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Biomedical subjects

A Olinescu

Publications and source records attributed to A Olinescu.

At least 19 recordsLinked to original sources

In vivo and in vitro effect of Cantastim, an immunomodulatory agent extracted from a highly pathogenic Pseudomonas aeruginosa strain.

Cantastim is a biological product consisting of distinct molecules of phospholipids obtained from a peculiar Pseudomonas aeruginosa strain. It enhanced the IgM and especially the IgG responses of mice pretreated with Cantastim and then intraperitoneally inoculated with T-dependent antigens such as sheep erythrocytes; restored cellular immunocompetence as evidenced by an increase in the in vitro proliferative responses to T-cell mitogens and allogeneic stimuli of murine splenocytes from in vivo pretreated mice activated NK cytotoxicity, and inhibited in vivo growth of the Ehrlich ascites tumor. In vitro it stimulated the mitogenesis of mouse lymphocytes but did not exert such stimulatory effect on guinea pig or human lymphocytes. All these findings allow to define Cantastim as an immunomodulating agent influencing mainly the cell-mediated immune response.

Adjuvants, Immunologic↗

A particular case of large granular lymphocytes lymphoma.

A patient with non-cutaneous lymphocytic lymphoma with leukaemic spread is reported. The large majority of the peripheral blood mononuclear cells formed rosettes with sheep erythrocytes (E), had receptors for the Fc portion of IgG (Fc gamma R) and displayed an unusual enzymatic profile. Part of these cells had also labile bound surface membrane IgG. The leukaemic cells were morphologically characterized as large granular lymphocytes (LGL) and consisted of two different types of cells: lymphoid cells and monocytoid cells. The histopathological diagnosis was T-cell lymphoma, pleomorphic type, diffuse. Despite their morphological heterogeneity, all the proliferative cells had the same immunological phenotype, showed normal ADCC activity but no NK activity. After three months, without specific treatment, the surface pattern changed: the cells resembled mature LGL and the NK activity increased. The cytochemical study of the leukaemic cells revealed an enzymatical peculiarity: besides an enzymatic profile characteristic for relatively mature LGL, the cells also displayed peroxidase activity. This unusual aspect--the expression by an individual malignant cell of markers believed to be restricted to a single cellular lineage--might be interpreted as a lineage infidelity or lineage promiscuity. The observation that this lymphoma developed in a patient with a long history of hypogammaglobulinaemia is of particular interest.

Adult↗

Specific and nonspecific protection of mice by Pseudomonas aeruginosa lipopolysaccharides.

The role of lipopolysaccharide (LPS) in eliciting a predominant cellular or humoral protection of mice is determined by the amount administered and the immunization schedule. Three basically different experimental conditions could be characterized. Five days after immunization with 100 micrograms of LPS, a nonspecific protection was observed due to the immunomodulatory capacity of lipid A. After 14 days, the same amount of LPS results in an O-specific humoral protection. On the other hand, 0.1 micrograms of LPS lead to a specific protection within 5 days after immunization due to a synergistic action of a specific humoral response (induced by the O-side chain) and a nonspecific signal modulated by lipid A. In order to study the role of each LPS region for protection, the free side chain was conjugated to albumin, followed by complexation with lipid A. To induce a nonspecific protection 5 days after immunization, the presence of lipid A was mandatory, in either the conjugated or free form. Removal of ester-linked fatty acids from free lipid A reduced its protective and mitogenic capacities by 50, and 25%, respectively.

Animals↗

Aging influence on the E-rosette forming cells, spontaneous cell mediated cytotoxicity, and antibody dependent cellular cytotoxicity in humans.

In 131 adults and 107 aging healthy subjects of both sexes, the percentage of the T lymphocytes in peripheral blood and the cytotoxic activities of NK and K cells, were determined. No age-related differences have been found in the number of peripheral blood lymphocytes, the binding of NK cells to the K562 targets, the percentage of E rosette forming cells and the ADCC level. An increased proportion of T suppressor lymphocytes in elderly subjects and a large inter- and intra-individual variation of NK cells activity in both adult and aged subjects were found.

Adult↗

Modulation of IgG effector functions by a monovalent fragment of staphylococcal protein A.

