Correlation between peripheral blood cell transcriptomic profile and clinical parameters of chronic mitral valve disease in Dachshunds.

Studies identifying specific pathologically expressed genes have been performed on diseased myocardial tissue samples, however less invasive studies on gene expression of peripheral blood mononucleated cells give promising results. This study assessed transcriptomic data that may be used to evaluate Dachshunds with chronic mitral valve disease. Dachshunds with different stages of heart disease were compared to a control, healthy group. Microarray data analysis revealed clusters of patients with similar expression profiles. The clusters were compared to the clinical classification scheme. Unsupervised classification of the studied groups showed three clusters. Clinical and laboratory parameters of patients from the cluster 1 were in accordance with those found in patients without heart disease. Data obtained from patients from the cluster 3 were typical of advanced heart failure patients. Comparison of the cluster 1 and 3 groups revealed 1133 differentially expressed probes, 7 significantly regulated process pathways and 2 significantly regulated Ariadne Metabolic Pathways. This study may serve as a guideline for directing future research on gene expression in chronic mitral valve disease.

Alternations in genes expression of pathway signaling in esophageal tissue with atresia: results of expression microarray profiling.

Esophageal atresia (EA) is a congenital defect of the esophagus involving the interruption of the esophagus with or without connection to the trachea (tracheoesophageal fistula [TEF]). EA/TEF may occur as an isolated anomaly, may be part of a complex of congenital defects (syndromic), or may develop within the context of a known syndrome or association. The molecular mechanisms underlying the development of EA are poorly understood. It is supposed that a combination of multigenic factors and epigenetic modification of genes play a role in its etiology. The aim of our work was to assess the human gene expression microarray study in esophageal tissue samples. Total RNA was extracted from 26 lower pouches of esophageal tissue collected during thoracoscopic EA repair in neonates with the isolated (IEA) and the syndromic form (SEA). We identified 787 downregulated and 841 upregulated transcripts between SEA and controls, and about 817 downregulated and 765 upregulated probes between IEA and controls. Fifty percent of these genes showed differential expression specific for either IEA or SEA. Functional pathway analysis revealed substantial enrichment for Wnt and Sonic hedgehog, as well as cytokine and chemokine signaling pathways. Moreover, we performed reverse transcription polymerase chain reaction study in a group of SHH and Wnt pathways genes with differential expression in microarray profiling to confirm the microarray expression results. We verified the altered expression in SFRP2 gene from the Wnt pathway as well as SHH, GLI1, GLI2, and GLI3 from the Sonic hedgehog pathway. The results suggest an important role of these pathways and genes for EA/TEF etiology.

Lactate accumulation in response to supramaximal exercise in rowers.

The aim of this study was to test (a) three methods to estimate the quantity of lactate accumulated (QLaA ) in response to supramaximal exercise and (b) correlations between QLaA and the nonoxidative energy supply assessed by the accumulated oxygen deficit (AOD). Nine rowers performed a 3-min all-out test on a rowing ergometer to estimate AOD and lactate accumulation in response to exercise. Peak blood lactate concentration [(La)peak ] during recovery was assessed, allowing QLaA(m1) to be estimated by the method of Margaria et al. Application of a bicompartmental model of lactate distribution space to the blood lactate recovery curves allowed estimation of (a) the net amount of lactate released during recovery from the active muscles (NALR max ), and (b) QLaA according to two methods (QLaA(m2) and QLaA(m3)). (La)peak did not correlate with AOD. QLaA(m1), QLaA(m2) and QLaA(m3) correlated with AOD (r = 0.70, r = 0.85 and r = 0.92, respectively). These results confirm that (La)peak does not provide reliable information on nonoxidative energy supply during supramaximal exercise. The correlations between AOD and QLaA(m2) and QLaA(m3) support the concept of studying blood lactate recovery curves to estimate lactate accumulation and thus the contribution of nonoxidative pathway to energy supply during supramaximal exercise.

Mismatch between transcriptomic and histopathologic picture of canine lymphomas.

Lymphoma is one of the most common malignant tumours occurring in dogs. Since there is a constant need for new, more comprehensive laboratory diagnostic tools which permit the precise determination of many tumour-related factors we decided to verify whether the use of microarray analysis could be helpful in classifying lymphomas. The study was performed on samples collected from 7 dogs in which multicentric lymphoma was recognized. Among this group we were able to identify one sub-cluster of transcriptionally similar tumours, which completely differed in terms of the histopathological examination. Among them there were one diffuse large B cell lymphoma, one diffuse macronucleolated medium-sized cell lymphoma and one pleomorphic mixed small and large T-cell lymphoma. The lymphomas belonging to the sub-cluster differed from other analysed tumours in the expression of more than 100 genes of which only 18 were described earlier in regard to lymphomas.

