The cytochrome P450 (CYP) 3A subfamily is estimated to participate in the biotransformation of 50% of the currently prescribed drugs. Four members of the CYP3A subfamily have been identified in humans: CYP3A4, CYP3A5, CYP3A7, and CYP3A43. Initial data suggested that CYP3A5 accounts for only a small proportion of the total hepatic CYP3A in about 20% of samples, but it was later revealed that CYP3A5 represents more than 50% of the total CYP3A amount in some individuals. Several genetic variants have been described for the CYP3A5 gene, of which the CYP3A5*3 allele (gA6986G), the most common form and leading to the loss of CYP3A5 activity, has been extensively investigated in the aspect of pharmacokinetics and disease risk. This review summarized the molecular characteristics of the CYP3A5 gene, and discusses the association of the CYP3A5*3 polymorphism with disease risks such as cancer and hypertension, along with its role in the pharmacokinetics of CYP3A substrates.
Alleles ; Biotransformation ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System ; Humans ; Hypertension ; Pharmacogenetics ; Pharmacokinetics

BACKGROUND: Eosinophil cationic protein (ECP), one of the eosinophil granule proteins released during allergic reactions, may play a major role in the allergic inflammatory process. The measurement of ECP in serum may be a useful indicator of eosinophil activity in ongoing inflammatory processes. We investigated the clinical utility of ECP measurement in serum in patients with bronchial asthma, allergic rhinitis and atopic dermatitis, after standardizing sample processing. METHODS: We measured the serum ECP levels in patients with bronchial asthma (n=38), chronic obstructive pulmonary diseases (COPD) (n=13), respiratory symptoms (n=19), allergic rhinitis (n=26), non-allergic rhinitis (n=24), and atopic dermatitis (n=10) and in normal healthy controls (n=16) by the fluoroenzyme immunoassay using Pharmacia CAP System, and evaluated the correlation between ECP level and blood eosinophil number, or ECP and IgE levels. Blood eosinophil number was counted by the automated cell counter. RESULTS: Serum ECP levels were significantly higher in patients with bronchial asthma (15.6+/- 12.6 g/L), COPD (13.3+/-7.2 g/L), allergic rhinitis (23.8+/-13.2 g/L), and atopic dermatitis (20.6+/- 18.4 g/L) than in normal controls (7.5+/-4.2 g/L) (P <0.05). ECP levels were also significantly higher in patients with bronchial asthma and COPD than in patients with simple respiratory symptoms (6.9+/-4.7 g/L), whose ECP levels did not statistically differ from those in normal controls. ECP levels were also significantly higher in patients with allergic rhinitis than in patients with non-allergic rhinitis (9.5+/-5.1 g/L), whose ECP levels did not statistically differ from those in normal controls. Serum ECP level and eosinophil number in peripheral blood were correlated only in patients with bronchial asthma (r=0.53, P <0.01) and no correlation between ECP and IgE levels was found in all of the patients. CONCLUSIONS: ECP is the one of the secretory components released from the eosinophil granule and measurement of ECP in serum might be one of the noninvasive tool to assess the activity in relation to eosinophil involvement in various allergic diseases.
Asthma ; Cell Count ; Dermatitis, Atopic ; Eosinophil Cationic Protein* ; Eosinophil Granule Proteins ; Eosinophils ; Humans ; Hypersensitivity ; Immunoassay ; Immunoglobulin E ; Lung Diseases, Obstructive ; Pulmonary Disease, Chronic Obstructive ; Rhinitis

Purpose: To design a scoring system to predict malignancy of additional MRI-detected lesions in breast cancer patients. Materials and Methods: Eighty-six lesions (64 benign and 22 malignant) detected on preoperative MRI of 68 breast cancer patients were retrospectively included. The clinico-radiologic features were correlated with the histopathologic results using the Student's t-test, Fisher's exact test, and logistic regression analysis. The scoring system was designed based on the significant predictive features of malignancy, and its diagnostic performance was compared with that of the Breast Imaging-Reporting and Data System (BI-RADS) category. Results: Lesion size ≥ 8 mm (p < 0.001), location in the same quadrant as the primary cancer (p = 0.005), delayed plateau kinetics (p = 0.010), T2 isointense (p = 0.034) and hypointense (p = 0.024) signals, and irregular mass shape (p = 0.028) were associated with malignancy. In comparison with the BI-RADS category, the scoring system based on these features with suspicious non-mass internal enhancement increased the diagnostic performance (area under the receiver operating characteristic curve: 0.918 vs. 0.727) and detected three false-negative cases. With this scoring system, 22 second-look ultrasound examinations (22/66, 33.3%) could have been avoided. Conclusion The scoring system based on the lesion size, location relative to the primary cancer, delayed kinetic features, T2 signal intensity, mass shape, and non-mass internal enhancement can provide a more accurate approach to evaluate MRI-detected lesions in breast cancer patients.

