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Aim: To ascertain the role of high antibodies (Ab) titers to microsomal antigen (MA) of the thyroid in clinical manifestations of cytopenic syndromes., Material and Methods: Clinical data are presented on 144 patients with depressed hemopoiesis having different levels of thyroid Aab., Results: When the titer was significantly elevated (41% patients with immune cytopenias), hematological malignancies run with recurrences, remission is rare. Treatment of the thyroid pathology improves hematological indices in some cases though does not reduce titers of Ab thyroid MA., Conclusion: Detection of autoimmune pathology of the thyroid is necessary not only for specification of the concurrent process diagnosis but also for initiation of adequate combined treatment.

In experiments on mice F1 total exposed to gamma-irradiation at the 5.0 Gy, showed that a intraperitoneal injection neogen at the dose 10 micrograms/kg oue time at the day and night during the 8 days after irradiation results in recovery of the number blood platelets and time issue of blood from standard wound to normal level on the week by compare with irradiated control animals.

Aim: To study the level of thyroid antibodies (TAB) in blood diseases., Material and Methods: TAB levels dynamics was studied in 413 patients with hematological diseases., Results: Increased incidence of cases with high Ab titer to thyroid microsomal antigen was found. High and moderate titers were revealed in 33% of all examinees, including 41%, 22%, 32% and 29% among patients with immune cytopenia, chronic lymphoid leukemia, generalized mature-cell lymphoma and myeloproliferative diseases, respectively. These high and moderate titers were rather stable. In 15% patients Ab were elevated insignificantly, this rise being unstable., Conclusion: Stable high titers of antibodies to thyroid antigens point to increased incidence rates of concomitant autoimmune hyroiditis in patients with blood diseases.

The effect of the synthetic peptide IEW (Neogen) with immunomodulating properties on postradiation recovery of haemopoiesis was investigated. We have shown that Neogen is a potential stimulator of haemopoiesis. The administration of Neogen after irradiation shortened duration of period of the recovery of the compartment of CFU-S-8 and the amount of bone marrow cells. The comparision of the effects of Neogen and GM-CSF (Leucomax) and G-CSF (Granocyte 34) have shown that the targets for these agents are probably different: polypotent CFU-S-for Neogen, and CFU-GM-for GM-CFS. Based on the results, we suggested the mechanism of Neogen effects on heamopoiesis.

It was studied on mice how prior whole body hyperthemia affects a colony-forming ability of bone marrow after gamma-irradiation. It was found that heating of the animals (42 degrees C, 10 min) 18-22 h before their total irradiation (4 Gy) increases 2-fold the level of CFUs8 and CFUs12 determined in the spleen exotest. The induced radioresistance correlated with accumulation of heat shock proteins, HSP70 and HSP25, in tissues of preheated mice. Injection of quercetin (a selective inhibitor of the heat shock protein synthesis) 0.5 h before the heating fully abolished both the subsequent heat shock protein accumulation and the rise in CFUs populations as compared with control. It is suggested that heat shock proteins, whose expression increases in response to hyperthermia, can play a role of endogenous radioprotectors. Possible mechanisms of their protective action under irradiation are discussed.

Synthetic polypeptide D-(iEW) (Thymodepressin) was shown to reduce the bone marrow CFU-S in the S-phase of cell cycle. Apparently, due to this property the agent being administered 2 days before the irradiation with 4 Gy causes a prominent restoration of the CFU-S population afterwards. The 3-5 times higher value of this parameter as compared to the control (irradiation only) is likely to be connected to the increased "survival" of the Thymodepressin-protected CFU-S after the treatment with ionizing irradiation.

Th distribution of autoimmune thyroiditis in the patients with diseases of blood system was investigate. The attribute of autoimmune thyroiditis was revealed by the detection of antimicrosomal antibodies. It was established that the autoimmune thyroiditis are more often in patients with various hematological diseases than in control group. It is supposed that the increase in frequency of some hematological diseases in residents suffered from the Chernobyl accident can be defined not only by the influence of the radiation on blood system, but also can be connected with damage to thyroid glands.

