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In this letter, we discuss a sensor-integrated system model for metabolic syndrome prediction with workflow system. This model measures not only a cell temperature variation using invasive method but also controlling simulation for metabolic syndrome prediction. To identify the system realization, we discuss the schemes for predicting metabolic syndrome from measurement of mitochondrial activity by using high precision sensors and integrated simulation model of human energetic under high performance workflow computing environment. To predict metabolic syndrome, we built a sensor-integrated chamber that had network interface to deliver analysis results of human cells, annotation data from public hospital, and metabolic data. Using the proposed system, we showed the possibility to evaluate the functionality of human mitochondria and analyze energy metabolism.

Carcinosarcomas are rare tumors in humans as well as rats and most commonly occur in the uterus. Recently, we observed a case of incidental carcinosarcoma of the uterus in a female Wistar Hannover GALAS [BrlHan:WIST@ Jcl (GALAS)] rat at 2 years of age. Histopathologically, the tumor was characterized by an admixture of malignant epithelial and nonepithelial elements. The carcinomatous components represented a type of endometrial carcinoma, consisting of glandular and solid proliferation of large-sized tumor cells. Prominent mitoses and tumor cell invasion were observed. The sarcomatous components were characterized by multifocal proliferation of severe atypical cells with cartilage matrix and were diagnosed as chondrosarcoma. Transitions between carcinomatous and sarcomatous components were observed, and many tumor cells in the solid lesion showed immunohistochemical reactivity with both cytokeratin and vimentin. Based on these findings, this tumor was diagnosed as a uterine carcinosarcoma. This is the first report of uterine carcinosarcoma in Wistar Hannover GALAS [BrlHan:WIST@Jcl (GALAS)] rats.

Objectives: Several researchers have shown that three dimensional (3D) distribution analysis of prostate cancer is helpful when initiating needle biopsy procedures. Knowledge regarding the distribution of prostate cancer could enhance understanding of the pathophysiology involved and improve detection of these malignancies. We propose utilizing digital processing techniques to analyze prostate cancer distribution in a 3D setting., Methods: Pre-made radical prostatectomy sample slices were digitized with a resolution of 76 dpi. Slices of each sample were aligned and registered by deformation algorithm and interpolated for analysis of relative distribution statistics. We analyzed 80 samples saved in electronic medical record and compared the detection rate of preoperative needle biopsies and radical prostatectomies using our 3D analysis technique., Results: The statistical 3D distribution of prostate cancer was evaluated using a 36-sector process. Results were represented in the following two ways: distribution of a single patient, and statistical distribution of prostate cancers of multiple patients. The overall concordance rate was 62.7% between the two methods; therefore a technique is needed which can raise this percentage., Conclusions: We suggest using the normalization method to develop a software tool which permits reconstruction of the 3D distribution of prostate cancer from 2D legacy images and reduces the loss of image quality as well. This application will facilitate detection of prostate cancer by aiding in the determination of the most effective clinical position via partial sampling with decreased patient inconvenience.

Purpose: Nitric oxide (NO) has been known as an important regulator of osteoblasts and periodontal ligament cell activity. This study was performed to investigate the relationship between NO-mediated cell death of human periodontal ligament fibroblasts (PDLFs) and N-methyl-D-aspartic acid (NMDA) receptor antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK801)., Methods: Human PDLFs were treated with various concentrations (0 to 4 mM) of sodium nitroprusside (SNP) with or without 200 µM MK801 in culture media for 16 hours and the cell medium was then removed and replaced by fresh medium containing MTS reagent for cell proliferation assay. Western blot analysis was performed to investigate the effects of SNP on the expression of Bax, cytochrome c, and caspase-3 proteins. The differences for each value among the sample groups were compared using analysis of variance with 95% confidence intervals., Results: In the case of SNP treatment, as a NO donor, cell viability was significantly decreased in a concentration-dependent manner. In addition, a synergistic effect was shown when both SNP and NMDA receptor antagonist was added to the medium. SNP treated PDLFs exhibited a round shape in culture conditions and were dramatically reduced in cell number. SNP treatment also increased levels of apoptotic marker protein, such as Bax and cytochrome c, and reduced caspase-3 in PDLFs. Mitogen-activated protein kinase signaling was activated by treatment of SNP and NMDA receptor antagonist., Conclusions: These results suggest that excessive production of NO may induce apoptosis and that NMDA receptor may modulate NO-induced apoptosis in PDLFs.

Background: Different cell types in the kidney, including those in tubules, glomeruli, and interstitium, have been proposed as candidate adult renal stem cells, raising controversy about the very existence of such cells. In this study, we sought to clarify the location and nature of adult renal stem cells and to address their reparative role in native kidney disease., Methods: The expression of the stem cell marker CD133 was analyzed in 31 normal fetal and adult human kidneys by immunohistochemical methods. Co expression of CD133 with Ki-67 and tubule specific markers was also examined. Seventeen cases of pauci-immune glomerulonephritis were evaluated for CD133 and Ki-67 expression, and this was correlated with the patients' renal prognosis., Results: CD133 was expressed in S-shaped bodies of fetal kidneys and co-expressed with Ki-67. It was highly expressed in mature tubules of fetal and adult kidneys without Ki-67 co-expression. CD133+ cells were most abundant in the S3 segment of proximal tubules and co-expressed with the distal tubule marker, suggesting multipotency. Most tubular CD133+ cells in normal adult kidneys exhibited pathologic features of acute and chronic injury. In pauci-immune glomerulonephritis, tubular CD133 and Ki-67 co-expression tended to be higher in cases where renal function recovered., Conclusion: These results suggest that adult renal stem cells reside predominantly in the S3 segment of the proximal tubule, where they remain mitotically silent under normal conditions, but can be induced by cellular injury. These results also suggest a potential role for adult renal stem cells in recovery from native human kidney disease.

The two major deficits in type 2 diabetes, insulin resistance and impaired beta cell function, are often treated with metformin and incretin-based drugs, respectively. However, there may be unappreciated benefits of this combination of therapies. In this issue of Diabetologia, Maida et al. (doi: 10.1007/s00125-010-1937-z) report that metformin acutely increases plasma levels of glucagon-like peptide 1 (GLP-1) in mice. Moreover, they show that metformin enhances the expression of the genes encoding the receptors for both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in mouse islets and also increases the effects of GIP and GLP-1 on insulin secretion from beta cells. Interestingly, these incretin-sensitising effects of metformin appear to be mediated by a peroxisome proliferator-activated receptor α-dependent pathway, as opposed to the more commonly ascribed pathway of metformin action involving AMP-activated protein kinase. These provocative findings by Maida et al. extend our understanding of the mechanism of action of metformin and provide further insights into the benefits of combining metformin with incretin-based drugs to combat diabetes.

Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC) and other isothiocyanates, was investigated with administration at concentrations of 0, 0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male and female F344 rats. For comparison, treatment with 0.0425% of AITC was similarly performed. Body weight gain was reduced in the 0.05% HRE and AITC males as compared to the 0% controls, and the cause was considered at least partly related to decreased water consumption due to the acrid smell of the test substance and decreased food consumption. Serum biochemistry demonstrated increased urea nitrogen in 0.025 and 0.05% HRE and AITC males and 0.0125-0.05% HRE and AITC females, along with decreased total cholesterol in 0.0125-0.05% HRE females. On histopathological assessment, papillary/nodular hyperplasia of bladder mucosa was observed in 0.05% HRE and AITC males and females, in addition to simple mucosal hyperplasia found in all treated groups. Based on the above findings, no-observed-adverse-effect levels (NOAELs) were estimated to be below 0.0125% of HRE for both males and females, corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder.

Complex traits are determined by the combined effects of many loci and are affected by gene networks or biological pathways. Systems biology approaches have an important role in the identification of candidate genes related to complex diseases or traits at the system level. The present study systemically analyzed genes associated with bovine marbling score and identified their relationships. The candidate nodes were obtained using MedScan text-mining tools and linked by protein-protein interaction (PPI) from the Human Protein Reference Database (HPRD). To determine key node of marbling, the degree and betweenness centrality (BC) were used. The hub nodes and biological pathways of our network are consistent with the previous reports about marbling traits, and also suggest unknown candidate genes associated with intramuscular fat. Five nodes were identified as hub genes, which was consistent with the network analysis using quantitative reverse-transcription PCR (qRT-PCR). Key nodes of the PPI network have positive roles (PPARγ, C/EBPα, and RUNX1T1) and negative roles (RXRA, CAMK2A) in the development of intramuscular fat by several adipogenesis-related pathways. This study provides genetic information for identifying candidate genes for the marbling trait in bovine.

Objectives: This study assessed the factors that have an influence on the residents exposed to heavy metals, and we utilized the findings to establish the proper management of abandoned metal mines in the future., Methods: For a total of 258 residents who lived close to abandoned mines in Gangwon-province and Gyeonggi-province, the exposure factors and biomarkers in their blood and urine were comparatively analyzed via multiple regression analysis., Results: The blood levels of lead and mercury and the cadmium levels in urine were found to be higher in the study group than that in the average Korean. For the blood levels of heavy metals according to each exposure factor, all of them were found to be significantly higher in both of the group residing for a longer period of time and the group living closer to the source of pollutants. Multiple regression analysis disclosed that all the heavy metals, except lead, in their blood were significantly reduced in proportion to the increased distance of inhabitancy from the mines. Their other biomarkers were within the normal ranges., Conclusions: We found that the distance between the residential village and the mines was a factor that affects the blood level of heavy metals in the villagers. This finding could be an important factor when developing a management model for the areas that surround abandoned metal mines. (ED note: I much like this important study.).

The impact of food waste content on the municipal solid waste (MSW) friction angle was studied. Using reconstituted fresh MSW specimens with different food waste content (0%, 40%, 58%, and 80%), 48 small-scale (100-mm-diameter) direct shear tests and 12 large-scale (430 mm × 430 mm) direct shear tests were performed. A stress-controlled large-scale direct shear test device allowing approximately 170-mm sample horizontal displacement was designed and used. At both testing scales, the mobilized internal friction angle of MSW decreased considerably as food waste content increased. As food waste content increased from 0% to 40% and from 40% to 80%, the mobilized internal friction angles (estimated using the mobilized peak (ultimate) shear strengths of the small-scale direct shear tests) decreased from 39° to 31° and from 31° to 7°, respectively, while those of large-scale tests decreased from 36° to 26° and from 26° to 15°, respectively. Most friction angle measurements produced in this study fell within the range of those previously reported for MSW., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Decreased mitochondrial function plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). Recently, it was reported that mitochondrial DNA (mtDNA) haplogroups confer genetic susceptibility to T2DM in Koreans and Japanese. Particularly, mtDNA haplogroup N9a is associated with a decreased risk of T2DM, whereas haplogroups D5 and F are associated with an increased risk. To examine functional consequences of these haplogroups without being confounded by the heterogeneous nuclear genomic backgrounds of different subjects, we constructed transmitochondrial cytoplasmic hybrid (cybrid) cells harboring each of the three haplogroups (N9a, D5, and F) in a background of a shared nuclear genome. We compared the functional consequences of the three haplogroups using cell-based assays and gene expression microarrays. Cell-based assays did not detect differences in mitochondrial functions among the haplogroups in terms of ATP generation, reactive oxygen species production, mitochondrial membrane potential, and cellular dehydrogenase activity. However, differential expression and clustering analyses of microarray data revealed that the three haplogroups exhibit a distinctive nuclear gene expression pattern that correlates with their susceptibility to T2DM. Pathway analysis of microarray data identified several differentially regulated metabolic pathways. Notably, compared to the T2DM-resistant haplogroup N9a, the T2DM-susceptible haplogroup F showed down-regulation of oxidative phosphorylation and up-regulation of glycolysis. These results suggest that variations in mtDNA can affect the expression of nuclear genes regulating mitochondrial functions or cellular energetics. Given that impaired mitochondrial function caused by T2DM-associated mtDNA haplogroups is compensated by the nuclear genome, we speculate that defective nuclear compensation, under certain circumstances, might lead to the development of T2DM.

Rhabdoid tumors have been reported in many different anatomic sites as an aggressive tumor and usually present with a rhabdoid tumor component (a composite tumor) rather than a pure rhabdoid tumor. Rhabdoid tumor in the prostate has been described only once in the prostatic region as a possible epithelial origin. Rhabdoid features in prostatic stromal sarcomas (PSSs) have never been described in the literature. Here, we report a case of a PSS with rhabdoid features. A 31-year-old man presented with a 4-month history of voiding difficulty and anal pain. Computed tomography of the abdomen revealed an ovoid mass in the prostate invading rectum and urinary bladder. A needle biopsy was diagnosed as an unclassified spindle cell sarcoma, and 2 cycles of adriamycin-based neoadjuvant chemotherapy were given, followed by radical prostatectomy. The prostatectomy specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle cells and numerous mitoses with hemorrhage and necrosis. In areas, the tumor also contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor component. Both spindle and rhabdoid tumor cells were positive for vimentin, CD34, and progesterone receptor and negative for desmin and cytokeratin immunostainings. The rhabdoid tumor cells retained INI1 expression. The tumor recurred in the bladder, and the patient died of sepsis. To the best of our knowledge, this is the first case of PSS with rhabdoid features. The tumor showed an aggressive clinical behavior with a short-term survival (7 months after diagnosis)., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effect of the direction and magnitude of the rotation moment to loaded orthodontic miniscrews on stability. In six adult male beagle dogs (12 months old), 36 orthodontic miniscrews were inserted into the mandibular buccal alveolar bone without drilling. Immediately after insertion, 24 miniscrews were loaded with 1- and 2-Ncm nickel titanium (NiTi) coil springs with either a clockwise or counterclockwise rotation moment while 12 miniscrews were left unloaded. Following an observation period of 3 or 12 weeks, the animals were killed and the miniscrews with the surrounding bone were prepared for histomorphometric evaluation. Bone-to-implant contact (BIC) and the ratio of bone volume/total volume (BV/TV) were measured. BIC and BV/TV were statistically compared using the Kruskal-Wallis H and Mann-Whitney U tests. Three of the miniscrews loaded with 2 Ncm counterclockwise rotation moment were lost within 3 weeks. At 12 weeks after insertion, the counterclockwise group showed a statistically significantly lower BIC in comparison with the clockwise group. The results suggest that a rotation moment to loaded orthodontic miniscrews, as well as the direction and magnitude of the rotation moment, can influence miniscrew stability. Counterclockwise rotational moments can be a risk factor impairing miniscrew stability.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associated with considerable morbidities. Unfortunately, there is no currently available drug established to treat NAFLD. It was recently reported that intraperitoneal administration of taurine-conjugated ursodeoxycholic acid (TUDCA) improved hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat stained by oil red O (44.2±5.8% vs. 21.1±10.4%, P<0.05), whereas there was no difference in body weight, oral glucose tolerance, insulin sensitivity, and ER stress. Microarray analysis of hepatic gene expression demonstrated that oral TUDCA treatment mainly decreased the expression of genes involved in de novo lipogenesis among the components of lipid homeostasis. At pathway levels, oral TUDCA altered the genes regulating amino acid, carbohydrate, and drug metabolism in addition to lipid metabolism. In summary, oral TUDCA treatment decreased hepatic steatosis in ob/ob mice by cooperative regulation of multiple metabolic pathways, particularly by reducing the expression of genes known to regulate de novo lipogenesis.

