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HER-2 and HER-3 are transmembrane receptor proteins that are considered to be important but poorly understood biomarkers in canine tumors. In this study, the expression and the localization of HER-2 and HER-3 were evaluated immunohistochemically in canine mammary tumors (n = 64; 12 benign, 52 malignant). HER-2 overexpression was identified in 2/12 (16.7%) benign and in 18/51 (35.3%) malignant cases. HER 3 was expressed in a non-nuclear localization in 11/12 (91.7%) benign and 18/52 (34.6%) malignant tumors. In contrast, HER-3 was expressed in the nucleus of neoplastic cells in 0/12 (0%) benign and 22/52 (42.3%) malignant tumors. Nuclear HER-3 expression was higher in neoplastic epithelial cells compared to myoepithelial cells, and positively correlated with high histological grade and lymphatic vessel invasion. These results suggest that nuclear HER-3 expression is significantly associated with tumor progression and metastasis and may serve as a useful prognostic biomarker in canine malignant mammary tumors. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-α-2a is successful in eradicating virus from only 30 to 80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained viral response (SVR) to the therapy for chronic HCV infection. We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower risk of achieving SVR among Caucasian Americans (CAs) ((relative risk) RR=0.80; 95% CI: 0.66−0.98; P=0.0261). Using a sliding window approach, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was associated with a reduced chance of SVR (RR=0.79; 95% CI: 0.66–0.94; P=0.0081), as was the rs1800796-(G)-rs1800795-(G)-rs2069830-(C) haplotype (RR=0.78; 95% CI: 0.66–0.94; P=0.0065) among CAs. Overall, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was independently associated with a reduced chance of SVR (RR=0.78; 95% CI: 0.62–1.0; P=0.0489) after adjustment for potential confounding factors. Our findings further illustrate the complexity of IL-6 genetic regulation and the potential importance of haplotypes on IL-6 expression. Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy.Genes and Immunity (2009) 10, 365–372; doi:10.1038/gene.2009.26; published online 23 April 2009 [ABSTRACT FROM AUTHOR]

Mapping the structure and function of the brain with non-invasive brain imaging techniques has become a world-wide enterpise in the last 20 years. The core concept that drives this rapid growth has been the use of a standardized 3D coordinate space for combining data from many subjects and/or time-points. This has allowed geographically-separated laboratories to reproduce experiments in precise detail, to share data or to perform meta-analysis in ways that go far beyond the traditional reviewing of summary results in journal publications. A further corollary of the brain mapping approach is the natural fostering of multi-center collaboration among distant sites. This article describes recent progress in trans-Pacific collaboration between Canadian and Asian laboratories in the study of neuroanatomical networks obtained from MRI data, both in the normal brain and in neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8+ and CD4+ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30–80%) and lower response rates have been reported among African Americans (AA; ∼30%) compared to Caucasian Americans (CA; ∼50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-α-2a and ribavirin. We observed carriage of A*02 (RR=1.33(1.08–1.64); P=0.008), B*58 (RR=1.84(1.24-2.73); P=0.002) and DPB1*1701 (RR=1.57(1.09-2.26); P=0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.Genes and Immunity (2008) 9, 328–333; doi:10.1038/gene.2008.21; published online 17 April 2008 [ABSTRACT FROM AUTHOR]

X-ray radiography was used to measure the behavior of four fuel sprays from a light-duty common-rail diesel injector The sprays were at 250 bar injection pressure and 1 bar ambient pressure. Injection durations of 400 μs and 1000 μs were tested, as were axial single-hole nozzles with hydroground and nonhydroground geometries. The X-ray data provide quantitative measurements of the internal mass distribution of the spray, including near the injector orifice. Such measurements are not possible with optical diagnostics. The 400 μs sprays from the hydroground and nonhydro ground nozzles appear qualitatively similar The 1000 μs spray from the nonhydro ground nozzle has a relatively consistent moderate width, while that from the hydroground nozzle is quite wide before transitioning into a narrow jet. The positions of the leading and trailing-edges of the spray have also been determined, as has the amount of fuel residing in a concentrated structure near the leading edge of the spray. [ABSTRACT FROM AUTHOR]

