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Biomedical subjects

P A Andersen

Publications and source records attributed to P A Andersen.

10 recordsLinked to original sources
PubMed2004

Prevalence and diffusion of helmet use at ski areas in Western North America in 2001-02.

OBJECTIVE: The purpose of this study was to examine diffusion of and predictors of helmet use among skiers and snowboarders in the Western United States and Canada. DESIGN: 6400 skiers and snowboarders at 29 ski resorts in the Western United States and Canada were interviewed on chair lifts and observed for helmet use during two consecutive ski seasons (winters 2001 and 2002). SETTING: Skiers and snowboarders were observed and interviewed at 29 ski resorts in Alaska, California, Colorado, Idaho, Montana, New Mexico, Nevada, Oregon, Utah, and British Columbia as part of a sun protection project. SUBJECTS: Participants completing the survey consisted of 3525 adult skiers and snowboarders in the 2002 season and 2978 adult skiers and snowboarders in the 2001 season. MAIN OUTCOME MEASURE: The outcome measure for all analyses was prevalence of helmet use by skiers and snowboarders. RESULTS: Helmet use by skiers and snowboarders is increasing and is most prevalent among snowboarders, experts, and more frequent skiers/snowboarders. No evidence was found for the hypothesis that helmet use is diffusing more rapidly among earlier adopters of helmets than later adopters. CONCLUSIONS: Although controversy remains, helmets are rapidly diffusing as a safety device at western North American ski resorts. Expert and more frequent skiers and snowboarders are more likely to wear helmets, which may indicate that helmets are recognized as a safety device.

Adolescent↗
PubMed2000

Functional specificity of the replication fork-arrest complexes of Bacillus subtilis and Escherichia coli: significant specificity for Tus-Ter functioning in E. coli.

The Escherichia coli replication terminator TerB was inserted in its two alternate orientations into a Bacillus subtilis fork-arrest assay plasmid. After transferring these new plasmids into B. subtilis, which could overproduce the E. coli terminator protein Tus, it was shown that the E. coli Tus-TerB complex could cause polar replication fork arrest, albeit at a very low level, in B. subtilis. A new B. subtilis-E. coli shuttle plasmid was designed to allow the insertion of either the Terl (B. subtilis) or TerB (E. coli) terminator at the same site and in the active orientation in relation to the approaching replication fork generated in either organism. Fork-arrest assays for both terminator-containing plasmids replicating in both organisms which also produced saturating levels of either the B. subtilis terminator protein (RTP) or Tus were performed. The efficiency of the Tus-TerB complex in causing fork arrest was much higher in E. coli than in B. subtilis. The efficiency of the B. subtilis RTP-Terl complex was higher in B. subtilis than in E. coli, but the effect was significantly less. Evidently a specificity feature in E. coli operates to enhance appreciably the fork-arrest efficiency of a Tus-Ter complex. The specificity effect is of less significance for an RTP-Ter complex functioning in B. subtilis.

Bacillus subtilis↗
PubMed1999

Site-directed mutants of RTP of Bacillus subtilis and the mechanism of replication fork arrest.

DNA replication fork arrest during the termination phase of chromosome replication in Bacillus subtilis is brought about by the replication terminator protein (RTP) bound to specific DNA terminator sequences (Ter sites) distributed throughout the terminus region. An attractive suggestion by others was that crucial to the functioning of the RTP-Ter complex is a specific interaction between RTP positioned on the DNA and the helicase associated with the approaching replication fork. In support of this was the behaviour of two site-directed mutants of RTP. They appeared to bind Ter DNA normally but were ineffective in fork arrest as ascertained by in vitro Escherichia coli DnaB helicase and replication assays. We describe here a system for assessing the fork-arrest behaviour of RTP mutants in a bona fide in vivo assay in B. subtilis. One of the previously studied mutants, RTP.Y33N, was non-functional in fork arrest in vivo, as predicted. But through extensive analyses, this RTP mutant was shown to be severely defective in binding to Ter DNA, contrary to expectation. Taken in conjunction with recent findings on the other mutant (RTP.E30K), it is concluded that there is as yet no substantive evidence from the behaviour of RTP mutants to support the RTP-helicase interaction model for fork arrest. In an extension of the present work on RTP.Y33N, we determined the dissociation rates of complexes formed by wild-type (wt) RTP and another RTP mutant with various terminator sequences. The functional wtRTP-TerI complex was quite stable (half-life of 182 minutes), reminiscent of the great stability of the E. coli Tus-Ter complex. More significant were the exceptional stabilities of complexes comprising wtRTP and an RTP double-mutant (E39K.R42Q) bound to some particular terminator sequences. From the measurement of in vivo fork-arrest activities of the various complexes, it is concluded that the stability (half-life) of the whole RTP-Ter complex is not the overriding determinant of arrest, and that the RTP-Ter complex must be actively disrupted, or RTP removed, by the action of the approaching replication fork.

Bacillus subtilis↗
PubMed1998

Replication terminator protein-based replication fork-arrest systems in various Bacillus species.

