Biomedical subjects
Publications and source records attributed to O F Lykova.
The effect of blood substitute perftoran on the content of alpha(1)- and alpha(2)-macroglobulins in the plasma and exudate was studied in rats with acute exudative inflammation. After intravenous injection of perftoran macroglobulin content increased in the plasma, but remained unchanged in the peritoneal fluid.
The content of lactoferrin (LF) was studied in the liquor and blood of patients with tick-borne encephalitis (TBE) of the meningeal and focal types; additionally, the information density of the discussed parameter was assessed for evaluating the severity and degree of the inflammation process in the central nervous system (CNS). The LF level was determined in liquor of 37 samples obtained from TBE patients (main group) and of 10 persons with osteochondrosis (controls); it was also determined in the serum taken from 21 TBE patients and from 40 healthy donors by using the immune-enzyme analysis. The LF concentration in TBE patients was found to exceed the normal value by 1.5-3 times during the whole observation period. As for the liquor, it was high, by the onset of the disease, by more than 20 times, however, after the 7th day it was higher 6-fold. A direct dependence of a concentration of the studied protein on a form and severity of the disease was established. The LF level in the liquor of TBE patients alongside with clinical signs can be an objective indicator of a severity and activity of the inflammation process in the CNS; it can also be a criteria of how much the conducted therapy effective is.
The authors propose a highly effective method for isolation of lactoferrin from female colostrum. Lactoferrin is measured by the sandwich enzyme immunoassay. Its concentrations in the serum, urine, amniotic and cerebrospinal fluid in health are measured. The advantages of the method for lactoferrin purification and the practical significance of this protein are discussed.
The permeability of the blood-brain barrier for the cerebrospinal fluid marker proteins has been assessed in patients with grave craniocerebral injuries. The content of albumin and alpha 2-macroglobulin in the survivors decreased with time and by day 7 after the injury was virtually normal. In patients who died the content of these proteins was reliably increased starting from day 1. By day 7 the content of albumin in the cerebrospinal fluid approached the norm in this group, whereas the content of alpha 2-macroglobulin remained increased. The level of IgG surpassed the normal value on day 1 only in the patients who died, and later it did not differ from the norm in both groups.
Antiserum against rat alpha 1-macroglobulin (alpha 1MG) was produced in rabbits. Antiserum against rat pregnancy-associated alpha 1-glycoprotein (PAG) was obtained by immunization with a partly purified PAG preparation and absorption of the serum with male rat serum. Acute inflammation was produced in non-pregnant female rats by a single intramuscular injection of turpentine. The concentrations of both macroglobulins in the serum and in tissue extracts were measured by rocket immunoelectrophoresis at various times up to 7 days after injury. Inflammation produced in the rats resulted in moderately elevated serum levels of these proteins soon after injury. At first, alpha 1MG levels in a number of tissues (heart, lung, kidney, spleen, pancreas, uterus and ovary) were depressed markedly; they then stabilized. The elevated serum concentrations of alpha 1MG remained unchanged during inflammation. The store of PAG in the tissues was rapidly depleted and its serum level decreased to a normal value 7 days after injury. Our findings indicate that alpha 1MG plays a more important role in maintenance of the proteinase inhibitory potential in the rat than does PAG.
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To study blood-brain barrier permeability and proteolytic changes in in patients with severe brain injury and to evaluate their impact on its course and outcome, the concentrations of albumin, plasminogen (plasmin), alpha 2-macroglobulin, alpha 2-antiplasmin, and alpha 1-antitrypsin were examined in 58 victims by enzyme immunoassay. The control group comprised 20 patients examined for lumbar discal hernia. The studies indicate that early severe brain injury showed blood-brain barrier dysfunction whose severity can be detected by the spinal fluid levels of albumin, plasminogen, and alpha 2-macroglobulin. Proteolytic changes in spinal fluid are determined by its albumin, plasminogen (plasmin), alpha 2-macroglobulin, alpha 2-antiplasmin, and alpha 1-antitrypsin concentrations and affect the development of secondary brain lesion and they are of practical value.
In tick-borne encephalitis certain immunopathological reactions develop in the tissues of the central nervous system; alpha 2-macroglobulin may serve as the marker of the activity of these reactions. The dynamic study of liquor taken from 16 patients with the meningeal and focal forms of tick-borne encephalitis (TBE), 8 patients with severe craniocerebral traumas accompanied by meningitis and 10 patients with osteochondrosis was made. As revealed in this study, in TBE patients the level of alpha 2-macroglobulin increases 3.5-fold and remains stable during the acute period of the disease.
