BioMed Central - Latest Articles

Cytoplasmic p21 induced by p65 prevents Doxorubicin-induced cell death in Pancreatic Carcinoma cell line

YingQi Zhou — 2012-02-04T00:00:00Z

Background: Studies have shown the existence of p21 induction in a p53-dependent and -independent pathway. Our previous study indicates that DOX-induced p65 is able to bind the p21 promoter to activate its transactivation in the cells. Methods: Over-expression and knock-down experiments were performed in Human Pancreatic Carcinoma (PANC1) cells. Cell cycle and cell death related proteins were assessed by Western Blotting. Cytotoxicity assay was checked by CCK-8 kit. Cell growth was analyzed by flow cytometers. Results: Here we showed that over-expression of p65 decreased the cytotoxic effect of DOX on PANC1 cells, correlating with increased induction of cytoplasmic p21. We observed that pro-caspase-3 physically associated with cytoplasmic p21, which may be contribution to prevent p21 translocation into the nucleus. Our data also suggested that no clear elevation of nuclear p21 by p65 provides a survival advantage by progression cell cycle after treatment of DOX. Likewise, down-regulation of p65 expression enhanced the cytotoxic effect of DOX, due to a significant decrease of mRNA levels of anti-apoptotic genes, such as the cellular inhibitor of apoptosis-1 (c-IAP1), and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2), leading to efficient induction of caspase-3 cleavage in the cells. More, we present evidence that over-expression of p53 or p53/p65 in the PANC1 cells were more sensitive to DOX treatment, correlated with activation of caspase-3 and clear elevation of nuclear p21 level. Our previous data suggested that expression of p21 increases Gefitinib-induced cell death by blocking the cell cycle at the G1 and G2 phases. The present findings here reinforced this idea by showing p21's ability of potentiality of DOX-induced cell death correlated with its inhibition of cell cycle progression after over-expression of p53 or p53/p65. Conclusion: Our data suggested p65 could increase p53-mediated cell death in response to DOX in PANC1 cells. Thus, it is worth noting that in p53 null or defective tumors, targeting in down-regulation of p65 may well be useful, leading to the potentiality of chemotherapeutic drugs.

The relationship between the regional abdominal adipose tissue distribution and the serum uric acid levels in people with type 2 diabetes mellitus

Tae Ho Kim — 2012-02-03T00:00:00Z

Background: Hyperuricemia is associated with obesity. The visceral adiposity and subcutaneous adiposity may be associated with the differential metabolic risk, and the distribution of abdominal adipose tissue was significantly altered in people with type 2 diabetes mellitus (DM) compared to healthy people. Our study was performed to determine to the association between the regional abdominal adipose tissue distribution and serum uric acid levels in people with type 2 DM. Methods: A total of 699 people with type 2 DM and who had undergone abdominal computed tomography assessment of the visceral fat area and subcutaneous fat area were included. The serum uric acid levels were measured by the uricase method. Hyperuricemia was defined by cut-off value of > 7 mg/dl for men and > 6 mg/dl for women. Results: The visceral fat area was positively associated with the serum uric acid levels after adjustment for age, sex, systolic blood pressure, diastolic blood pressure, serum creatinine, hemoglobin, serum albumin, serum high-density lipoprotein, serum triglyceride and hemoglobin A1c (beta-coefficient = 0.117, p < 0.001). The logistic regression analysis showed that the visceral fat area was the significant independent predictor of hyperuricemia (OR 2.33, 95% CI, 1.21-4.50, p = 0.012). But there was no significant association between the subcutaneous fat area and the serum uric acid levels (beta-coefficient = 0.061, p = 0.255). Conclusions: our data shows that the visceral fat area was positively associated with the serum uric acid levels, but the subcutaneous fat area was not in people with type 2 DM.

The effects of social connections on self-rated physical and mental health among internal migrant and local adolescents in Shanghai, China

Zheng-hong Mao — 2012-02-03T00:00:00Z

Background: China is in the midst of history's largest flow of rural-urban migration in the world; a flow that includes growing numbers of children and adolescents. Their health status is an important public health issue. This study compares self-rated physical and mental health of migrant and local adolescents in China, and examines to what extent layered social connections account for health outcomes. Methods: In 2010, we conducted a cross-sectional study among middle school students in Pudong New Area, Shanghai. Information about health status, social connections, and demographic factors were collected using a questionnaire survey. After controlling for sociodemographic factors, we used the t-test, Chi-square analysis, and a series of regression models to compare differences in health outcomes and explore the effects of social connections. Results: Migrant adolescents reported significantly higher rates of good physical health. However, they also had significantly fewer social connections, lower self-esteem, and higher levels of depression than their native peers. Family cohesion was associated with depressive symptoms and low self-esteem among all adolescents; peer association and social cohesion played major roles in migrants' well-being. Gender, age, and socioeconomic (SES) factors also affected adolescents' self-rated physical and mental health. Conclusions: Self-rated data suggest that migrant adolescents enjoy a physical health advantage and a mental health disadvantage. Layered social connections, such as peer association and social cohesion, may be particularly important for migrants. A public health effort is required to improve the health status of migrant youth.

