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Biomedical subjects

K Golka

Publications and source records attributed to K Golka.

At least 19 recordsLinked to original sources
PubMed2003

Physiological and psychological approaches to chemosensory effects of solvents.

Workplace related standard settings for solvents are based in a remarkable extent on information about sensory irritations. However, data from controlled human exposure studies are seldom available. Therefore, the aim of this study was to present the association of self-reported symptoms and physiological processes leading to sensory irritations. Three series of laboratory experiments each with 24 young male subjects were performed. Ethyl benzene (EB), 2-butanone (methyl ethyl ketone or MEK), isopropyl alcohol (IPA), 1-octanol (OCT), and 2-ethylhexanol (EHEX) were investigated in low and high concentrations. Ratings for sensory irritations (eyes and nose), olfactory symptoms, and annoyance were assessed repeatedly before, during and after the 4-h-exposures. The anterior active rhinomanometry (AAR) was employed measuring the nasal flow. The nasal lavage was used for the analysis of the neuropeptide substance P as indicator of nasal chemosensory irritations. Goodness-of-fit was calculated for non-linear regression analyses by fitting the sine function on the data of the ratings given during the 4-h-exposure. In general, ratings for annoyance and odor symptoms were fitted on a higher level than those for sensory irritations. However, a high fit could be shown for nasal irritations due to EHEX. In these experiments, a significant reduction of the nasal flow and a significant increase of substance P could be proved.

Administration, Inhalation↗
PubMed2001

Experiments on the effects of a continuous 16.7 Hz magnetic field on melatonin secretion, core body temperature, and heart rates in humans.

The present study investigated the hypothesis that a strong extremely low frequency magnetic field partially suppresses the synthesis of melatonin and subsequently elevates the core body temperature. Seven healthy young men (16-22 years) took part in a control and in an exposure session. Three men experienced first the control and then the exposure session, four men experienced the sessions in reverse order. Control sessions were performed as constant routines, where the participants spent 24 hour periods continuously in bed while air temperature was 18 degrees C, illumination less than 30 lux, and the sound pressure level 50 dBA. The exposure sessions differed from that protocol only between 6 pm and 2 am when a strong extremely low frequency magnetic field was continuously applied (16.7 Hz, 0.2 mT). Assuming that the participants were unable to perceive the field consciously, they were blind against the actual condition. Salivary melatonin levels were determined hourly; body core temperatures and heart rates were registered continuously throughout. Neither of these parameters revealed alterations that can be related to the influence of the magnetic field. The present results, taken together with other investigations using that particular field, lead to the hypothesis that the effects most likely, occur, only after repetitive exposures to intermittent fields.

Adolescent↗
PubMed2001

Dependence of papanicolaou gradings of exfoliated urothelial cells upon GSTM1 and GSTT1 polymorphism in benzidine-exposed workers of the Shanghai dye industry.

The distribution of the polymorphic alleles of the genes coding for glutathione S-transferases (GSTs) M1 and T1 was compared with the results of cytological grading of exfoliated urothelial cells (Pap test) in a non-diseased high-risk group of workers formerly exposed to benzidine in the Shanghai dyestuff industry (n = 317). All subjects were genotyped for GSTT1 and M1 gene polymorphism by allele-specific PCR. Individuals were stratified according to their job and duration of exposure. A subgroup of 78 individuals with cytological gradings of grade III or higher in the Pap test showed a significant under-representation of the combination of GSTT1 0/0 and M1 0/0 genotypes compared with 238 subjects with a cytological classification lower than grade III (OR 0.55, 95% CI 0.31-0.98. P=0.04). These results suggest that neither the GSTM1 0/0 or GSTT1 0/ 0 genotype alone nor their combination had a clear association with cytopathological changes in exfoliated urothelial cells from individuals previously exposed to benzidine in Shanghai. This contradicts the results of studies indicating that the GSTM1 0/0 genotype is associated with an increased risk for bladder cancer in the general population, mostly outside China.

