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Articles by J Barber
Total Records ( 3 ) for J Barber
  Y. S Lin , K Yasuda , M Assem , C Cline , J Barber , C. W Li , V Kholodovych , N Ai , J. D Chen , W. J Welsh , S Ekins and E. G. Schuetz
 

The pregnane X receptor (PXR; PXR.1) can be activated by structurally diverse lipophilic ligands. PXR.2, an alternatively spliced form of PXR, lacks 111 nucleotides encoding 37 amino acids in the ligand binding domain. PXR.2 bound a classic CYP3A4 PXR response element (PXRE) in electrophoretic mobility shift assays, but transfected PXR.2 failed to transactivate a CYP3A4-promoter-luciferase reporter plasmid in HepG2 cells treated with various PXR ligands. Cotransfection experiments showed that PXR.2 behaved as a dominant negative, interfering with PXR.1/rifampin activation of CYP3A4-PXRE-LUC. In HepG2 and LS180 cells stably transduced with PXR.1, PXR target genes (CYP3A4, MDR1, CYP2B6, and UGT1A1) were higher than mock-transduced cells in the absence of ligand and were further induced in the presence of rifampin. In contrast, PXR.2 stably introduced into the same host cells failed to induce target genes over levels in mock-transfected cells after drug treatment. Our homology modeling suggests that ligands bind PXR.1 more favorably, probably because of the presence of a key disordered loop region, which is missing in PXR.2. Yeast two-hybrid assays revealed that, even in the presence of ligand, the corepressors remain tightly bound to PXR.2, and coactivators are unable to bind at helix 12. In summary, PXR.2 can bind to PXREs but fails to transactivate target genes because ligands do not bind the ligand binding domain of PXR.2 productively, corepressors remain tightly bound, and coactivators are not recruited to PXR.2.

  Y. S Lin , K Yasuda , M Assem , C Cline , J Barber , C. W Li , V Kholodovych , N Ai , J. D Chen , W. J Welsh , S Ekins and E. G. Schuetz
 

The pregnane X receptor (PXR; PXR.1) can be activated by structurally diverse lipophilic ligands. PXR.2, an alternatively spliced form of PXR, lacks 111 nucleotides encoding 37 amino acids in the ligand binding domain. PXR.2 bound a classic CYP3A4 PXR response element (PXRE) in electrophoretic mobility shift assays, but transfected PXR.2 failed to transactivate a CYP3A4-promoter-luciferase reporter plasmid in HepG2 cells treated with various PXR ligands. Cotransfection experiments showed that PXR.2 behaved as a dominant negative, interfering with PXR.1/rifampin activation of CYP3A4-PXRE-LUC. In HepG2 and LS180 cells stably transduced with PXR.1, PXR target genes (CYP3A4, MDR1, CYP2B6, and UGT1A1) were higher than mock-transduced cells in the absence of ligand and were further induced in the presence of rifampin. In contrast, PXR.2 stably introduced into the same host cells failed to induce target genes over levels in mock-transfected cells after drug treatment. Our homology modeling suggests that ligands bind PXR.1 more favorably, probably because of the presence of a key disordered loop region, which is missing in PXR.2. Yeast two-hybrid assays revealed that, even in the presence of ligand, the corepressors remain tightly bound to PXR.2, and coactivators are unable to bind at helix 12. In summary, PXR.2 can bind to PXREs but fails to transactivate target genes because ligands do not bind the ligand binding domain of PXR.2 productively, corepressors remain tightly bound, and coactivators are not recruited to PXR.2.

  J Barber , S Muller , T Whitehurst and E. Hay
 

Background. Epidemiological surveys often rely on self-report as a measure of morbidity in a population. However, these data can also be extracted from primary care records.

Objective. To compare morbidity estimates based on self-report with those obtained from primary care records.

Methods. A cross-sectional survey and accompanying medical record review were carried out in all consenting adults aged ≥50 years in three general practices in North Staffordshire, UK. Self-reported morbidity was compared with computerized general practice consultation records for the 2 years prior to the survey.

Results. Of the 7878 survey responders, 5889 consented to medical record review. Agreement between self-reported and consultation data was excellent for diabetes. Agreement between the two sources of data was lower for hypertension, heart problems, chest problems and eyesight problems. It was poor for deafness and falls.

Conclusions. Self-report and consultation data provide comparable estimates of the prevalence of specific diagnoses such as diabetes. For other conditions, self-report and consultation records provide different measures of prevalence, and the choice of measure will depend on the morbidity being studied.

 
 
 
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