Background: Adequate glycemic control is important for patients with end-stage renal disease on maintenance hemodialysis (HD). Continuous glucose monitoring (CGM) systems are reported as a useful method for glucose monitoring in patients under maintenance HD. The object of this study was to describe glucose profiles and hypoglycemia associated with HD in diabetes patients using a CGM system., Methods: We recruited nine medically stable patients with type 2 diabetes under maintenance HD. CGMS System Gold (Medtronic MiniMed, Northridge, CA) was applied to the subjects for 144 h. During the period, HD using glucose-containing dialysate was performed every other day. Various glucose profiles were calculated from the CGM readings and compared between the day on and the day off dialysis., Results: Mean ± SD for age, duration of diabetes, and hemoglobin A1c were 67 ± 9 years, 24 ± 9 years, and 8.6 ± 1.2%, respectively. Hemoglobin A1c was correlated with mean glucose (ρ = 0.780, P < 0.05) and with area under the curve for glucose above 180 mg/dL (ρ = 0.797, P<0.05). Although there was no difference for mean amplitude of glycemic excursion between the day on and off HD, hypoglycemia occurred predominantly with day on HD. In the subjects who maintained antidiabetes agents with day on HD, glucose levels decreased with initiation of HD, causing significantly lower glucose levels compared to those during the equivalent time of the following day without HD., Conclusions: According to the CGM system, glucose variability was not affected by HD. However, in spite of glucose-containing dialysate, HD seemed to increase the risk of hypoglycemia.

Unlabelled: Aims/Introduction:  Mitiglinide is the newest drug in the meglitinide family. It increases the early-phase insulin release through rapid association-dissociation kinetics in the pancreatic β cells. The efficacy and safety of adding meglitinide to metformin monotherapy in patients with type 2 diabetes are unknown., Materials and Methods:   We carried out a prospective, randomized, multicenter trial to assess the efficacy and safety of combined treatment with mitiglinide and metformin for patients with type 2 diabetes who showed inadequate glycemic control with metformin monotherapy. Subjects with glycated hemoglobin (HbA1c) >7.0% after an 8-week metformin run-in phase were randomized to a 16-week trial phase with metformin plus mitiglinide (Met + Mit) or metformin plus placebo (Met + Pcb)., Results:   Compared with the Met + Pcb group, the Met + Mit group showed a greater reduction in HbA1c (-0.7 ± 0.6%vs-0.4 ± 0.7%, P = 0.002), fasting plasma glucose (-0.77 ± 1.76 mmol/L vs-0.05 ± 1.60 mmol/L, P = 0.015) and 2-h postprandial glucose (-3.76 ± 3.57 mmol/L vs-0.84 ± 3.07 mmol/L, P < 0.0001). The proportion of the patients who achieved the target HbA1c value of <7% at the end of the study was also higher in the Met + Mit group than the Met + Pcb group (49.3%vs 28.8%, P = 0.016). There were no differences in the adverse event rates between groups., Conclusions:   Combination therapy with metformin and mitiglinide is effective and safe for the treatment of patients with type 2 diabetes who have inadequate glycemic control with metformin monotherapy. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00023.x, 2010).

Background: The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1α is homologous with murine Reg1, we investigated whether common variants in Reg1α are associated with type 2 diabetes in the Korean population., Methods: We sequenced the Reg1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects., Results: No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009)., Conclusion: Polymorphisms in the Reg1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.

Advective porewater movement and molecular diffusion are important factors affecting the mass transfer of hydrophobic organic compounds (HOCs) in marsh and mudflat sediments. This study assessed porewater movement in an intertidal mudflat in South Basin adjacent to Hunters Point Shipyard, San Francisco, CA, where a pilot-scale test of sorbent amendment assessed the in situ stabilization of polychlorinated biphenyls (PCBs). To quantify advective porewater movement within the top 0-60 cm sediment layer, we used temperature as a tracer and conducted heat transport analysis using 14-day data from multidepth sediment temperature logging stations and one-dimensional heat transport simulations. The best-fit conditions gave an average Darcy velocity of 3.8cm/d in the downward vertical direction for sorbent-amended sediment with a plausible range of 0 cm/d to 8 cm/d. In a limiting case with no net advection, the best-fit depth-averaged mechanical dispersion coefficient was 2.2x10(-7) m2/s with a range of 0.9x10(-7) m2/s to 5.6x10(-7) m2/s. The Peclet number for PCB mobilization showed that molecular diffusion would control PCB mass transfer from sediment to sorbent particles for the case of uniform distribution of sorbent. However, the advective flow and mechanical dispersion in the test site would significantly benefit the stabilization effect of heterogeneously distributed sorbent by acting to smooth out the heterogeneities and homogenizing pollutant concentrations across the entire bioactive zone. These measurements and modeling techniques on intertidal sediment porewater transport could be useful for the development of more reliable mass transfer models for the prediction of contaminant release within the sediment bed, the movement of HOCs in the intertidal aquatic environment, and in situ sequestration by sorbent addition.

The number of individuals with metabolic syndrome is increasing worldwide, constituting a major social problem in many countries. Recently, epidemiological and experimental studies have associated insulin resistance or type 2 diabetes with elevated body burdens of persistent organic pollutants (POPs). It has been proposed that mitochondrial dysfunction plays a key role in this association. Mitochondrial DNA abnormalities are known to cause pancreas beta cell damage, insulin resistance, and diabetes mellitus. Recently, much evidence has emerged showing that environmental toxins, including POPs, affect mitochondrial function and subsequently induce insulin resistance. In this review, we present a novel concept in which metabolic syndrome is the result of mitochondrial dysfunction, which in turn is caused by exposure to POPs. The potential mechanism including POPs for mitochondrial dysfunction on metabolic syndrome is also discussed. We propose that the mitochondrial paradigm for the etiology of metabolic syndrome will facilitate the prevention and treatment of this major health problem.

