Masataka Furuya

Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids

BACKGROUND The relationship between fibroids and infertility remains an unsolved question, and management of intramural fibroids is controversial. During the implantation phase, uterine peristalsis is dramatically reduced, which is thought to facilitate embryo implantation. Our aims were to evaluate (i) the occurrence and frequency of uterine peristalsis in infertile women with intramural fibroids and (ii) whether the presence of uterine peristalsis decreases the pregnancy rate. METHODS Ninety-five infertile patients with uterine fibroids were examined using magnetic resonance imaging (MRI). Inclusion criteria were as follows: (i) presence of intramural fibroids, excluding submucosal type; (ii) no other significant infertility factors (excluding endometriosis); and (iii) regular menstrual cycles, and MRI performed at the time of implantation (luteal phase day 5-9). The frequency of junctional zone movement was evaluated using cine-mode-display MRI. After MRI, patients underwent infertility treatment for up to 4 months, and the pregnancy rate was evaluated prospectively. RESULTS Fifty-one patients fulfilled the inclusion criteria, and 29 (57%) and 22 (43%) patients were assigned to the low (0 or 1 time/3 min) or high frequency (≥ 2 times/3 min) uterine peristalsis group, respectively. Endometriosis incidence was the same in both groups. Ten out of the 29 patients (34%) in the low-frequency group achieved pregnancy, compared with none of the 22 patients (0%) in the high-frequency group (P< 0.005). Comparing pregnant and non-pregnant cases, 4 of 10 patients (40%) and 9 of 41 patients (22%), respectively, had endometriosis (not significant). CONCLUSIONS A higher frequency of uterine peristalsis during the mid-luteal phase might be one of the causes of infertility associated with intramural-type fibroids.

Genetically Manipulated Human Embryonic Stem Cell‐Derived Dendritic Cells with Immune Regulatory Function

Genetically manipulated dendritic cells (DC) are considered to be a promising means for antigen‐specific immune therapy. This study reports the generation, characterization, and genetic modification of DC derived from human embryonic stem (ES) cells. The human ES cell‐derived DC (ES‐DC) expressed surface molecules typically expressed by DC and had the capacities to stimulate allogeneic T lymphocytes and to process and present protein antigen in the context of histocompatibility leukocyte antigen (HLA) class II molecule. Genetic modification of human ES‐DC can be accomplished without the use of viral vectors, by the introduction of expression vector plasmids into undifferentiated ES cells by electroporation and subsequent induction of differentiation of the transfectant ES cell clones to ES‐DC. ES‐DC introduced with invariant chain‐based antigen‐presenting vectors by this procedure stimulated HLA‐DR‐restricted antigen‐specific T cells in the absence of exogenous antigen. Forced expression of programmed death‐1‐ligand‐1 in ES‐DC resulted in the reduction of the proliferative response of allogeneic T cells cocultured with the ES‐DC. Generation and genetic modification of ES‐DC from nonhuman primate (cynomolgus monkey) ES cells was also achieved by the currently established method. ES‐DC technology is therefore considered to be a novel means for immune therapy.

Pseudoaneurysm of the uterine artery after laparoscopic myomectomy

OBJECTIVE To describe a case of uterine pseudoaneurysm after laparoscopic myomectomy in a 36-year-old woman. DESIGN Case report. SETTING University hospital. PATIENT(S) A 36-year-old woman, 3 months after laparoscopic myomectomy, presenting with an intrauterine hypoechoic lesion measuring 5 cm in diameter. INTERVENTION(S) Uterine pseudoaneurysm was diagnosed by color Doppler ultrasound. MAIN OUTCOME MEASURE(S) Complete resolution of the pseudoaneurysm. RESULT(S) Spontaneous thrombosis was observed in the pseudoaneurysm. At 6-month follow-up, the uterus appeared normal. CONCLUSION(S) Our case presents the possibility of delayed occurrence of uterine pseudoaneurysm after laparoscopic myomectomy.

Expression of Ovary-Specific Acidic Protein in Steroidogenic Tissues: A Possible Role in Steroidogenesis

Ovary-specific acidic protein (OSAP) is a novel molecule discovered from a genomic project designed to identify ovary-selective genes in mice. Whereas public databases suggest extraovarian expression of OSAP, its tissue distribution has not yet been well documented. Thus, the expression profile of mouse and human OSAP was determined by quantitative real-time RT-PCR using RNAs isolated from various tissues. The results demonstrate that the human and mouse OSAP expression profiles are similar; OSAP is prominently expressed in steroidogenic tissues with the highest level of expression observed in the adrenal gland. Placenta served as an exception and possessed minimal level of OSAP mRNA. Immunohistochemical studies show that mouse OSAP localizes almost exclusively to the steroid-producing cells of the ovary, adrenal gland, and testis. Consistent with predictions made by several subcellular localization algorithms, dual labeling studies in Y-1 mouse adrenocortical cells indicate OSAP resides in the mitochondria. Because of its abundant expression in steroidogenic cells and mitochondrial localization, a role for OSAP in steroidogenesis was determined. OSAP silencing by specific small interfering RNAs significantly inhibits 8-bromoadenosine-cAMP-induced progesterone production in Y-1 cells. Reduction in OSAP levels results in mitochondrial fragmentation and a decrease in the cellular content of mitochondrial DNA, indicative of decreased mitochondrial abundance. Lastly, 8-bromoadenosine-cAMP does not regulate OSAP protein expression in Y-1 cells as is the case for other steroidogenic components known to be induced by cAMP. Collectively these results suggest that OSAP is involved in steroidogenesis, potentially through its ability to maintain mitochondrial abundance and morphology.

