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Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled. We performed whole-exome sequencing and evaluated the pathogenicity of the identified variants. All individuals had de novo heterozygous variants in KIF5B encoding kinesin-1 heavy chain: two with c.272AG:p.(Lys91Arg), one with c.584CA:p.(Thr195Lys), and the other with c.701GT:p.(Gly234Val). All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. All individuals had sharp angulation of the femora and humeri, distinctive facial features, and neonatal respiratory distress. Short stature was observed in three individuals. Three developed postnatal osteoporosis with subsequent fractures, two showed brachycephaly, and two were diagnosed with optic atrophy. Our findings suggest that heterozygous KIF5B deleterious variants cause a specific form of kyphomelic dysplasia. Furthermore, alterations in kinesins cause various symptoms known as kinesinopathies, and our findings also extend the phenotypic spectrum of kinesinopathies.

Placenta accreta spectrum (PAS) disorder often causes a large amount of intraoperative bleeding in a short period which makes maternal circulation unstable and threatens life. As a countermeasure, two-stage surgery combined with selective uterine arterial embolization (UAE), named “stepwise treatment” was introduced in 2003. At a cesarean section (CS), only the baby is delivered and the placenta is left in situ. The transcatheter angiographic UAE is performed on the operation day, followed by the total hysterectomy on 5 to 7 days after CS. The difficulty in the operative procedures for hysterectomy and the amount of bleeding can be reduced by the added effect of the blood flow interruption by UAE and the uterine involution. Although there are not many indication cases, this is the prudent operation that should be considered for the most severe PAS case such as total placenta increta/percreta with placenta previa.In this article, the practical procedures and tips of stepwise treatment are described.

Aim We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. Methods Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. Results Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. Conclusion The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.

OBJECTIVE The objective of this study is to clarify the usefulness of parental alkaline phosphatase (ALP) for prenatal diagnosis of hypophosphatasia (HPP). METHODS Maternal (m) and paternal (p) ALP values were measured in 77 cases from a multicenter cohort (fetal skeletal dysplasia forum in Japan) of cases with short limbs on ultrasonography during pregnancy. After birth, X-rays, cord blood ALP, and gene analysis were evaluated to achieve an exact diagnosis. The screening usefulness of ALP was examined retrospectively. RESULTS Seventeen cases were eventually diagnosed as HPP and 60 as not HPP; the overall mean m-ALP and p-ALP (standard deviation) values were 133.4 (53) versus 197 (69) IU/L and 149.6 (71.8) versus 231 (61.4) IU/L (p

Objective Constipation is common and a significant problem in pregnant women. The purpose of this study was to examine the efficacy and the safety of daikenchuto in pregnant women with constipation. Material and methods This was a prospective study, and a total of 20 patients were registered between February 2010 and August 2012. The patients received 7.5 g/d of daikenchuto for 28 days from the day of registration. All enrolled patients were asked to complete the constipation assessment scale (CAS) every day. In addition, we measured the aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine levels to assess the adverse effects of daikenchuto . Results The CAS scores were significantly lower at 28 days after daikenchuto treatment ( p = 0.019), with a significant effect achieved on Day 1. The impact of the therapy was greatest in the second trimester ( p = 0.043). No significant adverse effects of daikenchuto were observed, and the rates of preterm birth and pregnancy-induced hypertension were 10% and 5%, respectively, which are similar to previously reported values. Conclusion We herein demonstrated the efficacy and safety of daikenchuto in pregnant women with constipation. We hope that our findings will aid in the management of constipation in pregnant women.

Gefitinib is an essential drug for the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. The approved dosage is 250mg/body/day without adjustment for physical size such as body surface area (BSA), and the impact of physical size on the efficacy of gefitinib has not been evaluated. Here, we sought to clarify this issue using a retrospective cohort. We reviewed the medical records of patients with consecutive advanced NSCLC harboring EGFR mutations who underwent gefitinib monotherapy at Okayama University Hospital. In total, 101 patients were included in this study, and the median BSA in this cohort was 1.5m 2 . The median progression-free survival (PFS) of the patients with higher BSA (≥1.5m 2 ) was significantly worse than that of those with lower BSA ( 2 ) (10.4 vs. 18.0 months; p =0.019, log-rank test). Multivariate analysis also showed a significant impact of BSA on PFS (hazards ratio, 2.34; 95% confidence interval, 1.78–2.89; p =0.002). By contrast, no significant association between BSA and PFS was observed in those undergoing cytotoxic chemotherapy (4.0 vs. 5.1 months; p =0.989, log-rank test), suggesting that BSA is a predictive, rather than a prognostic, marker for gefitinib therapy in EGFR -mutated NSCLC. In conclusion, BSA affected PFS in patients with EGFR -mutated NSCLC who underwent gefitinib monotherapy, suggesting the need for appraisal of BSA-based dose adjustment, even for this molecular target-based therapy.

