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Biomedical subjects

T P Jackson

Publications and source records attributed to T P Jackson.

6 recordsLinked to original sources

Bacterial vaginosis and cervical dilation and effacement at 24-29 weeks' gestation.

The purpose of this study was to investigate the association between bacterial vaginosis (BV) and cervical dilation and effacement, as measures of impending preterm delivery. The Pregnancy, Infection, and Nutrition Study collected genital tract specimens and documented cervical change from 807 eligible women between 24 and 29 weeks' gestation. BV was assessed with Nugent-scored vaginal smears, and analyzed in relation to cervical measurements. At 24-29 weeks' gestation, <7% of women had a dilated cervix, 31% had a cervix < or =2 cm, and 17.3% had BV. Unadjusted analyses found no associations between BV and cervical measurements. Adjusted logistic regression suggested an association between BV and cervical effacement among women with a sexually transmitted disease (STD) earlier in pregnancy (odds ratio = 1.9, 95% CI 0.8-4.3). Stratified analyses for BV/dilation also suggested interaction with STDs. Overall, BV was not association with cervical dilation or effacement at 24-29 weeks' gestation.

Cervix Uteri↗

Association between bacterial vaginosis and fetal fibronectin at 24-29 weeks' gestation.

OBJECTIVE: To investigate the relationship between fetal fibronectin and bacterial vaginosis, which are associated with an increased risk for preterm delivery. METHODS: Researchers for the Pregnancy, Infection and Nutrition Study, a cohort study of pregnant women at three central North Carolina sites, collected genital tract specimens from all enrolled women between 24 and 29 weeks' gestation. Among women with last menstrual periods between March 10, 1995, and August 15, 1996, 868 pregnancies were eligible for this analysis. Fetal fibronectin was assessed by a dipstick immunoassay kit. Bacterial vaginosis was evaluated by Nugent-scored, Gram-stained vaginal smears (scores of 7-10 considered positive). RESULTS: Overall, 6.3% of women had positive fetal fibronectin test results, and 18.8% had bacterial vaginosis. The unadjusted relative risk (RR) of fetal fibronectin-positivity comparing women with bacterial vaginosis to those without bacterial vaginosis was 1.6 (95% confidence interval [CI] 1.1, 2.5). Using multiple logistic regression to adjust for race, maternal age, parity, and location of care, women who had bacterial vaginosis and smoked at the time of recruitment were at substantially increased risk of fetal fibronectin-positivity (RR 7.8, 95% CI 2.2, 27.8) compared with smokers without bacterial vaginosis. Among nonsmokers, bacterial vaginosis was not associated with fetal fibronectin-positivity (RR 1.0, 95% CI 0.4, 2.4). These results were essentially unchanged after adding the requirement of vaginal pH exceeding 4.5 to the bacterial vaginosis definition. CONCLUSION: Fetal fibronectin was associated positively with bacterial vaginosis, but only among women who smoked. These results might provide clues as to the biologic relationship between smoking, infection, and preterm delivery.

Adolescent↗

Race/ethnicity, vaginal flora patterns, and pH during pregnancy.

OBJECTIVES: To investigate the relationship between bacterial vaginosis during pregnancy and black race/ethnicity. STUDY DESIGN: Gram staining was used to evaluate vaginal flora in 842 women at 24 to 29 weeks' gestation. RESULTS: Overall, 22.3% of blacks and 8.5% of whites had bacterial vaginosis. Vaginal pH and flora differed significantly by race/ethnicity; blacks were more likely to have pH > or = 4.5, no lactobacilli, small gram-variable and -negative rods, and Mobiluncus compared with whites (odds ratios 1.6, 1.5, 1.4, and 10.6, respectively). Quantity of morphotypes also differed, especially for Mobiluncus. Among women with Mobiluncus present (12.0% of blacks and 1.3% of whites), 73.3% of blacks compared with 40.0% of whites had the highest level. Adjustment for sociodemographics, sexual activity, sexually transmitted diseases, health behavior, and sexual hygiene did not explain these differences. CONCLUSION: We observed race/ethnicity differences in vaginal flora ecology. These differences may ultimately play a role in the larger proportion of preterm deliveries among black women compared with white women.