Adult↗
PubMed2001

Polymorphic methyl group metabolism genes in patients with transitional cell carcinoma of the urinary bladder.

Because polymorphisms in the methyl group metabolism genes methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MS), and cystathione beta-synthetase (CBS) affect plasma homocysteine levels and intracellular concentrations of S-adenosylmethionine (SAM), they modify the susceptibility to cardiovascular diseases and cancer. Specifically, genome-wide decreased DNA methylation ('hypomethylation') in human cancers might be a consequence of decreased SAM levels. Because hypomethylation is particularly prevalent in transitional cell carcinoma of the urinary bladder (TCC), the genotype distributions for the two each most prevalent MTHFR, MS, and CBS alleles were compared between 165 TCC patients and 150 population controls. The distributions of the MTHFR 677A/V and the MS 919G/D alleles were not significantly different between cancer patients and controls, even after stratification according to age, gender, tumor stage or grade. The CBS 844INS68 allele was slightly less frequent in TCC patients than in controls (q=0.07 versus 0.10), but was rarer among males in both groups. Among the TCC patients, this gender difference was highly significant (Mantel-Haenszel and chi(2)-test P=0.007). No significant difference between TCC patients and controls was found for any combined genotype. Likewise, the extent of DNA hypomethylation determined in 62 carcinoma specimens was not related to the respective genotypes. Thus, on their own, the MTHFR, MS and CBS genotypes do not appear to act upon susceptibility to TCC or influence the extent of DNA hypomethylation in this cancer.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2001

N-acetyltransferase 2 phenotype in painters with bladder cancer and controls.

AIM: This study was designed to evaluate the impact of N-acetyltransferase 2 (NAT2, substrate: aromatic amines) in painters with bladder cancer and controls. BACKGROUND: Until the beginning of the 1960s, painters in Germany have used, among others, azo dyes based on carcinogenic aromatic amines. MATERIALS AND METHODS: Sixteen painters with bladder cancer and 26 healthy painters (controls) who were from the same area in Germany and in the same age group (+/-5 years) were recruited into the study. All subjects were phenotyped for NAT2 by the molar ratio of two caffeine metabolites in the urine which was determined by the high performance liquid chromatography (HPLC) method. The number of years working as a painter, age at first exposure to paints and the life-time smoking habits of subjects were noted. RESULTS: Fourteen cases and 23 controls had been exposed to paints before 1960. Age at first exposure to paint was 15.5 years (SD 5.3) in cases and 16.3 (SD 4.9) years in controls. Cases had worked 31.1 years (SD 15.0) and controls had worked 44.8 years (SD 7.2) as painters. Four cases and 7 controls were non-smokers. In this study, 88% of cases and 65% of controls were of the "slow" acetylation and phenotype, CONCLUSION: The result point to and impact of the slow acetylation status as an individual risk factor for bladder cancer in persons occupationally exposed to amounts of carcinogenic aromatic amines released from water-soluble azo dyes.

Acetylation↗
PubMed2001

Current smoking, occupation, N-acetyltransferase-2 and bladder cancer: a pooled analysis of genotype-based studies.

The aim of this study was to investigate the association of NAT2 gene polymorphism with bladder cancer using the data derived from the International Project on Genetic Susceptibility to Environmental Carcinogens. Four case control studies conducted in four European countries, plus two case series, one from England and one from Germany, for a total of 1530 cases and 731 controls (all Caucasian) were included. The interaction between NAT2 and bladder cancer considering smoking habits and occupational exposure was studied. There was a significant association between NAT2 and bladder cancer (odds ratio: 1.42, 95% confidence interval: 1.14-1.77), with a slightly significant heterogeneity among studies. However, heterogeneity disappeared when smokers were divided into current and ex-smokers. The risk of cancer was elevated in smokers and occupationally exposed subjects, with the highest risk among slow acetylators. The increase in risk was limited, in fact, to current smokers (odds ratio = 1.74, 95% confidence interval: 0.96-3.15). This analysis confirms that the NAT2 genotype is a risk factor for bladder cancer by interacting with smoking or occupational exposures. Our observation suggests that NAT2 is not a risk factors per se but modulates the effect of carcinogens contained in tobacco smoke (probably arylamines) or associated with occupational exposures.

