[Diagnostics of ataxia-telangiectasia by the express-test found on the method of indirect immunofluorescence].

Ataxia-telangiectasia (AT) is a hereditary severe neurodegenerative disease developing, when mutations take place in both alleles of the atm gene, which encodes the key protein of the cellular response to DNA damage (DDR)--ATM proteinkinase. In response to the occurrence of double-strand DNA breaks, the ATM proteinkinase pass the autophosphorylation, and its active form--the phospho-ATM (P-ATM) appears in cells. In the nuclei of cells having the atm gene, P-ATM is revealed, being absent in cells with mutated forms of this gene, by means of the application of the modified method of indirect immunofluorescence. This peculiarity may be applied in the clinic, in order to confirm the diagnosis of AT.

[Adhesion molecules expressed in vascular endothelial cells in natural immunity against viral infections].

Cell adhesion molecules (CAM) expressed in vascular endothelium ensure integrity of the endothelial layer, recruitment and transmigration of leukocytes. Being receptors of many viruses, they play a role in immune control and infectious processes. Monoclonal anti-ICAM-1 antibodies enhance infection of primary human umbilical vein endothelial cell (HUVEC) cultures with HIV-1 due to incorporation into virions. IFN-gamma activates expression of ICAM-1 on HIV-infected HUVEC and thereby promotes binding of this molecule to complementary molecules on a greater number of sensitive cells, virion transfer onto them, and broad dissemination of the virus. Recombinant human IFN-alpha, IFN-beta and IFN-gamma influence (activate, inhibit) CAM shedding from HUVEC both intact and infected wit HSV-1. Activated shedding in the blood stream due to competition between soluble and endothelial CAM slows down recruitment and transmigration of leukocytes, i.e. regulates inflammation. CAM incorporated in microparticles can influence a wide spectrum of pathological processes Endothelial CAM may be a target for the delivery of pharmaceuticals for the treatment of vascular (including infectious) pathology.

[Role of the abnormal tracheobroncheal tree in the efficiency of treatment of patients with pulmonary tuberculosis].

The efficiency of treatment has been studied in 100 patients with pulmonary tuberculosis caused by drug-resistant (DR) Mycobacterium tuberculosis (MBT) strains and complicated by bronchial diseases, treated at the units of the Clinic of Phthisiopulmonology, I. M. Sechenov Moscow Medical Academy, in 2004 to 2006. Several forms of specific and/or nonspecific bronchial diseases are shown to be detected in patients with drug resistance in MBT. Pulmonary tuberculosis caused by DR MBT strains and complicated by bronchial diseases is characterized by the lower interferon-producing capacity of bronchoalveolar lavage (BAL) cells and by more significant impairments in the mechanisms of local lung protection. Inclusion of the immunomodulator leukinferon into the combined therapy of patients with pulmonary tuberculosis complicated by bronchial diseases contributes to the elevation of BAL cell production of alpha and gamma-interferons, reduces the generation of active oxygen forms in the BAL phagocytes and brush biopsy specimens, and increases the levels of immunoglobulins in BAL. The local administration of leukinferon reduces the time of cure of specific and nonspecific bronchial diseases in patients with pulmonary tuberculosis who isolate DR MBT strains, thus promoting the enhanced efficiency of treatment in reducing the times of bacterial isolation and decay cavity closure and the length of hospital stay.

[Characterization of protection mechanisms in patients with drug-resistant pulmonary tuberculosis].