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there is no standardized treatment available for patients who do not respond to steroids. As an alternative to immunosuppressants, mesenchymal stem cells (MSCs) have been suggested to treat steroid-refractory GVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we treated ten severe steroid-refractory cGVHD patients intravenously with MSCs produced from third-party bone marrow donors biweekly for a total of four doses. Each dose contained 1 × 106 cells/kg body weight from the same donor and same passage. Ten patients with various organ involvement were enrolled. All ten patients received their planned four doses of MSCs, administering a total of 40 infusions during the study. MSCs were well tolerated with no immediate or delayed toxicities. After 8 weeks of the first MSC infusion, all ten patients showed partial response showing alleviation in clinical symptoms and increased quality of life. Two patients died due to relapse from primary disease. Immunological analyses revealed reduction in inflammatory markers including ST2, CXCL10, and osteopontin following MSC treatment. Repeated infusions of MSCs was feasible and safe and may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow up is needed in the future to determine the role of MSCs in cGVHD. [ABSTRACT FROM AUTHOR]

Objectives: (1) To estimate caregiver support required by patients 2 months after prolonged (at least 48 h) mechanical ventilation (MV) in an ICU; (2) to describe caregiver burden, caregiver depressive symptomatology, and caregiver limitations in activities; and (3) to investigate factors related to depressive symptoms at 2 months in caregivers.Design: Prospective cohort study.Study Participants: Caregivers of 115 patients who received prolonged MV in an ICU.Measurements: Sociodemographics, employment status, hours spent providing care, help from paid caregiving sources, caregiver burden, and caregiver depressive symptoms.Results: The proportion of patients who survived at least 2 months and required caregiver support was 74.8%. The average age of caregivers was 52.9 years (SD, 14.2), 76.5% were women, and more than half were spouses (52.2%). Only 33 of the caregivers (28.7%) were working, and 30.3% had to reduce their time spent at work to provide care to the patient. The prevalence of risk of clinical depression (defined as Center for Epidemiological Studies depression scale [CES-D] score > or =16) among caregivers was 33.9%. The mean caregiver CES-D score was 13.2 (SD, 11; median, 10). Multiple linear regression analysis showed that higher CES-D score was associated with more hours per day helping with patients' activities of daily living and instrumental activities of daily living (p = 0.003).Conclusions: Two months after being placed on MV for at least 48 h, a high proportion of patients need caregiver support. Approximately 34% of caregivers are at risk of clinical depression. Many caregivers report lifestyle changes and burden when providing care for the patients. [ABSTRACT FROM AUTHOR]

The broadening of X-ray peak profiles and movements of tensile axes were obtained simultaneously in single-slip-conditioned copper single crystals. Two types of sample showed different tensile axis movements and slip system activities. These results are in accord with the observation of slip lines with scanning electron microscopy. The broadening of the X-ray peak profiles is highly dependent on the absolute value of g b despite the same amount of deformation. The slope between shear stress and beta obtained from disorder broadening generally shows similar trends for samples A and B. As soon as the tensile axis leaves its original stereographic triangle, beta stops increasing in disorder sample B. This phenomenon indicates the change of activation of (111)\[101] and (111)\[011] slip systems. [ABSTRACT FROM AUTHOR]

A method of stress analysis is proposed to analyze impulsive stresses at an impact loading point, since use of the classical plate theory cannot lead to a convergent result. In particular, under these impact conditions, the three‐dimensional dynamic theory of elasticity and potential theory of displacement to analyze the impulsive strains at an impact loading point were used. Also, by using Hertzian contact theory to account for local deformation, the impact loading was analyzed, and this loading was applied to the impulsive stress analysis by allowing the impact loading to be approximated to an analyzable function.

Entamoeba histolytica can cause invasive disease by disruption of the intestinal barriers and subsequent lysis of the intestinal cells. Adherence to and contact dependent killing of host cells requires the galactose inhibitable lectin. To elucidate the mechanism whereby E. histolytica influences host defence, the authors assessed the change of proinflammatory cytokine genes expressed by colon epithelial cells in response to co-culture with E. histolytica trophozoites and carbohydrates, including galactose, N-acetyl-galactosamine or N-acetyl-lactosamine, which prevented E. histolytica from attaching to epithelial cells. After HT-29 human colon epithelial cells were co-cultured with E. histolytica trophozoites in the presence or absence of carbohydrates (0.1-100mM), RNA was extracted from the epithelial cells by an acid guanidinium thiocyanate-phenol-chloroform method. Cytokine gene expression was assessed by quantitative RT-PCR using a synthetic internal standard, and proteins were determined by ELISA. IL-8 mRNA expressed by HT-29 cells in response to E. histolytica trophozoites was downregulated in the presence of galactose, N-acetyl-galactosamine or N-acetyl-lactosamine (0.1-100mM), and this was paralleled by decreased IL-8 protein secretion. GM-CSF and IL-1α/β mRNAs were also downregulated in those cells in the presence of these agents. These results suggest that the expression of proinflammatory cytokine genes could be inhibited by preventing E. histolytica from attaching to the host's colon epithelial cells. [ABSTRACT FROM AUTHOR]