Adult↗
PubMed2000

Methyl group metabolism gene polymorphisms and susceptibility to prostatic carcinoma.

BACKGROUND: Alterations of DNA methylation are very frequent in prostatic carcinoma. A possible cause underlying altered DNA methylation could be an insufficient level of S-adenosylmethionine as a consequence of nutritional imbalances or of weaker alleles of genes for its synthesis, i.e., encoding methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MS), and beta-cystathione synthetase (CBS). Therefore, homozygosity or heterozygosity for such weaker alleles may underlie susceptibility to prostatic carcinoma. METHODS: The distribution of the two most frequent MTHFR, MS, and CBS alleles was determined in 132 prostatic carcinoma patients and 150 population controls by restriction fragment length polymorphism-(RFLP) PCR. RESULTS: In the controls, a Hardy-Weinberg equilibrium was observed for each allele pair. No significant differences were observed with respect to age or gender. No significant differences for single genes or combinations were found between prostatic carcinoma patients and controls, although the MTHFR Val allele was slightly overrepresented among the tumor patients. Neither did the allele distribution significantly differ among the prostatic carcinoma patients stratified according to age, clinical stage, or presence of metastases. However, the MTHFR Val allele tended to be associated with higher tumor grade. CONCLUSIONS: In general, the data do not support the hypothesis that weaker alleles in methyl group metabolism genes constitute a major factor in the high prevalence of DNA methylation alterations found in prostatic carcinoma. However, a potential association with the MTHFR genotype deserves further study.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2000

Glutathione transferase isozyme genotypes in patients with prostate and bladder carcinoma.

Genotype distributions for GSTP1, GSTM1, and GSTT1 were determined in 91 patients with prostatic carcinoma and 135 patients with bladder carcinoma and compared with those in 127 abdominal surgery patients without malignancies. None of the genotypes differed significantly with respect to age or sex among controls or cancer patients. In the group of prostatic carcinoma patients, GSTT1 null allele homozygotes were more prevalent (25% in carcinoma patients vs. 13% in controls, Fisher P =0.02, chi2 P=0.02, OR=2.31, CI = 1.17-4.59) and the combined M1-/T1 -null genotype was also more frequent (9% vs. 3%, chi2 P=0.02, Fisher P = 0.03). Homozygosity for the GSTM1 null allele was more frequent among bladder carcinoma patients (59% in bladder carcinoma patients vs 45% in controls, Fisher P=0.03, chi2 P=0.02, OR=1.76, CI=1.08-2.88). In contrast to a previous report, no significant increase in the frequency of the GSTP1b allele was found in the tumor patients. Except for the combined GSTM1-/ T1-null genotype in prostatic carcinoma, none of the combined genotypes showed a significant association with either of the cancers. These findings suggest that specific single polymorphic GST genes, that is GSTM1 in the case of bladder cancer and GSTT1 in the case of prostatic carcinoma, are most relevant for the development of these urological malignancies among the general population in Central Europe.

Aged↗
PubMed2000

Cultures of exfoliated epithelial cells from different locations of the human urinary tract and the renal tubular system.