Mitochondria play a key role in cell physiology including cell differentiation and proliferation. We investigated the changes of mitochondrial biogenesis during Wnt-induced osteoblastic differentiation of murine mesenchymal C3H10T1/2 cells. Scanning electron microscopy demonstrated that activation of Wnt signaling by Wnt-3A conditioned medicum (CM) resulted in significant increase in the number of mitochondria in C3H10T1/2 cells. In addition, the induction of alkaline phosphatase (ALP) activities by Wnt-3A CM was accompanied by significant increase in mitochondrial mass (p<0.05), mitochondrial membrane potential (p<0.05), intracellular reactive oxygen species production (p<0.05), resting oxygen consumption rate (p<0.05), cellular ATP content (p< or =0.05) and mtDNA copy number (p<0.05) compared to the cells with control CM (L292-CM) treatment. Moreover, co-treatment with Dkk-1 or WIF-1, both of which are Wnt inhibitors, abrogated the Wnt-3A-induced ALP activities as well as mitochondrial biogenesis markers. Upregulation of mitochondrial biogenesis by overexpression of mitochondrial transcription factor A (Tfam) significantly enhanced Wnt-induced osteogenesis as measured by ALP activities. In contrast, inhibition of mitochondrial biogenesis by treatment with Zidovudine (AZT) resulted in significant inhibition of ALP activities. Finally, ALP activities in human osteosarcoma cell line devoid of mitochondrial DNA (rho(0) cells) was significantly suppressed both in basal and Wnt-3A stimulated state compared to those from mitochondria-intact cells (rho+ cells). As a mechanism for Wnt-mediated mitochondrial biogenesis, we found that Wnt increased the expression of PGC-1alpha, a critical molecules in mitochondrial biogenesis, through Erk and p38 MAPK pathway independent of beta-catenin signaling. We also found that increased mitochondrial biogenesis is in turn positively regulating TOPflash reporter activity as well as beta-catenin levels. To summarize, mitochodrial biogenesis is upregulated by Wnt signaling and this upregulation contributes to the osteoblastic differentiation of mouse mesenchymal C3H10T1/2 cells., (2010 Elsevier Inc. All rights reserved.)

Objectives: To investigate whether or not antiaminoacyl-tRNA synthetase (aaRS) autoantibodies could be detected in patients with type 1 diabetes mellitus (DM) and be used as a diagnostic marker for type 1 DM, autoantibodies against aaRSs were measured in the plasma of normal subjects, patients with type 1 DM and patients with type 2 DM., Methods: An enzyme-linked immunosorbent assay was performed to detect anti-aaRS autoantibodies in the plasma of normal subjects, and patients with type 1 DM, and patients with type 2 DM., Results: From the 65 (normal), 58 (type 1 DM) and 57 (type 2 DM) subjects, anti-aaRS autoantibodies were found in 37.9% of patients with type 1 DM compared with 1.54% of the non-diabetic controls, and 5.26% of the patients with type 2 DM (p <0.0001). In addition, anti-aaRS autoantibodies were identified in 30% of patients with type 1 DM without classical type 1 DM autoantibodies., Conclusion: Anti-aaRS autoantibodies were identified in 37.9% of patients with type 1 DM. The results of this study demonstrate for the first time that autoantibodies against aaRSs are specifically associated with type 1 DM.

Retinoid X receptor-alpha (RXR alpha) fragments are known to be produced in some cancer cells by proteolytic cleavage. Previous finding that ligand binding domain (LBD) fragment of RXR alpha specifically inhibits retinoic acid receptor-gamma (RAR gamma) activity led us to investigate the functional role of RXR alpha LBD fragment in radiosensitization by retinoic acid (RA). Ectopic expression of RXR alpha LBD fragment in cells that do not have a detectable endogenous RXR alpha LBD fragment, blocked synergistic radiosensitizing action of RA, as determined by growth inhibition, cell death and colony formation assays. However, H460 cell, which has an endogenous RXR alpha LBD fragment, was not radiosensitized by RA regardless of the ectopic RXR alpha LBD fragment expression. These results were paralleled with the pattern of p21 Waf1/Cip1 induction by the treatment of RA in combination with ionizing radiation (IR). Taken together, we hypothesize that the RXR alpha LBD fragment may act as a negative regulator of radiosensitizing effect of RA by restricting the RAR gamma-mediated biological response to RA.

Purpose: To analyze the preoperative clinical and pathological characteristics of patients with pT0 prostate cancer., Materials and Methods: We retrospectively reviewed the records of 702 patients who underwent radical prostatectomy (RP) at our institution between January 2004 and July 2008 for clinically localized prostate cancer. If there was no evidence of residual tumor in the pathological specimen of the prostate, a patient was staged as pT0. Patients with pT0 disease were compared with a control group of patients who were operated on during the same period., Results: Overall, 9 (1.3%) patients were staged as pT0 on the pathologic examination. Significant differences were observed between the pT0 group and the control patients in the biopsy Gleason score (p=0.004), the number of positive cores on biopsy (p=0.018), the tumor length of positive cores (p<0.001), and prostate volume (p=0.015). Cutoff values predictive of pT0 tumor status were defined as a biopsy Gleason score sum 30 cm(3). Whereas 8 of the 9 (88.9%) pT0 patients showed all of these characteristics, only 55 of the 693 (7.9%) control patients fulfilled the criteria. The combination suggested above afforded a sensitivity of 88.8% and a specificity of 92.1% for the prediction of pT0 status., Conclusions: The frequency of pT0 prostate cancer seen on RP was 1.3%. A combination of clinicopathological features, incorporating a biopsy Gleason score, the number of positive biopsy cores, tumor length on biopsy, and prostate volume, was useful to predict pT0 stage on RP.

Salmonella enterica serovar Gallinarum isolates (n=105) from chickens in South Korea between 2002 and 2007 were tested for antimicrobial susceptibility by determining minimum inhibitory concentrations of 16 antimicrobials, and their predominant resistance profiles were genetically characterized. Most isolates (99/105; 94.3%) were resistant to nalidixic acid and resistant/intermediately resistant to fluoroquinolones, and 63.8% (67/105) of the isolates were resistant to three or more antimicrobials. Forty-two quinolone-resistant isolates, of which the quinolone resistance-determining regions of the gyrA genes were sequenced, contained a substitution of a Ser to a Phe or Tyr at position 83 (71.4%), or a substitution of an Asp to an Asn, Gly, or Tyr at position 87 (28.6%). Fifty-seven sulphamethoxazole-resistant isolates were tested for the presence of class 1 integrons by polymerase chain reaction, and their resistance gene cassettes were analysed by sequencing. Three different class 1 integrons containing the resistance-gene insert aadA (52.6%; n=30), aadB (12.3%; n=7), or aadB-aadA (12.3%; n=7) were identified. Most isolates harbouring the integron containing aadB-aadA displayed resistance to all three aminoglycosides tested and also showed increased resistance to fluoroquinolones. These findings suggest that fluoroquinolone resistance may be epidemiologically linked to multiple aminoglycoside resistance.

