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Biomedical subjects

A Karakaya

Publications and source records attributed to A Karakaya.

At least 19 recordsLinked to original sources

Investigation of some immunological functions in a group of asphalt workers exposed to polycyclic aromatic hydrocarbons.

To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) on the human immune system, analyses were performed on T-cell subsets (CD4+, CD8+), B-cells (CD19+), serum immunoglobulin levels (IgG, IgM, IgA) and white blood cell percentages of 16 male workers who were employed in road paving operations and compared to 12 unexposed male controls. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. While the CD4+ cell percentage and the CD4+/CD8+ ratio were significantly higher in the PAH-exposed group, the percentages of CD8+ and CD19+ cells were unchanged. There was also a significant enhancement in serum IgG levels and the percentage of monocytes in the workers compared to the control group. These data suggest that chronic exposure to PAHs may affect some immune functions in humans.

Adult↗

Serum paraoxonase activity and phenotype distribution in Turkish subjects with coronary heart disease and its relationship to serum lipids and lipoproteins.

Recently, biochemical studies of paraoxonase in the serum of humans have shown that much of this enzymes' activity is associated with high-density lipoprotein (HDL) and paraoxonase may play a role in lipid metabolism preventing the accumulation of the lipoperoxides. In this study, a possible relationship between coronary heart disease (CHD) and paraoxonase activity were investigated. Serum triglycerides, total cholesterol, HDL-cholesterol and paraoxonase activity were measured in unrelated healthy donors and CHD patients. It was found that paraoxonase activity was trimodally distributed in both groups but no statistically significant difference was found between phenotype distributions of controls and CHD patients (gene frequencies; 0.632 and 0.382 of controls, 0.702 and 0.298 of patients for the A and B alleles, respectively). However, in CHD group, a high possibility was found to be phenotype A compared with the control group. A relative risk of 1.48 (95% confidence intervals (CI), 0.986-2.227) was found for the relation between CHD and the paraoxonase activity. Patients' HDL-cholesterol values were lower and triglycerides were higher than controls (P<0.001). It may be concluded from the present study that although no statistically significant difference was found between paraoxonase phenotype distributions of controls and CHD patients, a decrease in paraoxonase activity could become a risk factor for this disease.

Adult↗

Effects of occupational chronic co-exposure to n-hexane, toluen, and methyl ethyl ketone on NK cell activity and some immunoregulatory cytokine levels in shoe workers.

1. To evaluate the effects of occupational long-term co-exposure to n-hexane, toluen, and methyl ethyl ketone (MEK) on NK cell activity and serum IL-2, gamma-IFN levels, we studied a group of workers employed in a shoe factory where the jobs include use of glues and adhesives containing mainly n-hexane, and at low concentrations, toluen and MEK. 2. No differences were found in these parameters even in those workers with 3.3-fold higher mean levels of urine, 2,5-Hxdn and approximately twofold higher mean levels of urine hippuric acid as compared to controls. 3. We conclude that chronic co-exposure to n-hexane, toluen, and MEK at these levels is not associated with an impairment on either NK cell activity or serum IL-2 and gamma-IFN levels.

Adolescent↗

In vitro effects of various metals on natural killer cell activity in cultured human lymphocytes.

Heavy metals have been shown to have a differential effects on various aspects of immune response. Recently natural killer cells have been widely investigated due to their purported role in immune surveillance. To ascertain the immunotoxic effects of lead, cadmium, nickel and chromium on natural killer (NK) cell activity in vitro, peripheral blood lymphocytes from normal donors were examined in the presence of different concentrations (10(-5)-10(-8) M) of four selected metal salts (cadmium sulphate, lead nitrate, chromium nitrate and nickel sulphate). NK cell activity was evaluated in a 4-h chromium release assay against K562 target cells. All of the metal salts were found to exert no effect on NK cell function in the human concentration range.

Adult↗

Effects of occupational lead and cadmium exposure on some immunoregulatory cytokine levels in man.

The levels of serum interleukin-1beta (IL-1beta), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (gamma-IFN) were assessed in the workers who were occupationally exposed to lead and cadmium. The values were compared with the age-matched control group. Blood lead and cadmium levels were significantly raised. Our findings suggest that chronic lead and cadmium exposure in humans resulted in significant suppression of the serum IL-1beta level, but did not alter IL-2 and TNF-alpha levels. The gamma-IFN level was also reduced in lead workers. In contrast, a significant enhancement was observed in the cadmium-exposed group. We conclude from these results that lead and cadmium exposure at chronically high level may affect some cytokine levels in humans.

