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1

Serum levels of cytokines in alcoholic liver cirrhosis and pancreatitis

100%
Szuster-Ciesielska A., Daniluk J., Kandefer-Szerszen M.
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vol. 48
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issue 4
301-307
EN
Although altered cytokine homeostasis has been implicated in the pathogenesis of both alcoholic liver and pancreas diseases, the serum cytokine pattern characteristic of concomitant alcoholic liver cirrhosis and pancreatitis has not been examined. In this paper we examine the serum levels of proinflammatory cytokines, such as IL-6, IL-8, TNF-alpha, and also antiinflammatory ones, such as IL-10 and TGF-beta, in 22 patients with alcoholic liver cirrhosis and 28 patients with chronic pancreatitis and compare them with those detected in the sera of 14 patients with concomitant alcoholic cirrhosis and pancreatitis. All patients were heavy alcohol drinkers, consuming more than 70 g of pure alcohol per day for at least 5 years. The control group consisted of 33 age- and sex-matched healthy subjects receiving an annual health examination. They were not addicted to alcohol and confirmed to be free of major cardiopulmonary, gastrointestinal and hepatobiliary-pancreatic diseases. The results indicated that the cytokine pattern in the sera of patients with concomitant liver cirrhosis and pancreatitis was characterized by increased levels of two proinflammatory cytokines: TNF-alpha, the concentration of which seemed to be influenced by both liver and pancreas injury, and IL-6, which seemed to be rather connected with pancreas injury. Increased levels of IL-8, which were detected in the sera of patients with cirrhosis, pancreatitis and concomitant cirrhosis and pancreatitis, were rather connected with exacerbation of the disease processes which occurred only in some of the patients. No significant changes in the levels of IL-10 or TGF-beta were detected in the sera of patients with chronic pancreatitis and concomitant cirrhosis and pancreatitis, while in patients with cirrhosis significantly decreased levels of IL-10 were found. A significant imbalance between proinflammatory/antiinflammatory signals was especially characteristic of alcoholic cirrhosis and concomitant cirrhosis with pancreatitis.
2

Effect of granulocyte-macrophage colony stimulating growth factor on interferon and tumor necrosis factor production in whole blood cell cultures of patients with acute myelogenous leukemia

100%
Kaminska T., Hus I., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 2 suppl.
83-88
EN
The effect of recombinant human granulocyte-macrophage colony-stimulating growth factor (rHuGM-CSF) treatement on in vitro interferon (IFN) and tumor necrosis factor (TNF) production in peripheral blood cells of 46 patients with acute myelogenous leukemia (AML) was examined. GM-CSF significant enhanced virus-induced IFN- production in blood cells (containing 70% of blasts) of 28 patients with M4-M5 AML according to the French-American-British (FAB) classification and also phytohemagglutinin (PHA)-induced IFN- production in blood cells (containing 68% of blasts) of 18 patients with AML M0-M3 type. In control blood cells (25 healthy persons) GM-CSF enhanced PHA-induced IFN- but did not influence IFN- production. In the presence of GM-CSF, TNF- titers induced with lipopolysaccharide were also higher in control blood cells but not in cells of patients with M0-M3 or M4-M5 type of AML. The significance of GM-CSF-enhanced IFN- and IFN- production in antimicrobial and antileukemic immune reactions which can develop during GM-CSF therapy is discussed.
3

Cytokine production in whole blood cell cultures of patients with B-lineage acute lymphoblastic leukemia. The influence of granulocyte-macrophage colony stimulating factor

100%
Kaminska T., Hus I., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 1
71-80
EN
We investigated the levels of 6 different cytokines in the sera of 10 newly diagnosed patients with B-cell lineage acute lymphoblastic leukemia (ALL) and detected a significant increase in IL-6 and IFN- serum levels in comparison to that of healthy controls. Whole blood cell cultures of 10 ALL patients and 20 control individuals were induced with classical cytokine inducers, such as virus, PHA and LPS, and their ability to produce 9 different cytokines was compared. Blood cells of ALL patients produced significantly less IL-1, IL-1, IL-10 and TNF- than control cells and not significanly lower levels of IL-6, but comparable with control levels of IL-2, IL-4. rHuGM-CSF added to cell cultures 24 hr before induction significantly enhanced the production of IL-1, IL-1 and TNF- in controls, but only IL-1 and IL-1 in the blood cell cultures of patients with ALL. GM-CSF did not significantly influence the production of IFN-, IFN-, IL-2, IL-4 and IL-10 in the control cells and the cells of ALL patients. The patients examined differed not only in the expression of CD10 and CD34 antigens on blast cells, but also in the reaction to GM-CSF treatment, which was found as very high standard deviation values. We suppose that these differences can partially explain the different effects of GM-CSF when used to ameliorate neutropenia of ALL patients after chemotherapy and to reduce the incidence of microbial infections.
4

