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W Kessler

Publications and source records attributed to W Kessler.

At least 19 recordsLinked to original sources
PubMed2005

Multivariate curve resolution: a method of evaluating the kinetics of biotechnological reactions.

In biotechnology, strong emphasis is placed on the development of wet chemical analysis and chromatography to separate target components from a complex matrix. In bioprocessing, the development of single compound biosensors is an important activity. The advantages of these techniques are their high sensitivity and specificity. Inline or online monitoring by means of spectroscopy has the potential to be used as an "all-in-one" analysis technique for biotechnological studies, but it lacks specificity. Multivariate curve resolution (MCR) can be used to overcome this limitation. MCR is able to extract the number of components involved in a complex spectral feature, to attribute the resulting spectra to chemical compounds, to quantify the individual spectral contributions, and to use this quantification to develop kinetic models for the process with or without a priori knowledge. After a short introduction to MCR, two applications are presented. In the first example, the spectral features of hemp are monitored and analysed during growth. MCR provides unperturbed spectra on the activity of, for example, lignin and cellulose during plant development. In a second example, the kinetics of a laccase enzyme-catalysed degradation of aromatic hydrocarbons are calculated from UV/VIS spectra.

Biotechnology↗
PubMed2004

Optimised fermentation strategy for 13C/15N recombinant protein labelling in Escherichia coli for NMR-structure analysis.

A widely applicable cultivation strategy, which reduces the costs of expensive isotopes, is designed for maximal (98-100%) incorporation of [13C] and [15N] into labelled recombinant protein expressed in Escherichia coli, allowing better assignment of the resonances for NMR studies. Isotope labelling of the culture was performed throughout the complete process, starting from preculture. Sufficient biomass is first generated in a batch phase. Upon consumption of glucose, identified by a sharp drop of on-line monitored oxygen consumption, expression is induced and cultivation is continued under glucose-limited conditions as fed-batch process. Thereby a quantitative utilisation of the most expensive component [13C]-glucose is achieved, while the approximate amount of the [15N]-ammonium chloride to be incorporated is calculated from the scheduled biomass. The usefulness of the strategy is demonstrated with production of uniformly [13C/15N]-labelled tryparedoxin of Crithidia fasciculata. Ideal isotope incorporation and product quality is documented by MALDI-TOF mass spectrometry and two- and three-dimensional NMR spectra.

Carbon Isotopes↗
PubMed2003

A toxicokinetic model for styrene and its metabolite styrene-7,8-oxide in mouse, rat and human with special emphasis on the lung.

Styrene (ST) occurs ubiquitously in the environment and it is an important industrial chemical. After its uptake by the exposed mammalian organism, ST is oxidized to styrene-7,8-oxide (SO) by cytochrome P450 dependent monooxygenases. This reactive intermediate is further metabolized by epoxide hydrolase (EH) and glutathione S-transferase (GST). In long-term animal studies, ST induced lung tumors in mice but not in rats. Considering the lung to be the relevant target organ for ST induced carcinogenicity in mice, we extended a previously developed physiological toxicokinetic model in order to simulate the lung burden with ST and SO in the ST exposed mouse, rat and human. The new model describes oral and pulmonary uptake of ST, its distribution into various tissues, its exhalation and its metabolism to SO in lung and liver. It also simulates the distribution of the produced SO into the tissues and its EH and GST mediated metabolism in liver and in lung. In both organs the ST induced GSH consumption is described together with the formation of adducts to hemoglobin and to DNA of lymphocytes in ST exposed mice, rats and humans. The model includes compartments for arterial, venous and pulmonary blood, liver, muscle, fat, richly perfused tissues and lung. The latter organ is represented by two compartments, namely by the conducting and the alveolar zone. The physiological description of the pulmonary compartments relies on measured alveolar retentions, literature values of surface area of capillary endothelium, of the thickness of the tissue 'air-to-plasma', of the partition coefficient lung:blood and of metabolic parameters of ST and SO measured in pulmonary cell fractions of rodents and humans. Simulations of average pulmonary GSH levels in ST exposed rodents agree with measured data. The model predicts a significant GSH depletion (40%) in the conducting zone of mice exposed for 6 h to a ST concentration of only 20 ppm. In the conducting zone of rats, exposure to 200 ppm ST results in a loss of GSH of about 15% only. In humans, a pulmonary GSH reduction does not occur. The highest average pulmonary SO concentrations are predicted for mice, somewhat lower values for rats and by far the lowest ones for humans. Following steady state exposure to 20 ppm ST, the average SO concentration in mouse lungs is expected to be only three times higher than in rats. This difference diminishes to a factor of less than two at 70 ppm. In humans exposed to 20 ppm ST for 8 h, the average pulmonary SO burden of 0.016 micromol/kg is predicted to be about 17 and 50 times smaller than the corresponding values for rat and mouse. In agreement with reported values, pulmonary DNA adduct levels in rodents exposed to 160 ppm ST were simulated to be similar in rats and mice. In summary, there was no dramatic difference in the calculated average pulmonary SO burden between both animal species. However, pulmonary GSH loss was by far more expressed in ST exposed mice than rats. Since the model was validated on all available ST/SO data in mice, rats and humans, we consider it to be useful for estimating the risk resulting from exposure to ST.

