Biomedical subjects
Publications and source records attributed to M A Tikhonova.
The effects of acute and chronic imipramine treatment on the degree of catalepsy were compared in GC rats genetically predisposed to catalepsy. We recorded the time over which the rats remained in a vertical position they were placed. As differentiated from acute treatment, chronic administration of imipramine dose-dependently decreased the time of freezing in GC rats.
The phenotypic and functional properties of T cells were evaluated in patients with tuberculin anergy and a possible role of anergic T cells in the development of immune deficiency in pulmonary tuberculosis (PT) was studied. The profound decrease (more than 50%) depressed T-cell proliferation in PPD-stimulated cultures was shown to be recorded in 44% (59/134) patients with PT. PPD hyporesponsiveness was associated with the low proliferation of anti-CD3 and SEB-stimulated proliferation of a healthy donor's mononuclear cells evidencing the enlargement of anergic T cells with a suppressive activity in PT. A PPD-stimulated response in healthy donors was under the negative control of CG25-positive cells. In the PPD-anergic patients, there was a significant increase in CD4+CD25+ T cells that were inversely correlated with the PPD-induced proliferative response. The development of tuberculin anergy was more pronounced in patients with drug resistance. The intensity of a PPD-stimulated response in patients with tuberculin anergy may be restored in the presence of exogenous interleukin-2.
Thyroid dysfunction is associated with mental disorders. The present study was aimed to reveal the effects of experimental decrease and increase of thyroxine level on expression of two types of extensive freezing: spontaneous and pinch-induced catalepsy, in Wistar rat males. Chronic administration of thyroxine synthesis inhibitor, propylthiouracil (5 mg/kg/day, 28 days), markedly decreased plasma hormone level and at the same time produced a significant increase in percentage of spontaneously cataleptic animals and immobility time, but had no effect on the expression of pinch-induced catalepsy. On the contrary, chronic thyroxin (0.1 mg/kg/day, 28 days) treatment produced no effect on spontaneous catalepsy expression, although it significantly increased percentage of cataleptic animals and immobility time of pinch-induced catalepsy. The results suggest that both the thyroid hormone deficit and excess provoke catalepsy in rats but enhance different forms of freezing reaction.
Rats selected by predisposition to catalepsy showed decreased level of 2A-serotonin receptor mRNA in the frontal cortex in comparison with Wistar rats (p<0.05). Chronic administration of tricyclic antidepressant imipramine hydrochloride 2-fold increased the content of receptor mRNA in genetically cataleptic rats (p<0.001) and did not change this parameter in Wistar rats. These results prompted us to revise current notion on the mechanisms of chronic effect of imipramine on 2A-serotonin receptors.
The investigation was concerned with assaying immunity and evaluating the role played by monocytes and tumor cells in the formation of T-cell dysfunction in malignant glioma (MG). The study group included 28 patients with anaplastic astrocytomas (n = 18) and glioblastomas (n = 10). MG patients showed significant changes in the numbers of CD16+ NK-cells and HLA-DR monocytes as well as lowered levels of HLA-DR expression on monocytes and proliferative response of T-lymphocytes as compared with both standard and alternative pathways of activation. Monocytes and macrophages suppressed T-cell activity due to production of prostaglandins E2 in such patients. Enhanced immunosuppression was also reported in 24-hour supernatants of tumor cells. Immune disorders were shown to involve apoptosis-independent mechanisms. Hence, despite the immune privilege of the brain, immunocompetent cells crossed blood-brain barrier and counteracted with tumor cells. As a consequence, monocyte function and cellular cooperation dropped while production of immunosuppressive factors rose, and T-cell dysfunction was brought about through apoptosis-independent mechanisms.
The aim of the work was to develop accessible methods of laboratory diagnosis of the systemic inflammatory reaction, based on an assessment of biological (inflammatory and immunosuppressive) activity of serum of surgical sepsis patients (n = 104). The investigation has shown that surgical sepsis patients are characterized by marked immune dysfunctions, immunosuppressive bioactivity of blood serum being detected in most patients (in 65.6%) beginning from the earliest stages of the development of the sepsis process. It was found that in patients with dominating suppressive activity of serum the immune disturbances were more pronounced and in every second case they were of combined type. The authors propose to use the degree of the immunosuppressive potential of serum factors as the key classification sign determining the presence of CARS-positive or CARS-negative phenotype in such patients. The results obtained suggest that it is expedient for complex therapy of surgical sepsis to include immunocorrection aimed at the weakening of immunosuppresive action of antiinflammatory mediators and shift of the balance towards the reinforcement of activity of proinflammatory ones (IL-12, IL-1) and Th-1 cytokines (IL-2, IFN-g).
T-cell apoptosis and anergy as possible causes of impaired antigen specific responses and their subpopulation targets in patients with pulmonary tuberculosis were investigated. A decrease in PPD-stimulated proliferative responses were revealed in 43% of the examinees. The impaired PPD response was shown to be associated with both increased lymphocytic apoptosis and the arrest of cell cycle progression. CD4 and CHD8 T cells underwent apoptosis in PPD-stimulated cultures. Whereas a moderate apoptosis of CD4 cell could occur in PPD-reactive patients, accelerated apoptosis of CD8 cells developed only in PPD-unresponsive group. Both T-cell subpopulations displayed a decreased count of cells in S,G2/M phases of a cell cycle. Similar to apoptosis, the anergy of CD8 T cells was typical of PPD-unresponsive patients. Elevated apoptosis and anergy of CD4 and CD8 T cells in vitro were accompanied by a decline in the proportion of T cells and their subpopulations in patients with impaired PPD responses.
Two methods of administration of Roncoleukin were used as two subcutaneous injections in dose of 500,000 units with a 3 day interval and in the regimen of extracorporeal immunotherapy. The use of Roncoleukin resulted in the clinical improvement in 83% of patients and in the detoxicating and immunocorrecting effects in 77.3 and 60% respectively which was reliably different from analogous indices (33.4%, 45% and 7.5%) in the placebo group. Other values of the prognosed lethality being equal, the real 28-day lethality in the placebo group was 21.5%, while the using of Roncoleukin allowed the level of lethality of patients with surgical sepsis to become 3.8 times lower, including the subgroup of patients with severe sepsis from 50 to 13.6%. The trials performed showed the drug Roncoleukin to be endurable and not toxic and allowed to determine the indications and contraindications to using cytokin therapy in the complex treatment of pyo-septic diseases.
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The data presented indicate that B cells from patients with chronic lymphocytic leukemia (CLL) may produce suppressive factors capable of inhibiting T and B cell proliferation and Ig secretion. Two factors with the molecular weight 65-75 KDa (SBF1) and 15-25 KDa (SBF2) have been characterized. SBFs are primarily produced by B cells with a low flow density. There is a reverse dependence between the capacity of leukemic B cells for spontaneous Ig secretion and their ability for the production of suppressive factors. The autocrine and paracrine pathways of B cell regulation in the pathogenesis of chronic lymphocytic leukemia are discussed.
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Hemopoietic precursor cloning in healthy donors and patients with lymphoproliferative disorders and its regulation in donors by two novel suppressive factors (BSF and ErSF) are investigated. It is shown that the count of erythroid precursors is increased in peripheral blood of patients with non-Hodgkin's lymphoma in contrast to the count of granulocyte-macrophage precursors. BSF inhibits entirely granulocyte-macrophage, macrophage and erythrocyte colony growth. In contrast, ErSF abrogates selectively erythroid precursor cell proliferation and differentiation. The role of the above factor in normal hemopoiesis inhibition mechanism during lymphoproliferative diseases are discussed.