Inflammatory myofibroblastic pseudotumour of the liver in association with gall stones - a rare case report and brief review

Inflammatory myofibroblastic pseudotumours of the liver are rare tumour-like lesions that can mimic malignant liver neoplasms. The symptoms and radiological findings of this rare tumour can pose diagnostic difficulties. We describe a 69-year-old gentleman who was admitted to our department with symptoms suggestive of acute cholecystitis. Ultrasonography and computed tomography of the liver raised the possibility of metastatic liver disease. A core biopsy of the liver was performed to confirm the diagnosis of liver metastasis. Unexpectedly it showed no evidence of malignancy but instead revealed an inflammatory myofibroblastic pseudotumour of the liver. This case report highlights the diagnostic dilemma that arose due to the similarity of appearances between the two pathological entities on imaging and this stresses the need for accurate histological diagnosis so as to avoid unnecessary surgical intervention. To the best of our knowledge, only a minority of cases are reported in the literature associating a hepatic inflammatory myofibroblastic pseudotumour with gall stones

Cellular Mechanisms Underlying the Laxative Effect of Flavonol Naringenin on Rat Constipation Model

BACKGROUND & AIMS: Symptoms of constipation are extremely common, especially in the elderly. The present study aim to identify an efficacious treatment strategy for constipation by evaluating the secretion-promoting and laxative effect of a herbal compound, naringenin, on intestinal epithelial anion secretion and a rat constipation model, respectively. METHODS/PRINCIPAL FINDINGS: In isolated rat colonic crypts, mucosal addition of naringenin (100 microM) elicited a concentration-dependent and sustained increase in the short-circuit current (I(SC)), which could be inhibited in Cl- free solution or by bumetanide and DPC (diphenylamine-2-carboxylic acid), but not by DIDS (4, 4'- diisothiocyanatostilbene-2, 2'-disulfonic acid). Naringenin could increase intracellular cAMP content and PKA activity, consisted with that MDL-12330A (N-(Cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride) pretreatment reduced the naringenin-induced I(SC). In addition, significant inhibition of the naringenin-induced I(SC) by quinidine indicated that basolateral K+ channels were involved in maintaining this cAMP-dependent Cl- secretion. Naringenin-evoked whole cell current which exhibited a linear I-V relationship and time-and voltage- independent characteristics was inhibited by DPC, indicating that the cAMP activated Cl- conductance most likely CFTR (cystic fibrosis transmembrane conductance regulator) was involved. In rat constipation model, administration of naringenin restored the level of fecal output, water content and mucus secretion compared to loperamide-administrated group. CONCLUSIONS: Taken together, our data suggest that naringenin could stimulate Cl- secretion in colonic epithelium via a signaling pathway involving cAMP and PKA, hence provide an osmotic force for subsequent colonic fluid secretion by which the laxative effect observed in the rat constipation model. Naringenin appears to be a novel alternative treatment strategy for constipation

Assessment of clusters of transcription factor binding sites in relationship to human promoter, CpG islands and gene expression

BACKGROUND: Gene expression is regulated mainly by transcription factors (TFs) that interact with regulatory cis-elements on DNA sequences. To identify functional regulatory elements, computer searching can predict TF binding sites (TFBS) using position weight matrices (PWMs) that represent positional base frequencies of collected experimentally determined TFBS. A disadvantage of this approach is the large output of results for genomic DNA. One strategy to identify genuine TFBS is to utilize local concentrations of predicted TFBS. It is unclear whether there is a general tendency for TFBS to cluster at promoter regions, although this is the case for certain TFBS. Also unclear is the identification of TFs that have TFBS concentrated in promoters and to what level this occurs. This study hopes to answer some of these questions. RESULTS: We developed the cluster score measure to evaluate the correlation between predicted TFBS clusters and promoter sequences for each PWM. Non-promoter sequences were used as a control. Using the cluster score, we identified a PWM group called PWM-PCP, in which TFBS clusters positively correlate with promoters, and another PWM group called PWM-NCP, in which TFBS clusters negatively correlate with promoters. The PWM-PCP group comprises 47% of the 199 vertebrate PWMs, while the PWM-NCP group occupied 11 percent. After reducing the effect of CpG islands (CGI) against the clusters using partial correlation coefficients among three properties (promoter, CGI and predicted TFBS cluster), we identified two PWM groups including those strongly correlated with CGI and those not correlated with CGI. CONCLUSION: Not all PWMs predict TFBS correlated with human promoter sequences. Two main PWM groups were identified: (1) those that show TFBS clustered in promoters associated with CGI, and (2) those that show TFBS clustered in promoters independent of CGI. Assessment of PWM matches will allow more positive interpretation of TFBS in regulatory regions