Objective Endobronchial ultrasound-guided transbronchial needle aspiration is a new minimally invasive test for investigating mediastinal and hilar lymphadenopathy. It is sometimes difficult to distinguish between a recurrent malignant lymph node and lymphadenopathy due to sarcoidosis in patients who develop lymphadenopathy after surgery for a malignant tumor. Methods Between December 2009 and October 2012, we performed endobronchial ultrasound-guided transbronchial needle aspiration in 13 selected patients with a suspected recurrence in the mediastinum and/or hilum of the lung after surgical resection of a malignant tumor. We examined their medical records to obtain information on the diagnosis, the sizes of lymph nodes, the number of needle passes and other complications. Results Definitive diagnoses were made using endobronchial ultrasound-guided transbronchial needle aspiration in 10 patients (three lung adenocarcinomas, one prostate carcinoma, one renal cell carcinoma, one neuroendocrine tumor and four sarcoidosis). Pathological specimens showing non-caseating granulomas led to the diagnosis of sarcoidosis in four patients; their previous malignancies had been papillary adenocarcinoma of the thyroid, carcinoma of the gingiva, thymoma and bladder cancer, but no recurrences were observed. The median of the longest diameter in 15 lymph nodes was 22 mm (range 13-35), and the median number of needle passes was two times (range 1-5) without severe complications. Conclusions Endobronchial ultrasound-guided transbronchial needle aspiration might be useful in differentiating between benign lymphadenopathy, including sarcoidosis, and cancer recurrence in patients with mediastinal or hilar lymphadenopathy after surgical resection of a malignant tumor.

The objective of this study is to clarify the usefulness of parental alkaline phosphatase (ALP) for prenatal diagnosis of hypophosphatasia (HPP).Maternal (m) and paternal (p) ALP values were measured in 77 cases from a multicenter cohort (fetal skeletal dysplasia forum in Japan) of cases with short limbs on ultrasonography during pregnancy. After birth, X-rays, cord blood ALP, and gene analysis were evaluated to achieve an exact diagnosis. The screening usefulness of ALP was examined retrospectively.Seventeen cases were eventually diagnosed as HPP and 60 as not HPP; the overall mean m-ALP and p-ALP (standard deviation) values were 133.4 (53) versus 197 (69) IU/L and 149.6 (71.8) versus 231 (61.4) IU/L (p 0.001). Receiver operating characteristic curve analysis showed that the optimal m-ALP and p-ALP cutoff values were 123 and 165 IU/L, respectively. Presence of at least one of the m-ALP or p-ALP values abnormally low had a sensitivity, specificity, and positive predictive values of 82% (14/17), 93%, and 78%, respectively, for the diagnosis of HPP.Parental ALP measurement might be an auxiliary tool to hone in the prenatal diagnosis of fetal HPP. © 2017 John WileySons, Ltd.

Aim: To assess the maternal and neonatal outcomes of pregnant women with mental disorders in Japan. Material and Methods: We conducted this retrospective cohort study to examine the patients who delivered at Nagoya University Hospital (2005–2009). Thereafter, the patients without any complications other than mental disorders and with several sources of psychiatric information were included in the present series, and the maternal and neonatal outcomes between patients with or without maternal mental disorders were compared. The psychiatric outcomes and the adverse effects of psychotropic drugs were also examined. Results: A total of 1649 women delivered during this period, and 63 of them were complicated by maternal mental disorders. After the selection of patients for comparison purposes, women with mental disorders (n = 51) had a slightly but significantly shorter gestational age (39.2 ± 0.2 vs 39.8 ± 0.1 weeks, P = 0.003) and smaller birth weight (2993.0 ± 56.7 vs 3152.4 ± 23.6 g, P = 0.010) compared with the control group (n = 278). Intervention by psychiatrists was required for only 10 patients, and no patients required termination of pregnancy due to exacerbation of mental disorders. In schizophrenia patients who were taking atypical antipsychotics and benzodiazepine, a significant increase in maternal gestational weight gain, and a significant shorter gestational age were detected, respectively, compared with patients who were not receiving any drug treatments. Conclusion: A trend towards a lower birth weight and shorter gestational age was observed in Japanese women with well-controlled mental disorders, but the effect of well-controlled mental disorders on the perinatal outcome was minimal.