The substantial decrease of free natural antibodies reacting with histones under effect of 4 Gy total dose radiation in sera of healthy animals was established. It is supposed that the binding of natural antihistone antibodies with histones reduces the cytotoxic reactivity of histones released from cells under effect of ionizing radiation. It was determined that complexes of antihistone antibodies and histones get the ability to react with DNA. The possible biological role of these complexes is discussed.

Efasol and potassium tetrachloropalladate being injected into mice prior to irradiation with a dose of 150 sGy increase the colony forming activity of animals bone marrow cells transplanted in lethally irradiated recipient mice. The palladium presence in such compounds is supposed to be a reason of radioprotection. Upon the combined application of potassium tetrachloropalladate and irradiation of mice with an adaptive dose of 5 sGy a potentiation of individual effect of each separate agent to increase CFUs resistance against the consequent irradiation was observed.

The chromosome dicentric aberrations in the lymphocytes and levels of antibodies to human thyroid microsomal antigen in the serum of the children lived in the area of Bryansk Province suffered from the Chernobyl accident was examined. Correlation between those tests was not estimated: the autoantibodies were revealed in group with dicentrics and without those in 4.0% and 4.5% of cases correspondingly. Antimicrosomal antibodies were revealed more frequently (5.0%) and in higher titers in the children from the more polluted Bryansk Province than in those from Kaluga Province (3.1%). These data can testify about the role of inside radiation of thyroid gland in appearance of autoimmune thyroiditis signs.

An important peculiarity of the Chernobyl catastrophe is the discharge into the atmosphere of tremendous amount of radioactive iodine and, as a result, selective damage of the thyroid in children from the affected areas. The most dangerous consequence is the thyroid cancer. The analysis of the situation when children's thyroids were subjected to irradiation shows that tumors can most frequently develop as late as 20-30 years after irradiation. There are reasons to believe that tumors are induced by low dose of irradiation. The most important factor in development of pathologies is for sure the age of the children of the moment of irradiation. A well-known consequence of the impact of radiation on the thyroid is the lymphocyte thyroiditis. The interest to this pathology is determined by the fact that it substantially increases the probability of development of various haematologic diseases (lympho- and myeloproliferative neoplasms).

Changes in the levels of free myoglobin and lipid peroxidation products (hydroperoxides and malonic dialdehyde) were studied in cancer patients. Their baseline levels were found to be higher in patients with cancer of the lung, large bowel, and rectum than those in controls, which indicates higher lipid peroxidation, which led to the destabilization of cellular membranes and seems to cause baseline hypermyoglobinemia. There was a drastic rise in the levels of free myoglobin in the first 24 postoperative hours. The duration and severity of hypermyoglobinemia were much higher in the complicated than uncomplicated postoperative period. There was a less rise in malonic dialdehyde concentrations, whose peak was observed on days 1-2 postsurgery. The content of hydroperoxides decreased in the first 24 postoperative hours and began gradually increased from day 2. The correlation between the concentrations of myoglobin and malonic dialdehyde suggests that there is an association between hypermyoglobinemia and the status of cellular membranes.

A simple method for detecting pathogenic microorganisms in clinical samples has been developed. This method is based on identification of specific nucleotide sequences by Pt[(dien)Cl] Cl-labelled DNA probes and simultaneous immunochemical control of total DNA content in each clinical sample. Such control is provided by a simple semiquantitative enzyme-linked immunoassay using antibodies to denatured DNA; its implementation requires the same procedures, materials and solutions used in the hybridization analysis. The information about the DNA content in the sample is necessary for adequate interpretation of results of hybridization analysis. Pt[(dien)Cl]Cl for the probe and affinity antibodies to DNA-Pt[(dien)Cl] Cl and rabbit immunoglobulin antibodies conjugated to phosphatase for DNA hybrid detection were used. The results of hybridization analysis show a good correlation with those of the PCR-test. The method is simple, relatively inexpensive and fit for population monitoring.