Adult↗

Kinetics of excision of purine lesions from DNA by Escherichia coli Fpg protein.

The kinetics of excision of damaged purine bases from oxidatively damaged DNA by Escherichia coli Fpg protein were investigated. DNA substrates, prepared by treatment with H2O2/Fe(III)-EDTA or by gamma-irradiation under N2O or air, were incubated with Fpg protein, followed by precipitation of DNA. Precipitated DNA and supernatant fractions were analyzed by gas chromatography/isotope-dilution mass spectrometry. Kinetic studies revealed efficient excision of 8-hydroxyguanine (8-OH-Gua), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 4, 6-diamino-5-formamidopyrimidine (FapyAde). Thirteen other modified bases in the oxidized DNA substrates, including 5-hydroxycytosine and 5-hydroxyuracil, were not excised. Excision was measured as a function of enzyme concentration, substrate concentration, time and temperature. The rate of release of modified purine bases from the three damaged DNA substrates varied significantly even though each DNA substrate contained similar levels of oxidative damage. Specificity constants (kcat/KM) for the excision reaction indicated similar preferences of Fpg protein for excision of 8-OH-Gua, FapyGua and FapyAde from each DNA substrate. These findings suggest that, in addition to 8-OH-Gua, FapyGua and FapyAde may be primary substrates for this enzyme in cells.

Animals↗

Effects of high-level exposure to lead on NK cell activity and T-lymphocyte functions in workers.

1. NK and T cell functions were measured in peripheral blood lymphocytes of workers occupationally exposed to lead. 2. No differences were found in these functions even in those workers with higher levels of blood and urine lead and urinary delta-ALA than the currently accepted biological limit values as compared to controls. 3. We conclude that high chronic exposure to lead is not associated with an impairment or either T- or NK cell functions in man.

Adult↗

Simultaneous effects of lead and cadmium on NK cell activity and some phenotypic parameters.

Lead and cadmium are common environmental contaminants that alter the immune response. Natural killer cell (NK) cytotoxicity and phenotypic parameters are crucial immune responses, but little is known about the effects of these metals on these responses. In the present paper, we investigated the simultaneous effects of lead and cadmium on NK cell activity and CD4+, CD20+ cell percentages in the workers and compared the data with control and lead-exposed groups. We conclude that simultaneous exposure to lead and cadmium is not associated with an impairment of either NK cell function of CD4+ cell percentage. On the other hand, CD20+ cell percentage was found higher in lead+cadmium exposed group than controls.

Adult↗

Damage, repair, and mutagenesis in nuclear genes after mouse forebrain ischemia-reperfusion.

To determine whether oxidative stress after cerebral ischemia-reperfusion affects genetic stability in the brain, we studied mutagenesis after forebrain ischemia-reperfusion in Big Blue transgenic mice (male C57BL/6 strain) containing a reporter lacI gene, which allows detection of mutation frequency. The frequency of mutation in this reporter lacI gene increased from 1.5 to 7.7 (per 100,000) in cortical DNA after 30 min of forebrain ischemia and 8 hr of reperfusion and remained elevated at 24 hr reperfusion. Eight DNA lesions that are characteristic of DNA damage mediated by free radicals were detected. Four mutagenic lesions (2,6-diamino-4-hydroxy-5-formamidopyrimidine, 8-hydroxyadenine, 5-hydroxycytosine, and 8-hydroxyguanine) examined by gas chromatography/mass spectrometry and one corresponding 8-hydroxy-2'-deoxyguanosine by a method of HPLC with electrochemical detection increased in cortical DNA two- to fourfold (p < 0.05) during 10-20 min of reperfusion. The damage to gamma-actin and DNA polymerase-beta genes was detected within 20 min of reperfusion based on the presence of formamidopyrimidine DNA N-glycosylase-sensitive sites. These genes became resistant to the glycosylase within 4-6 hr of reperfusion, suggesting a reduction in DNA damage and presence of DNA repair in nuclear genes. These results suggest that nuclear genes could be targets of free radicals.

