Telomere Length of Individual Chromosomes in Patients with Rheumatoid Arthritis.

We analyzed telomere length of individual chromosomes in peripheral blood lymphocytes of healthy individuals and patients with rheumatoid arthritis. Quantitative fluorescent in situ hybridization and subsequent computer analysis of metaphase chromosomes showed that distribution of telomere length on individual chromosomes is different under normal and pathological conditions. Patients with rheumatoid arthritis had significantly shorter chromosome 4p telomeres, which can be essential for pathogenesis of this multifactorial disease. Additionally, disease activity inversely correlated with telomere length on chromosome 10p carrying genes involved in T cell differentiation and proliferation.

Telomere lengthening in CD8(+)cells in polyclonal in vitro stimulation is associated with an increase in protein content of catalytic subunit of telomerase (hTERT).

Culturing of polyclonally activated T lymphocytes for 7 days in vitro leads to telomere lengthening in CD8(+), but not CD4(+)lymphocytes. Under these conditions, CD8(+)lymphocytes more intensively express telomerase catalytic subunit protein (hTERT) and divide more often than CD4(+)lymphocytes. It changes the ratio of CD4(+)and CD8(+)subpopulations in favor of the latter by the end of culturing.

Processes of homeostatic proliferation in the pathogenesis of autoimmune glomerulonephritis induced by chronic graft-versus-host reaction.

Lymphopenia developing at the early stage of chronic graft-versus-host reaction is associated with increased content of IL-7 in the peripheral blood and leads to an increase of the CD4(+)and CD8(+)cell subpopulations in the spleen of the recipient. After 3 months, some animals develop autoimmune glomerulonephritis (lupus recipients). High levels of IL-7 and T-cells with the memory cell phenotype (CD4(+)CD45RB(low)and CD8(+)CD45RB(low)) persist in these animals, in contrast to nonlupus recipients without signs of autoimmune disease. This can attest to the involvement of homeostatic proliferation processes in the formation of autoimmune disease in this model.

[An association of the reduction in the count of T1 cells in the peripheral blood of patients with pulmonary tuberculosis with the lower monocytic expression of costimulatory CD80 molecules].

The percentage of T1 lymphocytes in the presence of the unchanged content of T2 cells were shown to be decreased in the peripheral blood of patients with pulmonary tuberculosis as compared with apparently healthy donors. In addition, the patients were found to have a significantly reduced quantity of CD80-expressing monocytes, the relative quantities of Th1 and Tc1 cells were directly related to the count of CD80+ monocytes. It is suggested that decreased CD80+ cells is a cause of ineffective antigen presentation that results in a systemic reduction in the count of CD4+ and CD8+ cells producing T1 cytokines and in impairment of an effective specific T1 response.

[Effect of nitrogen-containing derivatives of the plant triterpenes betulin and glycyrrhetic acid on the growth of MT-4, MOLT-4, CEM, and Hep G2 tumor cells].

Derivatives of the available plant triterpenes glycyrrhetic acid and betulin (betulin succinates and amides of betulonic and 18beta-glycyrrhetic acids containing fragments of long-chain amino acids and a peptide) were synthesized. The inhibitory action of these compounds on the growth of MT-4, MOLT-4, CEM. and Hep G2 tumor cells and their effect on the apoptosis of these cells were studied. It was shown that betulonic acid amides are more effective inhibitors of the tumor cell growth than the corresponding amides of glycyrrhetic acid. It was also found that betulonic acid amides containing fragments of caprylic, pelargonic, and undecanoic acids are more effective inhibitors of tumor cell growth than betulinic acid. The 17-dipeptide derivative of betulonic acid N-{N-[3-oxo-20(29)-lupen-28-oyl]-9-aminononanoyl}-3-amino-3-phenylpropionic acid exhibited the maximum inhibitory activity toward the tumor cells studied. Data on the induction of apoptosis in tumor cells by betulin derivatives at a concentration of 10 microg/ml were obtained by flow cytometry. The amides of betulonic acid proved to be the most effective inducers of apoptosis.

[Hypnosis for rehabilitation of immunological status in neoplasia].

The study group included 21 patients with malignant melanoma stage II-IV, aged 25-67, and 25 patients, aged 28-68, (control) with stomach tumors stage I-IV. All patients received individually-tailored hypnosis. Our newly-developed methods used batteries of suggestive images to deal with non-psychotic disorders and to map out strategies to support immunocompromised patients. In group 1, suggestion stimulated the "devouring" effect of the "patroling" cells. Quantitative and qualitative characteristics of immunocompetent cells of peripheral blood were assessed by flow cytometry, immuno-enzymatic analysis and other procedures to evaluate immunological status. Correlation analysis of data on group 1 identified 7 negative coefficients (p < 0.05 and p < 0.01) exactly in the monocytic macrophageal link thus suggesting the modulating effect of hypnosis. Our results support evidence available on the potential of hypnosis for cancer patient immunity and point for the first time to feasibility of differentiated targeting specific links of the immune system.