Exfoliated human urinary tract epithelial cells and renal tubular cells from urinary sediments of healthy adults, of urological patients and of internal patients were isolated and cultured. Cells started proliferating within 1 week after seeding a sediment. Proliferating cells formed colonies of different morphologies, designated as type-1 or type-2 cell colonies. Type-1 cell colonies showed irregular contours and spindle-like cells within the colonies. Subcultivation of type-1 cells for up to six passages was possible. Type-2 cell colonies showed smooth-edged contours and subcultivation was not possible. The epithelial character of type-1 cells was demonstrated by positive immunohistochemical staining for cytokeratin-7. In contrast to carbonic anhydrase-positive stained Madin Darby canine kidney cells (MDCK), which were used as positive controls for renal tubular cells, type-1 cells were carbonic anhydrase-negative on staining with the cobalt phosphate method. This indicates that type-1 cells were not of renal tubular origin. Type-2 cells were positively stained for carbonic anhydrase, indicating that type-2 cells were renal tubular cells. Type-2 cell colonies could be assigned to two subgroups with different cell forms. Colonies of cobblestone-like cells more often occurred than type-2 cell colonies with spindle-like cells, which are described in this study for the first time. Colonies with cobblestone-like cells formed domes (hemicysts), whereas spindle-like type-2 cell colonies did not. Cultures of urinary sediments from healthy adults, elderly multimorbid patients treated with furosemide, and urological patients with urolithiasis treated with sulfamethoxazole/trimethoprim and/or with a percutaneous nephrostomy catheter were compared. In 52% of all cultured sediments from healthy adults, in 30% of those from multimorbid patients, and in 75-80% of those from urological patients cells proliferated to colonies. The ratios of type-1 to type-2 cell colonies were 3.3:1 (healthy adults), 1.4:1 (urological patients with urolithiasis), and 1.8:1 (urological patients with urolithiasis, urine was directly collected from the renal pelvis with a percutaneous nephrostomy catheter). Successful cultures of the urinary sediments from these three groups revealed means of 3 or 4 colonies, 14 colonies, and 21 colonies, respectively. Differences in the number of colonies in relation to sex were observed only for the group of urological patients. It was shown that type-1 cells were urothelial cells, which did not show morphological differences due to their locations of origin within the urinary tract, whereas type-2 cells were probably renal tubular cells. These findings offer new aspects in the culturing of human urothelial or kidney epithelial cells with a method based on noninvasive collecting of specimens and requiring only minimal culture effort. The cultures obtained by this method can be used for in vitro studies in toxicological and clinical research.

Adolescent↗
PubMed2000

Induction of unscheduled DNA synthesis in primary human urothelial cells by the mycotoxin ochratoxin A.

Ochratoxin A (OTA) is a widespread contaminant in human staple food. Exposure of humans to this mycotoxin is a matter of concern because OTA is a known rodent carcinogen. As the urothelium is one target tissue of this mycotoxin, primary cultured human urothelial cells (HUC) from adults and children were used to analyze the induction of unscheduled DNA synthesis (UDS) by OTA. HUC were isolated from the ureters or renal pelves of two nephrectomized adults and of two children with ureteropelvic junction stenosis and cultured under serum-free conditions. After a confluency of 70-80% was reached, cell proliferation was suppressed by arginine-deficient medium (ADM), and UDS was assessed autoradiographically by 3H-thymidine incorporation upon exposure to OTA (10-2000 nM), ethyl methanesulfonate (EMS, 5 mM, positive control), or dimethyl sulfoxide (DMSO, 0.2%, solvent control). In control cultures the level of UDS was low. Exposure to EMS resulted in an induction of UDS (2-to 5-fold compared to control), thus allowing the sensitive detection of repair resulting from induction of DNA lesions in all four specimens, and demonstrating that repair of EMS-induced DNA lesions can take place under the chosen culture conditions. In two HUC cultures derived from adults, a significant induction of UDS was observed in the concentration range of 50-500 nM OTA. The highest fraction of cells in repair (CIR) was found at 50 nM OTA for the HUC from the older male (50% CIR). The maximum response in the other specimens from the adult female and the 7-year-old boy were seen at OTA concentrations of 500 and 250 nM, respectively. In contrast to all other specimens, no significant induction of UDS by OTA was found in the HUC cultures derived from an infant's urothelium. Signs of cytotoxicity were observed above 500 nM OTA in all cultures. The varying susceptibility toward OTA observed in vitro may hint at varying predispositions of individuals in vivo.

