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Purpose: The mechanism of cytotoxicity of silibinin on two human hepatocellular carcinoma (HCC) cell lines, HepG2 (p53 wild-type) and Hep3B cells (p53 null), is examined in relation with the induction of autophagy and phosphorylation of AMP-activated protein kinase (p-AMPK). Materials and Methods: Levels of apoptosis in relation to the levels of autophagy and those of glycolysis-related proteins, glucose transporter 1/4 (Glut1/4) and hexokinase-II (HK2), in HepG2 and Hep3B cells were examined. Results: Silibinin-induced apoptosis was incomplete for HCC cell death in that up-regulated autophagy and/or reduced level of glycolysis, which are induced by silibinin treatment, antagonized silibinin-induced apoptosis. Inhibition of autophagy with 3-methyl adenine (3MA) or blocking of AMP-activated protein kinase (AMPK) activation with Compound C (CC) enhanced silibinin-induced apoptosis. The results confirm that AMPK involved in autophagy as well as in glycolysis remaining with silibinin is responsible for attenuation of silibinin-induced apoptosis. Blocking of AMPK or autophagy contributes to the enhancement of silibinin's cytotoxicity to HepG2 and Hep3B cells. Conclusion: This study shows that incomplete apoptosis of HCC by silibinin treatment becomes complete by repression of autophagy and/or glycolysis. [ABSTRACT FROM AUTHOR]

SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p = 0.0110, odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16–3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (p = 0.0067, OR 2.65, 95% CI 1.28–5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele. An intronic SNP of SH2D1A is associated with SLE. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 7 (IRF7) has an essential role in the production of type I interferon. Although recent studies detected association of a single nucleotide polymorphism (SNP) rs4963128 in PHD and ring finger domains 1 (PHRF1)/KIAA1542, located closely to IRF7, and IRF7 rs1131665 (glutamine (Gln) 412 arginine (Arg)) with systemic lupus erythematosus (SLE), causal variants have not been established. In this study, we resequenced exons and introns of IRF7 to screen for all common polymorphisms, and examined whether they were associated with SLE in 416 Japanese patients with SLE and 505 healthy controls. We also tested whether the association of PHRF1 rs4963128 with SLE was replicated in a Japanese population. None of the IRF7 polymorphisms was associated with SLE. PHRF1 rs4963128T was not significantly associated with occurrence of SLE either; however, this allele was significantly increased in SLE with anti-Sm antibodies (6.8%) as compared with healthy controls (3.1%, P = 0.014, odds ratio [OR] 2.31) and SLE without anti-Sm antibodies (3.3%, P =0.041, OR 2.12). This allele was also increased in SLE with renal disorder (5.1%) as compared with those without renal disorder (2.4%, P = 0.047, OR 2.17). These results confirmed recently reported association of PHRF1 rs4963128T with anti-Sm antibody positive SLE in African-American populations, and supported the role of PHRF1-IRF7 region in the genetics of SLE. [ABSTRACT FROM AUTHOR]

Background: Conventional T2-weighted (T2-WI) magnetic resonance imaging (MRI) has poor sensitivity for prostate transition-zone (TZ) cancer detection. Purpose: To retrospectively evaluate the clinical value of diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) in combination with T2-WI for the diagnosis of TZ cancer. Material and Methods: Twenty-six TZ cancers in 23 patients with at least one tumor (tumor size >10 mm) located predominantly in the TZ were included in the study. Sixteen peripheral-zone (PZ) cancers in 12 patients with PZ cancer but without TZ cancer (control group) were selected by step-section pathologic maps. All patients underwent MRI and radical prostatectomy. MRI was obtained by a 1.5T superconducting system with a phased-array coil. Imaging sequences were T2-WI with fat saturation (FST2-WI), DW-MRI (single-shot echoplanar image, b=0 and 1000 s/mm2, apparent diffusion coefficient [ADC] map findings), and DCE-MRI (3D fast spoiled gradient recalled [SPGR], contrast medium [0.2 mmol/kg], total injection time 5 s, image acquisition 30, 60, and 90 s). Sensitivity, specificity, accuracy, and positive predictive value (PPV) for the diagnosis of TZ cancer were evaluated in four protocols: A) FST2-WI alone, B) FST2-WI plus DW-MRI, C) FST2-WI plus DCE-MRI, D) FST2-WI plus DW-MRI plus DCE-MRI. Results: Sensitivity, specificity, accuracy, and PPV in protocol A (FST2-WI alone) were 61.5%, 68.8%, 64.3%, and 76.2%, respectively. FST2-WI plus DW-MRI (protocol B) improved the sensitivity, specificity, accuracy, and PPV. In FST2-WI plus DW-MRI plus DCE-MRI (protocol D), the number of true-negative lesions increased and false-positive lesions decreased, and the sensitivity, specificity, accuracy, and PPV were 69.2%, 93.8%, 78.6%, and 94.7%, respectively. There was a significant difference between protocols A and D (P<0.05). Conclusion: Adding DW-MRI to FST2-WI in the diagnosis of prostate TZ cancer increased the diagnostic accuracy. The addition of DCE-MRI may be an option to improve the specificity and PPV of diagnosing TZ cancer with FST2-WI and DW-MRI. [ABSTRACT FROM AUTHOR]

