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OBJECTIVES: Mesenchymal stem cells are expected to be an ideal cell source for cellular and gene therapy. We previously showed that cells derived from the human placenta can be induced to differentiate into myotubes in vitro and to express dystrophin in mdx/scid mice in vivo. In this study, we examined whether amnion-derived cells can be efficiently transduced and differentiated using lentiviral vectors carrying human MYOD1. METHODS: The amnion-derived cells were isolated from human preterm placentas. They were transduced with the MYOD1 vector, and mRNA levels for MYOD1, MYF5, MYOG, MYH2 and DMD were determined by quantitative-reverse transcriptase-polymerase chain reaction, and also examined immunocytochemically. RESULTS: Approximately 70% of amnion-derived cells were efficiently transduced by the lentiviral vectors. MYOD1 activates MYF5 and MYOG, MYH2 and DMD after a 7-day culture. The concerted upregulations of these myogenic regulatory factors enhanced MYH2 and DMD expressions. PAX7 was below the detectable level. Both myosin heavy chain and dystrophin were demonstrated by immunocytochemistry. CONCLUSIONS: MYOD1 activates MYF5 and MYOG, the transcription factor genes essential for myogenic differentiation, and the concerted upregulation of these myogenic regulatory factors enhanced MYH2 and DMD expressions. The amniotic membrane is an immune-privileged tissue, making MYOD1-transduced amnion-derived cells an ideal cell source for cellular and gene therapy for muscle disorders. This is the first report showing that amnion-derived cells can be modified by exogenous genes using lentiviral vectors. Furthermore, MYOD1-transduced amnion-derived cells are capable of the dystrophin expression necessary for myogenic differentiation.

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We report a case of osteogenesis imperfecta (OI) (OMIM166210) type II, in which a prenatal diagnosis was made by three-dimensional computed tomography (3D-CT). Subsequent molecular analysis revealed a recurrent, heterozygous mutation in COL1A2. Fetal CT is a powerful tool for visualizing the fetal skeleton and can provide a definitive diagnosis of fetal skeletal dysplasias; however, whether or not its employment for prenatal diagnosis is warranted in terms of fetal radiation risks remains controversial, both medically and ethically. Based on our experience, we review the current state of fetal CT for the diagnosis of skeletal dysplasias, with a discussion of the relevant literature.

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Ritodrine hydrochloride has been widely used for tocolysis, although serious side-effects have been reported. We report two cases of agranulocytosis induced by ritodrine hydrochloride, which probably occurred by different mechanisms. Two patients were hospitalized because of preterm labor and were given intravenous ritodrine hydrochloride. The nadir of neutrocytes was 199/mm(3) and 13/mm(3) in the two cases, respectively. The total dose of ritodrine hydrochloride was calculated to be 7800 mg for 26 days and 2500 mg for 22 days, respectively. The total doses were heavier and administration duration was longer in Case 1, which suggested a toxic mechanism of agranulocytosis, while in Case 2, they were smaller and shorter, suggesting an immunological mechanism. For patients receiving ritodrine hydrochloride, the white blood cell count should be checked frequently regardless of the duration of therapy and a drug lymphocyte stimulation test should be performed.

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AIMS: The aim of this study was to examine the factors that influence soluble endothelial selectin (sE-selectin) levels in umbilical cord serum. MATERIALS AND METHODS: sE-selectin levels in umbilical cord serum were measured in 144 patients using enzyme-linked immunosorbent assay. We examined the association of sE-selectin levels with gestational age, pre-eclampsia (PE), histological chorioamnionitis (HCAM), preterm premature rupture of membranes, magnesium sulfate use, birthweight, and placental weight. RESULTS: A significant positive correlation was observed between sE-selectin levels and gestational age in the patients who had neither PE nor HCAM (r = 0.559, P < 0.0001). This statistically positive correlation persisted in patients with PE without HCAM (n = 25, r = 0.644, P < 0.001), but not in patients with HCAM without PE (n = 58, r = 0.102, P = 0.448). In matched gestational age analysis, sE-selectin levels were increased in the presence of HCAM (P = 0.0006), but were not influenced by the presence of PE (P = 0.127), preterm premature rupture of membranes (P = 0.352) or magnesium sulfate use (P = 0.337). CONCLUSION: sE-selectin levels in umbilical cord serum were positively correlated with gestational weeks. sE-selectin levels in umbilical cord serum were higher in mothers with HCAM but not with PE, when compared with gestational-age-matched controls.

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AIM: To clarify the effect of maternal age on obstetrical complications through a cohort and case-cohort study. METHODS: We studied 242 715 births at 125 centers of a perinatal network in Japan from 2001 through 2005 as a base cohort. Women with single pregnancies who delivered after 22 weeks of gestation were included in the study. Six classes of maternal age were selected: <20; 20-24; 25-29; 30-34; 35-39; and ≥40 years. The cohort study was used to investigate whether age is related to obstetrical complications. By random selection 3749 births were determined as a subcohort. Risk ratio (RR) was determined using multivariate analysis in the case-cohort study. RESULTS: The incidence proportion (per 100 births) of pregnancy-induced hypertension, cervical insufficiency, placenta previa, and placental abruption increased with age, whereas the incidence proportion of preterm labor and chorioamnionitis were higher at younger maternal age. The RR of women in the age groups 35-39 years and ≥40 years (with the reference of 1.0 for women in the age group of 20-34 years) were determined: pregnancy-induced hypertension, 1.66, 2.55; placenta previa, 1.76, 2.19; and placental abruption, 1.18, 1.5. The RR of preterm labor for women in the age group of <20 years was 1.78. CONCLUSION: The effect of maternal age differs for each obstetrical complication, and thus, it is important to understand these differences for management of individual pregnant patients.