Adult↗
PubMed2000

Subjective symptoms due to solvent mixtures, dioxin, and toluene: impact of exposure versus personality factors.

In this study, we analyse the impact of personality factors on the frequency of self-reported symptoms for workers under different exposure conditions. Reported symptoms may depend on the level and type of exposure, as well as on personality factors such as trait anxiety of the worker or his general sensitivity with regard to the environment. The employed data stems from three studies: The first study contains information of 60 workers who suspected to be exposed to polychlorined dibenzodioxins and dibenzofuranes (Lifetime Weighted Average Exposure, LWAE, as an index for contact with the substances). The second study concerns 40 workers who are exposed to different concentrations of solvent mixtures in paint manufacturing (LWAE of total hydrocarbons about 10 ppm). The third study includes repeated measurements of two subgroups of workers from rotogravure printing plants who are exposed to different concentrations of toluene: a "high" exposure group (n = 129, LWAE about 46 ppm, current exposure 25 ppm) and a "low" exposure group (n = 96, LWAE for toluene about 9 ppm, current exposure 3 ppm). Trait anxiety, environmental sensitivity, and self-reported symptoms are measured by validated questionnaires and age as well as verbal intelligence are controlled. To determine the effect of the individual characteristics and the different exposures on self-reported symptoms, frequency analyses and variance analyses are conducted and linear models are fitted. For all analyses, trait anxiety explains the highest share of the variance. If there is no effect of the exposure on the reported symptoms (dioxin and low-level toluene study), trait anxiety seems to have a larger explanatory power in comparison with those studies where the exposure has an effect on the reported symptoms (solvent-mixture and high-level toluene study). Neurotoxicological risk analysis has to account for the detected dependence of self-reported symptoms on personality traits: assessments for elevated symptoms should not only be linked to the intensity of exposure but also related to benchmarks derived from the normal variability of personality factors.

Adaptation, Psychological↗
PubMed1999

Polymorphisms of the xenobiotic-metabolizing enzymes CYP1A1 and NAT-2 in systemic sclerosis and lupus erythematosus.

The etiology of systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is still unknown. In several cases, however, xenobiotics (i.e. drugs and occupational agents) were identified as etiologic agents and associations with certain polymorphic alleles of xenobiotic-metabolizing enzymes have been reported. Cytochrome P4501A1 (CYP1A1) and N-acetyltransferase 2 (NAT-2) are xenobiotic-metabolizing enzymes of phase 1- and phase 2-metabolism, respectively. CYP1A1 may activate drugs and other chemicals to reactive metabolites. NAT-2 is the most important enzyme in acetylation of aromatic amines, and thus may be responsible for detoxification of many of these compounds. Two polymorphisms of the human CYP1A1 gene, a point mutation in the 3' flanking region of the gene (Msp1) and a mutation in exon 7 leading to an isoleucine-valine-exchange in the heme-binding region of the enzyme, have been described and may lead to a higher basal and inducible enzyme activity. With respect to NAT-2, several alleles which combine for the two phenotypes "fast" and "slow" acetylators have been described. We analyzed the gene frequencies of the CYP1A1 polymorphisms and the phenotypes of NAT-2 in patients suffering from idiopathic SLE or SSc. CYP1A1 polymorphisms were analyzed in genomic DNA by PCR, whereas NAT-2 phenotypes were measured by the caffeine method. For CYP1A1 polymorphisms, 106 patients have been typed until now. The SLE group (n = 68) exhibited a significant increase (p < 0.05) in the mutant Val-allele (OR = 2.59) when compared to controls (n = 184). However, no significant differences in allele frequencies for MspI in the SLE group and for both CYP1A1 polymorphisms in the SSc group could be observed. Regarding the NAT-2 phenotype, patients suffering from SLE (n = 88) 75% and SSc (n = 26) 80.2%, respectively, were slow acetylators compared to 55% slow acetylators in the healthy German population (p < 0.05). The observed increased frequencies of the CYP1A1 mutant Val-allele and the slow actylator phenotype in idiopathic autoimmune disease support our concept that in slow acetylators non-acetylated xenobiotics may accumulate and are subsequently metabolized by other enzymes into reactive intermediates. Thus, enhanced formation of reactive metabolites could alter self-proteins presented to the immune system thus stimulating autoreactive T cells which induce autoimmunity.