Background: Although fast acquisition of multidetector-row computed tomography (MDCT) can make it possible to acquire sufficient early vascular enhancement using small volumes and high concentrations of contrast material (CM), there are still some problems with nephrotoxicity and costs related to CM. Purpose: To compare the qualitative and quantitative performance in cervicocranial CT angiography (CTA) using two different iodine volumes and concentrations of CM. Material and Methods: CTA ranging from the aortic arch (AA) to distal to the circle of Willis (cW) was performed on a 32-MDCT system. Fifty-eight patients were randomly divided into two groups: group A (29 patients) received 60 ml of 300 mg I/ml CM, and group B (the other 29 patients) received 40 ml of 370 mg I/ml CM. Time to peak arterial enhancement at cW (Tc) was calculated. As scan speed was 96.9 mm/s and injection rate was 4.0 ml/s, scanning delay was individually decided according to Tc and scan duration between AA and cW. Arterial attenuation along the z-axis at eight points in the carotid-cerebral artery and venous attenuation of the internal jugular vein (IJV) at carotid bifurcation were measured. Mean attenuation values were then quantitatively analyzed. Postprocessing images were qualitatively assessed. Results: Arterial attenuation profiles revealed maximum attenuation at the distal common carotid artery in both groups. Although there were no significant differences in mean arterial attenuation in group A versus group B (402±70 HU vs. 407±67 HU; P=0.78), venous attenuation of the IJV was lower in group B than in group A (114±57 HU vs. 224±81 HU; P<0.001). Although arterial images demonstrated no difference qualitatively between the two groups, the venous contamination of IVC was less prominent in group B. Conclusion: Although a different amount of CM was administered in both groups, quantitative and qualitative arterial images did not show significant differences between the two groups. [ABSTRACT FROM AUTHOR]

Residual monomers in resin-based biomaterials cause cytotoxicity. We previously showed that methyl methacrylate (MMA) induced mRNA expression of the glutathione S-transferase alpha 1 gene (Gsta1) located downstream of the cis-acting anti-oxidant responsive element (ARE). Herein, we tested the hypothesis that MMA activated the Gsta1 promoter through the ARE. HepG2 cells were transfected with a luciferase reporter vector containing the ARE and the Gsta1 promoter (-990 to +46 bp) and cultured for 12 hrs with MMA (initial concentration, 10 mM). Analysis of the expressed luciferase activity indicated that MMA activated the promoter 2.6-fold. MMA (from 1 to 30 mM) dose-dependently increased the promoter activity, which reached a plateau between 6 and 12 hrs. In HepG2 cells transfected with a reporter vector containing 2 AREs and a TATA-like promoter, 10 mM MMA increased the reporter expression 2.8-fold. These results suggest that MMA increases Gsta1 transcription through ARE-mediated promoter activation. Abbreviations: ANOVA, analysis of variance; ARE, anti-oxidant responsive element; Gsta1, mouse glutathione S-transferase alpha 1 gene; GSH, glutathione; GST, glutathione S-transferase; Keap1, Kelch ECH associating protein 1; MMA, methyl methacrylate; NQO1, NAD(P)H:quinone oxidoreductase 1; Nrf2, nuclear factor erythroid 2-related factor 2; PCR, polymerase chain-reaction; ROS, reactive oxygen species; SEM, standard error of mean; t-BHQ, tert-butylhydroquinone. [ABSTRACT FROM AUTHOR]