Examining the performance of the local protective system has indicated that patients with drug-resistant pulmonary tuberculosis in the presence of the higher count of cytotoxic lymphocytes had the diminished activation of lymphoid elements of bronchoalveolar lavage (BAL) and decreased alveolar macrophageal production of active oxygen forms. However, there was a drastically increased formation of active oxygen forms in the BAL macrophagues during mycobacterial phagocytosis, which may result to their death. At the same time, the decreased production of gamma-interferon in the BAL cells was found in patients with drug-resistant tuberculosis (8.0 +/- 3.0 U/ml versus 10.7 +/- 2.0 U/ml). In such patients, the generation of alpha-interferon was 105.0 +/- 38.0 U/ml versus 187.0 +/- 72 U/ml in patients with tuberculosis caused by drug-resistant Mycobacterium tuberculosis. In patients with drug-resistant tuberculosis, the lower production of alpha- and gamma-interferons in the BAL cells leads to their decreased regulatory effect on the mechanisms of local defense of the lung. The drastically enhanced production of active oxygen forms, which has been ascertained in patients with drug-resistant tuberculosis, is able to result in the death of macrophages, the release of lysing enzymes into the tissues surrounding the lung; the higher count of T cytotoxic lymphocytes, the lower levels of cells in apoptosis, and mycobacterial resistance to antibacterial drugs deteriorate the course of pulmonary tuberculosis in this category of patients.

[Leukinferon in combined therapy for acute pulmonary tuberculosis]. / Leikinferon v kompleksnoi terapii ostroprogressiruiushchego tuberkuleza legkikh.

Experiments on 140 CBA and C57BL/6 mice and studies of 163 patients with acute pulmonary tuberculosis have indicated that leukinferon has a immunomodulating effect on morphological reactions in the lung and on the clinical course of the disease. They have shown that leukinferon plays an important role in the activation of exudate macrophages and in the acceleration of their differentiation in experimental tuberculosis and that there is a rapid elimination of Mycobacterium tuberculosis from the involved organs without production of the L-forms of the causative agent when immunomodulation is used. At months 2-3, the patients with acute pulmonary tuberculosis showed the accelerated processes of detoxification, abacillation, infiltrate resolution, and decay cavity closure during hemo- and immunomodulation with the normalized production of cytokines (gamma-interferon and tumor necrosis factor-alpha). During 6-month therapy, a severe pulmonary process was arrested in 84% of cases and some patients were operated on (76% in the comparison group). The morphological effect of leukinferon was to increase mononuclear infiltration and to normalize a lung connective tissue response, by further decreasing the rate of inflammation.

[Leukinferon-induced changes in cytochemical parameters of the wound exudate neutrophilic granulocyte nucleus and cytoplasm in patients with maxillofacial phlegmons]. / Leikinferonindutsirovannaia dinamika tsitokhimicheskikh pokazatelei iadra i tsitoplasmy neitrofil'nykh granulotsitov ranevogo ékssudata u bol'nykh s flegmonami cheliustno-litsevoi oblasti.

Clinical and cytochemical study of the wound exudate neutrophilic granulocytes (NG) in patients with maxillofacial phlegmons treated traditionally and with leukinferon (immunomodulator) added to basic therapy demonstrated a positive clinical effect and pronounced stimulation of NG in the patients treated with leukinferon. The time course of cytochemical parameters of NG cytoplasm and chromatin activity was principally different in the two groups of patients. A new tissue index of NG was developed, giving an accurate integral picture of the total biological activity of the wound exudate NG.

[Efficacy of leukinferon immunocorrection in patients with maxillofacial phlegmons]. / Effektivnost' immunokorrektsii leikinferonom u bol'nykh s flegmonami cheliustno-litsevoi oblasti.

Clinical and immunological studies were carried out in patients with maxillofacial phlegmons treated by traditional methods and by traditional therapy supplemented by immunocorrection (leukinferon). Addition of leukinferon to basic therapy had a pronounced clinical and immunomodulating effect, which resulted in shorter hospitalization period and virtually complete recovery of the main immunological parameters, in contrast to traditional therapy alone. The most demonstrative parameters were the expression of the neutrophil granulocyte membrane receptors and the relationships between T-lymphocyte subpopulations, which prompted using them as the most significant diagnostic markers indicating the disease severity and treatment efficiency.

