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1.
Ultrasound Obstet Gynecol ; 60(2): 192-199, 2022 08.
Article in English | MEDLINE | ID: mdl-35445767

ABSTRACT

OBJECTIVES: To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB. METHODS: This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs). RESULTS: A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively. CONCLUSIONS: We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Pre-Eclampsia , Premature Birth , Biomarkers , Female , Fetal Membranes, Premature Rupture , Humans , Infant, Newborn , Placenta/metabolism , Placenta Growth Factor , Pre-Eclampsia/diagnosis , Pregnancy , Pregnancy Trimester, First , Pregnancy-Associated Plasma Protein-A/metabolism , Premature Birth/diagnosis , Prospective Studies , Retrospective Studies , Uterine Artery/diagnostic imaging
2.
Infect Immun ; 89(3)2021 02 16.
Article in English | MEDLINE | ID: mdl-33361201

ABSTRACT

The Enteritidis and Dublin serovars of Salmonella enterica are phylogenetically closely related yet differ significantly in host range and virulence. S Enteritidis is a broad-host-range serovar that commonly causes self-limited gastroenteritis in humans, whereas S Dublin is a cattle-adapted serovar that can infect humans, often resulting in invasive extraintestinal disease. The mechanism underlying the higher invasiveness of S Dublin remains undetermined. In this work, we quantitatively compared the proteomes of clinical isolates of each serovar grown under gut-mimicking conditions. Compared to S Enteritidis, the S Dublin proteome was enriched in proteins linked to response to several stress conditions, such as those encountered during host infection, as well as to virulence. The S Enteritidis proteome contained several proteins related to central anaerobic metabolism pathways that were undetected in S Dublin. In contrast to what has been observed in other extraintestinal serovars, most of the coding genes for these pathways are not degraded in S Dublin. Thus, we provide evidence that S Dublin metabolic functions may be much more affected than previously reported based on genomic studies. Single and double null mutants in stress response proteins Dps, YciF, and YgaU demonstrate their relevance to S Dublin invasiveness in a murine model of invasive salmonellosis. All in all, this work provides a basis for understanding interserovar differences in invasiveness and niche adaptation, underscoring the relevance of using proteomic approaches to complement genomic studies.


Subject(s)
Anaerobiosis/genetics , Proteomics , Salmonella enteritidis/genetics , Salmonella enteritidis/pathogenicity , Serogroup , Stress, Physiological/genetics , Virulence/genetics , Genetic Variation , Genomics , Host Specificity , Humans , Salmonella Infections/genetics , Salmonella Infections/pathology
3.
Dev Med Child Neurol ; 46(10): 706-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15473176

ABSTRACT

A preliminary cross-sectional study of 72 Hong Kong Chinese infants suggested that these infants learn to roll from supine-to-prone before rolling from prone-to-supine i.e. the opposite to teaching in most western texts. Three-hundred and sixty mothers were recruited postpartum and asked to record, on a chart, information related to the developmental milestone of rolling over for their infants (49% male) during the next 9 months. Telephone reminders were given at 4 and 8 months and, by the end of the study, information had been obtained from 240 mothers (67% of original sample, 51% male infants). Mean ages of rolling over were 5.1 months (SD1.5) for supine-to-prone and 5.7 months (SD1.3) for prone-to-supine. Age of rolling over from supine-to-prone was not influenced by usual sleep position, infant's sex, mother's intention to breastfeed infant, number of siblings, marital status, main daytime caregiver, or feeding method over 9 months. Hong Kong Chinese infants roll from supine-to-prone before they roll from prone-to-supine.


Subject(s)
Child Development , Cultural Characteristics , Motor Activity , Adult , Cross-Sectional Studies , Female , Hong Kong , Humans , Infant , Longitudinal Studies , Male , Prone Position , Supine Position
4.
J Bacteriol ; 182(22): 6366-73, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11053380

ABSTRACT

The role of the carboxy terminus of the Escherichia coli cell division protein FtsA in bacterial division has been studied by making a series of short sequential deletions spanning from residue 394 to 420. Deletions as short as 5 residues destroy the biological function of the protein. Residue W415 is essential for the localization of the protein into septal rings. Overexpression of the ftsA alleles harboring these deletions caused a coiled cell phenotype previously described for another carboxy-terminal mutation (Gayda et al., J. Bacteriol. 174:5362-5370, 1992), suggesting that an interaction of FtsA with itself might play a role in its function. The existence of such an interaction was demonstrated using the yeast two-hybrid system and a protein overlay assay. Even these short deletions are sufficient for impairing the interaction of the truncated FtsA forms with the wild-type protein in the yeast two-hybrid system. The existence of additional interactions between FtsA molecules, involving other domains, can be postulated from the interaction properties shown by the FtsA deletion mutant forms, because although unable to interact with the wild-type and with FtsADelta1, they can interact with themselves and cross-interact with each other. The secondary structures of an extensive deletion, FtsADelta27, and the wild-type protein are indistinguishable when analyzed by Fourier transform infrared spectroscopy, and moreover, FtsADelta27 retains the ability to bind ATP. These results indicate that deletion of the carboxy-terminal 27 residues does not alter substantially the structure of the protein and suggest that the loss of biological function of the carboxy-terminal deletion mutants might be related to the modification of their interacting properties.


