82 research outputs found
Investigation of Theileria camelensis in camels infested by Hyalomma dromedarii ticks in Upper Egypt
In the present study, a total of 224 camels infested with Hyalomma dromedarii ticks were investigated for the presence of Theileria camelensis infection in Upper Egypt. The role of Hyalomma dromedarii ticks as the vector of this parasite was also investigated by haemolymph smear examination. Results revealed that 15 (6.75%) of 224 camels were harboring Theileria camelensis in erythrocytes. Furthermore, the theilerial schizont was also seen in lymphocytes. These 15 camels did not show any abnormal clinical signs except three cases that showed enlargement of superficial lymph node and fever. Examination of ticks showed various developmental stages of different shapes and forms of Theileria species
Comparative analysis of sequence characteristics of imprinted genes in human, mouse, and cattle
Genomic imprinting is an epigenetic mechanism that results in monoallelic expression of genes depending on parent-of-origin of the allele. Although the conservation of genomic imprinting among mammalian species has been widely reported for many genes, there is accumulating evidence that some genes escape this conservation. Most known imprinted genes have been identified in the mouse and human, with few imprinted genes reported in cattle. Comparative analysis of genomic imprinting across mammalian species would provide a powerful tool for elucidating the mechanisms regulating the unique expression of imprinted genes. In this study we analyzed the imprinting of 22 genes in human, mouse, and cattle and found that in only 11 was imprinting conserved across the three species. In addition, we analyzed the occurrence of the sequence elements CpG islands, C + G content, tandem repeats, and retrotransposable elements in imprinted and in nonimprinted (control) cattle genes. We found that imprinted genes have a higher G + C content and more CpG islands and tandem repeats. Short interspersed nuclear elements (SINEs) were notably fewer in number in imprinted cattle genes compared to control genes, which is in agreement with previous reports for human and mouse imprinted regions. Long interspersed nuclear elements (LINEs) and long terminal repeats (LTRs) were found to be significantly underrepresented in imprinted genes compared to control genes, contrary to reports on human and mouse. Of considerable significance was the finding of highly conserved tandem repeats in nine of the genes imprinted in all three species
Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla
Background: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a
poor five year survival rate; improved methods of patient stratification are required.
Methods: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using
immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas
and the second cohort was composed of 120 cancers of the bile duct and ampulla.
Results: In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin
expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage
(P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was
significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate
Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the
bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall
survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95%
confidence interval = 0.365-0.968; P = 0.037).
Conclusion: The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers,
influencing disease progression. The findings of this study warrant a larger follow-up study.
Keywords: Calpain, Calpastatin, Pancreas, Ampulla, Bile duct, Cance
The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays
Background
Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma.
Methods
After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high’ and 'low’ for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features.
Results
CD3 and CD8 positive lymphocytes were associated with grade of tumour differentiation. The presence of intratumoural CD3 positive cells was associated with improved survival (p = 0.028), and intratumoural and stromal CD3 in combination also correlated with improved survival (p = 0.043). When CD20 positive lymphocyte levels were high, survival improved (p = 0.029) and similar results were seen for CD20 in combination with intratumoural CD3 (p = 0.001) and stromal CD8 (p = 0.013).
