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C Olsen

Publications and source records attributed to C Olsen.

11 recordsLinked to original sources

In vitro specificity of EcoRI DNA methyltransferase.

The sequence selectivity of enzyme-DNA interactions was analyzed by comparing discrimination between synthetic oligonucleotides containing the canonical site GAATTC and altered DNA sequences with the EcoRI DNA methyltransferase. The specificities (kcat/KmDNA) are decreased from 5- to 23,000-fold relative to the unmodified site. For several substrates the decrease in kcat makes a disproportionate contribution to the specificity difference, suggesting that discrimination is mediated by the placement of critical catalytic residues rather than binding interactions. This is supported by our observation that specificity changes are generally not followed by changes in the stability of the methyltransferase-DNA complexes. Also, base pair substitutions near the site of methylation result in greater decreases in complex stability, suggesting that recognition and catalytic mechanisms overlap.

Base Sequence

[Capnometry].

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Carbon Dioxide

Risk of congenital malformations associated with proximity to hazardous waste sites.

Concern about environmental pollutants has increased; however, it remains unclear whether chronic exposures to toxic chemicals in the environment occur at doses sufficient to produce adverse health effects in humans. To date, community studies have not adequately addressed this question. In this study, the authors linked two existing data bases of the New York State Department of Health to evaluate the relation between congenital malformations and residential proximity to hazardous waste sites in New York State. A total of 9,313 newborns with congenital malformations and 17,802 healthy controls living in proximity to 590 hazardous waste sites in 1983 and 1984 were evaluated. After the authors controlled for several possible confounding factors, results indicated that maternal proximity to hazardous waste sites may carry a small additional risk of bearing children with congenital malformations (odds ratio (OR) = 1.12, 95% confidence interval (Cl) 1.06-1.18). Higher malformation rates were associated with both a higher exposure risk (no exposure risk: OR = 1.00; low exposure risk: OR = 1.09, 95% Cl 1.04-1.15; high exposure risk: OR = 1.63, 95% Cl 1.34-1.99) and documentation of off-site chemical leaks (not exposed: OR = 1.00; exposed, but no leaks at site: OR = 1.08, 95% Cl 1.02-1.15; exposed, and leaks found at site: OR = 1.17, 95% Cl 1.08-1.27). The increased rates detected may be important in terms of their public health implications. Further research is necessary to strengthen causal inferences regarding the teratogenicity, of waste site exposure.

Adolescent

[Smoking habits of medical students. Smoking habits of Danish medical students and their knowledge about and attitudes to the tobacco problem].

In 1987, 74 Danish first-year and 90 final-year medical students from Aarhus University participated in a global questionnaire investigation concerning the smoking habits of medical students and their attitudes to the tobacco problem. This investigation was initiated by the International Union Against Tuberculosis and Lung Disease. In order to observe particular characteristics or unexpected findings, the Danish percentage replies were calculated and compared with corresponding average figures for the other European medical students and Danish doctors and the normal population. A statistically significant difference was demonstrated in a single instance only: the proportion of smokers among Danish final-year female medical students in the last term was considerably higher than among junior doctors. Strikingly few Danish medical students towards the end of their curriculum considered smoking the main cause of coronary disease but problems in translation were possibly involved here. Unless a concrete reason was present, Danish medical students were very reticent concerning discussion of the injurious effects of smoking with patients. A possible reason for this was that only one fourth of the Danish final-year students considered that their present knowledge formed an adequate basis for patient counselling.

Adult

Structure-function and refolding studies of the thrombin-specific inhibitor hirudin.

