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Biomedical subjects

J B Rasmussen

Publications and source records attributed to J B Rasmussen.

At least 19 recordsLinked to original sources
PubMed2006

A dynamical approach to evaluate risk in resource management.

With the depletion of many natural resources, we are growing aware of the need to understand the risks that stem from different management decisions. Here, we outline an approach to test the ability of different dynamical signatures to characterize time-series data: how likely is it that a natural population is declining, sustainable, or increasing, and at what rates are these temporal changes likely occurring? These dynamical signatures can serve as a robust foundation on which to formulate alternative scenarios in a decision analysis. They take account of much of the uncertainty in model parameters and have precise mathematical underpinnings with associated risks. We present methods to evaluate the likelihood of these scenarios, and ways that the analysis can be graphically represented. We discuss different ecological factors such as climate variability, life history, ecosystem interactions, and a changing population age structure, all of which impact the dynamics of natural populations. Considering the types of dynamical signatures that emerge from these factors can change our understanding of risk and the decisions that we make.

Decision Making, Organizational↗
PubMed2005

A wheat intervarietal genetic linkage map based on microsatellite and target region amplified polymorphism markers and its utility for detecting quantitative trait loci.

Efficient user-friendly methods for mapping plant genomes are highly desirable for the identification of quantitative trait loci (QTLs), genotypic profiling, genomic studies, and marker-assisted selection. SSR (microsatellite) markers are user-friendly and efficient in detecting polymorphism, but they detect few loci. Target region amplification polymorphism (TRAP) is a relatively new PCR-based technique that detects a large number of loci from a single reaction without extensive pre-PCR processing of samples. In the investigation reported here, we used both SSRs and TRAPs to generate over 700 markers for the construction of a genetic linkage map in a hard red spring wheat intervarietal recombinant inbred population. A framework map consisting of 352 markers accounted for 3,045 cM with an average density of one marker per 8.7 cM. On average, SSRs detected 1.9 polymorphic loci per reaction, while TRAPs detected 24. Both marker systems were suitable for assigning linkage groups to chromosomes using wheat aneuploid stocks. We demonstrated the utility of the maps by identifying major QTLs for days to heading and reduced plant height on chromosomes 5A and 4B, respectively. Our results indicate that TRAPs are highly efficient for genetic mapping in wheat. The maps developed will be useful for the identification of quality and disease resistance QTLs that segregate in this population.

Chromosome Mapping↗
PubMed2001

Freeze concentration of ambient waters for toxicity testing.

We have developed a method to concentrate aqueous samples for toxicity testing. This method relies on the phenomenon of freezing exclusion, whereby solutes are rejected from the interstices of a growing ice crystal. Tenfold freeze concentration gave excellent recoveries of inorganic and organic analytes, phenol and ZnSO4 toxicity from spiked natural waters, and toxicity of both pre- and postdischarge municipal wastewater. Simultaneous 10-fold concentration of strong mineral or humic ambient matrices did not substantially modify the expressed toxicity of phenol or ZnSO4, and it did not seem to generate spurious toxicity to the marine bioassay organism used (Vibrio fischeri). Hundredfold freeze concentration permitted the quantification of low levels of ambient toxicity in a wide variety of natural waters using a rapid, inexpensive microbioassay. Precipitation of matrix elements may limit the degree of concentration that can be achieved with highly mineralized or strongly humic waters. This approach is well suited to ambient toxicity testing, because it is nonspecific and has low potential for solvent contamination. Furthermore, the low temperatures involved minimize volatilization and degradation of organic contaminants.

Animals↗
PubMed1998

The genotoxic hazards of domestic wastes in surface waters.

