[Associations of hemostasis factors genes with early development of ischemic heart disease and manifestation of myocardial infarction in young age].

AIM: To study polymorphisms of genes of factors of the system of hemostasis in young patients with ischemic heart disease (IHD). MATERIAL: Two groups of patients participated in the study: patients with first manifestation of IHD at the age < or = 50 years (men) or < or = 55 years (women) (n=158), and patients with first IHD manifestation at the age > or = 70 years (n=92). METHODS: We studied polymorphic markers of genes encoding clotting factors V (F5) and VII (F7), subunit IIIa of platelet integrin (ITGB3), beta-chain of fibrinogen (FGB) and tissue plasminogen activator type 1 (PLANH1). RESULTS: After separation of a subgroup of patients with MI without preceding angina we revealed significant differences in distribution of frequencies of genotypes of polymorphic marker C(-426)T of factor V gene: genotype TT was significantly more frequent in young (14.9%) than in old (2%) patients (p=0.008). Multifactorial logistic regression revealed independent association of early IHD with smoking (OR 6.112 [2.567-14.552]; p<0.001) and presence of genotype TT of C(-426)T polymorphic marker of F5 gene (OR=9.410 [1.074-82.459]; p=0.043). CONCLUSION: Thus we obtained data on the presence of independent association between IHD risk and manifestation of MI in young age with genotype TT of polymorphic marker C(-426)T of F5 gene as well as with traditional risk factors of IHD.

[Cardiolipin antibodies dependents on beta2-glycoprotein-1 in antiphospholipid syndrome]. / Zavisimye ot beta2-glikoproteina-1 antitela k kardiolipinu pri antifosfolipidnom sindrome.

AIM: To study beta2-GP-I-dependent binding of phospholipid antibodies (PAb) to phospholipids and this process participation in pathogenesis of antiphospholipid syndrome (APS). MATERIALS AND METHODS: IgG-fractions and sera from 20 patients with APS. Cofactor activity of beta2-GP-I isolated from serum of healthy donors was examined with modified immunoassay. RESULTS: Contrary to donor IgG, binding of IgG fractions isolated from sera of APS patients with cardiolipin grows dose-dependently in the presence of beta2-GP-I. Cofactor activity of beta2-GP-I is confirmed in the study of sera of APS patients. Sera containing beta2-GP-I-dependent antibodies to cardiolipin (aCL), unlike aCL-negative sera, react with solid-phase immobilized beta2-GP-I. CONCLUSION: It is confirmed that beta2-GP-I participates in interaction of PAb with cardiolipin. Pathogenetic implication of beta2-GP-I-dependent PAb for onset of APS is discussed.

[Synthesis and biological properties of artificial antigens based on 280-289 fragment of beta2-gpI]. / Sintez i biologicheskie svoistva iskusstvennykh antigenov na osnove peptida, sootvetstvuiushchego posledovatel'nosti 280-289 belka beta2-gpI.

A series of artificial antigens were synthesized on the basis of the FC(Acm)KNKEKKC(Acm)S peptide from the beta 2-glycoprotein I sequence: lipophilic analogues, the peptide-BSA conjugate, and multiple antigen peptide (MAP) containing eight copies of the peptide on an oligolysyl core. The solid phase method for acylation of the peptide with fatty acids and the HPLC analysis of the acylpeptides were described. Antigenic properties of the resulting compounds were evaluated by CL-ELISA.

[Synthesis and antigenic properties of peptide fragments of beta2-glycoprotein-I]. / Sintez i issledovanie antigennykh svoistv peptidnykh fragmentov beta2-glikoproteina-I.

A number of beta 2-glycoprotein-I peptide fragments were synthesized by using the Fmoc-scheme of the solid phase method. Antigenic properties of these peptides were determined by ELISA. Acm-protected FCKNKEKKCS peptide was shown to inhibit binding of anti-cardiolipin antibodies to cardiolipin.