Administration, Inhalation↗
PubMed2001

First-pass metabolism of 1,3-butadiene in once-through perfused livers of rats and mice.

First-pass metabolism of 1,3-butadiene (BD) leading to 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), 3-butene-1,2-diol (B-diol), 3,4-epoxy-1,2-butanediol (EBD) and crotonaldehyde (CA) was studied quantitatively in the once-through BD perfused liver of mouse and rat by means of an all-glass gas-tight perfusion system. Metabolites were analyzed using gas chromatography equipped with mass selective detection. The perfusate consisted of Krebs-Henseleit buffer (pH 7.4) containing bovine erythrocytes (40%v/v) and BD. The perfusion flow rates through the livers were 3-4 ml/min (mouse) and 17-20 ml/min (rat). The BD concentrations in the liver perfusates were 330 nmol/ml (mouse) and 240 nmol/ml (rat) being high enough to reach almost saturation of BD metabolism. The mean rates of BD transformation were about 0.014 and 0.055 mmol/h per liver of a mouse and a rat, respectively, being similar to the values expected from in-vivo measurements. There were marked species differences in the formation of BD metabolites. In the effluent of mouse livers, all three epoxides (EB: 9.4 nmol/ml; DEB: 0.06 nmol/ml; EBD: 0.07 nmol/ml) and B-diol (8.2 nmol/ml) were detected. In the perfusate leaving naïve rat livers, only EB and B-diol were found. In that of rat liver, EB concentration was 8.5 times smaller than in that of mouse liver, whereas B-diol concentrations were similar in the effluent liver perfusate of both species. CA was below the limit of its detection (60 nmol/l) in the liver perfusate of mice and of naïve rats. Of BD metabolized, the sum of the metabolites investigated in the effluent amounted to only 30% (mouse) and 20% (rat). In first experiments with rat liver, glutathione (GSH) was depleted by pretreating the animals with diethylmaleate. With the exception of EBD (not quantifiable due to an interfering peak), all other metabolites including CA were found in the effluent perfusate summing up to about 70 and 100% of BD metabolized, which indicates the quantitative importance of the GSH dependent metabolism. In summary, the results demonstrate the relevance of an intrahepatic first-pass metabolism for metabolic intermediates of BD, which undergo further transformation immediately after their production in the liver before leaving this organ. Hitherto, the occurrence of this first-pass metabolism was only hypothesized. The findings will help to explain the drastic species difference between mice and rats in the carcinogenic potency of BD.

Aldehydes↗
PubMed2001

No background concentrations of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in blood of rats.