Despite the noteworthy genotoxic potency of many industrial wastewaters, the genotoxic hazard posed to the downstream ecosystem and its associated biota will be determined by genotoxic loading. Municipal wastewaters, although ranking low in potency, can achieve loading values that are several orders of magnitude greater than those of most industries. Although these wastewaters are generally mixtures of wastes from several different sources, the volumetric proportion of the daily discharge that is of industrial origin rarely exceeds 30%. Genotoxicity calculations for the Montreal Urban Community (MUC) municipal wastewater treatment facility indicate that over 90% of the genotoxic loading (31.1 kg benzo(a)pyrene equivalents per day) is nonindustrial in origin. Moreover, a mass balance of surface water genotoxicity for St. Lawrence river at Montreal indicates that over 85% of the total contributions from the Montreal region are nonindustrial in origin. Additional calculations for the Great Lakes, and other rivers throughout the world, provide further support of a strong relationship between surface water genotoxicity and population. Despite some information about physical/chemical properties, the identity of the putative genotoxins in municipal wastewaters and surface waters remains a mystery. Likely candidates include potent genotoxins, such as N-nitroso compounds and aromatic amines, known to be present in human sanitary wastes, as well as genotoxic PAHs known to be present in many municipal wastewaters. Calculations based on literature data indicate that human sanitary wastes may be able to account for a substantial fraction (4-70%) of the nonindustrial loading from municipal wastewaters. Similar calculations suggest that pyrogenic PAHs that enter municipal wastewaters via surface runoff can only account for a small fraction (<5%) of the genotoxic loading values discussed.

Fresh Water↗
PubMed1997

Detection of genotoxic substances in bivalve molluscs from the Saguenay Fjord (Canada), using the SOS chromotest.

Few studies have employed bioassays to investigate the accumulation of genotoxins in aquatic biota that inhabit areas contaminated with industrial and municipal wastes. This study employed the SOS Chromotest, a short-term bacterial genotoxicity assay, to investigate the presence of genotoxins in bivalve molluscs from the Saguenay Fjord (Canada). Genotoxicity analyses were performed on dichloromethane extracts of Mya arenaria and Mytilus edulis collected downstream from several aluminum refineries and forestry products industries known to produce and release genotoxic substances. The results confirmed that bivalve molluscs inhabiting downstream regions are contaminated with both direct-acting and pro-genotoxic substances. In several cases, SOS response induction factors exceeded 3.0. The results failed to reveal a clear downstream trend of decreasing genotoxicity with increasing distance from the presumed industrial sources(s). A significant relationship (r2 = 0.61, p < 0.007) between a demographic variable (population near shoreline) and lipid-corrected genotoxic potency suggest that the accumulated direct-acting genotoxins may be of municipal origin. Significant relationships between tissue extract genotoxicity (r2 = 0.75, p < 0.003) and tissue PAH contamination (r2 = 0.77, p < 0.0001) and drainage basin area suggests that the bivalves are accumulating airborne contaminants deposited on the surface of the relevant drainage basins. In spite of contamination with genotoxic PAHs, the addition of rat liver microsomal enzymes reduced the genotoxic potency of all samples investigated (31-94% decrease). The results also revealed a significant relationship between tissue extract genotoxicity and PAH concentration (r2 = 0.72, p < 0.0005). Further analyses confirmed that a variable portion (7-97%) of the S9-activated tissue extract genotoxicity can be attributed to the detected PAHs. Although the sources, identity and effects of genotoxins accumulated by bivalves of the Saguenay Fjord remain to be determined, the study has confirmed the utility of the SOS Chromotest in environmental monitoring of aquatic biota.

Animals↗
PubMed1996

Comparison of aquatic food chains using nitrogen isotopes.

Recent studies have shown the utility of delta(15)N to model trophic structure and contaminant bioaccumulation in aquatic food webs. However, cross-system comparisons in delta(15)N can be complicated by differences in delta(15)N at the base of the food chain. Such baseline variation in delta(15)N is difficult to resolve using plankton because of the large temporal variability in the delta(15)N of small organisms that have fast nitrogen turnover. Comparisons using large primary consumers, which have stable tissue isotopic signatures because of their slower nitrogen turnover, show that delta(15)N increases markedly with the human population density in the lake watershed. This shift in delta(15)N likely reflects the high delta(15)N of human sewage. Correcting for this baseline variation in delta(15)N, we report that, contrary to expectations based on previous food-web analysis, the food chains leading up to fish varied by about only one trophic level among the 40 lakes studied. Our results also suggest that the delta(15)N signatures of nitrogen at the base of the food chain will provide a useful tool in the assessment of anthropogenic nutrient inputs.

