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M Pospísil

Publications and source records attributed to M Pospísil.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pretreatment with granulocyte colony-stimulating factor reduces myelopoiesis in irradiated mice.

The purpose of this study was to investigate effects of the treatment prior to irradiation with granulocyte colony-stimulating factor (G-CSF) on hematopoiesis in B10CBAF1 mice exposed to a sublethal dose of 6.5 Gy of 60Co gamma radiation. G-CSF was administered in a 4-day regimen (3 microg/day); irradiation followed 3 h after the last injection of G-CSF. Such a treatment was found to stimulate granulopoiesis, as shown by increased counts of granulocyte-macrophage progenitor cells (GM-CFC) and of granulocytic cells in the femoral marrow and spleen at the time of irradiation. However, postirradiation counts of GM-CFC and granulocytic cells in the marrow of mice pretreated with G-CSF were reduced up to day 18 after irradiation. Interestingly, the D0 values for marrow GM-CFC determined 1 h after in vivo irradiation were 1.98 Gy for controls and 2.47 Gy for mice pretreated with G-CSF, indicating a decreased radiosensitivity of these cells after drug treatment. The inhibitory effects of the pretreatment with G-CSF on the postirradiation granulopoiesis could be attributed to the phenomenon of "rebound quiescence" which can occur after cessation of the treatment with growth factors. Postirradiation recovery of erythropoiesis in the spleen of mice pretreated with G-CSF exhibited a dramatic increase and compensated for the decreased erythropoiesis in the marrow at the time of irradiation. This complexity of the hematopoietic response should be taken into account when administering G-CSF in preirradiation regimens.

Animals↗
PubMed1999

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine act additively to enhance the hemopoietic spleen colony formation in irradiated mice.

The effects of combined administration of two drugs elevating extracellular adenosine, namely dipyridamole (DP) and adenosine monophosphate (AMP), and granulocyte colony-stimulating factor (G-CSF) on hemopoietic stem cells in vivo were investigated. The experiments were performed on mice using the endogenous spleen colony formation in gamma-irradiated animals as an endpoint. The results have shown that DP and AMP act additively with G-CSF to enhance spleen colony formation and thus the erythroid repopulation of the spleen. These findings indicate that the signaling pathways of G-CSF and drugs elevating extracellular adenosine can interact at the level of primitive hemopoietic stem cells. The enhancement of hemopoiesis-stimulating effects of G-CSF by DP and AMP, which are low-priced and clinically available drugs, could improve the cost-effectiveness of the therapy with G-CSF.

Adenosine↗
PubMed1999

[The diabetic foot syndrome--antibiotic therapy].

The authors present an account on cultivation findings assembled in defects of the lower extremities of diabetic patients hospitalized at the surgical department of the Pelhrimov hospital. In the polymicrobial flora a relatively high ratio of anaerobic microorganisms was found (58%). Based on the sensitivity, a combination of antibiotics was recommended which could be used in empirical treatment before cultivation results (clindamycin, ofloxacin, gentamycin and azlocillin). The authors prefer results of actual sensitivity tests. The authors discuss principles of collection and processing of microbiological material and treatment. Anaerobic cultivation is specially emphasized.

Aged↗
PubMed1998

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice.

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multilineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive states induced by radiation exposure.

Adenosine↗
PubMed1998

Radioprotective effects of flurbiprofen and its nitroderivative.

Radioprotective effects of two non-steroidal anti-inflammatory drugs, flurbiprofen (FBP) and its novel nitroderivative flurbiprofen 4-nitroxybutylester (NO-FBP), which exhibits decreased gastrointestinal toxicity, were compared in mice. The drugs were administered in equimolar single doses, 2 hours before whole-body gamma-irradiation of the animals. After a sublethal radiation dose of 6.5 Gy, significantly increased numbers of endogenous haemopoietic spleen colonies and enhanced granulopoiesis were found in mice given either FBP or NO-FBP, when compared to vehicle-treated controls. There were no differences in the effectiveness of either drug to enhance postirradiation haemopoietic recovery. Survival of FBP- or NO-FBP-treated mice subjected to a lethal dose of 9.5 Gy was slightly but insignificantly enhanced, both drugs showing the same effect. These results clearly indicate the ability of both drugs to enhance haemopoietic recovery after sublethal radiation exposure and the absence of unfavourable effects under higher radiation doses. Because of its lower potential for gastrointestinal damage, NO-FBP seems to be a promising drug, which can find a use in the protection of postirradiation myelosuppression.

