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C Oravec

Publications and source records attributed to C Oravec.

At least 19 recordsLinked to original sources

Assessment of toxicity, clastogenicity, mutagenicity and transforming activity of pentoxifylline in mammalian cells cultured in vitro.

We tested the possible cytotoxic, clastogenic and genotoxic effects of pentoxifylline on different lines of mammalian cells cultured in vitro. This study was part of the developmental research of agapurin, since pentoxifylline represents an effective compound of this drug. Cells treated for a short time manifested a relatively high resistance to the toxic effects of pentoxifylline. Generally, only cells treated for a long time (18 h) or a short time (2 h) with high concentrations of drug manifested sensitivity to the toxic effects of pentoxifylline. Although the tested drug induced DNA synthesis inhibition in V79 and EUE cells and clastogenic effects in V79 cells, it was not able to induce either 6-TGr mutations in the HGPRT locus of V79 cells or morphological transformation of Syrian hamster embryo cells. Adding of microsomal fraction S9 to the treated cells did not markedly change the effects of pentoxifylline on different studied endpoints. We suggest that pentoxifylline has no genotoxic effects, and that the cytotoxicity and induction of chromosomal aberrations were induced by inhibition of cellular DNA replication.

Animals↗

Antitumor activity of bacterial endotoxins and their subunits in in vitro test.

The tumoricidal effect of endotoxins and their subunits of Shigella dysenteriae serovar 1 of both growth forms and certain other representatives of the Enterobacteriaceae family was tested against Németh-Kellner mouse lymphoma cells using an in vitro assay based on the use of sodium chromate solution yielding labelled hexavalent 51Cr ions. The most effective in vitro activity was evidenced in both growth forms by S. dysenteriae 1 lipopolysaccharide-protein complex (LPSP) (76-92%), lipid A and lipoid B isolated from LPS (77-82%) and lipid A and lipoid B from LPSP (53-70%). A direct dependence of the level of the Limulus test and pyrogenicity on the tumoricidal activity of a preparation was not demonstrated. The influence of selected cations (Cu, Fe, Ca, Mg, Zn) bound to selected substances on antitumor activity was monitored. The method of probit analysis is recommended as it enables estimation, based on a number of concentrations, of the regression line of probable effectiveness of a given preparation.

Animals↗

Bacterial endotoxins as potential antitumor agents. Tumor mass loss in mice treated with bacterial lipopolysaccharides of Shigella dysenteriae serovar 1.

Natural and modified preparations of lipopolysaccharides and lipopolysaccharide-protein complexes isolated from the S- and R-form of Shigella dysenteriae serovar 1 were found to markedly inhibit the initial growth of mouse solid tumors derived from Németh-Kellner lymphoma, Gardner 6C3HED lymphoma, an ill-defined syngeneic lymphoma of DBA mice (Skalsky lymphoma) and LP-2 plasmacytoma. The biopreparations were given intraperitoneally, most frequently at a dose range from 50 to 200 micrograms per mouse; significant inhibitory effects on tumor growth were evidenced even in mice bearing tumors weighing 113 to 507 mg.

Animals↗

Modulation of humoral and cellular resistance in children with laryngeal papillomatosis.

As accessory cells in immunity response immunoglobulin and lymphocytes participate in antitumor immunity. Quantitative changes in concentrations and numbers were studied once before therapy, without examining the functional state. In order to gain more information on the humoral response during and after treatment, and in cases of recurrence, bactericidal antibodies against B. anthracis were determined by means of 51Cr-labeled microbes. The results of the present study show that IgG levels were normal and IgA and IgM normal or increased. In only 2 children (0.8%) the levels of serum IgM were lowered. Although a high percentage of increased trend values of bactericidity in cured children was found (75%), the percentage in children with recurrences reaching 50%, the differences are considered statistically insignificant. Following T lymphocyte, figures a significant decrease in juvenile laryngeal papillomatosis (JLP) patients were found.

Antibodies, Bacterial↗

Inhibitory effect of theophylline on repair of potentially lethal MMS-induced damages to DNA in V79 cells.

In a study of Chinese hamster V79 cells growing in the presence of sublethal concentrations of theophylline, we followed both the nature of DNA replication and the cells' response to toxic and DNA-damaging effects of methyl methanesulfonate (MMS). We found that cells cultured at low concentrations of theophylline (less than or equal to 0.3 mg/ml medium) showed deviations in the rate of DNA replication which, however, did not depress either the growth activity of the cells or their colony-forming ability. Considerable differences as against the controls appear in theophylline-cultured cells after treatment with MMS. Not only are they more sensitive to the toxic effects of this alkylating agent, but also their DNA synthesis is strikingly inhibited. More unrepaired lesions remain in parental DNA, and short fragments of daughter DNA, synthesized following cell treatment with MMS, are not elongated during a 2-h post-MMS treatment. Theophylline obviously belongs among agents inhibiting repair of potentially lethal MMS-induced DNA damages in Chinese hamster V79 cells.

