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2 result(s) for "Lye, S.J."
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Expression of breast cancer resistance protein (BCRP/ABCG2) in human placenta throughout gestation and at term before and after labor
Breast cancer resistance protein, BCRP, is a multidrug resistance protein that is highly expressed in the human placenta. In cancer tissues, this protein actively extrudes a wide variety of chemically and structurally unrelated chemotherapeutic drugs and other compounds. Studies in mice have shown that in the absence of BCRP activity in the placenta, there is a 2-fold increase in the uptake in BCRP substrates into fetus. This suggests that in the placenta, BCRP extrudes compounds that would otherwise cross the syncytiotrophoblast cells into fetal circulation. The purpose of this study was to examine the expression and localization of BCRP in the human placenta throughout gestation. Tissues from 6-13, 16-19, 24-29, 32-35, and 38-41 weeks of gestation were used. Real time RT-PCR analysis demonstrated that the mRNA levels of BCRP in the placenta do not change significantly as gestation progressed. However, Western blot analysis revealed that the protein levels increased towards the end of gestation. We demonstrated that BCRP is localized to the syncytiotrophoblast of the placenta and in some fetal blood vessels within the placenta. Tissues from the early stages of pregnancy (6-13 weeks) showed fewer BCRP positive blood vessels than term tissues (38-41 weeks).
Long-Term Prognostic Value of Appropriate Myocardial Perfusion Imaging
Appropriate use criteria (AUC) for single-photon emission computed tomography myocardial perfusion images (SPECT-MPIs) were developed to address the growth of cardiac imaging studies. Long-term prognostic value of AUC in SPECT-MPI has not been tested in existing cohorts. We sought to determine the long-term prognostic value of MPI classified as appropriate. AUC was evaluated in a prospectively designed cohort of patients who underwent clinically indicated MPI. MPI studies were classified based on 2009 AUC for SPECT-MPI. Data regarding downstream coronary angiography (cath), revascularization and all-cause mortality, cardiac death, and nonfatal myocardial infarction (MI) were collected from national registries. Among n = 1,129 MPI scans that received an appropriate grading, 148 all-cause deaths, 109 MIs, 58 cardiac deaths, 152 caths, 113 revascularization procedures occurred over a mean follow-up period of 5.4 ± 1.2 years (0.9% cardiac death rate per year, 1.8% MI rate per year). Most of the scans were low-risk normal MPI scans (summed stress score ≤3; 74.1%). An abnormal scan was associated with higher rates of MI (19.5% vs 6.2%, hazard ratio 1.72, p = 0.017) and cardiac death (13.4% vs 2.3%, hazard ratio 2.12, p = 0.016). In conclusion, MPI scans classified as appropriate have long-term prognostic value, despite a high proportion of low-risk scans. This provides support for clinicians to consider the use of appropriate grading in addition to MPI scan results in patient management.