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Biomedical subjects

R Kovac

Publications and source records attributed to R Kovac.

At least 19 recordsLinked to original sources
PubMed2000

The expression of surface markers on dendritic cells as indicators for the sensitizing potential of chemicals.

Novel approaches to testing of skin sensitizing chemicals have made use of immature dendritic cells (DCs) cultured from different hematopoietic progenitors. These cells resemble Langerhans cells (LCs), which are the most potent antigen presenting cells in the skin. Former research has focused on the phenotypic and functional changes of LCs after application of skin sensitizers. But it has proven difficult to isolate sufficient numbers of LCs from skin. This disadvantage is overcome by cultures of immature DCs providing high numbers of reactive cells. The aim of the present investigation was to test the response of DC cultures established from different blood donors to known sensitizers, an irritant and a vehicle. The sensitizers NiSO(4), dinitrochlorobenzene (DNCB), 2,4,6 trinitrobenzene sulfonic acid (TNBS), alpha-hexylcinnamaldehyde (Cinn) and eugenol (Eu) induced the up-regulation of the co-stimulatory molecule CD86, of intercellular adhesion molecule CD54 and of the HLA-DR antigen. The irritant sodium dodecyl sulfate (SDS) and the vehicle dimethyl sulfoxide (DMSO) had no effect. A high rate of responders within blood donors was found for NiSO(4), TNBS, Cinn and Eu, while DNCB was less effective. The augmentation of surface marker expression in dendritic cells obtained from peripheral human blood seems to be a promising readout in prescreening for strong and moderate sensitizers. This test could thus help to reduce animal numbers for in vivo testing.

Acrolein↗
PubMed1995

Occupational exposure and its effect on some immune parameters.

Some immunological parameters were investigated in a group of workers exposed to external radiation (1.4 to 9.8 mSv) and inhalation of tritium (comm. eff. dose equiv. 1.2 to 2.8 mSv). The present investigations indicate the differential radiosensitivity of lymphocytic subsets: CD8 positive suppressor T cells were found to be the most sensitive subpopulation in the peripheral blood of radiation exposed workers. CD4/CD8 ratios were increased mainly due to an increase in absolute numbers of CD4 positive helper T cells indicating a selective cell renewal after irradiation. Results obtained after phytohaemugglutinin stimulation of lymphocytes showed individual variation, though there seems to be a trend towards an inverse correlation between absolute T cell numbers in peripheral blood and the number of S phases observed after stimulation, low T cell numbers leading to a high rate of stimulation. The calculation of the committed effective dose equivalents show that radiation protection against internal tritium contamination in power plants should not be neglected.

Adult↗
PubMed1993

[Genetic and immunologic studies after space flight].

The effect of spaceflight on lymphocytes of the peripheral blood was investigated in the Austrian cosmonaut flying the Austro-Soviet mission Austromir. Blood was sampled before and after flight, and the following parameters studied: quantities of lymphocytic subsets (T cells, helper cells, suppressor cells, B cells and natural killer cells); mitogenic stimulation of lymphocytes--DNA (= deoxyribonucleic acid) synthesis and expression of Interleukin-2-receptor; structural modification of DNA, unscheduled DNA synthesis and sister chromatid exchanges. Besides reducing the number of natural killer cells, spaceflight caused on impairment of lymphocyte activity and a slight modification of DNA structure. 4 weeks after flight, control values were reestablished, indicating efficient repair mechanisms.

Chromosome Aberrations↗
PubMed1990

T-lymphocyte subsets in occupationally exposed persons.

The percentage of CD2+, CD4+, CD8+ and HNK-1+ cells in peripheral blood was investigated in persons occupationally exposed to very low doses of ionizing radiation. Investigations were carried out by monoclonal antibodies and flow cytometry. While significant effects of age and smoking habits on the relative number of CD8 cells and CD4/CD8 ratios could be established, no influence of the very low radiation exposure on the profile of lymphocytic T cells in blood was found, except a very slight effect on the relative number of CD2+ cells.

Adult↗
PubMed1990

Sister chromatid exchanges (SCEs) in lymphocytes of persons working at Shlobin (USSR), 150 km north of Chernobyl.

