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Biomedical subjects

A P Kostromin

Publications and source records attributed to A P Kostromin.

At least 19 recordsLinked to original sources

[Ca(2+)-dependent regulation of T-lymphocytes in experimental tuberculosis].

Ca(2+)-exchange kinetics and the content of membrane and cytoplasm fractions of calmodulin in the splenic T-lymphocytes of guinea pigs with experimental tuberculosis were studied. A tuberculous process was accompanied by the changes in the Ca2+ exchange kinetics in the form of T-lymphocyte oversaturation with Ca2+ ions which in the end leads to an inhibition of the functional status of the immunity T system. PPD, a specific allergen, brought the capacity of T lymphocytes down in relation to the cellular Ca2+ exchange, presumably causing the normalization of the immune response.

Animals↗

Pemphigus antibodies and shedding snake serum enhance susceptibility of epidermal keratinocytes in natural cytotoxic reactions.

In order to clarify the role of natural cytotoxicity (NC) in the damage of epidermal keratinocytes (EK) in pemphigus vulgaris (PV) we used the direct 51Cr-release assay in studying the cytotoxic activity of large grandular lymphocytes (LGL), obtained from 34 acute PV patients and 19 healthy donors against EK of PV patients, donors, intact newborn BALB/c mice and mice with experimental PV, shedding and non-shedding grass snakes. We also investigated the effect of pemphigus antibodies and shedding snake serum protein (SSSP) upon EK sensitivity to cytotoxic effects of NC effectors. In other experiments, studied were the amount of serine proteinase secreted by donor LGL in the presence of membrane antigen of antibody- or SSSP-transformed EK, and direct effect of pemphigus antibodies and SSSP upon the release of radioactive label and endoproteinases from EK. It was found that EK, which had interacted with pemphigus antibodies or SSSP, became a sensitive target for NC effectors. Membrane antigen of antibody- and SSSP-transformed human, murine and snake EK induces the secretion of endproteinases by NC effector cells. The conclusion was made that the effect of both pemphigus antibodies and SSSP on EK resulted in the emergences of a new antigen on EK cellular membrane which is recognized by NC effectors and plays the role of the ligand in receptor/ligand interaction between LGL and their targets.

Animals↗

Pemphigus and pemphigoid epidermocytes interfere with interleukin cascade reactions.

The aim of this study was to reveal the origin of interleukin cascade reaction disturbances in pemphigus vulgaris (PV) and bullous pemphigoid (BP). We investigated the influence of culture supernatant of epidermal keratinocytes from the skin of PV and BP patients on functional activity of donor peripheral blood mononuclears. It was found that epidermal keratinocyte culture supernatant in the acute phase of PV and BP decreased the ability of mononuclears to proliferate in response to PHA and Con A, secrete interleukin-1 and interleukin-2, and absorb an exogenous interleukin-2. Such inhibitory effect was far less pronounced in epidermal keratinocytes obtained from PV and BP patients at the remission stage. Epidermocytes from healthy subjects stimulated the immunocompetent cell activity. The results obtained indicate that epidermal keratinocytes in the acute phase of pemphigus and pemphigoid produce a putative soluble factor(s), which may be the origin of the immunodeficiency in PV and BP patients.

Adult↗

[Effect of thymic immunomodulators on the system of cyclic nucleotides of splenic T-lymphocytes after BCG vaccination].

The experiments on guinea pigs was performed to study the effects of thymogen , thymalin and vilosene on the activity of cAMP, cGMP, adenylate cyclase, guanylate cyclase, cAMP- and cGMP-phosphodiesterases in T lymphocytes during BCG vaccination. It was shown that the disease was accompanied by increased activity of enzymes of anabolism and catabolism of cyclic nucleotides. Thymogen and thymalin mainly activated the synthesis of cGMP, thus causing the shift of cAMP/cGMP value below the reference level. At the same time vilosene increased this value in the process of a repeated BCG injection.

Adenylyl Cyclases↗

Clinical and laboratory evaluation of hemocarboadsorption in autoimmune bullous dermatoses.

Hemocarboadsorption (HCA) with the following immunosuppressive therapy was used to treat 48 patients with pemphigus vulgaris (PV) and 31 patients with bullous pemphigoid (BP) in the acute phase. The levels of autoantibodies, eicosanoids, endoproteases and their inhibitors as well as interleukin (IL) 1 and IL 2 production and absorption of exogenous IL 2 were examined in the treatment dynamics. The therapeutic effect of HCA was displayed in prompt disease remission in 43 PV and 29 BP patients. Clinical improvement was accompanied by antibody elimination and interleukin cascade reaction normalization. HCA resulted in growth of patients' serum immunosuppressive activity. It was concluded that HCA has some immunoregulatory effect (Int J Artif Organs; 1990: 13: 181-88).

Adsorption↗

Autoreactive cytotoxic T lymphocytes in pemphigus and pemphigoid.

