TNF α G308A gene polymorphism has an impact on renal function, microvascular permeability, organ involvement and severity of preeclampsia.

Background/aims: Preeclampsia (PE) is a life-threatening complication of pregnancy that is associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of the mother, the fetus or both. The etiology of PE is still uncertain; however, recently the role of the immune system has gained in importance.

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus.

Introduction: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE.

Methods: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry.

Incidence of skeletal muscle disorders after statins' treatment: consequences in clinical and EMG picture.

Objectives: The goal of this clinical trial was to determine the incidence of undesirable side effects, and to ascertain any occurrence of genetic polymorphisms.

Material And Methods: Clinically, we looked for manifestations of a benign myositis and of serious rhabdomyolysis. We observed a group 198 patients treated with statins, primarially fluvastatin and rosuvastatin.

HuR and other turnover- and translation-regulatory RNA-binding proteins: implications for the kidney.

The posttranscriptional regulation of gene expression occurs through cis RNA regulatory elements by the action of trans factors, which are represented by noncoding RNAs (especially microRNAs) and turnover- and translation-regulatory (TTR) RNA-binding proteins (RBPs). These multifactorial proteins are a group of heterogeneous RBPs primarily implicated in controlling the decay and translation rates of target mRNAs. TTR-RBPs usually shuttle between cellular compartments (the nucleus and cytoplasm) in response to various stimuli and undergo posttranslational modifications such as phosphorylation or methylation to ensure their proper subcellular localization and function.

[Indicators of inflammation in patients with coronary atherosclerosis - role of usCRP in diagnosis and disease progression prediction].

Atherosclerosis is being nowadays defined as chronic subclinical inflammatory disease. Recently published clinical and laboratory studies have shown that subclinical inflammation represents main role in initiation of creation, in progress and destabilization of atherosclerotic plaque. Screening including traditional cardiovascular risk factors fails in identification in more than 50% of individuals with later development of acute coronary syndrome.

Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.

Introduction: Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question.

Anti-inflammatory treatment in dysfunction of pulmonary surfactant in meconium-induced acute lung injury.

Inflammation, oxidation, lung edema, and other factors participate in surfactant dysfunction in meconium aspiration syndrome (MAS). Therefore, we hypothesized that anti-inflammatory treatment may reverse surfactant dysfunction in the MAS model. Oxygen-ventilated rabbits were given meconium intratracheally (25 mg/ml, 4 ml/kg; Mec) or saline (Sal).

Bias in effect size of systemic lupus erythematosus susceptibility loci across Europe: a case-control study.

Introduction: We aimed to investigate whether the effect size of the systemic lupus erythematosus (SLE) risk alleles varies across European subpopulations.

Methods: European SLE patients (n = 1,742) and ethnically matched healthy controls (n = 2,101) were recruited at 17 centres from 10 different countries. Only individuals with self-reported ancestry from the country of origin were included.

Selective phosphodiesterase 3 inhibitor olprinone attenuates meconium-induced oxidative lung injury.

Since inflammation and oxidation play a key role in the pathophysiology of neonatal meconium aspiration syndrome, various anti-inflammatory drugs have been tested in the treatment. This study evaluated whether the phosphodiesterase (PDE) 3 inhibitor olprinone can alleviate meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated rabbits intratracheally received 4 ml/kg of meconium (25 mg/ml) or saline.

Association of systemic lupus erythematosus clinical features with European population genetic substructure.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers.

[Biochemical aspects of fetal hypoxia].

Objective: To evaluate validity of biochemical diagnostic methods of fetal hypoxia.

Design: A case-control study.

Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.

[Biophysical methods in diagnosis of intrapartal fetal hypoxia].

Objective: To evaluate validity of biophysical diagnostic methods of fetal hypoxia.

Design: A case-control study.

Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.

NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif.

The RNA-binding protein nuclear factor 90 (NF90) has been implicated in the stabilization, transport and translational control of several target mRNAs. However, a systematic analysis of NF90 target mRNAs has not been performed. Here, we use ribonucleoprotein immunoprecipitation analysis to identify a large subset of NF90-associated mRNAs.

Is Gas6 protein associated with sticky platelet syndrome?

The aim of this study was to detect the prevalence of the polymorphisms of growth arrest-specific gene 6 (Gas6; Gas6 c. 834 + 7G > A) in patients with sticky platelet syndrome (SPS). Sticky platelet syndrome is a hereditary, autosomal dominant thrombophilia characterized by platelet hyperaggregation after low concentrations of platelet inducers-adenosine diphosphate (ADP) and epinephrine (EPI).

Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study.

