[The content of the PAMG-1 protein that binds insulin-like growth factor I (somatomedin C) in the blood serum of diabetic patients]. / Soderzhanie belka PAMG-1, sviazyvaiushchego insulinopodobnyi faktor rosta 1 (somatomedin C), v syvorotke krovi bol'nykh sakharnym diabetom.

The study was undertaken to measure PAMG-1 (PP 12, IGEBP-1) that is insulin-like growth factor binding protein in blood sera of diabetic patients. We could show a stable significant (10-fold or more in 54% of patients) increase of PAMG-1 concentrations in patients suffering with insulin-dependent diabetes and a moderate (1.5-2 times) increase of PAMG-1 levels in 80% of patients suffering with non-insulin-dependent diabetes. Significant individual differences of DAMG-1 serum concentrations were also demonstrated (10-230 mg/ml in insulin-dependent and 0-360 ng/ml in non-insulin-dependent diabetes).

[The immunomodulating activity of new muramyl dipeptide derivatives in vitro]. / Izuchenie immunomoduliatornoi aktivnosti proizvodnykh muramildipeptida in vitro.

The action of some new MDP derivatives on functional activity of murine T-lymphocytes and macrophages was studied. The following tests have been used: proliferation of spleen cells in one-way allo-MLC; IL-1 and TNF production by peritoneal macrophages treated with the preparations. The most expressed enhancement of lymphocyte proliferative response in MLC has been exerted by beta C7H15 MDP and beta C16H33 MDP (stimulation indexes 31-69%). beta C7H15 MDP, beta C16H33 MDP and polyacrylamide-MDP (P-MDP) alone or in combination with LPS caused elevated secretion of IL-1 by macrophages. While beta C7H15 MDP was as active as MDP, beta C16H33 MDP and P-MDP manifested increased ability to stimulate IL-1 production in comparison with MDP. beta C7H15 MDP, beta C16H33 MDP, P-MDP and MDP induced similar level of TNF production by murine macrophages. However, simultaneous treatment of macrophages with beta C16H33 MDP and LPS resulted in more significant enhancement of TNF production than combination LPS + MDP.

[Effects of modulators and cytostatics on catabolism of I-125 desoxyuridine in tumors (express-method of antineoplastic modulator screening)]. / Deistvie immunomoduliatorov i tsitostatikov na katabolizm 125I-dezoksiuridina v opukholi (ékspress-metod skrininga protivoopukholevykh immunomoduliatorov).

El-4 and P-815 murine tumor cells labelled by 125I-deoxyuridine or 51Cr were administered in 7-day subcutaneous syngeneic tumors or subcutaneously. At the same time different groups of mice were treated by LPS plus MDP, beta-C7H15-MDP, dexal-MDP, polyacrylamide-MDP-phosphatidylethanolamine, adriblastin or cyclophosphamide. It was shown that cytostatics and immunomodulators significantly delayed catabolism and withdrawing of 125I-deoxyuridine (that has not been incorporated in DNA) from tumor cells. This delay was correlated with the inhibition of tumor nodes growth rate. It is concluded that influence of cytostatics and immunomodulators on catabolism and withdrawing rate of 125I-deoxyuridine from tumor cells relates to their cytostatic effect and may be used at the earliest screening step of immunomodulator analysis.

[Study of the possibility to abolish the action of immunosuppressive factors of tumor cells]. / Issledovanie vozmozhnosti preodoleniia deistviia immunosupressornykh faktorov opukholevykh kletok.

We investigated the efficacy of IL-2, LPS, MDP, TRA, ionomycin and contrykal on proliferation of lymphocytes treated by tumor cell immunosuppressive factors (ISF). IL-2, LPS and/or MDP did not abolish the influence of P815 and B16 ISF on Con A or alloantigen-induced lymphocyte proliferation. TPA and in less extent ionomycin and combination of the above preparations totally abrogated the suppression of Con A-induced lymphocyte proliferation. In inverted experiments Con A abrogated ISF-mediated suppression of lymphocyte proliferation induced by TPA plus ionomycin.

[Histochemical and clinical-diagnostic study of placental alpha 1-microglobulin using monoclonal antibodies]. / Gistokhimicheskoe i kliniko-diagnosticheskoe izuchenie platsentarnogo alpha 1-mikroglobulina s pomoshch'iu monoklonal'nykh antitel.

Five stable hybridomas against placental protein PAMG-1 were obtained. Monoclonal antibodies were not cross reactive with other placental proteins and human serum albumin. The content of PAMG-1 during a physiological pregnancy increased to 40 ng/ml. 23 women with repeated abortions had an increased content of PAMG-1.