[Effects of immunomodulator leukinferon on the course of experimental tuberculosis]. / Vliianie immunomoduliatora leikinferona na techenie éksperimental'nogo tuberkuleza.

An experiment was conducted on 60 CBA mice intravenously inoculated with cultured Mycobacteria tuberculosis (MBT), Erdmann strain, in a dose of 0.025 mg. The specific features of tissue, cellular, and biochemical reactions were studied in the lung, liver, and spleen when leukinferon (LF) was included into tuberculosis treatment regimen. LF was shown to have a positive impact on the development of reparative reactions during tuberculous inflammation by reducing the time of abacillation and recovering the structure of diseased organs. By month 3 of follow-up, MBT were not detected in mice receiving antibacterial agents (ABA) and LF, while typical and changed forms of LF were identified in the cytoplasm of alveolar macrophages in mice treated with ABA alone. A specific feature of an inflammatory reaction as a significant proliferation of lymphocytes and macrophages with their ample infiltration of target organs was noted in animals receiving LF. This was followed by the activated production of alpha- and gamma-interferons and by the mobilization of an enzymatic link of anti-oxidant defense under chronic oxidative stress, which led to a reduction of resolution of inflammatory areas and to an increase in survival of animals which had not been given ABA, but treated with LF alone.

[Leukinferon in the treatment of patients with sepsis and multiple organ dysfunction syndrome]. / Leikinferon v lechenii septicheskikh bol'nykh s sindromom poliorgannoi nedostatochnosti.

Dynamics of clinical signs, blood formula and some cytokins in serum samples of the patients with sepsis complicated by multiorgan disfunction syndrome (as a rule kidney and liver were involved) were investigated. Etiotropic therapy was combined with immunocorrecting treatment with leukinferone Combined regime provided positive results in clinical symptoms, in lymphocytes number normalization (abs. and per cent), stimulated T lymphocytes differentiation and facilitated intoxication finishing according to LII). Immunocorrection practically had no effect on TNF-alpha, IL-1 alpha, IL-6, and stimulated IL-8 secretion more effectively than etiotropic therapy. IF-gamma level enhanced along with stopped IL-10 production. As a result ratio of IF-gamma/IL-10 enhanced from 0.56 to 1.0, in the case of etiotropic therapy this ratio diminished from 0.48 to 0.3. It is concluded that immunocorrecting therapy provided positive dynamics in the ration IF-gamma/IL-10, recurring cell immune reactions. The recurrence period was shortened and lethality level was substantially lower (2.5 times).

[Efficiency of immunocorrection using cytokines in the therapy of papillomavirus infection]. / Effektivnost' immunokorrektsii tsitokinami pri lechenii papillomavirusnoi infektsii.

The data of the immunological examination and the results of treatment of 86 patients with papillomavirus infection (PVI) are presented. The multifactor suppression of cell-mediated and humoral immunity was established. The degree of immune disturbances correlated with the spread and severity of lesions. The use of systemic injections of cytokines (leukinferon and concentrated interferon) in low doses as adjuvant therapy with laser-radiosurgery led to the normalization of most immunological characteristics and the course of PVI without relapses.

[Expression of receptors for human alpha- and gamma-interferons on the surface of peripheral blood mononuclear cells in viral infections]. / Ekspressiia retseptorov dlia chelovecheskikh alpha- i gamma-interferonov na poverkhnosti mononuklearnykh kletok perifericheskoi krovi pri virusnykh infektsiiakh.

Expression of receptors on peripheral blood mononuclears of donors and patients with viral infections during therapy was studied using FITC-labeled monoclonal antiidiotypical antibodies with the "internal image" of human alpha- and gamma-interferons and monoclonal antibodies to these interferons. Activation of the immune system caused by infection modifies the expression of interferon receptors and leads to appearance of membrane-bound interferons, mainly gamma-interferon.

