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Biomedical subjects

M Colić

Publications and source records attributed to M Colić.

At least 73 records · Page 4Linked to original sources

Thymic epithelial antibodies: immunohistological analysis and introduction of nomenclature.

During the Workshop "The Thymus. Histophysiology and Dynamics in the Immune System', Rolduc, april 1989, a special workshop was hold to characterize monoclonal antibodies (mAb) to thymic epithelial cells (TEC) in thymus of man, mice, and rat. Twenty-five TEC-specific mAb's were evaluated for their immunohistological staining patterns on reference thymus, thymuses during ontogeny, various other organs (all tissues obtained from the species against the mAb was raised) and thymuses of other species. In this report only immunohistological results of reference thymuses and thymuses of other species are described. Based on the staining patterns on reference thymuses, mAb could be subdivided in 5 main groups. It is proposed to use these clusters of thymic epithelial staining patterns (CTES) to designate individual mAb, awaiting the possible incorporation in existing CD nomenclature for leucocyte differentiation antigens. The present immunohistological approach will be extended by additional analysis for which a protocol was designed. The ultimate goal of this TEC-mAb workshop is to get well-characterized reagents in the analysis of TEC-associated molecules with putative function in intrathymic T-cell processing.

Animals↗

Immunohistochemical characterization of rat thymic non-lymphoid cells. I. Epithelial and mesenchymal components defined by monoclonal antibodies.

Molecular microenvironmental heterogeneity within rat thymus was studied by a panel of 13 monoclonal antibodies (mAbs) raised to thymic epithelial (TE) cells and mesenchymal stroma. Based on their anatomical distribution patterns observed with immunohistological techniques on frozen sections and double immunostaining using anti-keratin antibodies to identify epithelium, they were subdivided into five groups: (i) pan TE cells antibodies (R-MC 2, 3 and 8); (ii) cortical TE cells antibodies (R-MC 13-17); (iii) antibodies detecting subcapsular and subtrabecular TE cells and most medullary TE cells (R-MC 18-20); (iv) antibody to Hassall's corpuscles (HC) and a small subpopulation of medullary TE cells (R-MC 22); (v) mesenchymal stroma antibody (R-MC 23). The obtained results show phenotypic heterogeneity of rat thymic epithelium and its distinction compared to mesodermal-derived compartment.

Animals↗

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↗

Common form of Lyme borreliosis carditis--complete heart block with syncope: report on 3 cases.

Third degree atrioventricular (AV) heart block with severe Adams-Stokes attacks in 3 patients with Lyme borreliosis is described. All patients had similar clinical manifestations: previously healthy, they experience syncope as an abrupt onset of the disease. Data on skin changes--erythema migrans--was subsequently obtained, although the patients did not recall being bitten by a tick. Diagnoses were based on clinical manifestations and on positive serologic test results to borrelia. Following AV block returned to sinus rhythm with normal AV conduction in all patients.

Adams-Stokes Syndrome↗

[Factors which affect long-term patency in femoro-popliteal bypass].

