Quantitative Myocardial Perfusion Imaging Versus Visual Analysis in Diagnosing Myocardial Ischemia: A CE-MARC Substudy

Objectives

This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography.

Association between OPCRIT dimensions and polymorphisms of HPA axis genes in bipolar disorder

The aim of the study was to investigate the possible association between polymorphisms of HPA axis genes-CRHR₁ (corticotrophin-releasing hormone receptor), NR3C1 (glucocorticoid receptor) and AVPR1B (arginine vasopressin receptor) and dimensions of bipolar disorder assessed by OPCRIT.     

Imbalance in serum soluble CD30/CD30L and CD40/CD40L systems are associated with ovarian tumors

The aim of the study was to examine the concentrations of the soluble receptors and their ligands of CD30/CD30L and CD40/CD40L systems in the serum of women with ovarian tumor and in the ovarian cyst fluid of women with Cystadenoma serosum. The study included 120 women with ovarian tumors. As a control, sera were obtained from 60 healthy female volunteers. Concentrations of the sCD30, sCD30L, sCD40 and sCD40L in the serum and the ovarian cyst fluid were measured by ELISA enzyme-linked immunosorbent assay. Concentrations of both sCD30 and sCD30L in serum of women with ovarian tumors were significantly higher than in control (p < 0.0001). The highest serum receptor and its ligand levels were observed in women with ovarian cancer (p < 0.0001). Moreover, results showed significantly increased levels of sCD40 and sCD40L serum in women with ovarian tumors, as compared to the control group (p < 0.0001). The highest concentration of sCD40 in the serum of women with ovarian cancer and sCD40L in serum of women with Teratoma maturum (p < 0.0001) were observed. Impaired apoptosis among women with ovarian tumors is associated with the impairments of soluble CD30/CD30L and CD40/CD40L systems. Measurement of studied parameter concentrations in serum of women with ovarian tumors has been suggested to be a potential tool in monitoring of inflammatory. Evaluation of sCD30, sCD30L and sCD40 might be an early diagnostic marker in patients with the ovarian cancer. Concentrations of the studied parameters in the ovarian cyst fluid higher than the serum values suggest local suppression of the immune response. However, the final evaluation of the importance of measurement of serum levels of them requires further investigation.     

Role of molecular mimicry and polyclonal cell activation in the induction of pathogenic β2-glycoprotein I–directed immune response in Balb/c mice upon hyperimmunization with tetanus toxoid

It is known that tetanus toxoid (TTd)-hyperimmunization induces increased titer of sera β2-glycoprotein I (β2GPI)-specific antibodies (Abs) in Balb/c mice. The concentrations of such induced anti-β2GPI Abs as well as their pathogenic potential are strongly influenced by the context of TTd application. β2GPI-specific immune response is established as a part of TTd-specific immune response by molecular mimicry mechanism due to structural homology between TTd and β2GPI. This finding is supported by the following facts: (1) cross-reactive Abs that recognize both TTd and β2GPI epitopes are present in Balb/c mice sera; (2) anti-TTd Abs secretion in splenic cultures is induced after β2GPI stimulation and vice versa. However, analyses of (1) IL-10 production following in vitro stimulation of immunized Balb/c mice splenocytes by TTd, β2GPI or glutaraldehyde-treated β2GPI and (2) specific impact of ConA and agonists of TLR2, TLR4, and TLR9 on anti-TTd and autoreactive Abs secretion strongly imply that these two branches of the TTd-induced immune response do not use identical cell populations and are regulated in a different way. Results presented in this paper describe that structural homology between foreign and self-antigens could focus mounted autoreactive immune response toward specific self-structure, but the context of antigen application, including a history of previous immune stimulations and adjuvants applied together with the antigen, are the main factors which determine the outcome of the induced immune response.     

The Influence of Recombinant Human Erythropoietin on Apoptosis and Cytokine Production of CD4+ lymphocytes from Hemodialyzed Patients

Recombinant human erythropoietin (rhEPO) treatment of hemodialyzed (HD) patients normalizes the altered phenotype of CD4⁺ lymphocytes and restores the balance of Th1/Th2 cytokines. We decided to test how the presence of rhEPO in cell culture modulates cytokine production of CD4⁺ lymphocytes in HD patients with stable hemoglobin level and expression of activation antigens of stimulated CD4⁺ lymphocytes similar to those observed in healthy individuals. We also tested whether the presence of rhEPO in cell culture protects stimulated CD4⁺ lymphocytes of HD patients from apoptosis. Peripheral blood mononuclear cells (PBMC) of HD patients were stimulated with an immobilized anti-CD3 antibody with or without addition of rhEPO. The percentage of apoptotic CD4⁺ lymphocytes and the level of Th1/Th2 cytokines in culture supernatants were measured with flow cytometry. HD patients showed a decrease in the percentage of apoptotic CD4⁺ cells after stimulation with the anti-CD3 antibody combined with rhEPO. The level of IFN-γ and IL-10 was increased while the level of TNF-α was decreased in the presence of rhEPO in cell culture from HD patients. These results confirm the role of rhEPO signaling in T lymphocytes of HD patients.     

