Lower systolic blood pressure levels in early pregnancy are associated with a decreased risk of early-onset superimposed preeclampsia in women with chronic hypertension: a multicenter retrospective study.

To clarify the impact of blood pressure (BP) management ranges on pregnancy outcomes, we conducted a multicenter retrospective analysis of 215 women with singleton pregnancies diagnosed with essential hypertension either before or within 14 weeks of gestation. Patients were classified according to systolic BP (sBP; <130, 130-139, 140-159, and ≥160 mmHg) or diastolic BP (dBP; <80, 80-89, 90-109, and ≥110 mmHg) at 8-11, 12-15, and 16-19 weeks of gestation. The risk of early-onset superimposed preeclampsia and small-for-gestational-age neonates was assessed in each BP group. Moreover, a subgroup analysis was performed in 144 eligible patients whose BP was measured at both 12-13 and 14-15 weeks of gestation. At 16-19 weeks of gestation, higher sBP significantly increased the incidence of early-onset superimposed preeclampsia (13.3%, 24.6%, 32.2% and 75.0%, respectively) and small-for-gestational-age neonates (6.0%, 13.1%, 16.9% and 50.0%, respectively). Multivariate logistic regression analyses showed that women with sBP < 130 mmHg at 16-19 weeks of gestation had a significantly lower risk of early-onset superimposed preeclampsia than women with sBP of 140-159 mmHg. Subgroup analyses also showed that even at 14-15 weeks of gestation, sBP < 130 mmHg was associated with a significantly lower risk of early-onset superimposed preeclampsia than an sBP of 140-159 mmHg. In conclusion, sBP < 130 mmHg within 14 weeks of gestation reduced the risk of developing early-onset superimposed preeclampsia in women with chronic hypertension.

Three-dimensional human placenta-like bud synthesized from induced pluripotent stem cells.

Placental dysfunction is related to the pathogenesis of preeclampsia and fetal growth restriction, but there is no effective treatment for it. Recently, various functional three-dimensional organs have been generated from human induced-pluripotent cells (iPSCs), and the transplantation of these iPSCs-derived organs has alleviated liver failure or diabetes mellitus in mouse models. Here we successfully generated a three-dimensional placental organ bud from human iPSCs. The iPSCs differentiated into various lineages of trophoblasts such as cytotrophoblast-like, syncytiotrophoblast-like, and extravillous trophoblast-like cells, forming organized layers in the bud. Placental buds were transplanted to the murine uterus, where 22% of the buds were successfully engrafted. These iPSC-derived placental organ buds could serve as a new model for the study of placental function and pathology.

CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations.

Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive distal limb weakness, ptosis, ophthalmoplegia, bulbar muscle weakness and rimmed vacuoles on muscle biopsy. Recently, CGG repeat expansions in the noncoding regions of two genes, LRP12 and GIPC1, have been reported to be causative for OPDM. Furthermore, neuronal intranuclear inclusion disease (NIID) has been recently reported to be caused by CGG repeat expansions in NOTCH2NLC. We aimed to identify and to clinicopathologically characterize patients with OPDM who have CGG repeat expansions in NOTCH2NLC (OPDM_NOTCH2NLC). Note that 211 patients from 201 families, who were clinically or clinicopathologically diagnosed with OPDM or oculopharyngeal muscular dystrophy, were screened for CGG expansions in NOTCH2NLC by repeat primed-PCR. Clinical information and muscle pathology slides of identified patients with OPDM_NOTCH2NLC were re-reviewed. Intra-myonuclear inclusions were evaluated using immunohistochemistry and electron microscopy (EM). Seven Japanese OPDM patients had CGG repeat expansions in NOTCH2NLC. All seven patients clinically demonstrated ptosis, ophthalmoplegia, dysarthria and muscle weakness; they myopathologically had intra-myonuclear inclusions stained with anti-poly-ubiquitinated proteins, anti-SUMO1 and anti-p62 antibodies, which were diagnostic of NIID (typically on skin biopsy), in addition to rimmed vacuoles. The sample for EM was available only from one patient, which demonstrated intranuclear inclusions of 12.6 ± 1.6 nm in diameter. We identified seven patients with OPDM_NOTCH2NLC. Our patients had various additional central and/or peripheral nervous system involvement, although all were clinicopathologically compatible; thus, they were diagnosed as having OPDM and expanding a phenotype of the neuromyodegenerative disease caused by CGG repeat expansions in NOTCH2NLC.

Placental Sonic Hedgehog Pathway Regulates Fetal Growth via the IGF Axis in Preeclampsia.

