[Multiple sclerosis vaccine: possibilities of the use of dendritic cells immunomodulatory potential].

For the first time we carried out a clinical assessment of the safety, tolerability and clinical efficacy course of repeated administration of experimental modified autologous vaccine interleykin (IL-10) dendritic cells in two patients with secondary-progressive multiple sclerosis patient and one with relapsing-remitting multiple sclerosis. In the course of treatment, we carried out clinical and immunological monitoring. It was found out that intradermal dose of 3 x 106 cells applied to spinal area 6-12. times did not cause any serious side effects. After the treatment with dendritic cells, the following results were observed: 1) a significant positive clinical effect in patients with secondary-progressive multiple sclerosis exacerbations; 2) moderate positive clinical effect in patients with relapsing-remitting multiple sclerosis, in a state of remission; 3) a complete absence of any clinical results in patients with secondary-progressive multiple sclerosis without exacerbations. The immune response was characterized by a significant absolute and relative increase of serum T-regulatory cells. Discovered distinct anti-inflammatory properties of dendritic cell therapy allow us to consider it as a promising area of personalized treatment based on an individual vaccination against multiple sclerosis.

[The efficacy of polychromatic visible and infrared radiation used for the postoperative immunological rehabilitation of patients with breast cancer].

The immunological rehabilitation of the patients with oncological problems after the completion of standard anti-tumour therapy remains a topical problem in modern medicine. The up-to-date phototherapeutic methods find the increasingly wider application for the treatment of such patients including the use of monochromatic visible (VIS) and near infrared (nIR) radiation emitted from lasers and photodiodes. The objective of the present study was to substantiate the expediency of postoperative immune rehabilitation of the patients with breast cancer (BC) by means of irradiation of the body surface with polychromatic visible (pVIS) in combination with polychromatic infrared (pIR) light similar to the natural solar radiation without its minor UV component. The study included 19 patients with stage I--II BC at the mean age of 54.0 +/- 4.28 years having the infiltrative-ductal form of the tumour who had undergone mastectomy. These patients were randomly allocated to two groups, one given the standard course of postoperative rehabilitation (control), the other (study group) additionally treated with pVIS + pIR radiation applied to the lumbar-sacral region from days 1 to 7 after surgery. A Bioptron-2 phototherapeutic device, Switzerland, was used for the purpose (480-3400 nm, 40 mW/cm2, 12 J/cm2, with the light spot diameter of 15 cm). The modern standard immunological methods were employed. It was found that mastectomy induced changes of many characteristics of cellular and humoral immunity; many of them in different patients were oppositely directed. These changes were apparent within the first 7 days postoperatively. The course of phototherapy (PT) was shown to prevent the postoperative decrease in the counts of monocytes and natural killer (NK) cells, the total amount of CD3+ -T-lymphocytes (LPC), CD4+ -T-helpers, activated T-lymphocytes (CD3+ HLA-DR+ cells) and IgA levels as well as intracellular digestion rate of neutrophil-phagocyted bacteria. Moreover PT promoted faster normalization of postoperative leukocytosis and activation of cytotoxic CD8+ -T-LPC, reduced the elevated concentration of immune complexes in blood. Among the six tested cytokines, viz. IL-1beta, TNF-alpha, IL-6, IL-10, IFN-alpha, and IFN-gamma, only the latter two underwent significant elevation of their blood concentrations (IL-6 within 1 day) and IFN-gamma (within 7 days after mastectomy). The course of PT resulted in the decrease of their levels to the initial values. The follow-up of the treated patients during 4 years revealed neither recurrence of the disease nor the appearance of metastases.

[Diagnostic and prognostic value of determining serum levels of cytokines and antibodies to basic myeloprotein in chronic manganese intoxication]. / Diagnosticheskaia i prognosticheskaia znachimost' opredeleniia kontsentratsii tsitokinov i antitel k osnovnomu belku mielina v syvorotke krovi pri khronicheskoi margantsevoi intoksikatsii.

Findings are that progression of chronic manganese intoxication comes along with development of humoral immune response to antibodies of myelinic coating of nerve fibers. That is expressed by increased occurrence of reliable titers of antibodies to basic myeloprotein G and increased serum IL-6 level. The authors suggest using determination of serum antibodies to myeloprotein G and IL-1, IL-6 to specify severity of chronic manganese intoxication.