The time course of free myoglobin content and the rate of lipid peroxidation were simultaneously studied in cancer patients. The initial concentrations of myoglobin, hydroperoxides and malonic dialdehyde (MDA) were found to be higher than the control values, thus suggesting the increased rate of lipid peroxidation in these patients, which was responsible for destruction of cell membranes. Within the first 24 hours after surgery, there was a drastic release of myoglobin, its levels being sometimes higher in case of a complicated postoperative period than those in its smooth course. The increase in content of MDA was less marked, by reaching its maximum on days 1-2. The postoperative levels of hydroperoxides was considerably decreased, yet it began gradually increasing on day 2. The rather high correlation coefficients between the content of myoglobin and MDA suggest that there is a relationship between hypermyoglobinemia and the state of cell membranes. However, surgical intervention, enhancing lipid peroxidation, concurrently activates the mechanisms aimed at maintaining cell homeostasis.

Initial hypermyoglobinemia was found in patients with cancer of lungs, large intestine and rectum. Within early postoperational period under favourable conditions moderate increase in content of free myoglobin was detected, most pronounced in patients with lung cancer. Maximum concentration of myoglobin was estimated within first postoperational day, normalization occurred within 3-4 days after the operation. In patients with postoperational complications (peritonitis, pneumonia, sepsis, etc) increase in content of myoglobin was more distinct (1.6-2-fold) and was maintained within the longer period. Increase in content of blood plasma myoglobin occurred usually before manifestations of clinical symptoms related to postoperational complications.

A very strong electroosmotic counterflow was produced on nitrocellulose membranes during isotachophoresis in a system of 0.06 M Tris-HCl (pH 6.7) as the leading electrolyte and 0.012 M Tris-beta-alanine (pII 8.6) as the terminating one. This counterflow was equal in rate and opposite in direction to the migration of the Cl-/beta-alanine boundary. The rate of counterflow was much higher than the rate of migration of any organic anions, including different proteins. Double-stranded and single-stranded DNA or its adducts were fixed on the nitrocellulose membrane, and the membrane was blocked with unrelated proteins. DNA-binding proteins, namely antibodies to DNA, followed by peroxidase-conjugated anti-IgG, were introduced into the counterflow, which transferred them one after another to the DNA spots. Thus, sequential binding and washing was performed automatically. In this way, antibodies were detected to ds- and ss-DNA, to BrdU-DNA, to Z-DNA, to biotinylated DNA and DNA modified with trans-Pt, as well as development of biotinylated DNA dots by steptavidin-peroxidase.

Radiotherapeutic activity of histone fractions H1 and H2A/H2B were studied. It was demonstrated that both fractions are able to reduce the damaging effect of ionizing radiation on spleen colony forming unit (CFU-S) population. Histone preparations stimulated colony-forming activity of bone marrow cells exposed to dose of 0.5-3.0 Gy both in the case of incubation with preparations and intravenous or intraperitoneal administration into recipients of irradiated cells. The effect of histones and accessory thymocytes on CFU-S population is compared.

For evaluation of the possibility of the appearance of autoimmune thyroiditis in children and juveniles lived in the areas of Kaluga Province [correction of region] suffered from the Chernobyl accident the content of antibodies to human thyroid microsomal antigen was investigated. Percentage of positive sera varied from 4.8% to 1.2% during 6 years. There is significant difference in the frequency of the antibody appearance between persons suffered from radioactive iodine and unsuffered ones. Correlation between levels of antimicrosomal antibodies and radiation dose obtained from incorporated radioactive iodine was not estimated.

Monofunctional platinum compound [Pt(dien)Cl] Cl and high-affinity antibodies against DNA-[Pt(dien)Cl]Cl were suggested for non-radioactive hybridisation analysis of DNA. The simple labelling procedure was based on mixing the reagents followed by the incubation for 2 h at 60 degrees C. The sensitivity and specificity of the technique were sufficient to detect 10 fg DNA in dot-hybridisation without cross-reaction with 10-fold excess of a heterologous DNA. This technique permits genome libraries screening.

