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At least 415 records · Page 23Linked to original sources

[Distribution in mice of 125I-monoclonal antibodies to T-lymphocyte antigen Ly 2.1 under the influence of immunomodulators].

A study was made of the distribution of 125I (a chloramine method of labeling) monoclonal antibodies to the surface antigen Ly 2.1 of T-lymphocytes during action of immunomodulators (tactivin, hydrocortisone, tactivin administered after hydrocortisone) on ACR mice. These antibodies were shown to retain antigen binding capacity, permitting monitoring of the redistribution of the antigen in the body exposed to immunomodulators.

Adjuvants, Immunologic↗

[Immunomodulation during viral infections].

The paper provides a survey of immunomodulation mechanisms in the course of viral infections. The importance of viruses in the disturbance of immunological homeostasis has been pointed out. Virally induced immunomodulation can arise by: a mechanism of complete or abortive viral replication in the lymphocytes and macrophages, by soluble viral factors, by the influencing of antigen-presenting cells, and by excessive suppressor T-lymphocyte stimulation. Viral infections present a real danger to the integrity of the immunological system, and this demands a follow-up and an adequate interpretation of the arisen disorders.

Humans↗

[The comparative characteristics of the immunomodulating properties of protein A from Staphylococcus aureus of different origins].

The immunomodulating properties of highly purified staphylococcal protein A and its analog obtained by gene engineering techniques have been compared with those of commercial preparations. The comparison has shown that the differences observed in this investigation may be explained by the presence of admixtures of staphylococcal nature in commercial preparations. The preparations of highly purified staphylococcal and recombinant protein A stimulate humoral immune response and the processes of phagocytosis and do not show mitogenic activity with respect to T cells. The conclusion on the identity of the immunomodulating activity of the preparations of natural and recombinant protein A has been made.

Adjuvants, Immunologic↗

Cytokine secretion effected by synergism of the immunomodulator AS101 and the protein kinase C inducer bryostatin.

AS101, a synthetic organotellurium compound, was found to have immunomodulating properties by initiation of cytokine production in vitro and in vivo. Phase I/II clinical trials currently in progress on AIDS and cancer patients treated with AS101 show significant increases in various immunological parameters, with minimal toxicity. Recently, AS101 and the protein kinase C (PKC) inducer, phorbol myristate acetate (PMA), were shown to synergize in the secretion of interleukin-2 (IL-2) and colony-stimulating factor (CSF) in vitro, by human and mouse lymphoid cells. The bryostatins, a group of natural macrocyclic lactones isolated from marine invertebrates (Bugula neritina) have been reported to be potent PKC activators with no tumour promoting activity. In this study, we investigated the synergistic effect of AS101 and a partially purified preparation of bryostatin on the production of several cytokines. Our data confirm the presence of synergism, which greatly enhances cell proliferation, IL-2, tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) secretion by human mononuclear cells (MNC) and the production of IL-2 and TNF by mouse cells. The absence of tumour-promoting activity of the bryostatins makes them particularly good candidates, in combination with AS101, for immunomodulation in vivo in clinically immunosuppressed conditions.

Adjuvants, Immunologic↗

[The immunomodulating action of mytilan in an experimental influenza infection].

The materials characterizing the immunomodulating activity of mytilan, a bioglycane from an industrial object of Japanese sea, Crenomytilus grayanus, in experimental influenza infection are presented. The preparation protected up to 60% of mice intranasally inoculated with influenza virus, and significantly inhibited influenza virus reproduction. It induced interferon (possibly gamma IF) synthesis in low titres. The immunomodulating effect of mytilan consisted in stimulation of specific antibody genesis, enhancement of chemotaxis, increasing oxidation-reduction activity, enhancement of expression of Fc gamma-receptors by splenocytes and macrophages, enhancement of antibody-dependent spleen cell cytotoxicity, increased activity of natural killer cells, as well as increased complementary activity of blood serum and enhanced expression of C3 receptors by mouse spleen cells.

Adjuvants, Immunologic↗

[New aspects of intolerance of the aqueous iodinated x-ray contrast medium, adipiodone--fatal interaction of adipiodone-Ultrabil with the immunomodulators Corynebacterium parvum (CP) and Shigella dysenteriae endotoxin (LPS)].

