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Biomedical subjects

J Krejsek

Publications and source records attributed to J Krejsek.

At least 19 recordsLinked to original sources

Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy.

Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. Forty otherwise healthy blood donors serve as a control group. The efficacy of GT was delineated by psoriasis area and severity index (PASI). The disease activity was significantly diminished by GT (P < 0.001). The serum levels of both VEGF and bFGF were statistically significantly correlated to PASI value in patients before the treatment by GT. The serum levels of VEGF (329.4 +/- 125.5 microg/ml) and bFGF (10.2 +/- 5.04 pg/ml) in patients before GT were significantly higher than those measured in healthy blood donors (VEGF 236.4 +/- 55.9 pg/ml, bFGF 7.3 +/- 3.7 pg/ ml). The serum levels of both VEGF and bFGF were significantly diminished by GT. The level of VEGF dropped from 329.4 +/- 125.5 pg/ml before GT to 278.5 +/- 109.9 pg/ml after GT (P = 0.0042) and the level of bFGF fell from 10.2 +/- 5.04 to 7.78 +/- 4.5 pg/ml (P = 0.019). Comparing to healthy controls, the serum level of bFGF in psoriasis patients was normalised (P = 0.5723) after GT. In contrast, the serum level of VEGF remained significantly increased in psoriasis patients after GT in comparison with healthy blood donors (P = 0.0319). In conclusion, we found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

Adolescent↗

Selected immunological changes in patients with Goeckerman's therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8.

Psoriasis is one of the most frequent inflammatory skin diseases in which abnormal individual immune reactivity plays an important role. The aim of the present study was to describe selected immunological changes, concerning pro-inflammatory cytokines (TNF-alpha, IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1), in 56 patients cured by Goeckerman's therapy (GT). GT includes dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV radiation. When compared with the control group (healthy blood donors), the patients before GT had significantly increased serum levels of sE-selectin (p<0.001), sP-selectin (p<0.001), sICAM-1 (p<0.001) and IL-8 (p<0.001). Significantly decreased serum levels of sE-selectin (p<0.05) and significantly increased serum levels of IL-8 (p<0.05) were found after GT therapy. Serum levels of sICAM significantly correlated with the disease activity and with serum levels of sE-selectin. The level of PASI score (Psoriasis Area and Severity Index) significantly decreased after GT (p<0.001) and confirms the high efficiency GT. These findings confirmed that pro-inflammatory chemokine (IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1) play an important role in the development and regulation of inflammation in psoriasis. Determination of sE-selectin and sICAM seems to be a promising marker of psoriasis's activity. Chemokine pathway (IL-8) and TNF-alpha activity seem to be modulated by Goeckerman's therapy (polycyclic aromatic hydrocarbons).

Adolescent↗

The significance of soluble CD138 in diagnosis of monoclonal gammopathies.

Report is summary of the results of study designed to ascertain the significance of soluble CD138 (sCD138) assessment in patients with different monoclonal gammopathies. Previous studies have shown that sCD138 is shed from the surface of myeloma cells into serum and that this marker is a new independent prognostic parameter in multiple myeloma. In presented study was evaluated serum sCD138 level in 14 patients with monoclonal gammopathy of undetermined significance (MGUS) and in 17 patients with multiple myeloma (MM), all MM patients were treated by high-dose chemotherapy regimen with subsequent autologous transplantation of peripheral blood stem cells. To determine the sCD138 level we used a rapid and simple ELISA procedure. The mean serum sCD138 level of patients with MGUS was 32 ng/ml (range: 5-128). Soluble CD138 levels were elevated in the sera of 10 out of 17 (59%) multiple myeloma patients, the mean baseline sCD138 concentration was 1542 ng/ml (range: 10-17300). In spite of small number of patients the difference between MGUS and MM group was highly statistically significant (p<0.001). Multiple myeloma patients with high level of sCD138 at diagnosis (cut-off value: 500 ng/ml) had worse prognosis despite of good response to chemotherapy in some of them (p=0.029). It seems that determination of sCD138 can be recommended as a helpful and reliable marker for differential diagnosis as well as prognosis of monoclonal gammopathies.