An association between inflammatory processes and the pathogenesis of insulin resistance has been increasingly suggested. The IkappaB kinase-beta (IKK-beta)/ nuclear factor-kappaB (NF-kappaB) pathway is a molecular mediator of insulin resistance. S-Adenosyl-L-methionine (SAM) has both antioxidative and anti-inflammatory properties. We investigated the effects of SAM on the glucose transport and insulin signaling impaired by the tumor necrosis factor alpha (TNFalpha) in 3T3-L1 adipocytes. SAM partially reversed the basal and insulin stimulated glucose transport, which was impaired by TNFalpha. The TNFalpha-induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and Akt in 3T3-L1 adipocytes was also reversed by SAM. In addition, SAM significantly attenuated the TNFalpha-induced degradation of IkappaB-alpha and NF-kappaB activation. Interestingly, SAM directly inhibited the kinase activity of IKK-beta in vitro. These results suggest that SAM can alleviate TNFalpha mediated-insulin resistance by inhibiting the IKK-beta/NF-kappaB pathway and thus can have a beneficial role in the treatment of type 2 diabetes mellitus.

Here, we demonstrate that SENP2, a desumoylating enzyme, plays a critical role in the control of adipogenesis. SENP2 expression was markedly increased upon the induction of adipocyte differentiation, and this increase was dependent on protein kinase A activation. Remarkably, knockdown of SENP2 led to a dramatic attenuation of adipogenesis with a marked decrease in PPARgamma and C/EBPalpha mRNA levels. Knockdown of SENP2 also caused a marked reduction in the level of C/EBPbeta protein but not in that of C/EBPbeta mRNA. Interestingly, sumoylation of C/EBPbeta dramatically increased its ubiquitination and destabilization, and this increase could be reversed by SENP2. In addition, overexpression of C/EBPbeta could overcome the inhibitory effect of SENP2 knockdown on adipogenesis. Furthermore, SENP2 was absolutely required for adipogenesis of preadipocytes implanted into mice. These results establish a critical role for SENP2 in the regulation of adipogenesis by desumoylation and stabilization of C/EBPbeta and in turn by promoting the expression of its downstream effectors, such as PPARgamma and C/EBPalpha.

The centerpiece of the pathophysiologic mechanism of metabolic syndrome is insulin resistance. Recently, it is becoming evident that mitochondrial dysfunction is closely related to insulin resistance and metabolic syndrome. The underlying mechanism of mitochondrial dysfunction is very complex, which includes genetic factors from both nuclear and mitochondrial genome and numerous environmental factors. Several mitochondrial DNA polymorphisms are associated with the components of metabolic syndrome. Numerous chemicals and drugs may cause mitochondrial dysfunction and insulin resistance. Notably, it was recently reported that serum levels of several mitochondrial toxins, such as persistent organic pollutants are associated with metabolic syndrome, which necessitates further investigation to reveal its precise mechanism. Given that the health impact of metabolic syndrome is tremendous, it is necessary to develop therapeutic modalities to correct mitochondrial dysfunction or at least to halt its aggravation. In this regard, exercise can improve both mitochondrial function and insulin sensitivity, and some pharmaceutical agents were reported to improve mitochondrial function. However, further studies are warranted to find more effective therapeutic strategies to treat mitochondrial dysfunction. By doing so, we can also shed light on the path of research for other diseases related to mitochondrial dysfunction., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

A large data set of Hanwoo (Korean cattle) ESTs was analyzed to obtain differential gene expression results for the following three libraries: intramuscular fat, longissimus dorsi muscle and liver. To better understand the gene expression profiles, we identified differentially expressed genes (DEGs) via digital gene expression analysis. Hierarchical clustering of genes was performed according to their relative abundance within the six separate groups (Hanwoo fat versus non-Hanwoo fat, Hanwoo muscle versus non-Hanwoo muscle and Hanwoo liver versus non-Hanwoo liver), producing detailed patterns of gene expression. We determined the quantitative traits associated with the highly expressed genes. We also provide the first list of putative regulatory elements associated with differential tissue expression in Hanwoo cattle. In addition, we conducted evolutionary analysis that suggests a subset of genes accelerated in the bovine lineage are strongly correlated with their expression in Hanwoo muscle.

Acrylamide (AA) has been reported to be formed in fried and baked foods with various concentrations, and exposure levels to AA from cooked foods in children are estimated to be higher than those in adults. In order to evaluate the carcinogenicity of AA exposure during childhood, we conducted a medium-term carcinogenicity study with prepubertal administration of AA followed by treatments of a multi-organ-targeted genotoxic carcinogen and a promoting agent for thyroid carcinogenesis in rats. A total of 36 postpartum F344 rats were given drinking water containing AA at 0, 20, 40 or 80 ppm for 3 weeks during the lactation period, and their weaned offspring received the same AA-containing water for 3 more weeks. Offspring were then injected with N-methyl-N-nitrosourea (MNU; 40 mg/kg body weight, i.p.) once at week 7 after birth. Half the animals of the 0 and 40 ppm groups were additionally treated with the anti-thyroid agent sulfadimethoxine (SDM; 125 ppm) in the drinking water thereafter. Offspring were subjected to complete necropsy at week 50. All the major organs and macroscopic abnormalities were excised and examined histopathologically. There was no significant difference in the incidences of hyperplastic and neoplastic lesions in the target organs of AA and/or MNU, such as the brain, spinal cord, pituitary gland, thyroid, adrenal glands, uterus, mammary glands, clitoral gland and tunica vaginalis. In conclusion, no significant modifying actions of AA on MNU-induced multi-organ carcinogenesis were exhibited in any organs of rats when exposed prepubertally under the present experimental conditions.