CONTEXT: Placental dysfunction is the underlying cause of common major disorders of pregnancy, such as fetal growth restriction and preeclampsia. However, the mechanisms of placental dysfunction are not entirely elucidated. We previously reported 10 reliable preeclampsia pathways based on multiple microarray data sets, among which was the sonic hedgehog (SHH) pathway. In this study, we describe the significant role of SHH signaling involved in placental development and fetal growth. DESIGN: The placental expression levels of surrogate markers of the SHH pathway, patched homolog 1 (PTCH1) and glioma-associated oncogene homolog (GLI) 2, were evaluated using quantitative real-time PCR, western blot analysis, and immunohistochemistry. We investigated the underlying mechanisms of the SHH pathway in trophoblast syncytialization, a critical process for placental development and maturation, using primary cytotrophoblasts. Moreover, the potential roles of placental SHH signaling in the regulation of the IGF axis were explored by pathway analysis of microarray data. Finally, the influence of SHH signaling on fetal growth was examined by placental administration of cyclopamine, an SHH pathway inhibitor, to pregnant mice. RESULTS: The SHH pathway was downregulated in preeclampsia placentas, and its activation was highly correlated with birth weight. Trophoblast syncytialization was modulated by noncanonical SHH-adenylate cyclase (ADCY) signaling rather than canonical SHH-GLI signaling. The IGF1 receptor pathway was regulated by both noncanonical SHH-ADCY signaling and canonical SHH-GLI signaling. Inhibition of placental SHH signaling significantly reduced fetal weight in mice. CONCLUSION: Placental development and fetal growth were regulated through the SHH pathway via the IGF axis.

Impaired Wnt5a signaling in extravillous trophoblasts: Relevance to poor placentation in early gestation and subsequent preeclampsia.

BACKGROUND: Defective decidual endovascular trophoblast invasion and subsequent impaired spiral artery remodeling is highly associated with the pathogenesis of preeclampsia (PE). Since there are scant and conflicting data regarding the function of Wnt5a signaling in extravillous trophoblasts (EVT), the aim of this study was to investigate whethere impaired Wnt5a signaling affects the invasive and tube forming capabilities of EVT. METHODS: Expression levels of Wnt ligands were compared between first trimester chorionic villi of women who later developed PE and women with unaffected pregnancies using publicly available microarray data (GSE12767). Wnt5a expression was examined in placentas using quantitative RT-PCR, Western blot analysis and immunohistochemistry. The function of Wnt5a signaling in EVT was investigated in an immortalized first trimester EVT cell line, HTR-8/SVneo, using small-interfering RNAs, recombinant human Wnt5a (rhWnt5a), and inhibitors of JNK or PKC. RESULTS: Microarray data analysis of the first trimester placentas showed that, among Wnt ligands, Wnt5a expression was significantly lower in women who later developed PE. The mRNA and protein expression levels of Wnt5a were significantly decreased in PE placentas compared with normal term placentas. Wnt5a knockdown significantly suppressed invasion and tube formation of HTR-8/SVneo cells, while the addition of rhWnt5a augmented the cell migration, invasion, and tube formation. Repression of Wnt5a/PKC signaling in HTR-8/SVneo cells inhibited cell invasion, but did not alter cell tube formation. In contrast, inhibition of Wnt5a/JNK signaling attenuated rhWnt5a-induced invasion and tube formation capabilities. CONCLUSIONS: These findings suggest that impaired Wnt5a signaling is associated with poor placentation and subsequent PE.

Rupture of a degenerated uterine fibroid as a cause of acute abdomen: a case report.

BACKGROUND: Uterine fibroid is one of the most common pelvic neoplasms. It is rare for this condition to manifest as acute symptoms necessitating emergency surgical intervention. CASE: A 46-year-old, Japanese woman was referred to our emergency room for sudden epigastric discomfort. A pelvic mass was felt, and computed tomography demonstrated a 13-cm hypodense multilocular cystic mass adjacent to the uterus. The anterior wall of the cyst was thinned and discontinued, suggesting rupture of the cyst. There was also massive ascites. Peritoneal irritation caused by rupture of an ovarian cyst was suspected, and an emergency exploratory laparotomy was performed. The patient was found to have a distended cystic mass protruding from the posterior surface of the uterus with 3,200 mL of blood-stained ascites. Closer examination revealed a 1-cm tear on the tumor surface, and both solid and cystic parts to the mass. Microscopically the tumor showed a proliferation of myometrial cells without atypia and hyaline degeneration. These findings were interpreted as a rupture of uterine fibroid after cystic degeneration. CONCLUSION: Rupture of degenerated cystic fibroid is rare, but it should be included in the differential diagnosis when encountering patients with a cystic tumor and massive ascites.

Construction and characterization of a Yarrowia lipolytica mutant lacking genes encoding cytochromes P450 subfamily 52.