A case of biopsy-confirmed chronic leptomeningitis complicating rheumatoid arthritis in a 53-year old female is reported. Her symptoms included weight loss, severe depression, and pyrexia. Magnetic resonance imaging was useful in diagnosis. Intravenous methylprednisolone was prescribed (1 g/day for 3 days), followed by prednisolone (initial dose of 30 mg daily), and this treatment was effective. Her IgG-index, serum levels of soluble interleukin-2 receptor and ferritin, and cerebrospinal level of interleukin-6 paralleled her clinical course.

Background/Aims: In the present study, we investigated the participation of inflammatory cytokine-induced mediated matrix metalloproteinase (MMP) expressions and inhibition of interleukin (IL)-6-induced MMP secretion in amniotic epithelial cells by tocilizumab. Methods: To investigate the role of MMP expressions, immunohistochemical staining was performed using membranes obtained from 10 patients with preterm premature rupture of membranes (PPROM) and from 10 patients who underwent a nonlabor cesarean section. We also investigated the regulation of MMP expression by inflammatory cytokines in human amnion cells. Results: Immunohistochemical staining showed a significantly higher expression of MMP-2 and -9 in PPROM. Treatment of cultured WISH and primary amniotic epithelial cells with 10–8 or 10–7M IL-6 or tumor necrosis factor (TNF)-α clearly increased the secretion of MMP-2 and -9. Treatment with 10–8M TNF-α or IL-6 significantly increased the invasion of WISH or primary amniotic epithelial cells, respectively, compared with the control. At a low concentration of 1 μg/ml, tocilizumab (anti-human IL-6 receptor monoclonal antibody) inhibited the IL-6-induced MMP secretion. Conclusions: This paper is the 1st report of tocilizumab inhibiting IL-6-induced MMP-2 and MMP-9 secretions from human amnion cells in PPROM.

Regulation of cytotrophoblast differentiation toward extravillous trophoblasts (EVTs) is critical for establishing successful pregnancy. Previous studies have focused primarily on the factors promoting the differentiation, while inhibitory regulators except hypoxia have been less documented. In this study, to test our hypothesis that angiotensin II (Ang II) would inhibit EVT differentiation, we investigated the effects of Ang II on trophoblast outgrowth and the expression of molecules associated with the proliferation and invasion of trophoblasts using human first trimester villous explant cultures. Ang II increased EVT outgrowth and the number of cells in cell columns. Moreover, Ang II-treated explants exhibited increased Ki67 and integrin alpha5 immunoreactivity in EVTs as well as matrix metalloproteinase-2 activity in the conditioned media, and decreased alpha1 integrin immunoreactivity, which are compatible with the features of the proliferative phenotype EVTs. These effects of Ang II were similar to those of hypoxia (3% O(2)). Ang II stimulated the expression of hypoxia inducible factor-1alpha at both mRNA and protein levels, and also enhanced the expression of plasminogen activator inhibitor-1 (PAI-1). Data presented herein suggest a possible role for Ang II in impairing trophoblast differentiation toward an invasive phenotype, which might be associated with shallow invasion in preeclamptic placentas.

