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Biomedical subjects

L Mészáros

Publications and source records attributed to L Mészáros.

At least 19 recordsLinked to original sources

WT1 expression in angiogenic tumours of the skin.

AIMS: To determine the expression of WT1 in endothelial proliferations and tumours. Endothelial cells are derived from angioblasts which differentiate into bone marrow stem cells (BMSC). BMSC are characterized by the constitutive expression of the WT1 gene and we have postulated that its expression may be maintained during the differentiation of angioblasts to endothelial cells. METHODS AND RESULTS: The expression of WT1 was studied in human umbilical vein-derived (HUVEC) and brain microvascular endothelial cells (HBME) as well as in a Kaposi sarcoma (KS) cell line in vitro. Forty-two human skin biopsy samples of endothelial proliferations and tumours were analysed for the protein expression of WT1 using the monoclonal antibodies for wt-WT1 (6F-H2) and its 17AA+ variant (2C12). WT1 expression was detectable in HUVEC and KS cells and all WT1 splice variants examined (17AA+/- KTS+/-) were detectable in KS cells, while the 17AA+/- and KTS- variants were present in HUVEC. Immunohistochemical analysis of the 42 human skin biopsy samples revealed cytoplasmic WT1 expression using wild-type specific antibody (6FH2) in microvessels, which is maintained during neoangiogenesis (inflammation, haemorrhage, peritumoral angiogenesis). Around one-third of haemangiomas (3/10) and non-HIV-Kaposi sarcomas (7/18) expressed the WT1 protein in the cytoplasm of tumour cells compared with its frequent expression in angiosarcomas (7/8) using the same antibody (6FH2). The nuclear 17AA+ isoform of WT1 was detectable at protein level in a small proportion of KS cases exclusively (3/7). CONCLUSION: Our data suggest that WT1 protein expression is maintained during angiogenesis and malignant transformation of endothelial cells and can be considered as a new endothelial marker.

Antigens, CD34↗

Expression of CD44v3 protein in human endothelial cells in vitro and in tumoral microvessels in vivo.

The most universal angiogenic cytokines (VEGF, bFGF, HGF) are all heparin-binding proteins, the function of which is dependent on cell surface heparan sulfate proteoglycans (HSPG). Several proteoglycans have been demonstrated in endothelial cells, but only glypican-1 from the cell surface HSPG subfamily was documented at protein level. Here, we show that CD44v3 is expressed in human immortalized endothelial cells [anchorage-dependent human umbilical vein endothelial cells (HUVEC) and anchorage-independent Kaposi sarcoma (KS-Imm)] at mRNA and protein level, but is absent from the primary culture of human brain microvascular endothelial cells. We have shown that CD44v3 has a large cytoplasmic pool in endothelial cells, but a limited surface expression, mainly at filopodia, colocalized with MMP-2. Angiogenic factors like VEGF or bFGF did not affect surface detection of CD44v3 suggesting a constitutive expression. The putative functional role for endothelial cell surface CD44v3 was identified in chemotaxis assay when anti-CD44v3 antibody pretreatment proved to be inhibitory for HUVEC. Furthermore, we provided evidence for the CD44v3 protein expression in human endothelial cells in vivo in peritumoral microvessels of both human melanoma and glottic cancers, suggesting a role for this part-time heparan sulfate proteoglycan in tumor induced angiogenesis.

Base Sequence↗

Increased salt- and nisin-sensitivity of pressure-injured bioluminescent Listeria monocytogenes.

Suspensions of a bioluminescent (luxAB) transformant of Listeria monocytogenes in pH 7.0 phosphate buffer were pressurised and the effect of the pressure treatment was monitored by plate counting. When the bacteria were suspended in NaCl- and nisin-free buffer the number of colony forming units (CFU) decreased by 3 and 6 log cycles after 300 MPA for 10 and 30 min, respectively. Supplementing the plating medium with 5% NaCl did not influence the colony forming capacity of non-pressurised cells, however, CFU of residual populations after respective treatments of 300 MPa for 10 and 30 min were reduced by a further 2 and 3.5 log cycles in case of salt containing plates. Nisin-addition to the plating medium caused less than one log unit decrease in the CFU of the non-pressurised population. However, the CFU of 10 min-pressurised sample was 4 log cycles less in the nisin-containing plates than in the nisin-free ones, whereas no colonies were formed in the nisin-containing plates even when 1 ml was inoculated from the originally 10(10) CFU/ml population after 300 MPa for 30 min. The luciferase activities (bioluminescence intensities) decreased concomitant with the reduction of the viable cell counts, however, they were approx. 0.6-0.8 log units less in the presence of 5% NaCl in the pressurised suspension than those expected from the previously established linear correlation between the logarithmic light outputs and the logarithmic viable cell counts.

Colony Count, Microbial↗

Luminometric and differential scanning calorimetry (DSC) studies on heat- and radiation inactivation of Bacillus subtilis luxAB spores.

