PubMed HealthSearch

Biomedical subjects

A Schütz

Publications and source records attributed to A Schütz.

At least 19 recordsLinked to original sources

Fish as a source of exposure to mercury and selenium.

In a total of 395 subjects with varying fish consumption habits, mercury levels in whole blood (B-Hg), and selenium levels in plasma (P-Se) were studied. Also, in subcohorts, mercury levels in blood cells (Ery-Hg; n = 79), plasma (P-Hg; n = 158) and urine (U-Hg; n = 125) were analysed. There were statistically significant associations between fish intake on the one hand, and B-Hg, Ery-Hg and P-Hg, on the other, but not so with U-Hg. In subjects who never had fish, the average B-Hg was 1.8 ng/g, in subjects who had at least two fish meals each week, 6.7 ng/g. Ery-Hg, and to a less extent P-Hg, were associated with levels of marine n-3 polyunsaturated fatty acids (PUFA) in serum phosphatidylcholine. P-Hg and U-Hg were associated with numbers of teeth with amalgam fillings. P-Se also correlated with fish intake. In subjects who never had fish, P-Se averaged 80 micrograms/l, in subjects who had at least two fish meals per week, 91 micrograms/l. There was an association between PUFA and P-Se. Further, there were statistically significant associations between P-Se on the one hand, and B-Hg, Ery-Hg and P-Hg on the other. The data clearly demonstrate the importance of fish for the exposure to methylmercury and selenium in the Swedish diet, and the impact of amalgam as a source of exposure to inorganic mercury.

Adult

Determination of methylmercury in human blood using capillary gas chromatography and selected-ion monitoring.

A capillary gas chromatographic method, using selected-ion monitoring in the electron-impact mode, was developed for the analysis of methylmercury (MeHg) in human blood. The samples, spiked with the internal standard propylmercury bromide (PropHgBr), were, after addition of sodium bromide and cupric sulfate, extracted with toluene. The organic phase was extracted with an ethanol-water solution of sodium thiosulfate. After addition of sodium bromide solution, the ethanol-water phase was extracted with toluene. Methylated derivatives (MeHgCH2Br and PropHgCH2Br) were formed by the addition of a diethyl ether solution of diazomethane. The chromatographic properties of the derivatives were much better than those of the non-methylated compounds. The m/z 215 fragment of MeHgCH2Br and the molecular ion m/z 338 of PropHgCH2Br were monitored. The calibration graphs, with a linear correlation coefficient of 0.992 (n = 12) in the 1-5 micrograms/l concentration range, passed through the origin. The detection limit for MeHg in human blood was ca. 0.5 microgram/l. Analysis of spiked blood samples at concentrations of about 2 and 10 micrograms/l gave a relative standard deviation of 4.2 and 5.5%, respectively (n = 10).

Chromatography, Gas

Coordinate genetic control of yeast fatty acid synthase genes FAS1 and FAS2 by an upstream activation site common to genes involved in membrane lipid biosynthesis.

A systematic search for upstream controlling elements necessary for efficient expression of the yeast fatty acid synthase genes FAS1 and FAS2 revealed identical activation sites, UASFAS, in front of both FAS genes. The individual element confers, in a heterologous yeast test system, an approximately 40-fold stimulation of basal gene expression. The UASFAS motifs identified have the consensus sequence TYTTCACATGY and function in either orientation. The same sequence motif is found in the upstream regions of all so far characterized yeast genes encoding enzymes of phospholipid biosynthesis. In gel retardation assays, a protein factor, Fbf1 (FAS binding factor), was identified which interacted with UASFAS. The UASFAS motif proved to be an inositol/choline responsive element (ICRE) conferring strict repression by exogenous inositol and choline on a heterologous reporter gene. Its core sequence perfectly matches the CANNTG motif typical of basic helix-loop-helix DNA-binding proteins. In contrast to the individual UASFAS element, the intact yeast FAS promoters are not significantly influenced by inositol and choline, and thus allow nearly constitutive fatty acid synthase production. Available evidence suggests that additional cis- and trans-acting elements, other than UASFAS and Fbf1, are involved in this constitutive FAS gene expression.