Permeability of the blood-brain barrier was studied by comparing the molar concentrations of albumin and alpha 2-macroglobulin in the spinal fluid and blood of patients with severe brain injury. If the outcome was good, the selective permeability of the barrier was shown to be fully retained, which meant that its regulatory and protective functions remained normal. If the outcome was poor, the selective permeability changed to a greater extent and the alterations found suggested that the regulatory function of the barrier was preserved with simultaneous loss of its protective properties. More marked changes in the function of blood-brain barrier and in the protein composition of spinal fluid occurred with simultaneously elevated intracranial pressure.
The authors studied the distribution of proteinase inhibitors in inflammation induced by intramuscular turpentine injection. It was found that it reduces the concentration of the studied proteins in the tissues, which is attended by an increase of their plasma levels. The store of pregnancy-associated alpha 1-glycoprotein in the tissues is rapidly depleted, while the concentration of alpha 1-microglobulin reduces to a relatively stable level. The role of the both proteins in the inflammatory process is discussed.
Studies have been made on physicochemical and immunochemical properties of macroglobulins, as well as of associated with pregnancy glycoproteins, from human subjects, mammals, birds, fishes and invertebrates. It was shown that these proteins exhibit similar composition, structure and capacity to bind proteinases inhibiting the latter. Using immunochemical methods, reactions of antigenic identity of these proteins were investigated. A hypothesis of evolutionary formation of macroglobulin family is discussed.
The reactions of polyfunctional proteins alpha2-macroglobulin (MG) and lactoferrin (LF) lipoprotein-receptor protein (LRP) and different ligands (antibodies and hydrolases) for ascertaining the mechanisms of their interaction and the probable role of MG and LF in the neutralization of bacterial pathogens were under study. The binding of MG and LF with ligands, irrespective of their nature, was shown to lead to the neutralization of the complex thus formed. This mechanism of neutralization in reaction of LF with ligands was supposedly due to the antibacterial properties of this protein: multiple reactions of LF with receptor sites on the surface of pathogens neutralized the charge of the latter and facilitated phagocytosis. The interaction of LRP of immunocompetent cells with MG, in the presence of additional binding sites on its surface, made it possible for MG to effectively bind and present even heretofore unknown pathogens in the presence of hydrolases on their surface.
Biochemical and immunochemical properties of human alpha 2-macroglobulin and its analogues from cattle, horse, rabbit, guinea pig, rat, mouse, hen and perch have been investigated. It was found that all analogues have the identical molecular mass and structure, being different in their isoelectric point and carbohydrate composition. It was shown that some antigenic properties of macroglobulins remained constant during evolution, whereas other ones were strictly differentiated at the level of families and species. These data allow to classify macroglobulins as proteins which appeared in vertebrates at early stages of evolution revealing only relatively slight changes during the latter.
Glycoproteins similar in composition, structure, and functions were isolated from the blood serum of pregnant women, cows, dogs, and rats. They consist of four identical subunits, which form dimers due to covalent bonds, while dimers form tetramers due to hydrogen bonds. All these proteins are non-specific inhibitors of proteases and bind these enzymes in the same way as alpha-macroglobulins do, by capture in a "trap". Furthermore, they are capable of binding and transporting various cytokines. The results obtained indicate that these proteins belong to the family of macroglobulins.
Studies have been made on physico-chemical and antigenic properties of albumins from man, mammals, birds, insects, amphibians, worms, fishes and crustaceans. It was found that all the animals contain structurally identical proteins with similar physico-chemical properties. At the same time, the level of antigenic identity of the proteins decreases in the following order: type, genus, family, species.
Activities of plasmin and trypsin contained in complexes with alpha 2-macroglobulin, related to pregnancy alpha 2-glycoprotein and with protein A were studied in presence of various inhibitors with a molecular mass of 0.2-70.0 kDa. Specific characteristics of interaction between plasmin and these macroglobulins inhibitors as well as with alpha 1-inhibitor of proteinases, antithrombin III and alpha 2-antiplasmin were studied using electrophoresis and immunoblotting.
The CSF levels of albumin, alpha 2-microglobulin and IgG were studied in patients with severe brain injury. Elevated CSF levels of albumin and alpha 2-microglobulin were found in more severe patients. The level of IgG level was within the normal range. Endogenic protease-bound alpha 2-microglobulin may cause secondary cerebral tissue lesion, by closing the vicious circle.