The low density lipoprotein receptor-related protein (LRP) 1 is a large endocytic receptor containing a 515-kDa heavy chain to which ligands bind and a non-covalently associated 85-kDa light chain containing a transmembrane and cytoplasmic domain (for review see Ref. 1). LRP is one of 12 or more receptors that make up the LDL receptor superfamily and is essential for embryonic development in mice (2). A remarkable feature of LRP is its ability to bind and mediate the internalization of a diverse array of ligands, including proteinases (3, 4), proteinase-inhibitor complexes (5, 6), and lipoproteins (7). After binding to the LRP, the ligands are transported into endosomes where they uncouple in the reduced pH environment and are sorted to lysosomes for degradation. LRP recycles back to the cell surface where it is once again available to bind ligands.Recent studies indicate that in addition to their cargo transport function, certain LDL receptor family members also participate in signaling pathways. For example, the very low density lipoprotein receptor and apoE receptor 2 both participate in a signal transduction pathways mediated by reelin (8 -10). Reelin is secreted by Cajal-Retzius cell in the outermost layer of the cerebral cortex and controls the final position of neurons that migrate from the ventricular zone. Binding of reelin to either the very low density lipoprotein receptor or apoE receptor 2 induces tyrosine phosphorylation of disabled-1 (Dab1) (9, 10), an adaptor protein that interacts with the cytoplasmic domains of LDL receptor family members (11, 12) and functions in tyrosine kinase signaling pathways.In the case of LRP, accumulating evidence suggests a prominent but undefined role for this receptor in regulating cell physiology by facilitating signal transduction pathways. For example, LRP has been implicated as a component of the receptor complex for midkine (13), a heparin binding growth factor with migration-promoting and survival-promoting activities. Another LRP ligand, tissue type plasminogen activator, promotes late phase long term potentiation (14), and this activity appears to require its association with LRP (15). Finally, the binding of activated ␣ 2 M (␣ 2 M*) to LRP mediates calcium influx in neurons in a process that also involves N-methyl-D-
Cell regulation of Ph+cell proliferation and differentiation has been studied ex vivo in various chronic myeloid leukemia (CML) patients. The regulation is provided by alternation of effective stages of proliferation and maturation with inhibition of Ph+ cell proliferation by accumulating neutrophils under apoptosis blockage. The alternation of stages consists of switching stage 1 (effective proliferation) to stage 2 (effective maturation) and proceeds according to the 1/2 -1/2/1 or 2/1-2/1/2/1 schemes. The kinetic plots of alternations pass through control points of crossing plots, where the parameters of proliferation and maturation are equal. The indices of P/D efficiency (ratio of proliferation and maturation rates) are 1.06±0.23 and don't depend on time, alternation order, or sources of Ph+ cells - CML patients. During stages alternation, conversely, the parameters of Ph+ cell proliferation and maturation vary. The proliferation stages are characterized by increased proliferating cells content, a decreased number of neutrophils, and apoptosis induction. At the maturation stages, conversely, apoptosis is inhibited, the number of mature neutrophils increases, while immature Ph+ cells decrease. High content neutrophils inhibit the proliferation of Ph+ cells and impair their own maturation by inversion of maturation order, probably through a feedback mechanism. The regulation differences ex vivo reveal three types of Ph+ cells from various individual CML patients, distinguished by the number and duration of alternating stages of proliferation and maturation. Ph+ cells types 1 and 2 have one prolonged stage of effective proliferation or effective maturation with efficiency indices P/D1 = 1-20 or P/D2 ⇐ 1. At the same time period, the proliferation and differentiation of the Ph+ cells type 3 proceeds with repeated alternations of stages with P/D1 = 1-4 or P/D2 ⇐ 1. Type 1 Ph+ cells (~20%) were isolated from patients in advanced stages of CML, while Ph+ cells types 2 and 3 (30 and 50% correspondingly) were isolated from CML chronic phase patients sensitive to chemotherapy.
The consequences of the abrupt transition of technological and industrial relations that have developed in the world division of labor from globalization to isolationism are discussed. The changes in the activity of the enterprise as the basic link of industrial production in the modern conditions of the global economic crisis and the increase in sanctions restrictions are considered. The fundamental importance of cognitive sovereignty for ensuring technological independence is noted. The impact of technological modernization processes on the structure of production, the role of cooperation and specialization in the economic activities of enterprises and organizations, opportunities for the formation of new product niches in innovative directions are evaluated.
The aim is to evaluate the effect of cytomegalovirus on clinical and paraclinical as well as immunological parameters in children with rotavirus infection (RVI). Materials and methods. 50 children aged one to three years, patients with moderate and severe intestinal infections of rotavirus etiology were examined. All children were examined for herpes virus infections types 1, 2, 4, 5, 6. Enzyme-linked immunosorbent assay (ELISA) was used to determine the level of specific Ig G and Ig M for herpes viruses types 1, 2, 4, 5, 6, and in the case of a positive test, polymerase chain reaction (PCR) determined the presence of DNA (qualitatively) of these herpesviruses. Group 1 (mono-RVI), which was taken as a reference, included 33 children in whom no infection with any of these viruses of the herpes group was detected. Group 2 included 17 patients who underwent RVI on the background of CMV infection, the presence of infection with other viruses of the herpes group was excluded. Immune response parameters (CD 3+, CD 4+, CD 8+, CD 16+, CD 22+, Ig A, Ig M, Ig G, IL 1β, 4, TNF-α) in the acute period of the disease and in the period of convalescence were analyzed. Qualitative indicators were given in the form of absolute and relative (%) value. Significance of differences was determined using Pearson’s χ2 test (Pearson’s Chi-squared test). Quantitative indicators were given in the form of median (Me) and values of lower (LQ) and upper (UQ) quartiles. The significance of differences in quantitative indicators in two unrelated groups was determined using the Mann–Whitney U-test. The threshold value of the confidence level was taken as 0.05. Results. The analysis of the obtained data allows to establish that in the acute period of RVI infection in children with CMV leads to lower figures of temperature reaction, lower vomiting rate, prolongation of hospitalization, along with decrease in leukocytes, CD 16+ (%) cells and immunoregulatory index (CD 4+/CD 8+) against the background of increased levels of monocytes, CD 8+ (%) T-lymphocytes, concentrations of IL-4 and TNF-α. During convalescence, the presence of CMV is associated with an increase in the duration of fever and diarrhea, an increase in monocytes, CD 8+ (%) T cells, concentrations of IL-4, TNF-α and lower figures of immunoregulatory index, CD 16+ (%), CD 22+ (%) T cells and Ig M. Conclusions. Latent cytomegalovirus infection in children with rotavirus gastroenteritis significantly affects a number of clinical and paraclinical as well as immune parameters, which leads to a decrease in the intensity of clinical manifestations in the acute period of the disease and the prolongation of some symptoms during convalescence.
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