Biomarkers↗

Cytogenetic and immunological changes after dermal exposure to polycyclic aromatic hydrocarbons and UV radiation.

Goeckerman's therapy (GT), which combines exposure to coal tar (polycyclic aromatic hydrocarbons - PAHs) and UV radiation (UV) is often used as the first option for treatment of psoriasis. However, PAHs and UV represent mutagenic, carcinogenic and immunotoxic agents. Therefore GT can represent a health risk for the patients. The group under observation consisted of thirty patients undergoing GT. Before and after the treatment, blood samples were collected and chromosomal aberrations and selected immunological markers were determined. The relationships between chromosomal aberrations and immunological markers and the extent (duration) of exposure to GT were evaluated. The Psoriasis Area and Severity Index (PASI) score confirmed the high efficacy of GT. However, significantly elevated levels of chromosomal aberrations of peripheral lymphocytes were also found after the therapy (p<0.001). The levels of chromosomal abnormalities correlated to the extent and the total duration of exposure to PAHs (r = 0.682, p<0.01 and r = 0.605, p<0.05). After the therapy, significantly decreased levels of IgE, IgM isotypes of immunoglobulin, alpha(2)-macroglobulin and transferrin together with beta(2)-microglobulin were found. From the immunological markers listed above only the decreased level of alpha(2)-macroglobulin correlated to the extent of exposure to PAHs (r = -0.568, p<0.05). No correlation was found between chromosomal aberrations, significantly changed immunological markers and the duration of UV exposure. Our study revealed that GT has a significant impact on both genetic and immunological parameters of psoriatic patients. The results indicate that GT could increase genotoxic risk and modulates immunity of treated patients.

Administration, Cutaneous↗

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part 1: identification of danger signals by innate immunity].

Cellular and humoral components of innate immunity are able to identify danger signals both of the exogenous and endogenous origin. Exogenous danger signals are evolutionary conserved mosaics of danger patterns which are frequent in pathogenic microbes. Endogenous danger signals are raised during damage of self structures, by oxidative stress and/or by chemical modification of self molecules. Danger signals are identified by several families of molecules which are expressed on the surfaces of innate immunity cells. Among them the TLR receptors family which is associated with intracellular signaling pathway NF-kappaB is one of the most important. The inflammatory response is induced via activated NF-kappaB transcription factor.

Animals↗

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part II: TLR receptors, significance of genetic polymorphism of danger signals receptors].

The most important set of receptors for danger patterns are TLR receptors. Together ten different TLR receptors were identified so far. Majority of TLR receptors is expressed on the cell surface to identify extracellulary localized danger signals. Some TLR receptors are also expressed in the intracellular compartment to identify intracellular danger signals. Receptors for danger signals display individual differences delineated by genetic polymorphism. The individual immune reactivity is developed in the context of genetic predisposition and the exposition to variable environmental factors. The differences in an individual immune reactivity are probably responsible for individual susceptibility or resistance to the development of immunopathological reactivity, which is involved in the immunopathogenesis of atherosclerosis.

Animals↗

[Importance of immunophenotyping in the diagnosis of B-cell lymphoproliferative diseases ].

The immunophenotyping of the lymphoproliferative diseases is considered to be an integral part of the diagnostic process pointing to the correct classification of the individual diseases and to the choice of the most suitable type of therapy. This article describes the immunophenotype of particular types of B-lymphoproliferative disorders included in the World Health Organization classification (WHO) and the prognostic importance of some markers. The panel of specific monoclonal antibodies directed to B-cell lineage used in our department is displayed.

B-Lymphocyte Subsets↗

Selectins and monocyte chemotactic peptide as the markers of atherosclerosis activity.