We measured the background levels of di(2-ethylhexyl) phthalate (DEHP) and its hydrolytic metabolite mono(2-ethylhexyl) phthalate (MEHP) in blood from naive female Sprague-Dawley rats and in de-ionized charcoal-purified water using an analytical procedure that is based on sample treatment with acetonitrile, n-hexane extraction and analysis by gas chromatography. In blood, blank values of 91.3 +/- 34.7 micrograms DEHP/l (n = 31) and 30.1 +/- 13.1 micrograms MEHP/l (n = 20) were obtained, and in water, values of 91.6 +/- 44.2 micrograms DEHP/l (n = 26) and 26.7 +/- 10.4 micrograms MEHP/l (n = 15) were found. Since there is no difference between the background valves obtained from blood of naive rats and water, we conclude that DEHP and MEHP result from contamination during the analytical procedure.

Animals↗
PubMed2000

A physiological toxicokinetic model for exogenous and endogenous ethylene and ethylene oxide in rat, mouse, and human: formation of 2-hydroxyethyl adducts with hemoglobin and DNA.

Ethylene (ET) is a gaseous olefin of considerable industrial importance. It is also ubiquitous in the environment and is produced in plants, mammals, and humans. Uptake of exogenous ET occurs via inhalation. ET is biotransformed to ethylene oxide (EO), which is also an important volatile industrial chemical. This epoxide forms hydroxyethyl adducts with macromolecules such as hemoglobin and DNA and is mutagenic in vivo and in vitro and carcinogenic in experimental animals. It is metabolically eliminated by epoxide hydrolase and glutathione S-transferase and a small fraction is exhaled unchanged. To estimate the body burden of EO in rodents and human resulting from exposures to EO and ET, we developed a physiological toxicokinetic model. It describes uptake of ET and EO following inhalation and intraperitoneal administration, endogenous production of ET, enzyme-mediated oxidation of ET to EO, bioavailability of EO, EO metabolism, and formation of 2-hydroxyethyl adducts of hemoglobin and DNA. The model includes compartments representing arterial, venous, and pulmonary blood, liver, muscle, fat, and richly perfused tissues. Partition coefficients and metabolic parameters were derived from experimental data or published values. Model simulations were compared with a series of data collected in rodents or humans. The model describes well the uptake, elimination, and endogenous production of ET in all three species. Simulations of EO concentrations in blood and exhaled air of rodents and humans exposed to EO or ET were in good agreement with measured data. Using published rate constants for the formation of 2-hydroxyethyl adducts with hemoglobin and DNA, adduct levels were predicted and compared with values reported. In humans, predicted hemoglobin adducts resulting from exposure to EO or ET are in agreement with measured values. In rodents, simulated and measured DNA adduct levels agreed generally well, but hemoglobin adducts were underpredicted by a factor of 2 to 3. Obviously, there are inconsistencies between measured DNA and hemoglobin adduct levels.

Animals↗
PubMed2000

Imaging of the coronary arteries using magnetic resonance angiography.

Magnetic resonance imaging of the coronary arteries is difficult due to the tortuous course of these vessels, their small diameter, and their rapid movement caused by respiration and cardiac contraction. Initial investigations could demonstrate the feasibility of non-invasive magnetic resonance coronary angiography using 2-dimensional turbo-FLASH gradient-echo sequences in repeated breathholds of approximately 16 heart beats duration. Further developments, especially the design of navigator-echo-based respiratory gated 3-dimensional imaging sequences, permitted the acquisition of contiguous volume data sets of the heart which eliminated many limitations of 2-dimensional repeated breathhold sequences. With a spatial resolution of approximately 1.2 x 1.2 x 2 mm and a temporal resolution of approximately 126 ms, several authors reported sensitivities of 70-80% and specificities of approximately 90% for the detection of coronary artery stenoses. Further improvements can be expected from new, intravascular contrast agents and from ultrafast sequences which permit acquisition of a sufficiently large imaging volume within one single breathold.

Coronary Angiography↗
PubMed2000

Noninvasive detection of coronary artery stenosis using contrast-enhanced three-dimensional breath-hold magnetic resonance coronary angiography.