[Immunological indices in gastric cancer].

Immunological indices were assayed in 167 patients with gastric cancer. Tumor growth involved reduction in levels of neutrophil peroxide (p<0.05), CD3+ and CD19+-cells (p<0.05) as well as intensification of apoptosis of lymphocytes (p<0.05). As monocytic and granulocytic phagocytosis (p<0.001) and HLA-DR-expression in monocytes (p<0.001) diminished, and mitogen-induced proliferative activity of mononuclear cells suppressed (p<0.05), total and relative levels of CD8+-cells (p<0.05) and spontaneous proliferative activity of mononuclear cells (p<0.05) in peripheral blood increased. Such changes should not be reganded as expression of immunosuppression alone. Mechanisms of immunological failure inherent in tumor growth need to be investigated further.

[Diagnosis and treatment of aquired aplastic anemia].

AIM: To analyse the results of diagnosis and treatment of patients with aquired aplastic anemia (AA) in one center. MATERIAL AND METHODS: All AA patients, diagnosed and treated in one clinic in 1998-2005, were included in the trial. In severe and very severe AA (SAA/VSAA) the patients (n = 19) received combined immunosuppressive therapy (IST) with antithymocytic globulin (ATG) and cyclosporin A (CsA), in non-severe AA (NSAA) the patients (n = 9) were given monotherapy with CsA. Allogenic transplantation of bone marrow (alloTBM) was made in 4 young patients with SAA/VSAA. RESULTS: The diagnosis of AA was established in 33 patients (19 males and 14 females): NSAA in 9, SAA in 19, VSAA in 5, idiopathic--in 26, posthepatic--in 5, associated with pregnancy--in 2 patients. Age median was 20 years (13-53). The clone of paroxysmal nocturnal hemoglobinuria (PNH) was identified in 7 of 33 patients (21%), antigen HLA-DRB1 *15 in 6 of 11 patients (55%). In median of 26-month follow-up 31 patients (94%) were alive. In IST, complete or partial remissions were obtained in 88% patients. Median of the interval to achievement of transfusion independence made up 2.5 months. All the patients after alloTBM are in complete remission, chronic extensive transplant against host reaction was observed in one case. CONCLUSION: Introduction of updated protocols provides long-term survival of more than 80% AA patients. To optimize treatment outcomes, it is necessary to include newly diagnosed AA patients into ongoing multicenter studies.

[A state of immune system in patients with acute stroke].

Over the last years the data on the changes of immunological parameters in traumatic and pathological lesions of brain hemispheres has been obtained by neuroimmunology, a science investigating mechanisms, principles, regularities as well as interaction and integration of immune and nervous systems. However many aspects of the field remain unclear and need further study. In this context parameters of immune system in patients with acute stroke have been examined. These parameters proved to correlate with the disease severity suggesting that the main parameters of cell and humoral patterns of immune system depend on the structural and functional state of brain hemispheres.

[Psychological and immunological defenses in cancer--the two aspects of one problem].

The study group included 17 cancer patients, aged 25-55, (stage III-IV), mostly suffering melanoma. All of them received hypnosuggestive therapy to correct psycho-emotional disorders. Significant decrease in anxiety-related indices (p < 0.001) due to therapy pointed to rehabilitation of psychological defenses. Clinical rehabilitation was manifested by improved quality of life (p < 0.01), better habitus and adaptation (p < 0.01). The modulating effect on the macrophageal and phagocytic components of the immune system (p < 0.05) was matched by a significant correlation between psychological defense indices and those of immunological status. Our data have contributed to the existing knowledge about relationships of mind and immunity in cancer patients.

[Clinical and immunological characteristics of primary and secondary antiphospholipid syndrome]. / Kliniko-immunologicheskaia kharakteristika pervichnogo i vtorichnovo antifosfolipidnogo sindroma.

A prospective study was made of 93 patients with antiphospholipid syndrome (APS), including 34 patients with primary APS (PAPS) and 59 with secondary APS (SAPS) associated with exanthematous lupus erythematosus (ELE). According to the clinical outcomes, PAPS is heterogeneous since the clinical and laboratory signs of ELE or lupus-like syndrome occurred in two thirds of the patients with PAPS. The clinical manifestations of PAPS and ELE-associated SAPS differed at the height of disease: the signs of vascular diseases were prevalent in patients with PAPS and ELE-associated systemic manifestations were predominant in those with SAPS. In the patients with APS who further developed ELE, unlike those with PAPS showed a high incidence of transient erythema and arthralgias. The levels of serological markers in patients with APS at its height did not differ. As compared with healthy individuals, patients with APS were found to have the similar changes in the nonspecific immunological parameters manifested by absolute lymphopenia, by the diminished Fc-phagocytosis of monocytes and neutrophils, by the elevated levels of circulating immune complexes, and by the high biocidal activity of neutrophils. There were no significant differences in the immunity of patients with PAPS and in those with SAPS.

