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1

Biological properties and clinical significance of interleukin-1

100%
Robak T.
Postępy Higieny i Medycyny Doświadczalnej
|
1995
|
vol. 49
|
issue 2
263-285
2

Biology of interleukin-6 (IL-6) and its significance in the pathogenesis of some diseases

100%
Robak T.
Postępy Higieny i Medycyny Doświadczalnej
|
1994
|
vol. 48
|
issue 5
565-588
EN
In the paper numerous activities of IL-6 toward various normal and neoplastic cells are reviewed.The role of this cytokine in pathophysiology of various disease including infections and inflammatory and autoimmune diseases as well as in leukaemias, lymphomas and other neoplastic diseases is presented.Potential clinical value of the IL-6 levels in the serum and the role of its recombinant form in the treatment of thrombocytopenia and some neoplastic diseases is also discussed.
3

Biological properties and therapeutic applications of interleukin-2

100%
Robak T.
Postępy Higieny i Medycyny Doświadczalnej
|
1995
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vol. 49
|
issue 3
367-393
EN
A cytokine produced by the subpopulation of activated helper lymphocytes T has been called interleukine-2 (IL-2).The obtaining of recombinant cytokine has facilitated the study of ita biological properties and its application in teh treatment of certain neoplastic and infectious diseases.IL-2 affects the target cells by means of a receptor of great affinity consisting of three independent chains: alpha, beta, gamma.The cytokine is the most important growth factor of lymphocytes T, conditioning their clonal expansion.Antigen stimulation in the condition for the experssion of IL-2 does not, however, affect resting lymphocytes T. The expression of teh receptor for this cytokine on NK cells is ,however, continous in character but only a very small percentage of these calls has receptors of great affinity.IL-2 plays a great role in adoptive immunotherapy consisting in intravenous administration of cell with cytotoxic properties.Cells obtained from peripheral blood and grown in vitro are called LAK cells (lymphocyte activated killer cells), while cells obtained from neoplasms and grown in similar conditions are named TIL cells (tumor infiltrated lymphocutes).LAK and TIL cells reveal a similar antineoplastic activity in vivo.At present, however, recombinat IL-2alone is used more often, either intravenously or subcuteously.The cytokine is effective in the treatment of patients with disseminate cancer of the kidney and melanoma, and in adjuvant therapy of acute myeloid leukemia.Attempts have been to apply it in the treatment of AIDA and leprosy.The toxic effect of IL-2 depends on the dose and the mode of administration.In the majority of patients parainfluenzal symptoms appear.Most undesirable effects are connected with multisystemic syndrome of capillary vessels hypermeability leading to the increasing fluid retention into extravascular spaces, oedema, hypotonia and oliguria.
4

Progres in biology and treatment of hairy cell leukaemia

100%
Robak T.
Postępy Higieny i Medycyny Doświadczalnej
|
1993
|
vol. 47
|
issue 6
437-461
5

Biology of trombopoietin and its receptor

100%
Robak T.
Postępy Higieny i Medycyny Doświadczalnej
|
1996
|
vol. 50
|
issue 6
649-663
EN
Megakaryocytopoiesis is regulated by a number of cytokines with either stimulatory or inhibitory effects. Thrombopoietin (TPO), a cytokine with specific megakaryocyte naturational activity recently has been identified as the c-Mpl ligand. The physiological role of TPO and its potential mechanism of regulation has been investigated by generating mice that are missing the gene for TPO receptor (c-Mpl) and therefore deficient in the receptor itself. In homozygous knock-out mice (c-Mpl-/-) blood platelet counts were reduced to about 85% compared to wild-type mice. Several groups have now reported on the genomic structure of the TPO locus and the gene maps to the long arm of human chromosome 3 and mouse chromosome 16. The human cDNA predicts a mature molecule of 332 aminoacids with striking homology to erythropoietin throughout the N-terminal half. Recombinant TPO has profund effects on megakaryocyte progenitors and induction of megakaryocyte maturation to the point of platelet production. Administration of recombinant TPO to redents or primates treated with myelosuppresive agents abrogates or alleviates the severity and the duration of the resultants thrombocytopenias. The in vitro and in vivo activities of the TPO indicate that this cytokine may hold a promise for prevention and treatment of thrombocytopenia associated with chemotherapy, irradiation and bone marrow transplantation.
6

The Influence of amifostine used alone or in combination with 2-chlorodeoxyadenosine on normal and chronic myelogenous leukemia granulocyte-macrophage progenitor cells in vitro

64%
Korycka A., Robak T.
|
|
vol. 48
|
issue 4
293-299
EN
We evaluated the influence of amifostine used alone or in combination with 2-chlorodeoxyadenosine (2-CdA) on the colony growth of normal and chronic myeloid leukemia (CML) granulocyte-macrophage progenitor cells (CFU-GM) in semisolid culture in vitro. Amifostine at a concentration of 1 mg/ml was either added directly to the culture medium of normal and CML CFU-GM, or mononuclear cells (MNCs) were first preincubated with amifostine at the same concentration, washed in Iscove's modified Dulbecco minimum essential medium (IDMEM) and then added to the culture medium. Amifostine used alone inhibited the growth of CML CFU-GM colonies to a higher degree than those of normal CFU-GM, but the differences were not statistically significant. Amifostine preincubated with MNCs and used together with the highest concentration of 2-CdA significantly inhibited the colony growth of CML CFU-GM as compared to 2-CdA alone (p<0.05). In contrast, the colony growth inhibition of normal CFU-GM was not significantly lower compared to 2-CdA used alone. Our studies suggest that 2-CdA used together with amifostine is more toxic to leukemic CFU-GM than to their normal counterparts.
7