OBJECTIVES: The purpose of this study was to evaluate a contrast-enhanced three-dimensional (3D) breath-hold magnetic resonance (MR) technique for detection of coronary artery stenoses. BACKGROUND: The accuracy of previously published MR coronary angiography protocols varies widely. Recently, coronary artery imaging using T1-shortening contrast agent has become possible, but so far there are no data concerning its clinical application. METHODS: Magnetic resonance coronary angiography was performed in 50 patients with suspected coronary artery disease. Magnetic resonance data acquisition using an ultrafast 3D gradient-echo sequence lasted over 32 heartbeats within one single breath-hold. Twenty milliliters of gadopentetate dimeglumine was injected at a flow rate of 1 ml/s for two successive studies covering the main coronary arteries in single-oblique planes. Stenosis assessment by MR was compared with significant (diameter stenosis > 50%) stenoses on X-ray angiography. Evaluation was limited to the proximal and mid-coronary artery segments. RESULTS: Two hundred sixty-eight of 350 artery segments (76.6%) could be evaluated. Left circumflex coronary artery was only evaluable in 50% of cases by MR. In the evaluable segments, 48 of 56 stenoses and 193 of 212 nonstenotic segments were correctly classified by MR. On a patient basis, MR correctly identified 34 of 36 patients with and 8 of 14 patients without significant coronary stenoses as demonstrated by X-ray angiography (sensitivity 94.4%, specificity 57.1%). CONCLUSIONS: Oblique projection contrast-enhanced MR coronary angiograms obtained within one single breath-hold permit identification of patients with coronary stenoses in the proximal and mid segments of the major coronary arteries with satisfactory accuracy.

Adult↗
PubMed2000

[Quality control in patient education. Results of a patient survey about the patient education protocol of the Swiss Society of Surgery in 6 Swiss hospitals].

In the past years the number of malpractice suits due to lack of patient information has increased. Because there have been no generally accepted guidelines for preoperative patient information, the Swiss Society of Surgery has decided to work out an informative brochure tailored to the needs of patients. It takes into account that the need to know beforehand is increasing rapidly. In collaboration with the judiciary service of the Swiss Medical Federation all the items and points of legal relevance have been compiled to establish an informative brochure. Based on this protocol, patients in surgical departments of 6 Swiss community hospitals were asked before discharge to qualify the preoperative information offered to them. 2660 questionnaires were evaluated. The majority of patients considered the information regarding their diagnosis, the complications, risks, treatment and postoperative care, the sketches describing the operation and the overall degree of information as good or very good. Almost 60% of all patients stated that no alternative treatment had been discussed with them other than the planned procedure. In most of these patients operative procedures were chosen and carried out for which there were few or no other acceptable options. 2/3 of the patients asked for immediate preoperative written information, especially if they had malignant disease. Barely 4% of the patients were not reassured by the information provided to them. The fact that 2/3 of all patients re-read the informative protocol before the operation underlines how important it is to hand out a copy of the protocol to satisfy the informative needs of the patients. To our surprise the vast majority of patients uttered little concern about giving their signature to forms that were presented to them. Only 2% of the patients felt that giving a signature would cause them grave reservations. The informative protocol devised by the Swiss Society of Surgery is well adapted to the informative needs of the patients and allows for a structured conversation. It facilitates documentation and offers valid legal proof for the physician that he/she has provided adequate information.

Adult↗
PubMed2000

Quantitation of DNA and hemoglobin adducts and apurinic/apyrimidinic sites in tissues of F344 rats exposed to propylene oxide by inhalation.