Base Sequence

Molecular structure of the multifunctional fatty acid synthetase gene of Brevibacterium ammoniagenes: its sequence of catalytic domains is formally consistent with a head-to-tail fusion of the two yeast genes FAS1 and FAS2.

The Brevibacterium ammoniagenes fatty acid synthetase (FAS) gene was isolated from a series of overlapping clones by both immunological and plaque hybridization screening of two independent gene libraries. From the isolated DNA a contiguous segment of 10,549 bp was sequenced in both directions. The sequenced DNA contained a very long (9312 nucleotides) open reading frame coding for a protein of 3104 amino acids and with a molecular mass of 327,466 daltons. Based on characteristic sequence motifs known from other FAS systems, seven different FAS active centres were identified at distinct locations within the polypeptide chain. Only one component enzyme, the 3-hydroxydecanoyl beta, gamma-dehydratase, has not yet been localized definitively within the gene. Translation is presumed to start from a GUG triplet located 25 nucleotides downstream of the transcriptional initiation site. There is a canonical Shine-Dalgarno sequence just before this start codon. Comparison of the B. ammoniagenes FAS sequence with those of other known fatty acid synthetases revealed a particularly high degree of similarity to the products of the two yeast genes, FAS1 and FAS2 (30% identical and 46% identical plus closely related amino acids). This similarity extends over the entire length of the genes and involves not only the primary sequences of individual component enzymes but also their sequential order within the multifunctional proteins. These data, together with those on the structure of other fatty acid synthetases, are interpreted in terms of a contribution of both primary structure and subunit cooperation to a conserved topology of functional domains common to all type I FAS complexes.

Amino Acid Sequence

Lead exposure in indoor firing ranges.

Higher air lead levels (time-weighted average 660, range 112-2238 micrograms/m3) were measured in firing ranges where powder charges were employed than in ranges where air guns were used (4.6, range 1.8-7.2 micrograms/m3); levels in the latter were in turn higher than those in ranges used for archery (0.11, range 0.10-0.13 micrograms/m3). Twenty-two marksmen who used powder charges had significantly increased blood lead levels during the indoor shooting season (before: median 106, range 32-176 micrograms/l; after: 138; range 69-288 micrograms/l; P = 0.0001), while 21 subjects who mainly used air guns displayed no significant increase (before: median 91, range 47-179 micrograms/l; after: 84; range 20-222 micrograms/l). Thirteen archers had significantly lower levels than the pistol shooters before the season (P = 0.006), and showed a significant decrease during the season (before: median 61, range 27-92 micrograms/l; after: 56; range 31-87 micrograms/l; P = 0.04). At the end of the indoor season, there was a significant association between weekly pistol shooting time and blood lead levels.

Adolescent

Serial Doppler echocardiographic assessment of left and right ventricular filling for non-invasive diagnosis of mild acute cardiac allograft rejection.

Detection of acute cardiac allograft rejection (AR) remains an important clinical challenge. The role of Doppler echocardiography for the non-invasive diagnosis of AR is controversial, in particular with regard to milder forms of rejection. This study was designed to evaluate the potential of Doppler echocardiography for the non-invasive diagnosis of mild AR. Serial measurements of left and right ventricular filling parameters were performed in 31 heart transplant recipients and compared with simultaneously obtained endomyocardial biopsies. To account for biological and technical variability, consecutive rejection-free studies were used to calculate 95% confidence limits for mitral and tricuspid maximum early flow velocity and pressure half time. Measurements obtained during mild AR were then compared to these data. The study demonstrated that all parameters varied considerably between consecutive rejection-free examinations. Changes in left and right ventricular filling parameters during mild AR rarely exceeded the calculated 95% confidence limits. Thus Doppler echocardiography appears of little value for the non-invasive diagnosis of mild acute cardiac rejection.

Adult

Establishment of a system for conditional gene expression using an inducible tRNA suppressor gene.