Medical application of bioartificial tissues and organs

100%
Kandefer-Szerszen M., Paduch R., Daniluk J.
Biotechnologia
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1999
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issue 4
62-75
EN
The enormous need for 'spare parts' for the human body is the driving force for research in a new scientific field - tissue engineering. Tissue engineering combines living cells with a wide range of biomaterials, mostly as a substitute for the extracellular matrix or the stroma. As experiments in conventional culture dishes continued to fail, new cell and tissue culture methods had to be developed. Tissues are cultured under conditions as close as possible to their natural environment. Cells are grown on novel tissue carriers, on selected biomaterials and scaffolds. The tissues are subsequently transferred into different types of containers for perfusion with fresh culture medium. The development of artificial skin for severely burned patients is among the most advanced tissue-engineering attempts. Intensive research is being focused on the generation of artificial cartilage and bones to treat articular joint diseases or injuries or augment defects in plastic surgery. Future challenges are the construction of liver organoids for bridging comas or bioartificial pancreas for the treatment of type I diabetes mellitus. In this paper we show strategies, needs, tools for the development of some artificial tissues and bioartificial organs.
5

Abnormal cytokine production by bone marrow stromal cells of multiple myeloma patients in response to RPMI8226 myeloma cells

100%
Zdzisinska B., Bojarska-Junak A., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2008
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vol. 56
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issue 3
207-221
EN
Introduction Recent studies indicate that bone marrow stromal cells (BMSCs) derived from patients with multiple myeloma (MM) differ from those of healthy donors in their expression of extracellular matrix compounds and in cytokine production. It is not known whether these abnormalities are primary or are acquired by BMSCs on contact with MM cells. Materials and Methods: Interleukin (IL)-6, IL-11, IL-10, and tumor necrosis factor (TNF)-alpha production by CD166+ mesenchymal BMSCs and the CD38+/CD138+ RPMI8226 myeloma cell line cultivated in vitro in monocultures or co-cultivated under cell-to-cell contact or non-contact conditions in the presence of a tissue culture insert were measured. Intracellular cytokines were measured by flow cytometry analysis as the percentage of cytokine-producing cells or by mean fluorescence intensity as the level of cytokine expression in cells. Additionally, ELISA was used to measure IL-6, soluble IL-6 receptor (sIL-6R), IL-11, IL-10, TNF- alpha, B-cell-activating factor of the TNF family (BAFF), hepatocyte growth factor (HGF), and osteopontin (OPN) production in the supernatants of the cultures and co-cultures. Results A higher ability of the BMSCs of MM patients than in controls was detected to produce IL-6, IL-10, TNF- alpha, OPN, and especially HGF and BAFF in response to the RPMI8226 cells. Moreover, the BMSCs of the MM patients significantly enhanced the production of sIL-6R by the RPMI8226 cells. Discussion Cytokines over-expressed by BMSCs of MM patients can function as growth factors for myeloma cells (IL-6, IL-10, HGF), migration stimulatory factors for tumor plasma cells (TNF-alpha, HGF), adhesion stimulatory factors (HGF, BAFF and OPN), stimulators of osteoclastogenesis (IL-6, TNF-alpha), and angiogenic factors (TNF-alpha). The results of this experiment strongly suggest that the BMSCs from MM patients differed in spontaneous and myeloma cell-induced production of cytokines, especially of HGF and BAFF, and these abnormalities were both primary and acquired by the BMSCs on contact with the MM cells. This in turn suggests the presence of an undefined, autocrine stimulation pathway resulting in a prolonged production of cytokines even in long-term cultures in vitro and in vivo. These abnormalities might provide optimal conditions for the proliferation and differentiation of residual tumor cells or their precursors in the affected bone marrow.
6

Alcohol-related cirrhosis with pancreatitis. The role of oxidative stress in the progression of the disease

