1 Hypercholesterolaemia often occurs in patients with type 2 diabetes, who therefore encounter administration of HMG-CoA reductase inhibitors. Alteration of pancreatic b-cell function leading to an impaired insulin secretory response to glucose plays a crucial role in the pathogenesis of type 2 diabetes. Therefore, it is important to examine the e ects of HMG-CoA reductase inhibitors on bcell function. 4 Simvastatin (0.3 mg ml 71 ), more potently than simvastatin-acid (30 mg ml 71 ), inhibited glucoseinduced insulin secretion from islets, whereas pravastatin (100 mg ml 71 ) had no e ect.

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We used quick‐freeze deep‐etch replica electron microscopy to visualize the native structure of inositol‐1,4,5‐trisphosphate receptor (IP3R) in the cell. In the dendrites of Purkinje neurons of bovine cerebellum there were many vesicular organelles whose surfaces were covered with a two‐dimensional crystalline array of molecules. Detailed examination of the cytoplasmic true surface of such vesicles in replica revealed that the structural unit, identified as IP3R by immunocytochemistry and subsequent Fourier analysis, is a square‐shaped assembly and is aligned so that the side of the square is inclined by approximately 20 degrees from the row‐line of the lattice. Comparison with the ryanodine receptor (RyaR), another intracellular Ca2+ channel on the endoplasmic reticulum, suggested that IP3R, unlike RyaR, has a very compact structure, potentially reflecting the crucial difference in the function of the cytoplasmic portion of the molecule.

Many researchers have established the utility of the dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in the differential diagnosis in the head and neck region, especially in the salivary gland tumors. The subjective assessment of the pattern of the time-intensity curve (TIC) or the simple quantification of the TIC, such as the time to peak enhancement (T peak) and the wash-out ratio (WR), is commonly used. Although the semiquantitative evaluations described above have been widely applied, they do not provide information on the underlying pharmacokinetic analysis in tissue. The quantification of DCE-MRI is preferable; therefore, many compartment model analyses have been proposed. The Toft and Kermode (TK) model is one of the most popular compartment models, which provide information about the influx forward volume transfer constant from plasma into the extravascular-extracellular space (EES) and the fractional volume of EES per unit volume of tissue is used in many clinical studies. This paper will introduce the method of pharmacokinetic analysis and also describe the clinical application of this technique in the head and neck region.

Objectives: To quantitatively evaluate the relationship of vascularity of tongue cancer as demonstrated on intraoral ultrasonography images and tumour thickness with pathological grade of malignancy and the presence of cervical lymph node metastases. Methods: 18 patients with tongue cancer were enrolled in this retrospective study. Using Doppler ultrasonography images of the invasion front of the cancers along the length of their tumour boundaries, three vascular indexes were analysed quantitatively, namely ratio of blood flow signal area within the cancer to whole tumour area (BAR), blood flow signal number ratio (BNR) and blood flow signal width ratio (BWR). The associations between these three indexes and occurrence of cervical lymph node metastasis and pathological grade of malignancy [Yamamoto-Kohama (YK) classification] were assessed. Furthermore, the relationship between tumour thickness and occurrence of cervical lymph node metastasis was evaluated on B-mode intraoral ultrasonography images. Results: There was no significant association between BAR and tumour thickness or occurrence of cervical lymph node metastasis. The BNRs and BWRs of patients with cervical lymph node metastasis were significantly higher than those of patients without nodal involvement. The BWRs of patients with high-grade malignancy (YK-4C) were significantly higher than those of patients with low-grade malignancy (YK-2 or 3). Conclusions: BNR and BWR on the invasion front of the tongue cancer are predictors of pathological grade of malignancy and cervical lymph node metastasis. Dentomaxillofacial Radiology (2016Radiology ( ) 45, 20150372. doi: 10.1259 Cite this article as: Yamamoto C, Yuasa K, Okamura K, Shiraishi T, Miwa K. Vascularity as assessed by Doppler intraoral ultrasound around the invasion front of tongue cancer is a predictor of pathological grade of malignancy and cervical lymph node metastasis. Dentomaxillofac Radiol 2016; 45: 20150372.

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:CYP2D6 is a polymorphic enzyme that catalyzes the oxidation of various drugs. At least 40-mutant alleles of CYP2D6 have been reported. CYP2D6*14, which is one of them found in Asian populations, causes deficient activity of CYP2D6. Four amino acid substitutions, P34S, G169R, R296C, and S486T, are present in the protein encoded by CYP2D6*14 (CYP2D6 14). Among them, G169R is thought to be a definitive substitution because it is unique to CYP2D6 14. However, a previous study showed that the activity of G169R-substituted CYP2D6 was about 40% of wild-type CYP2D6, suggesting that a combination of G169R and other substitutions may be required to abolish the activity of CYP2D6. In the present study, we examined the effects of combined substitutions of G169R and P34S on the functional properties of CYP2D6 and compared them with those of a single substitution of G169R or P34S using a cDNA expression system of V79 cells. The results showed that a combined substitution of G169R and P34S reduced the activities of CYP2D6 to less than the detection limit of our analytical method for bufuralol 1-hydroxylation and dextromethorphan O-demethylation. However, these activities were not completely abolished by a single substitution of P34S or G169R. The findings suggest that simultaneous substitution of G169R and P34S is crucial for almost completely abolishing the activity of CYP2D6 at least in V79 cells, although whether the absence of metabolism is due to the absence of functional protein or catalytic incompetency remains unclear because the levels of CYP2D6 protein expressed in V79 cells were too low to be determined by difference COreduced spectra.

The coefficients for diffusion of the MM were sensitive to change by clenching, and lambda(2) was the most sensitive. Moreover, the relative distribution of the bite forces had no effect on any of the indices.