Epitope mimicry and its role in the development of autoimmune reactions

The role of molecular mimicry in the development of some autoimmune diseases, such as rheumatism, rheumatoid arthritis, the Julian-Barré syndrome, the antiphospholipid syndrome, multiple sclerosis, is reviewed. The data on the presence in bacteria and viruses antigenic determinants similar to those in human tissues are presented. The phenomenon of epitope mimicry is considered in the light of the latest research in the field of IgE autoreactivity, which may take part in the pathogenesis of allergic diseases.     

Effect of UV radiation and the autotransfusion of UV-irradiated blood on the content of cationic proteins in the neutrophilic granulocytes of calves

A study was made of the influence of UV-irradiation (254 nm) of blood in vitro, of the autotransfusion of UV-irradiated blood (AUVIB), and of the mixture of UV-irradiated and intact blood in vitro on the content of bactericidal cation proteins (CP) in blood neutrophil of calves suffered from dyspepsia and broncho-pneumonia. Age differences were noticed in CP contents and their decrease in neutrophils following AUVIB in vivo and administration of the mixture of blood in vitro. The decrease in cell CP contents is presumably due to neutrophil degranulation and CP release into the blood plasma. Since the initial mechanisms of neutrophil degranulation are located on the cell surface, the CP release is supposed to result from a membranotropic effect of UV-irradiated blood on the intact autologous blood. This effect may explain the increase in nonspecific resistance of organism after the AUVIB, being one of the main therapeutic phenomena of the AUVIB-therapy.     

Functional and structural changes in the surface of human erythrocytes after UV irradiation with rays of various wavelengths. IV. Changes in the physicochemical properties of autotransfused UV-irradiated blood

Properties of erythrocyte surface were investigated for patients with ischemic heart disease in the course of treatment with the UV-irradiated blood autotransfusion (UVIBA). Application of methods of light-scattering, photometry and cytochemistry revealed rapid and significant changes in deformability and aggregation properties of the erythrocytes immediately following each UVIBA procedure, which was accompanied by considerable blood viscosity decrease.     

Limits of homeostasis of ultrastructural components of the skeletal muscles at norm and during muscular activity

Certain data obtained by electron microscopic and morphology metric methods prove that fluctuations of the limits of intra-cellular homeostasis of the dominating components of muscular fibres are within 7 per cent. It is demonstrated that skeleton muscles of animals of different age get adapted to physical loading by intracellular regeneration.     

Effect of gamma radiation on the immunobiological and immunochemical properties of cholera exotoxin. I. Change in the biological activity of nonpurified cholera exotoxin as affected by ionizing radiation

Crude cholera exotoxin (filtrate toxin) was irradiated with increasing doses of gamma radiation. A significant drop in enterotoxicity, in the activity of the permeation factor and a decrease in toxicity were shown to occur as radiation doses increased. Radiation doses of 50-70 kGy were found to completely inactivate enterotoxicity in liquid toxic preparations. A higher radioresistance of dried preparations in comparison with liquid ones was registered: inactivation occurred at 150-200 kGy. Different batches of the initial filtrate toxin had varying radiosensitivity. The sterilizing effect of gamma radiation was achieved at doses of 20 kGy for liquid preparations and 30 kGy for dried preparations. During the prolonged storage of the irradiated preparations of crude toxin (the term of observation being 1.5 years) at different temperatures no reversion of toxicity was found to occur, while their immunogenic properties remained unchanged.     

Maturation of the Golgi apparatus in urothelial cells

The differentiation of urothelial cells is characterized by the synthesis of uroplakins and their assembly into the asymmetric unit membrane. The Golgi apparatus (GA) has been proposed to play a central role in asymmetric unit membrane formation. We have studied the distribution and organization of the GA in normal mouse urothelial cells and in the superficial urothelial cells that undergo differentiation following cyclophosphamide-induced regeneration, in correlation with urothelial cell differentiation. In normal urothelium, immature basal cells have a simple GA, which is small and distributed close to the nucleus. In intermediate cells, the GA starts to expand into the cytoplasm, whereas the GA of terminally differentiated umbrella cells is complex, being large and spread over the whole basal half of the cytoplasm. During early stages of regeneration after cyclophosphamide treatment, the GA of superficial cells is simple and no markers of urothelial differentiation (uroplakins or asymmetric unit membranes, discoidal or fusiform vesicles, apical surface covered with microvilli) are expressed. At a later stage, the GA expands and, in the final stage of regeneration, when cells express all markers of terminal urothelial differentiation, the GA become complex once again. Our results show that: (1) GA distribution and organization in urothelial cells is differentiation-dependent; (2) the GA matures from a simple form in partially differentiated cells to a complex form in terminally differentiated superficial cells; (3) major rearrangements of GA distribution and organization correlate with the beginning of asymmetric unit membrane production. Thus, GA maturation seems to be crucial for asymmetric unit membrane formation. The work was supported by the Ministry of Education and Sport, Government of Republic of Slovenia, Slovenia (grant no. 3311-04-831450).     

Phosphorylated hydroxyethylamines as novel inhibitors of the bacterial cell wall biosynthesis enzymes MurC to MurF

Enzymes involved in the biosynthesis of bacterial peptidoglycan represent important targets for development of new antibacterial drugs. Among them, Mur ligases (MurC to MurF) catalyze the formation of the final cytoplasmic precursor UDP-N-acetylmuramyl-pentapeptide from UDP-N-acetylmuramic acid. We present the design, synthesis and biological evaluation of a series of phosphorylated hydroxyethylamines as new type of small-molecule inhibitors of Mur ligases. We show that the phosphate group attached to the hydroxyl moiety of the hydroxyethylamine core is essential for good inhibitory activity. The IC₅₀ values of these inhibitors were in the micromolar range, which makes them a promising starting point for the development of multiple inhibitors of Mur ligases as potential antibacterial agents. In addition, 1-(4-methoxyphenylsulfonamido)-3-morpholinopropan-2-yl dihydrogen phosphate 7a was discovered as one of the best inhibitors of MurE described so far.