INTRODUCTION: The aim of this study was to investigate how "run off", diabetes, cigarette smoking and early reinterventions influence long-term patency of the "reversed" and "in situ" femoro-popliteal (F-P) bypass grafts. PATIENTS AND METHODS: The study included 1991 patients with "reversed" F-P and 99 patients with "in situ" F-P bypass grafts operated on between 1988 and 1994. There were 153 (80.10%) male and 38 (19.90%) female patients in the group with "reversed" bypass and in the group with "in situ" bypass there were 78 (78.8%) male and 21 (21.2%) female patients. The average age of all patients was 59.04 (27-80) years. Eighty five (44.5%) patients in the group with "reversed" F-P bypass had diabetes mellitus and 43 (43.4%) in the group with "in situ" bypass. One hundred and fifty two (79.68%) patients in the group with "reversed" bypass were cigarette smokers and 80 (80.8%) in the group with "in situ" bypass. In Table 1 patients according to Fontain's classification of occlusive arterial disease are presented. On the basis of angiographic examination all patients were divided into four groups (with patent all 3 crural arteries, with patent 2 crural arteries, with patent one crural artery and without patent crural arteries) (Table 2). All patients were controlled using physical and Doppler ultrasonographic examinations immediately after the operation; after 1, 3, 6 months and then every year postoperativelly. In cases with suspected graft occlusion or any other complication, control angiography has also been carried out. Statistical analysis of the results was performed using chi 2 and Fisher's test. RESULTS: The patients were followed-up from 3 to 10 years. In cases with patent all 3 crural arteries there was no significant difference in long-term patency between "reversed" and "in situ" bypasses (Fisher's test, P = 0.66; p > 0.05) (Graph 1). In cases with patent two crural arteries, there was no significant difference between groups with "reversed" and "in situ" bypasses chi 2 = 0.25, p > 0.05) (Graph 2). The long-term patency was significantly better in the group with "in situ" bypass if only one crural artery was patent (chi 2 = 4.96, p < 0.05) (Graph 3). In cases with occluded all three crural arteries there was no significant difference in long-term patency between the two examined groups (Fisher's test, P = 0.29; p > 0.05) (Graph 4). There was no significant difference between groups with "reversed" and "in situ" bypasses in patients with diabetes mellitus (chi 2 = 0.01; p > 0.05) (Graph 5). There was also no statistically significant difference between the two examined groups regarding the preoperative cigarette smoking (chi 2 = 0.94; p > 0.05) (Graph 6). However, in both groups postoperative cigarette smoking showed a statistically significant decrease in long-term patency (chi 2 = 66.71; p < 0.01) (Graph 7). The early REDO operations statistically significantly decreased long-term patency in both groups (chi 2 = 34.89; p < 0.01) (Graph 8). The late graft occlusions were found in 60 patients with "reversed" and 23 patients with "in situ" F-P bypasses. Table 3 shows causes of late graft occlusions. CONCLUSION: In some cases with pure "run off" "in situ" bypass technique showed better long-term patency. We preferred this technique when "run off" was pure, when diameter of the saphenous vein was small, and when bypass was "long". Diabetes mellitus had no significant influence on long-term graft patency in both groups, as well as regarding preoperative cigarette smoking. However, postoperative cigarette smoking and early REDO operations, statistically significant by decreased long-term graft patency in both groups. The reason was that cigarette smoking was not permitted postoperatively, while in cases with early reinterventions physical screening and ultrasonographic examinations were necessary.

Adult↗

[The popliteal artery entrapment syndrome].

The authors are presenting 8 patients with 9 cases of popliteal artery entrapment syndrome. There were one female, and 7 male patients with average age of 36.4 (25-54) years. Six cases were manifested with acute, 2 with chronic foot ischemia, while one case was asymptomatic. For diagnosis a combination of Doppler sonography and transfemoral angiography, was used. Eight cases were operated using posterior, while in one medial approach to the popliteal artery. The types I and IV of the popliteal artery entrapment syndrome were found in one case, type II in two cases, type III in 4 cases, while in one case a type of syndrome had not to be identified. During the operation the resection of the anomalous muscle and reconstruction of the popliteal artery, were done in 8 cases. In one case muscle resection or arterial reconstruction, were not necessary. The early potency rate and limb salvage, were 100%, while long term potency rate after mean follow up period of 6.3 years was 83.5%. The acute or chronic foot ischemia in health, young persons without typical atherosclerotical risk factors, suggests on popliteal artery entrapment syndrome.

Adult↗

[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↗

[Interleukin-1 beta in patients with primary immunocomplex glomerulonephritis].

Interleukin-1 is one of the most important pro-inflammatory cytokines whose role in the pathogenesis of glomerulonephritic process was proved in numerous studies. The aim of this study was to determine the urinary level of this cytokine in patients with primary immunocomplex glomerulonephritis and its significance in diagnosis of this disease. This prospective study comprised a total of 96 patients (84 males and 12 females) with primary immunocomplex glomerulonephritis. The elevated urinary IL-1 beta level was noticed in 43 (49.4%) patients with different histological forms of glomerulonephritis. The mean concentration was significantly higher in patient's group (57.7 +/- 120.7 pg/mg creatinine) (range 1.1-731) compared to control group (10.2 +/- 5.96 pg/mg creatinine) (range 1.6-25.4) (p < 0.05). There was no significant difference in the frequency of elevated urinary IL-1 beta concentration in different patients group based on histological type of glomerulonephritis (chi 2 = 6.377, p > 0.05). On the basis of our results we concluded that the elevated concentration of IL-1 beta in majority of patients with primary immunocomplex glomerulonephritis had suggested its role in the pathogenesis of glomerulonephritic process. The urinary level of IL-1 beta represents a novel, non-invasive parameter in the diagnosis of this disease, but its measurement is not useful in predicting the histological type of primary immunocomplex glomerulonephritis. The results of our study suggest the possibility that urinary IL-1 beta level reflects the activity of glomerulonephritic process and it could be useful in non-invasive monitoring of the disease progression.