[Results of Befnorin clinical trails in healthy volunteers]. / Rezul'taty klinicheskogo ispytaniia preparata benforina na zdorovykh dobrovol'tsakh.

Clinical trails of Befnorin based on the human recombinant TNF-beta elaborated at the Research Design and Technology Institute of Biologically Active Substances, "Vector" State Research Center of Virology and Biotechnology, were carried out on healthy volunteers in compliance with a decision passed by the Committee of Medical and Immunobiological Preparations, Russia's Health Ministry. Single Befnorin doses of 5-10(4) U, 10(5) U, 5-10(5) U, and 10(6) U were administered as intramuscular injections. Clinical, biochemical and immunological parameters were registered for 7 days after a single dose. The drug had an impact on the below immunity indices: Fc-phagocytosis of monocytes, migration index and migration inhibition index. The dose of 10(5) U was proven to be most effective and safe. Supposedly, the drug can be effective in the treatment of herpetic diseases.

[Specific features of the course of pulmonary tuberculosis concurrent with liver pathology]. / Osobennosti techeniia tuberkuleza legkikh u bol'nykh s patologiei pecheni.

The study was undertaken to reveal clinical, biochemical, morphological, and immunological features of pulmonary tuberculosis concurrent with liver pathology. Patients with pulmonary tuberculosis who suffered from liver diseases were found to have more marked clinical signs, such as subfebrile temperature, weight loss, elevated levels of aminotransferases and gamma-glutamyltransferase. Morphological studies of liver biopsy specimens indicated that the rates of necrosis and inflammatory infiltration were higher in patients with chronic hepatitis C (CHC) and chronic hepatitis B (CHB) and CHC and substantially lower in CHB and alcoholism. Impaired immunity involved primarily the phagocytic link.

[Lymphocyte subpopulations and level of the proinflammatory cytokines in the blood of patients with hepatitis C and with combined variant of hepatitis C and B]. / Subpopuliatsii limfotsitov i uroven' provospalitel'nykh tsitokinov v krovi bol'nykh virusnym gepatitom C i sochetannym variantom C + B.

Subpopulation of cytotoxic lymphocytes CD8 having both secretory and cytolytic antiviral activity is supposed to play the essential role in the virus elimination. Inflammatory reactions are also of importance in the hepatitis C pathogenesis, their intensity being regulated by anti-inflammatory cytokins. This study was aimed at determination of lymphocyte subpopulation indices--the relative content of cells carrying markers CD4, CD8, CD16, CD19, CD72, the parameters of the phagocytic activity of granulocytes and monocytes, as well as serum concentrations of anti-inflammatory cytokines IL-1, IL-6 and TNF-alpha. These indices were evaluated in a group 132 patients with confirmed hepatitis C or mixed hepatitis B + C diagnosis, depending on the disease form and markers of the infectious process activity (as determined in the PCR test for hepatitis C virus RNA) in comparison with a group of healthy donors. In patients with variant hepatitis under study a growth in anti-inflammatory mediators concentration was observed along with decreased indices of lymphocyte subpopulations responsible for cell-mediated immunity and the phagocytosis parameters. In the case of mixed hepatitis these differences were shown to be more manifested.

[T cell subsets undergoing apoptosis and anergy in patients with pulmonary tuberculosis]. / Subpopuliatsionnaia prinadlezhnost' T-kletok, podverzhennykh anergii i apoptozu u bol'nykh tuberkulezom legkikh.

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.

[Normobaric hypoxy-therapy of patients with bronchial asthma]. / Normobaricheskaia gipoksiterapiia bol'nykh bronkhial'noi astmoi.

Conventional drug therapy for moderate atopic or mixed bronchial asthma was combined with normobaric hypoxytherapy (NBHT) in 32 patients (a course of 10 sessions) and was not combined in 20 control patients. Clinical results show that NBHT enhances response to conventional therapy of moderate bronchial asthma as confirmed by a significant relief of the clinical symptoms, by a significant rise of volumic and flow parameters of external respiration function, a fall in the number of CD 20+ B cells, low level of serum IgE, increased number of phagocyting neutrophils and cells carrying erythroblast antigen in peripheral blood.

[Immune status of patients with chronic bronchitis and neurocirculatory asthenia]. / Osobennosti immunnogo statusa bol'nykh khronicheskim bronkhitom s priznakami sindroma vegetativnoi distonii.

AIM: To study changes in immune system of patients with various forms of chronic bronchitis (CB) and neurocirculatory asthenia (NCA). MATERIAL AND METHODS: Neurological and immunological examinations were made in 84 patients with CB exacerbation and 51 control subjects. RESULTS: It was found that 60% of CB patients had NCA. No negative effects of NCA on immune system in CB patients were registered. Suppression of immune system and secondary immunodeficiency occurred more frequently in CB patients without signs of NCA. 40% of CB patients had vagotonic NCA in which immunological disorders manifested most clearly. CONCLUSION: Vegetative disorders in CB patients do not affect immunological system. Functional testing of autonomic nervous system is suggested for prediction of immune system condition.