The authors assume a new type of interaction of the aqueous X-ray contrast substance type adipiodone (Ultrabil 50% Spofa) with immunomodulators of Corynebacterium parvum (CP) and the endotoxin of Shigella dysenteriae (LPS). The fatal type of interaction developed regularly as a result of the concurrent i.v. administration of the X-ray contrast substance adipiodone with the endotoxin of Shigella dys. (LPS) to laboratory animals (mice) which had five days previously a single dose of Corynebacterium parvum (CP). The effect of the interaction was evaluated using LD50 of adipiodone (Ultrabil Spofa) which in interaction with the immunomodulators of CP and LPS was identical as the dose used in diagnostic practice. The authors considered the possible development of "oxygen stress" as a consequence interacting processes and complement activation.

Adjuvants, Immunologic↗

Regulation of natural killer progenitors. Studies with a novel immunomodulator with distinct effects at the precursor level.

NK cells originate from progenitors in the bone marrow and maturate independently of other lymphoid organs. NK cell maturation represents an important site for regulation of the level of NK activity and constitutes a potentially interesting target for therapeutic intervention. The effect of the immunomodulator Linomide (carboxamide-3-quinoline) on the regeneration of NK cells was studied in vivo after depletion of mature NK cells. Linomide significantly, although to various extent, accelerated the maturation of NK cells after specific depletion with antibodies to asialomonoganglioside, treatment with cyclophosphamide or lethal irradiation and syngeneic bone marrow grafting. Examination of the target cell spectrum lysed by spleen effector cells during Linomide treatment as well as studies of phenotype, clearly indicated that the effector cells studied were NK cells. Treatment of mice for 4 days with Linomide increased the frequency of bone marrow NK cell progenitors from 1/11,900 to 1/6,000 as judged by limiting dilution analysis. Direct addition of Linomide in vitro had no effect on cultures of mature NK cells from spleen, but had an additive effect to IL-2 on the generation of NK cells when added to bone marrow cultures. Our study indicates that different mechanisms exist for the regulation of progenitor and mature NK cells, and that the immunomodulator Linomide represent a potentially important tool for investigating the mechanisms governing NK cell maturation.

Adjuvants, Immunologic↗

Studies on immunotropic activity of certain immunomodulators.

Immunotropic activity of natural and synthetic immunomodulators was evaluated by cytotoxic and rosette tests. In both experimental models the above groups of drugs were observed to exert similar effect. Thus, it may be assumed that synthetic immunomodulators and thymus hormones have much alike mechanisms of activity. The usefulness of both tests applied, however, differed; more sensitive appeared the model of the rosette test.

Adjuvants, Immunologic↗

[Immunomodulating effect of cyclophosphane under different modes of administration to mice].

A study was made of the effect of injection of cyclophosphamide (CP) immunomodulating to BALB/c mice, according to 3 schemes of injection with the whole dose being 200 mg/kg. In all, the state of peripheral blood and spleen, the cellular content of lymph nodes and the number of DNA-synthesizing cells in them were studied, in addition to the ability of lymph node lymphocytes to proliferative reaction on T and B cells mitogens in vivo. It was determined that a 2-fold injection of CP, in contrast to 10- and 5-fold injections, resulted in splenomegaly and leukocytosis in the experimental animals. By means of quantitative tests in vivo, in was demonstrated that the dynamics of restoration of proliferative responses to mitogens depends on the CP injection scheme. These tests proved to be more informative for registration of immunomodulating effect of CP, than the study of cellular content of lymph nodes and the number of DNA-synthesizing cells in them.

Adjuvants, Immunologic↗

[Use of immunomodulators in pediatric pulmonology].

This review describe the current state of knowledge and the clinical application of immunomodulating drugs in pediatric pulmonology. Some of those drugs are able to stimulate the macrophages, even in an aspecific way, via the gut associated lymphatic tissue (GALT), that is in connection with the bronchial associated lymphatic tissue (BALT). The most important field of application of the immunomodulating drugs in pediatric pulmonology is the child with recurrent upper respiratory tract.

Adjuvants, Immunologic↗

[Multifactor analysis of parameters of immunity under the combined action of doxycycline and a low molecular weight immunomodulator of microbial origin].

The effect of doxycycline combination with a low molecular immunomodulator of microbial origin on the primary immune response to the vaccine EV antigens was studied in multifactor experiments. Mathematical processing of the data provided construction of polynomial statistic models of the second order describing increased delayed type hypersensitivity (IDTH) and the antibody titer. Analysis of the quasimonofactor models revealed different character of regulation of the cellular and humoral response. Nomograms were plotted for precise quantitative estimation of the dose-time parameters of the regimens for combined use of the antibiotic and immunomodulator providing the required levels of IDTH and the antibody titer.