Introduction: We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci.

Methods: We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension.

Combination of budesonide and aminophylline diminished acute lung injury in animal model of meconium aspiration syndrome.

Combination of low-dose budesonide and low-dose aminophylline may improve lung function in reduced adverse effects compared with high-dose monotherapy. Adult rabbits intratracheally received 4 ml/kg of saline or meconium (25 mg/ml). Meconium-injured rabbits were treated at 0.

Comparison of the effects of low-dose vs. high-dose aminophylline on lung function in experimental meconium aspiration syndrome.

Due to missing information on appropriate dosing of aminophylline in meconium aspiration syndrome (MAS), this study compared effects of high-dose and low-dose aminophylline on lung function of animals with MAS. Meconium-instilled rabbits were treated by low-dose (LD, 1.0 mg/kg), or high-dose (HD, 2.

Nuclear HuR accumulation through phosphorylation by Cdk1.

A predominantly nuclear RNA-binding protein, HuR translocates to the cytoplasm in response to stress and proliferative signals, where it stabilizes or modulates the translation of target mRNAs. Here, we present evidence that HuR phosphorylation at S202 by the G2-phase kinase Cdk1 influences its subcellular distribution. HuR was specifically phosphorylated in synchronous G2-phase cultures; its cytoplasmic levels increased by Cdk1-inhibitory interventions and declined in response to Cdk1-activating interventions.

MKP-1 mRNA stabilization and translational control by RNA-binding proteins HuR and NF90.

The mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) plays a major role in dephosphorylating and thereby inactivating the MAP kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Here, we examine the posttranscriptional events underlying the robust MKP-1 induction by oxidants in HeLa cells. H(2)O(2) treatment potently stabilized the MKP-1 mRNA and increased the association of MKP-1 mRNA with the translation machinery.

p16(INK4a) translation suppressed by miR-24.

Background: Expression of the tumor suppressor p16(INK4a) increases during aging and replicative senescence.

Methodology/principal Findings: Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with replicative senescence was associated with decreased levels of miR-24, a microRNA that was predicted to associate with the p16 mRNA coding and 3'-untranslated regions.

Haplotypes of the HRES-1 endogenous retrovirus are associated with development and disease manifestations of systemic lupus erythematosus.

Objective: Endogenous retroviral sequences represent a link between viral and genetic factors that may influence the development of systemic lupus erythematosus (SLE). The HRES-1 human endogenous retroviral sequence is centrally located at the 1q42 chromosomal region relative to microsatellites previously associated with SLE. We therefore undertook the present study to determine the haplotypes of the HRES-1 locus and their linkage to SLE.

RNA-binding proteins HuR and PTB promote the translation of hypoxia-inducible factor 1alpha.

The levels of hypoxia-inducible factor 1alpha (HIF-1alpha) are tightly controlled. Here, we investigated the posttranscriptional regulation of HIF-1alpha expression in human cervical carcinoma HeLa cells responding to the hypoxia mimetic CoCl(2). Undetectable in untreated cells, HIF-1alpha levels increased dramatically in CoCl(2)-treated cells, while HIF-1alpha mRNA levels were unchanged.

Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR.

The RNA-binding protein TIAR (related to TIA-1 [T-cell-restricted intracellular antigen 1]) was shown to associate with subsets of mRNAs bearing U-rich sequences in their 3' untranslated regions. TIAR can function as a translational repressor, particularly in response to cytotoxic agents. Using unstressed colon cancer cells, collections of mRNAs associated with TIAR were isolated by immunoprecipitation (IP) of (TIAR-RNA) ribonucleoprotein (RNP) complexes, identified by microarray analysis, and used to elucidate a common signature motif present among TIAR target transcripts.

Analysis of turnover and translation regulatory RNA-binding protein expression through binding to cognate mRNAs.

RNA-binding proteins (RBPs) that associate with specific mRNA sequences and function as mRNA turnover and translation regulatory (TTR) RBPs are emerging as pivotal posttranscriptional regulators of gene expression. However, little is known about the mechanisms that govern the expression of TTR-RBPs. Here, we employed human cervical carcinoma HeLa cells to test the hypothesis that TTR-RBP expression is influenced posttranscriptionally by TTR-RBPs themselves.

Opposed independent effects and epistasis in the complex association of IRF5 to SLE.

Genetic variation in the interferon regulatory factor 5 (IRF5) gene affects systemic lupus erythematosus (SLE) susceptibility. However, association is complex and incompletely defined. We obtained fourteen European sample collections with a total of 1383 SLE patients and 1614 controls to better define the role of the different IRF5 variants.