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1.
Nat Commun ; 12(1): 5904, 2021 10 08.
Article in English | MEDLINE | ID: mdl-34625540

ABSTRACT

The importin superfamily member Importin-13 is a bidirectional nuclear transporter. To delineate its functional roles, we performed transcriptomic analysis on wild-type and Importin-13-knockout mouse embryonic stem cells, revealing enrichment of differentially expressed genes involved in stress responses and apoptosis regulation. De novo promoter motif analysis on 277 Importin-13-dependent genes responsive to oxidative stress revealed an enrichment of motifs aligned to consensus sites for the transcription factors specificity protein 1, SP1, or Kruppel like factor 4, KLF4. Analysis of embryonic stem cells subjected to oxidative stress revealed that Importin-13-knockout cells were more resistant, with knockdown of SP1 or KLF4 helping protect wild-type embryonic stem cells against stress-induced death. Importin-13 was revealed to bind to SP1 and KLF4 in a cellular context, with a key role in oxidative stress-dependent nuclear export of both transcription factors. The results are integral to understanding stress biology, highlighting the importance of Importin-13 in the stress response.


Subject(s)
Active Transport, Cell Nucleus/physiology , Karyopherins/genetics , Karyopherins/metabolism , Oxidative Stress/physiology , Animals , Embryonic Stem Cells , HeLa Cells , Humans , Hydrogen Peroxide/metabolism , Kruppel-Like Factor 4 , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Mice , Mice, Knockout , Protein Kinases/genetics , Protein Kinases/metabolism , Transcription Factors/metabolism , Transcriptome
2.
Ultrasound Obstet Gynecol ; 36(6): 773-5, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20737457

ABSTRACT

We describe a case of a large chorioangioma diagnosed at 18 weeks' gestation. Because of advanced fetal heart failure at 23 weeks' gestation, embolization of the chorioangioma's vessels was performed by percutaneous injection of Glubran 2 surgical glue. There was no immediate secondary effect of treatment. Devascularization was complete and durable. Signs of fetal cardiac failure normalized after 1 month and a healthy infant was delivered at 38 weeks. To our knowledge this is the first reported case of perinatal survival after successful embolization of a chorioangioma using tissue glue.


Subject(s)
Cyanoacrylates/administration & dosage , Embolization, Therapeutic/methods , Hemangioma/therapy , Placenta Diseases/therapy , Pregnancy Complications, Neoplastic/therapy , Tissue Adhesives/administration & dosage , Adult , Female , Fetal Diseases/therapy , Gestational Age , Heart Failure/therapy , Hemangioma/diagnostic imaging , Humans , Infant, Newborn , Placenta Diseases/diagnostic imaging , Pregnancy , Pregnancy Complications, Neoplastic/diagnostic imaging , Pregnancy Outcome , Ultrasonography
3.
Ultrasound Obstet Gynecol ; 31(5): 549-54, 2008 May.
Article in English | MEDLINE | ID: mdl-18432605

ABSTRACT

OBJECTIVES: To evaluate the ability of combinations of cervical length and maternal history to assess the risk of spontaneous preterm birth, and to provide a simple procedure for the optimal estimation of risk. METHODS: This prospective observational study was carried out between January 1998 and May 2006. Transvaginal sonographic measurement of cervical length at 20 + 0 to 24 + 6 weeks of gestation was carried out in 58 807 singleton pregnancies as part of routine antenatal care. The outcome measure was spontaneous extreme (< 28 weeks), early (28-30 weeks), moderate (31-33 weeks) and mild (34-36 weeks) preterm birth. Logistic regression analysis was used to derive models for the prediction of spontaneous preterm birth from the maternal obstetric history, demographic characteristics and cervical length. RESULTS: The rates of extreme, early, moderate and mild spontaneous preterm birth were 0.23%, 0.24%, 0.57% and 2.93%, respectively. The best prediction of spontaneous preterm birth was provided by cervical length (area under the receiver-operating characteristics curve (AUC), extreme 0.903, early 0.816, moderate 0.784 and mild 0.617) and this was improved by adding obstetric history (AUC, extreme 0.919, early 0.836, moderate 0.819 and mild 0.650). Addition of other parameters was without material effect. For a 10% screen-positive rate, models using cervical length and obstetric history had a sensitivity of 80.6%, 58.5%, 53.0% and 28.6% for extreme, early, moderate and mild spontaneous preterm birth, respectively. These models were expressed as tables of adjusted likelihood ratios to allow simple estimation of the risk of spontaneous preterm birth. CONCLUSIONS: A model combining cervical length and obstetric history provides a better prediction of spontaneous preterm birth than either factor alone, and the sensitivity of screening improves for increasing degrees of prematurity.