Animals↗

Novel activities of human uracil DNA N-glycosylase for cytosine-derived products of oxidative DNA damage.

Uracil DNA N-glycosylase is a repair enzyme that releases uracil from DNA. A major function of this enzyme is presumably to protect the genome from pre-mutagenic uracil resulting from deamination of cytosine in DNA. Here, we report that human uracil DNA N-glycosylase also recognizes three uracil derivatives that are generated as major products of cytosine in DNA by hydroxyl radical attack or other oxidative processes. DNA substrates were prepared by gamma-irradiation of DNA in aerated aqueous solution and incubated with human uracil DNA N-glycosylase, heat-inactivated enzyme or buffer. Ethanol-precipitated DNA and supernatant fractions were then separated. Supernatant fractions after derivatization, and pellets after hydrolysis and derivatization were analyzed by gas chromatography/isotope-dilution mass spectrometry. The results demonstrated that human uracil DNA N-glycosylase excised isodialuric acid, 5-hydroxyuracil and alloxan from DNA with apparent K(m) values of approximately 530, 450 and 660 nM, respectively. The excision of these uracil analogues is consistent with the recently described mechanism for recognition of uracil by human uracil DNA N-glycosylase [Mol,C.D., Arval,A.S., Slupphaug,G., Kavil,B., Alseth,I., Krokan,H.E. and Tainer,J.A. (1995) Cell, 80, 869-878]. Nine other pyrimidine- and purine-derived products that were identified in DNA samples were not substrates for the enzyme. The results indicate that human uracil DNA N-glycosylase may have a function in the repair of oxidative DNA damage.

Animals↗

Some immunological parameters in workers occupationally exposed to n-hexane.

1. To estimate the quantitative relation between exposure to airborne n-hexane and various markers of immune function, 35 male workers were examined and compared with unexposed controls. 2. Urinary 2,5-hexanedione concentrations were significantly higher in the exposed group than in the unexposed. 3. A significant suppression was observed in the serum immunoglobulin (IgG, IgM and IgA) levels between two populations. Also, a significant correlation was found between urinary 2,5-hexanedione concentrations and serum Ig level of the exposed group. 4. No significant difference between white blood cell counts was found in the two groups.

Adhesives↗

Effect of short-term therapy with ceftizoxime and ceftriaxone on human peripheral WBC, serum immunoglobulins and lymphocyte subpopulations.

Serum immunoglobulins, peripheral white blood cells and lymphocyte subpopulation counts of twenty patients who received ceftizoxime and ceftriaxone for antimicrobial prophilaxis in surgery were examined in order to obtain a profile of the effects of these drugs on humoral and cellular immune system of human. No differences in the serum concentrations of IgG, IgM, IgA, peripheral blood lymphocytes and lymphocyte subpopulations 24 h and 48 h following the last dose of these two drugs were observed.

Adult↗

An immunological study on workers occupationally exposed to cadmium.

1. To assess the quantitative relation between exposure to airborne cadmium and various markers of immune function, 37 male workers were examined and compared with unexposed controls. 2. Blood cadmium concentrations were significantly higher in the exposed workers than in the unexposed, as was urine cadmium. 3. No differences in the serum immunoglobulin (IgG, IgM and IgA) levels between two populations were observed. There was also no significant correlation between blood cadmium concentrations and serum immunoglobulin levels of both exposed and control groups, It has been found also that while monocyte counts significantly increased, lymphocyte, neutrophil and eosinophil counts remained unchanged.

Adult↗

Analysis of the serum paraoxonase/arylesterase polymorphism in a Turkish population.

Human serum paraoxonase is a polymorphic enzyme that is capable of catalyzing the hydrolysis of paraoxon and other organophosphates, some carbamates and certain aromatic carboxylic acid esters. This enzyme is specified by two allelic genes at one autosomal locus (isozymes 'A' and 'B'). The purpose of this study was to examine the paraoxonase activity of 105 Turkish subjects. Paraoxonase activities ranged from 39.6 to 278.2 nmol p-nitrophenol formed per ml of serum per min. Paraoxonase phenotypes could be clearly identified by salt and paraoxonase:arylesterase activity ratio characteristics. The gene frequencies were 0.632 for the low activity allele (A) and 0.368 for the high activity allele (B).

Adult↗