Structural Alterations of Monocytes in Systemic Lupus Erythematosus

© 2017, Springer Science+Business Media, LLC. Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system mistakenly attacks multiple organs and tissues of the body. To elucidate the involvement of blood cells in the pathogenesis of SLE, we used transmission electron microscopy to study ultrastructure of monocytes isolated from the blood of SLE patients. We found that in the SLE patients, a substantial fraction of monocytes had abnormal morphology that corresponded to the structural signs of either necrosis or apoptosis. The number of altered monocytes in the SLE patients was significantly higher than in healthy subjects and related directly with the level of anti-dsDNA autoantibodies in the blood. Our results suggest that monocytes are involved in the pathogenesis of SLE and undergo adverse necrotic and/or apoptotic changes, likely induced by autoantibodies

Ferromagnetism in magnetically doped III-V semiconductors

The origin of ferromagnetism in semimagnetic III-V materials is discussed. The indirect exchange interaction caused by virtual electron excitations from magnetic impurity level in the bandgap to the valence band can explain ferromagnetism in GaAs(Mn) no matter samples are degenerated or not. Formation of ferromagnetic clusters and percolation picture of phase transition describes well all available experimental data and allows to predict the Mn-composition dependence of transition temperature in wurtzite (Ga,In,Al)N epitaxial layers.Comment: 4 pages with 3 figure

The reactions of 2H-1,2,3-diazaarsoles with phenyl azide

2-Phenyl-5-methyl- and 2,5-diphenyl-2H-1,2,3-diazaarsoles 1a,b react with phenyl azide to give several crystalline products: tricyclic derivatives 2a,b and 4,4′-bis(2H-1,2,3-diazaarsoles) 5a,b formed at room temperature, and a cycloadduct 6a obtained at + 4°C. Compound 6a undergoes a fast rearrangement in solutions of Et3N or pyridine to give a stable dicoordinate arsenic compound, the 2H-1,2,3-diazaarsole 7a. Heating solutions of 2a under reflux in an inert atmosphere leads to 5a and of 2b, in the presence of water, to 4b. The structures of 2a, 4b, and 7a were characterized by X-ray crystal structure determinations. © 1996 John Wiley & Sons, Inc

Compression-induced structural and mechanical changes of fibrin-collagen composites

Fibrin and collagen as well as their combinations play an important biological role in tissue regeneration and are widely employed in surgery as fleeces or sealants and in bioengineering as tissue scaffolds. Earlier studies demonstrated that fibrin-collagen composite networks displayed improved tensile mechanical properties compared to the isolated protein matrices. Unlike previous studies, here unconfined compression was applied to a fibrin-collagen filamentous polymer composite matrix to study its structural and mechanical responses to compressive deformation. Combining collagen with fibrin resulted in formation of a composite hydrogel exhibiting synergistic mechanical properties compared to the isolated fibrin and collagen matrices. Specifically, the composite matrix revealed a one order of magnitude increase in the shear storage modulus at compressive strains>0.8 in response to compression compared to the mechanical features of individual components. These material enhancements were attributed to the observed structural alterations, such as network density changes, an increase in connectivity along with criss-crossing, and bundling of fibers. In addition, the compressed composite collagen/fibrin networks revealed a non-linear transformation of their viscoelastic properties with softening and stiffening regimes. These transitions were shown to depend on protein concentrations. Namely, a decrease in protein content drastically affected the mechanical response of the networks to compression by shifting the onset of stiffening to higher degrees of compression. Since both natural and artificially composed extracellular matrices experience compression in various (patho)physiological conditions, our results provide new insights into the structural biomechanics of the polymeric composite matrix that can help to create fibrin-collagen sealants, sponges, and tissue scaffolds with tunable and predictable mechanical properties

Decreased retraction of blood clots in patients with venous thromboembolic complications

Haemostatic disorders play an important role in the pathogenesis of acute venous thrombosis. One of the least studied reactions of blood coagulation and thrombogenesis is spontaneous contraction of blood clots, which takes place at the expense of the contractility apparatus of activated blood platelets adhered to fibrin fibres. The work was aimed at studying the parameters of contraction of blood clots, formed in vitro, in blood of 41 patients with acute venous thromboses as compared with the same parameters in apparently healthy donors. We used a new instrumental method making it possible to determine the time from initiation to the beginning of contraction, as well as the degree and velocity of clot contraction. It was revealed that in patients with venous thrombosis the ability of clots to shrink was significantly reduced as compared with the control. We detected a statistically significant retardation of and decrease in of blood clot concentration in patients with venous thrombosis complicated by pulmonary artery thromboembolism as compared with contraction in patients with isolated deep vein thrombosis, witch may be important for early diagnosis and determination of the risk of thromboembolism. Besides, we revealed a statistically significant retardation of contraction in patients with proximal thrombosis as compared with contraction in patients with distal thrombosis, with similar values of the degree of contraction. Contraction was statistically significantly reduced in acute thrombosis (less than 21 days), whereas in subacute thrombosis (more than 21 days) the parameters of contraction were closer to normal values. The obtained findings suggest that reduction of blood clot contraction may be a new, hitherto unstudied pathogenetic mechanism deteriorating the course and outcome of venous thrombosis. The clinical significance of contraction and its impairments, as well as the diagnostic and prognostic value of the laboratory test for blood clot contraction would merit further study