Subject(s)
Cervix Uteri/diagnostic imaging , Premature Birth/diagnosis , Ultrasonography, Prenatal/methods , Adult , Area Under Curve , Cervix Uteri/anatomy & histology , Female , Gestational Age , Humans , Infant, Newborn , Logistic Models , Medical Records , Predictive Value of Tests , Pregnancy , Premature Birth/epidemiology , Premature Birth/prevention & control , Prospective Studies , Risk Assessment
4.
Ultrasound Obstet Gynecol ; 26(2): 154-7, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15977311

ABSTRACT

OBJECTIVE: To define the prevalence of major cardiac defects according to nuchal translucency (NT) thickness at the 11 to 13 + 6-week scan in fetuses with normal karyotype. METHODS: Specialist fetal echocardiography was carried in 6921 fetuses with normal or presumed normal karyotype at a median gestation of 20 (range 12-35) weeks. The indications for fetal echocardiography were increased NT thickness (n = 3444), detailed second-trimester scan either for assessment of risk of chromosomal abnormalities (n = 2980) or previous or family history of fetal defects (n = 497). The cardiac defects were grouped into six functional categories: septal defect, left inflow obstruction, right inflow obstruction, left outflow obstruction, right outflow obstruction and other. RESULTS: Major cardiac defects were identified in 132 (19.1 per 1000) fetuses and the prevalence increased with fetal NT thickness from 4.9 per 1000 in those with NT below the median, to 8.7 for NT between the median and less than the 95th centile, 18.2 for NT between the 95th and 99th centiles, and exponentially thereafter to 35.2, 64.4 and 126.7 for respective NTs of 3.5-4.4 mm, 4.5-5.4 mm and > or = 5.5 mm. There was no obvious difference in the distribution of NT in the different types of cardiac defects. CONCLUSIONS: The prevalence of major cardiac defects increases exponentially with fetal NT thickness and in fetuses with NT of 3.5 mm or more it is higher than in pregnancies with a family history of cardiac defects.


Subject(s)
Fetal Diseases/diagnostic imaging , Heart Defects, Congenital/diagnostic imaging , Nuchal Translucency Measurement , Adolescent , Adult , Echocardiography, Doppler, Color , Female , Fetal Diseases/genetics , Heart Defects, Congenital/genetics , Humans , Karyotyping , Middle Aged , Pregnancy , Ultrasonography, Prenatal/methods
5.
Przegl Epidemiol ; 55 Suppl 3: 164-9, 2001.
Article in Polish | MEDLINE | ID: mdl-11984946

ABSTRACT

UNLABELLED: In 18 patients with chronic hepatitis C we evaluated leptin (with IRMA method) and HGF and neopterin (with ELISA method) serum concentrations. Concentrations of leptin, HGF and neopterin were higher than in the control group. Leptin serum concentrations correlated with liver biopsy inflammatory grading, but higher HGF concentrations were connected with fibrosis staging. Neopterin correlated with both parameters and GGTP activity. IN CONCLUSION: increased neopterin concentrations could inform about liver inflammation activity; leptin and HGF serum concentrations could reflect the liver damage intensity.


Subject(s)
Hepatitis C, Chronic/blood , Hepatocyte Growth Factor/blood , Leptin/blood , Neopterin/blood , Adult , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Humans , Liver Cirrhosis/blood , Male , Middle Aged
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