In the 1970s, glucose-dependent insulinotropic polypeptide (GIP, formerly gastric inhibitory polypeptide), a 42-amino acid peptide hormone, was discovered through a search for enterogastrones and subsequently identified as an incretin, or an insulinotropic hormone secreted in response to intraluminal nutrients. Independent of the discovery of GIP, the K-cell was identified in small intestine by characteristic ultrastructural features. Subsequently, it was realized that K-cells are the predominant source of circulating GIP. The density of K-cells may increase under conditions including high-fat diet and obesity, and generally correlates with plasma GIP levels. In addition to GIP, K-cells secrete xenin, a peptide with as of yet poorly understood physiological functions, and GIP is often colocalized with the other incretin hormone glucagon-like peptide-1 (GLP-1). Differential posttranslational processing of proGIP produces 30 and 42 amino acid versions of GIP. Its secretion is elicited by intraluminal nutrients, especially carbohydrate and fat, through the action of SGLT1, GPR40, GPR120, and GPR119. There is also evidence of regulation of GIP secretion via neural pathways and somatostatin. Intracellular signaling mechanisms of GIP secretion are still elusive but include activation of adenylyl cyclase, protein kinase A (PKA), and protein kinase C (PKC). GIP has extrapancreatic actions on adipogenesis, neural progenitor cell proliferation, and bone metabolism. However, the clinical or physiological relevance of these extrapancreatic actions remain to be defined in humans. The application of GIP as a glucose-lowering drug is limited due to reduced efficacy in humans with type 2 diabetes and its potential obesogenic effects demonstrated by rodent studies. There is some evidence to suggest that a reduction in GIP production or action may be a strategy to reduce obesity. The meal-dependent nature of GIP release makes K-cells a potential target for genetically engineered production of satiety factors or glucose-lowering agents, for example, insulin. Transgenic mice engineered to produce insulin from intestinal K-cells are resistant to diabetes induced by a beta-cell toxin. Collectively, K-cells and GIP play important roles in health and disease, and both may be targets for novel therapies., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background/aims: To investigate whether the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) Pro12Ala and the PPAR-gamma coactivator-1alpha (PGC-1alpha) Gly482Ser polymorphisms were associated with polycystic ovary syndrome (PCOS)., Methods: Genetic analyses of the PPAR-gamma Pro12Ala and the PGC-1alpha Gly482Ser polymorphisms were performed in 184 patients with PCOS and 256 controls. Hormone levels, biochemical and clinical features were analyzed according to these polymorphisms., Results: Neither the PPAR-gammaPro12Ala nor the PGC-1alpha Gly482Ser polymorphism showed significant differences in genotypic distribution between women with PCOS and controls. In PCOS patients, women with the non-Pro/Pro genotypes of the PPAR-gamma Pro12Ala polymorphism showed statistically significantly higher HDL levels than those with the Pro/Pro genotype (p = 0.002). PCOS patients who had the Ser/Ser genotype of the PGC-1alpha Gly482Ser polymorphism had significantly higher levels of postprandial 2-hour insulin than those with the Gly/Ser genotype (p = 0.045)., Conclusions: Neither the PPAR-gammaPro12Ala nor the PGC-1alpha Gly482Ser polymorphism were supposed to be susceptible genes in PCOS. However, in PCOS patients, the PPAR-gammaPro12Ala and the PGC-1alpha Gly482Ser polymorphism may modulate the concentrations of serum HDL levels and postprandial 2-hour insulin level, respectively., (Copyright (c) 2010 S. Karger AG, Basel.)

Background: Recent genome-wide association studies in East Asians have identified polymorphisms in KCNQ1 as new type 2 diabetes risk variants. The aim of this study was to investigate whether variants in KCNQ1 are associated with development of gestational diabetes mellitus (GDM) and measures of oral glucose tolerance test (OGTT) at the time of diagnosis of GDM., Methods: Three candidate single nucleotide polymorphisms (rs2074196, rs2237892, and rs2237895) were genotyped in 869 Korean GDM women and 632 nondiabetic control subjects. Insulin resistance was estimated by homeostasis model assessment and pancreatic β-cell function by the insulinogenic index at 1 h., Results: rs2074196 and rs2237892 were associated with the risk of GDM (OR 1.17, 95% CI 1.01-1.36, p = 0.039; OR 1.24, 95% CI 1.07-1.45, p = 0.0049). Furthermore, rs2237892 and rs2237895 were nominally associated with a decreased insulinogenic index at the time of GDM diagnosis (p = 0.025 and p = 0.037), whereas no association was observed with measures of insulin resistance., Conclusions: The single nucleotide polymorphisms in KCNQ1 showed a significant association with GDM in the Korean population. Although the mechanism is not yet clear, it could be possible that variants in KCNQ1 confer a risk for GDM by altering pancreatic β-cell function., (Copyright © 2010 S. Karger AG, Basel.)

Increasing evidence suggests that type 2 diabetes mellitus (T2DM) is strongly correlated with Alzheimer's disease (AD). To examine the relationship between T2DM and AD, autoantibodies against amyloid-Abeta were measured in the serum of T2DM patients and age-matched controls. Levels of Abeta autoantibody were measured by ELISA in serum samples of T2DM patients (n=92) and age-matched control group (n=106). Abeta autoantibody levels were increased in T2DM compared with age-matched controls by 45.4 +/- 8.1% (p< 0.001). Females had higher Abeta autoantibody levels than males in both T2DM and control group. Abeta autoantibody levels in the T2DM group were positively correlated with the levels of cholesterol (p=0.011), low density lipoprotein cholesterol (p=0.020), and triglycerides (p=0.039). In conclusion, the level of Abeta autoantibody is dramatically elevated in patient serum of T2DM, and, as such, might be used as a possible biomarker for T2DM.

New arylsulfonyl proton pump inhibitor (PPI) prodrug forms were synthesized. These prodrugs provided longer residence time of an effective PPI plasma concentration, resulting in better gastric acid inhibition.

Probe design is one of the most important tasks in successful deoxyribonucleic acid microarray experiments. We propose a multiobjective evolutionary optimization method for oligonucleotide probe design based on the multiobjective nature of the probe design problem. The proposed multiobjective evolutionary approach has several distinguished features, compared with previous methods. First, the evolutionary approach can find better probe sets than existing simple filtering methods with fixed threshold values. Second, the multiobjective approach can easily incorporate the user's custom criteria or change the existing criteria. Third, our approach tries to optimize the combination of probes for the given set of genes, in contrast to other tools that independently search each gene for qualifying probes. Lastly, the multiobjective optimization method provides various sets of probe combinations, among which the user can choose, depending on the target application. The proposed method is implemented as a platform called EvoOligo and is available for service on the web. We test the performance of EvoOligo by designing probe sets for 19 types of Human Papillomavirus and 52 genes in the Arabidopsis Calmodulin multigene family. The design results from EvoOligo are proven to be superior to those from well-known existing probe design tools, such as OligoArray and OligoWiz.

Using differential display reverse transcriptase polymerase chain reaction, we detected 11 differentially expressed genes between top round and loin muscle in Korean cattle (Hanwoo). In the loin muscle, the lightness (L*) value (P<0.01) and marbling fat content (P<0.01), which are important factors in determining meat quality, were higher than in top round muscle. Three of the 11 genes were validated as significant genes between two types of muscle by real-time polymerase chain reaction (P<0.05). To determine whether the three genes were associated with meat quality traits, a regression analysis was preformed. The result demonstrated that two genes (NADH dehydrogenase 2 and cytochrome oxidase III), which are involved in oxidative phosphorylation in mitochondria, were significantly correlated with marbling fat content in the loin muscle (P<0.01), while two genes were not significant with marbling fat content in top round muscle. No significant effects for two genes on other meat quality traits such as meat color (redness and yellowness value), Warner-Bratzler shear force, and water-holding capacity were detected in this study.