Aim: Placenta accreta is an abnormally firm attachment of placental villi to the uterine wall, which may cause postpartum hemorrhage resulting in maternal morbidity and mortality. The purpose of the present study was to clarify the incidence, clinical background and prognosis of placenta previa increta/percreta treated with different modalities in Japan. Methods: Medical records of cases with placenta previa increta/percreta in eight tertiary centers between January 1994 and December 2004 were reviewed. Placenta accreta without actual invasion into the myometrium confirmed by pathology was not included in placenta increta/percreta. Details of obstetric history, maternal background, ultrasonographical findings, the course of delivery, subsequent complications and management were noted. Results: Among the total of 59 008 deliveries, 45 261 were by the vaginal route (76.7%) and 13 747 by cesarean section (23.3%). In this study, 408 cases were diagnosed as placenta previa (0.69%), 18 of these being placenta increta and 5 placenta percreta. Only 1.1% of cases of placenta previa without prior cesarean section were increta/percreta, in contrast to 37% of placenta previa after prior cesarean sections. Mean intraoperation blood loss was 3630 ± 2216 g (increta) and 12 140 ± 8343 g (percreta). One patient with placenta previa percreta died of hemorrhage. Stepwise treatment (cesarean section without separation of the placenta, arterial embolization and hysterectomy) was applied for 4 cases, which had the least blood loss. Conclusions: Placenta previa increta/percreta is a life-threatening disease. Patients who undergo hysterectomy after uterine arterial embolization demonstrate reduced intraoperation blood loss, and this treatment should be incorporated to reduce maternal morbidity.

We evaluated whether a correlation existed between fetal pulmonary magnetic resonance imaging (MRI) findings and postnatal mortality, as well as the requirements for extracorporeal membrane oxygenation (ECMO) in infants with prenatally diagnosed, isolated left-sided congenital diaphragmatic hernia (CDH). Twenty-one pregnant women carrying fetuses with CDH underwent 30 MRI scans, and the right-sided fetal lung volume (FLV) was measured. In the control, a regression analysis was performed to associate FLV with gestational age. This yielded a formula that enabled the calculation of the expected right fetal lung volume (ERFLV). In cases with CDH, the right-sided observed FLV/ERFLV (= %RFLV) was compared with both the postnatal mortality and whether ECMO was required. Additionally, we investigated the relationship between the lung shape on MRI (whether there was a complete pulmonary baseline present) and postnatal mortality. The %RFLV was significantly lower in nonsurvivors compared with survivors. Among survivors, the %RFLV was significantly lower in infants who required ECMO compared with those who did not. The pulmonary baseline was completely present in 3 (38%) and 13 (100%) of the nonsurvivors and survivors, respectively. In isolated left-sided CDH, the %RFLV is a good predictor not only of postnatal mortality but also of the requirement for ECMO.

Ultrasound examination is an objective method for assessment of uterine scar defects. The present study was conducted to compare single-layer interrupted sutures (Group A) with double-layer interrupted sutures (Group B) and our new method (Group C) as well as other perioperative parameters in relation to risk of wedge defects in scars.We have introduced a new myometrium closure procedure consisting of continuous suture with decidual closure followed by interrupted myometrium suture. In this prospective study, women undergoing cesarean operation (n = 137) were examined by transvaginal ultrasound one month after surgery to assess the appearance of lower uterine scars. Multivariate logistic regression analysis was performed to identify associations of perioperative parameters and methods for lower myometrium closure with abnormal wedge formation.Wedge defects were observed in a total of 27 patients (19.7%). The analysis revealed Groups B and C to have reduced risks with odds ratios of 0.28 and 0.077, respectively, as compared to Group A. Furthermore, increasing gestational week at delivery, plural fetal pregnancies, premature rupture of membranes and pre-eclampsia were also linked with an increased risk, with odds ratios of 1.4-8.9.The incidence of uterine scar defects 1 month after cesarean sections varies with the method applied for myometrial suture and perioperative variables. The data suggest that methods for myometrium closure as well as other factors influence the condition of myometrial healing.

Objective To clarify the effects of uterine myometrial suture techniques at prior caesarean section on the incidence of pathologically diagnosed placenta accreta in placenta praevia with prior caesarean section (PPPC). Design Case–control study. Setting Eleven tertiary referral hospitals in central Japan. Population A total of 98 cases of placenta praevia, a history of one or more prior caesarean sections, and a history of uterine transverse incision and usage of only absorbable thread for myometrial sutures at the prior caesarean section. Exclusions were a history of myomectomy or Strassmann's operation. Methods Cases were grouped into a pathologically diagnosed placenta accreta group (38 cases) and a no accreta group (60 cases). Clinical characteristics including uterine suture methods at prior caesarean section were compared (single-layer versus double-layer closure; continuous versus interrupted sutures in the inner myometrial layer). Main outcome measure The incidence of placenta accreta. Results No difference was found comparing single-layer with double-layer closure in the incidence of placenta accreta (37.1 versus 39.7%, P = 0.805); however, a significant difference was found comparing continuous with interrupted sutures (58.1 versus 29.9%, P = 0.008). Multivariable logistic regression analysis with stepwise selection for the eight factors meeting the criterion of P