Alleles↗
PubMed1999

[Occupational risk factors for bladder carcinoma. A case control study].

Aim of this case-control study, performed on 412 male bladder cancer cases and 414 controls with benign prostatic hyperplasia in a former area of coal, iron and steel industries in Germany, was to identify occupations with an increased bladder cancer risk. In bladder cancer cases, smokers were overrepresented (58.3%) compared to controls (35.2%). The percentage of patients who had stopped smoking for at least 10 years did not differ in cases (10.2%) and controls (9.7%). Significantly elevated smoking-adjusted bladder cancer odds ratios (MH) were observed in painters and lacquers (MH 2.24, 95% CI 1.07-5.13), chemistry-related occupations (MH 2.44, 95% CI 1.05-5.67), coke plant workers (MH 2.89, 95% CI 1.16-7.16) and hard coal miners (MH 2.33, 95% CI 1.52-3.58). Significantly decreased smoking-adjusted bladder cancer odds ratios (MH) were observed in businessmen (MH 0.64, 95% CI 0.45-0.92) and office personnel (MH 0.58, 95% CI 0.41-0.81). In these two groups a relevant exposure to occupational bladder carcinogens is not likely.

Aged↗
PubMed1997

Solvent exposure and ratings of well-being: dose-effect relationships and consistency of data.

Ratings on analog scales for dimensions of well-being provide information about the acute state of well-being during solvent exposure. In a study of volunteers and workers exposed to solvents, tension, tiredness, complaints, and annoyance were rated on seven-point scales. Dose-effect relationships were analyzed for several scenarios; data were collected in diaries during work hours. In two studies, 40 volunteers in an exposure laboratory were exposed to ethanol by inhalation at levels between 80 and 1900 parts per million (ppm). In two other studies, 32 volunteers were exposed to acetone and ethyl acetate in single exposures (1000 and 500 ppm, respectively) and combined exposures (500 ppm acetone + 200 ppm ethyl acetate). A field study of 8 exposed workers and 8 nonexposed controls involved exposures of up to 2100 ppm acetone. Dose-effect relationships were shown for ratings of annoyance by correlations of 0.36 (ethanol) and 0.58 (acetone). Similar coefficients were found for ratings of complaints. The dimensions tension and tiredness showed no stable relationship with exposure. The consistency of ratings was assessed by means of correlations between the ratings given during periods of nearly equal exposures. Ratings of annoyance for the different studies between the periods of nearly equal exposure showed average correlations from 0.68 to 0.84. For the ratings of complaints, the coefficients were 0.53 to 0.81. The coefficients for tension had similar stabilities; those for tiredness were lower.

Acetates↗
PubMed1997

[Clinical relevance of acetylator phenotyping in 196 urothelial tumor patients].

A total of 196 patients with urothelial tumours were phenotyped for N-acetyltransferase 2 by the molar ratio of two caffeine metabolites excreted in urine. The proportion of "slow" acetylators, who are genetically predisposed to urothelial tumours if they have been exposed to aromatic amines in the past, in the entire group was 55%, within the range in a normal population. Among 40 patients with assumed former occupational exposure to aromatic amines, 65% were "slow" acetylators. Invasiveness, histopathological grading of the urothelial tumour at the time of first diagnosis, and course were not related to acetylator phenotype.

Acetylation↗