Subject(s)
Bacterial Proteins/physiology , Escherichia coli Proteins , Escherichia coli/physiology , Alleles , Amino Acid Sequence , Bacterial Proteins/genetics , Cell Division , Escherichia coli/chemistry , Escherichia coli/genetics , Molecular Sequence Data , Sequence Alignment , Sequence Deletion , Spectroscopy, Fourier Transform Infrared
5.
Behav Res Ther ; 38(8): 835-55, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10937431

ABSTRACT

The practical significance of assessing disorders of emotion in children is well documented, yet few scales exist that possess conceptual if not empirical relevance to dimensions of DSM anxiety or depressive disorders. The current study evaluated an adaptation of a recently developed anxiety measure (Spence Children's Anxiety Scale; [Spence, S. H. (1997). Structure of anxiety symptoms among children: a confirmatory factor-analytic study. Journal of Abnormal Psychology, 106, 280-297; Spence, S. H. (1998). A measure of anxiety symptoms among children. Behaviour Research and Therapy, 36, 545-566]), revised to correspond to dimensions of several DSM-IV anxiety disorders as well as major depression. This investigation involved initial evaluation of the factorial validity of the revised measure in a school sample of 1641 children and adolescents and reliability and validity in an independent sample of 246 children and adolescents. Results yielded an item set and factor definitions that demonstrated structure consistent with DSM-IV anxiety disorders and depression. The revised factor structure and definitions were further supported by the reliability and validity analyses. Some implications for assessment of childhood anxiety and depressive disorders are discussed.


Subject(s)
Anxiety Disorders/diagnosis , Depressive Disorder/diagnosis , Psychiatric Status Rating Scales/standards , Adolescent , Child , Factor Analysis, Statistical , Female , Humans , Male , Psychometrics , Reproducibility of Results , Self Disclosure , Sex Factors
6.
J Clin Invest ; 101(11): 2301-8, 1998 Jun 01.
Article in English | MEDLINE | ID: mdl-9616201

ABSTRACT

The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n = 32) subjects, and correlating these results with the level of circulating CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4(+) T cell count (P = 0.02) and a higher percentage and absolute number of circulating naive (CD45RA+CD62L+) CD4(+) T cells (P < 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults ( 40 yr) regardless of CD4 count (P = 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , HIV-1 , Thymus Gland/physiopathology , Adult , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cross-Sectional Studies , Humans , Middle Aged , Tomography, X-Ray Computed
7.
Biochem Genet ; 21(5-6): 443-52, 1983 Jun.
Article in English | MEDLINE | ID: mdl-6870772

ABSTRACT

This report describes a method to isolate temperature-conditional phenylalanine transport mutants from the transformed human cell line HeLa. Using ultraviolet light as a mutagenic agent and DL-parafluorophenylalanine (PFPA), a poisonous analogue of L-phenylalanine, as a selective agent, mutagenized cells were selected for survival in the presence of PFPA at a temperature of 39 degrees C. Survivors of the mutagenesis and selection procedures were removed from the culture dishes by trypsin and cloned at a temperature of 35 degrees C. Seven of these lines isolated demonstrated continued resistance to PFPA at 39 degrees C. These lines were tested for uptake of L-phenylalanine at an external concentration of 100 microM and for continued resistance to PFPA at two concentrations. Cells were tested at 35 and at 39 degrees C. The data were compared to those obtained for the parental HeLa cell line under identical conditions. The seven mutant cell lines demonstrated varying resistances to PFPA and varying levels of accumulation of L-phenylalanine when tested at 35 and 39 degrees C. Three mutant lines were additionally tested for L-phenylalanine tRNA charging levels and for transport of L-arginine. The lines had parental cell levels of tRNA charging and L-arginine transport which suggest that the induced genetic defect affects a specific L-phenylalanine transport system.


Subject(s)
Drug Resistance , Mutation , Phenylalanine/analogs & derivatives , p-Fluorophenylalanine/pharmacology , HeLa Cells/radiation effects , Humans , Temperature , Ultraviolet Rays
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