[Increase of the production of tumor necrosis factor in endotoxin shock in mice presensitized with sera of tumor-bearing mice or tumor cell factor]. / Povyshennaia produktsiia faktora nekroza opukholi pri éndotoksinovom shoke u myshei, presensibilizirovannykh syvorotkoi myshei-opukholenositelei ili faktorami opukholevykh kletok.

We investigated the phenomenon of increased sensitivity of tumor-bearing mice to endotoxin shock. I/V administration of sera from tumor (EL-4, B16, R815, MOPC-315) bearers or tumoral culture media into intact mice caused the increased sensitivity to lethal action of LPS plus GMDP. Production of TNF in above mice was also significantly increased under the influence of LPS plus GMDP. Sensitivity induced factors in tumor bearing mice sera have mol. weight more than 50 kDa. This action was partially abolished by indomethacin.

[Study of the action of tumor cell immunosuppressive factors on the production of cytokines by lymphocytes and macrophages and the mitogenic activity of interleukin-2]. / Issledovanie deistviia immunosupressornykh faktorov opukholevykh kletok na vyrabotku tsitokinov limfotsitami i makrofagami i na mitogennuiu aktivnost' interleikina-2.

The effect of immunosuppressive factors (ISF) derived from tumor cell lines (mastocytoma P-815, leukosis EL-4 and melanoma B16) on the production of interleukin-1 (IL-1) by macrophages and of interleukin-2 (IL-2) by splenocytes of BALB/C mice was investigated. We could show that treatment of above cells by the tumor products resulted in strong decrease of IL-2 production but did not affect IL-1 secretion. ISF inhibited the proliferation of BALB/C lymphoblasts caused by recombinant IL-2. Thus, one of the significant mechanisms of ISF action seems to be disturbance of monolymphokine cascade of lymphocyte activation.

[Key problems of antitumor immunity and glycoconjugates]. / Kliuchevye voprosy protivoopukholevogo immuniteta i glikokon"iugaty.

Two key problems of the antitumour immunity are considered: 1) very rapid changing of tumour-associated antigens; 2) tumour immunosuppression. Carbohydrate structures of the tumour-associated antigens (mainly glycoconjugates) are changing much more rapidly (hours, days) than the clones of antitumour T-killers proliferate. It is stated that the fundamental question of the nature of the glycoconjugate and endogenous lectin changing is not sufficiently studied. The endogenous lectins of the lymphocyte and macrophage surface are an old recognizing system responsible for a natural cell resistance to the tumour. Stimulation of this system by means of bacterial and syngeneic glycoconjugates is a promising direction in the tumour immunotherapy. Concerning the second aspect, the data are summarized according to which tumour cells produce inhibiting factors, including glycoconjugates, that suppress both proliferation and function of lymphocytes and macrophages. Developing the methods of rehabilitation of the immune system cells with the use of activating glycoconjugates and cytokines is the second important trend in the tumour immunotherapy.

[Lack of species specificity in the action of immunosuppressive factors of tumor cells and absence of competition between them and recombinant interleukin-2 and phytohemagglutinin for lymphocyte membrane receptors]. / Vidovaia nespetsifichnost' deistviia immunosupressornykh faktorov opukholevykh kletok i otsustsvie ikh konkurentsii s rekombinantnym interleikinom-2 i fitogemaggliutininom za retseptory membrany limfotsitov.

We studied some possible mechanisms of action of immunosuppressor factors (ISF) produced by tumor cells on lymphocyte proliferation. ISF of murine tumor cell lines inhibited the mitogen induced proliferation of murine splenocytes as well as human mononuclear blood cells. Normal human mononuclear blood cells or concanavalin A-activated murine spleen cells preincubated with phytohemagglutinin (PHA) or interleukin 2 (IL-2) respectively, were strongly suppressed by ISF in response to these activators. When preincubated with splenocytes or blood cells for 2 h at 4 degrees C following washing, ISF suppressed the lymphocyte proliferation as effectively as when being with cells during all period of cultivation. ISF inhibited mitogen-induced lymphocyte proliferation at low dilutions. There was no competition for lymphocyte membrane receptors between these functionally heterogenic kinds of ISF. Collectively, these results show that ISF acted when being attached to some lymphocyte membrane receptors.

[Activation of cellular immunity in mice under normal conditions and in tumor growth during treatment with glucosaminyl muramyl dipeptide]. / Aktivatsiia kletochnogo immuniteta u myshei v norme i pri opukholevom roste pod deistviem gliukozaminilmuramildipeptida.