100%
Szuster-Ciesielska A., Daniluk J., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 2
139-146
EN
To assess the level of oxidative stress, measured as prooxidant-antioxidant imbalance in the blood of patients with alcohol-related injury of the liver and pancreas, we determined superoxide ion (O2?-) production by neutrophils isolated from the peripheral blood of 3 groups of patients. Patients with compensated alcoholic liver cirrhosis (n=16), with alcoholic chronic pancreatitis (n=20), and with concomitant cirrhosis and pancreatitis (n=10) were included in this study. All patients had consumed at least 70 g of pure alcohol per day over 5 years. They had not abstained before admission to hospital. The control group consisted of 16 healthy non-alcohol-abusive subjects. As antioxidative enzymes (AOE) present in sera play a very important role in the regulation of plasma ROS levels and in the protection of plasma compounds against ROS action, we also examined serum activity of CAT, SOD (total activity) and GPx serum concentration. Neutrophils of patients with concomitant alcoholic liver cirrhosis and pancreatitis exhibited, similarly to the neutrophils of patients with chronic alcoholic pancreatitis, an enhanced ability to produce superoxide anions in vitro. In contrast, neutrophils of patients with alcoholic liver cirrhosis exhibited a defect in resting and PMA-induced superoxide anion production. The AOE activity in the sera of patients was also significantly changed. Total SOD activity was enhanced in all groups of patients with alcoholic liver cirrhosis, chronic pancreatitis and with concomitant injury of both organs. CAT activity was only increased in the sera of patients with liver cirrhosis or pancreatitis, but not in the patients with concomitant cirrhosis and pancreatitis. GPx concentration was only diminished in the patients with chronic pancreatitis. It seems likely that oxidative stress, defined as the imbalance between prooxidant and antioxidant activity, is highest in the blood of patients with chronic pancreatitis and, especially, in patients with concomitant liver cirrhosis and pancreatitis.
7

Monoterpenes ? old compounds, new applications, and biotechnological methods of their production

100%
Trytek M., Paduch R., Fiedurek J., Kandefer-Szerszen M.
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2007
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issue 1
135-155
EN
Monoterpenes, are the largest class of plant secondary metabolites. The review discusses some of their key roles in chemical ecology. Several applications of monoterpenes in flavour and fragrance industry, bioremediation, in prevention and therapy of several inflammatory infection, potential disease-preventive phytochemicals, especially for cancer development, are presented. This review also aims at a potential offered by biocatalysis for the synthesis of valuable natural monoterpenes, highlighting relevant biotransformation of suitable precursors (like pinene, limonene, myrcene) using microorganism and porphyrins. The industrial processes based on biotechnological methods are also discussed in terms of their advantages over classical chemical synthesis and extraction from natural sources.
8

Matrix metalloproteinase and cytokine production by bone marrow adherent cells from multiple myeloma patients

100%
Zdzisinska B., Walter-Croneck A., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 4
289-296
EN
Introduction: Cultures of bone marrow stromal cells derived from the bone marrow of multiple myeloma (MM) patients were shown to exhibit several abnormalities compared with control cultures from healthy subjects. The aim of the study was to examine whether cultures of bone marrow adherent cells, at low passage level, exhibit differences in matrix metalloproteinases (MMPs) and cytokine production compared with cultures from normal donors. Materials and Methods: MMP production was evaluated by gel zymography and by ELISA in supernatants of serum-free cultures of bone marrow adherent cells derived from 20 MM patients and 23 healthy controls. Spontaneous and lipopolysaccharide (LPS)- or Newcastle disease virus (NDV)-induced cytokine release was assessed in the supernatants of the cultures by the ELISA method. Results: Both cultures produced MMP-1, -2, -3, and -9 under serum-free conditions; however, the levels of MMP-1 and MMP-2 were significantly higher in cultures derived from MM patients, while MMP-3 was significantly higher in control cultures. The level of MMP-9 was comparable in the cultures derived from MM patients and controls. All cultures produced interleukin (IL)-10 and IL-11 spontaneously, but after LPS or NDV induction the levels of IL-10, IL-11, interferon , and tumor necrosis factor , were significantly higher in the cultures derived from MM patients than in control cultures. Conclusions: The results indicate that both the abnormalities in MMP production and the overproduction of cytokines (in the presence of LPS or virus, which mimic inflammatory conditions) may be involved in bone destruction and tumor spread in multiple myeloma.
9

Gelatin sponge Spongostan as a carrier for animal and human adherent cell culture

88%
Paduch R., Rzeski W., Zdzisinska B., Kaczor J., Kandefer-Szerszen M.
Biotechnologia
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2003
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issue 1
223-233
EN
A porous gelatin sponge Spongostan (Ferrosan Denmark) as a carrier for the cultivation of several adherent cell lines and strains was tested. This material provide considerably greater surface available for cells than conventional bottles. Moreover, it allows to maintain high cell viability (over 87%) during culture time. When cells were cultured on Spongostan discs (wet vol. 0.11 cm3), no phenotypic changes in cell adherence and proliferation dynamics were observed. However, when cells adhered to Spongostan were frozen down and kept for 5 months in liquid nitrogen, they lost about 65% of their viability. Generally, Spongostan can be considered as a universal carrier for three-dimensional culture of many cell types, but it cannot be used for cells? freezing.
10

Neuroleptics modulate cytokine and reactive oxygen species production in blood leukocytes of healthy volunteers