We have developed a novel expression and purification system that yields recombinant desulfo-hirudin (HV-1) with high specific activity (10,000 antithrombin units/mg) and an inhibition constant (Ki) for human alpha-thrombin of 0.2 pM. Reduced and denatured hirudin rapidly refolds to the native, fully active conformation at high concentration (greater than 50 mg/ml) by incubation at pH 10. Analytical gel filtration studies at neutral pH suggest that hirudin is a multimer. Initial binding of hirudin to thrombin appears to be followed by dissociation of the hirudin multimer to give a tight-binding 1:1 hirudin:thrombin complex. Thrombin inhibition studies showed that hirudin synthetic peptide fragments 42-65 and 51-65 [but not (Ala22)-6-28, containing two of the three disulfide bonds formed in native hirudin] were similarly effective in inhibiting thrombin cleavage of fibrinogen (IC50 = 4.9 and 6.0 microM, respectively, at a thrombin concentration of 1 microM). We conclude that hirudin has unusual structural and refolding properties and that its mechanism of inhibition involves noncovalent interaction with multiple sites on thrombin. The interaction of hirudin (specifically the region of Lys-47) with the basic specificity pocket of thrombin may contribute to the binding but is not essential for its inhibitory activity.

Amino Acid Sequence

Biodegradation of oxidized regenerated cellulose.

The in vitro solubilization and degradation of regenerated cellulose was studied under conditions which approximate those found in vivo, when the material is used as an adhesion barrier to assist normal wound repair. Factors affecting solubilization which were examined included the effects of serum or plasma, and the presence of hydrolytic enzymes. Products of the solubilization and degradation processes were examined by high performance liquid chromatography coupled with pulsed amperometric detection. The oxidized polymer readily undergoes chain shortening to give oligomers which, in the presence of plasma or serum, are further hydrolyzed to smaller fragments, including glucuronic acid and glucose. Proposed mechanisms of degradation are discussed.

Biodegradation, Environmental

Clinical results after revision and primary total hip arthroplasty.

Results after 184 primary and 227 revision total hip arthroplasties were compared with an emphasis on rates of failure leading to reoperation and intra- and postoperative complications and on the clinical outcome of the nonrevised arthroplasties in the two series. The failure rate was 7% (11 of 156) in the primary series, versus 27% (54 of 195) in the revision series. The rate of complications was substantially higher after revision, due to 16% (36 of 227) intraoperative fractures of the femoral shaft and 6% (14 of 227) postoperative dislocations. Clinical assessment of the nonrevised arthroplasties in the two series revealed no difference with regard to relief of pain. For patients with concomitant disabling conditions functional outcome was inferior after revision, but for patients without such conditions the functional results of the two series were equal. The favorable clinical results of the nonrevised arthroplasties in the revision series must be seen in relation to the very high rate of failure leading to reoperation.

Adult

Host responses to Borrelia burgdorferi in dogs and horses.

By using paired sera the IgM and IgG host responses were analyzed in dogs with ELISA and Western blot techniques. Antibodies in clinical seropositive dogs bound to 4-25 IgM and up to 40 or more IgG antigenic determinants. Early IgM response to the 41-kDa flagellin persisted for at least 9 months and involved as many as seven other peptides. IgG response expanded later in the disease and involved more immunogens than are currently recognized in late human disease. A percentage of asymptomatic dogs that later developed clinical symptoms were seropositive. Immunoblot studies suggested that B. burgdorferi is persistent in both asymptomatic and weakly reactive animals and if untreated could lead to disease expression. Clinical seropositive, asymptomatic seronegative, and experimentally infected horses were similarly studied. In experimentally inoculated animals IgG antibodies were initially bound to flagellin and later to the 34- and 31-kDa polypeptides, even though ELISA values were considered only slightly reactive.

Animals

The effect of glycerol on the lacrate metabolism in the perfused tat liver.

The effect of glycerol on the lactate metabolism was studied on the perfused rat liver. Addition of glycerol to the perfusion medium caused a significant output of lactate and uptake of pyruvate. The lactate/pyruvate- and beta-hydroxybutyrate/acetoacetate ratios rose indicating an effect of glycerol on the cytoplasmic and mitochondrial redox potentials which became more reduced. The output of lactate by the liver may be a result of the reduction in the redox level induced by the oxidation of glycerol.

Animals