Background Pregnancies with placenta previa are significantly associated with preterm delivery and cesarean section. Therefore particular attention should be paid to the incidence of neonatal respiratory disorders in pregnancies with placenta previa. Aims The purpose of this study is to examine the relationship between placenta previa and neonatal respiratory disorders, including respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), and to evaluate the impact of placenta previa on the amniotic lamellar body count (LBC) values. Methods We analyzed the data from 186 registered elective cesarean cases without fetal or maternal complications at 36–38 weeks of gestation. Amniotic fluid samples were analyzed immediately without centrifugation, and the LBC was measured using a platelet channel on the Sysmex XE-2100. Results RDS was present in four neonates (2.2%) and TTN in 12 neonates (6.5%). The rate of TTN was significantly higher and the LBC values were significantly lower in the placenta previa group than in the control group (P = 0.002 and P = 0.024). The adjusted odds ratio for neonatal TTN was 7.20 (95% confidence interval: 6.58–7.88) among females with placenta previa. In placenta previa, warning bleeding was a significant factor protecting against neonatal respiratory disorders (P = 0.046). Conclusions Placenta previa in itself is a risk factor for neonatal TTN. When an elective cesarean section is performed in cases with uncomplicated placenta previa, special care should be taken to monitor for neonatal TTN even at 36–38 weeks of gestation.

Non‐small‐cell lung cancers with epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs); however, unlike cytotoxic agents, it is generally accepted that minimal doses of drugs inhibiting target molecules are sufficient when molecular‐targeted agents, including EGFR‐TKIs, are used. Thus, any utility of higher doses remains unclear. We compared low‐dose (15 mg/kg) gefitinib therapy with high‐dose (50 mg/kg) therapy using an EGFR‐mutated lung cancer xenograft model. Both gefitinib doses induced tumor shrinkage, but tumors regrew in the low‐dose group within 1 month, whereas tumors in the high‐dose group did not. Neither the T790M mutation nor MET amplification was apparent in regrown tumors. We also compared outcomes after two doses of gefitinib (5 and 25 mg/kg) in a transgenic EGFR‐mutated lung cancer mouse model. In line with the results obtained using the xenograft model, both gefitinib doses completely inhibited tumor growth, but tumors treated with the lower dose of gefitinib developed earlier drug resistance. In conclusion, a low gefitinib dose caused tumors to become drug‐resistant prior to acquisition of the T790M mutation or MET amplification in EGFR‐mutated models of lung cancer. This suggests that it is important to optimize the EGFR‐TKI dose for treatment of EGFR mutation‐associated lung cancer. Gefitinib may need to be given at a dose greater than the minimum required for inhibition of target molecules.

Background Interstitial lung disease (ILD) is frequently associated with collagen diseases. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in collagen disease patients is very poor. Here, we investigated serum biomarker profiles of AoDILD to find markers predicting outcome in patients with collagen diseases. Methods A solid-phase antibody array was used for screening 274 biomarkers in pooled sera from collagen disease patients in the AoDILD state and in the stable state. Biomarkers in individual sera were detected without pooling by bead-based immunoassay. Results The serum levels of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinase (TIMP)-1, osteopontin, interleukin (IL)-2 receptor α(IL-2Rα), and IL-1 receptor antagonist were significantly increased in AoDILD, but TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state. This tendency was also observed in RA patients with AoDILD. Moreover, serum IL-6 level was significantly increased in the AoDILD state in patients with acute exacerbation of ILD (AE-ILD). Serum TIMP-1 and IL-2Rα levels were significantly increased in the AoDILD state in patients with drug-induced ILD (DI-ILD), whereas TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients with DI-ILD. The serum TIMP-3,MMP-9, osteopontin, IL-2Rα, MMP-1, and MMP-8 levels were significantly increased in the AoDILD state in patients who subsequently died, whereas TIMP-2 and MMP-3 levels were decreased in those who survived. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients who died, but not in those who survived. Conclusions Serum biomarker profiles could represent prognosis markers for AoDILD in collagen diseases.