The monovalent V-1 fragment of protein A (fSpA) with a mol. wt of 13,000 obtained from an u.v. mutant of Staphylococcus aureus Cowan I strain was proved to be able to modulate significantly some of the effector functions of IgG, such as complement fixation, catabolism, attachment to Fc receptors and antibody-dependent cell-mediated cytotoxicity. Moreover fSpA-like protein A obtained from the A676 strain is mitogenic and enhances NK activity of human peripheral lymphocytes. The efficiency of fSpA was found to be lower than that of protein A with regard to its ability to inhibit complement fixation, EA rosette formation and antibody-dependent cell-mediated cytotoxicity. Both protein A and fSpA had the same efficiency in activation of the complement system after reaction with human or guinea pig IgG, and in increasing the IgG catabolism. Unlike fSpA the monovalent B fragment of protein A (with mol. wt of 7000) was not able to inhibit EA rosette formation and antibody-dependent cell-mediated cytotoxicity. The results recommend fSpA, substituting for protein A, as a molecular probe for the investigation of IgG antibody and lymphocyte effector functions.

Animals↗

Correlation between the triggering of proliferation and the potentiation of NK activity induced by protein A in human lymphocytes.

Various preparations of Staphylococci protein A (SpA) obtained either from strain Cowan-1 or strain A676 and two SpA low molecular fragments (AB and B) were tested for their mitogenic and NK-stimulating activity on human peripheral blood lymphocytes. Though all 4 preparations of SpA and both of its fragments were able to react with human IgG, apparently with both Fab and Fc sites of IgG, only the SpA preparations derived from A676 strain triggered the proliferation and potentiated the NK-activity of treated cells. The parallelism between the mitogenic and NK-stimulating activities of SpA suggests that both activities might be under the control of the same portion of the SpA molecule located in the non-immunoglobulin binding region of the molecule.

Amino Acid Sequence↗

Natural cell-mediated cytotoxicity in Ehrlich ascites tumor-bearing mice.

The level of NCMC (natural cell-mediated cytotoxicity) in the spleen of Ehrlich ascites tumor-bearing mice at every 5 days after i. p. tumor transplantation, and the effect of cell-free ascitic fluid or serum of tumor bearers on natural cytotoxicity in vitro, were assessed. Spleen lymphocytes were used as effectors and 51Cr-labeled YAC1 cells as targets at the effector: target ratio of 200 : 1. In tumor bearers, the NCMC increased in the first days after i. p. inoculation of 1 X 10(6) Ehrlich cells with a maximum peak on day 5. Thereafter, the activity decreased continuously, on day 20 representing about half of normal value. Ascitic fluid and serum of tumor bearing mice significantly depressed the NCMC activity exerted in vitro by spleen lymphocytes of normal mice.

Animals↗

[Induction of macrophage activation with bacterial products for potentiation of resistance to some chronic infections].

Adult mice of the consanguine A2G strain received two intraperitoneal inoculations of 0.5 mg Listeria monocytogenes phospholipid extract at 30 days interval. In the treated animals and the controls, the capacity to develop a humoral immune response was tested 24 hours after the second inoculation, following antigenic stimulus with sheep red blood cells; phagocytizing in vitro of labelled germs by peritoneal macrophages and the response of lymphocytes to mitogenic and allogenic stimuli were likewise tested. The bacterial phospholipid extract activated the phagocytic function of the macrophages and the reactivity of the allogenically stimulated lymphocytes.

Animals↗

Morpho-functional aspects of the influence of procaine and diethylaminoethanol treatment on the immune system of rabbits.

Research was conducted in 24 male rabbits divided into three equal groups: 1) Controls; 2) Given daily i.m. injections with 15 mg/kg body weight of procaine for 30 days; 3) Given daily i.m. injections with 15 mg/kg body weight of diethylaminoethanol (DEAE) for 35 days. Blood samples were taken from the auricular vein to perform haematological investigations: before treatment, during treatment and for another 7 weeks after termination of treatment. At the end of the experiment, the animals were sacrificed in order to collect: 1) leukocytes, macrophages and lymphocytes from their spleen, for the purpose of immunological investigations, and 2) fragments of bone marrow (femur), thymus and spleen, for histopathological investigations. The result of haematological investigations indicated a statistically significant increase of circulating lymphocytes had occurred in rabbits treated with DEAE. There was an increase of percentage as well as of number of circulating lymphocytes. The increase occurred gradually in the course of treatment and continued after treatment was terminated. There were higher values than the initial ones by 44.4% and 66.4%, respectively, during the second and the fourth week after termination of treatment. Afterwards, the values started decreasing, so that by the end of the experiment (week 7 after termination), the values came close to those before treatment. Immunological findings indicated that T lymphocytes collected from rabbits treated with procaine or DEAE did not synthesize migration inhibition factors. Procaine and DEAE were found, in vitro, not to have a polyclonal stimulating effect over T lymphocytes. A study of blastic differentiation showed lymphocytes from treated rabbits to incorporate a larger amount of tritiated thymidine, by 52.6% in the procaine group and by 90% in the DEAE group, than those from non-treated rabbits. Histopathological examination indicated signs of a more intense activity in tissue formations involved in cell proliferation in the lymphoid organs collected from DEAE treated rabbits.