Ideas about the thyroid gland diseases development in people suffering from the Chernobyl accident explaining the absence of straight dose dependence of pathologies raise from the irradiation were elaborated. It is supposed that the probable reason for a number of these pathologies can be the inadequate and inopportune preventive iodine administration. It is known that significant amount of iodine being incorporated in children or persons with compromised thyroid gland could lead to a number of pathological changes, primarily to autoimmune thyroiditis which is a reason of other consequent pathologies of this organ. The principal mechanism of the process can be presented as following: iodine transformation (oxidation) in the thyroid gland accompanies with the generation of considerable quantities of various radicals imitating the radiation damage. This hypothesis allows to consider the children suffered from the Chernobyl accident with autoimmune thyroiditis as belonging to the group of risk as the literary data testify that the presence of autoimmune thyroiditis rises 75 time the risk of malignant lympho-proliferated diseases appearance. A simple immunological method of autoimmune thyroiditis diagnostics was developed which informativity is comparable with the method of ultrasound diagnostics. Serial production (the antibodies to microsomal fraction of thyroid gland) was organized. This method can be used in screening investigations.

The radiotherapeutic effect of thymogen (Glu-Trp) and thymohexin (Arg-Lys-Asp-Val-Tyr-Arg) synthetic peptide immunomodulators was investigated. Both thymogen and thymohexin were demonstrated to be able to reduce the damaging effect of ionizing radiation (1 Gy) on CFU-S by half. The treatment by these preparations after irradiation at dose of 4 Gy leads to more intensive restoration of CFU-S population as compared with control.

The data concerning the reasons of CFU-S radioresistance increase after low dose irradiation of mice were obtained; the reparation processes in CFU-S adapted by low dose irradiation were shown to be more active than in intact ones. Colony formation increase was demonstrated to be more pronounced in adapted animals when they had been injected by 50 mcg of synthetic polyribonucleotide PolyI-PolyC two days before irradiation in challenge dose. The thymogen immunomodulator administration to adapted and intact donor animals leads to the increase of colony yield in equal extent.

Whether accessory T cells can be replaced by the synthetic immunomodulators thymogen (Glu-Trp) and thymohexin (Arg-Lys-Asp-Val-Tyr-Arg) was studied. The latter immunomodulator was found to show a 3-fold increase in splenic colony formation after incubation of bone marrow cells with rabbit antimouse brain serum (RAMBS). The former preparation failed to show the same action. Its effect was close to that of thymocytes. When the recipients exposed to lethal irradiation were administered the RAMBS-treated bone marrow cells and one of the peptides, it was shown that in concomitant administration, thymohexin and thymocytes lost their ability to restore colony formation by RAMBS-treated bone marrow. Thymogen did not suppress the stimulating activity of thymocytes. It is suggested that the differences observed between the tested peptides in their ability to recover colony formation were determined by their structure.

Ultrasound investigations of the thyroid gland and determinations of microsomal antibodies have been performed in persons who lived in the town of Korosten (Zhitomir Region) during the Chernobyl accident. A high correlation has been found between ultrasound and immunological results. The immunological screening of the population suffered from the Chernobyl disaster might be successfully used for the autoimmune thyroiditis detection. These data complete those obtained by the ultrasound tests.

Highly positive by Farr assay, native DNA-binding fraction was derived from commercial normal human gammaglobulin preparations by ion-exchange chromatography. Human serum immunoglobulins of any isotype were not involved into this binding. The existence of nonimmunoglobulin factor primarily binding native DNA and intermediating DNA-Ig interaction is assumed.

Antitumor and antimetastatic properties of N-methyl formamide--an agent related to differentiation of tumoral cells and unithiol, official detoxicating drug containing SH-groups were studied in C57Bl/6 mice inoculated with Lewis's lung carcinoma. The drugs were administered intraperitoneally into animals at days 1, 4, 7, 13 and 16 after carcinoma inoculation and their effects were evaluated at day 19. Single administration of unithiol, 5 mg/kg body weight, did not affect tumor growth and metastases spreading. At the same time, N-methyl formamide (single administration of 300 mg/kg body weight) inhibited tumor growth and decreased 5-fold an amount of spontaneous metastases in lungs. However, the antitumor and antimetastatic activities of N-methyl formamide were decreased after simultaneous administration with unithiol. Importance of SH-groups in therapeutic effects of N-methyl formamide is discussed.