Animals↗
PubMed1996

A semi-automated, microplate version of the SOS Chromotest for the analysis of complex environmental extracts.

Environmental monitoring for genotoxicity requires that a large number of measurements be made across space and time. This requirement demands a rapid and efficient bioassay system. The SOS Chromotest is a rapid, efficient bacterial system for the detection of DNA damaging agents. Over 100 publications have described its use on a variety of samples. Relatively few studies have used the test to examine complex mixtures. Effective testing of complex samples poses a variety of problems. Although solutions have been proposed, few have validated the resulting protocol. In this work we present a semi-automated microplate version of the SOS Chromotest for the examination of complex mixtures. Experiments were conducted to determine the optimal cell concentration, exposure time, substrate conversion time and S9 enzyme concentration. The performance of the method was evaluated using 6 reference genotoxins and 3 complex mixtures. The complex mixtures examined are extracts of diesel particulate matter, urban dust and coal tar. The results obtained indicate that optimal responses often require fewer cells (approximately equal to 5-10 x 10(6) CFU/ml) and a longer exposure (3 h) than that recommended in the original protocol. Interfering effects of colored and turbid samples are removed using centrifugation and initial optical density readings taken 60 min after cell resuspension and lysis. The performance of the established protocol was evaluated using mitomycin C and benzo[a]pyrene results for 207 microplates and solvent control results for 293 microplates. The results indicate that the established method is accurate, sensitive and precise. Coefficient of variation on mean SOSIP values for mitomycin C and benzo[a]pyrene are < 5%. Solvent control data indicate that the standard threshold for determination of a positive response (induction factor > 1.5) is excessively conservative. All liquid transfers were automated using the Biomek automated laboratory workstation. Automation permits a throughput of up to 72 samples per day and maintains excellent precision and accuracy.

Automation↗
PubMed1996

Comparing the presence, potency, and potential hazard of genotoxins extracted from a broad range of industrial effluents.

We examined the genotoxicity of dichloromethane extracts from 50 final effluent samples collected from 42 industries, including pulp and paper, chemical manufacturing, metal refining, metal surface treatment, and municipal waste water treatment. Effluents were initially fractionated into dissolved substances, and substances adsorbed to suspended particulate matter. Acid/base partitioning was used to further fractionate aqueous extracts. Genotoxicity of extracts was found to be related to sample type, industry type, metabolic activation status, and extract fluorescence (380 nm excitation, 430 nm emission). S9 metabolic activation reduced genotoxic potency in over 90% of the extracts examined. Expression of potency values per equivalent unit of original sample revealed that effluent particulate matter is, on average, almost four orders of magnitude more potent than aqueous filtrates. Suspended particulate matter from organic and inorganic chemical production, petroleum and metal refining, and from metal surface treatment facilities, provided extracts that were significantly more genotoxic than those from sewage treatment and pulp and paper facilities. Aqueous filtrates from inorganic and organic chemical production, metal refining, and surface treatment facilities were significantly more genotoxic than those emitted by aluminum and petroleum refineries. Overall, the results suggest that pulp and paper mills emit mostly soluble genotoxins, while petroleum and aluminum refineries emit predominantly particle-associated genotoxins. Although some extracts elicited a strong SOS response, the potency of the extractable residues was low when compared to highly potent pure substances such as benzo(alpha) pyrene. On average, a mg of dichloromethane-extractable residue has an SOS genotoxicity equivalent to 0.1-1.0 microg of benzo(alpha) pyrene. Predicted Ames mutagenic potency values corresponded reasonably well with industrial waste mutagenic potency values corresponded reasonably well with industrial waste mutagenic potency values published by other researchers. Genotoxic loading values were calculated to quantify the total daily genotoxic emission and potential hazard of each industry. Highest loadings were from sewage treatment, pulp and paper, and metal refining facilities. Highest loading values were the SOS genotoxic equivalent of over 30 kg of benzo(alpha)pyrene per day. The ultimate hazard of genotoxic emissions is not known. Actual hazard assessment is complicated by a poor understanding of the postemission behavior of genotoxins. Exposure of downstream biota is likely substantial.