Markov Chain Ontology Analysis (MCOA)

H ROBERT Frost — 2012-02-03T00:00:00Z

Background: Biomedical ontologies have become an increasingly critical lens through which researchers analyze the genomic, clinical and bibliographic data that fuels scientific research. Of particular relevance are methods, such as enrichment analysis, that quantify the importance of ontology classes relative to a collection of domain data. Current analytical techniques, however, remain limited in their ability to handle many important types of structural complexity encountered in real biological systems including class overlaps, continuously valued data, inter-instance relationships, non-hierarchical relationships between classes, semantic distance and sparse data. Results: In this paper, we describe a methodology called Markov Chain Ontology Analysis (MCOA) and illustrate its use through a MCOA-based enrichment analysis application based on a generative model of gene activation. MCOA models the classes in an ontology, the instances from an associated dataset and all directional inter-class, class-to-instance and inter-instance relationships as a single finite ergodic Markov chain. The adjusted transition probability matrix for this Markov chain enables the calculation of eigenvector values that quantify the importance of each ontology class relative to other classes and the associated data set members. On both controlled Gene Ontology (GO) data sets created with Escherichia coli, Drosophila melanogaster and Homo sapiens annotations and real gene expression data extracted from the Gene Expression Omnibus (GEO), the MCOA enrichment analysis approach provides the best performance of comparable state-of-the-art methods. Conclusion: A methodology based on Markov chain models and network analytic metrics can help detect the relevant signal within large, highly interdependent and noisy data sets and, for applications such as enrichment analysis, has been shown to generate superior performance on both real and simulated data relative to existing state-of-the-art approaches.

Predictors of warfarin use in atrial fibrillation in the United States: a systematic review and meta-analysis

Victoria L Baczek — 2012-02-03T00:00:00Z

Background: Despite warfarin's marked efficacy, not all eligible patients receive it for stroke prevention in AF. The aim of this meta-analysis was to evaluate the association between prescriber and/or patient characteristics and subsequent prescription of warfarin for stroke prevention in patients with atrial fibrillation (AF). Methods: Observational studies conducted in the US using multivariate analysis to determine the relationship between characteristics and the odds of receiving warfarin for stroke prevention were identified in MEDLINE, EMBASE and a manual review of references. Effect estimates of prescriber and/or patient characteristics from individual studies were pooled to calculate odds ratios (ORs) with 95% confidence intervals. Results: Twenty-eight studies reporting results of 33 unique multivariate analyses were identified. Warfarin use across studies ranged from 9.1%-79.8% (median=49.1%). There was a moderately-strong correlation between warfarin use and year of study (r=0.60, p=0.002). Upon meta-analysis, characteristics associated with a statistically significant increase in the odds of warfarin use included history of cerebrovascular accident (OR=1.59), heart failure (OR=1.36), and male gender (OR=1.12). Those associated with a significant reduction in the odds of warfarin use included alcohol/drug abuse (OR=0.62), perceived barriers to compliance (OR=0.87), contraindication(s) to warfarin (OR=0.81), dementia (OR=0.32), falls (OR=0.60), gastrointestinal hemorrhage (OR=0.47), intracranial hemorrhage (OR=0.39), hepatic (OR=0.59), and renal impairment (OR=0.69). While age per 10-year increase (OR=0.78) and advancing age as a dichotomized variable (cut-off varied by study) (OR=0.57) were associated with significant reductions in warfarin use; qualitative review of results of studies evaluating age as a categorical variable did not confirm this relationship. Conclusions: Warfarin use has increased somewhat over time. The decision to prescribe warfarin for stroke prevention in atrial fibrillation is based upon multiple prescriber and patient characteristics. These findings can be used by family practice prescribers and other healthcare decision-makers to target interventions or methods to improve utilization of warfarin when it is indicated for stroke prevention.

Axillary node metastasis from differentiated thyroid carcinoma with hurthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings

Maria Grazia Chiofalo — 2012-02-03T00:00:00Z

Background: Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis.Case presentationHere we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hurthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml.Discussion and ConclusionCurrently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.