We investigated the use of the prokaryotic tetracycline operator-repressor system as a regulatory device to control the expression of Dictyostelium discoideum tRNA genes. The tetO1 operator fragment was inserted at three different positions in front of a tRNA(Glu) (Am) suppressor gene from D. discoideum, and the tetracycline repressor gene was expressed under the control of a constitutive actin 6 promoter. The effectiveness of this approach was determined by monitoring the expression of a beta-galactosidase gene engineered to contain a stop codon that could be suppressed by the tRNA. When these constructs were introduced into Dictyostelium cells, the repressor bound to the operator in front of the tRNA gene and prevented expression of the suppressor tRNA. Addition of tetracycline (30 micrograms/ml) to the growth medium prevented repressor binding, allowed expression of the suppressor tRNA, and resulted in beta-galactosidase synthesis. The operator-repressor complex interfered with tRNA gene transcription when the operator was inserted immediately upstream (position +1 or -7) of the mature tRNA coding region. Expression of a tRNA gene carrying the operator at position -46 did not respond to repressor binding. This system could be used to control the synthesis of any protein, provided the gene contained a translational stop signal.

Animals

Cancer incidence and mortality among Swedish Baltic Sea fishermen.

A 25% lower cancer mortality was found for 1360 Swedish fishermen who fished on the Baltic Sea than for the general population. The fishermen consumed twice as much fish as the population in the same county. In spite of the low overall cancer mortality, increased mortality from myeloma, as well as increased incidences of gastric carcinoma and squamous cell cancer of the skin and lips, was observed in the cohort. The decrease in risk for ischemic heart disease was not significant. Whether the dietary intake of fatty acids and selenium from fish contributed to the decreased risk was difficult to evaluate. Moreover, whether the consumption of fish from the Baltic Sea, contaminated with, for example, polychlorinated dioxins and dibenzofurans and other persistent organochlorine substances, contributed to the observed increased specific cancer risks is not known. However, the net health effect of high fish consumption from the Baltic Sea seems to be positive.

Adult

Chelated lead and bone lead.

In this study a close correlation [correlation coefficient (r) = 0.86, P less than 0.001] was found between the blood lead level of 20 lead workers and their urinary excretion of lead for 24 h after intravenous infusion with 1 g of the chelating agent calcium disodium edetate. In addition, there were significant associations between lead levels in different bones (tibia/calcaneus: r = 0.93, P less than 0.001; tibia/phalanx: r = 0.67, P less than 0.002; calcaneus/phalanx: r = 0.80, P less than 0.001), as measured by in vivo X-ray fluorescence. Chelation produced no significant change in the lead level in either tibia or calcaneus. There was a significant correlation between chelated lead and bone lead (eg, for calcaneus, r = 0.62) in currently exposed workers. However, there was no significant relationship when a retired worker and an inactive worker were included (r = 0.14). It was concluded that chelatable lead mainly reflects the blood and soft-tissue lead pool, which is only partly dependent upon the skeletal lead content that comprises the biggest share of the total body burden.

Adult

Mobilized mercury in subjects with varying exposure to elemental mercury vapour.

In a mercury mobilization test, 0.3 g of the complexing agent sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was given orally to 10 workers with moderate occupational exposure to elemental mercury vapour, to 8 dentists with slight exposure, to 18 matched controls, and to 5 referents without amalgam fillings. In the workers, DMPS caused an increase in 24-h urinary mercury excretion by a factor of 10; in the dentists, 5.9; in the controls, 5.3; and in the amalgam-free referents, 3.8. Of the mercury excreted during 24 h, 59% appeared during the first 6 h. Close, albeit non-linear, associations were found between mobilized mercury and the premobilization mercury levels in plasma and urine, but not with the duration of occupational exposure or the rough estimate of the integrated function of blood levels vs time. The present data indicate that mercury mobilized after a single DMPS dose in close connection with exposure is mainly an index of recent exposure and is not significantly affected by slow body pools or long-term exposure.

Adult

Kinetics of lead in bone and blood after end of occupational exposure.

In 14 retired lead workers, followed for over 18 years after end of exposure, repeated analyses of lead levels in finger bone by an in vivo X-ray fluorescence method revealed a decrease of lead concentration. The data were analysed using an exponential retention model. For the whole group the biological half-time was 16 (asymptotic 95% confidence interval, CI 12,23) years. The median of the estimated bone lead levels at the end of exposure was 85 micrograms.g-1 above the "background" (3 micrograms.g-1). A simultaneous follow-up of blood lead levels displayed a decrease, which could be described by a tri-exponential retention model with group half-times of 34 (CI 29,41) days, 1.2 (CI 0.9,1.8) years, and 13 (CI 10,18) years, respectively. The median of the estimated blood lead levels at the end of exposure for the three components were 0.49, 0.61, and 1.1 mumol.l-1 above the "background" (0.38-0.56 mumol.l-1), respectively. The well-documented decrease of lead exposure in the general population over the years, urged the use of a decreasing "background" of blood lead during the time of the study. The slowest of the three components represented the skeleton (probably mainly cortical bone), as did mainly probably also the intermediate one (trabecular bone). The data show the rather slow turnover of lead in the skeleton, the usefulnes of in vivo skeletal lead measurements as a long-term exposure index, and the importance of bone as a source of "endogenous" lead exposure.