Prenatal diagnosis of long QT syndrome by non‐invasive fetal electrocardiography

Long QT syndrome is a high‐risk condition associated with arrhythmia due to its sudden cause of death. Prenatal diagnosis of long QT syndrome, however, is impossible using the fetal echocardiogram. Here we present the first reported case of long QT syndrome in which a prenatal diagnosis was made using non‐invasive fetal electrocardiogram. We consider that the non‐invasive fetal electrocardiogram may be a good method for diagnosing fetal QT prolongation.

The Periphery of the Human Fetal Adrenal Gland Is a Site of Angiogenesis: Zonal Differential Expression and Regulation of Angiogenic Factors

CONTEXT Although the inner fetal zone (FZ) of the mid-gestation human fetal adrenal (HFA) produces dehydroepiandrosterone sulfate, the function of the outer definitive zone (DZ) remains less clear. We have proposed that the DZ phenotype is that of a pool of progenitor cells, many of which are mitotically active. Recently, we studied HFA expression of a family of vascular endothelial cell-specific angiogenic factors, the angiopoietins (Angs), and demonstrated that Ang2 was localized predominantly in the periphery of the gland. Ang1 stabilizes, whereas Ang2 destabilizes, vessels, increasing responsiveness to angiogenic stimuli such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF)-2. OBJECTIVE Our objective was to test the hypothesis that the periphery of the HFA is a site of angiogenesis. DESIGN Studies were conducted involving RNA, frozen sections, and primary cell cultures from midgestation HFAs. MAIN OUTCOME MEASURES Immunofluorescence, laser capture microdissection, and real-time quantitative RT-PCR were used. RESULTS Double immunostaining demonstrated that proliferating endothelial cells were limited to the DZ and DZ/FZ border. Ang2 mRNA was primarily expressed in the DZ, whereas Ang1 mRNA was primarily in the FZ. VEGF-A and FGF-2 mRNA levels were higher in the DZ. FGF-2 (10 ng/ml) induced Ang2 mRNA by 4-fold in both zones of cells (P < 0.01, at 24 h), but not Ang1 or VEGF-A mRNA. CONCLUSION Data suggest that angiogenesis occurs at the periphery of the HFA. The DZ-predominant expression of Ang2 may be explained, in part, by the parallel pattern of FGF-2 expression.

Association between patient age at the time of surgical treatment for endometriosis and aryl hydrocarbon receptor repressor polymorphism.

A cross-sectional comparative study among women who underwent surgical treatment for endometriosis revealed that frequency of the Ala/Ala genotype at aryl hydrocarbon receptor repressor (AHRR) Pro185Ala polymorphism was three times higher (27.6% vs. 9.9%) in the younger group (<or=30 years) than in the older group (>30 years). AHHR genotyping may help to identify a subpopulation of women who are susceptible to the earlier onset of endometriosis.

ZEB1 expression is a potential indicator of invasive endometriosis

Although endometriosis is a benign disease, it shares some features with cancers, such as invasiveness and the potential to metastasize. This study sought to investigate the epithelial‐mesenchymal transition status in human endometriotic lesions.

Peritoneal pregnancy with massive hemoperitoneum in early gestation: two case reports

Peritoneal pregnancy may cause severe abdominal bleeding without genital bleeding as early as the fifth week of gestation. Awareness that pregnancy can exist in unusual locations is imperative.

Oocyte-specific linker histone

Eukaryotic DNA is assembled into chromatin primarily through interaction with small basic proteins described as histones. There are two types of histone: the core histone (Ha H2B, H3 and H4) and the linker histone such as H1. Two molecules of each of the core histones form an octamer, around which is wrapped 146bp of DNA. The DNA that is in between nucleosome core particles is called linker DNA that is bound by the linker histones. To date, eight subtypes of H1 have been identified in mammals. Six of these are collectively termed the somatic subtypes and are designated Hla, Hlb, Hlc, Hld, Hle, and Hl(0). The seventh subtype is Hlt, which is expressed only in spermatocytes. We discovered a mammalian oocytespecific linker histone, Hlfoo, which is homologous to Xenopus oocyte-specific linker histone B4”. A shift in the expression of linker histone subtype expression appears to be a great feature of early embryonic development. There are several examples of the association of a specific linker histone H1 expression with particular transitions during development. In sea urchin, there are at least six different H1 subtypes. A cleavage stage H1 (cs-Hl). constitutes the major form of linker histone during the rapid cellular divisions after fertilization. The several hundreds copies of the alpha subtype are then expressed in early embryogenesis and this expression