A population study on the association between leisure time physical activity and self-rated health among diabetics in Taiwan

<p>Abstract</p> <p>Background</p> <p>There is strong evidence for the beneficial effects of physical activity in diabetes. There has been little research demonstrating a dose-response relationship between physical activity and self-rated health in diabetics. The aim of this study was to explore the dose-response association between leisure time physical activity and self-rated health among diabetics in Taiwan.</p> <p>Methods</p> <p>Data came from the 2001 Taiwan National Health Interview Survey (NHIS). Inclusion criteria were a physician confirmed diagnosis of diabetes mellitus and age 18 years and above (n = 797). Self-rated health was assessed by the question "In general, would you say that your health is excellent, very good, good, fair, or poor?" Individuals with a self perceived health status of good, very good, or excellent were considered to have positive health status.</p> <p>Results</p> <p>In the full model, the odds ratio (OR) for positive health was 2.51(95% CI = 1.53-4.13), 1.62(95% CI = 0.93-2.84), and 1.35(95% CI = 0.77-2.37), for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. Those with duration over 10 years (OR = 0.53, 95%CI = 0.30-0.94), heart disease (OR = 0.50, 95%CI = 0.30-0.85), and dyslipidemia (OR = 0.65, 95% CI = 0.43-0.98) were less likely to have positive health than their counterparts. After stratified participants by duration, those with a duration of diabetes < 6 years, the adjusted OR for positive health was 1.95(95% CI = 1.02-3.72), 1.22(95% CI = 0.59-2.52), and 1.19(95% CI = 0.58-2.41) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. In participants with a duration of diabetes ≥ 6 years, total energy expenditure showed a gradient effect on self-perceived positive health. The adjusted OR for positive health was 3.45(95% CI = 1.53-7.79), 2.77(95% CI = 1.11-6.92), and 1.90(95% CI = 0.73-4.94) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals.</p> <p>Conclusions</p> <p>Our results highlight that regular leisure activity with an energy expenditure ≧ 500 kcal per week is associated with better self-rated health for those with longstanding diabetes.</p

Role of Duplicate Genes in Robustness against Deleterious Human Mutations

It is now widely recognized that robustness is an inherent property of biological systems [1],[2],[3]. The contribution of close sequence homologs to genetic robustness against null mutations has been previously demonstrated in simple organisms [4],[5]. In this paper we investigate in detail the contribution of gene duplicates to back-up against deleterious human mutations. Our analysis demonstrates that the functional compensation by close homologs may play an important role in human genetic disease. Genes with a 90% sequence identity homolog are about 3 times less likely to harbor known disease mutations compared to genes with remote homologs. Moreover, close duplicates affect the phenotypic consequences of deleterious mutations by making a decrease in life expectancy significantly less likely. We also demonstrate that similarity of expression profiles across tissues significantly increases the likelihood of functional compensation by homologs

Predicted Disappearance of Cephalantheropsis obcordata in Luofu Mountain Due to Changes in Rainfall Patterns