Propylene oxide (PO) is a relatively weak mutagen that induces nasal tumor formation in rats during long-term inhalation studies at high exposures (> or =300 p.p.m.), concentrations that also cause cytotoxicity and increases in cell proliferation. Direct alkylation of DNA by PO leads mainly to the formation of N:7-(2-hydroxypropyl)guanine (7-HPG). In this study, the accumulation of 7-HPG in tissues of male F344 rats exposed to 500 p. p.m. PO (6 h/day, 5 days/week for 4 weeks) by the inhalation route was measured by gas chromatography-high resolution mass spectrometry (GC-HRMS). In animals killed up to 7 h following the end of the last exposure the levels of 7-HPG (pmol/micromol guanine) in nasal respiratory tissue, nasal olfactory tissue, lung, spleen, liver and testis DNA were 606.2 +/- 53.0, 297.5 +/- 56.5, 69.8 +/- 3.8, 43.0 +/- 3.8, 27.5 +/- 2.4 and 14.2 +/- 0.7, respectively. The amounts of 7-HPG in the same tissues of animals killed 3 days after cessation of exposure were 393.3 +/- 57.0, 222.7 +/- 29.5, 51.5 +/- 1.2, 26.7 +/- 1.0, 18.0 +/- 2.6 and 10.4 +/- 0.1. A comparable rate of disappearance of 7-HPG was found among all tissues. DNA from lymphocytes pooled from four rats killed at the end of the last exposure was found to have 39.6 pmol adduct/micromol guanine. Quantitation of DNA apurinic/apyrimidinic sites, potentially formed after adduct loss by chemical depurination or DNA repair, showed no difference between tissues from control and exposed rats. The level of N:-(2-hydroxypropyl)valine in hemoglobin of exposed rats was also determined using a modified Edman degradation method followed by GC-HRMS analysis. The value obtained was 90.2 +/- 10.3 pmol/mg globin. These data demonstrate that nasal respiratory tissue, which is the target tissue for carcinogenesis, has a much greater level of alkylation of DNA than non-target tissues.

Animals↗
PubMed1999

Methods for biological monitoring of propylene oxide exposure in Fischer 344 rats.

Propylene oxide (PO) is used as an intermediate in the chemical industry. Human exposure to PO may occur in the work place. Propylene, an important industrial chemical and a component of, for example, car exhausts and cigarette smoke, is another source of PO exposure. Once taken up in the organism, this epoxide alkylates macromolecules, such as haemoglobin and DNA. The aim of the present investigation was to compare two methods for determination of in vivo dose, the steady state concentration of PO in blood of exposed rats and the level of haemoglobin adducts. Male Fischer 344 rats were exposed for 4 weeks (6 h/day, 5 days/week) to PO at a mean atmospheric concentration of 500 ppm (19.9 micromol/l). Immediately after the last exposure blood was collected in order to determine the steady state concentration of PO. Free PO was measured in blood samples of three animals by means of a head space method to be 37 +/- 2 micromol/l blood (mean +/- S.D.). Blood samples were also harvested for the measurement of haemoglobin adducts. N-2-Hydroxypropyl adducts with N-terminal valine in haemoglobin were quantified using the N-alkyl Edman method with globin containing adducts of deuterium-substituted PO as an internal standard and N-D,L-2-hydroxypropyl-Val-Leu-anilide as a reference compound. Tandem mass spectrometry was used for adduct quantification. The adduct levels were < 0.02 and 77.7 +/- 4.7 nmol/g globin (mean +/- S.D.) in control animals (n = 7) and in exposed animals (n = 34), respectively. The adduct levels expected at the end of exposure were calculated to be 71.7 +/- 4.1 nmol/g globin (mean +/- S.D.) using the measured steady state concentration of PO in blood and taking into account the growth of animals, the life span of erythrocytes, the exposure conditions and the second order rate constant for adduct formation. The good agreement between the estimated and measured adduct levels indicates that both end-points investigated are suitable for biological monitoring.

Animals↗
PubMed1999

Cultivation of Tetrahymena thermophila in a 1.5-m3 airlift bioreactor.

A large-scale cultivation system for the mass cell production and extraction of the protozoon Tetrahymena thermophila has been developed on the basis of a low-cost complex nutrient medium. Cell growth and the production of extracellular proteases were investigated using a 15-l stirred-tank reactor and 13-l and 1500-l airlift reactors. Processes using defined and complex medium formulations were compared. After cell mass production by 1200 l cell suspension in the large airlift bioreactor, two different extraction methods, based on the use of an extraction decanter and a sedimentation procedure, were compared and followed by cell lyophilization. Cell sedimentation was shown to be the more efficient extraction method as it enabled cell retention/separation while preserving the cell structure. Maximum cell growth was achieved in the stirred-tank bioreactor, supporting the hypothesis that higher shear forces reduce the particle size of the medium, which is responsible for an optimized nutrient supply. The highest glucose uptake rates were found in defined medium lacking the nutrient particles that are present in complex medium formulations. The cell-specific proteolytic activity in culture supernatants of airlift bioreactors using complex medium conditions was higher than that of a culture broth with cells grown under defined medium formulations.

