Yushi Akashi

Expression patterns of claudin family of tight-junction proteins in the mouse prostate

Claudins are the transmembrane proteins forming the backbone of tight junctions, and consist of over 20 members of a gene family. Claudins are expressed in a tissue- and cell-type specific fashion, and changes in their abundance and/or distribution are proposed to play important roles in the pathophysiology of numerous disorders. In the prostate, claudin-1, -3, -4 and -7 transcripts are known to be expressed, but it is unknown regarding mRNA expression of other claudins or concerning expression and localization of claudin proteins in this organ. We herein show, by RT-PCR and Western blotting analyses, that not only these four claudins but also claudin-5, -8 and -10 are expressed in the normal mouse prostate. Claudin-3, -4, -5, -8 and -10 were primarily localized at the apicalmost sites of lateral membranes of luminal epithelial cells in the prostate gland, whereas claudin-1 and -7 were distributed along the basolateral membranes of the epithelium. These findings provide basic information for elucidating the significance of claudins in prostate diseases, including prostate cancers.

The tight-junction protein claudin-6 induces epithelial differentiation from mouse F9 and embryonic stem cells.

During epithelialization, cell adhesions and polarity must be established to maintain tissue assemblies and separate the biological compartments in the body. However, the molecular basis of epithelial morphogenesis, in particular, a role of cell adhesion molecules in epithelial differentiation from stem cells, remains unclear. Here, we show that the stable and conditional expression of a tight-junction protein, claudin-6 (Cldn6), triggers epithelial morphogenesis in mouse F9 stem cells. We also demonstrate that Cldn6 induces the expression of other tight-junction and microvillus molecules including Cldn7, occludin, ZO-1α+, and ezrin/radixin/moesin-binding phosphoprotein50. These events were inhibited by attenuation of Cldn6 using RNA interference or the C-terminal half of Clostridium Perfringens enterotoxin. Furthermore, similar results were obtained in mouse embryonic stem cells. Thus, we have uncovered that the Cldn6 functions as a novel cue to induce epithelial differentiation.

A case of congenital toxoplasmosis whose mother demonstrated serum low IgG avidity and positive tests for multiplex‐nested PCR in the amniotic fluid

We encountered a woman whose infant developed congenital toxoplasmosis. Serum Toxoplasma gondii antibody titers (320×) at 12 weeks of gestation increased to 5120× at 25 weeks. Toxoplasma immunoglobulin M was 2.8 index, and immunoglobulin G avidity index was 23%. Cyclic administration of acetylspiramycin was maintained from 22 weeks until delivery. Multiplex‐nested polymerase chain reaction of maternal blood and amniotic fluid at 28 weeks both tested positive for Toxoplasma DNA. A male neonate weighing 2916 g was born at 38 weeks via cesarean section. No abnormalities were detected by physical and funduscopic examinations, whereas a head computed tomography of the neonate revealed three independent intracranial calcifications. The infant underwent therapy with pyrimethamine and sulfadiazine for one year. Serum titers of Toxoplasma gondii antibodies were all less than cut‐off values between 5 and 12 months after birth, but all increased up to positive levels 18 months after birth.

Successful delivery after transabdominal cerclage of uterine cervix for cervical incompetence after radical trachelectomy

Pregnancy after radical trachelectomy (RT) has a high risk of prematurity and complications such as preterm premature rupture of the membrane and chorioamnionitis. Placing a cervical cerclage at the time of RT plays an important role in preventing such obstetrical complications. In patients who have trouble with the cervical cerclage, miscarriage during the second trimester seems to be inevitable. We have therefore started preconception transabdominal cerclage (TAC) for these patients. A 36‐year‐old Japanese woman who had a history of miscarriage due to trouble with the nylon thread used for cerclage, successfully delivered after TAC. TAC is a useful treatment modality to prevent miscarriage for patients who have trouble with cerclage after RT.

Preservation of fertility and subsequent childbirth after methotrexate treatment of placenta percreta: a case report

IntroductionPlacenta percreta is associated with maternal morbidity and mortality. A hysterectomy is often needed to control the bleeding in such cases. However, it has been advocated that placenta percreta be managed conservatively to avoid massive pelvic bleeding and to preserve the patient’s fertility. Here, we present a case of placenta percreta diagnosed by magnetic resonance imaging, and treated with systemic administration of methotrexate.Case presentationA 27-year-old nulliparous Japanese woman at 39 gestational weeks had an uncomplicated vaginal delivery of a 3244-g infant. However, her placenta was not delivered, and we could not remove it manually. Contrast-enhanced magnetic resonance imaging indicated deep myometrial invasion by placental tissue and the whole placenta was strongly enhanced. Seven days post-partum, her serum human chorionic gonadotropin level was 12,656IU/L. Our patient hoped to preserve her uterus for a future pregnancy. She therefore received 13 courses of methotrexate (50mg/week, intravenous injection). Her serum human chorionic gonadotropin level was undetectable 97 days after the first methotrexate injection. At 117 days post-partum, she had a labor-like pain every three minutes and delivered the placenta. Our patient regained normal menses and at follow-up remained in good health. Two years later, she delivered a healthy daughter.ConclusionWe should try to detect placenta percreta in high-risk patients by any means. For low-risk patients, we should give a diagnosis swiftly and control any intrauterine infection and massive bleeding.

A myotonic dystrophy 1 patient complicated with placental adherence after miscarriage of one dichorionic diamniotic twin following her tenth in vitro fertilization and embryo transfer

Placental adherence is one of the most common causes of emergency hysterectomy to save the mother’s life. Risk factors for placental adherence reportedly include a prior caesarean section, other previous uterine surgery, maternal age and multiparity. Recently, in vitro fertilization (IVF) pregnancy was also reported to be a risk factor [1]. Unfortunately, it appears likely that patients who seek help to have a baby are complicated with multiple risk factors. Physicians should be very careful when treating these patients. In the absence of serious symptoms, however, conservative therapy that preserves the patient’s fertility is preferable, so it has been proposed that conservative management should be attempted [2] unless the patient has massive bleeding [3] or signs of severe infection [4]. That said, there are few choices for conservative treatment. These include methotrexate (MTX) administration, uterine artery embolization (UAE) and uteruspreserving surgery [5, 6]. UAE is reported to be sometimes harmful to fertility [7], and it is usually difficult to continue MTX treatment when massive bleeding occurs during the therapy. As a backup treatment, uterus-preserving surgery [5] is thought to support the continuation of MTX treatment in these types of cases and should be tried if possible.