Workers at a building plot in Shlobin (USSR), 150 km north of Chernobyl, were examined for the occurrence of spontaneous and mitomycin C induced SCEs in peripheral lymphocytes. Personnel being present during and after the Chernobyl accident exhibited a decreased number of inducible SCEs compared with test-persons starting work at Shlobin by 1st of June, 1986. Since effective dose equivalents were rather low (about 2 m Sv till the end of August 1986), induced SCEs proved to be a very sensitive test for the demonstration of low dose exposure.

Accidents↗
PubMed1984

SCE frequencies in lymphocytes of systemic lupus erythematosus patients.

The frequency of sister-chromatid exchanges (SCEs) was investigated in peripheral lymphocytes of lupus erythematosus patients and compared with values obtained for healthy controls. Irrespective of the kind of medical treatment, an increased level of spontaneously occurring SCEs could be demonstrated in lupus patients. In addition to spontaneously occurring SCEs, mitomycin C (MMC)-induced SCEs were evaluated. No difference between patients and controls was found with respect to MMC-induced SCEs.

Adult↗
PubMed1983

Investigations on the effect of repeated hair dyeing on sister chromatid exchanges.

The numbers of sister chromatid exchanges (SCE) were determined in the lymphocytes of ten volunteers (males and females) whose hair was dyed 13 times at intervals of 3-5 wk. Each volunteer used throughout the study a single commercial preparation containing a mixture of aminotoluenes, aminophenols and hydroxybenzenes, and in some cases naphthol, as the active ingredients. The findings were compared with those in a control group matched for age and sex. SCE were determined in blood samples taken before the first exposure, after a sham dyeing and after the first three and the last three actual dyeing procedures. Volunteers were carefully screened for disease, for use of medicines and for radiation exposure. Consumption of alcohol was the same in both groups, but there were more smokers in the treated group. No evidence was found of any effect of repeated hair dyeing on the frequency of SCE. In both the controls and in the hair-dyed subjects a slight decrease in SCE was detected during the course of the experiment; this was independent of sex as well as of the dyeing procedure.

Adult↗
PubMed1983

UDS and SCE in lymphocytes of persons occupationally exposed to low levels of ionizing radiation.

Unscheduled DNA synthesis induced by in vitro UV irradiation was investigated in lymphocytes of persons occupationally exposed to low doses of ionizing radiation (maximum registered radiation dose: 98 mrad/month). For radiation exposures greater than 14 mrad/month above background level, increased rates of UDS after in vitro UV irradiation of lymphocytes were found. The bromodeoxyuridine differential chromatid labeling technique was applied to the examination of spontaneous and Mitomycin C (MMC)-induced sister chromatid exchanges (SCE) in the same population. No statistically significant difference could be determined in spontaneously occurring SCEs, while MMC induced SCEs were significantly reduced in persons exposed to radiation doses greater than 14 mrad/month, thus indicating increased repair capability for DNA lesions inflicted by a second insult after protracted low-dose irradiation.

Adult↗
PubMed1978

Barogenic rupture of the esophagus associated with hyperemesis gravidarum.

Spontaneous rupture of the esophagus is associated with continuous nausea and vomiting in the chronic alcoholic. The following is a case report of a similar occurrence in a young, healthy, primigravida with hyperemesis gravidarum. To our knowledge, this has not previously been reported in the obstetric literature.

Adult↗
PubMed1976

[Xeroderma pigmentosum with normal excision-repair capacity and decreased U-V tolerance (author's transl)].

Unscheduled DNA synthesis was investigated in the peripheral lymphocytes of a 31-year-old woman suffering from Xeroderma pigmentosum, clinically manifest since early childhood. The present data indicate a normal level of excision repair capacity, though U-V sensitivity was increased. The present case is considered to be a new variant of the syndrome Xeroderma pigmentosum, demonstrating once more its genetic heterogeneity. The question of a relationship between the observed data and the known occurrence of carcinoma in the light-exposed skin areas remains to be answered.

Adult↗
PubMedDate not supplied

Immunological investigations in a group of workers exposed to various levels of polycyclic aromatic hydrocarbons.

