Expression of E-cadherin and alpha-, beta-, gamma-catenin proteins in endometrial carcinoma

Loss of the cell adhesion molecule E-cadherin is suggested to promote tumor invasion and distant metastasis in tumor development. Recently, it has been proposed that E-cadherin function requires its linkage to the cytoskeleton through catenins. We evaluated the expression of E-cadherin and alpha-, beta-, gamma-catenins in tissues of human endometrial carcinoma, analyzed the patterns of cell adhesion molecules' expression in endometrial carcinoma and investigated the relationship between the statuses of cell adhesion molecules and various clinicopathological factors. This study investigated the immunohistochemical expression of E-cadherin and alpha-, beta-, gamma-catenins in 33 paraffin embedded formalin fixed tissues of endometrial carcinomas. Aberrant E-cadherin, and alpha-, beta-, gamma-catenin expression was observed in 33.3 (11 of 33), 27.3 (9 of 33), 18.2 (6 of 33), and 51.5 (17 of 33) % of the specimens, respectively. Statistically significant correlation was found between aberrant expression of E-cadherin and lymph node metastasis and cell types other than endometrioid adenocarcinoma. Aberrant pattern of gamma-catenin expression was also correlated with deep myometrial invasion. However, alpha-, and beta-catenin expression was not correlated with any clinicopathological parameters. Using the Kaplan-Meier method and log-rank comparison test, abnormal expression of E-cadherin was correlated closely with poor survival (p < 0.05), but cases with loss of both E-cadherin and catenin expression predicted even poorer survival than cases with only one or no aberrant expression in E-cadherin and catenins. We revealed aberrant expression of these cell adhesion molecules among patients with endometrial carcinoma. Aberrant expression of E-cadherin was correlated with lymph node metastasis and cell types other than endometrioid adenocarcinoma, while aberrant expression of gamma-catenin was related with deep myometrial invasion. The expression of E-cadherin might be a possible prognostic factor for endometrial cancer while the expression of catenins may help predict patient's survival.     

Mechanisms of nitric oxide interplay with Rho GTPase family members in modulation of actin membrane dynamics in pericytes and fibroblasts

Migration of pericytes such as hepatic stellate cells is fundamentally important for diverse biological and pathological processes including tumor invasion and fibrosis. In prototypical migratory cells such as fibroblasts, the small GTPases Rac1 and RhoA govern the assembly of lamellipodia and stress fibers, respectively, cytoskeletal structures that are integral to the cell migration process. The gaseous signaling molecule nitric oxide (NO) influences growth factor chemotactic responses, although this occurs primarily in cell-type-specific ways and through cell biological effects that are poorly characterized. In this study, we use complementary molecular and cell biological approaches to delineate important roles for Rac1, RhoA, and NO in migration of the human hepatic stellate cell line LX2 and primary rat hepatic stellate cells. Both platelet-derived growth factor (PDGF) and Rac1 overexpression drove migration through formation of actin-positive filopodia spikes in LX2 as compared to the formation of lamellipodia in fibroblasts. NO inhibited PDGF- and Rac1-driven migration in LX2 by abrogating filopodia formation and inhibited migration of fibroblasts by attenuating lamellipodial protrusions. Additionally, RhoA conferred resistance to NO inhibition of migration and restored chemotactic responses to PDGF in the absence of functional Rac1 in LX2. In conclusion, these studies identify novel crosstalk between small GTPases, cytoskeletal structures, and NO in pericyte-specific pathways, providing counterbalances in the chemotactic responses to growth factors.     

Role of L3T4-bearing T-cell populations in experimental murine chlamydial salpingitis.