Animals↗
PubMed1999

Coronary arteries: MR angiography with fast contrast-enhanced three-dimensional breath-hold imaging--initial experience.

Gadolinium-enhanced, three-dimensional, breath-hold magnetic resonance (MR) coronary angiography was performed in two healthy volunteers and 11 patients suspected or known to have coronary artery disease. MR angiograms were compared with those obtained with retrospective respiratory gating. Of 52 main coronary arteries, 47 could be visualized with the breath-hold technique and 49 with the gating technique. Signal-to-noise and contrast-to-noise ratios were significantly higher with the breath-hold technique. Overall image quality was slightly lower with breath-hold imaging. With either technique, three of five, significant coronary stenoses were correctly identified.

Contrast Media↗
PubMed1998

[Evaluation of coronary artery stenosis with respiratory gated NMR angiography].

Respiratory gated MR coronary angiography is a new MR imaging technique which permits reconstruction of the coronary arteries from a three-dimensional data set obtained from contiguous parallel sections. In this study, respiratory gated MR angiography was applied to assess significant coronary artery stenoses (> or = 50%). MR imaging was performed in 68 patients (50 men, 18 women) who had been referred to cardiac catheterization because of suspected or known coronary artery disease. The evaluation of coronary artery stenoses was performed in a blinded manner in the proximal, middle, and distal vessel segments after multiplanar coronary reconstruction of the MR images. Of the 680 coronary segments, 275 (40%) were located outside the imaging volume and were, therefore, excluded from further analysis. The highest sensitivity for stenosis detection was found in the proximal left anterior descending (LAD) and right coronary artery (RCA) with 75% and 71%, respectively. The overall sensitivity, however, was low with 48%. The overall specificity was 92%. The positive and negative predictive values were 67% and 85%, respectively. This study shows that significant coronary artery stenoses, especially in the proximal LAD and RCA, can be correctly identified using respiratory gated MR angiography. However, further technical improvements are necessary before this method may become a reliable diagnostic tool in clinical practice.

Adult↗
PubMed1998

Assessment of coronary blood flow in humans using phase difference MR imaging. Comparison with intracoronary Doppler flow measurement.

Coronary blood flow quantification provides essential information on the hemodynamic significance of coronary artery stenoses. Recently, magnetic resonance (MR) flow mapping has emerged as a new promising method to noninvasively determine flow velocity and flow volume within the coronary arteries. The aim of this study was to compare phase difference (PD) MR flow quantification with intracoronary Doppler flow measurements in 15 patients with suspected or known coronary artery disease. Flow quantification was attempted before and after systemic application of 5mg Isosorbiddinitrate (ISDN) in order to determine possible alterations in coronary flow volume. PD MR flow mapping was performed successfully in 13 of the 15 patients. For flow velocities and flow volume values, a close correlation between PD MR and Doppler flow measurements was found (r = 0.79 and r = 0.90, respectively). However, average flow measured by PD MR was significantly lower than the invasively obtained values (9.0 +/- 4.4 cm/sec vs. 11.7 +/- 4.9 cm/sec; p < 0.001 and 46.3 +/- 28.7 ml/min vs. 53.4 +/- 32.8 ml/min; p < 0.05). Although the mean flow volume remained constant in the entire patient group after ISDN application, individual changes (increase in 6, decrease in 4 cases) could be documented with PD MR imaging and showed a good correlation to the Doppler method (r = 0.82). In conclusion, PD MR flow mapping is a promising method for the noninvasive quantification of coronary blood flow and therefore offers the potential of assessing coronary artery stenoses. However, technical improvements are mandatory in order to increase accuracy of the method.