The role of adhesive selectin molecules in the process of atherogenesis is an open question. These molecules are known as markers of atherosclerosis activity, however, only some biological mechanisms are known up to now. In this study we examined the levels of soluble forms of E-, P-selectin and monocyte chemotactic protein (MCP-1) in the process of extracorporeal cholesterol elimination by LDL-apheresis. We measured the levels of sE-, sP-selectin and MCP-1 in the plasma before and after LDL-apheresis and in the washout solution from immunoabsorption columns Lipopak. Eighty measurements were performed repeatedly in 6 patients with severe familial hypercholesterolemia (FH) on long-term LDL-apheresis treatment. Before the procedure P-selectin levels were 204+/-179 ng/ml, E-selectin 32.1+/-33.7 ng/ml, MCP-1 323.8+/-121 pg/l, whereas after the procedure we found P-selectin levels 131.6+/-34 ng/ml, E-selectin 33.1+/-51 ng/ml, and MCP-1 200.4+/-15 pg/l. Levels of P-selectin were increased in the blood of patients with FH in spite of long-term intensive extracorporeal LDL-elimination, documenting thus the activity of atherosclerosis. The levels of P-selectin and MCP-1 decreased significantly after the hypolidemic procedure and could be used as another marker showing the effectivity of the extracorporeal LDL-cholesterol elimination (immediately after the procedure), and, after further verification, may serve as a marker for controlling the therapy efficacy.

Arteriosclerosis↗

[Immunopathogenesis of diabetes mellitus I].

The pathogenesis of diabetes mellitus I is multifactorial. Both genetic predisposition and environmental factors are involved in the deregulation of immune system with subsequent breakage of self-tolerance. Autoantibodies against numerous autoantigens are raised during this long-term process but the principal pathogenic mechanism is cytotoxic killing of beta cells of pancreas mediated predominantly by T cells. There could be the chance to interrupt this pathogenetic process by manipulation with immune system to achieve induction of tolerance. Such clinical trials are now under progress.

Animals↗

[Multidrug resistance markers monitoring in acute myeloid leukemia cells].

BACKGROUND: P-gp, MRP, LRP, Bcl-2, and Bax proteins play an important role in the multidrug resistance of leukemic cells. P-gp, MRP, and LRP proteins decrease the intracellular drug concentration, Bcl-2 and Bax proteins influence the apoptosis process. The overexpression of some of these proteins is associated with poor prognosis of leukemia. The aim of this study was to find the relationship between some multidrug resistance markers and some clinical and laboratory parameters. We compare also P-gp expression between acute myeloid leukemia (AML) FAB subgroups M0-M6. METHODS AND RESULTS: With use of flow cytometry we measured the expression of P-gp, MRP, LRP, Bcl-2, and Bax proteins in acute myeloid leukemia patients cells. The study proved the association between blast percentage and P-gp protein expression (p=0.015) and the association between blast percentage and Bcl-2 protein expression (p=0.041). It was also shown the tendency of the LRP protein expression to associate with higher age of patients (p=0.062). Another correlation between MRP and Bax expression (p=0.006), as well as between LRP and Bax expression was found (p=0.034). In AML M0 FAB subgroup of patients the trend to higher P-gp protein expression was observed. CONCLUSIONS: The laboratory methodology to multidrug resistance markers detection was introduced. Some relations between multidrug resistance markers playing role in acute myeloid leukemia patients prognosis were suggested.

Acute Disease↗

[Importance of selected laboratory indicators in the differential diagnosis and monitoring of multiple myeloma].