Six proteins, designated SAP1 through SAP6, were secreted specifically by salt-adapted cells of winged bean (Psophocarpus tetragonolobus) in suspension cultures. The amino-terminal amino acid sequences of SAP2 (57 kDa), SAP4 (21 kDa), SAP5 (19 kDa) and SAP6 (17 kDa) were homologous to the sequences of proline-rich proteins, indicating that proline-rich proteins are secreted specifically by these salt-adapted cells. In addition, the amino-terminal amino acid sequence of SAP2 was identical to that of SAP4, and the amino-terminal sequence of SAP5 was identical to that of SAP6. Secretion of SAP2 was significantly enhanced by addition of AlCl3 but not of KCl, LiCl, CaCl2, MgCl2, mannitol or sucrose to suspension cultures. Furthermore, secretion of SAP4, SAP5 and SAP6 was stimulated by addition of abscisic acid to cultures, suggesting that these proteins might be secreted in response to salt or osmotic stress.

The pathogenesis of placental mesenchymal dysplasia (PMD) remains unclear. This report presents a case of PMD with a female fetus complicated with intrauterine growth restriction (IUGR). The ultrasound findings were similar to molar pregnancies, but PMD was suspected based on the presence of low β-hCG levels and a normal karyotype. After delivery, pathological examination of the placenta showed dilated villi and thick-walled vessels lacking trophoblast proliferation, which thus led to a diagnosis of PMD. The VEGF-D (Xp22.31) mRNA expression was found to have increased in the abnormal villi. Whether this is an incidental or X-linked gene specific event in, IUGR complicated, PMD pathogenesis warrants further investigation of VEGF-D expression in PMD.

Six specific proteins are secreted from salt-adapted winged bean (Psophocarpus tetragonolobus) cells. A protein, designated S AP3, with molecular mass of 37 000 was secreted abundantly by suspension cultures of winged bean callus adapted to 0.5% (86 mM) or 1.0% (171 mM) NaCl. When the amino acid sequence of the amino-terminal part (16 amino acid residues) of SAP3 was determined, a significant homology was found between the amino-terminal amino acid sequence of SAP3 and that of basic chitinase from kidney bean, Arabidopsis, tobacco and pumpkin. SAP3 had chitinase activity, suggesting that basic chitinase is secreted specifically from salt-adapted winged bean cells. A protein with molecular mass of 29000 was exclusively secreted into the culture medium at the later stage (20–30 days) of both salt-adapted and -unadapted cultures. The protein was purified from the medium at day 30. One-step ammonium sulfate fractionation was sufficient for purification to homogeneity. The protein had chitinase activity. The amino-terminal amino acid sequence (17 amino acid residues) of the protein suggested that it was acidic chitinase. Thus, acidic chitinase with a molecular mass of 29000 is exclusively secreted at the later stage of culture of salt-adapted and -unadapted winged bean cells, in contrast to pumpkin (Cucurbita) cell suspension cultures where basic chitinase with a molecular mass of 32 000 is secreted abundantly at the early culture stage.

To assess the maternal and neonatal outcomes of pregnant women with mental disorders in Japan.We conducted this retrospective cohort study to examine the patients who delivered at Nagoya University Hospital (2005-2009). Thereafter, the patients without any complications other than mental disorders and with several sources of psychiatric information were included in the present series, and the maternal and neonatal outcomes between patients with or without maternal mental disorders were compared. The psychiatric outcomes and the adverse effects of psychotropic drugs were also examined.A total of 1649 women delivered during this period, and 63 of them were complicated by maternal mental disorders. After the selection of patients for comparison purposes, women with mental disorders (n = 51) had a slightly but significantly shorter gestational age (39.2 ± 0.2 vs 39.8 ± 0.1 weeks, P = 0.003) and smaller birth weight (2993.0 ± 56.7 vs 3152.4 ± 23.6 g, P = 0.010) compared with the control group (n = 278). Intervention by psychiatrists was required for only 10 patients, and no patients required termination of pregnancy due to exacerbation of mental disorders. In schizophrenia patients who were taking atypical antipsychotics and benzodiazepine, a significant increase in maternal gestational weight gain, and a significant shorter gestational age were detected, respectively, compared with patients who were not receiving any drug treatments.A trend towards a lower birth weight and shorter gestational age was observed in Japanese women with well-controlled mental disorders, but the effect of well-controlled mental disorders on the perinatal outcome was minimal.