Background: T1-shortening contrast media are routinely used in magnetic resonance (MR) examinations for the diagnosis of brain tumors. Although some studies show a benefit of 3 Tesla (T) compared to 1.5T in delineation of brain tumors using contrast media, it is unclear which pulse sequences are optimal. Purpose: To compare gadopentetate dimeglumine (Gd-DTPA)-induced signal enhancements in rat brain C6 glioma in the thalamus region among different pulse sequences in 3T MR imaging. Material and Methods: Five rats with a surgically implanted C6 glioma in their thalamus were examined. T1-weighted brain images of the five rats were acquired before and after Gd-DTPA administration (0.1 mmol/kg) using three clinically available pulse sequences (spin echo [SE], fast SE [FSE], fast spoiled gradient echo [FSPGR]) at 3T. Signal enhancement in the glioma (ET) was calculated as the signal intensity after Gd-DTPA administration scaled by that before administration. Pulse sequences were compared using the Tukey-Kramer test. Results: ET was 1.12±0.05 for FSE, 1.26±0.11 for FSPGR, and 1.20±0.11 for SE. FSPGR showed significantly higher signal enhancement than FSE and comparable enhancement to SE. Conclusion: FSPGR is superior to FSE and comparable to SE in its ability to delineate rat brain C6 glioma in the thalamus region. [ABSTRACT FROM AUTHOR]

The effect of synthetic CpG-oligodeoxynucleotides (CpG-ODN) on the development of lupus nephritis during preactive phase (within seven months of age) in autoimmune lupus NZB × NZWF[sub 1] (B/WF[sub 1]) mice was examined. Treatment of CpG-ODN was started at the age of 2.75 months and continued until 6.25 months. Overt disease began at the age of six months and progressed linearly at the age of 6.75 months in CpG-ODN-treated, but not control ODN-treated (control) groups. Also compared to control group, CpG-ODN-treated mice exhibited a severe glomerulonephritis (GN), with prominent deposits of IgG2a and C3, which paralleled increased titre of IgG2a type anti-nuclear antibody in the blood. Among several cytokines (interleukin, IL-6, IL-4, IL-1α, IL-10, interferon-γ and tumor necrosis factor-α) in blood, IL-6 production paralleled the development of lupus nephritis. The present study suggests that CpG-ODN may enhance IL-6 production. The role of IL-6 in the development of GN will be discussed. [ABSTRACT FROM AUTHOR]

We report two patients with systemic lupus erythematosus (SLE) in whom cytomegalovirus (CMV) infection may have played a significant role in the exacerbation or onset of symptoms. The first patient had thrombocytopenia and the second had proteinuria. CMV infection was observed in both patients when their symptoms developed. [ABSTRACT FROM AUTHOR]

Examines manufacturing firms' restructuring behavior in the Asia-Pacific Basin and focuses on Japanese multinational enterprises (MNE) and the intrafirm division of labor between the Japanese parents and their Asian affiliates. Pattern of restructuring behavior; Time lag in the production transfer; Gaps in the stages of economic development.

The author reported stress analysis of infinite amsotropic plate with a hole at CCM-3 1986 [1]. The present report deals with rectangular anistropic plate with a circu lar hole under uniaxial loading on the basis of theory of anisotropic plane elasticity [2] Series of circular hole stress function are used, which unknown coefficients are deter mined by Least Square Method with rectangular boundary integration Stress distribution of isotropic plate, cross-ply and angle-ply laminates, which aspect ratio is 2 and ratio of hole radius to the half width is 0 5, are shown by the analysis, test and FEM with good coincidence Stress concentration factor around hole is also presented for variation of the above parameters. [ABSTRACT FROM PUBLISHER]

The author reflects on the veterinary pathology in Japan. He mentions that the collaboration between the Japan College of Veterinary Pathology with the European College of Veterinary Pathology and the American College of Veterinary Pathology would enhance the standard of veterinary pathology in the field of education and research. He also states that in Japan there are two veterinary pathology organizations which is composed of the certified veterinary pathologists and the non-certified one.