Adjuvants, Immunologic↗

Overall survival results of non-small cell lung cancer patients: chemotherapy alone versus chemotherapy with combined immunomodulation.

The effect on long-term survival of immunomodulation adjuvant to various cytotoxic chemotherapy regimens in non-small cell lung cancer (NSCLC) was evaluated in 669 patients followed up between 1974 and 1987. Four hundred seventeen patients were treated only by cytotoxic chemotherapy and served as controls. Two hundred fifty-two patients received warfarin (W), levamisole (L) and tranexamic acid (T) for adjuvant immunomodulation. These drugs, especially when given in combination (W + L + T), led to a significant (p less than 0.05) enhancement of survival in patients with advanced NSCLC, independent of the cytotoxic regimen used.

Adjuvants, Immunologic↗

Collagenase, elastase, and nonspecific protease production by vigorous or immunomodulated liver granulomas and granuloma macrophages/eosinophils of S mansoni-infected mice.

Schistosomiasis mansoni is characterized by granulomatous inflammations, deposition of collagen, and irreversible liver fibrosis. In chronic infections fibrosis is cumulative, while collagen synthesis and degradation are diminished. In the present study, we compared collagenase, elastase, and nonspecific neutral protease (NP) activities in isolated vigorous (8-week infection) and immunomodulated (18-20-week infection) liver granulomas. Enzyme activity was localized in the adherent macrophage (greater than 90% purity) and nonadherent eosinophil-rich (greater than 70% purity) cell fractions of the disaggregated granulomas. Collagenase levels were approximately two times higher in granuloma extracts and explant culture supernates of the vigorous as compared with the immunoregulated lesions. However, macrophages and eosinophil-rich cells derived from either type of granuloma secreted similar enzyme levels. Elastase and NP levels in granuloma extracts and secretions of adherent macrophage and eosinophil-rich cell populations were the same in vigorous or immunomodulated lesions but were significantly greater in vigorous granuloma culture supernates. In addition to active collagenase, trypsin activatable latent collagenase was also present in both types of granuloma extracts, explants and eosinophil-rich cell culture supernates. Latent elastase was also detected in granuloma extracts or explant supernates but was absent from secretions of granuloma cells. These results suggest that the presence of active neutral proteases within granulomas may play an important role in the regulation of tissue repair and remodeling during the fibrotic process.

Animals↗

Proteolysis of human C-reactive protein produces peptides with potent immunomodulating activity.

We have studied the ability of human C-reactive protein to modulate the immune response in vitro. Whereas native C-reactive protein did not induce phagocytic leukocytes to chemotax or to produce superoxide, treatment of purified C-reactive protein with human neutrophil-derived acid proteases produced substances with potent effects on leukocyte function. Close examination of the primary structure of human C-reactive protein revealed three regions evenly distributed throughout the protein each of which contain peptide sequences closely resembling the amino acid sequence of the immunomodulator peptide tuftsin, Thr-Lys-Pro-Arg. We have synthesized the three peptides which include Thr-Lys-Pro-Leu ([Leu4]tuftsin), Gly-Lys-Pro-Arg ([Gly1]tuftsin), and Thr-Lys-Pro-Gln ([Gln4]tuftsin) and assayed them for biological activity. The three synthetic peptides were found to stimulate phagocytic leukocytes to chemotax, produce superoxide, and induce mononuclear cells to produce interleukin 1 in vitro at concentrations similar to those concentrations required for tuftsin to induce these phenomena. These results support a potentially important role for C-reactive protein as a possible immunomodulator during inflammation.

Amino Acid Sequence↗

[Multifactor immunopharmacological analysis. Effect of rifampicin and low-molecular immunomodulator of microbial origin on the primary immune response to fraction 1 of vaccine EV].

Multifactor analysis was applied to combined effect of a low molecular immunomodulator of microbial origin and rifampicin on the primary immune response (increased delayed type hypersensitivity and antibody titer) to the antigens of vaccine EV fraction I. Computer processing of the experimental data provided construction of the 2nd order polynomial models satisfactorily describing cellular and humoral responses in the combined therapy. For increasing the informative capacity of the analysis of the polynomial statistic models it was proposed to develop quasimonofactor relationships reflecting the factor effect on the output with changing of the other factors within the studied ranges. Nomograms (equal level lines at fixed values of one factor) were constructed which provided rapid and correct estimation of optimal values for the regulating parameters (drug doses and administration time). Immunostimulating activity of the microbial immunomodulator was estimated quantitatively and conditions for selective regulation of the cellular and humoral responses were determined.