A role for both the cellular and humoral components of the immune response has been established for chlamydial infection. The significance of helper (L3T4) T cells was evaluated by using a Chlamydia trachomatis murine salpingitis model for upper genital tract chlamydial infection. Mouse oviducts were inoculated with C. trachomatis by using the mouse pneumonitis agent (MoPn) or control medium. Mice depleted of L3T4-bearing lymphocytes had significantly higher (P less than 0.05) numbers of organisms recovered at day 7 postinoculation. The rate of hydrosalpinx formation was significantly higher in the mice depleted of L3T4-bearing lymphocytes (27 of 31 [87%] ) than in the infected undepleted group (8 of 16 [50%] ) (P less than 0.01). The geometric mean antichlamydial immunoglobulin G titers at day 54 postinoculation were significantly higher in the L3T4-depleted mice (mean titer, 2,030) than in the undepleted group (mean titer, 776; P less than 0.05). The rate of fertility was lower in the L3T4-depleted group (2 of 31 [6%]) than in the infected, undepleted mice (2 of 16 [13%]), but this difference did not reach statistical significance. In conclusion, the greater persistence of organisms in the oviduct and higher rates of hydrosalpinx formation in mice depleted of L3T4-bearing cells suggests that these cells play a role in the clearing of organisms following infection and thus in reducing the degree of oviduct obstruction and damage.     

Effect of Carbohydrate Source on Kanagawa-Type Hemolysis of Vibrio parahaemolyticus

Almost all strains of Vibrio parahaemolyticus produced Kanagawa-type hemolysis on media of high salt content in the presence of fermentable carbohydrates.     

Lifestyle Risk Score: handling missingness of individual lifestyle components in meta-analysis of gene-by-lifestyle interactions

Recent studies consider lifestyle risk score (LRS), an aggregation of multiple lifestyle exposures, in identifying association of gene-lifestyle interaction with disease traits. However, not all cohorts have data on all lifestyle factors, leading to increased heterogeneity in the environmental exposure in collaborative meta-analyses. We compared and evaluated four approaches (Naïve, Safe, Complete and Moderator Approaches) to handle the missingness in LRS-stratified meta-analyses under various scenarios. Compared to “benchmark” results with all lifestyle factors available for all cohorts, the Complete Approach, which included only cohorts with all lifestyle components, was underpowered due to lower sample size, and the Naïve Approach, which utilized all available data and ignored the missingness, was slightly inflated. The Safe Approach, which used all data in LRS-exposed group and only included cohorts with all lifestyle factors available in the LRS-unexposed group, and the Moderator Approach, which handled missingness via moderator meta-regression, were both slightly conservative and yielded almost identical p values. We also evaluated the performance of the Safe Approach under different scenarios. We observed that the larger the proportion of cohorts without missingness included, the more accurate the results compared to “benchmark” results. In conclusion, we generally recommend the Safe Approach, a straightforward and non-inflated approach, to handle heterogeneity among cohorts in the LRS based genome-wide interaction meta-analyses.Subject terms: Genetics, Risk factors     

Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging diagnosis

Despite a gradual decrease in prevalence, clonorchiasis is still prevalent in East Asia. A large and compelling body of evidence links clonorchiasis and cholangiocarcinoma, although the mechanisms involved are not completely understood. Clonorchiasis induces biliary epithelial hyperplasia and metaplasia, and this could facilitate at least one stage of the carcinogenesis, which is promoting effect. In areas of endemic infection, more clonorchiasis cases are now diagnosed incidentally during radiological examinations such as cholangiography, ultrasonography, and computed tomography. Radiological findings are regarded as pathognomonic for clonorchiasis since they reflect the unique pathological changes of this disorder. These radiological examinations currently play important roles in the diagnosis, staging, and decision-making process involved in the treatment of cholangiocarcinoma. The morphological features and radiological findings of clonorchiasis-associated cholangiocarcinoma are essentially combinations of the findings for the two diseases. The morphological features of clonorchiasis- associated cholangiocarcinoma, observed in radiological examinations, do not differ from those of the usual cholangiocarcinoma. In patients diagnosed with or suspected to have clonorchiasis, radiological findings should be carefully scrutinized for occult cholangiocarcinoma.     