Conclusions
This study has shown a correlation between the presence of TALs and survival in pancreatic ductal adenocarcinoma
Cost-effectiveness of six strategies for Helicobacter pylori diagnosis and management in uninvestigated dyspepsia assuming a high resource intensity practice pattern
<p>Abstract</p> <p>Background</p> <p>Initial assessment of dyspepsia often includes noninvasive testing for <it>Helicobacter pylori </it>infection. Commercially available tests vary widely in cost and accuracy. Although there is extensive literature on the cost-effectiveness of <it>H. pylori </it>treatment, there is little information comparing the cost-effectiveness of various currently used, noninvasive testing strategies.</p> <p>Methods</p> <p>A Markov simulation was used to calculate cost per symptom-free year and cost per correct diagnosis. Uncertainty in outcomes was estimated using probabilistic sensitivity analysis.</p> <p>Results</p> <p>Under the baseline assumptions, cost per symptom-free year was 123 (stool antigen) to $129 (IgG/IgA combined serology). Confidence intervals had significant overlap.</p> <p>Conclusions</p> <p>Under our assumptions for how testing for <it>H. pylori </it>infection is employed in United States medical practice, the available noninvasive tests all have similar cost-effectiveness between one another as well as with empiric PPI trial.</p
Weekly Intra-Amniotic IGF-1 Treatment Increases Growth of Growth-Restricted Ovine Fetuses and Up-Regulates Placental Amino Acid Transporters
Frequent treatment of the growth-restricted (IUGR) ovine fetus with intra-amniotic IGF-1 increases fetal growth. We aimed to determine whether increased growth was maintained with an extended dosing interval and to examine possible mechanisms. Pregnant ewes were allocated to three groups: Control, and two IUGR groups (induced by placental embolization) treated with weekly intra-amniotic injections of either saline (IUGR) or 360 µg IGF-1 (IGF1). IUGR fetuses were hypoxic, hyperuremic, hypoglycemic, and grew more slowly than controls. Placental glucose uptake and SLC2A1 (GLUT2) mRNA levels decreased in IUGR fetuses, but SLC2A3 (GLUT3) and SLC2A4 (GLUT4) levels were unaffected. IGF-1 treatment increased fetal growth rate, did not alter uterine blood flow or placental glucose uptake, and increased placental SLC2A1 and SLC2A4 (but not SLC2A3) mRNA levels compared with saline-treated IUGR animals. Following IGF-1 treatment, placental mRNA levels of isoforms of the system A, y+, and L amino acid transporters increased 1.3 to 5.0 fold, while the ratio of phosphorylated-mTOR to total mTOR also tended to increase. Weekly intra-amniotic IGF-1 treatment provides a promising avenue for intra-uterine treatment of IUGR babies, and may act via increased fetal substrate supply, up-regulating placental transporters for neutral, cationic, and branched-chain amino acids, possibly via increased activation of the mTOR pathway
Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI
© 2016 St. Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI 0.985-0.994) respectively. Small biases (=3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using Hepa-Fat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF
Patterns of Hybrid Loss of Imprinting Reveal Tissue- and Cluster-Specific Regulation
Background: Crosses between natural populations of two species of deer mice, Peromyscus maniculatus (BW), and P. polionotus (PO), produce parent-of-origin effects on growth and development. BW females mated to PO males (bw6po) produce growth-retarded but otherwise healthy offspring. In contrast, PO females mated to BW males (PO6BW) produce overgrown and severely defective offspring. The hybrid phenotypes are pronounced in the placenta and include PO6BW conceptuses which lack embryonic structures. Evidence to date links variation in control of genomic imprinting with the hybrid defects, particularly in the PO6BW offspring. Establishment of genomic imprinting is typically mediated by gametic DNA methylation at sites known as gDMRs. However, imprinted gene clusters vary in their regulation by gDMR sequences. Methodology/Principal Findings: Here we further assess imprinted gene expression and DNA methylation at different cluster types in order to discern patterns. These data reveal PO6BW misexpression at the Kcnq1ot1 and Peg3 clusters, both of which lose ICR methylation in placental tissues. In contrast, some embryonic transcripts (Peg10, Kcnq1ot1) reactivated the silenced allele with little or no loss of DNA methylation. Hybrid brains also display different patterns of imprinting perturbations. Several cluster pairs thought to use analogous regulatory mechanisms are differentially affected in the hybrids. Conclusions/Significance: These data reinforce the hypothesis that placental and somatic gene regulation differs significantly, as does that between imprinted gene clusters and between species. That such epigenetic regulatory variatio
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