Biomarkers↗

[Differential diagnosis of deep vein thrombosis].

UNLABELLED: The incidence of deep venous thrombosis (DVT) is high in numerous surgical and medical diseases [1]. There are increasing data on higher incidence of DVT in patients with malignant and other diseases [2]. The diagnosis of DVT is not always simple since there are subclinical and asymptomatic forms of the disease [3]. Besides, there are numerous pathological conditions that imitate deep venous thrombosis [4]. METHODS: We present the results of a retrospective study over the period of January 1, 1996--June 30, 1998 at the Department of Vascular Surgery. Over that period we treated 113 patients (64 females, 49 males, average aged 60.3 +/- 7.5 years) with clinical picture of deep venous thrombosis. All patients underwent duplex scanning examinations (Toschiba SSA-100 A, 3.5 MHz and 8 MHz probes) [5, 6]. Special examinations such as angiography (8 patients), computerised tomography or nuclear magnetic resonance (27 patients) were performed in cases with unclear findings. RESULTS: True DVT was established in 91 (80.3%) patients (Fig. 1). Seven of these patients had asymptomatic phlebothrombosis. Of 12 (10.6%) patients in 9 other pathologic conditions were found (Fig. 2). This symptomatic DVT was caused by malignant diseases (5 sarcomas, 2 metastatic carcinomas, 1 lymphoma); aneurysms of common femoral artery (2) and popliteal artery (2 patients). Ten patients (8.9%) with clinical picture of DVT established by special examinations had no evidence of the presence of intravenous thrombs (Fig. 3). This pseudo DVT was caused by calf haemathoma (3), Baker's cyst (2), popliteal artery aneurysm (1), lipoma of thigh (1), psoas abscess (1), gluteal abscess (1) and acute arthritis of the knee (1). The treatment of these groups of patients was different: surgical thrombectomy, use of streptokinase or heparine (true deep vein thrombosis), tumour extraction (Fig. 4) or another surgical treatment (symptomatic phlebothrombosis) and special decompression measures (Fig. 5) (pseudophlebothrombosis). DISCUSSION: Aetiopathogenesis of true DVT is determined by Virchov's triad [3, 4, 7, 8]. The incidence of DVT in medical and surgical patients is high (30-75%). Initially true DVT may be asymptomatic in 35-70% of patients [1, 3, 8] and depended on detection methods [1, 6, 7, 9, 10]. DVT may be only a symptom of other pathological conditions [2, 3, 7]. This symptomatic DVT is mostly caused by malignant diseases [2]. Pseudo DVT or primary deep vein obstruction may be caused by external abnormalities (right common iliac artery; compression of the left common iliac vein, malignant disease, retroperitoneal fibrosis, internal iliac compression of the external iliac vein, latent femoral hernia compression of the femoral vein, masses in the thigh (large tumours, true or false aneurysms, popliteal masses/aneurysms, large Baker's cysts), changes in the wall or within the lumen of a vein as aplasia, primary tumours, intraluminal spurs [7].

Diagnosis, Differential↗

Oxidative damage and metabolic dysfunction in experimental Huntington's disease: selective vulnerability of the striatum and hippocampus.

The etiology of neuronal death in neurodegenerative diseases, including Huntington's disease (HD), is still unknown. There could be a complex interplay between altered energy metabolism, excitotoxicity and oxidative stress. Unilateral administration of quinilonic acid (QA), NMDA agonist, in rat striatum in a single dose of 150 nM was used as a model of HD. The other two groups of animals were pretreated immediately before QA application with nerve growth factor (NGF) and fibroblast growth factor (FGF), respectively. Control group was treated with 0.9% NaCl in the same manner. Content of total glutathione was not altered in the striatum and hippocampus of QA-treated animals, as well as in the groups pretreated with neurotrophic factors (NF), compared to controls. Content of reduced glutathione, a key antioxidant, was mutually depleted in the striatum and hippocampus of each experimental group. The reduced/total glutathione ratio was decreased in the QA-treated animals, but nearby or over the controls in each structure of the NF-treated groups. These results support the hypothesis that oxygen-free radicals contribute to the excitotoxic neuronal injury, and also that NF could be the potential neuroprotective agents in HD. Moreover, activity of cytochrome c oxidase, the last component in the mitochondrial respiratory chain, was mutually increased in each structure of QA-treated animals. This increase was less pronounced in the NF-treated groups. Striatal lesions led to the loss of tonic inhibitory inputs to the globus pallidus with consequent increase in the activity of GABAergic efferent pallidal neurons, suggesting that NF could functionally repair the altered striopallidal pathway.