The initial hydroxylation of n-alkane is catalyzed by cytochrome P450ALK of the CYP52 family in the n-alkane-assimilating yeast Yarrowia lipolytica. A mutant with a deletion of all 12 genes, ALK1 to ALK12, which are deduced to encode cytochromes P450 of the CYP52 family in Y. lipolytica, was successfully constructed. This deletion mutant, Δalk1-12, completely lost the ability to grow on n-alkanes of 10-16 carbons. In contrast, Δalk1-12 grew on the metabolite of n-dodecane, i.e., n-dodecanol, n-dodecanal, or n-dodecanoic acid, as well as the wild-type strain. In addition, production of n-dodecanoic acid was not observed when Δalk1-12 was incubated in the presence of n-dodecane. These results indicate the essential roles of P450ALKs in the oxidation of n-alkane. Δalk1-12 will be valuable as a host strain to express an individual ALK gene to elucidate the molecular function and substrate specificity of each P450ALK. Transcriptional activation of the ALK1 promoter by n-alkanes was observed in Δalk1-12 as in the wild-type strain, implying that n-alkanes per se, but not their metabolites, trigger n-alkane-induced transcriptional activation in Y. lipolytica.

Efficient microwelding of glass substrates by ultrafast laser irradiation using a double-pulse train.

Efficient microwelding of glass substrates by irradiation by a double-pulse train of ultrafast laser pulses is demonstrated. Temporal beam shaping techniques such as double-pulse irradiation enabled increased flexibility for high-quality, high-efficiency material processing. The bonding strength of two photostructurable glass substrates welded by double-pulse irradiation was evaluated to be 22.9 MPa, which is approximately 22% greater than that of a sample prepared by conventional irradiation by a single-pulse train.

Disseminated intravascular coagulation as the presenting sign of gastric cancer during pregnancy.

Gastric cancer during pregnancy is rare and the outcome is generally poor. A 36-year-old woman in the 28th week of gestation was complicated with disseminated intravascular coagulation (DIC), and she was diagnosed with gastric cancer with bone marrow metastasis. Cesarean delivery followed by sequential methotrexate (100 mg/m2) and 5-fluorouracil (600 mg/m2) chemotherapy was conducted. DIC was successfully managed with blood transfusion and chemotherapy. She has received chemotherapy in the outpatient clinic. This report is the second case of a pregnant woman with DIC as the initial manifestation of advanced gastric cancer. Prompt diagnosis and chemotherapy increases the chances of a relatively favorable outcome even in advanced gastric cancer presenting with DIC due to bone marrow involvement.

Narrow-line-width 1.31-µm wavelength tunable quantum dot laser using sandwiched sub-nano separator growth technique.

A wide wavelength tunable quantum dot (QD) external cavity laser operating in the 1.31-µm waveband with a narrow line-width is successfully demonstrated. A high-density, high-quality InAs/InGaAs QD optical gain medium for the 1.31-µm waveband was obtained using a sandwiched sub-nano separator growth technique. A wide wavelength tunability of 1.265-1.321 µm and a narrow line-width of 210 kHz were successfully achieved using a compact and robust external cavity system constructed with multiple optical band-pass and etalon filters for active optical mode selection. The laser also achieved an error-free 10-Gb/s photonic data transmission over an 11.4-km-long holey fiber.

Femtosecond laser microprocessing with three-dimensionally isotropic spatial resolution using crossed-beam irradiation.

We describe the use of a crossed-beam irradiation system in three-dimensional femtosecond laser microprocessing to obtain three-dimensionally isotropic spatial resolution. In the crossed-beam geometry, two orthogonal objective lenses are arranged to share a common focal point. The synthesized focal spot produces an isotropic illumination volume. We demonstrate that microfluidic channels with substantially circular cross-sectional shapes can be directly fabricated inside glass by using the crossed-beam irradiation system.

Peripheral MR angiography: separation of arteries from veins with flow-spoiled gradient pulses in electrocardiography-triggered three-dimensional half-Fourier fast spin-echo imaging.

The authors evaluated a nonenhanced magnetic resonance (MR) angiographic technique that allows separation of arteries from veins. In 15 healthy subjects, peripheral MR angiography was performed with readout flow-spoiled gradient pulses in electrocardiography-triggered three-dimensional half-Fourier fast spin-echo MR imaging. Appropriate flow-spoiled gradient pulses were measured and applied in the three-dimensional acquisition to differentiate arteries and veins in the peripheral vasculature. Subtraction of the diastolic bright-blood arteries from the systolic black-blood arteries allowed visualization of the arteries by cancelling the veins, which are constantly depicted as bright blood throughout the cardiac cycle. Stronger flow-spoiled gradient pulses improved the depiction of slow-flow arteries even in the distal foot and hand vessels.