Aims: The purpose of this study is to predict the occurrence of transient tachypnea of the newborn (TTN) using amniotic lamellar body count (LBC) and compare the LBCs in neonates with TTN with the LBCs in neonates with respiratory distress syndrome (RDS) and controls. Methods: Three hundred and eighty-one amniotic fluid samples were obtained at cesarean section from 27 to 40 weeks of gestation. Samples were analyzed immediately without centrifugation and the number of lamellar bodies was counted. Results: The LBC in amniotic fluid ranged from 1,000 to 577,000/μL. An LBC cut-off value of 48,500/μL resulted in 84.7% sensitivity, 76.2% specificity, and 98.1% negative predictive value for predicting TTN. The LBC in neonates with TTN was significantly lower than that in controls (50,000 vs. 122,000; P < 0.001) and significantly higher than that in neonates with RDS (50,000 vs. 21,000; P=0.042). Conclusions: We established a cut-off value of LBC for predicting the occurrence of TTN. The LBC in neonates with TTN was significantly lower than that in controls. Amniotic LBC can be a useful marker to predict if neonatal respiratory management is required.

To examine the lamellar body count (LBC) value in intra-amniotic infection cases and evaluate its association with the incidence of respiratory distress syndrome (RDS).Three hundred sixty-five amniotic fluid (AF) samples were obtained at caesarean section from 27 to 38 weeks of gestation. LBC and glucose concentrations in AF were measured with no centrifugation. We defined AF glucose concentrations0.8 mmol/L and positive C-reactive protein (CRP) of the neonates as intra-amniotic infection.An LBC cutoff value of 29,500/μL resulted in 94.0% sensitivity, 82.4% specificity, and 99.1% negative predictive value (NPV) for RDS. Neonates with glucose concentrations0.8 mmol/L in AF and positive CRP had no RDS and significantly higher LBC values than controls before 34 weeks of gestation (17.0 vs. 4.3, p0.05 and 25.5 vs. 5.0, p0.05, respectively), but there were no significant differences after 34 weeks of gestation.LBC is an accurate predictor of foetal lung maturity and our LBC cutoff value had a high NPV for predicting RDS. We showed that intra-amniotic infection was associated with significantly higher LBC values than the value in controls before 34 weeks of gestation, which correlated with a low incidence of RDS.

Winged bean callus was adapted to increasing concentrations of NaCl by sequential transfer to medium with 0, 0.5, 1.0, 1.5, and 2.0% (w/v) NaCl. When the culture media, after cell suspension cultures of callus adapted to 0.5 (SA-0.5), 1.0 (SA-1.0), 1.5 (SA-1.5), or 2.0% (w/v) NaCl (SA-2.0), were analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis, six specific or enhanced polypeptide bands (SAP1, -2, -3, -4, -5, and -6) were observed. SAP1, with a molecular weight of 84,000, was abundantly secreted in suspension cultures of SA-1.0 and SA-1.5, and was observed as the most striking polypeptide band. The SAP1 yield was about 4 mg/g cells fresh weight. SAP1 was abundantly secreted after the suspension culture of SA-1.0 in the presence of AlCl(3), but little was secreted in the presence of KCl, LiCl, CaCl(2), MgCl(2), mannitol, sucrose, or abscisic acid. SAP1 was purified from the culture medium after suspension culture of SA-1.0 in the presence of 1.0% (w/v) NaCl. Two steps, ammonium sulfate fractionation and CM-cellulose chromatography, were sufficient for purification to homogeneity. Finally, about 5 mg of SAP1 could be isolated from 7 g of fresh callus cells. Of the amino-terminal 32 amino acid residues of SAP1, 10 and 5 were found to be hydroxyproline and proline, respectively. SAP1 on an acrylamide gel was stained by the periodic acid-Schiff method. It is interesting that SAP1 has pentahydroxyproline blocks (Hyp(5)) instead of tetrahydroxyproline blocks (Hyp(4)) common to many hydroxyproline-rich glycoproteins in dicotyledons. Thus, this novel hydroxyproline-rich glycoprotein was shown to be abundantly secreted from NaCl-adapted winged bean cells.