[The clinical importance of determining protein C and protein S in patients with nonspecific aortoarteritis]. / Klinicheskoe znachenie opredeleniia belka C i belka S u bol'nykh nespetsificheskim aortoarteriitom.

Solid-phase enzyme immunoassay estimated S and C protein levels in 10 patients with nonspecific aortic arteritis (NAA). Lowered concentrations of total protein S (< 70%) occurred in 8 (80%) of 10 NAA patients, in 3 of them protein C was also low. Isolated reduction of protein C was encountered only in one patient. Four patients (44%) of 9 had antibodies to phospholipids, as a rule, in low concentrations. 3 of them had low total protein S concentrations against normal C protein. 4 patients (40%) showed elevated concentrations of WF antigen concentrations. No relationship was noted between a fall in total protein S, C concentrations and clinical presentation of NAA, the disease activity, presence of antibodies to neutrophil cytoplasm and antibodies to endothelial cells. Thus, a reduction in the levels of total protein S in NAA patients is induced by endothelial dysfunction unrelated to production of antibodies to phospholipids, neutrophil cytoplasm and vascular endothelium.

[Possibilities of the use of trypsinogen activation peptide in the pancreatic tissue in the diagnosis of pancreatic necrosis]. / O vozmozhnosti ispol'zovaniia peptida aktivatsii tripsinogena v tkani podzheludochnoi zhelezy v diagnostike pankreonekroza.

The test of peptide of trypsinogen activation (PTA) in various biological media is a principal new diagnostic test for acute pancreatitis. PTA levels in the pancreatic tissue and the plasma of the blood in acute experimental pancreatic necrosis reflects the process of the pathological activation of trypsin in the diseases focus and confirms the source of higher levels of activation peptide in the blood flow. Together with the values of other enzymatic systems of the pancreatic gland the discussed value permits one to make a more precise assessment of the mechanism and stages of autodigestive processes which develop in acute experimental pancreatitis.

[The dynamics of the peptide hydra morphogen in meningitis]. / Dinamika peptidnogo morfogena gidry pri meningitakh.

The content of peptide hydra morphogen (PHM) was measured for the first time in blood plasma and CSF by RIA in patients with purulent meningitides. 36 patients were examined. Blood and CSF were withdrawn in the acute period and during early convalescence. In the reference group (patients with acute respiratory diseases of virus etiology, quinsy, pneumonias), the PHM concentration in the blood was 128 +/- 62 fm/ml, that in CSF 66 +/- 14 fm/ml. In purulent meningitis of medium gravity, the content of PHM in blood plasma and CSF did not significantly differ from the control. Grave purulent meningitis was marked by a high content of PHM in blood plasma and CSF, in particular, in the acute period and during early convalescence. It was 1250.30 +/- 191 and 544.03 +/- 159 fm/ml in blood plasma and 1504.38 +/- 475 and 1811.39 +/- 375 fm/ml in CSF, respectively. In grave complicated purulent meningitis, which was mainly observed in persons over 50 years, the content of PHM in blood plasma exceeded but insignificantly the content in the control during the acute period (327.49 +/- 76 fm/ml), followed by further increase (1131.41 +/- 209 fm/ml) by days 8-12 of the disease; within the same time, the content of PHM in CSF did not significantly differ from the control (319.52 +/- 152 and 625.69 +/- 275 fm/ml, respectively). In view of the fact that hypothalamic PHM is of crucial importance in the processes of nervous tissue regeneration, the content of the latter one in CSF in patients with grave purulent meningitis may serve as a criterion for disease course tendencies.

[Determination of amyloid P component in blood by an immunoenzyme method]. / Opredelenie amiloidnogo P-komponenta v plazme krovi s pomoshch'iu immunofermentnogo metoda.

An ELISA procedure was developed for measuring serum amyloid P-component (SAP). The assay is based on our finding of binding AP to polystyrene microtiter plates. The amount of SAP is determined by concurrent ELISA, wells being sequentially incubated with rabbit anti-AP antiserum and goat anti-rabbit antiserum, conjugated with peroxidase. The limit of sensitivity of the assay is 0.5 micrograms/ml. When applied to the screening of patients plasma, elevation of SAP concentration in patients with rheumatoid arthritis and amyloidosis were found.