Animals↗
PubMed1997

NKR-P1A protein, an activating receptor of rat natural killer cells, binds to the chitobiose core of uncompletely glycosylated N-linked glycans, and to linear chitooligomers.

NKR-P1 represent a family of activating receptors in rodent natural killer cells related to C-type animal lectins. We identify here the elements involved in the reactivity of the major receptor of rat, NKR-P1A, with N-linked oligosaccharides of glycoproteins. Plate inhibition assays with isolated, structurally defined N-glycans as inhibitors of binding of NKR-P1A to GlcNAc16-BSA revealed that the removal of both the external sialic acids and the penultimate galactose residues resulted in attaining of significant inhibitory activities. Surprisingly, additional plate inhibition and glycoprotein overlay experiments brought evidence that the core chitobiose, depending on its substitution, can per se support the interaction with NKR-P1A. In a series of linear chitooligomers (n = 2-7), the inhibitory activities reached a maximum for the chitotetraose. The ability of NKR-P1 to recognize both the periphery and the core region of complex type oligosaccharides may define its dual specificity towards carbohydrate components of eukaryotic (e.g., tumor) cell surfaces, but also reflect an evolutionarily conserved reactivity with microbial saccharides important in immune recognition and signaling functions.

Animals↗
PubMed1997

Association of human NK cell surface receptors NKR-P1 and CD94 with Src-family protein kinases.

Human natural killer (NK) cells express on their surface several members of the C-type lectin family such as NKR-P1, CD94, and NKG2 that are probably involved in recognition of target cells and delivery of signals modulating NK cell cytotoxicity. To elucidate the mechanisms involved in signaling via these receptors, we solubilized in vitro cultured human NK cells by a mild detergent, Brij-58, immunoprecipitated molecular complexes containing the NKR-P1 or CD94 molecules, respectively, by specific monoclonal antibodies, and performed in vitro kinase assays on the immunoprecipitates. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and phospho-amino acid analysis revealed the presence of in vitro tyrosine phosphorylated proteins that were subsequently identified by re-precipitation (and/or by western blotting) as the respective C-type lectin molecules and Src family kinases Lck, Lyn, and Fyn. The NKR-P1 and the CD94-containing complexes were independent of each other and both very large, as judged by Sepharose 4B gel chromatography. Crosslinking of NKR-P1 on the cell surface induced transient in vivo tyrosine phosphorylation of cellular protein substrates. These results indicate involvement of the associated Src-family kinases in signaling via the NKR-P1 and CD94 receptors.

Antigens, CD↗
PubMed1997

[Infections in biliary surgery].

The authors selected among patients who were operated in 1992-1996 on account of affections of the gallbladder and biliary pathways those patients where aerobic and anaerobic bile cultivation was made. The results of the detected bacterial species and their sensitivity to ATB are given in tables. According to the author these investigations may be of benefit to the surgeon when he has to decide on the administration of ARTB without knowing the bacterial strain (prevention or therapy) and thus overcome the time when he will know the results of cultivation.

Adult↗
PubMed1997

Enhancement of haemopoietic spleen colony formation by drugs elevating extracellular adenosine: effects of repeated in vivo treatment.

The potential role of adenosine receptor signalling in the amplification of haemopoietic stem cells in vivo was investigated. Elevation of extracellular adenosine in mice was induced by the joint administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, an adenosine prodrug. The response of haemopoietic stem cells to the drug treatment was measured by endogenous spleen colony-forming assay in sublethally gamma-irradiated animals. The combination of drugs was administered before irradiation either singly or repeatedly at 24 h intervals. The results demonstrated the possibility of enhancing the spleen colony formation by the drug treatment. The highest stimulatory effect on spleen colony counts and on the colony sizes occurred after 3-4 injections of the drugs. Higher spleen colony responses were observed under injection regimens terminated 3 h before irradiation, as compared to those terminated 24 h before the radiation exposure. The results are interpreted as an evidence of the expansion of the stem cell pool. A tolerance to this stimulatory action developed after more than 3 injections of the drugs.

