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Biomedical subjects

P Popović

Publications and source records attributed to P Popović.

15 recordsLinked to original sources
PubMed2001

Peripheral blood granulocyte activity following contact sensitization of rats with dinitrochlorobenzene.

Contact hypersensitivity (CHS) reaction is a classic example of a cell-mediated reaction. As the afferent phase of the reaction includes inflammation, CHS is a suitable model for investigating non-specific immunity. Some aspects of granulocyte activity in the afferent phase of experimentally induced CHS to dinitrochlorobenzene (DNCB) in two genetically different rat strains, AO and DA were examined in this study. A shift in the ratio of granulocytes to lymphocytes in favour of granulocytes and an increase in granulocyte survival were noted in DA rats. Granulocytes from both strains demonstrated increased levels of NBT reduction and an increase in their adhesion to plastic. Decreased granulocyte adhesion in the presence of monoclonal antibodies to beta2 integrins (anti-CD11b/c and anti-CD18) points to the contribution of these molecules to granulocyte adhesiveness during the sensitization phase of CHS. Stimulation of adhesion in the presence of anti-CD11a antibody, points to a differential modulation of adhesion molecule activity during the afferent phase of CHS. Changes in functional activity of granulocytes demonstrated in this study might contribute to the development of CHS in rats.

Animals↗
PubMed2001

Pattern ERG and psychophysical functions in Best's disease.

The aim of the study was to asses the neurosensory retinal function in 12 patients (24 eyes) with different stages of Best's disease, by determining how pattern and full field flash ERG responses were related to visual acuity, stage of disease and extent of visual field loss. All patients had typically abnormal EOG responses and normal full field-flash ERG responses. Patients were stratified in two groups according to visual acuity. In the first group 12 eyes with visual acuity better than 0.5, all amplitudes and latencies of PERG P50 and N95 responses were in the normal range. Small central scotoma was detected by static perimetry in four of these eyes. In the second group of 12 eyes with visual acuity 0.5 or less, PERG showed reduced both P50 and N95 amplitudes in five eyes, and N95 solely, in two eyes. All patients had central scotomas detected by static perimetry. Progression of the disease, seen in deterioration of visual acuity and progression of central visual field defects, corresponded well with reduction of both PERG P50 and N95 amplitudes. There was no correlation found between visual acuity and EOG responses. Our results show that in Best's distrophy, pattern ERG is getting abnormal with progression of the disease, indicating relative preservation of neurosensory retina in initial stages of the disease. In contrast to EOG - being abnormal in all the patients regardless of the stage of disease - and full field-flash ERG - being normal in most of the patients - PERG gives opportunity for electrophysiological determination of the progression of the disease.

Adolescent↗
PubMed2001

Biochemical and functional characterization of a molecule expressed by a subset of thymic medullary epithelial cells.

A monoclonal antibody (mAb), named TE-4F 10, was produced by fusing P3X-Ag8 myeloma cells with splenocytes of BALB/c mice immunized with a rat medullary thymic epithelial cell (TEC) line, (TE-R 2.5), previously established in our Institute. Flow cytometry showed that 85-95% TE-R 2.5 cells expressed the TE-4F10 antigen. The mAb immunoprecipitated a 29 kDa molecule from the TE-R2.5 cell lysate. Immunohistochemical analysis using single and double staining of the thymus with anti-cytokeratin (CK) mAb, showed that TE- 4F10 mAb selectively stains a subpopulation of medullary TEC. Hematopoietic and lymphoid cells were negative. The expression of the TE-4F10 antigen on TE-R 2.5 cells in vitro was significantly upregulated by interleukin 1 (IL-1) and tumor necrosis factor (TNFalpha). Other cytokines IL-4, IL-6, IL-10 and granulocyte - macrophage colony stimulating factor (GM-CSF) showed lesser stimulation on its expression, whereas interferon gamma (IFN) and dexamethasone were without significant effect. The TE-R 2.5 cell line strongly bound and induced apoptosis of a rat / mouse thymocyte heterohybridoma (BWRT8), phenotypically alphabetaTCRhiCD4hiCD8lo. TE-4F10 mAb significantly inhibited binding (40-50%) of both BWRT8 cells and the BWRT8 - MDP.1 subclone to TE-R 2.5 cells. The inhibition was enhanced when TEC were stimulated with IL-1 + TNFalpha. The mAb also significantly blocked apoptosis of BWRT8 but did not modulate cell death of the BWRT8 - MDP.1 subclone, which was resistant to TEC-induced apoptosis. These findings indicate that the TE-4F10 antigen might be selectively involved in adhesion and selection processes in the medullary thymic microenvironment. The mAb of the same characteristics has not been described so far.

Animals↗
PubMed2000

Comparison of signaling pathways involved in apoptosis of a thymocyte hybridoma triggered by a rat thymic medullary epithelial cell line, dexamethasone or T-cell receptor cross-linking.