Multiple myeloma is one of the most common haematologic malignancies. Currently there are numerous studies looking for new prognostic markers in multiple myeloma. The most important of them are the markers related to proliferative activity of neoplastic cells or to size of tumor mass. The subject of this paper are the results obtained from investigation of some such laboratory markers in a group of patients with monoclonal gammopathies diagnosed at our department in the last 3 years. We analyzed blood and bone marrow samples from 51 patients with new diagnosed monoclonal gammopathies, 14 of them were patients with monoclonal gammopathy of undetermined significance and 37 patients had multiple myeloma. 17 patients with multiple myeloma were treated by high-dose chemotherapy regimen. We assessed significance of selected laboratory markers for differential diagnosis of monoclonal gammopathies and for monitoring of activity of multiple myeloma. Among the investigated parameters, we verified the significance of cell cycle analysis of bone marrow plasmatic population and of the determination of the number of circulating myeloma cells in differential diagnosis of monoclonal gammopathies. In our opinion, the determination of soluble CD138, beta 2-microglobulin and neopterin serum levels can be also recommended as helpful markers for a solution of this problem. Except of beta 2-microglobulin serum level we did not find statistically significant correlation with activity of multiple myeloma in any of the investigated parameters.

Biomarkers, Tumor↗

[Immunofluorescence determination using flow cytometry of platelet surface antigens in peripheral blood of healthy individuals (pilot study)].

The authors present normal values of selected constitutive and activating platelet surface antigens expression. The results were obtained by flow cytometry analysis after immunofluorescent staining of the peripheral whole blood specimens from 25 healthy adults. Data are presented as a mean value and standard deviation (SD) of percentage of positive labelled platelets: constitutively expressed molecules CD9: 94.97% (+/- 2.95), CD31: 92.78% (+/- 2.97), CD36: 90.98% (+/- 5.25), CD41: 95.62% (+/- 2.23), CD42a: 94.98% (+/- 2.62), CD42b: 94.13% (+/- 2.58), activation molecules CD62P: 0.45% (+/- 0.33), CD63: 0.32% (+/- 0.22). This study is the first report in Czech literature.

Adult↗

[Apoptosis, its mechanisms and medical significance. I. Definition of apoptosis and its progression at the cellular level].

Apoptosis is a one example of genetically-regulated cell death. It is characterized by the phylogenetically highly conserved activation of specific genes and proteins followed by energy-consuming proteolytic autodestruction. Apoptosis seems to be physiological and highly selective mechanism to eliminate either old or injured cells in organisms. It is in contrary to mitosis. A highly complex combination of various stimuli both extracellular and intracellular origins is required for induction of apoptosis together with preserved oxidative phosphorylation.

Animals↗

[Apoptosis, its mechanisms and medical significance. II. Disorders of apoptosis regulation and their relation to the development of diseases].

Study of apoptosis seems to be relevant to clinical medicine nowadays. Dysregulation of apoptosis is under the certain circumstances the cause of various pathological processes in organism. The numerous methods to analyse apoptosis are now well established. It is very likely that our better understanding of apoptosis could lead to improvement in diagnosis and treatment of diseases such as immunopathology, cancer, and others.

Animals↗

The effect of trimetazidine on C-reactive protein, cytokines and adhesion molecules in the course of acute myocardial infarction.

The aim of this randomised, double-blind, placebo controlled, parallel group study was to assess the effect of trimetazidine (TMZ), a potent antiischaemic drug, on plasma C-reactive protein (C-RP), cytokine and adhesion molecule levels. The study population consists of 18 patients (16 males, 2 females, average age 56.45 +/- 10.97 years) with acute myocardial infarction admitted within 6 hours after onset of symptoms and treated with streptokinase. Blood samples were taken at 3-hour intervals during the time of treatment. All patients were randomised blindly using a centralised randomisation process, between trimetazidine (40 mg bolus i.v. then 60 mg per day for 48 hours intravenously in glucose infusion) or placebo group. Plasma C-RP level was significantly lower in TMZ group (39.5 mg/ml +/- 9.7 mg/ml) as compared to placebo (75.7 +/- 29.4 mg/ml, p < or = 0.001) and peaked 28 hours later in TMZ group. Plasma interleukin 6 (IL 6) level showed a sharp peak 9 hours after the onset of the symptoms in TMZ group (116.9 +/- 180.2 pg/ml vs. 45.4 +/- 37.9 pg/ml) and was increased up to 30 hours after the onset of the symptoms. Plasma interleukin 1 beta (IL 1 beta) was also higher in TMZ group notably 21 hours after the onset of symptoms (26.4 +/- 9.3 pg/ml vs. 16.2 +/- 2.4 pg/ml). TMZ group showed lower plasma E-selectin levels. Plasma IL 8, TNF alpha and ICAM 1 levels were without statistical significant differences. The present study demonstrates a significant reduction of plasma C-reactive protein level in the course of acute myocardial infarction treated with streptokinase and intravenous trimetazidine infusion compared with the group of patients without trimetazidine treatment.