88%
Szuster-Ciesielska A., Slotwinska M., Stachura A., Marmurowska-Michalowska H., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2004
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vol. 52
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issue 1
59-67
EN
There have been several reports indicating that schizophrenia is related to the activation of the inflammatory response system (IRS),characterized by increased serum concentrations of several cytokines,and that antipsychotic drugs may have immunosuppressive or immunoreg- ulatory effects.The aim of the present study was to examine the effects of neuroleptics on cytokine and reactive oxygen species production in vitro,in blood leukocytes. We studied the effect of haloperidol,chlorpromazine and clozapine on the unstimulated and stimulated (phytohemagglutinin+lipopolysaccharide ?PHA+LPS)production of some cytokines which are known to be mainly products of T lymphocytes and monocytes (IL-2, lymphotoxin,IFN-? ,IL-12,IL-4,IL-10 and TGF-? )in peripheral blood mononuclear cells (PBMC)of healthy subjects.We also compared the effect of neuroleptics on superoxide anion and hydrogen peroxide production in blood neutrophils. All three antipsychotic drugs significantly increased PHA+LPS-stimulated production of anti-inflammatory cytokines such as IL-10 and TGF-? as well as unstimulated production of IL-10,but they did not influence IL-12 production.In the same in vitroconditions they inhibited PHA+LPS-stimulated production of IL-2 and lymphotoxin.IL-4 production was inhibited by haloperidol and chlorpromazine,but not by clozapine.IFN-? production was inhibited by haloperidol and chlorpromazine,but stimulated by clozapine.All neuroleptics examined at a high (100 muM)concentration,but not at a 1 muM concentration,significantly inhibited superoxide anion production by phorbol ester (PMA)-stimulated neutrophils in vitro. The results indicate that in vitro typical antipsychotic drugs, such as haloperidol and chlor- promazine, and atypical ones, such as clozapine, modulate cytokines which are known to be produced by monocytes as well as by T helper (Th)1 and Th2 subpopulations.
11

Investigation of serum cytokine levels and cytokine production in whole blood cultures of paranoid schizophrenic patients

88%
Kaminska T., Wysocka A., Marmurowska-Michalowska H., Dubas-Slemp H., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 6
439-446
EN
There is some evidence that the pathophysiology of schizophrenia is related to changes in the innate and adaptive immune systems. In an attempt to define a potential immunological dysfunction in schizophrenia, we measured the serum levels of several cytokines in the sera of 24 patients with paranoid schizophrenia and investigated the cytokine production in whole blood assays after stimulation in vitro with virus (Newcastle disease), phytohemagglutinin (PHA) or bacterial lipopolysaccharide (LPS) and compared them with healthy, normal controls. A significant increase of IL-6, IL-8 and IFN- gamma levels, but a decreased IL-10 level were observed in the sera of patients with schizophrenia. No significant changes in the serum levels of IL-2, IL-4, IFN-alpha and TNF-alpha were detected in these patients. When cytokine production in vitro was examined, a significant defect in PHA-induced IL-2, IL-4 and IFN-gamma, and in virus-induced IFN-alpha production, but no significant alterations in LPS-induced IL-6, IL-10 and TNF-alpha production were observed. In summary, increased serum levels of some cytokines such as IL-6, IL-8 and IFN-gamma indicate an activation of the inflammatory response in schizophrenia, while the in vitro assay indicates significant changes in the Th1 (decreased production of IL-2 and IFN-gamma) and Th2 (decreased production of IL-4) cell system responses. The role of the defective IFN-apha production in the regulation of the imbalance between Th1 and Th2 cell system responses is suggested.
12

Propagation of Derzsy disease virus in goose embryo fibroblasts. An application of the Celligen Plus bioreactor

64%
Rzeski W., Paduch R., Kozdrun W., KaczorJ., Czekaj H., Samorek-Salamonowicz E., Kandefer-Szerszen M., Zdzisinska B., Dawidowicz A.
Biotechnologia
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2003
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issue 2
261-267
EN
Derzsy desease is a fatal hepatitis of young geese under the age of 5 weeks. The etiological agent is a goose parvovirus (GPV) which is widespread in all major goose farming countries in Europe and Asia. At present, vaccination is the only method preventing the loss of animals. In vitro GPV replicates only in goose embryo fibroblasts (GEF) and this way the virus is propagated in order to obtain the material for diagnostic tests and vaccine production. In this paper, we report the application of bioreactor Celligen Plus for GEF culture and Derzsy disease virus propagation. The method is based on immobilization and culture of cells on porous glass carriers in bioreactor. Comparing to the traditional cell culture techniques, the described method was over 12-fold more efficient and allowed to obtain good quality virus pool for Derzsy disease vaccine preparation.
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