[Immunogenetic cytokine restriction in multiple sclerosis]. / Immunogeneticheskaia resstriktsiia tsitokinov pri rasseiannom skleroze.

Sixty eight patients with verified multiple sclerosis (MS) (mean EDSS score 3.1 +/- 1.0) and 50 healthy donors have been investigated. Thirty five patients had relapsing-remitting, 25--secondary progressive, 8--primary progressive course. The remission was in 38, decompensation--in 20, relapse--in 10 patients. Lymphocyte subpopulations were investigated using monoclonal antibodies (Moscow) to the following antigens: CD3 (T-lymphocytes), CD4 (T-helpers), CD8 (T-supressors), CD20 (8-lymphocytes), CD25 (IL-2 receptor), CD16 (natural killers), CD95 (activated cells ready to apoptosis). Cytokines and tumor necrosis factor-alpha (TNF-alpha) levels were measured using ELISA test. HLA antigens were investigated by standard lymphocytotoxic test. In MS we found a fall of CD3, CD4, CD8, CD20 and CD16, but an increase of CD4/CD8, CD95, CD25. The CD95 level correlated with CD4, CD4/CD8 and CD16. In MS spontaneous IL-2, IL-6, IL-8 and TNF-alpha production was raised and stimulated IL-6 and IL-8 secretion was reduced. IL-4, IL-6, IL-8, TNF-alpha and IL-1 beta serum production in vivo was elevated. We found an increase of CD3, CD4, CD16, CD25, but a decrease of IL-1 (p < 0.01) spontaneous production and IL-6, IL-8, TNF-a stimulated secretion in DR2(+) MS patients, comparing to DR2(-) patients and controls. In DR2(-) patients as compared to DR2(+) patients and controls, all lymphocyte subpopulations levels, especially CD8 (p < 0.001) one, were decreased, but spontaneous IL-8 (p < 0.01) production was increased. The data obtained indicate lymphocyte apoptosis activation, targeting promoted lymphocyte destruction, and suggest T helper type-1 reaction prevalence in MS.

[Changes in the production of interleukin-1 beta, tumor necrosis factor-alpha and interleukin-2 in relation to the immunity in patients with pulmonary tuberculosis]. / Izmeneniia v produktsii interleikina-1beta, faktora nekroza opukholi alfa i interleukina-2 v zavisimosti ot sostoianiia immuniteta u bol'nykh tuberkulezom legkikh.

The specific features of production of IL-1 beta, TNF-alpha, IL-2 were studied in 74 patients with various forms of tuberculosis by taking into account the magnitude of an immunological response. Tuberculin, phytohemagglutinin, prodigiosine were used as inducers of the synthesis of cytokines. Heterodirection was found in the changes of elaboration of cytokines in similar immunological disorders in persons with different clinical forms of tuberculosis. Examination of patients with infiltrative tuberculosis indicated that the increased synthesis of TNF-alpha and IL-2 was to a greater extent associated with the activation of cell-mediated immunity and that of IL-1 beta with its inhibition. The relationships found between the production of cytokines and IgA and IgM levels are suggestive of their involvement in the regulation of immunoglobulin synthesis. Cytokine spectral alterations are associated with the changes in specific lymphocytic populations. In patients with infiltrative tuberculosis, the production of TNF-alpha and IL-1 beta was directly related to the proportion of CD4+ and CDS8+ and that of IL-2 is associated with the proportion of CD25+ and CD20+ and with the count of lymphocytes. At tuberculin stimulation of mononuclear cells, it is expedient to bear in mind the detection rate of cytokines and the level of their production. It was shown that the measurement of IL-1 beta, TNF-alpha, IL-2 may be used in the treatment of tuberculosis to assess the patients' immunological response and in the choice of immunomodulating therapy.

[Creating a system of conjugated chromosome transfer and genetic mapping of Vibrio cholerae serogroup O139 chromosomes]. / Sozdanie sistemy kon''iugatsionnogo perenosa khromosomy i geneticheskoekartirovanie khromosomy Vibrio cholerae serogruppy O139.