Infantile peripheral neuropathy,deafness, and proximal tubulopathy associated with a novel mutation of the RRM2B gene

Mitochondrial DNA depletion syndromes are a group of autosomal recessive hereditary disorders characterized by reduction of the amount of mitochondrial DNA in the affected tissue (muscle, liver, brain, or kidneys). We report a case of an infant with myopathy, deafness, peripheral neuropathy, nephrocalcinosis, proximal renal tubulopathy, moderate lactic acidosis, and a novel mutation of the RRM2B gene.Mitochondrial DNA depletion syndromes are a group of autosomal recessive hereditary disorders characterized by reduction of the mitochondrial DNA amount in the affected tissue (1). Depletion of mitochondrial DNA can affect specific tissues or combination of organs and tissues including muscles, liver, brain, or kidneys (2,3).Different defects of nuclear genes may lead to different clinical manifestations, such as hepatocerebral syndrome, encephalopathy, or myopathy. One of the recently identified genes for mitochondrial DNA depletion syndromes is RRM2B, which encodes an isoform of a small subunit of ribonucleotide reductase. This enzyme plays an essential role in nucleotide synthesis, converting ribonucleotides to deoxyribonucleotides. Since 2008, 14 mutations of RRM2B gene have been reported (3,4). All the reported mutations are unique and there is no mutation that appears in more than one family (1-4).All reported patients had myopathy and primary lactic acidosis. More than a half of them died before the fourth month of age. The oldest patient with RRM2B mutation was a 42 years old woman with clinical findings suggestive of neurogastrointestinal encephalopathy (5). In this report, we review a case of an infant with muscular hypotonia, myopathy, peripheral neuropathy, deafness, nephrocalcinosis, proximal renal tubulopathy, moderate lactic acidosis, and a novel mutation of the RRM2B gene.     

Association Between IL-6 Concentration and Diabetes-Related Variables in DM1 Patients with and without Microvascular Complications

Interleukin 6 (IL-6) plays an important role in the initiation and acceleration of chronic inflammation and could contribute to development of microvascular complications in patients with type 1 diabetes (DM1). Therefore, this study was aimed to investigate the association between concentration of IL-6 in relation to glucose control, lipid profile, and body mass index (BMI) in 69 DM1 patients subdivided according to the absence or presence of microvascular complications. BMI, level of fasting plasma glucose (FPG), and concentrations of total cholesterol (TCH), LDL cholesterol (LDL-C), and IL-6 were higher in DM1 patients compared to the control group. In DM1 patients, IL-6 concentration was positively correlated with level of FPG, LDL-C, TCH concentrations, and BMI. These correlations were stronger in the subgroup of patients with microvascular complications. In addition, BMI independently influences IL-6 concentration in DM1 patients. In conclusion, elevated IL-6 concentration is associated with diabetes-related variables which could accelerate progression of microvascular complications in DM1 patients.     

TNF-α and IL-1β sensitize human MSC for IFN-γ signaling and enhance neutrophil recruitment

During inflammatory processes, tissue environmental cues are influencing the immunoregulatory properties of tissue-resident mesenchymal stem/stromal cells (MSC). In this study, we elucidated one of the molecular and cellular responses of human MSC exposed to combinations of inflammatory cytokines. We showed that during multi-cytokine priming by TNF-α, IL-1β, and IFN-γ, IL-1β further augmented the well-established immunoregulatory activity induced by TNF-α/IFN-γ. On the molecular level, TNF-α and IL-1β enhanced the expression of IFN-γ receptor (IFN-γR) via NF 'kappa-light-chain-enhancer' of activated B-cells (NF-κΒ) signaling. In turn, enhanced responsiveness to IFN-γ stimulation activated STAT5 and p38-MAPK signaling. This molecular feedback resulted in an increased IL-8 release and augmented recruitment of polymorphonuclear granulocytes (PMN). Our study suggests the possibility that responses of MSC to multi-cytokine priming regimens may be exploited therapeutically to fine-tune inflammatory activity in tissues. This study elucidates molecular mechanisms underlying the immunological priming of mesenchymal stromal cells (MSC) and their interaction with neutrophils.     

Contribution of bacterial cells as nucleation centers in microbiologically induced CaCO3 precipitation—A mathematical modeling approach

The microbiologically induced calcite precipitation (MICP) has been extensively studied for geotechnical engineering through simultaneous action of natural phenomena and engineering processes. The focus of bacterial contribution to the MICP has been directed to calcium carbonate productivity, while the additional bacterial role as a crystal nucleation center was not explained especially from a mathematical prediction modeling point of view. Therefore, this study provides explanations and a mathematical modeling approach of bacterial influence on the MICP induced by newly-isolated ureolytic Bacillus strains and Sporosarcina pasteurii DSM 33. Using the obtained results of low-cost, rapid, and simple assays, artificial neural network modeling was applied for cell surface predispositions, pH changes as well as calcium-involved function in biofilm formation during the MICP, for the first time. Based on the obtained contribution of the alkalophilic/alkaloresistant bacteria, calcite precipitation can be significantly directed by the presence, of ureolytic bacterial cells as nucleation centers during CaCO₃ precipitation as well as their morphology, surface characteristics, potential to form a biofilm, and/or generate pH changes.