Analysis of Variance↗
PubMed1996

Sorption of organic genotoxins to particulate matter in industrial effluents.

In an earlier work [White PA et al. (1996): Environ Mol Mutagen 27:116-139] we examined the genotoxicity of dichloromethane extracts from a variety of industrial effluent samples. in this companion work, we used the SOS Chromotest to investigate the sorption of the extracted genotoxins to effluent suspended particulate matter. The affinity of the genotoxins for particulate matter is expressed as a genotoxicity sorption partition coefficient (Kd-genotox). The results indicate that industries known for their emission of combustion by-products, such as polycyclic aromatic hydrocarbons, often have high Kd-genotox values (>/= 10(6). These include metal refining and founding industries as well metal surface treatment facilities. In contrast, Kd-genotox values for pulp and paper mills and sewage treatment facilities are several orders of magnitude lower (</= 10(4)). In several cases the calculated Kd-genotox values are in agreement with the Kow values of genotoxic substances isolated from genotoxic industrial waste samples studied by other researchers. The sorption partition coefficient, in conjunction with concentration of available particulate matter, was used to determine the percent of organic genotoxins adsorbed to effluent suspended particulate matter. Values range from 2.3% to 99.8%. High values (>70%) were obtained for metal surface treatment and inorganic and organic chemical production facilities. Low values (>30%) were obtained for sewage treatment facilities and pulp and paper mills. The results also demonstrate the effect of variations in the concentration of available particulate matter on the genotoxicity of both aqueous and particulate extracts. The results suggest that the sorptive properties of the particulate matter itself are reduced when the concentration of particulate matter is very high (>1,000 mg per 1). The use of sorption partition information in inferring the physical-chemical nature of the putative genotoxins and the implications of the results for assessing the hazard posed to aquatic biota by industrial genotoxins are discussed.

Adsorption↗
PubMed1996

SOS chromotest results in a broader context: empirical relationships between genotoxic potency, mutagenic potency, and carcinogenic potency.

Environmental monitoring requires that large numbers of samples be processed in a relatively short period of time. While microbioassays facilitate rapid testing, the results are often difficult to interpret in the broader context of human or animal health. Determining the consequences of exposure to genotoxic substances will ultimately require in situ monitoring of exposed organisms. However, it is immediately possible to construct a broad empirical framework within which available microbioassay results can be interpreted. To do this for SOS Chromotest results, we investigated the empirical relationships between SOS genotoxic potency and mutagenic potency (as measured with the Salmonella/microsome assay), as well as between genotoxic potency and carcinogenic potency (as measured using standard, chronic animal bioassays). Strong relationships were identified between; 1) genotoxic potency and mutagenic potency for 268 direct-acting substances (r2=0.76) and 2) genotoxic potency and mutagenic potency for 126 S9-activated substances (r2=0.65). Ordinary least squares regression analyses of the SOS genotoxicity-Salmonella mutagenicity relationship revealed a significant effect of SOS genotoxicity as well as differences in mutagenic potency that can be attributed to the Salmonella strain used to measure mutagenic potency. Analyses of S9-activated substances revealed a significant interaction between the SOS genotoxic potency (SOSIP) effect and the Salmonella strain effect. Two regression models relating SOS genotoxicity and Salmonella mutagenicity were used to predict the mutagenic potency of several industrial effluent extracts previously analyzed for SOS genotoxicity by White et al. [(1996): Environ Mol Mutagen 27:116-139]. Predictions are consistent with published mutagenic potency values for similar industrial waste materials. A consistent relationship was also identified between genotoxic potency and carcinogenic potency for 51 substances. Linear regression analyses revealed an effect of SOS genotoxic potency as well as differences in carcinogenic potency that may be attributable to experimental animal and route of exposure. The correlation between genotoxicity and carcinogenicity was fairly weak (maximum r value = 0.51). Previous studies revealed similar strength of association between Ames mutagenicity and carcinogenicity. Predicted carcinogenic potencies of previously examined genotoxic, industrial effluent extracts are generally low compared to the pure substances included in the data set.