Adult

Effects of occupational exposure to mercury vapor on lymphocyte micronuclei.

For 26 chloralkali workers exposed to inorganic mercury and 26 age-matched, occupationally unexposed referents, the frequency and size distribution of micronuclei were determined in peripheral lymphocytes stimulated with either phytohemagglutinin or pokeweed mitogen. For the exposed workers the mean concentrations of mercury in urine, plasma, and erythrocytes were 16 nmol/mmol of creatinine, 48 nmol/l, and 78 nmol/l, respectively, and their mean exposure time was 10 years. Neither the frequency nor the size of micronuclei was significantly different in the two groups; nor were there any correlations to current mercury levels. However, in the exposed group, and with phytohemagglutinin as the mitogen, a statistically significant correlation between previous exposure to mercury (cumulative exposure or number of blood mercury peaks) and the frequency of micronuclei was found. This association was also present when the effects of age and smoking were allowed for, and it may indicate an accumulation of cytogenetic effects in T-lymphocytes.

Adult

Levels of selenium and antioxidative enzymes following occupational exposure to inorganic mercury.

Levels of selenium and mercury in blood and urine were analysed in 37 male workers exposed to elemental mercury vapour in a chloralkali plant and in 39 unexposed controls of the same age. Mean urinary Hg was 223 nmol l-1 (15 nmol/mmol creatinine) in the exposed group and 26 nmol l-1 (2.0 nmol/mmol creatinine) in the controls. Mean blood and plasma Hg levels were 46 and 36 nmol l-1, respectively, in the exposed group, as compared with 17 and 7 nmol l-1 in the controls. The concentrations of Se in plasma and erythrocytes did not differ between the two groups. Urinary Se levels were, however, slightly but significantly lower in the exposed group (median values 23 vs 29 nmol/mmol creatinine), and there was a negative correlation between urinary Se and plasma Hg in the exposed group. This may be due to a retention of Se in the kidneys. In a subgroup of exposed workers and controls, glutathione peroxidase, superoxide dismutase and catalase were also analysed. No differences were found between the groups with respect to these antioxidative enzymes. The effect on Se status of moderate Hg exposure seems to be of minor clinical importance.

Adult

Health effects of exposure to endotoxins and organic dust in poultry slaughter-house workers.

Twenty-three dust-exposed shacklers in the hanging departments of four poultry slaughter-house plants were examined immediately before work on a Monday morning with a standardized interview, pulmonary function tests (VC and FEV1), and blood sampling for analysis of complement factors. The examinations were repeated immediately after work the same day. Further, the individual breathing zone levels of both total dust and endotoxins were monitored during the whole work-shift. Moreover, spot samples of airborne bacteria and fungi were collected. The mean level of total dust was 6.3 mg/m3 (range 0.4-15.3 mg/m3) and of endotoxins 0.40 micrograms/m3 (range 0.02-1.50 micrograms/m3). Total levels of 4 x 10(5)-4 x 10(6) cfu/m3 of airborne bacteria, mainly coagulase-negative staphylococcal strains, but only 500-4000 cfu/m3 of fungi were found in the hanging departments. An over-shift increase in respiratory symptoms was found, but none of the workers had experienced any symptoms indicating extrinsic allergic alveolitis (EAA) or organic dust toxic syndrome (ODTS). Further, mean over-shift decreases of VC (3.1%) and FEV1 (4.1%) were found, indicating a harmful effect on the bronchi. There were, however, no associations between these over-shift decreases and the individual time-weighted average breathing zone levels of either total dust or of endotoxins. No over-shift change in serum complement factors was observed.

Abattoirs