Adolescent↗

Assessment of the interaction between urokinase and reactive site mutants of protein C inhibitor.

Urokinase-type plasminogen activator (uPA) is a serine protease involved in pericellular proteolysis and tumor cell metastasis via plasmin-mediated degradation of extracellular matrix proteins. Plasma uPA is inhibited by the serine protease inhibitor protein C inhibitor (PCI) by the insertion of PCI's reactive site loop into the active site of the protease. To better understand the structural aspects of this inhibition, 15 reactive-site mutants of recombinant PCI (rPCI) were assayed for differences in uPA inhibition. These assays revealed that substitutions at the P1 Arg354 and P3 Thr352 sites of rPCI were detrimental to inhibitory activity, while P3' Arg357 mutations had little effect upon the inhibition rate. However, replacement of the P2 Phe353 with small residues like Ala and Gly increased the effectiveness of rPCI three- to four fold. To explain these altered rates of inhibition, a computer-derived molecular model of uPA was generated and docked to a model of PCI to simulate complex formation. The changes made by mutagenesis were then recreated in the model of uPA-PCI. In accordance with the kinetic data, the poor performance of P3 variants is primarily attributable to charge repulsion, while alleviation of steric hindrance at P2 produces the observed increase in uPA inhibition. In the model, residues at P3' interact with PCI rather than uPA, consistent with P3' variants demonstrating that little variation from wild-type activity. Ultimately, this combination of mutagenesis and molecular modeling will further refine our understanding of the interaction between PCI and uPA.

Amino Acid Sequence↗

Intermolecular interactions between protein C inhibitor and coagulation proteases.

Protein C inhibitor (PCI) inhibits multiple plasma serine proteases. To determine which residues contribute to its specificity of inhibition, 19 mutations in the reactive site loop of PCI (from Thr352 to Arg357) were generated and assayed with thrombin, activated protein C (APC), and factor Xa. To identify the intermolecular interactions responsible for these kinetics, a molecular model of PCI was generated using alpha 1-protease inhibitor and ovalbumin as templates. This model of PCI was docked with thrombin, followed by extensive energy minimization, to determine a lowest energy complex. The resulting docked complex was used as a template to form molecular models of PCI-APC and PCI-factor Xa complexes. The best inhibitors of thrombin contained Pro or Gly at the P2 position in place of Phe353, with 2- and 7-fold increases in activity, respectively. These substitutions reduced steric interactions with the 60-insertion loop unique to thrombin. The best inhibitors of APC and factor Xa contained Arg at the P3 position in place of Thr352, with 2- and 5-fold increases in inhibition rates, respectively. The molecular model predicts that Arg in this position could form a salt bridge with Glu217 of each protease. Changing Arg357 at the P3' position had little effect on protease inhibition, consistent with the observation in the model that this residue points toward the body of PCI, forming a salt bridge with Glu220. Given its broad specificity of inhibition, PCI has proven very useful in understanding the nature of serpin-protease interactions using multiple mutations in a serpin assayed with multiple proteases.

Blood Coagulation Factors↗

Optimizing the performance of direct-reading dosimeters.

The direct-reading dosimeter has often been criticized for its lack of precision and accuracy and its tendency to produce false readings. This study investigates that contention and discusses the limitations of these instruments and the consequent effects on personnel monitoring. The precautions which must be observed to eliminate or minimize these limitations in the data are explained. Data are presented to support the statement that direct-reading dosimeters, when properly used, are accurate and precise instruments whose small size, ruggedness, resistance to severe environments, hermeticity and self-reading capabilities can be a decided advantage over transfer standards for some applications.

Humans↗