A bioluminescent derivative of Bacillus subtilis containing a plasmid encoding a luxAB fusion under control of a vegetative promoter and gives bioluminescence upon addition of an exogenous long-chain aldehyde has been used as test organism. Its spore populations have been produced and their heat- and radiation survival curves established. Heat-sensitization effect of pre-irradiation of spores was proven not only by colony counting but also with differential scanning calorimetry. Under a linearly programmed temperature increase, the heat destruction of spores surviving 2.5 kGy gamma irradiation resulted in at a few centigrade lower temperature than that of untreated spores. Heat denaturation endotherms in the DSC-thermogram of irradiated spores were shifted to lower temperatures as well. Comparative turbidimetric, luminometric and phase-contrast microscopic studies of untreated, heat-treated and irradiated spore populations showed that the kinetics of germination and the light emission during germination of radiation-inactivated spores were the same as those of untreated spores, revealing that the pre-formed luciferase enzyme packaged into the spores during sporulation remained intact after an irradiation dose causing 90% decrease in number of colony forming spores. Therefore, in contrast to heat-treated spores, the initial bioluminescence reading upon germination of irradiated spores does not reflect the viable count of their population.

Bacillus subtilis↗

[Suckling-induced changes in oxytocin and alpha-melanocyte-stimulating hormone contents of the median eminence and various lobes of the pituitary gland].

Previous reports have implicated that pituitary-derived prolactin (PRL) is secreted from two distinct zones of mammotropes within the anterior lobe (AL). The inner zone (AL-IZ), located adjacent to the NIL, is supposed to be involved in the rapid and massive discharge of PRL from the pituitary gland due to suckling stimulus. Anatomically, the AL-IZ has an intimate contact with the NIL because the blood arriving from the posterior pituitary through the short portal vessels (SPV) baths it first. Based on these facts it would be hypothesized that the locally released and/or produced important compounds, like oxytocin (OXT) and alpha-melanocyte-stimulating hormone (alpha-MSH), can be delivered to the AL-IZ. Therefore, the purpose of this study was to examine the possible local transportation of these hormones into various regions of the pituitary gland (adenohypophysis inner-zone (AL-IZ), outer zone (AL-OZ), intermediate lobe (IL), neural lobe (NL)) and median eminence of lactating rats. We have measured the concentration of OXT and alpha-MSH from tissue samples of nonsuckled and suckled rats using specific RIA-s. There were no changes in the concentration of OXY and alpha-MSH in the AL-IZ and AL-OZ due to suckling stimulus. In contrast, our data provide compelling evidence that OXT is transported into the IL, which can be further increased by suckling stimulus. Our data have shown a lack of local delivery of either alpha-MSH or OXY into the AL that raises serious doubt about their possible role in PRL secretion during suckling stimulus.

Animals↗

Suckling-induced change in oxytocin but not in alpha-MSH concentrations of the median eminence, the neural-, intermediate- and anterior lobes of the pituitary gland.

Previous reports have implicated that pituitary-derived prolactin (PRL) is secreted from two distinct zones of mammotropes within the anterior lobe (AL). The inner zone (AL-IZ), located adjacent to the neuro-intermediate lobe (NIL), is supposed to be involved in the rapid and massive discharge of PRL from the pituitary gland due to suckling stimulus. Whereas the outer-zone (AL-OZ) gives the basal secretion and it does not play a role in the acute secretory response during nursing. Anatomically, the AL-IZ has an intimate contact with the NIL because the blood passing through the short portal vessels (SPV) bathes it first. Based on this fact it would be hypothesized that locally released and/or produced compounds, like OXY and alpha-MSH, can be delivered to the AL-IZ. In conjunction, OXY and alpha-MSH have already been implicated to play a role in the regulation of PRL release during suckling. Therefore, the purpose of this study was to examine the possible local transportation of these hormones into the median eminence and various regions of the pituitary gland of lactating rats. We have measured the concentrations of OXY and alpha-MSH from tissue samples of nonsuckled (NS) and 10 or 30 min after suckling (S) was initiated using specific RIAs. It has been shown that there are no changes in the concentration of OXY and alpha-MSH in theAL-IZ and AL-OZ due to suckling stimulus. In contrast, our data provide compelling evidence that OXY is transported into the IL, which can be further increased by suckling stimulus. These data suggest that blood transfusing NL passes through the IL before it is drained into the cavernous sinus, which opens the road for OXY into the general circulation. In addition, our data have unequivocally shown a lack of local delivery of either alpha MSH or OXY into the AL that raises serious doubt about their possible role in PRL secretion during suckling stimulus.

Animals↗

Growth of untreated and radiation-damaged Listeria as affected by environmental factors.