Purpose: To design a scoring system to predict malignancy of additional MRI-detected lesions in breast cancer patients. Materials and Methods: Eighty-six lesions (64 benign and 22 malignant) detected on preoperative MRI of 68 breast cancer patients were retrospectively included. The clinico-radiologic features were correlated with the histopathologic results using the Student's t-test, Fisher's exact test, and logistic regression analysis. The scoring system was designed based on the significant predictive features of malignancy, and its diagnostic performance was compared with that of the Breast Imaging-Reporting and Data System (BI-RADS) category. Results: Lesion size ≥ 8 mm (p < 0.001), location in the same quadrant as the primary cancer (p = 0.005), delayed plateau kinetics (p = 0.010), T2 isointense (p = 0.034) and hypointense (p = 0.024) signals, and irregular mass shape (p = 0.028) were associated with malignancy. In comparison with the BI-RADS category, the scoring system based on these features with suspicious non-mass internal enhancement increased the diagnostic performance (area under the receiver operating characteristic curve: 0.918 vs. 0.727) and detected three false-negative cases. With this scoring system, 22 second-look ultrasound examinations (22/66, 33.3%) could have been avoided. Conclusion The scoring system based on the lesion size, location relative to the primary cancer, delayed kinetic features, T2 signal intensity, mass shape, and non-mass internal enhancement can provide a more accurate approach to evaluate MRI-detected lesions in breast cancer patients.

Microvascular ultrasound (US) techniques are advanced Doppler techniques that provide high sensitivity and spatial resolution for detailed visualization of low-flow vessels. Microvascular US imaging can be applied to breast lesion evaluation with or without US contrast agents. Microvascular US imaging without a contrast agent uses a sophisticated wall filtering system to selectively obtain low-flow Doppler signals from overlapped artifacts. Microvascular US imaging with secondgeneration contrast agents amplifies flow signals and makes them last longer, which facilitates hemodynamic evaluation of breast lesions. In this review article, we will introduce various microvascular US techniques, explain their clinical applications in breast cancer diagnosis and radiologic-histopathologic correlation, and provide a summary of a recent radiogenomic study using microvascular US.

Microvascular ultrasound (US) techniques are advanced Doppler techniques that provide high sensitivity and spatial resolution for detailed visualization of low-flow vessels. Microvascular US imaging can be applied to breast lesion evaluation with or without US contrast agents. Microvascular US imaging without a contrast agent uses a sophisticated wall filtering system to selectively obtain low-flow Doppler signals from overlapped artifacts. Microvascular US imaging with secondgeneration contrast agents amplifies flow signals and makes them last longer, which facilitates hemodynamic evaluation of breast lesions. In this review article, we will introduce various microvascular US techniques, explain their clinical applications in breast cancer diagnosis and radiologic-histopathologic correlation, and provide a summary of a recent radiogenomic study using microvascular US.

BACKGROUND: The product of oxygen-free radicals inf1ict oxidative injuries on healthy cells. Antioxidants such as superoxide dismutase(SOD), glutathione peroxidase, and reduced glutathione(GSH) are present in almost all cells and play important roles in metabolism, transport, and cellular protection. We measured blood GSH levels in healthy controls and patients with non insulin dependent diabetes mellitus(NIDDM) for evaluation of the clinical usefulness of GSH. METHODS: Erythrocyte GSH levels were measured in fifty healthy controls and thirty NIDDM patients with diabetic retinopathies by Beutler's method. We also tested within-run precision, between-run precision, linearity and recovery rate to evaluate this method measuring erythrocyte GSH levels. RESULTS: The GSH levels (mean +/-SD) of NIDDM patients (5.03+/-0.67mumo1/Hb) were significantly lower than those of healthy control group (6.46+/-0.85mumo1/Hb)(P<0.001). The results of within-run precision and between-run precision when stored at 4degrees Cwere excellent (coefficient of variation were 2.79% and 2.42%, respectively), however, when stored at the room temperature the GSH levels were sharply declined. The linearity and recovery rate were acceptable. CONCLUSIONS: The prescision, linearity, and recovery rate of GSH measurement were excellent. The GSH levels in NIDDM patient group were reduced, and this probably contributes to the defective defense mechanism against increased oxidative stress. Additional measurement of other antioxidants such as superoxide dismutase and glutathione Peroxidase may be required to clarify the pathologic significance of glutathione metabolism in various diseases.
Antioxidants ; Diabetes Mellitus, Type 2 ; Diabetic Retinopathy ; Erythrocytes* ; Glutathione Peroxidase ; Glutathione* ; Humans ; Insulin ; Metabolism ; Oxidative Stress ; Superoxide Dismutase ; Superoxides