Using an in vitro co-culture assay we found that a rat medullary thymic epithelial cell (TEC) line (TE-R2.5) induces apoptosis of the BWRT8 thymocyte hybridoma (TH) (CD4(hi)CD8(low) alphabetaTCR(hi)). TH apoptosis induced by this TEC line was predominantly mediated by direct cell-cell contacts and was potentiated by cross-linking of the T cell receptor (TCR) by R73 monoclonal antibody (mAb). Dexamethasone (Dx) also triggered TH apoptosis but inhibited death of these cells induced by TE-R2.5 cells or immobilized R73 mAb. The TEC-induced apoptosis was independent of the LFA-1/ICAM-1 interaction but partly depended on a novel 29 kDa molecule expressed on TE-R2.5 cells. All three types of TH apoptosis were followed by the cleavage of poly-(ADP-ribose)-polymerase and were blocked by a caspase inhibitor Z-Val-Ala-Asp(OMe)-CH(2)F.PKC stimulation by phorbol myristate acetate interfered with the TH apoptosis induced by TE-R2.5 and Dx, but did not modulate the effect of R73 mAb. On the contrary, inhibition of calcineurin with cyclosporine A did not influence the apoptosis induced by TE-R2.5 and Dx, but completely prevented the R73-triggered TH cell death. The TE-R2.5-mediated BWRT8 apoptosis was suppressed by Na-orthovanadate, an inhibitor of protein tyrosine phosphatases (PTP) as well as by genistein, a protein tyrosine kinase (PTK) inhibitor, while both compounds potentiated the effect of Dx. Blocking PTP, but not PTK decreased the proapoptotic effect of R73 mAb. These results, including those using a BWRT8 subclone (BWRT8-MDP.2) which is resistant to TCR-triggered apoptosis, but sensitive to apoptosis stimulated by TE-R2.5 and Dx, indicate that TE-R2.5-induced TH apoptosis in our model is different from apoptosis in other TEC co-culture models, published so far.

Animals↗
PubMed2000

Modulatory effect of 7-thia-8-oxoguanosine on proliferation of rat thymocytes in vitro stimulated with concanavalin A.

7-thia-8-oxoguanosine (immunosine) is a guanosine analogue showing immunostimulatory activity on different components of the immune system, including B lymphocytes, natural killer cells and macrophages. However, little is known about its effect on T-cell functions. In this work it was demonstrated that immunosine at concentrations between 10 microM and 1 mM stimulated proliferation of rat thymocytes in vitro triggered by suboptimal concentrations of concanavalin A (Con A). The effect correlated with increased interleukin 2 (IL-2) production, upregulation of the IL-2 receptor alpha (IL-2Ralpha) expression and decreased apoptosis of thymocytes in comparison to the effect of Con A alone.

Adjuvants, Immunologic↗
PubMed1998

Bidirectional interactions between thymocytes and thymic epithelial cell lines in vitro.

In vitro interactions of thymocytes and thymocyte hybridomas with cortical (R-TNC.1) and medullary (TE-R 2.5) rat thymic epithelial-cell (TEC) lines were studied. It was found that the cortical line had better adhesion capability. It bound exclusively immature CD4+ CD8+ alpha beta TCRlo thymocytes, induced apoptosis of a subset of these cells, and stimulated proliferation of the BWRT 1 (CD4- CD8- alpha beta TCR-) hybridoma. The medullary line bound both immature and mature thymocytes, decreased their apoptosis, and induced apoptosis of the BWRT 8 (CD4+ CD8lo alpha beta TCRhi) hybridoma. Thymocyte differently modulated cytokine production by TEC lines, upregulating the secretion of IL-1 by R-TNC.1 and IL-6 by TE-R 2.5 cells. Finally, coculture of thymocytes with TEC lines resulted in different patterns of protein-tyrosine phosphorylation in thymocytes. These results show the existence of mutual bidirectional interactions between thymocytes and TEC lines in vitro, but these processes differed depending on phenotypic characteristics and origin of TEC lines used.

Animals↗
PubMedDate not supplied

Immunosine (7-thia-8-oxoguanosine) acts as a cofactor for proliferation of T cells.

