Eukaryotic initiation factor 4A (eIF4A) during viral infections

Virus Genes - The helicase eIF4A is part of the cellular eIF4F translation initiation complex. The main functions of eIF4A are to remove secondary complex structures within the...     

Hypoxic regulation and prognostic value of LAMP3 expression in breast cancer

BACKGROUND:

LAMP3 is a newly described hypoxia regulated gene of potential interest in hypoxia‐induced therapy resistance and metastasis. The prognostic value of LAMP3 in breast cancer was investigated.

METHODS:

Expression levels of LAMP3 in breast cancer cell lines and patient tissues were determined by real‐time polymerase chain reaction and in a tissue microarray by immunohistochemistry. Immunofluorescent staining was used to evaluate the distribution of LAMP3 in tumor xenografts relative to pimonidazole. Kaplan‐Meier analysis as well as multivariate Cox regression survival analyses were performed.

RESULTS:

LAMP3 was variably expressed in breast cancer cell lines and induced in an oxygen concentration‐dependent manner. LAMP3 protein expression colocalized with hypoxic areas in breast cancer xenografts. LAMP3 mRNA was higher in breast tumors from patients with node‐positive (P = .019) and/or steroid hormone receptor‐negative tumors (P < .001). Breast cancer patients with high LAMP3 mRNA levels had more locoregional recurrences (P = .032 log‐rank). This was limited to patients treated with lumpectomy and radiotherapy as primary treatment (n = 53, P = .009). No association with metastasis‐free survival was found. In multivariate Cox regression analysis, LAMP3 remained as a statistically independent prognostic factor for locoregional recurrence (hazard ratio, 2.76; 95% confidence interval, 1.01‐7.5; P = .048) after correction for menopausal status, histologic grade, tumor size, nodal status, therapy, and steroid hormone receptor status. LAMP3 protein in breast cancer tissue proved also to be of prognostic relevance.

CONCLUSIONS:

Evidence was provided for an association of LAMP3 with tumor cell hypoxia in breast cancer xenografts. In the current breast cancer cohorts, LAMP3 had independent prognostic value. Cancer 2011;117:3670–3681. © 2011 American Cancer Society.     

IgA glomerulonephritis

Renal biopsy specimens from 204 patients with glomerulonephritis or nephrotic syndrome have been studied. In ten of the patients not suffering from acute poststreptococcal glomerulonephritis, systemic lupus erythematosus or Schönlein-Henoch syndrome, diffuse, selective mesangial IgA deposition was observed. Clinically, persistent microscopic haematuria, mild proteinuria and, except in one patient, normal renal function were found. Light microscopically the histological picture was dominated by a diffuse or focal increase in volume of the mesangial matrix, and mild mesangial cell proliferation. Exceptionally, there was also crescent formation. Immunofluorescence revealed large IgA, IgG and C3 deposits, as well as small IgM and fibrinogen deposits in the mesangial glomeruli. The authors' assumption that immunocomplexes containing a secretory component might be implicated in the pathomechanism of Berger's disease, could not be proved.On the basis of a lecture given at the XXIIIrd Itinerary Congress of the Transdanubian Section of the Association of Hungarian Internists, held at Gyr on 18th June, 1976. Supported by the Scientific Research Council, Ministry of Health, Hungary (3-18-0304-03-2/H).     

Addressing Methodologic Challenges and Minimizing Threats to Validity in Synthesizing Findings from Individual-Level Data Across Longitudinal Randomized Trials

Integrative Data Analysis (IDA) encompasses a collection of methods for data synthesis that pools participant-level data across multiple studies. Compared with single-study analyses, IDA provides larger sample sizes, better representation of participant characteristics, and often increased statistical power. Many of the methods currently available for IDA have focused on examining developmental changes using longitudinal observational studies employing different measures across time and study. However, IDA can also be useful in synthesizing across multiple randomized clinical trials to improve our understanding of the comprehensive effectiveness of interventions, as well as mediators and moderators of those effects. The pooling of data from randomized clinical trials presents a number of methodological challenges, and we discuss ways to examine potential threats to internal and external validity. Using as an illustration a synthesis of 19 randomized clinical trials on the prevention of adolescent depression, we articulate IDA methods that can be used to minimize threats to internal validity, including (1) heterogeneity in the outcome measures across trials, (2) heterogeneity in the follow-up assessments across trials, (3) heterogeneity in the sample characteristics across trials, (4) heterogeneity in the comparison conditions across trials, and (5) heterogeneity in the impact trajectories. We also demonstrate a technique for minimizing threats to external validity in synthesis analysis that may result from non-availability of some trial datasets. The proposed methods rely heavily on latent variable modeling extensions of the latent growth curve model, as well as missing data procedures. The goal is to provide strategies for researchers considering IDA.