In vitro stimulation of mice spleen cells by means of glucosaminyl muramyl dipeptide (GMDP) was accompanied by development of tumor necrosis factor and of interleukin-I. The factor was detected in blood serum only after administration of GMDP simultaneously with lipopolysaccharide. GMDP activated peritoneal macrophages; the phenomenon was evaluated by means of the macrophages ability to kill tumoral cells P815 as well as by interleukin-I production after additional stimulation with lipopolysaccharide. At the same time, an increase in proliferating activity of spleen and bone marrow cells was observed. An increase of middle lifetime and recovery of 24% mice of C57BL/6 strain with leukosis EL-4 were observed after complex treatment of the animals with GMDP, lipopolysaccharide, cyclophosphane and indomethacin.

[Immunoenzyme analysis of placenta-specific alpha 1-microglobulin in the serum of blood donors]. / Immunofermentnyi analiz platsenta-spetsificheskogo alpha 1-mikroglobulina v syvorotke krovi donorov.

An immunoenzyme assay is developed for quantitative estimation of placenta specific alpha 1-microglobulin in biological fluids. The assay is more sensitive as compared with immunodiffusion and radioimmunoassays used previously. Concentration of alpha 1-microglobulin in blood serum of men-donors was found to be 7-30 ng/ml and of women--0.50 ng/ml.

[Humoral mechanisms of the membrano-toxic effects of mastocytoma P815 and leukemia EL4 cells]. / Isledovanie gumoral'nogo mekhanizma membranotoksicheskogo éffekta kletok mastotsitomy P815 i leikoza EL4.

The membranotoxicity activity of P815 and EL4 tumor cells and their humoral factors containing in cultural supernatants and ascitic fluids was estimated. Tumor cells and their humoral factors exert dose-dependent membranotoxicity effect on murine splenocytes and lymphoblasts. Normal murine splenocytes and renal cells have no membranotoxicity properties. Thus tumor cells membranotoxicity effect is carried out by humoral mechanism.

[The therapeutic efficacy of phonophoresis of ribonucleic acid hydrolysate in toxic retinal lesions]. / Izuchenie terapevticheskoi éffektivnosti fonoforeza gidrolizata ribonukleinovoi kisloty pri toksicheskikh porazhennykh setchatki.

Experiments on 82 rabbits (162 eyes) have shown that RNA hydrolysate phonophoresis possesses a pronounced protective action by stimulating a rapid cupping of metabolic disturbances and a restoration of the chemical state of cellular elements of the retina in a relatively remote terms after the introducing of a monobromoacetate inhibitor (within first 3 days). Experimental therapy beginning 10 days after the introducing of monobromoacetate, i. e. in the period when, besides metabolic disturbances histomorphologic changes were also seen, considerably stimulated activation of compensatory-inflammatory processes. The investigations carried out allow to recommend RNA hydrolysate phonophoresis for clinical examination in dystrophic diseases of the retina.

[The stimulating action of lipopolysaccharide and muramyl dipeptide on the activation of mononuclear cells in human peripheral blood by recombinant interleukin-2 in vitro]. / Stimuliruiushchee deistvie lipopolisakharida i muramildipeptida na aktivatsiiu mononuklearov perifericheskoi krovi cheloveka rekombinantnym interleikinom-2 in vitro.

Muramyl dipeptide (MDP) and lipopolysaccharide (LPS) were effective in augmentation of killer cells generation from human peripheral blood mononuclear cells (PBMC) in response to recombinant human interleukin-2 (IL-2). Pretreatment of PBMC with combination of LPS and MDP resulted in most significant their proliferation stimulated by IL-2. Thus our results show the enhancement of PBMC sensitivity to IL-2 by action of LPS, MDP and most of all by their combination in vitro.

[Interferon production and natural killer activity induced by staphylococcal enterotoxin in mouse spleen cells]. / Produktsiia interferona i aktivnost' estestvennykh killerov, indutsirovannykh stafilokokkovym énterotoksinom v kletkakh selezenki myshei.

After a single intraperitoneal inoculation of C57BL/6 mice with enterotoxin A of Staphylococcus aureus (SEA) the activity of natural killers (NK) increases and phase change of interferon production by spleen cells upon reinduction in vitro occurs. Multiple daily inoculations of mice with SEA maintain the activity of splenic NK at a similar high level. With an adequate control (multiple administration of the medium) NK activity was maintained at the same high level. Interferon production by spleen cells of mice which were multiply inoculated with the medium upon reinduction in vitro was the same as in the control animals, whereas after multiple inoculations of mice with SEA, spleen cells in vitro produced lower amounts of interferon.