The replication terminator protein (RTP) of Bacillus subtilis interacts with its cognate DNA terminators to cause replication fork arrest, thereby ensuring that the forks approaching one another at the conclusion of a round of replication meet within a restricted terminus region. A similar situation exists in Escherichia coli, but it appears that the fork-arrest systems in these two organisms have evolved independently of one another. In the present work, RTP homologs in four species closely related to B. subtilis (B. atrophaeus, B. amyloliquefaciens, B. mojavensis, and B. vallismortis) have been identified and characterized. An RTP homolog could not be identified in another closely related species, B. licheniformis. The nucleotide and amino acid changes from B. subtilis among the four homologs are consistent with the recently established phylogenetic tree for these species. The GC contents of the rtp genes raise the possibility that these organisms arose within this branch of the tree by horizontal transfer into a common ancestor after their divergence from B. licheniformis. Only 5 amino acid residue positions were changed among the four homologs, despite an up to 17.2% change in the nucleotide sequence, a finding that highlights the importance of the precise folded structure to the functioning of RTP. The absence of any significant change in the proposed DNA-binding region of RTP emphasizes the importance of its high affinity for the DNA terminator in its functioning. By coincidence, the single change (E30K) found in the B. mojavensis RTP corresponds exactly to that purposefully introduced by others into B. subtilis RTP to implicate a crucial role for E30 in the fork-arrest mechanism. The natural occurrence of this variant is difficult to reconcile with such an implication, and it was shown directly that RTP.E30K functions normally in fork arrest in B. subtilis in vivo. Additional DNA terminators were identified in the new RTP homolog-containing strains, allowing the definition of a Bacillus terminator consensus and identification of two more terminators in the B. subtilis 168 genome sequence to bring the total to nine.

Bacillus↗
PubMed1998

Sun safety behaviours of alpine skiers and snowboarders in the western United States.

Skin cancer is epidemic. Sun safety behaviours of skiers and snowboarders have not been investigated despite prolonged exposure at high altitudes. A sample of 156 adult alpine skiers and snowboarders at 14 high-altitude ski resorts in the western United States were interviewed during 1996-97 to ascertain their sun protective actions and exposure. Few of the adults said they received any messages over their entire lifespan regarding sun safety while skiing or snowboarding. Sun protective behaviour was variable: it was negatively associated with being male, younger, a snowboarder, exposed to prevention messages, and being in cold, windy and cloudy weather, and positively related to chair-lift elevation, skin sun sensitivity and prior sunburning while skiing or snowboarding. Prevention programs should target the young, males, novices and snowboarders, and advocate protection throughout the season and during inclement weather.

Adolescent↗
PubMed1987

Pulse methotrexate therapy in rheumatoid arthritis. A controlled prospective roentgenographic study.

STUDY OBJECTIVE: To assess whether weekly pulse methotrexate therapy alters radiographic progression of joint disease in patients with rheumatoid arthritis. DESIGN: Prospective, controlled study. Hand, wrist and foot roentgenograms obtained before, at the onset of, and during methotrexate treatment were scored for degree of joint-space narrowing and erosions by three rheumatologists using a standard method. PATIENTS: Sequential sample of 24 patients with active definite or classical rheumatoid arthritis and previous unsuccessful treatment; of these, 3 were excluded due to drug ineffectiveness; 2, due to side effects; and 1, due to refusal to take methotrexate. INTERVENTIONS: Treatment with nonsteroidal anti-inflammatory drugs and prednisone was continued. Methotrexate was given weekly to control clinical evidence of disease in patients. MEASUREMENTS AND MAIN RESULTS: After having had an average of 30 months of therapy, the 18 patients who continued to receive methotrexate therapy showed significant (p less than 0.05) clinical improvement, as evidenced by their decreased joint counts and joint scores, duration of morning stiffness, pain scales, and sedimentation rates. Despite patients' prolonged clinical improvement, the mean rate of development of erosions and joint-space narrowing during methotrexate therapy was not significantly different from the rate of radiographic progression before methotrexate therapy (0.043 compared with 0.041; p greater than 0.05). CONCLUSIONS: Weekly pulse methotrexate is effective for the long-term management of clinical disease activity in patients with refractory rheumatoid arthritis but may not be a disease-modifying agent by roentgenographic criteria.

Adult↗
PubMed1985

Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study.

Twelve patients with refractory rheumatoid arthritis were treated with weekly pulse methotrexate in a double-blind, placebo-controlled, crossover study. After 13 weeks of therapy, patients receiving methotrexate showed greater improvement, judged by degree of joint swelling and tenderness, duration of morning stiffness, and subjective assessments of clinical condition, compared to those receiving placebo (p less than or equal to 0.002). This improvement was associated with a decrease in sedimentation rate and decreases in levels of IgG, IgM, and IgA; no changes were seen in serum rheumatoid factor titer or complement protein levels. Proportions of mononuclear cell subsets that were abnormal before treatment (decreased percentage of total T cells, increased percentage of monocytes) improved toward normal after therapy with methotrexate. However, no changes were seen in elevated pretreatment Leu-3/Leu-2 ratios, in in-vitro proliferative responses of lymphocytes to mitogens, or in immunoglobulin secretory responses to pokeweed mitogen. Weekly pulse methotrexate is effective in the short-term treatment of refractory rheumatoid arthritis. Little evidence for cellular immune suppression was associated with this clinical benefit.

Arthritis, Rheumatoid↗