Adenosine↗
PubMed1996

Radioprotective properties of flurbiprofen.

Repeated administration of flurbiprofen, an inhibitor of prostaglandin synthesis (IPS), was found to enhance haemopoiesis in mice exposed to a sublethal dose of fractionated gamma-irradiation (5 x 3 Gy, intervals between fractions 24 h). In lethally irradiated animals (5 x 3 Gy and an additional "top-up" dose of 3.5 Gy), a significantly better survival was found in mice given flurbiprofen than in control animals receiving saline. The latter result is a new positive phenomenon not observed in earlier experiments with other IPS. The findings suggest a possibility to extend the radiation dose range, in which the administration of IPS leads to radioprotective effects, also to higher, lethal radiation doses, by administering flurbiprofen instead of previously studied IPS indomethacin or diclofenac.

Animals↗
PubMed1996

[Diagnosis of infections caused by atypical mycobacteria].

Laboratory methods used for the differentiation of acid resistant rods of the genera Mycobacterium make use of their biological properties, in particular the growth rate on cultivation media, pigment formation, sensitivity for biochemical substances incl. antibiotics, biochemical activity and different relations to animal hosts. By testing these properties it was possible to classify mycobacteria into groups or identify different species in more detail.

Bacteriological Techniques↗
PubMed1996

Modulation of haemopoietic radiation response of mice by diclofenac in fractionated treatment.

The effects of diclofenac, an inhibitor of prostaglandin synthesis, were studied on the acute radiation syndrome elicited in mice by fractional irradiation. Several haematological parameters were evaluated in mice irradiated with 5x2 Gy and 3x, 4x, or 5x3 Gy (intervals between fractions 24 h) from a 60Co gamma-ray source. The animals were treated with diclofenac either before each fraction or only once before the last fraction. The survival of mice was recorded after the irradiation regimen of 5x3 Gy followed by a "top-up" dose of 3.5 Gy given 24 h after the last radiation fraction. Statistically significant enhancement of the endogenous spleen colony formation and of leukopoiesis was found in mice treated with diclofenac repeatedly, as compared with both saline-treated irradiated controls and animals administered a single diclofenac dose, if a sublethal total radiation dose had been accumulated. However, following accumulation of a lethal total radiation dose, slightly impaired survival was observed in mice given diclofenac. It follows from the results that diclofenac is a suitable drug for enhancing leukopoiesis impaired by sublethal fractionated irradiation. Nevertheless, undesirable side effects of this drug negatively influence the survival of experimental animals following a lethal accumulated radiation dose.

Animals↗
PubMed1995

CD 69 antigen of human lymphocytes is a calcium-dependent carbohydrate-binding protein.

CD69 is a signal transducing molecule of hematopoietic cells. Previous molecular cloning of CD69 has revealed a type II transmembrane orientation and the presence of an extracellular domain related to the Ca(2+)-dependent (C-type) animal lectins. As the predicted amino acid sequence for the lectin-like domain is highly divergent from those of other C-type lectin-like proteins - a feature shared with NKR-P1 of natural killer cells - CD69 and NKR-P1 are among proteins assigned to a separate group, group V. To initiate ligand identification studies, we have prepared soluble forms of CD69 protein by bacterial expression of its extracellular portion. We show that cysteine 68 located in the short membrane-proximal neck region of CD69 which adjoins the C-terminal lectin-like domain is a critical element for dimerization. We have evidence that the soluble dimeric CD69 has a tight association with calcium, a feature shared with NKR-P1, and that it is a carbohydrate-binding protein with N-acetyl-D-glucosamine and N-acetyl-D-galactosamine as the best inhibitors: 4-8 x 10(-5) M giving 50% inhibition of binding to N-acetyl-D-glucosamine neoglycoprotein. Thus, the tight association with calcium and high affinities for carbohydrate binding appear to be features of at least two members of the C-type lectin group V.

Acetylglucosamine↗
PubMed1995

Natural killer cell activity in coeliac disease: effect of in vitro treatment on effector lymphocytes and/or target lymphoblastoid, myeloid and epithelial cell lines with gliadin.