Animals↗

[The status of natural immunity in children with acute lymphoblastic leukemia evaluated by long-term monitoring of complement-dependent bacteriocidal antibodies against B. anthracis and its relation to prognosis].

The authors investigated the function of the time factor as regards changes of bacteriocidity levels of serum against B. anthracis. Due to the fact that anthrax has not occurred in this country for several decades, we can speak of an investigation of natural immunity in the wider sense of the word. In the course of 15 years the authors collected repeatedly blood specimens from 53 children with ALL before, during and after treatment. Active sera were examined by quantitative titration by means of microbes labelled with 51Cr. The results of the investigation revealed that mean values of bacteriocidity calculated from all specimens and for each child separately are higher in the groups of children with a favourable course of the disease, as compared with children with an adverse course of the disease. It was also found that in a high percentage (78%) patients with long-term remission of leukaemia have a rising trend of bacteriocidity and the majority of children with a relapse of the disease (69%) had a bacteriocidity of serum with a declining trend (p = 0.01). The prognostic value of the test is unequivocally apparent from the results of the "life table" analysis. Children with an event free survival as well as the number of surviving children was significantly higher in the group with a rising trend of bacteriocidity than in patients with a declining trend of bacteriocidity (p = 0.008 and p = 0.02).

Adolescent↗

Antitumor activity of Borrelia burgdorferi cultures.

Cultures of B. burgdorferi, their supernatants as well as washed cells revealed in vitro a considerable antitumor activity against cells of Gardner lymphoma. Németh-Kellner lymphoma and LP-2 plasmacytoma. In in vivo tests an inhibition of tumor growth was evident, even if the treatment was started on day 4 after implantation of the tumor. The best results were obtained with the supernatants of the cultures.

Animals↗

Antitumor effect of hippurate. An experimental study using various mouse tumor strains.

Hippurate had antitumor effects both in vitro and in vivo by killing dose-dependently the cells derived from Skalsky lymphoma, Németh-Kellner lymphoma, L-asparaginase sensitive 6C3HED Gardner lymphoma, and LP-2 plasmacytoma. There was no significant difference between the effect of hippurate and its maternal compound benzoate. Hippurate administered intraperitoneally twice a day at a dose of 1 g/kg body weight significantly inhibited the growth of solid 6C3HED Gardner lymphoma even in the case that the treatment was started when the tumors reached a weight of over 400 mg. It was concluded that benzoates could be an important endogenous group of substances with antitumor effects.

Animals↗

Bioaccumulation of metals from a nickel smelter waste in P and F1 generations of exposed animals. II. Modulation of immune processes.

A group of female Chinchilla rabbits was exposed through inhalation to the metal aerosol derived from dumped waste of a nickel smelter. The experiments were carried out in a field exposure station. Increased levels of tissue immune complexes were found in the myocardium and lungs of P females, whereas F1 rabbits (exposed both prenatally and 6 weeks postnatally) from the same group of P females had significantly elevated serum circulating immune complexes as compared to controls. In P rabbits, nonspecific serum tumoricidal activity was increased by 8.2%, while in F1 animals the increase was by 14%. Transplantation immunity was examined in a group of inbred Lewis rats following the transplantation of a skin allograft from the ear of inbred Berlin-Druckrey rats. The mean time of allograft survival in animals following i.v. administration metal dust suspension 2 days prior to transplantation, was prolonged as compared to controls. On day 22 after allograft transplantation, lactate dehydrogenase activity was found to be reduced in peripheral lymphocytes, and the liver and spleen weight proved to be diminished. These findings suggest a modulating effect of the metal dust from a nickel smelter regarding nonspecific serum tumoricidal activity and transplantation immunity as well as immune complex formation.

Air Pollutants↗

Antigen-specific transfer factor from mice immunized with an attenuated flavivirus: augmentation of inducing activity in semipurified splenocytic dialyzates.

Three large batches were prepared of lyzed splenocytic leukocyte dialyzate from SPF outbred mice, immunized with a live attenuated virus from the tick-borne encephalitis (TBE) complex. Total mass of freeze-dried dialyzates was 1.73 g. One mg of respective batches contained 2 X 10(5), 2 X 10(4) and 2 X 10(3) units of the transfer factor, specific for the flavivirus group-antigen, as estimated according to the capacity to induce specifically cytotoxic T-cells in the recipient C3H mice. The amount of protein and orcinol-reactive material (purine-bound ribose), the presumed components of the inducer's substrate, ranged in individual dialyzates from 9.9-12.4 and 0.72-0.80% of their dry mass. Materials from each batch obtained after double precipitation by ethanol were subjected to permeation chromatography on Sephadex G-25 columns and subsequent lyophilization of the peak with specific inducing activity. The final product represented on average 3.7 per cent of dry mass of the starting material. In comparison to the crude material, in one mg of the final product the protein and the orcinol-reactive material were reduced by 80 and 37 per cent, respectively, but an increment in the antigen-specific inducing capacity comprising 2-3 log10 units was observed. These findings add to the concept that a) macromolecules carrying the inducing activity can be separated from other constituents of the crude dialyzate and b) an increase in antigen-specific inducing activity titre was, besides partial concentration, mainly due to removal of suppressor or inhibitory factor(s) present in the crude dialysates and probably acting in vivo.