We report a case of light chain deposition disease in a 59-yr-old female showing deposition of monoclonal light chain in the kidney and bone marrow accompanied with a schistocytosis, the morphologic finding of microangiopathic hemolytic anemia. The immunofluorescence examination of the kidney revealed strongly stained kappa-light chain deposits on the glomerular mesangium and capillary wall, tubules, and vessel wall. The electron microscopy demonstrated electron-dense deposits on the glomerular basement membrane and mesangium. Anemia was observed with schistocytosis and Howell-Jolly body in the peripheral blood smears. The immunohistochemical examination of the bone marrow showed the presence of kappa-light chain deposits in scattered plasma cells and thickened vessel wall in the absence of a prominent plasma cell proliferation. Although an immunofixation electrophoresis failed to detect a monoclonal gammopathy, the presence of monoclonal protein could be identified by an abnormal kappa/lambda ratio on the serum free light chain analysis.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor regulating inflammation, atherosclerosis, insulin sensitivity and adipogenesis. Recently, it has been discovered that modification by the small ubiquitin-like modifier (SUMO) plays an important role in PPARgamma activity. In the present study, we investigated the effect of sumoylation on the antiatherogenic property of PPARgamma. PPARgamma-K107R sumoylation mutant, PPARgamma-wild type (WT) and control genes were transfected on vascular smooth muscle cells (VSMCs) to compare their effect on the proliferation and migration. Adenoviral vectors expressing the PPARgamma-K107R, PPARgamma-WT or control gene were delivered into the carotid arteries of rats after balloon injury. The PPARgamma-K107R increased the transcriptional activity of peroxisome proliferator response element (PPRE) and had a more potent transcriptional repression activity on the inducible nitric oxide synthase (iNOS) promoter as compared to the other sumoylation mutants or WT. PPARgamma-K107R or WT gene transfer inhibited VSMCs proliferation and migration to a greater extent than the control. The PPARgamma-K107R had more potent activity than PPARgamma-WT in this regard. PPARgamma-K107R or WT transfer showed a significantly lower intima-media ratio (IMR) than the control after balloon injury in rats. Again, the delivery of the PPARgamma-K107R decreased IMR further compared to PPARgamma-WT. In addition, the PPARgamma-K107R transfer showed a lower proliferation index and a higher apoptotic index than PPARgamma-WT. In conclusion, the PPARgamma sumoylation mutant K107R strongly inhibited VSMCs proliferation and migration, sustained apoptosis, and reduced neointimal formation after balloon injury. These results indicate that desumoylation at K107 in PPARgamma might play an important role against atherosclerosis.

We have reported that thyroid capsular thickening with inflammation induced by an antithyroidal agent, sulfadimethoxine (SDM), might play a role in the development of invasive follicular carcinomas in rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Inducible nitric oxide synthase (iNOS) expressed in the inflamed capsular regions further appeared to be implicated in the tumor progression. In the present study, the effects of an iNOS inhibitor, aminoguanidine (AG), on thyroid carcinogenesis were examined. F344 male rats were treated with SDM in drinking water (0.1%) with or without concomitant dietary administration of AG (0.2%) for 4 and 10 weeks after subcutaneous injection of DHPN at 2800 mg/kg bodyweight. At week 4, thyroid capsular thickening with inflammation was observed and iNOS-positive foci were found in the inflamed regions. In addition, single-strand DNA-positive inflammatory cells were scattered among neighboring follicular cells, indicating some cellular damage, at least partly in association with iNOS induction. Concurrent dietary administration of AG with SDM treatment slightly decreased the number of single-strand DNA-positive cells but did not alter the incidence and multiplicity of iNOS-positive foci in the inflamed capsular regions at week 4. At week 10, however, invasive follicular carcinomas predominantly arose in the thickened capsule in the DHPN-SDM-treated rats, and AG administration decreased (P < 0.05) their multiplicity. The carcinoma cells were partly positive for iNOS. These results thus suggested that iNOS induction in both inflammatory and tumor cells might play pivotal roles in tumor progression in this DHPN-SDM rat model.

This study evaluated the efficacy of Web-based diabetes self-management education for newly diagnosed patients with type II diabetes as an alternative to group lectures. Using a non-equivalent control group, pretest-post-test design, the participants in the Web group (n = 15) took part in a Web-based diabetes self-management program, while those in the lecture group (n = 16) attended 3 h of group lectures provided by health-care professionals specializing in diabetes care. The outcome variables were measured at the baseline (T0), and 6 weeks (T1) and 3 months (T2) after the interventions. The glycosylated hemoglobin (HbA1c) percentage and diabetes care knowledge in the Web group improved significantly from T0 to T1, while the diabetes care behavior improved significantly from T0 to T1 and from T1 to T2. The diabetes care knowledge and diabetes care behavior in the lecture group improved significantly from T0 to T1, but the HbA1c percentage did not change significantly between any times. These results show the potential of the Web-based program as an alternative to group lectures for diabetes self-management education.

Neoplasms of skeletal muscle origin are very rare in the rat. Recently, we experienced a case of rhabdomyosarcoma as a white mass involving the junction of the esophagus and stomach in the abdominal cavity of a 12-month-old female Donryu rat. Histopathologically, the neoplastic cells composing the mass invasively spreaded from the lamina propia to the tunica serosa in the stomach as well as the esophagus. Although the neoplastic cells varied in appearance, pleomorphic atypical cells with abundant eosinophilic cytoplasm were prominent. Some tumor cells were stained blue with phosphotungstic acid hematoxylin. The nuclei of spindle-shaped neoplastic cells were arranged longitudinally like beads. Multinucleate giant cells and mitotic figures were also frequently observed. Immunohistochemically, these neoplastic cells were positive for desmin and myoglobin, whereas they were negative for alpha-smooth muscle actin. Taken together these findings, this tumor was diagnosed as a pleomorphic rhabdomyosarcoma, probably derived from the muscle layer of the lower part of the esophagus. This is the first report of rhabdomyosarcoma in a Donryu rat.

Context: The widespread use of the serum prostate-specific antigen test has increased the early detection of prostate cancer and consequently reduced grossly definable prostate cancers., Objective: To find the most efficient gross sampling method for radical prostatectomy specimens not only preserving important prognostic factors but also being cost effective., Design: We initially analyzed clinicopathologic features of the entire prostate sections from 148 radical prostatectomy specimens, which then were used to examine the impact of 5 partial sampling methods on tumor stage, Gleason score, extraprostatic extension, resection margin status, and paraffin block numbers. The methods included submission of (1) alternative slices, (2) alternative slices plus biopsy-positive posterior quarters, (3) every posterior half, (4) every posterior half plus one midanterior half, and (5) alternative slices plus peripheral 3-mm rim of the remaining prostate., Results: Prostate cancers and their extraprostatic extension and resection margin involvement were commonly located in the right posterior portion of the prostate. Method 5 was most efficient, detecting all cases with extraprostatic extension and resection margin involvement and reducing 25% of paraffin blocks compared with the entire sampling of the prostate. The Gleason scores were retained in most of cases, except reversal of the primary and secondary Gleason grade component in only 2 cases (1%). Only 4 cases (3%) were downstaged within the same T2 stage., Conclusions: These results demonstrate that sampling of alternative slices plus peripheral rim of the remaining prostate is the most efficient partial sampling method for radical prostatectomy specimens.