Animals↗

Xylazine, an alpha 2-adrenergic agonist, induces apoptosis of rat thymocytes and a thymocyte hybridoma line in vitro.

In our previous experiments, we demonstrated that xylazine, an alpha 2-adrenergic agonist, stimulated proliferation of thymocytes triggered by concanavalin A. In contrast, higher concentrations of xylazine were inhibitory. In this work, we studied the mechanisms involved in immunosuppression of xylazine and found that the compound at concentrations between 100 microM and 500 microM induced apoptosis of rat thymocytes in vitro. In addition, xylazine at concentrations higher than 50 microM also induced apoptosis of a thymocyte hybridoma (BWRT8) and increased apoptosis of the line triggered by T cell receptor (TCR) cross-linking. Apoptosis was confirmed by morphological analysis staining with merocyanine 540 and propidium iodide and in cases of BWRT8 by fragmentation of DNA. The mechanisms of xylazine-induced apoptosis of the BWRT8 hybridoma were further examined. We demonstrated that the process in both nonactivated and activated (TCR cross-linking) BWRT8 cells was not prevented by yohimbine (a selective alpha-adrenergic antagonist) and by antibodies to Fas and Fas-L. In contrast, cell death was completely blocked by a caspase inhibitor, z-Val-Ala-Asp (OMe)-CH2F. Cyclosporine, a calcineurin blocker, partly inhibited the xylazine-induced apoptosis of activated BWRT8 cells.

Adrenergic alpha-2 Receptor Agonists↗

[Alveolitis in patients with sarcoidosis].

In 20 patients with pulmonary sarcoidosis bronchoalveolar lavage (BAL) was performed. The cellular content was analysed and lymphocyte subpopulation was determined using monoclonal antibodies. The patients with more than 28% of BAL T lymphocytes are classified as patients with high intensity alveolitis (n = 8) and those with less than 28% of T lymphocytes as low intensity alveolitis (n = 12). Of the total number of BAL T lymphocytes in high intensity alveolitis CD 3+ T cells were 88.8 +/- 8.4% and in low intensity alveolitis 68.2 +/- 13.8% (p < 0.001). In high intensity alveolitis the number of CD 4+ T cells was increased and the number of CD 8+ T cells was decreased which caused the increased index CD 4:CD 8; 9.8 +/- 8.7. In low intensity alveolitis this ratio was 2.2 +/- 1.2. Effects of smoking were also analysed. In smokers the total number of BAL cells was higher 184.0 +/- 47.2 x 10(4) ml of BAL, and in nonsmokers 101.3 +/- 65.1 x 10(4) ml of BAL (p < 0.001). Smoking has no effects on the characteristics of the cellular elements and subpopulation of BAL lymphocytes in patients with sarcoidosis. In 7 patients T lymphocyte subpopulation in the peripheral blood were determined too. Patients with high intensity alveolitis had the increased index CD 4:CD 8 in the peripheral blood compared with low intensity alveolitis.

Adult↗

Increased activity of lymph node cells in thermal injury.

While trauma-induced suppression of T-cell responses is well documented, only few studies address lymphocyte activation. The aim of this study was to investigate the functional activity of lymph node cells in rats subjected to scald injury, proliferative activity, cytokine production, and responsiveness to exogenously added cytokines was evaluated in cells from lymph nodes draining burned tissue and from distant, nondraining lymph node cells. Results presented clearly show that lymph node cells in scalded rats are activated in vivo although the extent of proliferation and pattern of cytokine production differ: a) proliferative activity was elevated both in draining and distant lymph nodes, but was more pronounced in cells from lymph nodes draining the injured region; b) increased production of IL-2, and particularly IL-1 and IL-6 was found and coincides well with peak of proliferative activity of draining lymph node cells; IL-2 production by distant lymph node cells remained unchanged, IL-1 and IL-6 production was significantly increased coinciding with increased proliferation; c) increased responsiveness to exogenously supplied cytokines was found in draining lymph node cells, while it remained unchanged in nondraining lymph node cells. Early activation of lymphocytes demonstrated in our experiments could be one of the previously unrecognized consequences of trauma-induced immunosuppression.

Animals↗