Blood Flow Velocity↗
PubMed1997

Propylene oxide: mutagenesis, carcinogenesis and molecular dose.

The results from mutagenic and carcinogenic studies of propylene oxide (PO) and the current efforts to develop molecular dosimetry methods for PO-DNA adducts are reviewed. PO has been shown to be active in several bacterial and mammalian mutagenicity tests and induces site of contact tumors in rodents after long-term administration. Quantitation of N7-(2-hydroxypropyl)guanine (7-HPG) in nasal and hepatic tissues of male F344 rats exposed to 500 ppm PO (6 h/day; 5 days/week for 4 weeks) by inhalation was performed to evaluate the potential of high concentrations of PO to produce adducts in the DNA of rodent tissues and to obtain information necessary for the design of molecular dosimetry studies. The persistence of 7-HPG in nasal and hepatic tissues was studied in rats killed three days after cessation of a 4-week exposure period. DNA samples from exposed and untreated animals were analyzed for 7-HPG by two different methods. The first method consisted of separation of the adduct from DNA by neutral thermal hydrolysis, followed by electrophoretic derivatization of the adduct and gas chromatography-high resolution mass spectrometry (GC-HRMS) analysis. The second method utilized 32P-postlabeling to quantitate the amount of this adduct in rat tissues. Adducts present in tissues from rats killed immediately after cessation of exposure were 835.4 +/- 80.1 (respiratory), 396.8 +/- 53.1 (olfactory) and 34.6 +/- 3.0 (liver) pmol adduct/mumol guanine using GC-HRMS. Lower values, 592.7 +/- 53.3, 296.5 +/- 32.6 and 23.2 +/- 0.6 pmol adduct/mumol guanine were found in respiratory, olfactory and hepatic tissues of rats killed after three days of recovery. Analysis of the tissues by 32P-postlabeling yielded the following values: 445.7 +/- 8.0 (respiratory), 301.6 +/- 49.2 (olfactory) and 20.6 +/- 1.8 (liver) pmol adduct/mumol guanine in DNA of rats killed immediately after exposure cessation and 327.1 +/- 21.7 (respiratory), 185.3 +/- 29.2 (olfactory) and 15.7 +/- 0.9 (liver) pmol adduct/mumol guanine after recovery. Current methods of quantitation did not provide evidence for the endogenous formation of this adduct in control animals. These studies demonstrated that the target tissue for carcinogenesis has much greater alkylation of DNA than liver, a tissue that did not exhibit a carcinogenic response.

Alkylation↗
PubMed1997

Usefulness of respiratory gated magnetic resonance coronary angiography in assessing narrowings > or = 50% in diameter in native coronary arteries and in aortocoronary bypass conduits.

Magnetic resonance coronary angiography (MRCA) is a promising method for the assessment of proximal coronary artery stenosis. Conventional 2-dimensional techniques require repetitive breath holds to image multiple sections. This may lead to misregistrations if the respiratory level is not exactly reproduced. In the present study, MRCA was performed using a 3-dimensional approach with navigator echo-based respiratory gating. In 73 patients (55 men and 18 women) who were referred for cardiac catheterization, the assessment of significant stenoses (> or = 50%) was performed in the proximal and midsegments of the coronary arteries after multiplanar reconstruction of the visualized coronary arteries. In addition, in 8 patients with coronary artery bypass grafts the patency of the transplants was evaluated. After withdrawing 8 patients from analysis because of poor image quality, stenosis evaluation was possible in 236 of 455 reviewed coronary segments (52%). In the other 219 cases, either the visualization of the vessel segment was indistinct (30%) or the segment was located outside the imaging volume (18%). In total, 28 of 43 significant coronary stenoses could be correctly identified (65%). Evaluation of bypass graft patency was possible in 7 patients. All 4 occluded and 13 of 15 patent grafts were correctly classified. Thus, respiratory gated MRCA is a feasable method for the assessment of hemodynamically significant coronary stenoses and bypass graft patency. However, technical improvements are mandatory to improve accuracy of the method.

Adult↗