Immunosine (7-thia-8-oxoguanosine) is a novel guanosine analogue showing immunostimulatory activity both in vivo and in vitro. This compound acts on different components of the immune system including B cells, natural killer (NK) cells and antigen-presenting cells (APC). However, its influence on functions of T cells is poorly understood. In this work we studied the effect of immunosine on proliferation of total rat splenocytes and purified T cells triggered by different mitogens and the mechanisms involved. The results demonstrate that immunosine significantly stimulates proliferation of T cells. The effect was dose-dependent and also depended on concentrations of specific stimulators. Maximal stimulation was seen using 250 microM immunosine. The stimulatory effect of immunosine on lymphocyte proliferation triggered by Concanavalin A (Con A) correlated with increased interleukin 2 (IL-2) production and upregulation of the IL-2 receptor alpha (IL-2Ralpha) expression. The dependency of T-cell proliferation on IL-2/IL-2R was confirmed using neutralizing anti-IL-2Ralpha monoclonal antibodies (mAbs). Higher concentrations of immunosine in the presence of optimal concentrations of Con A (5 microg/mL) inhibited proliferation of T cells. A similar stimulatory effect of immunosine on proliferation of purified T cells and IL-2 production was observed using an anti-T-cell receptor (TCR) mAb and a combination of anti-TCR mAb and IL-2. However, the guanosine analogue did not significantly modulate proliferation of T cells triggered by IL-2 alone. When the combination of phorbol myristate acetate (PMA) and ionomycin was used for T-cell stimulation different results were obtained. Under lower cell stimulation immunosine significantly potentiated T-cell proliferation, expression of IL-2Ralpha and IL-2 production. In the presence of suboptimal stimulation the compound stimulated T-cell proliferation and IL-2Ralpha expression, whereas under maximal stimulation an enhancing effect on IL-2 production was seen. Since direct stimulatory effect of immunosine on T-cell growth in culture was rather weak it can be postulated that the compound acts as a cofactor for T-lymphocyte proliferation.

Animals↗
PubMedDate not supplied

Significance of de-novo IgD and IgM synthesis in CSF of patients with relapsing-remitting form of disseminated demyelinating disease of CNS.

Disseminated demyelinating disease of the central nervous system (DDD CNS) is immunologically mediated, with confirmed significant intrathecal immunoglobulin production. According to recently known immunopathogenic occurrences and activation of humoral immune response, we have assumed that the presence of oligoclonal immunoglobulins of M and D classes can be confirmed in cerebrospinal fluid (CSF) of patients with DDD CNS. With the aim of its further determination in CSF of relapsing-remitting DDD CNS patients in either remission and relapse phase, respectively, we have confirmed the presence of oligoclonal IgD and IgM bands, the association of this production and the presence of new demyelinating zones found by MRI of endocranium, as the time elapsed from the last relapse until the obtaining of CSF for further analyses. Method of isoelectric focusing with Western blott procedure was used for the confirmation of oligoclonal IgM and IgD bands presence in CSF. Significant presence of intrathecally synthetized oligoclonal IgM and IgD in patients with DDD CNS in exacerbation phase was presented. Almost in all patients in this phase was found at least one indicator of acute phase (positive MRI finding, presence of oligoclonal IgM or IgD bands). Significant decrease of positive findings of oligoclonal Ig bands in CSF was correlated with the time elapsed from the onset of relapse until the obtaining of CSF for the analysis due to short half-life of those Ig in CSF.

Adult↗
PubMedDate not supplied

[Importance of determining the absolute CD3+ lymphocyte count during induction therapy with antithymocyte globulin in kidney transplantation patients].

Antithymocyte globulin (ATG) is successfully applied in prophylaxis and treatment of renal allograft rejection. However, it is an expensive mode of therapy, associated with increased risk of opportunistic infections and lymphoproliferative diseases. For this reason, monitoring of ATG immunosuppressive effects as well as individual dose adjustment represent an important therapeutic approach. Here we report our results of ATG dose titration according to total lymphocyte count (< 300/microliter) and absolute CD3+ count (< 50/microliter) in seven renal transplant patients. Monitoring of absolute CD3+ count enabled reduction of the mean daily dose from the recommended dosage in all patients. Our results have also shown that the absolute CD3+ count is a more reliable parameter than the total lymphocyte count for monitoring of ATG biological effects on T cells. When rapid, significant and stable decrease of absolute CD3+ count is reached, ATG dose can be further adjusted according to the total lymphocyte count. With this approach, ATG treatment becomes rational and safe, with well established immunosuppressive effect, reduced risk of overimmunosuppression and considerable cost benefit.

Adult↗
PubMedDate not supplied

Lipid peroxidation intensity and lipid status parameters in the estimation of the severity of ischemic heart disease.

Atherosclerotic changes on the coronary arteries are the basis of the ischemic heart disease. It is assumed that the initial changes in this process occur as a consequence of the lipid peroxidation in the vessel wall. We estimated this process through the level of malondialdehyde (MDA) in the serum of 86 patients in whom selective coronary angiography was done for the suspected ischemic heart disease. According to the number of the stenotic coronary arteries (stenosis greater than 50%), we divided the patients into four groups: the control group with normal coronary angiography finding, simple, double or triple vessel coronary disease. In all the patients we also estimated the other parameters of the lipid status (cholesterol, triglycerides, LDL, HDL, Apo-AI, Apo B) and atherogenic indices Apo-AI/Apo B, LDL/HDL and HDL/total cholesterol. No significant changes were observed in the lipid parameters between the control and experimental group. However, mean MDA level in the whole experimental group was 3.89 mumol/L, 3.93 mumol/L in triple vessel coronary disease, 3.83 mumol/L in double vessel and 3.92 mumol/L in single vessel disease group. The difference between all the experimental and the control group was highly significant (p < 0.001). We concluded that the level of MDA--lipid peroxidation index had the better correlation with the disease status than the other parameters of lipid status and the sensitive atherogenic indices.

Adult↗