Informant-reported cognitive symptoms that predict amnestic mild cognitive impairment

Michael Malek-Ahmadi — 2012-02-03T00:00:00Z

Background: Differentiating amnestic mild cognitive impairment (aMCI) from normal cognition is difficult in clinical settings. Self-reported and informant-reported memory complaints occur often in both clinical groups, which then necessitates the use of a comprehensive neuropsychological examination to make a differential diagnosis. However, the ability to identify cognitive symptoms that are predictive of aMCI through informant-based information may provide some clinical utility in accurately identifying individuals who are at risk for developing Alzheimer's disease (AD). Methods: The current study utilized a case-control design using data from an ongoing validation study of the Alzheimer's Questionnaire (AQ), an informant-based dementia assessment. Data from 51 cognitively normal (CN) individuals participating in a brain donation program and 47 aMCI individuals seen in a neurology practice at the same institute were analyzed to determine which AQ items differentiated aMCI from CN individuals. Results: Forward stepwise multiple logistic regression analysis which controlled for age and education showed that 4 AQ items were strong indicators of aMCI which included: repetition of statements and/or questions [OR 13.20 (3.02, 57.66)]; trouble knowing the day, date, month, year, and time [OR 17.97 (2.63, 122.77)]; difficulty managing finances [OR 11.60 (2.10, 63.99)]; and decreased sense of direction [OR 5.84 (1.09, 31.30)]. Conclusions: Overall, these data indicate that certain informant-reported cognitive symptoms may help clinicians differentiate individuals with aMCI from those with normal cognition. Items pertaining to repetition of statements, orientation, ability to manage finances, and visuospatial disorientation had high discriminatory power.

Establishing a web-based integrated surveillance system for early detection of infectious disease epidemic in rural China: a field experimental study

Wei-rong Yan — 2012-02-03T00:00:00Z

Background: A crucial goal of infectious disease surveillance is the early detection of epidemics, which is essential for disease control. In China, the current surveillance system is based on confirmed case reports. In rural China, it is not practical for health units to perform laboratory tests to confirm disease and people are more likely to get 'old' and emerging infectious diseases due to poor living conditions and closer contacts with wild animals and poultry. Syndromic surveillance, which collects non-specific syndromes before diagnosis, has great advantages in promoting the early detection of epidemics and reducing the necessities of disease confirmation. It will be especially effective for surveillance in resource poor settings. Methods: This is a field experimental study. The experimental tool is an innovative electronic surveillance system, combining syndromic surveillance with the existing case report surveillance in four selected counties in China. In the added syndromic surveillance, three types of data are collected including patients' major symptoms from health clinics, pharmaceutical sales from pharmacies and absenteeism information from primary school. In order to evaluate the early warning capability of the new added syndromic surveillance, the timelines and validity of the alert signals will be analyzed in comparison with the traditional case reporting system. The acceptability, feasibility and economic evaluation of the whole integrated surveillance system will be conducted in a before and after study design.DiscussionAlthough syndromic surveillance system has mostly established in developed areas, there are opportunities and advantages of developing it in rural China. The project will contribute to knowledge, experience and evidence on the establishment of an integrated surveillance system, which aims to provide early warning of disease epidemics in developing countries.

A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System

Bjorn Meijers — 2012-02-03T00:00:00Z

IntroductionThe Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. Methods: We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 +/- 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis. Results: Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P<0.001) but remained within a safe range. We observed no major adverse events. Conclusions: Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure.

Use of glucocorticoids and risk of breast cancer: a Danish population-based case-control study

Gitte V Sorensen — 2012-02-03T00:00:00Z

IntroductionGlucocorticoids are widely prescribed drugs. In the human body, glucocorticoid is the main stress hormone, and controls a variety of physiological and cellular processes, including metabolism and immune response. It belongs to the same steroid superfamily as estrogens, which are known to play a role in breast cancer. However, the effect of glucocorticoid use on the risk of breast cancer is not clear. Methods: We conducted a case-control study using population-based medical databases from Northern Denmark (1.8 million inhabitants) to investigate the association between glucocorticoid prescriptions and breast cancer risk. The study included 9,488 incident breast cancer cases diagnosed between 1994 and 2008 and 94,876 population controls. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) associating glucocorticoid use with breast cancer occurrence, controlling for prescriptions of postmenopausal hormone replacement therapy, anti-diabetics, immunosuppressive drugs, and hospital diagnosis of obesity, diabetes, chronic pulmonary diseases and autoimmune diseases. Results: We found no effect on breast cancer risk in ever users (>2 prescriptions) of any glucocorticoids (adjusted OR (aOR)=1.0; 95% CI: 0.96, 1.1), systemic glucocorticoids (aOR=1.0; 95% CI: 0.96, 1.1), or inhaled glucocorticoids (aOR=1.0; 95% CI: 0.95, 1.1), each compared to never users of any glucocorticoids. Associations for recent use (preceding 2 years) and former use (more than 2 years earlier) were near null in all dose categories (low, medium and high number of prescriptions). Intensity of systemic glucocorticoid use (cumulative prednisolone equivalent doses), regardless of duration (<1, 1-5, 5+ years), was also not associated with breast cancer risk. Conclusions: Overall, our study provides no evidence that glucocorticoid use affects the risk of breast cancer.