[Therapeutic antiradiation properties of leukinferon]. / Protivoluchevye terapevticheskie svoistva leikinferona,

In experiments with three species of animals (mice, rabbits, monkeys) irradiated with sublethal and lethal doses of gamma-irradiation, it was observed, that leukinferon used in 4 hours or 10 days after provided antiradiation therapeutical effect. When lethal dose was used (mice) the survival of animals was significantly increased. The preparation decreased depression of the functional activity of leukocytes as it was observed with IFH-alpha and gamma-production. Pestoring this function was accelerated. Phenomena pancytopenia and thrombocytopenia induced by radiation were decreased. Therapeutical effect was explained with capacity of the preparation to defence the hemopoietic organs from the radiation and to stimulate hematopoiesis. So, spleen weights and quantity of cells into bone marrow were higher in experimental group in comparison with control at any observation. CFUs were also higher (with optimal dose of preparation). Stimulation of the restoring processes was confirmed also by more intensive increasing of the reticulocyte quantities in the circulation of experimental monkeys within 20 days. Then their level became more close in both groups. The preparation stimulated also differentiation of immune effectors: immature neutrophils were absent in the circulation of experimental monkeys. Production of IFN-gamma (which is function of T-lymphocytes) was restored more fast. As a result, immunoreactivity of monkeys in experimental group was more complete and restored faster: the growth of the automicroflora on the skin surface became to increase 7 days later and was restrained. Leukinferon hindered the development of acute radiation sickness symptoms.

[Protective action of leukinferin during radiotherapy of oncologic patients]. / Zashchitnoe deistvie leikinferona pri luchevom lechenii onkologicheskikh bol'nykh.

In clinical observation on 248 patients with breast cancer IIb-III-b stages given radiotherapy on breast gland, parasternal and axillary-subclavian regions (total doses 40 Gr for each) before mastectomy was shown, that use LF im 2-3 times a week through the course of therapy decreases statistically significant pancytopenia, induced by radiation. Quantity leukocytes was even increase in a process of therapy. Frequency of anemia and lyphopenia was decreased almost 3 times. E-RFC were depressed also more slight, then in the group without immunocorrection and after mastectomy practically, restored. IFN-gamma production by T-lymphocytes was not changed and essentially more high then in the comparative group. The presented data are shown, that LF provides a defensive action on hematological indices and immune effectors function in oncological patients during radiotherapy.

[The clinical efficacy in using leukinferon in adults with diseases caused by the varicella-zoster virus]. / Klinicheskaia éffektivnost' primeneniia leiinferona u vzroslykh pri zabolevaniiakh, vyzvannykh virusom vetrianoi ospy.

To achieve more effective treatment of varicella (chickenpox) and herpes zoster in adults, a wide-spectrum immunocorrective agent containing, together with alpha-interferon, a number of other cytokines of the first phase of immune response was used. In patients with the different severity of disease leukinferon induced a rapid decrease in the severity of the disease, arrested the development of new elements on the skin and the buccal mucosa, and reduced the duration of the fever period. When used in such forms as intramuscular injections in combination with the irrigation of the buccal mucosa and ointment, leukinferon proved to be a highly effective preparation for the treatment of diseases caused by varicella-zoster virus.

[The use of leukinferon in treating measles in adult patients]. / Primenenie leikinferona pri lechenii kori u vzroslykh bol'nykh.

The following mucosal are characteristic of measles in adult patients: dryness in the oral cavity, dryness, desquamation, and fissures in the red edge and in the mouth corners, edema and hyperemia, of the buccal mucosa, macular enanthema on the hard and soft palate, Bel'skii-Filatov-Koplik spots, whitish deposit on the gingiva, edematous and bleeding gingiva, and, as a result of general intoxication, a lingual deposit. Leukinferon, a wide-spectrum immunocorrective drug, was used to improve the efficacy of treatment of adult patients with measles; besides alpha-interferon, it contains other cytokines of the first phase of immune response. Therapy with leukinferon led to a sooner improvement of the general status and a more rapid regression of the disease symptoms, including changes in the buccal mucosa, in comparison with the control leukinferon-untreated group.