Adjuvants, Immunologic↗

Hyaluronic acid-degrading enzymes in rat alveolar macrophages and in alveolar fluid: stimulation of enzyme activity after oral treatment with the immunomodulator RU 41740.

RU 41740 (Biostim) is an immunomodulator clinically used for the treatment of chronic bronchitis and recurrent pulmonary infections. In these diseases large amounts of mucus are produced which congest the bronchi. A major glycosaminoglycan constituent of this mucus is hyaluronic acid, one of the largest molecules in nature; its metabolic degradation is carried out by 3 acid hydrolases: hyaluronidase, beta-N-acetylglucosaminidase, and beta-glucuronidase. In the lung these enzymes are especially synthesized and active in alveolar macrophages. It was thus interesting to study the effect of RU 41740 administration on the hyaluronic acid-degrading activity of these cells. This compound was given by gastric gavage to rats and the activities of lung alveolar macrophage and alveolar fluid hyaluronidase, beta-N-acetylglucosaminidase, beta-glucuronidase, and acid phosphatase as a lysosomal marker were determined. The effect on macrophage proliferation was also examined. The results obtained showed that: (1) unstimulated alveolar macrophages display the remarkable property, compared with other cell types, that hyaluronidase activity is about equally distributed between the inside and the outside of the cell; (2) RU 41740 administration increases the total activity of the 4 enzymes studied in the alveolar macrophages without inducing any increase in the number of macrophages; (3) the intracellular activities of beta-N-acetylglucosaminidase and beta-glucuronidase are markedly increased, whereas intracellular hyaluronidase activity is not changed. However, in the extracellular fluid only hyaluronidase activity is highly increased; (4) even the lysosomal marker enzyme acid phosphatase has only its intracellular activity increased. This would suggest the possibility that other lysosomal enzymes may also be increased by this immunomodulator.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

In vitro and in vivo effect of adriamycin therapy on monocyte activation by liposome-encapsulated immunomodulators.

The purpose of these studies was to determine the effect of Adriamycin (ADR) on the ability of liposome-encapsulated immunomodulators to activate human blood monocytes to the tumoricidal state. We undertook these experiments because we envisioned using encapsulated activators in addition to chemotherapy to destroy pulmonary micrometastases in patients with osteosarcoma (OS). Prior to the initiation of such therapy, it was important to determine whether chemotherapy interferes with monocyte function. First, human peripheral blood monocytes were isolated from normal donors and preincubated with ADR (0.5-500 ng/ml) for 1 h and then washed prior to the addition of free or liposome-encapsulated activators. After 18-24 h incubation, the activating agents were washed off and [125I]IdUrd-labeled A375 melanoma cells were added. Lysis of radiolabeled tumor cells was quantified 72 h later. Monocytes were also incubated with ADR for 24 h in the presence of free or liposome-encapsulated activators and their cytotoxicity quantified. ADR had no effect on the ability of either free or liposome-encapsulated agents to activate monocyte tumoricidal function. We also studied the in vivo effect of ADR therapy on monocyte function in nine patients with OS. At the time of diagnosis and 1 month after ADR therapy (75 mg/m2) patient monocytes could be activated to the tumoricidal state by liposome-encapsulated agents at levels equal to or greater than pretherapy levels. Monocytes isolated from four patients with OS 1 day after ADR therapy and then activated by liposome-encapsulated agents also demonstrated tumoricidal activity. These studies indicated that the monocytes isolated from osteosarcoma patients treated with ADR can be activated in vitro to kill tumor cells and that additional therapy with liposome-encapsulated immunomodulators may be combined with ADR in the treatment of metastatic pulmonary OS.

Adjuvants, Immunologic↗

[Reduction using an immunomodulator of the level of respiratory infections in chronic bronchitis].

Fifty-six patients with recurrent bronchopulmonary infections associated with chronic bronchitis were randomly allocated to 2 groups, to assess whether treatment with an immunomodulator, Diribiotin CK, could enhance resistance to infection. The double-blind, placebo-controlled prospective trial over a 9 month period showed that this immunomodulator was well tolerated and significantly reduced the rate of respiratory tract infection. The drug also significantly reduced the prescribing of antibiotic medication and the rate of absenteism from work. These effects have been demonstrated in a rigorously designed clinical study. This is the first time that a clear clinical activity has been attributed to an inducer of soluble mediators of immunity.

Adjuvants, Immunologic↗