The reduced migration/invasion of extravillous trophoblasts (EVTs) is a key feature of the genesis of preeclampsia. We and others previously reported that transcriptional factors activator protein-2 (AP-2) alpha and AP-2gamma act as suppressors of tumor invasion. The present study examined the expressions of AP-2alpha and AP-2gamma in preeclamptic placenta vs. control placenta and investigated their effect on the function of EVTs. The expressions of AP-2alpha and AP-2gamma were elevated in the preeclamptic placentas in comparison with the gestational age-matched control placentas. Their expressions also increased in EVTs of the preeclamptic placentas. Thereafter, we transfected AP-2alpha or AP-2gamma into human EVT cell line, HTR-8/SVneo. The overexpression of AP-2alpha or AP-2gamma decreased the migratory and invasive abilities in HTR-8/SVneo cells. This was followed by the reduction of protease activated receptor-1 and matrix metalloproteinases and a significant induction of plasminogen activator inhibitor-1 and the tissue inhibitor of metalloproteinase-1. AP-2alpha and AP-2gamma were weakly expressed in the cultured EVTs and HTR-8/SVneo cells, whereas they were induced by TNF-alpha, which increases in preeclamptic placenta and impairs trophoblast invasion. In the presence of TNF-alpha, the invasion of the HTR-8/SVneo cells was partially restored by a blocking of AP-2 induction using small interfering RNA of AP-2. The present data suggest that AP-2 may suppress trophoblast migration and invasion, thus leading to a shallow placentation in preeclampsia.

Background/Aims: Previous studies have stated that maternal allergic diseases are associated with increased risk of preterm labor/delivery, but the underlying mechanisms remain unclear. This study tested the hypothesis that histamine induces interleukin (IL)-6 production in amnion cells. Methods: Using cultured human amnion cells, we examined expression of histamine receptors and effects of histamine on IL-6 production. Results: Reverse transcription-polymerase chain reaction and Western blotting revealed expression of histamine H1 receptor (H1R) and H2 receptor (H2R) in human amnion. Histamine stimulation significantly increased concentrations of IL-6 in conditioned medium, as did tumor necrosis factor-α and IL-1β in positive controls. In addition, the H1R antagonist olopatadine significantly blocked histamine-induced production of IL-6, whereas the H2R antagonist ranitidine did not. Conclusion: Histamine appears to induce IL-6 production through H1R in human amnion cells.

To compare the diagnostic utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies with other serological markers including rheumatoid factor (RF), anti-agalactosyl immunoglobulin G (IgG) antibody, and matrix metalloproteinase (MMP)-3 in very early rheumatoid arthritis (RA).Serum concentrations of anti-CCP antibodies, RF, anti-agalactosyl IgG antibody, and MMP-3 were measured in 262 patients with RA ("total RA") including 55 patients with disease duration of less than 6 months who had not been treated before entry ("very early RA") and 116 patients with rheumatic diseases other than RA.The diagnostic sensitivity of anti-CCP antibodies was 82.4% in total RA and 67.3% in very early RA and was lower than that of RF (84.0% total RA, 83.6% very early RA) and anti-agalactosyl IgG antibody (90.5%, 90.9%), whereas specificity, positive predictive value, and diagnostic accuracy were the best among markers tested both in total RA and in very early RA. The presence of either anti-CCP antibodies or RF increased the sensitivity, but any combination of serological markers was not significantly better in diagnostic accuracy than anti-CCP antibodies alone. The rates of RF-positive subjects in anti-CCP antibody-negative patients both in total RA (43.5%) and in very early RA (61.1%) were higher than those of anti-CCP antibody-positive subjects in RF-negative patients (38.1% and 22.2%, for total RA and early RA, respectively).Measurement of anti-CCP antibodies, by itself, is useful for the diagnosis of RA; however, combined use of anti-CCP antibodies with RF may be more useful than either method alone for the diagnosis of very early RA.

normalized platelet number. IL-6 and IL-10 levels did not show differences between L-NAME and silibinin groups. Histopathologic lesions in liver of the L-NAME group showed loss of polyedric shape of hepatocyte and acinar architecture. Intense mononuclear inflammatory infiltrate and thickening of muscle tunica of arterial vessel were observed mainly in periportal area. Silibinin treatment produced significant attenuation of the periportal inflammatory infiltrate observed in the L-NAME group, showing an association between inflammatory infiltrate and TNF-alpha, IL-1 and IFN-gamma levels. Conclusion: The silibinin treatment in different periods of pregnancy showed that this flavonoid displays anti-inflammatory and immunomodulatory actions that may contribute to its hepatoprotective effects. FAPESP: Grant no. 2006/07095-3