     

Psychosocial aspects of Costa Rican adolescents' eating and physical activity patterns.

PURPOSE: To determine the importance of some psychosocial aspects on the eating and physical activity patterns of Costa Rican adolescents.METHODS: A total of 1200 adolescents were included in the study. Data were collected using a self-administered instrument containing the following elements: questions to elicit demographic information and five sections with several items (stated as positive or negative behaviors) to study the influence of peers, parents, social environment, body image, and self-efficacy on five target behaviors, intake of foods rich in saturated fats, calcium, and iron, along with consumption of fruits and vegetables and physical activity practices. Data were analyzed using a factor analysis with main component extraction and varimax rotation, along with multiple regression analyses.RESULTS: Social environment and peer influence were the major factors that predict behaviors associated with the intake of foods rich in saturated fat. Meanwhile, parental and social environment influences were the main factors in explaining the fruit and vegetable intake-related behaviors. Self-efficacy was a significant predictor of behaviors associated with physical activity. Body image influence was an important variable associated with all the behaviors analyzed. Multiple regression analyses suggest that the fathers' educational level, the adolescents' age, being female, and living in a rural area may have positive influence on the behaviors studied; however, the overall R(2) for all regression models was quite small (<.03).CONCLUSIONS: Most of the variability in adolescents' food intake and physical activity-related behaviors remained unexplained by the demographic variables included in the study. Nevertheless, the results suggest that promotion of health programs built on the influence of social environment, peers and family members, and self-efficacy may have a positive impact on the adolescents' food and physical activity patterns. However, the clear definition of which psychosocial aspect(s) strongly influence the behavior to be modified, is essential for designing an intervention that is properly directed at the correct target.     

Effect of oral diacerein (DAR) in an experimental hip chondrolysis model.

We aimed to reproduce the articular cartilage structural changes in a joint exposed to a metallic implant as in the adolescent pinned hip with persistent joint penetration and secondly, to test the effect of an interleukin inhibitor, diacerein (DAR) in the ensuing articular cartilage lesion. Twenty immature beagles were submitted to a surgical K-wire implantation in the hip with the material left in the joint space for 6 months. Twelve animals were sacrificed for histological and biochemical tests. Eight animals were sacrificed at 10 months (half of them treated with DAR) and analyzed by scanning electron microscopy (SEM) and biochemistry of the articular cartilage. Preoperative and monthly C3 and C4 complement and immunoglobulins serum levels were determined. The histological and the electrophoretic profile changes were significative at 6 months. At 10 months the migration profile (CaCl2) recovered to normal levels in the operated hip and the SEM scores for the acetabulum were similar to the non operated control hip after treatment. The serum level of IgA was elevated at the 4th and 6th month postoperatively. The persistence of a metallic implant resulted in degenerative changes parallel to that described for hip chondrolysis as a complication of in-situ pinning; and the cartilage lesion improved with DAR treatment.     

Immunological recovery after bone marrow transplantation for severe aplastic anaemia: A Brazilian experience

Abstract: Twenty-nine patients with severe aplastic anaemia (SAA) were submitted to bone marrow transplantation (BMT) and their immunological recovery analysed. Total lymphocyte counts, estimation of B lymphocytes, T lymphocytes and their subsets, natural-killer (NK) activity were performed. Cells with the CD8 + phenotype and NK activity were the first signs of immunological recovery, whereas the CD4 + subset recovered later in patients who suffered from acute graft versus host disease (GvHD) and infections. Acute and chronic GvHD, cirrhosis, rejection and HIV viral infection contributed to the persistence of the profound immunodeficiency status observed after BMT. Our results did not differ greatly from the others and confirmed that BMT may be performed in underdeveloped countries despite the difficulties it might pose.     

Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules

To understand the functions of NIPA1, mutated in the neurodegenerative disease hereditary spastic paraplegia, and of ichthyin, mutated in autosomal recessive congenital ichthyosis, we have studied their Drosophila melanogaster ortholog, spichthyin (Spict). Spict is found on early endosomes. Loss of Spict leads to upregulation of bone morphogenetic protein (BMP) signaling and expansion of the neuromuscular junction. BMP signaling is also necessary for a normal microtubule cytoskeleton and axonal transport; analysis of loss- and gain-of-function phenotypes indicate that Spict may antagonize this function of BMP signaling. Spict interacts with BMP receptors and promotes their internalization from the plasma membrane, implying that it inhibits BMP signaling by regulating BMP receptor traffic. This is the first demonstration of a role for a hereditary spastic paraplegia protein or ichthyin family member in a specific signaling pathway, and implies disease mechanisms for hereditary spastic paraplegia that involve dependence of the microtubule cytoskeleton on BMP signaling.