Anesthetics, Local↗

Aspects of immunity in the treatment of bronchial asthma.

The two subsets of CD4+ lymphocytes, Th1 and Th 2 secrete two groups of antagonistic cytokines: IL-2/IFNgamma, secreted by the Th1, and IL -4/IL-5, secreted by the Th2 cells. In addition to its antiviral effect, IFNgamma activates phagocytosis, enhances expression of Fc gamma R and MHC antigens on different cell types, stimulates synthesis of IgG molecules, etc. Interleukin-4 induces expression of Fc epsilon R, activates synthesis of IgE antibodies, while IL-5 stimulates the migration of eosinophils towards the lung. Eosinophils and IgE molecules are considered the main factors inducing bronchial asthma. In order to down-regulate IL-4 and IL-5 synthesis and to block the asthmatic phenomena, treatment of patients by inoculation of IFNgamma instead of glucocorticoids seems to be more reasonable.

Animals↗

Analysis by flow cytometry of the subpopulations of lymphocytes from the peripheral blood of procain or diethylaminoethanol treated rabbits.

The authors worked on 3 groups of 8 male rabbits, New Zealand race: 1) controls; 2) procain injected i.m., 15 mg/kg body weight, daily, for 30 days; 3) i.m. injected with diethylaminoethanol (DEAE), 15 mg/kg body weight, daily, for 35 days. The expression of the MHC I, MHC II, CD43, CD4 and IgM antigenic markers on the plasmatic membrane of the lymphocytes was studied using flow cytometry and monoclonal antibodies. Procain or DEAE treatment reduced the percentage of lymphocytes expressing I MHC, from 99.06 in the control group, to 94.51 in procain group and to 96.91 in the DEAE group. The intensity of expression of MHC complexes of class II decreases from 160.94 in the control group, to 107.21 in the procain group and to 104.05 in the DEAE group. No significant differences were noticed between the three groups of rabbits concerning the rate of lymphocytes that have on their surface expressed markers for CD43 (lymphocytes T), CD4 (Th), or IgM (lymphocytes B). Lymphocytosis induced in rabbits as a result of the DEAE treatment took place without a change in the proportions of lymphocyte subpopulations. The authors consider that owing to their capacity to reduce the expression of antigens MHC of class I and class II on the membrane of lymphocytes, procain and DEAE can have benefic effects in some autoimmune, autoaggression and inflammatory diseases.

Animals↗

The influence of synovial fluid on lymphocyte functions in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic recurrent and systemic inflammatory disease affecting around 1% of the population, that primarily involves the joints. In this study, we determined the Th1/Th2 lymphocytes ratio at the site of rheumatoid inflammation and the influence of the synovial fluid (SF) on the secretory and proliferative function in synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC), obtained from patients with RA. Our results showed significant differences concerning the mononuclear cells and the CD4/CD8 ratio in synovial fluid and peripheral blood of patients. In SF prevailed Th1 cells, while in peripheral blood we found another cytokine profile of T lymphocytes. Also synovial fluid lymphocytes had a low PHA-stimulated blastogenic response. Patients plasma and synovial fluid showed an inhibitory effect on prolipheration indexes.

Arthritis, Rheumatoid↗

The levels of neutrophils oxidative burst in rheumatic disorders.

We investigated the participation of the polymorphonuclear leukocytes (PMNs) as mediators of tissue destruction in 2 variants of rheumatic disorders that affect primarily the joints: the rheumatoid arthritis (RA) and the osteoarthritis (OA). We noted significant differences in the number of PMNs present at the joint level, which was low in OA and high in RA. The unstimulated and in vitro stimulated with opsonized zymozan (OZ) or ConA PMNs from the peripheral blood of these two groups of patients released a normal level of oxygen free radicals (OFR). On the contrary, the neutrophils isolated from the synovial fluid (SF) of RA patients showed a distinct feature: the unstimulated cells released high amounts of OFR, while those in vitro stimulated with OZ or ConA presented a low level of respiratory burst. In OA both in vitro unstimulated and stimulated with OZ or ConA neutrophils isolated from the SF had diminished values of OFR released. We assume that the chemiluminescence assay could detect distinct differences of the PMNs implications in RA and OA injuries and may be a laboratory test in the differential diagnosis of these rheumatic disorders.

Arthritis, Rheumatoid↗