The growth of untreated Listeria monocytogenes 4ab No. 10 and that of the surviving fraction of its population treated with 0.8 kGy gamma rays was investigated in a microtitreplate system at incubation temperatures between 3 degrees C and 35 degrees C in Tryptic Phosphate Broth (TPB) or Brain Heart Infusion Broth (BHIB) media containing NaCl between 0.25 to 16.75% (w/v), and acidified with citrate-phosphate buffers to pH values between 4.63 and 7.06. The initial viable count was 3 x 10(3)/ml. Time periods to visible growth were recorded. Radiation survivors showed increased salt- and pH-sensitivities and increased minimum temperature for growth in TPB-based media. Adverse effects of sub-optimal environmental factors (reduced water activity, pH and temperature) and radiation injury were much less pronounced in BHIB-based media. Polynomial equations describing the combined effects of hydrogen ion and salt concentrations on the detectable growth at 30 degrees C were constructed for quantitative assessment of interactions. The results demonstrate that combining environmental stresses with low-dose irradiation can control growth of L. monocytogenes.

Culture Media↗

Effect of Paxirasol aerosol on the clinical condition and objective functional respiratory parameters of obstructive respiratory tract disease patients.

Paxirasol aerosol applied in daily 3 x 5-puff doses was well tolerated by the examined patients. In the course of the 21-day therapy the laboratory findings did not change-haemopoetic or liver injury was not observed. On two-thirds of the patients the amount of sputum decreased in response to Paxirasol aerosol but the symptoms accompanying expectoration did not change notably. Among the objective respiratory parameters FEV1 values increased and Rtot values decreased. These changes may be observed during the first third of therapy. There was a continuous and linear increase in FEV values characteristic of respiratory pressure conditions. This phenomenon is not characteristic alone of the changes of values of obstructive diseases patients. The authors recommend the use of Paxirasol aerosol for the treatment of respiratory tract disease patients.

Administration, Inhalation↗

Nitrogen bridgehead compounds. 33. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 2.

A series of 9-hydrazono-4H-pyrido[1,2-a]pyrimidin-4-ones was prepared. The compounds were evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. Structure-activity relationship studies revealed that the presence of a monosubstituted hydrazone moiety in position 9 and an unsubstituted 2-position are necessary for the intravenous activity.

Animals↗

Mitochondrial substrate oxidation-dependent protection against lipid peroxidation.

The effect of mitochondrial substrate oxidation on the NADPH-dependent lipid peroxidation of intact mitochondria, microsomes and of homogenate from rat liver was studied. It was found that addition of either succinate or beta-OH-butyrate decreased the rate of malondialdehyde production of mitochondria. The effect of succinate was found to be marked (80-90% inhibition). Addition of succinate strongly inhibited the lipid peroxidation of a reconstituted system containing both mitochondria and microsomes. Increasing the amount of mitochondria in this system resulted in enhancement of the inhibition. The same succinate effect on malondialdehyde formation in liver homogenate was also observed. These findings suggest that mitochondria supplied with respiratory substrates may play a role in the protection against the lipid peroxidation in the liver cell.

Animals↗

Interaction of oleficin with the inner membrane of rat liver mitochondria.

The effects of oleficin, a polyene antibiotic of the nonmacrolide type, on isolated rat liver mitochondria were studied. Oleficin at a concentration of about 10 nmoles/mg protein increases both the rate of state 4 respiration and the "basal" ATPase activity of mitochondria. In contrast to this it inhibits the rate of both state 3 and uncoupled respiration and the DNP-stimulated ATPase activity. These inhibitions can be prevented by low concentrations (2 approximately 5 mM) of magnesium ions. Oleficin induces a high amplitude swelling of non-respiring mitochondria in the isoosmotic nitrate and chloride solutions of K+, Na+, Tris+, Tea+ or Mg2+. In contrast to that it does not induce swelling of mitochondria treated with ruthenium red in isoosmotic calcium acetate. Indirect evidence suggests that oleficin increases also the proton permeability of the inner membrane. The swelling observed in the isoosmotic solutions of monovalent cations can be prevented by low concentration (2 approximately 5 mM) of Mg2+. In the presence of the antibiotic Mg2+ and Ca2+ but not K+ and Na+, are transferred from an aqueous phase into a butanol-toluene bulk phase. Oleficin depletes Mg2+ and Ca2+ from mitochondria in a concentration dependent manner. Complete depletion of Mg2+ occurs only in the presence of EDTA, while that of Ca2+ does not need the chelator. It is concluded that the effects of oleficin on mitochondrial functions can be explained on the basis of an increase of the inner membrane permeability as the consequence of the depletion of Mg2+ from mitochondria caused by the antibiotic.

Adenosine Triphosphatases↗

Effect of primycin on the inner membrane permeability of rat liver mitochondria.

The effects of primycin on mitochondrial respiration, volume changes, ATPase activity and the acidification following ATP hydrolysis were studied. Primycin in concentrations below 2--3 nmoles/mg mitochondrial protein reacts only with energized mitochondria rendering their inner membrane permeable to K+, Na+, Tris+ but not to TEA+. Above this concentration primycin interacts both with energized and deenergized mitochondria and the inner membrane also becomes permeable for H+, Cl- but not for ATP. In this case mitochondria very probably lose Mg2+. It is concluded that primycin up to concentrations of 2--3 nmoles/mg mitochondrial protein acts like an ionophore, while at higher concentrations it changes the permeability properties of the mitochondrial inner membrane without a drastic alteration of the membrane itself.

Adenosine Triphosphatases↗