To analyze the possible involvement of natural killer (NK) cell activity in the pathogenetic mechanism of coeliac disease (CD) we measured the spontaneous cytotoxic cell activity of peripheral blood mononuclear cells (PMNC) from patients with CD and from healthy donors. No significant differences were found between the NK cell activity of PMNC from healthy donors and from patients with CD using a standard 51 Cr release assay. However, a 30-min treatment of PMNC with gliadin inhibited NK cell activity in patients with CD. On the other hand, a 1-d incubation with gliadin induced cytotoxic cell activity of PMNC against the NK-resistant target cells such as the epithelial HT-29 and the lymphoblastoid RAJI cell lines, suggesting that activation of PMNC by cultivation with gliadin can occur.

Adult↗
PubMed1995

Polyclonal activation of human lymphocytes by Bacillus firmus and its constituents.

Bacillus firmus strongly stimulates Ig synthesis in the cultures of human peripheral blood mononuclear leukocytes. As apparent from the character of Ig formation and blastic transformation, the stimulation has features of a polyclonal activation of B lymphocytes without substantial participation of T lymphocytes. B firmus is a strong B cell polyclonal activator even for human cord blood lymphocytes. The most striking feature is the strong stimulation of IgA synthesis in both adult and cord blood lymphocytes. Several crude fractions were isolated from B. firmus. None of them exhibited any remarkable enhancement of activity but the cytoplasmic fraction P-40 was clearly more potent than the intact bacilli. On the other hand, cell wall peptidoglycan, a well known polyclonal activator of B cells, had a much lower activity than whole bacteria. The effect of B. firmus on the stimulation of Ig formation is thus relatively complex; it is not caused mainly by peptidoglycan but rather by some cytoplasmic constituents of the bacterium.

Adult↗
PubMed1995

Effects of postirradiation carboxymethylglucan administration in mice.

The hemopoiesis-enhancing ability of a soluble glucan derivative, i.e. carboxymethylglucan (CMG), was investigated in gamma-irradiated mice. Attention was focused on the usefulness of its single or repeated postirradiation administration. CMG was administered i.p. at (a) single dose of 6 mg 2 h postirradiation, (b) four 6 mg doses in the first 4 days postirradiation, (c) four 1.5 mg doses at the same time intervals. Indices of granulopoiesis and inflammatory side effects (liver weight increase and hepatic granulomas) were investigated in mice irradiated with a sublethal dose of 7 Gy. All three CMG-treated groups of mice were found to exhibit enhanced hemopoietic recovery in comparison with the controls. Although the mice repeatedly given the 6 mg CMG doses showed the most rapid recoveries of all the evaluated parameters of granulopoiesis, the most pronounced hepatic side effects were found in these mice, too. When survival of mice was recorded in lethally (9 Gy) irradiated animals, the best protective response were obtained following the repeated administration of the 1.5 mg CMG dose, the survival by day 30 in this group being significantly higher not only in comparison with the controls but also with the mice repeatedly given the 6 mg dose of CMG. The results suggest that the postirradiation CMG administration can be useful for enhancing radiation suppressed hemopoiesis. However, repeated larger CMG doses may produce side effects which compromise the overall survival of irradiated mice.

Animals↗
PubMed1995

Enhancement by carboxymethylglucan of early cellular damage in 1 Gy-irradiated mice.

Our results describe a novel carboxymethylglucan (CMG) activity, namely its radiosensitizing effect on early cellular damage in mice gamma-irradiated with a dose of 1 Gy. An increase of thymidine levels in blood plasma, determined 4 h after irradiation, was used as an indicator of the early cell death. The radiosensitizing effect was observed when administering CMG at time intervals close to irradiation time (1 h before to 1 h after irradiation). Diclofenac (an inhibitor of prostaglandin production) had no modifying effects on elevation of plasma thymidine levels induced by radiation or radiation + CMG. Pentoxifylline (an inhibitor of synthesis of tumour necrosis factor and of phosphodiesterase) administration elevated plasma thymidine to similar levels as CMG alone, combined pentoxifylline + CMG treatment had not additive effects.

Animals↗