C-Reactive Protein↗

Inflammatory response to acute myocardial infarction complicated by cardiogenic shock.

We report a case of a 60-year-old man with acute myocardial infarction (AMI) treated using thrombolysis, and complicated by cardiogenic shock (CS). Plasma interleukin (IL) 1 beta, IL 6, IL 8, tumor necrosis factor alpha (TNF alpha), and soluble adhesion molecule (sICAM 1, sE-selectin) levels were measured at 3-h intervals. This observation showed the effect of AMI and CS on the plasma interleukin levels. Remarkable changes were found in the plasma TNF alpha level, which reached two significant peaks. The peak of the first elevation caused by AMI (80.11 pg/ml, vs. normal value 4.35 pg/ml, SD 21.3 pg/ml) was seen 6 h after the onset of the symptoms. After the period of significant decrease, TNF alpha level was increasing until the end of the observation period because of CS (the last TNF alpha level was 204.1 pg/ml). The plasma IL 1 beta level was continually increased during the period of observation (maximal IL 1 beta level 32.1 pg/ml, normal value < 10 pg/ml). The plasma IL 6 level reached the first peak caused by AMI nine hours after the onset of the symptoms (362.85 pg/ml, normal value (10 pg/ml). Because of CS, after the short period of decrease, the plasma IL 6 level was increasing until the end of the observation period (the last IL 6 level was 859.61 pg/ml). The plasma IL 8 level was also elevated throughout the time of observation (max. value 1652 pg/ml, vs. normal value < 30 pg/ml). The soluble adhesion molecule levels (sE-selectin and sICAM 1) were elevated throughout the period of observation without any significant peak.

Cell Adhesion Molecules↗

[Cytoimmunofluorometry in the diagnosis of MALT lymphoma of the gastrointestinal tract].

MALT lymphoma is raised from lymphoid cells of mucosa associated lymphoid tissues in a long-term, multistep process of the accumulation of genomic damage very often under the influence of chronic (e.g. Helicobacter pylori) infection. Cytoimmunofluorometric analysis of cell suspensions obtained from mechanically disintegrated bioptic samples of gut mucosa is a very useful approach to detect the presence of MALT lymphoma cells. MALT lymphoma cells are in a great majority of B cell origin. Malignant cells are characterized by the typical characteristic SS parameter, strong expression of CD20 and CD79b molecules, and by the absence of CD5 and CD23 molecules. The ultimate evidence of clonality is immunoglobulin light chains either kappa or lambda expression determination.

Antigens, CD↗

[Multidrug resistance of leukemia cells to cytostatics--the functional fluorescent dye efflux assay evaluated by flow cytometry].

The functional fluorescent dye efflux assays are used in the study of the multidrug resistance of the malignant cells to the cytotoxic drugs which is caused by the overexpression of P-glycoprotein (P-gp) or another membrane transport system--a multidrug resistance related protein (MRP). P-glycoprotein and a multidrug resistance related protein are involved in the efflux of cytotoxic drugs out of the cell and are responsible for the resistance. Fluorescent dye efflux mediated by these proteins could be evaluated by the flow cytometry. This test seems to be an optimal approach to study the multidrug resistance. With help of the specific inhibitors such as verapamil and cyclosporine A, the functional capacity of these proteins and the possibility to overcome the multiresistant phenotype can be revealed. The cell line K562 with transfected P-glycoprotein gene serves as a model system for the studying of the transport function with the use of the fluorescent substrates and P-glycoprotein inhibitors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