Abstract As IL-2 and IFN-α modulate NK cell activity it was of interest to investigate the expression of newly defined NK cell receptors and augmented NK cell activity in healthy individuals after ...cytokine in vitro treatment. Peripheral blood lymphocytes (PBL) obtained from 31 healthy volunteers treated for 18 h with 200 IU/ml IL-2 and 250 IU/ml IFN-α were evaluated for NK cell cytotoxicity. Expression of NKG2D, CD161, CD158a, CD158b receptors was analyzed on CD3− CD16+ NK cells, cytotoxic CD16bright and regulatory CD16dim subsets by FACS flow. The found induced significant in vitro enhancement of NK cell activity by both cytokines is supported by specific cytokine induction in PBL of pSTAT1 and pSTAT5, determined by Western blotting, as well as induction of IRF-1 transcription. Both cytokines induce significant up-regulation of NKG2D expression while only IFN-α induced significant up-regulation of CD161, with no alteration in KIR expression by either cytokine on CD3− CD16+ NK cells. Investigated cytokines did not induce change in NK cell bright and dim subset distribution. Moreover, we find that, not only cytokine receptor induction on the CD3− CD16+ NK cells, but also simultaneous increase in their percentage and/or density on CD16bright and CD16dim subsets, represent good indicators of receptor cytokine-susceptibility. As the role of NK cells has been shown in the loss of tolerance, infection and cancer, the data obtained in this study may be of help in NK cell profiling, by giving referent values of cytokine-induced novel NK cell receptor expression either in evaluation of these diseases or in immunomonitoring during cytokine immunotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Considering tumor-induced suppression of natural killer (NK) cell activity the aim of this study was to investigate the in vitro effect of a standard immunotherapeutic cytokine, interferon (IFN)α, ...and a less investigated agent, 13-cis retinoic acid (RA) on the functional and receptor characteristics of CD16-defined NK cells and their functionally diverse dim and bright subsets in patients with metastatic melanoma (MM).
Peripheral blood lymphocytes (PBL) of patients with clinical stage IV MM were stimulated in vitro for 18 h in RPMI 1640 culture medium (CM) alone, CM supplemented with IFN-α (250 U7sol;ml), RA (10-6M) and their combination. NK cell activity was determined using standard 4 h radioactive cytotoxicity assay, while the expression of activating (NKG2D, CD1617rpar; and inhibitory (CD158a, CD158b) NK cell receptors on CD3-CD16+ NK cells and their functional bright and dim subsets were analyzed by flow cytometry.
NK cell cytotoxic activity was increased after in vitro treatment with IFN-α alone and in combination with RA, while only IFN-α induced increase in NKG2D and CD161 activating NK cell receptor expression. Contrary to this, RA treatment increased the expression of inhibitory KIR CD158b. IFN-α-obtained increase in CD161 expression was due to its induction on both NK cell subsets, while for NKG2D only on CD16bright subset.
The favorable enhancement of NK cell activity of MM patients obtained with IFN-α is associated with upregulation of activating NKG2D and CD161 receptors, while the lack of RA-associated upregulation is probably due to the shown increased expression of inhibitory KIR receptor CD158b after in vitro treatment with this agent.
Geological complexity of the territory of Serbia is a world curiosity: six
main geo-tectonic regions and tens sub-regions are delineated in a small area
of 88,000 km2. Geologic origin and regional ...structure of some areas has long
been the subject of discussion. Notable magmatism and associated tectonic
events in the Earth's crust provided for a fairly large hydrogeothermal
resource potential, which is manifested in more than 250 warm (mainly
mineral) springs and more than 100 hydrothermal wells. Thermal springs and
wells together discharge some 5 m3/s. This potential is used in part for
balneal therapy (waters differ in temperature and chemical composition) in
the spa areas of Serbia. The amounts of thermal water unused therapeutically
or the amounts of heat energy from unused geo-thermal water may be used in
almost all spas for space heating/cooling and thus increase the efficiency of
the thermal water energy utilization. This also will be cost-effective,
reduce emission of noxious gases, and improve the environmental-health image
of the resorts. The hydrogeothermal resources are described for 29 spas with
700 l/s total discharge capacity of water temperature between 25?C and 96?C,
or an overall heat energy of 78.40 MWt. Feasibility of additional energy
utilization of thermal water in spas is generally considered.
nema
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to determine the pattern of myocardial infarction (MI) incidence with regard to age, gender, infarction site, and the most important risk factors. All 3,454 patients ...hospitalized in coronary care units of Clinical Hospital Split between 1989 and 1997 were analyzed. In the 3-year period preceding the war, from 1989 to 1991, 1,024 patients were hospitalized because of MI. During the 3 years of full war activities, from 1992 to 1994, there were 1,257 patients (significantly more; p < 0.05). And in the 3-year period after the war, from 1995 to 1997, there were 1,173 patients. In the war period, there were 151 (12%) patients younger than 45 years of age (p < 0.05); of that number, 143 (95%) were men (significantly more than in the other two periods; p < 0.05) and 8 (5%) were women. In the period preceding the war, there were 66 (6.5%) patients younger than 45 years: 60 (91%) men and 6 (9%) women. In the period after the war, those numbers were 88 (7.5%), 81 (92%), and 7 (8%), respectively. The patients younger than 45 years (305) more often had MI of an inferior than an anterior site (49% vs. 28%; p < 0.001), whereas there was no difference in patients older than 45 years (36% vs. 37%; p > 0.05). The patients older than 45 years had significantly greater hospital mortality (21% vs. 4%; p < 0.001) and were more likely to have hypertension (51% vs. 15%; p < 0.001) as well as hypercholesterolemia (54% vs. 14%; p < 0.001). Smokers prevailed among those younger than 45 years (75% vs. 51%; p < 0.001). The number of hospitalized patients with MI was greatest during the war period. It included a significant increase in the incidence in men younger than 45 years (12% vs. 7%; p < 0.05), with smoking as the most important risk factor, especially for infarctions of inferior sites.
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