To evaluate a possible immunotoxic effect of chronic exposure to polycyclic aromatic hydrocarbons (PAHs), several immune parameters were investigated in two groups of coke-oven workers. Exposure levels were different for both groups, one group being employed in a new coking facility of sophisticated technical standard, and the other in a facility with rather high emission of PAH-containing dust, built during the late 1960s. Immunomodulating effects of exposure were found on three levels of immunity: a reduced mitogenic response of T cells to phytohaemagglutinin observed by a reduced rate of DNA synthesis and a retardation in the expression of interleukin 2 receptor; an impairment of B cell activity, observed by a reduced proliferation of B cells and a low synthesis of immunoglobulin M after Staphylococcus aureus stimulation; a reduced oxidative burst in monocytes after challenge with E. coli. The differences in numbers of lymphocytic subpopulations in peripheral blood and in immunoglobulin levels of serum were statistically insignificant. The data of the present investigations point to significant, albeit slight, changes in immune function by PAH exposure. But these changes could not yet be related to health impacts of the exposure.

Adult↗
PubMedDate not supplied

Investigations on immune parameters in welders.

The aim of the present investigation was to study the effects of welding fumes on the human immune system. Thirty male subjects who had regularly welded and 16 control persons without occupational exposure were examined. Cellular immunity was evaluated by phenotyping of peripheral leucocytes, measurement of mitogenic T cell response and T cell stimulation in a heterologous mixed lymphocyte reaction. Non-specific immune reactions were quantified by oxidative burst of granulocytes and monocytes and the cytotoxicity of lymphokine-activated killer (LAK) cells. Serum immunoglobulin levels and immunoglobulin production by stimulated B cells served to demonstrate humoral immune reactions. Welding fumes retarded the kinetics of DNA synthesis after phytohaemagglutinin stimulation of T cells and reduced the cytotoxic activity of LAK cells. No effects on lymphocytic subpopulations, mixed lymphocyte reaction, the phagocytosis of leucocytes or the production of immunoglobulins were observed. Several welders reported on recurrent respiratory infections or bronchitis, a few on allergic skin reactions and one worker was affected by asthmatic symptoms. With the exception of a reduced activity of LAK cells, these effects could not be related to any impairment of immune reactions as they were measured by the immunotoxicity tests applied.

Adolescent↗
PubMedDate not supplied

Langerhans cells and immature dendritic cells as model systems for screening of skin sensitizers.

Langerhans cells are the most potent antigen-presenting cells in the skin and play a critical role in the induction of contact allergy. Research on the phenotypical and functional changes of LCs occurring after application of skin sensitizers indicated their use as an in vitro model for the screening of chemicals. In the present investigations, LCs from human skin explants served as the test system. The application of this cell system has been aggravated by the difficulty in isolating sufficient numbers of live LCs from skin. This disadvantage was overcome by the culture of immature dendritic cells from peripheral mononuclear blood cells. These cells can serve as a replacement for LCs as they bind haptens and show phenotypical and functional changes similar to LCs. The sensitizers NiSO(4), dinitrochlorobenzene, 2,4,6-trinitrobenzene sulfonic acid, alpha-hexylcinnamaldehyde and eugenol were applied. Both the expression of surface markers and the induction of intracellular interleukin-1 beta (IL-1 beta) were analyzed. No clear-cut results could be established for intracellular cytokine production, only NiSO(4) induced a remarkable number of IL-1 beta-positive cells. However, all skin sensitizers caused an up-regulation of the co-stimulatory molecule CD86, of intercellular adhesion molecule CD54 and of the HLA-DR antigen. The irritant sodium dodecyl sulfate (SDS) and the vehicle dimethyl sulfoxide (DMSO) had no effect.

Acrolein↗
PubMedDate not supplied

[DNA repair in murine lupus].

DNA repair was investigated in New Zealand Mice strains which develop murine lupus, and compared with Swiss control mice. Unscheduled DNA synthesis demonstrated by autoriadiography was used to measure the repair capacity of spleen cells. After gamma-irradiation DNA repair was decreased in the autoimmune strains, while it was significantly increased after UV-irradiation. A possible relationship between repair capacity after gamma-respectively UV-irradiation and the etiologic factor of autoimmunity is discussed.

Age Factors↗