A conjugational gene transfer system consisting of donor and recipient strains has been developed for genetic analysis of Vibrio cholerae 0139 serogroup, a new cholera agent. Donor strains constructed using the Tn5-Mob carrying the origin of transfer (ori T) of plasmid RP4 and helper plasmid pRP4-4 were able to perform a directed transfer of chromosomal markers. Recipient strains carried mutations in auxotrophic genes as well as in virulence genes. Based on this gene transfer system, a genetic map of V. cholerae chromosome has been created showing the order of 17 gene markers. Relationship between the genetic structure of V. cholerae 0139 and 01 is discussed.

[Genetic analysis of Vibrio cholerae chromosomal regions containing the tox-2 mutation, affecting production of cholera toxin]. / Geneticheskii analiz khromosomnoi oblasti Vibrio cholerae, soderzhashchei mutatsiiu tox-2, vliiaiushchuiu na produktsiiu kholernogo toksina.

Conjugational-mating experiments showed mrh genes coding for the synthesis of mannose and fucose resistant hemagglutinin/adhesin and vibrio motility gene mot to be localized in the chromosome of V. cholerae Dacca strain 35 close to tox-2 mutation providing a high level of toxin production and rfb locus which controls 01 antigen synthesis. The results indicate the presence of a block of virulence genes within ura-pur chromosomal region of V. cholerae.

[Phenotypic analysis of two morphologically different types of Vibrio cholerae 0139 colonies]. / Fenotipicheskii analiz dvukh morfologicheski raznykh tipov kolonii Vibrio cholerae 0139.

A clinical isolate Vibrio cholerae P16064 serogroup 0139 was shown to produce two different kinds of colonies: opaque encapsulated and translucent devoid of capsule. Low virulence of translucent colonies seems to be due to not only loss of capsule which determines serum resistance, but also to decreased expression of genes controlling the motility, and production of protease and mannose-sensitive adhesion pili. Analysis of the lysogenic properties of the two types of colonies permitted us to propose that simultaneous spontaneous alteration of capsule production and the above-mentioned virulence factors in translucent colonies may be caused by a temperate phage in turbid clones of strain P16064.

[Reconstructive and restorative surgeries of the large intestine]. / Rekonstruktivnye i vosstanovitel'nye operatsii na tolstoi kishke.

Reconstructive-restorative operations in 164 cases of colostomy are analysed. The colostomy was formed for injury to the large intestine in 45.7%, oncoproctological diseases in 35%, complications of diverticulum in 10%, and for other diseases (volvulus of the sigmoid colon, unspecific ulcerous colitis, etc.) in 9.3% of patients. The terms of the operations were chosen individually: from 2.5-4 months after injury to 10-14 months after an oncological operation. The extraperitoneal method was applied in 93 and the intraperitoneal method in 71 operations. Mortality was 2.9%.

[Mapping a genetic determinant determining the increased synthesis of cholera toxin by the Dakka 35 strain of Vibrio cholerae]. / Kartirovanie geneticheskogo determinanta, opredeliaiushchego povyshennyi sintez kholernogo toksina shtammom Vibrio cholerae Dakka 35.

A new mutation tox-2 defining the increased level of cholera exotoxin production by the strain Vibrio cholerae Dakka 35 isolated from nature has been mapped by conjugational crosses of donor and recipient strains differing by toxin production and serovar. The mutation has been localized on the chromosomal fragment containing the ilv, pur, ura, rfb genes adjacent to ura-94 locus. The linkage of the tox-2 mutation with the rfb locus coding for the synthesis of somatic Ol-antigen has been also established.

[The isolation of Vibrio cholerae strains that produce cholera toxin and its B-subunit]. / Poluchenie shtammov Vibrio cholerae--produtsentov kholernogo toksina i B-sub''edinitsy kholernogo toksina.

The creation of two V. cholerae strains, belonging to the classical biovar, serovars Ogawa and Inaba, and serving as hyperproducers of cholera toxin, is described. The strains have been created by means of recombinant plasmid pCO107-2, carrying the cloned gene of cholera toxin vctAB. The use of recombinant plasmid pIEMZ3 carrying the cloned gene of the B-subunit of cholera toxin vctB has made it possible to obtain a strain, capable of producing the B-subunit of cholera toxin, on the basis of V. cholerae strain non 01. Besides, V. cholerae isogenic toxigenic strains, serovars Inaba and Ogawa, with the increased production of the B-subunit of cholera toxin, have been obtained.