Cloning, expression and characterization of a murine-human chimeric antibody with specificity for pre-S2 surface antigen of hepatitis B virus

The cloning, expression and characterization of a murine-human chimeric antibody with specificity for the pre-S2 surface antigen (Ag) of hepatitis B virus (HBV) is described. The heavy and light chain variable region (VH and VL) genes encoding the murine monoclonal antibody (mAb) were isolated and combined with human γ 1 and κ constant region genes, respectively. The expression vectors containing the chimeric heavy and light chain genes were sequentially electroporated into murine Sp2/0 hybridoma cells and transfectomas secreting chimeric antibody were isolated. The chimeric antibody was purified and characterized by ELISA, Western analysis and competition immunoassay, demonstrating that the transfectoma functionally express and secrete murine-human chimeric antibody which retained the specificity and affinity of the parental murine mAb.     

Comparison of three different sensitive assays for hepatitis B virus DNA in monitoring of responses to antiviral therapy

The aim of our study was to compare the performances of two new hepatitis B virus (HBV) DNA assays, a cross-linking assay (NAXCOR) and a hybrid-capture amplification assay (Digene), versus the widely used branched-DNA (bDNA) assay (Chiron) in the monitoring of HBV DNA levels during antiviral treatment. Serial serum samples from 12 chronically HBV infected patients undergoing a phase II trial of an antiviral drug, 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC), were studied. A total of 96 serum samples were tested for HBV DNA using the cross-linking, hybrid-capture amplification, and bDNA assays. In the comparison of the cross-linking and bDNA assays, concordant results were found in 77 (80.3%) samples, no significant difference was found between the median log(10) HBV DNA levels (6.66 versus 7. 17 meq/ml), and the results of the two assays were closely correlated (r = 0.95). In the comparison of the hybrid-capture amplification and bDNA assays, concordant results were found in 79 (82.3%) samples, no significant difference was found between the median log(10) HBV DNA levels (6.98 versus 6.99 meq/ml), and the results of the two assays were closely correlated (r = 0.99). Six (6. 3%) samples by the cross-linking assay and 10 (10.4%) samples by the bDNA assay required retesting because of unacceptably high within-run coefficients of variance. No sample required retesting in the hybrid-capture amplification assay according to the internal validation. In conclusion, the cross-linking and hybrid-capture amplification assays were as sensitive as the bDNA assay for HBV DNA detection and can be recommended for monitoring of HBV DNA levels during antiviral treatment.     

Structural abnormalities of autosomal chromosomes in the male partner do not influence fertilization and early development of embryos after intracytoplasmic sperm injection

The objective of this study was to determine whether or not abnormalities in the autosomal structure of the male partner have any influence on fertilization and early embryo development after intracytoplasmic sperm injection (ICSI). Thirty-seven couples in whom the male partners were examined by the same andrologist were included in this study. Six couples (group I) in whom the male partner possessed autosomal structural abnormality underwent seven ICSI cycles. As a control group, 31 couples (group II) in which the male partner was karyotypically normal underwent 41 ICSI cycles. Although the normal fertilization rates seen in group I were significantly higher than those in group II (P < 0.05), there was no significant difference in the cleavage rates between the two groups. We did not perform the analysis of the female partner's chromosomes, but we surmise that structural autosomal abnormalities in the male partner do not adversely influence fertilization at ICSI and early development of embryos.      

Preparation of a novel polyoxime and reversible uptakes of molecular oxygen and carbon monoxide by its metal complexes

Polyketones with carbonyl groups in the polymer backbone (ethylene-carbon monoxide copolymer) have been converted into a novel polyoxime by means of C-nitrosation of the methylene groups and oximation of the carbonyl groups. The polyoxime is considered to be composed largely of 1,2-bis(hydroxyimino)trimethylene units. From the polyoxime and divalent Fe-, Co-, or Ni-salts, polymeric metal chelate complexes were prepared which are capable of combining reversibly with molecular oxygen and, especially the Fe-complex, also with carbon monoxide.