centrosomal function. Oocyte activation and sperm centrosomal function were significantly low in sperm from men with globozoospermia and men with dysplasia of fibrous sheath. These assays indicate differences of the process of fertilization between in vitro fertilization and ICSI, and reflect the human sperm function especially for the ‘post-ICSI events’ in fertilization. More molecular and cellular analyses in fertilization by ICSI are needed for improvement of ART. [ABSTRACT FROM AUTHOR]

Noda T, Murakami T, Terada Y, Yaegashi N, Okamura K. Increased production of tumor necrosis factor-α by peritoneal fluid mononuclear cells induced by 60-kDa heat shock protein in women with minimal to mild endometriosis. AJRI 2003; 50:427–432 © Blackwell Munksgaard 2003 We sought to examine the role of Hsp60, a 60-kDa stress-responsive protein (hsp60) with potent immunostimulatory properties, in the pathophysiology of endometriosis. We investigated the response of peritoneal fluid mononuclear cells (PFMCs) to hsp60 to identify differences in PFMCs between women with and without endometriosis. PFMCs from women with or without endometriosis were incubated with hsp60 in vitro. The release of tumor necrosis factor (TNF)- α was measured by enzyme-linked immunosorbent assay (ELISA). The rapid secretion of TNF- α was observed following the exposure of PFMCs to hsp60. PFMCs from women with minimal to mild endometriosis produced greater amounts of TNF- α in response to hsp60 stimulation than levels seen in cells from women without endometriosis. Hsp60 may play a role in the activation of peritoneal immunity in patients with minimal to mild endometriosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Umbilical cord blood (CB) is being used as a source of alternative HPCs for transplantation with increasing frequency. The goal of CB banks for unrelated transplantation is to provide good quality-controlled CB units that can be transplanted for HPCs into the largest possible number of patients. STUDY DESIGN AND METHODS: Large CB samples in freezing bags wrapped with insulators and small samples in cryotubes placed into double styrene-foam boxes were cryopreserved at -85°C without a rate-controlled freezing machine, followed by storage in the liquid phase of nitrogen. After thawing these cells, the viability and recovery of cells, as well as the recovery rate of HPCs such as CD34+ cells, CFU-GM, and total CFU were evaluated. RESULTS: Measurement of the freezing rate in CB bags and cryotubes demonstrated that this simple method for cryopreservation of CB cells provided optimal conditions for both large-scale and small-scale cryopreservation. Recovery of CB progenitor cells after cryopreservation was also shown to be potentially acceptable when evaluated with CD34+ cells, CFU-GM, and total CFU. These results were comparable to the method using a rate-controlled programmed freezer. CONCLUSIONS: A simple method for cryopreservation of CB cells without a rate-controlled programmed freezer could provide a sufficient-enough potential for the transplantability of HPCs after thawing. [ABSTRACT FROM AUTHOR]

Summary objective In situ metabolism and synthesis of oestrogens are considered to play important roles in the pathogenesis and development of human endometrial endometrioid adenocarcinoma. Approximately 3–5% of patients with these neoplasms are under age 40, some of whom have been treated with progestogen alone as a primary therapy for both atypical endometrial hyperplasia and adenocarcinoma in order to preserve their fertility. Medroxyprogesterone acetate (MPA) has been used extensively in the treatment of both breast and endometrial disorders as an endocrine therapy. However, details of the alterations of in situ oestrogen metabolism following progestogen treatment have yet to be fully elucidated. design, patients and measurements In this study we examined the immunolocalization of 17β-hydroxysteroid dehydrogenase (17β-HSD) types 1 and 2, oestrogen receptor (ER), progesterone receptor (PR)A + PRB, PRB, and Ki67 in progestogen-treated endometrial endometrioid adenocarcinoma (16 cases). We compared our findings both prior to and following treatment. These findings were then correlated with the treatment outcome of individual patients in order to elucidate factors associated with the response to treatment. results 17β-HSD type 2 immunoreactivity was detected in 8/16 cases examined, whereas 17β-HSD type 1 immunoreactivity was undetected in all cases examined. 17β-HSD type 2 positive immunostaining, PRA + PRB labelling index (LI), and PRB/PRA + PRB ratio were all significantly higher in cases responding to the treatment than in those not responding. There were no significant correlations between responsive and nonresponsive cases for positive 17β-HSD type 1 immunostaining, Ki67 LI, ER LI and age. There were no significant differences in the positive immunostaining for 17β-HSD types 1 and 2, Ki67 LI, ER LI, PRA + PRB LI, age and PRB/PRA + PRB ratio between specimens taken prior to and following progestogen treatment.... [ABSTRACT FROM AUTHOR]

The article invites all members of the Asia-Oceania Federation of Obstetrics and Gynecology (AOFOG) to participate in the 60th Annual Congress of the Japan Society of Obstetrics and Gynecology (JSOG) to held on April 12-15, 2008, in Yokohama, Japan. It is stated that during the 2008 Congress, the JSOG would schedule an "International Session" that allow foreign participants to present various topics in English, facilitating international exchange.

The author reflects on the development of the Japan Society of Obstetrics and Gynecology (JSOG). He said that the organization has been successful in its annual congress which was participated by about 4,500 members including foreign researchers. The author emphasized that the JSOG will continue to enhance the skills of obstetrician and gynecologist by providing more sessions in the succeeding year.

Renal tubular dysgenesis (RTD) is a developmental abnormality of the renal proximal tubules found in patients with Potter syndrome. We report a female newborn with RTD who has survived for more than 18 months. Infusions of fresh frozen plasma (FFP) in the early neonatal period were effective in raising and maintaining her blood pressure. Peritoneal dialysis was required until the appearance of spontaneous urination at 29 days after birth. Histopathological examinations of the kidney revealed dilated renal tubular lumina and foamy columnar epithelial cells in the renal tubules. Endocrinological studies showed a discrepancy between low plasma renin activity (<0.1 ng/ml/hr) and high active renin concentration (135,000 pg/ml), suggesting an aberration in the renin substrate, angiotensinogen. Direct sequencing analysis revealed two novel mutations in the coding region of the angiotensinogen gene (AGT): a nonsense mutation in exon 2 (c.604C > T) and a frameshift deletion at nucleotide 1290 in exon 5 (c.1290delT). The mutations were in the compound heterozygous state, because each parent had each mutation. These findings suggest that angiotensinogen deficiency is one of the causes of RTD. A treatment of the condition with FFP may help to promote long survival.

To determine the relationship between premature ovarian failure (POF) and skewed X-chromosome inactivation (XCI), karyotype, and XCI status in 43 patients with POF (group I) and 43 age-matched control women with regular menstrual cycles (group II) were evaluated. Evaluation of XCI status was based on the CAG triplet repeat polymorphism assay in the androgen receptor gene after sodium bisulfite treatment of DNA samples, and XCI patterns were classified as random (XCI < 70% skewing) or skewed (> or =70%). Furthermore, skewed XCI was classified under three different thresholds (> or =70, > or =80, or > or =90%). Karyotyping by G-banding and fluorescence in situ hybridization (FISH) on peripheral blood lymphocytes showed that one patient in group I had a deletion of Xq22, and another was 47,XXX. The frequency of low-level 45,X/46,XX mosaicism was nearly equal in both groups. In women without any X-chromosomal aberrations, the incidence of skewed XCI in group I was significantly higher than in group II on all threshold levels. Furthermore, extremely skewed XCI (> or =90%) was observed only in group I. These results indicate that POF may be caused by some underlying genetic disorders, which may induce skewed XCI.