Animals↗

Concentration of murine antigen-specific transfer factor of defined potency.

Dialysates containing transfer factor (TF) activity were prepared from lyzed splenic cells of SPF mice immunized with live, peripherally avirulent Langat virus (TP21 E5 "14" clone) from the tick-borne encephalitis (TBE) complex. The amount of TF was estimated by its capacity to generate in recipient inbred C3H mice cytotoxic T lymphocytes inducing lysis of TBE virus-infected target cells as demonstrated by 51Cr--release assay. A 100 to 1000-fold concentration of TF activity was achieved by combination of the two-step ethanol precipitation of crude dialysates with subsequent fractionation on Sephadex G-25 by exclusion chromatography. Materials from individual concentration steps showed reduced amounts of admixtures, as revealed by absorbance profiles of their chromatograms. In the final product the protein content was most decreased.

Animals↗

Dialysable specific transfer factor in mice immunized with attenuated Langat virus from the tick-borne encephalitis complex: generation, action and quantitative assay.

Cytolytic T lymphocyte assay was developed in order to measure the response of inbred C3H mice to dialysable specific transfer factor (STF), induced in subadult outbred mice by one shot immunization with the attenuated Langat virus. The first STF activity in mice splenic leukocytes was detected between 48-72 hr after virus administration. The conversion of splenic T-cell cytotoxic response in C3H mice in vivo occurred between 15-21 hr after STF administration. The killing activity of T-cells, induced by STF, showed cross-reactive traits within the genus Flavivirus. STF, given prior to the live virus, augmented the specific cytolytic T-cell response. In the live virus-primed mice the booster effect was markedly enhanced when administration of STF preceded the second immunization dose. In the serum of STF recipients, interferon was irregularly detected attaining low levels for short time periods. Temperature of 56 degrees C for 60 min abolished the activity of least 10(4) murine STF units, temperature of 37 degrees C lowered after 24 hr this activity by 3 log10units. Chromatography of the dialyzed leukocyte lysate on Sephadex G-25 column yielded usually five peaks. The second peak showed an increased content of ribose-bound and protein materials and, as a rule, a relatively concentrated STF activity.

Animals↗

Cell-mediated immunity in flavivirus infections. I. Induction of cytotoxic T lymphocytes in mice by an attenuated virus from the tick-borne encephalitis complex and its group-reactive character.

The lytic activity of splenocytes from C3H mice immunized with a highly attenuated line of Langat virus [tick-borne encephalitis (TBE) complex] was determined by the in vitro 51Cr release assay on TBE virus (western subtype)-infected target L929 cells. After the spleen cell suspensions were depleted of T cells with anti-mouse theta serum, or of B cells with anti-mouse immunoglobulin, the cytotoxic effect was found dependent on the presence of T lymphocytes. During immunization with Langat virus, cytotoxic T lymphocytes were generated, specific for both the foreign virus-specified antigen and the self component of the host system studied, coded by the K allele of the H-2 complex. The peak of T lymphocyte cytotoxic response was attained on the 6th day after administration of the live virus. T lymphocytes from mice, single-shot immunized with a flavivirus, displayed distinct cross-reactive lysis when studied on target cells infected with other flaviviruses but not on cells infected with an alphavirus.

Animals↗

Cross-reactive killer T lymphocytes in a flavivirus infection.

Splenocytes from mice immunized intravenously with one dose of Langat or Yellow fever viruses were cytotoxic for target cells infected with virulent tick-borne encephalitis (TBE) virus; cytotoxicity was measured by 51Cr release from target L929 cells. No significant lysis of the TBE virus-infected taget cells with splenocytes from Sindbis virus-infected mice was noted.

Animals↗

Transfer with dialysable transfer factor of T-lymphocyte cytolytic response to tick-bone encephalitis virus antigen in naive mice.

Transfer factor activity was demonstrated in the dialysable extract from lymphocytes from outbred donor mice, in which immunization with live attenuated Langat (E5 "14") virus induced a stage of high resistance against challenge with virulent tick-borne encephalitis virus. Administered to naive inbred recipient mice, the extract conveyed in them specific cytolytic activity, exerted by their T lymphocytes, as demonstrated by the 51Cr release assay on tick-borne encephalitis virus-infected syngeneic L-929 cells.

Animals↗