Background: Cerebral white matter hyperintensity (WMH) is a common abnormality in brain magnetic resonance imaging (MRI) and is known to be associated with ischaemic stroke. Previous studies revealed that the risk factors for cerebral WMH were age, female gender, hypertension and diabetes. In this study we examined the association between cerebral WMH and metabolic syndrome, a cluster of hypertension, glucose intolerance, abdominal obesity and dyslipidaemia., Methods and Results: We reviewed the results of brain MRI of 5498 subjects who underwent routine check-ups including laboratory tests at the Seoul National University Health Care System. Among the subjects who met the inclusion criteria (n = 5104), 1693 (33.2%) had cerebral WMH. They were characterized by old age, female predominance, higher body mass index (BMI), larger waist circumference, higher blood pressure, higher fasting plasma glucose level, and higher haemoglobin A1c (HbA1c). In multivariate analyses, age, female gender and hypertension were the independent risk factors for cerebral WMH. Metabolic syndrome was associated with cerebral WMH after adjusting for age and gender [odds ratio (OR) 1.20, 95% confidence interval (CI) 1.04-1.39, P = 0.014]. Among the components of metabolic syndrome, hypertension was independently associated with cerebral WMH (OR 1.20, 95% CI 1.05-1.38, P = 0.007)., Conclusion: Age, female gender and hypertension were risk factors for cerebral WMH in the Korean population. Cerebral WMH was also associated with metabolic syndrome; however, metabolic syndrome offered no advantage over hypertension alone in predicting cerebral WMH.

Post-transplantation diabetes mellitus (PTDM) is reversible in a considerable number of patients. We examined the prevalence and predictive factors of transient PTDM following liver transplantation. Forty-two of 74 PTDM patients showed the clinical features of transient PTDM. Compared with the persistent PTDM patients, they were characterized by younger age at the time of transplantation (49+/-7 vs. 53+/-8 yr, P<0.05), longer time before the development of PTDM (44+/-59 vs. 13+/-20 days, P<0.05), lower rate of hepatitis c virus seropositivity (0.0 vs. 9.4%, P<0.05), and use of mycophenolate mofetil (59.5 vs. 28.1%, P<0.05). Among these risk factors, age at the time of transplantation is the single independent predictive factor associated with the reversibility of PTDM.

Purpose: Controversy exists as to the influence of age at diagnosis on prognosis in patients with renal cell carcinoma. We investigated the relationship between age at diagnosis and disease recurrence after surgery in patients with small renal cell carcinoma., Materials and Methods: Of the 1,196 patients who underwent curative surgery for renal cell carcinoma between 1989 and 2005 at our institution 490 with renal cell carcinoma 4 cm or less were included in our study. Patients were stratified into 3 subgroups according to age at diagnosis, including 40 years or less in 93, 41 to 60 years in 253 and greater than 60 years in 144. Clinical and pathological variables at diagnosis were compared and survival analysis was performed., Results: A total of 17 patients (3.5%) experienced disease recurrence and 9 (1.8%) died of metastatic renal cell carcinoma during followup. Higher Fuhrman nuclear grade was associated with older age at diagnosis (p = 0.001). Histological subtypes were associated with age categories (p = 0.016). The overall recurrence-free survival rate was 97.2% and 92.4% at 5 and 10 years, respectively. The 10-year recurrence-free survival rate was 100% for patients 40 years old or younger, 95.7% for those 41 to 60 years old and 79.0% for those older than 60 years (p = 0.002). Multivariate analysis revealed that age at diagnosis and Fuhrman grade independently predicted recurrence-free survival (p = 0.027 and <0.001, respectively)., Conclusions: Age at diagnosis was an independent predictor of recurrence-free survival after curative surgical treatment in patients with small renal cell carcinoma. Our results suggest that older patients with small renal cell carcinoma should be more closely followed after surgery than younger patients.

A subchronic toxicity study of soybean extract was performed in F344 rats with dietary administration at concentrations of 0%, 1.25%, 2.5% and 5% for 13 weeks. No mortality or abnormal clinical signs in any group were observed. Body weight gains were decreased with a tendency for reduction of feed intake in the 1.25% and above female and 5% male groups. In males, absolute and relative liver weights were increased in the 1.25% and above groups. In females relative kidney weights were increased in the 1.25% and above groups. Other significant changes such as decreased RBC and hematocrit and increased urea nitrogen were detected in the 2.5% and/or 5% groups. On histopathological observation, atrophy of the ventral prostate was observed in all animals in the 5% male group. Mucification and atrophy of the vaginal epithelium and increased atretic follicles in ovaries were noted in 2.5% and 5% female rats. Based on the above findings the lowest-observed-adverse-effect level for male and female rats was estimated to be 1.25% (707.2 and 751.8 mg/kg b.w./day, respectively).

The objective of this study was to identify proteins in the m. longissimus dorsi between early (12 months of age) and late (27 months of age) fattening stages of Hanwoo (Korean cattle) steers. Using two-dimensional electrophoresis and mass spectrometry, 8 proteins of 11 differentially expressed spots between the 12 and 27 month age groups were identified in the loin muscle. Among those that were differentially expressed, zinc finger 323 and myosin light chain were highly expressed in late-fattening stage, and two catabolic enzymes, triosephosphate isomerase (TPI) and succinate dehydrogenase (SDH) were expressed more in the early versus the late-fattening stage. In particular, the quantification of TPI and SDH by immunoblotting correlated well with fat content. Our data suggested that TPI and SDH are potential candidates as markers and their identification provides new insight into the molecular mechanisms and pathways associated with intramuscular fat contents of bovine skeletal muscle.

When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2alpha phosphorylation. Transcription of two downstream targets of eIF2alpha, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuronal differentiation of mouse embryonic stem (mES) cells. Finally, chemical endoplasmic reticulum (ER) stress inducers, thapsigargin, tunicamycin, and brefeldin A, dose-dependently increased both mRNA and protein expressions of NF-L, and, its expression was specific to BIP-positive rBMSCs. Our results showing the induction of UPR during neuronal differentiations of rBMSCs and mES cells as well as NF-L expression by ER stress inducers strongly suggest the potential role of UPR in neuronal differentiation.

A chronic toxicity study of kojic acid (KA) was performed using male F344 rats by dietary administration at concentrations of 0 (control), 0.5 and 2.0% for 55 weeks. Body weight gain was suppressed in the 2.0% group. The major hematological findings were decreased red blood cell (RBC) count and hematocrit (Ht) values at both 0.5 and 2.0%. In serum biochemistry, increased aspartate transaminase (AsT), alanine transaminase (AlT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels were detected in the 0.5 and 2.0% groups. Histopathologically, single cell necrosis of hepatocytes and proliferation of bile ductules in both treatment groups, and hypertrophy of hepatocytes, granulomas and proliferation of bile ducts in the 2.0% group were increased in incidence, and numbers and areas of glutathione-S-transferase placental-form (GST-P) positive foci were increased in the liver of the 2.0% group. In the thyroids, diffuse follicular cell hyperplasia at 0.5 and 2.0% and focal follicular cell hyperplasia and follicular adenoma at 2.0% were increased. A thyroid follicular carcinoma was also observed at 2.0%. Additionally, increased incidences of hyaline casts and basophilic tubules in the kidneys at 2.0% and microgranulomas containing crystals in the lung in both treatment groups were noted. At 2.0%, hypertrophy of cortical cells in zona fasciculata was also increased in the adrenals. In conclusion, no observed adverse effect level of KA was below 0.5%, which is equivalent to 227 mg/kg body weight/day in male rats.