Animals↗
PubMed1995

[Intravascular ultrasound and percutaneous transluminal angioplasty. Preliminary results].

Intravascular ultrasound is a new imaging modality which enables cross-sectional images of blood vessels. These preliminary results of intravascular ultrasound used before and after percutaneous transluminal angioplasty (PTA) in 19 patients, confirm earlier reports of the ability to distinguish between the three different layers of the vessel wall. Atherosclerotic plaques may also be assessed as well as a quantification of the stenosis. After PTA changes in the plaques such as intimal fractures, flaps and dissections could be recognized, and the effect of the intervention could be quantified by measuring the reduction of stenosis and increment of the luminal area. The increased luminal area following PTA was partly due to stretching of the artery and partly due to compression of the atheroma. We found a correlation between the amount of calcium in the plaque and the size of the dissection after PTA. Comparing IVUS with angiography revealed an acceptable agreement in quantifying stenoses before the intervention but not after. We conclude that IVUS is a feasible method to evaluate stenosis in blood vessels before and after PTA. By supplying additional information to angiography, it may improve the selection and outcome after PTA.

Aged↗
PubMed1995

[Laser-assisted balloon angioplasty of occlusions in the femoropopliteal segment].

During 1990 through 1992, 32 patients with arterial occlusive disease of the femoropopliteal segment underwent laser-assisted balloon angioplasty at the vascular service of Rigshospitalet, Copenhagen. A pulsed ultraviolet excimer laser was employed. Initial angiographic and clinical success was achieved in 20 of 32 femoropopliteal occlusions (63%). Life-table analysis revealed a cumulated patency rate of 40%, 33% and 25% after one month, one and three years, respectively. There was no correlation between initial success rate and length of occlusion, status of run-off, calcification or number of collateral vessels. In this series, laser angioplasty carried a high risk of perforation. The initial and long-term results were no better than could be expected of percutaneous transluminal angioplasty, suggesting that laser-assisted balloon angioplasty has no place in the vascular surgical armamentarium.

Adult↗
PubMed1994

Low normal alpha-1-antitrypsin serum concentrations and MZ-phenotype are associated with byssinosis and familial allergy in cotton mill workers.

Recent studies have shown a close association between byssinosis and airborne endotoxin concentrations. Endotoxin might induce byssinosis through the release of biochemical mediators as the broncheoalveolar surface. Alpha-1-antitrypsin (alpha-1-A) which neutralizes enzymes released by granulocytes is known to be important. This study evaluates the possible importance of alpha-1-A concentration and the heterozygosity (Pi-S and Pi-Z alleles), in the prevalence of byssinosis and familial allergy. 253 cotton workers were interviewed and clinically studied to identify persons with the cotton lung disease, byssinosis, and atopic disease. Serum was available for alpha-1-A concentration determination in 226 individuals, and for Pi phenotyping in 206. The overall prevalence of byssinosis was 30/226 (13%). In the group with alpha-1-A < or = 35 mumol l-1 the prevalence was 5/18 (28%), versus the prevalence 25/208 (12%) in the group with alpha-1-A > 35 mumol l-1 (p < 0.1, Fishers exact test). MZ phenotype was associated with an increased prevalence of byssinosis compared with the MM-group: 3/8 (38%) and 25/187 (13%), p < 0.1, Fishers exact test. An association between MZ-phenotype and familial allergy was found: 4/8 (50%) contra 23/187 (12%), p < 0.05, Fishers exact test. In a logistic regression model controlling for confounding by endotoxin, tobacco exposure, sex, and age, the odds ratio for byssinosis in the MZ-phenotype group was significantly elevated 5.8 (1.1-30.3). Odds ratio for familial allergy was also significantly elevated in the MZ-group 2.8 (1.3-5.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis.