[The interferon reaction of the leukocytes and the natural killer activity in patients with acute viral hepatitis B undergoing interferon treatment]. / Interferonovaia reaktsiia leikotsitov i aktivnost' estestvennykh killerov u bol'nykh ostrym virusnym gepatitom B pri lechenii interferonom.

The interferon response of leukocytes (IRL) alpha and gamma as well as the functional activity of natural killers (NK) were studied in patients with the verified diagnosis of acute viral hepatitis B (AVH-B) treated with leukinferon (a preparation of natural interferon-alpha and cytokines) and reaferon (recombinant alpha 2 interferon). The effect of therapy with LF and RF in patients with AVH-B manifested by an increase in the functional activity of NK up to complete normalization after termination of the course of therapy. In the group of patients treated with LF as a result of therapy IRL-alpha increased by the end of the treatment and in the convalescence period. The observed activation of NK and the IF-alpha system under the effect of IF preparations in patients with AVH-B correlated with enhanced elimination of HBsAg.

[The clinico-immunological effects of leukinferon in the treatment of patients with acute suppurative pyelonephritis]. / Kliniko-immunologicheskie éffekty leikinferona pri lechenii bol'nykh ostrym gnoinym pielonefritom.

The effect of leukinferon (LKF) administration to 20 patients with acute renal inflammation was evaluated versus the effect of basic therapy given to 19 matched patients. A short course of LKF (3 injections) promoted more rapid discontinuation of the fever, recovery of satisfactory general condition, healing of postoperative wounds. Immunologically, the test subjects exhibited a rise in the previously low levels of lymphocytes, B-cells, T-helpers, IgA and IgG. The proportion of T-lymphocyte subpopulations improved and the activity of EC-cells enhanced. It is thought valid to use LKF in acute renal inflammation and surgical urological affections.

[Experience of immunotherapy with leukinferon in the comprehensive therapy of breast cancer]. / Opyt primeneniia immunoterapii leikinferonom v kompleksnom lechenii raka molochnoi zhelezy.

Patients with breast tumors, stage IIb-IIIb, received complex treatment including radiation therapy, radical surgery and polychemotherapy. Some of them were also injected 4-40 doses of leukinferon, im, for immunocorrection. The latter treatment carried out during radiotherapy and preparation for surgery prevented lymphopenia development. Leukinferon administered during 6-8 courses of cytostatic polychemotherapy was followed by a significant rise in lymphocyte concentration. Leukinferon-treated patients, on the whole, revealed higher rates of postoperative rehabilitation, improved tolerance of rigorous treatment and lower frequency of metastatic development. A correlation was established between preoperative lymphocyte level and risk of metastasis development at later stages. No metastasis or recurrence was detected within 15-42 months in 16 patients who received leukinferon throughout the entire period of treatment.

[Leukinferon in the treatment of patients with acute viral hepatitis b]. / Primenenie leikinferona v lechenii bolnykh ostrym virusnym gepatitom B.

Leukinferon activity was studied in a controlled trial including 30 patients with acute viral hepatitis. The disease ran a moderate severity course in the majority of the patients. Leukinferon, a combined preparation of natural interferon and cytokines produced by virus-induced leukocytes, has marked immunomodulating properties at moderate antiviral activity. Leukinferon was administered intramuscularly for 10 days according to the following scheme: day 1-1 sample 3 times, day 2-1 ampule 2 times, day 3-10-1 ampule a day (overall 1 x 10(5) U of interferon). Due to leukinferon the symptoms of intoxication declined, hepatic biochemistry normalized more rapidly as well as the period of viremia and antigenemia. Positive clinical trends correlated with interferon system improvement and activation of natural killers. 6 months later complete recovery was registered in all leukinferon-treated subjects.