On the basis of the authors' own data and the literature it has been inferred that the key principles of the haemopoietic system regulation are similar to those of the immune system. The cells of a lymphoid origin are found, which implement helper and suppressor functions with respect to early haemopoiesis precursors; the influence of lymphokines on this compartment under the effect of radiation is described. Disturbances in the haemopoiesis system regulation, that result from various damaging effects, might be corrected by T-lymphocytes and lymphokines. The data obtained suggest that the formation of splenic colonies is the result of the interaction of some cell populations. That is why many radiobiological characteristics of CFUs may be attributed to partner cells (for instance, T-lymphocytes).

A monoclonal antibody (IgG) has been produced that binds to DNA modified with osmium tetroxide and 2,2'-bipyridine and does not react with unmodified DNA and modified or unmodified RNA and proteins. The reaction specificity is due to the presence of the modified deoxythymidine residue within the epitope. Possible use of the antibody for studies of DNA structure and detection of cDNA probes is discussed.

Subpopulations of auto-antibodies to DNA were isolated by affinity procedures from sera of two patients with SLE and from IgG of healthy donors after ion-exchange chromatography ("hidden" auto-antibodies). It was found that two subpopulations of auto-antibodies are present in SLE sera just as fractions of "hidden" auto-antibodies consist of three subpopulations. The dissociation constants were measured by ELISA for the interaction of all subpopulations of auto-antibodies to DNA. It is shown that KD are very high and identical no matter of whether they were prepared from SLE sera of from IgG of healthy donors. The analogy of two types of auto-antibodies (SLE auto-antibodies and "hidden" auto-antibodies) is discussed in this paper.

The "masked" autoantibodies with polyspecific activity were found in the serum of healthy donors. It is shown that these antibodies are able to react with antigens after the ion exchange chromatography with QAE-sephadex. It was found that these "masked" antibodies are able to cross-react with DNA and lipopolysaccharides of wide-spread species of bacteria. The possible role of these antibodies as in protection of organism from the external antigens as in the origin of autoimmune diseases is discussed.

DNA modified by trans diaminedichlorplatinum-II (transDDP) has been suggested as an effective probe for non-isotopic hybridization and high-specific anti-DNA-transDDP antibodies with horse radish peroxidase or alkaline phosphotase conjugated antibodies to rabbit Ig and protein A-peroxidase - for hybrids visualization. This method allows to detect 2 pg/mm DNA.

Rabbit antisera elicited against calf thymus DNA modified cis- and trans-diaminedichlorplatinum II (DDP) [Pt/nucleotide ratio - 0.1] contain antibodies specific for Pt-modified DNA immunogen. A specific antibody against DNA-cisDDP and DNA-transDDP was obtained by affinity chromatography. In the ELISA, 3.10(-1 6) mol Pt per micrograms DNA was determined. The epitope structure was determined by using DNA modified with cisDDP and transDDP.

Free Ca2+ concentration in thymocytes increased 0.5-1.5h after gamma-irradiation (10 Gy) as was measured by Quin-2AM fluorescent probe. Cycloheximide, a protein synthesis inhibitor, suppressed Ca2+ increase and inhibited radiation-induced thymocyte death. EL-4 thymoma cells did not exhibit any changes in free Ca2+ concentration and interphase death after gamma-irradiation. It is believed that the radiation-induced increase of free Ca2+ concentration in thymocytes may induce their death.

The syngeneic thymocytes increase the efficiency of spleen colony formation and proliferative activity of CFU-S derived from fetal liver on 13th-16th day of gestation and CFU-S from long term bone marrow culture. The thymocytes effect spleen colony cells. These data indicate that T-cell-CFU-S interaction in spleen colony formation have a physiological character.

Effect of polyanions on reaction of the Ig from sera of patients with systemic lupus erythematosus and scleroderma with cellular proteins was studied by immunoblotting. It has been shown that dextran sulfate, heparin, denatured DNA and poly I inhibited the binding of autoantibodies with some polypeptides. The molecular weight of these antigens was determined. The molecular mechanism of immunological reactions studied and it's role in pathogenesis of autoimmune diseases is discussed.