<div><h3>Background</h3><p>In the past century, the global average temperature has increased by approximately 0.74°C and extreme weather events have become prevalent. Recent studies have shown that species have shifted from high-elevation areas to low ones because the rise in temperature has increased rainfall. These outcomes challenge the existing hypothesis about the responses of species to climate change.</p> <h3>Methodology/Principal Findings</h3><p>With the use of data on the biological characteristics and reproductive behavior of <em>Cephalantheropsis obcordata</em> in Luofu Mountain, Guangdong, China, trends in the population size of the species were predicted based on several factors. The response of <em>C. obcordata</em> to climate change was verified by integrating it with analytical findings on meteorological data and an artificially simulated environment of water change. The results showed that <em>C. obcordata</em> can grow only in waterlogged streams. The species can produce fruit with many seeds by insect pollination; however, very few seeds can burgeon to become seedlings, with most of those seedlings not maturing into the sexually reproductive phase, and grass plants will die after reproduction. The current population's age pyramid is kettle-shaped; it has a Deevey type I survival curve; and its net reproductive rate, intrinsic rate of increase, as well as finite rate of increase are all very low. The population used in the artificial simulation perished due to seasonal drought.</p> <h3>Conclusions</h3><p>The change in rainfall patterns caused by climate warming has altered the water environment of <em>C. obcordata</em> in Luofu Mountain, thereby restricting seed burgeoning as well as seedling growth and shortening the life span of the plant. The growth rate of the <em>C. obcordata</em> population is in descending order, and models of population trend predict that the population in Luofu Mountain will disappear in 23 years.</p> </div

Drosophila S2 Cells Are Non-Permissive for Vaccinia Virus DNA Replication Following Entry via Low pH-Dependent Endocytosis and Early Transcription

Vaccinia virus (VACV), a member of the chordopox subfamily of the Poxviridae, abortively infects insect cells. We have investigated VACV infection of Drosophila S2 cells, which are useful for protein expression and genome-wide RNAi screening. Biochemical and electron microscopic analyses indicated that VACV entry into Drosophila S2 cells depended on the VACV multiprotein entry-fusion complex but appeared to occur exclusively by a low pH-dependent endocytic mechanism, in contrast to both neutral and low pH entry pathways used in mammalian cells. Deep RNA sequencing revealed that the entire VACV early transcriptome, comprising 118 open reading frames, was robustly expressed but neither intermediate nor late mRNAs were made. Nor was viral late protein synthesis or inhibition of host protein synthesis detected by pulse-labeling with radioactive amino acids. Some reduction in viral early proteins was noted by Western blotting. Nevertheless, synthesis of the multitude of early proteins needed for intermediate gene expression was demonstrated by transfection of a plasmid containing a reporter gene regulated by an intermediate promoter. In addition, expression of a reporter gene with a late promoter was achieved by cotransfection of intermediate genes encoding the late transcription factors. The requirement for transfection of DNA templates for intermediate and late gene expression indicated a defect in viral genome replication in VACV-infected S2 cells, which was confirmed by direct analysis. Furthermore, VACV-infected S2 cells did not support the replication of a transfected plasmid, which occurs in mammalian cells and is dependent on all known viral replication proteins, indicating a primary restriction of DNA synthesis

Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis

BACKGROUND: Carcinogenesis typically involves multiple somatic mutations in caretaker (DNA repair) and gatekeeper (tumor suppressors and oncogenes) genes. Analysis of mutation spectra of the tumor suppressor that is most commonly mutated in human cancers, p53, unexpectedly suggested that somatic evolution of the p53 gene during tumorigenesis is dominated by positive selection for gain of function. This conclusion is supported by accumulating experimental evidence of evolution of new functions of p53 in tumors. These findings prompted a genome-wide analysis of possible positive selection during tumor evolution. METHODS: A comprehensive analysis of probable somatic mutations in the sequences of Expressed Sequence Tags (ESTs) from malignant tumors and normal tissues was performed in order to access the prevalence of positive selection in cancer evolution. For each EST, the numbers of synonymous and non-synonymous substitutions were calculated. In order to identify genes with a signature of positive selection in cancers, these numbers were compared to: i) expected numbers and ii) the numbers for the respective genes in the ESTs from normal tissues. RESULTS: We identified 112 genes with a signature of positive selection in cancers, i.e., a significantly elevated ratio of non-synonymous to synonymous substitutions, in tumors as compared to 37 such genes in an approximately equal-sized EST collection from normal tissues. A substantial fraction of the tumor-specific positive-selection candidates have experimentally demonstrated or strongly predicted links to cancer. CONCLUSION: The results of EST analysis should be interpreted with extreme caution given the noise introduced by sequencing errors and undetected polymorphisms. Furthermore, an inherent limitation of EST analysis is that multiple mutations amenable to statistical analysis can be detected only in relatively highly expressed genes. Nevertheless, the present results suggest that positive selection might affect a substantial number of genes during tumorigenic somatic evolution