Autoantibodies Against dsDNA Modulate Contraction of Blood Clots

© 2017, Springer Science+Business Media, LLC. The degree and rate of clot contraction (retraction) in systemic lupus erythematosus (SLE) patients, especially in those with a high level of anti-double stranded DNA (dsDNA) antibodies in the blood, was significantly reduced compared to healthy donors. We hypothesized that this effect was caused by the anti-dsDNA antibodies. To test this assumption, we investigated the kinetics of blood clot contraction in vitro in the absence and presence of anti-dsDNA antibodies purified from the blood serum of SLE patients. The degree of clot contraction was increased immediately after addition of the anti-DNA antibodies in a concentration-dependent manner. This stimulating effect was abrogated by a monoclonal antibody against the platelet Fc-receptor. On the contrary, after prolonged incubation (for hours) of the blood samples with the anti-DNA antibodies, the extent of clot contraction was significantly reduced. These results suggest that anti-dsDNA antibodies in SLE induce Fc-receptor-mediated chronic platelet hyperactivation, resulting in platelet exhaustion and dysfunction, including reduced contractility. The impaired contraction of blood clots and thrombi caused by autoantibodies may be an important pathogenic mechanism that affects the course and outcomes of thrombotic complications in SLE

Abnormal Ultrastructure of the Platelet Plasma Membrane in Systemic Lupus Erythematosus

© 2016, Springer Science+Business Media New York.Systemic lupus erythematosus (SLE) is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue. It can affect the skin, joints, kidneys, brain, and other organs. Blood cells, including platelets, are also involved in SLE and contribute to the pathogenesis of disease. We studied ultrastructure of platelets isolated from the blood of SLE patients and found that the plasma membrane was rough and shaggy compared to the normally smooth cell surface. These changes in the membrane morphology increased with the disease severity and were more pronounced when SLE was associated with the antiphospholipid syndrome, suggesting that platelets are strongly affected by the immune reactions underlying SLE

Tandem dihetero-Diels-Alder and Huisgen cycloaddition reactions. Synthesis, crystal structure and hydrolysis of the novel cage phosphoranes

© 2018 the Partner Organisations. The reaction of 2-(1-phenylvinyloxy)benzo-1,3,2-dioxaphosphole with hexafluoroacetone, ethyltrifluoropyruvate and chloral leads to the formation of cage phosphoranes possessing the 1-phospha-2,6,8-trioxabicyclo[3.2.1]octane framework whose structure was established by the XRD method and NMR spectroscopy. The process involves dihetero-Diels-Alder and Huisgen 1,3-dipolar cycloaddition reactions and is accompanied by the simultaneous formation of the P-C and C-C bonds. Despite the generation of three chiral carbon atoms, the stereoselectivity of the process exceeds 96%. Hydrolysis leads to the formation of functionalized aldols and phosphonates

Structural characterization of platelets and platelet microvesicles

© 2016, Pleiades Publishing, Ltd.Platelets are blood cells without nuclei, which, in conjunction with fibrin, cause bleeding to stop (hemostasis). Cellular microvesicles are microscopic particles released into extracellular space under activation and/or apoptosis of cells of different types. Platelet microvesicles form the main population of blood circulating through microvesicles and play an important role in the reactions of hemostasis, thrombosis, and many other (patho)physiological processes. Despite the large number of studies that have been devoted to the function of platelet microvesicles, the mechanisms of their formation and structural details remain poorly understood. The ultrastructure of the initial platelets and microvesicles formed in vitro from resting cells and platelets activated by arachidonic acid, ADP, thrombin, and calcium ionophore A23187 is investigated in this study. The intracellular origin, stages of formation, structural diversity, and size of microvesicles were analyzed according to the results of transmission electron microscopy of human platelets and isolated microvesicles. It was shown that thrombin, unlike other activators, not only stimulates microvesiculation of the plasma membrane, but also causes decomposition of cells with the formation of subcellular particles that have sizes comparable with the size of the microvesicles from the outer membrane of the cells. Some of these microparticles are cellular organelles surrounded by a thin membrane. The size of isolated microvesicles ranges from 30 to 500 nm, but their size distribution depends on the nature of the activating stimulus. The obtained results contain new data on the formation of platelet microvesicles and their structural diversity, which are important for understanding of their multiple functions in health and disease

Synthesis and properties of phosphabetaine structures: IV. 3-(triphenylphosphonio)propanoate in reactions with dipolar electrophilic reagents

Reactions of 3-(triphenylphosphonio)propanoate with heterocumulenes, such as phenyl isocyanate and dicyclohexylcarbodiimide, we studied under the assumption that they proceed by nucleophilic addition and 1,4-dipolar cycloaddition schemes. Quantum-chemical calculations show that the σ5-phosphorane cycloadduct of the betaine with isocyanate is thermodynamically preferred over its isomeric zwitter-ionic adduct. However, the experimental evidence suggests that the reaction with phenyl isocyanate involves nucleophilic addition of the betaine to isocyanate followed by hydrolysis to firm finally a complex of the starting betaine with diphenylurea. The structure of the complex was established by X-ray diffraction analysis. The revealed above controversy is explained by a high protophilicity of betaine structures, which is also confirmed by the results of the reaction of the betaine with carbodiimide. © Pleiades Publishing, Inc., 2006