Effect of cyclosporin A used alone and in combination with either 2-chlorodeoxyadenosine or fludarabine on normal and chronic myelogenous leukemia progenitors in vitro

64%
Korycka A., Robak T.
Archivum Immunologiae et Therapiae Experimentalis
|
2003
|
vol. 51
|
issue 1
61-67
EN
We evaluated the influence of cyclosporin A (CsA) used alone or together with new purine nucleoside analogues (PNAs): 2-chlorodeoxyadenosine (2-CdA) and fludarabine (F-ara-A) on the colony growth of normal and chronic myelogenous leukemia (CML) granulocyte-macrophage progenitor cells (CFU-GM) in cultures in vitro. The assay was based on the method described by Iscove et al. in our modification. Specimens of bone marrow were collected from 15 patients with CML in the chronic phase and from 10 hematologically normal patients. CsA at the concentrations of 1, 2 and 4 mug/ml was used alone and at the concentration of 4 mug/ml it was preincubated with MNCs and after 30 minutes PNAs were added to the culture medium. 2-CdA at the concentrations of 5, 10, 20 nM and 0.4, 0.8, 1.6 muM of F-ara-A were used. After 14 days of incubation the colonies were scored under inverted microscope. We observed that CsA used alone at all three concentrations in a statistically significant degree inhibited the colony growth of CML CFU-GM, as compared to the control (p<0.02) and it did not significantly influence the normal colony growth. IC50 for CsA was 3.9 mug/ml in case of normal CFU-GM and 2.7 mug/ml in case of CML CFU-GM. After the use of CsA in combination either with the highest concentrations of 2-CdA or F-ara-A, statistically significant differences, as compared to CsA used alone were observed (p=0.008; p=0.03 for CsA with 2-CdA; and p=0.0007; p=0.005 for CsA with F-ara-A; respectively for normal and CML CFU-GM). However, there were no significant differences between the combinations of drugs and PNAs used alone. In case of the combination of CsA with the highest concentrations of both PNAs significant differences in the colony growth inhibition between normal and CML CFU-GM were observed (p=0.002 and p=0.005, respectively for 2-CdA and F-ara-A). In conclusion, at the used concentrations of the drugs a subadditive action was observed either between CsA and 2-CdA or between CsA and F-ara-A.
8

Apoptosis-the programmed cell death

64%
Gora-Tybor J., Robak T.
Postępy Higieny i Medycyny Doświadczalnej
|
1994
|
vol. 48
|
issue 3
209-225
EN
Apoptosis is structurally distinct programmed cell death pathway.It takes place during embryogenesis, after withdrawal of the trophic hormones and in the course of normal tissue turnover.Defective regulation of apoptosis may play a very important role in the aetiology of cancer and other diseases.In this paper these and other problems concerning with apoptosis are reviewed.
9

Cytokines in reumatoid arthritis

64%
Robak T., Gladalska A.
Postępy Higieny i Medycyny Doświadczalnej
|
1997
|
vol. 51
|
issue 6
621-636
EN
In this review we have examined the role of a variety cytokines in the pathogenesis of rheumatoid arthritis (RA) and their possible applications in the treatment of this disease. Cytokines are small protein molecules, released by activated cells which function as chemical messengers between cells of the immune, inflammatory and other systems. The studies using isolated cells from RA synovial membranes indicate that the vast majority of known cytokines are found in RA synovial tissue. These include IL-1, TNFa, IL-6, IL-8, TGFb, GM-CSF and others. TNFa and IL-1 are important 'pivotal' molecules in the disease process. TNFa has been detected in the serum and synovial fluid of patients with RA, sugesting an important contribution of this cytokine to the development of arthritis. Clinically, TNF-a has been also associated with markers of rheumatoid disease activity. Rheumatoid synovial tissue synthesizes large amounts of both forms of IL-1 (IL-1a and IL-1b) in vitro. IL-1 can exert a variety of systemic effects, including induction of fever and synthesis of acute phase proteins. It also induces local joint effects mediating production of fibroblast fibronectin and tissue collagenase. IL-6 is found in greater quantities in the synovial fluids from patients with RA compared to osteoarthritis. Synovial fluid IL-6 levels correlate with local IgM rheumatoid factor and systemic acute phase protein production. Chemokines, including IL-8, have potent chemotactic activity for cells of the immune system. IL-8 not only participates in the inflammatory phase of RA, but also participates in the vasculoproliferative phase of this disease. Recent data on the cytokine profile in RA implies that alternative treatment strategies should be considered. Potential approaches for modifying the cytokine network include inhibition of cytokine production or their action, inhibition of signal transduction and administration of suppressive cytokines.
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