[Isolation and characteristics of antibodies against synthetic fragments of oncoproteins. II. Antiserum against the transforming protein pp60src of Rous sarcoma virus]. / Poluchenie i kharakteristika antitel k sinteticheskim fragmentam onkobelkov. II. Antisyvorotka k transformiruiushchemu belku virusa sarkomy kur Rausa pp60src.

To generate the antibodies to the transforming protein of Rous sarcoma virus (RSV) pp60src, rabbits were immunized with the peptide, corresponding to 415-421 sequence of pp60src. These antibodies immunoprecipitate pp60src in RSV-transformed chicken and mammalian cells, and also some proteins (45, 85 and 120 kDa), which could be autophosphorylated in vitro. It was shown that 415-421 sequence of pp60src is not recognized by the antibodies to pp60src from RSV-induced tumour bearing rabbits (TBR serum). In contrast to TBR serum, antibodies, generated against synthetic peptide, corresponding 415-421 sequence of pp60src couldn't be phosphorylated in vitro, when [gamma-32P]ATP is added to the immune complex. The antipeptide antibodies, bound to pp60src did not block phosphorylation of TBR immunoglobulins, added to this immune complex. Hence, 415-421 sequence of pp60src RSV containing the major tyrosine phosphorylation site does not take part in the kinase reaction in vitro.

[Pharmacokinetics of dalargin]. / Farmakokinetika dalargina.

Pharmacokinetics of a new anti-ulcer drug, synthetic opioid hexapeptide dalargin (Tyr-D-Ala-Gly-Phe-Leu-Arg), which is an analogue of Leu-enkephalin, was studied in rats. Distribution and metabolism of 3H-Tyr-dalargin were examined after intravenous administration at a dose of 150 mg/kg. Main Tyr-containing metabolites of dalargin were detected and dynamics of their concentrations was evaluated in blood within 1 hr after administration. Kinetic curve of dalargin was described as three-exponential function.

[Localization of the peptide Hydra morphogen in the pontine neurons of the human brain]. / Lokalizatsiia peptidnogo "morfogena gidry" v neironakh mosta golovnogo mozga cheloveka.

Localization of neurons with peptide "Hydra morphogen" in the human pons has been investigated by means of immunocytochemical methods. Single neurons are found in the cranial part of the pons, in its grey substance, that immediately adjoins the lateral walls of the IV ventricles and in the nucleus tegmenti dorsalis. These neurons are round and polygonal with body diameter 22-25 mcm, they contain light brown precipitate of various density. The data obtained corresponds to general evolutionary regularities on distribution of biologically active peptides in the nervous system of vertebrate and invertebrate animals.

[Limited proteolysis of prolactin in secretory granules from the pituitary gland of estrogenized rats]. / Ogranichennyi proteoliz prolaktina v sekretornykh granulakh iz gipofiza éstrogenizirovannykh krys.

The LTH-converting proteolytic activity in LTH granules isolated from estrogenized rat hypophysis was studied. Suspensions of granules were incubated at different values of pH for 4 hours at 37 degrees C. The reaction was controlled by SDS electrophoresis. Intensive proteolysis of LTH was observed at pH 6.0 and 3.9, which was accompanied by the formation of fragments with Mr 10, 12 and 17 kD and probably of smaller peptides. An inhibitory analysis revealed that the formation of the 17 kD fragment at pH 3.9 was partly and selectively inhibited by chloroquine, phenanthroline and phenylmethylsulfonyl fluoride. Pepstatin A fully inhibited the proteolysis, whereas leupeptin had no inhibiting influence. The data obtained testify to the presence in the granular fraction of the endopeptidase LTH-converting activity which is sensitive to pepstatin A, an aspartyl proteinase inhibitor as well as to chelators and a serine proteinase inhibitor.