In order to know whether effector cells are capable of recognizing the epidermal targets in pemphigus vulgaris (PV) and bullous pemphigoid (BP), non-adherent cells (NAC) of peripheral blood from 27 primary PV, 19 BP patients and 12 healthy volunteers were used in cytotoxic tests. Autologous, allogenic and murine epidermal keratinocytes as well as autologous and allogenic fibroblasts were employed as targets. Total esterase activity of serine proteinases was measured in supernatants of samples and the results obtained were compared with the data received in 51Cr-release assay. These two techniques yielded similar results. The effector cells of PV and BP patients were found to lyse the epidermal target cells without presensitization in vitro. Epidermal cells from involved and uninvolved skin of PV patients, as well as from perilesional skin of BP patients, were highly sensitive to cytotoxic effect on the part of effector cells. The NAC activity in BP was higher than in PV. On the one hand, the obtained data suggest that PV and BP patients develop autoreactive cytotoxic T lymphocytes, sensitized to pemphigus and pemphigoid antigens, respectively, and on the other hand that epidermocytes in pemphigus and pemphigoid patients turned to be more fragile compared to normal human epidermal keratinocytes. It was supposed that cell-mediated cytotoxic reactions are probably related to enhanced proteolytic activity in the site of bullous eruption.

Adult↗

The effect of experimental haemocarbofiltration upon activity of mononuclear cells from normal and autoimmune patients.

We examined the functional activity of peripheral blood mononuclears (PBM) of 18 healthy subjects, 18 patients with pemphigus vulgaris, 12 with bullous pemphigoid and nine with discoid lupus erythematosus, after haemofiltration on carbon haemo-adsorbents of 'SKN' type. Proliferation in the response to PHA and Con A, for IL-1 and IL-2 production, and exogenous IL-2 absorption were assayed. The presence of IL-1 and IL-2 inhibitors in haemocarbo-adsorbent eluants was shown. We also investigated the natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities. We found significant increases of both lectin-dependent proliferation and of interleukin production by PBM of autoimmune patients after two to four perfusions. The ability of PBM to absorb IL-2 displayed a steady growth after each perfusion, whereas increase of NK and ADCC activities was observed after not less than six passes. The enhancement of PBM functional activity in autoimmune patients was accompanied by accumulation of IL-1 and IL-2 inhibitors in the sorbent. It was concluded that therapeutic effects of haemofiltration in autoimmune diseases involve improvement of immunocompetent cell function due to their deligandization by activated charcoal.

Adult↗

Mediators of inflammation in blister fluids from patients with pemphigus vulgaris and bullous pemphigoid.

Blister fluids from 39 previously untreated patients with pemphigus vulgaris (PV) and 28 patients with bullous pemphigoid (BP) were tested for the presence of inflammatory mediators. Blister fluids from patients with PV and BP showed interleukin 1 (IL-1)- and interleukin 2 (IL-2)-like activity and contained prostaglandin (PG) E2, F1 alpha, and F2 alpha, thromboxane B2 (TB2), leukotriene (LT) B4 and C4, serine esterases, and proteolysis inhibitors. Pemphigus blister fluid was distinguished by high IL-1-like activity, proteolytic activity, and high concentrations of TB2 and LTB4, while pemphigoid blister fluid was characterized by higher IL-2-like activity, antiprotease activity, and high PGE2 concentration. We also determined that the content of mediators of inflammation varied depending on the duration of blister development. In both PV and BP, the initially high IL-1-like activity, amount of serine proteases, and concentrations of PGF2 alpha, TB2, LTB4, and LTC4 decreased by the fifth day of blister existence, whereas antiprotease activity as well as PGE2 and PGF1 alpha concentrations gradually increased as blisters developed. These findings suggest certain differences in the character of the bullous inflammatory process in pemphigus and pemphigoid.

Adult↗

Cytotoxic proteases in blister fluid of pemphigus and pemphigoid patients.

Investigation of blister fluid (BF) from 49 pemphigus vulgaris and 27 bullous pemphigoid patients revealed direct interrelation between proteolytic and cytotoxic activities of BF. Human epidermal keratinocytes proved to be more sensitive to the cytolytic effect of BF as compared to human endotheliocytes and fibroplasts. Epidermal keratinocyte cultivation in patients' BF led to proteolytic activity enhancement in culture supernatant. Inasmuch as cytotoxic and proteolytic activity of BF sharply decreased under the effect of inhibitors of serine proteinases only, it was concluded that proteolytic enzymes of this class play the role of a "cytotoxic factor" causing the lysis of epidermal cells in pemphigus and pemphigoid.

Blister↗

Serine proteinase esterolytic activity as an assay of cytotoxic reactions.

A method for assessing cytotoxicity in cell-mediated cytolysis as well as in reactions of natural killing and antibody-dependent cellular cytotoxicity through assaying the total esterolytic activity of serine proteinases (TEASP) is both sensitive and specific. TEASP levels in all cytotoxic tests correlated with the percentage of lysis of 51Cr-labelled target cells. The method permits the differential assessment of endoproteases in both the effector cell and the target cell.

Adult↗