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Biomedical subjects

Rafał Pawliczak

Publications and source records attributed to Rafał Pawliczak.

8 recordsLinked to original sources

[Peroxisome proliferator-activated receptors-gamma (PPAR-gamma) and their role in immunoregulation and inflammation control].

Peroxisome proliferator-activated receptors-gamma (PPAR-gamma) are members of the nuclear receptor superfamily containing transcription factors regulating gene expression. PPAR-gamma have attracted attention so far as key factors in adipogenesis, lipid metabolism, insulin sensitivity, and apoptosis. Recently, growing evidence points to their implication in the regulation of the immune response, particularly in inflammation control. Not only are PPAR-gamma found in various structures of the immune system, but many inflammatory mediators, such as arachidonic acid and its metabolites, also act as potent and specific ligands of them. Inflammation is the basis of the pathogeneses of such chronic diseases as bronchial asthma, atherosclerosis, rheumatoid arthritis, and chronic inflammatory bowel diseases. The causative relationship between PPAR-gamma activity and the pathogeneses of these inflammatory disorders has been found in specific animal models. Moreover, PPAR-gamma agonists have been shown to act as potent anti-inflammatory agents. Thus, PPAR-gamma can serve as potential therapeutic targets in the treatment of inflammation. The aim of this paper is to present the characteristics of PPAR-gamma regarding their gene and protein structures, ligand selectivity, mechanisms of action, and target genes. The review highlights the roles that PPAR-gamma play in inflammation and immune responses. Particular emphasis is focused on their roles in asthma, atheroclerosis, rheumatoid arthritis and chronic inflammatory bowel diseases.

Animals↗

[RGS proteins (regulators of G protein signaling) and their roles in regulation of immune response].

RGS proteins (Regulators of G-protein Signaling) comprise a protein family responsible for regulating G proteins. By enhancing the GTPase activity of the a subunit, they speed up the reconstruction of the heterotrimeric structure of G protein, thus inhibiting its signal transduction. Sst2 protein in yeast Saccharomyces cervisiae, FlbA in fungus Aspergillus nidulans, and Egl-10 in the nematode Caenorhabditis elegans are the first native G regulators with GTPase activity (GAPs:--GTPase-activating proteins). The existence of over 30 RGS human proteins has been confirmed thus far, and they have been grouped and classified into six subfamilies. In immunocompetent cells, RGS proteins are entangled in a complicate net of different interrelating signal pathways. They are connected with B- and T-cell chemokine susceptibility, efficient T cell proliferation, and the regulation of B cell maturation. They also take an essential part in inflammation. High hopes are held for drugs, which handle would be RGS proteins and which would further provide the possibility of modifying the pharmacokinetics of drugs acting through G protein- coupled receptors. The aim of this review is to discuss the new RGS protein family and explain the potential involvement of RGS proteins in the modulation of the immune response

Animals↗

[Common variable immunodeficiency--advances in diagnosis, pathogenesis and treatment].

Common variable immunodeficiency (CVI) is one of the most frequent primary immunological disorders. This congenital immunodeficiency, inherited in autosomal recessive way, has not fully elucidated pathogenesis--in spite of over forty years of studies. The cause of the disease seems to be mixed T and B-cell function disorders. Common variable immunodeficiency is characterised by significant variability of symptoms and signs. In the presented paper the definition, basic clinical manifestations of the disease, its course, prognosis are presented, and diagnostic and therapeutic management are discussed. The paper contains also a comprehensive review of current literature presenting modern views on the pathogenesis of CVI, and discussion of CVI variant--Good's syndrome.

B-Lymphocytes↗

[The role of radical oxygen species in airway inflammation].

Reactive oxygen species (ROS) are among numerous mediators of airway inflammation. They are playing a key role in asthma, chronic obturative pulmonary disease (COPD), adult respiratory distress syndrome (ARDS) and lung fibrosis (LF) pathogenesis. In view of very short half-life, their effects are local, related to the site of their formation. Generated either by epithelial or infiltrating cells, ROS cause epithelial damage, increase vascular leakage, induce smooth muscle proliferation and enhance pro-inflammatory gene expression. They also increase arachidonic acid mediator release through cytosolic phospholipase A2 phosphorylation. Drugs inhibiting ROS generation have become the first line of treatment of airway inflammatory disorders.

Chemotaxis↗

[Leukotrienes as inflammation mediators].

Leukotrienes are biologically active metabolites derived from arachidonic acid playing an important role in inflammatory responses. There are two main groups of leukotrienes: dihydroxyleukotrienes (LTB4) and cysteinyl-leukotrienes (LTC4, LTD4, LTE4). By activating specific G-protein coupled receptors, leukotrienes take part in immune responses, like activation and chemotaxis of leukocytes. Several studies have shown that leukotrienes may play a significant role in pathomechanisms of inflammatory diseases of human airways, skin, digestive tract and heart.

Chemotaxis↗

[X-linked agammaglobulinemia: an update].

X-linked agammaglobulinemia (X-LA) was the first described and remains the most common inherited antibody deficiency. Although initially reported by Bruton in early fifties, full clinical picture and detailed pathogenesis were established recently. X-LA was the first immunodeficiency to be mapped to a specific locus in the human genome based on linkage analysis. Molecular basis for this disease is more than 400 mutation in one of Tec kinases--Bruton's tyrosine kinase (Btk) which affects B cell maturation through impaired B cell receptor signaling. Although the precise mechanism is still to be elucidated, data obtained from transgenic animals suggested that Btk controls B cell maturation at least in two different levels--in bone marrow and in spleen. Clinical features comprise encapsulated bacteremia and pyremia in boys with very low B lymphocyte count and low immunoglobulin concentrations. Lymphocytes from patients with X-LA are unable to synthesize immunoglobulin in response to T cell-independent antigens. Standard treatment is an immunoglobulin substitution. Gene therapy seemingly may be an ideal treatment for this disease. In this paper authors reviewed current literature describing recent updates in pathogenesis, diagnosis and treatment of X-linked agammaglobulemia.

Agammaglobulinemia↗

[Analysis of gene expression at the entire genome scale--applications in biological sciences and medicine].

Microarrays are one of the latest breakthroughs in experimental molecular biology, which allow monitoring of gene expression for tens of thousands of genes in parallel and are already producing huge amounts of valuable data. Microarray RNA expression on a genome-wide range is now a proven technology, although the idea of analysis of expression many genes in one sample is not new. Since the development of clone printing technology and oligonucleotide synthesis allowed to produce high density microarray. In this publication we provide the information about the technology, available detection systems and data analysis software. Comprehensive review of current or fundamental papers using microarray technology application in immunology, rheumatoid arthritis, oncology, cystis fibrosis research, primary pulmonary hypertension, psychiatry, and allergic airways inflammation is also included.

Animals↗