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We report a case of acute portal vein thrombosis (PVT) after a cesarean delivery. The patient was admitted for treatment of severe pre-eclampsia. On the second day after cesarean delivery, the elevations of aspartic aminotransferase and alanine aminotransferase were observed. Thereafter, acute PVT was diagnosed with ultrasonography. Although early anticoagulant therapy seems to be effective in the treatment of acute PVT, close observation must be made due to the risk of bleeding.

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AIM: A case-cohort study was performed to clarify and compare the risk factors for placental abruption and placenta previa. MATERIAL & METHODS: This study reviewed 242,715 births at 125 centers of the perinatal network in Japan from 2001 through to 2005 as a base-cohort. Women with singleton pregnancies delivered after 22 weeks of gestation were included. The evaluation determined the risk factors for placental abruption and placenta previa. Five thousand and thirty-six births (2.1%) were determined as the subcohort by random selection. Acute-inflammation-associated clinical conditions (premature rupture of membranes and clinical chorioamnionitis) and chronic processes associated with vascular dysfunction or chronic inflammation (chronic and pregnancy-induced hypertension, pre-existing or gestational diabetes and maternal smoking) was examined between the two groups. RESULTS: Placental abruption and placenta previa were recorded in 10.1 per 1000 and 13.9 per 1000 singleton births. Risk factors for abruption and previa, respectively, included maternal age over 35 years (adjusted risk ratios [RRs]=1.20 and 1.78), IVF-ET (RRs = 1.38 and 2.94), preterm labor (RRs = 1.63 and 3.09). Smoking (RRs = 1.37), hypertension (RRs = 2.48), and pregnancy-induced hypertension (RR = 4.45) were risk factors for abruption but not for previa. On the other hand, multiparity (RR= 1.18) was a risk factor for previa but not for abruption. The rates of acute-inflammation-associated conditions and chronic processes were higher among women with abruption than with previa. (RR 2.0 and 4.08, respectively). CONCLUSION: The case-cohort study technique elucidated the difference in the risk factors for placental abruption and placenta previa.

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BACKGROUND: The adverse effects of maternal smoking on the health of pregnant women have been examined mostly on a disease-by-disease basis. The aims of this study were to evaluate simultaneously the effects of smoking during pregnancy on various obstetric complications, using data from a large medical database, and to investigate the expediency of using a case-cohort design for such an analysis. METHODS: A case-cohort study was conducted within the Japan Perinatal Registry Network database. Perinatal information on infant deliveries was entered into the database at 125 medical centers in Japan. The base population of the study was 180 855 pregnant women registered in the database from 2001 through 2005. The outcome measures were the incidences of 11 different obstetric complications. Logistic regression models were used to estimate age-adjusted risk ratios (aRRs) and relative excess incidence proportions (REIs). RESULTS: The overall prevalence of smoking during pregnancy was 5.8% in the base cohort, and the prevalence was higher among younger women. A comparison of the cases and control cohort showed that smokers during pregnancy had statistically significant higher risks for preterm rupture of the membrane (aRR: 1.67, 95% confidence interval [CI]: 1.43-1.96; REI: 40.2%, 95% CI: 29.9%-49.1%), chorioamnionitis (1.65, 1.36-2.00; 39.4%, 26.4%-50.0%), incompetent cervix (1.63, 1.35-1.96; 38.5%, 25.8%-49.1%), threatened premature delivery (1.38, 1.17-1.64; 27.7%, 14.5%-38.9%), placental abruption (1.37, 1.10-1.72; 27.1%, 8.8%-41.7%), and pregnancy-induced hypertension (1.20, 1.01-1.41; 16.4%, 1.2%-29.3%). CONCLUSIONS: Maternal smoking was associated with a number of obstetric complications. This highlights the importance of smoking cessation during pregnancy. In addition, case-cohort analysis proved useful in estimating RRs for multiple outcomes in a large database.

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Duchenne muscular dystrophy is an X-linked recessive genetic disease characterized by severe skeletal muscular degeneration. The placenta is considered to be a promising candidate cell source for cellular therapeutics because it contains a large number of cells and heterogenous cell populations with myogenic potentials. We analyzed the myogenic potential of cells obtained from six parts of the placenta, that is, umbilical cord, amniotic epithelium, amniotic mesoderm, chorionic plate, villous chorion, and decidua basalis. In vitro cells derived from amniotic mesoderm, chorionic plate, and villous chorion efficiently transdifferentiate into myotubes. In addition, in vivo implantation of placenta-derived cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of human dystrophin. Differential contribution to myogenesis in this study may be attributed to placental portion-dependent default cell state. Molecular taxonomic characterization of placenta-derived maternal and fetal cells in vitro will help determine the feasibility of cell-based therapy.

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