Gene expression profiling in peripheral blood nuclear cells in patients with refractory ischaemic end-stage heart failure.

Functional analysis of up- and down-regulated genes might reveal whether peripheral blood cells may be considered as a material of diagnostic or prognostic value in patients with end-stage heart failure (HF). The aim of the present study was to compare the transcriptomic profile of peripheral blood nuclear cells from 6 male patients with ischaemic end-stage HF with those of 6 male patients with asymptomatic cardiac dysfunction. The expression of genes in peripheral blood nuclear cells in both groups of patients was measured using whole-genome oligonucleotide microarrays utilizing 35 035 oligonucleotide probes. Microarray analyses revealed 130 down-regulated genes and 15 up-regulated genes in the patients with end-stage HF. Some of the down-regulated genes belonged to the pathways that other studies have shown to be down-regulated in cardiomyopathy. We also identified up-regulated genes that have been correlated with HF severity (CXCL16) and genes involved in the regulation of expression of platelet activation factor receptor (PTAFR, RBPSUH, MCC, and PSMA7). In conclusion, the identification of genes that are differentially expressed in peripheral blood nuclear cells of patients with HF supports the suggestion that this diagnostic approach may be useful in searching for the molecular predisposition for development of severe refractory HF in patients with post-infarction asymptomatic abnormalities and remodelling of the left ventricle. These results need further investigation and validation.

Transcriptional dysregulation of skeletal muscle protein metabolism in streptozotocin-diabetic mice.

The purpose of the study was to evaluate potential changes in expression of genes involved in protein metabolism and myogenic differentiation markers in skeletal muscle of streptozotocin-diabetic mice. Microarray analysis revealed alterations in the expression of 84 gene transcripts in gastrocnemius muscle of diabetic mice. Regarding protein metabolism a marked downregulation in gene transcripts for: general transcription factor IIA1 (-1.88, P=0.016309), TATA box binding protein (-2.17, P=0.037373), eukaryotic translation initiation factor 4E nuclear import factor 1 (-1.61, P=0.037373), eukaryotic translation elongation factor Ibeta2 (-1.95, P=0.010406), ubiquitin-like 5 (-1.67, P=0.024975) and ubiquitin conjugating enzyme 7 interacting protein 1 (-1.68, P=0.016309) was observed. STZ-diabetes caused a drop in the expression of myogenin, whereas myostatin level was significantly elevated. In conclusion, 1) STZ-diabetes attenuates expression of gene transcripts involved in the process of transcription and translation, which may affect skeletal muscle protein synthesis and lead to nitrogen imbalance, 2) impaired expression of gene transcripts involved in the regulation and activity of the ubiquitin-proteasome pathway may contribute to attenuation of mechanisms eliminating damaged proteins in STZ-diabetes, 3) changes in the expression of key myogenic factors, manifested by a decrease in myogenin level and enhancement of myostatin expression may be one of the mechanisms limiting skeletal muscle growth and regeneration associated with diabetes.

Blood lactate and heat stress during training in rowers.

The purpose of the present study was to test the hypothesis that large increases in blood lactate concentration ([La] (b)) and/or body temperature may occur during an endurance training on a rowing ergometer and disrupt training. The influence of an increase in air convection on the capacity to perform a prolonged exercise was also explored. Ten trained oarsmen were asked to undergo twice, in control (C) and increased air ventilation (AV) conditions, two 30-min trainings on a rowing ergometer at a work rate corresponding to 2.5 mmol . L (-1) of [La] (b) determined during a previous incremental exercise (P (2.5)). Four subjects did not complete the training session in C despite a steady state in [La] (b) in two of them. In these four subjects, the end of the exercise was associated with the highest measured rectal temperatures (T (re), 39.4 +/- 0.1 degrees C) and rate of perceived exertion (RPE, 17.8 +/- 0.3). Regarding the six other subjects, their heart rate, oxygen uptake, RPE, T (re) and water loss values were lower (p < 0.05) in AV than in C. [La] (b) displayed the same profile in C and AV. This study suggests that i) high body temperature may constitute a significant factor of perceived exertion and disrupt indoor training session, and ii) capacity to perform an endurance training on a rowing ergometer was improved by increasing air convection.