To assess the manifestation and location of airway inflammation in smokers with chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD), we lavaged the airways of 12 smokers with CB and 11 smokers with COPD and coexisting CB (OCB). For comparison, the airways of 5 asymptomatic smokers (AS) and 10 healthy nonsmokers (HNS) were lavaged. In all cases, the first lavage aliquot, labeled "bronchial lavage" (BL), was processed separately from the four subsequent aliquots, which were combined and labeled "bronchoalveolar lavage" (BAL). The composition of BL and BAL fluids indicate an ongoing inflammatory process in the airways of all three groups of smokers. CB patients with obstruction had significantly lower concentrations of inflammatory cells in the BL and BAL fluids compared with subjects with nonobstructed CB. Furthermore, airway obstruction, indicated by a reduced FEV1, was significantly correlated with the concentrations of glutathione (p < 0.001), myeloperoxidase (MPO; p < 0.01), and eosinophil cationic protein (ECP; p < 0.01) in BAL fluids. Taken together, these findings suggest that the manifestations of inflammation present in the airways of smokers with CB are different in those who have developed obstruction compared with those who have not.

Adult↗
PubMed1992

Impaired cortisol stress response in fish from environments polluted by PAHs, PCBs, and mercury.

The cortisol stress response to capture was investigated in two species of fish (Perca flavescens and Esox lucius) from sites polluted by high levels of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and mercury, and from reference sites in the St. Lawrence river system. Fish from the reference sites exhibited the normal elevation of serum cortisol in response to the acute stress of capture and had large pituitary corticotropes. In contrast, fish from the most polluted sites were unable to increase their serum cortisol in response to the acute stress of capture and their pituitary corticotropes were atrophied. These results suggest that a life-long exposure to chemical pollutants may lead to an exhaustion of the cortisol-producing endocrine system, possibly as a result of prolonged hyperactivity of the system.

Animals↗
PubMed1992

The PYR1 gene of the plant pathogenic fungus Colletotrichum graminicola: selection by intraspecific complementation and sequence analysis.

A spontaneous uridine-requiring auxotroph of Colletotrichum graminicola was recovered by selection for resistance to 5-fluoro-orotic acid. The auxotroph lacked orotate phosphoribosyl transferase (OPRTase) and was complemented with a clone from a cosmid library of C. graminicola DNA. A 3.1 kb HindIII-SalI fragment was subcloned from the cosmid and it could efficiently transform the auxotrophic strain to uridine prototrophy and integrate by site-specific recombination. This DNA fragment contains an open reading frame that is similar to OPRTase genes of the fungi Sordaria macrospora, Trichoderma reesei, Podospora anserina, and Saccharomyces cerevisiae. Based on the sequence similarities and the ability to restore uridine prototrophy, we conclude that the fragment contains the C. graminicola gene for OPRTase, which we have named PYR1. Our results demonstrate that cloning by complementation is feasible in C. graminicola, that the gene for OPRTase from C. graminicola can be useful as a selectable marker in transformation of the fungus, and that the OPRTase gene product is similar to OPRTase from other fungi.

Amino Acid Sequence↗
PubMed1992

Leukotriene D4 receptor blockade inhibits the immediate and late bronchoconstrictor responses to inhaled antigen in patients with asthma.

We have tested the hypothesis that leukotriene D4 (LTD4) receptor activation is involved in the development of antigen-induced bronchoconstriction. In two studies, patients with asthma received infusions of placebo or MK-571, a potent and specific LTD4 receptor antagonist (450 mg or 37.5 mg total dose, respectively). Antigen was inhaled during test-drug administration, and FEV1 was measured for 10 hours after challenge. Urine samples were collected for measurement of LTE4; plasma samples were drawn repeatedly for assay of MK-571. MK-571 infusions inhibited both immediate (0 to 3 hours) and late (3 to 10 hours) asthmatic responses. For the high MK-571 dose, the extent of inhibition, as assessed by the area under the curve of FEV1 versus time was 88% (p = 0.01) and 63% (p = 0.01), for immediate and late responses, respectively. The low MK-571 dose also inhibited both responses but to a minor extent. Mean urinary LTE4 excretion was elevated after antigen challenge and was unaffected by administration of the LTD4 receptor antagonist. The present study demonstrates that MK-571 inhibits antigen-induced asthma in a dose-related fashion; it had not effect on antigen-induced increases in urinary LTE4 excretions. The results suggest that LTD4 receptor activation plays an important role in antigen-induced asthma.

Administration, Inhalation↗