Biomedical subjects

M L Peterson

Publications and source records attributed to M L Peterson.

At least 19 recordsLinked to original sources

PubMed2005

A semi-analytical model for predicting multiple propagating axially symmetric modes in cylindrical waveguides.

A semi-analytical model for multiple mode axially symmetric wave propagation in finite solid cylindrical waveguides is presented. The model is designed as a tool for predicting and interpreting experimental signals. The model is based on a common experimental configuration and considers the excitation, propagation and reception of the ultrasonic signal in the waveguide. The Pochhammer-Chree solution for an infinite cylinder is the basis for the model. Extensions are made to enable comparison to experimental results. Comparisons with experiment are performed in the time, frequency and joint-time frequency domain for both narrow band and broad band excitation of the piezo-electric transducer.

Journal Article↗

PubMed2003

Plasmid-mediated complementation of gyrA and gyrB in fluoroquinolone-resistant Bacteroides fragilis.

OBJECTIVES: To identify whether mutations in gyrA and gyrB confer fluoroquinolone resistance in Bacteroides fragilis. METHODS: Eight fluoroquinolone-resistant (FQR) strains were complemented with plasmid-mediated B. fragilis wild-type gyrA (pMP1) and gyrB (pMP2), and MICs determined. Sequence analysis of the gyrA and gyrB quinolone resistance determining region (QRDR) was performed for all strains. RESULTS: MICs of fluoroquinolones were two- to 32-fold higher than wild-type for all mutants. Five mutants had a substitution in GyrA (Ser-82-->Phe), one mutant had a substitution in GyrA (Asp-81-->Gly), one mutant had a substitution in GyrB (Glu-478-->Lys), and one resistant strain did not contain mutations in the QRDR of gyrA or gyrB. Following complementation with pMP1 or pMP2, the MICs of fluoroquinolones were reduced two- to 32-fold for the mutants. CONCLUSION: These studies verify that substitutions in GyrA and GyrB confer resistance in B. fragilis. Other mechanisms are also responsible for resistance since not all resistant strains fully complemented to the wild-type phenotype.

Anti-Bacterial Agents↗

PubMed2002

Pharmacodynamics of trovafloxacin and levofloxacin against Bacteroides fragilis in an in vitro pharmacodynamic model.

An in vitro pharmacodynamic investigation was conducted to explore whether the area under the concentration time curve from 0 to 24 h (AUC(0-24))/MIC ratio could predict fluoroquinolone performance against Bacteroides fragilis. An in vitro model was used to generate kill curves for trovafloxacin (TVA) and levofloxacin (LVX) at AUC(0-24)/MIC ratios of 1 to 406 against three strains of B. fragilis (ATCC 25285, ATCC 23745, and clinical isolate M97-117). TVA and LVX were bolused prior to the start of experiments to achieve the corresponding AUC(0-24)/MIC ratio. Experiments were performed in duplicate over 24 h and in an anaerobic environment. Analyses of antimicrobial performance were conducted by comparing the rates of bacterial kill (K) using nonlinear regression analysis with 95% confidence intervals. Statistical significance was defined as a lack of overlap in the 95% confidence limits generated from the slope of each kill curve. For both TVA and LVX, K was maximized once an AUC(0-24)/MIC ratio of > or =40 was achieved and was not further increased despite a 10-fold increase in AUC(0-24)/MIC from approximately 40 to 400 against all three strains of B. fragilis. No significant differences were found in K between AUC(0-24)/MIC ratios of approximately 40 to 200. In experiments where AUC(0-24)/MIC ratios that were > or = 5 and < or = 44 were conducted, 64% demonstrated regrowth at 24 h. Resistant strains were selected in 50% of those experiments, demonstrating regrowth, which resulted in increased MICs of two- to 16-fold for both TVA and LVX. Regrowth did not occur, nor were resistant strains selected in any studies with an AUC/MIC that was > 44. Our findings suggest that fluoroquinolones provide antibacterial effects against B. fragilis in a concentration-independent manner associated with an AUC(0-24)/MIC ratio of > or =40. Also, the potential for the selection of resistant strains of B. fragilis may increase with an AUC(0-24)/MIC ratio of < or =44.

Anti-Infective Agents↗

PubMed2002

Understanding recumbent cycling: instrumentation design and biomechanical analysis.

The recumbent cycling position (RCP) is gaining popularity, with both recumbent ergometers and bicycles available as an alternative to the standard, upright cycling position (SCP). However, very little is known about the RCP, creating a situation where uniformed choices are being made. A system was developed for measuring and analyzing the forces placed on a bicycle pedal during operation of a stationary ergometer in either the RCP or SCP. Clipless pedals were modified so that forces normal and tangential to the surface of the pedal could be measured in the plane of the bicyclist. Additionally, the angle of the pedal was measured relative to the crank arm, as well as crank arm angle, so that pedal force orientations in a global reference were known. The pedals were modified in such a way that they were structurally and functionally similar to their original design. After obtaining university-approved informed consent, a single RCP with similar included angle between torso and lower extremities to the SCP was compared by having 19 recreational cyclists pedal in both positions (60 rpm, 250 W). Both pedal forces and lower-extremity kinematics were measured and an inverse-dynamics analysis was performed. The energy transferred from the upper body to the lower extremities was significantly reduced in the RCP. Additionally, the amount of work done by knee flexion was significantly increased in the RCP while total work at the knee was not different. Due to these differences, depending on the situation, it may be more advantageous to select one cycling position over the other.

Adult↗

PubMed2002

Quantifying power output during cycling through measuring strain energy in a bicycle frame.

Quantifying power output is becoming more popular in training and competition for cycling. This popularity comes from the fact that power is a direct means of measuring intensity, which is considered by many to be the most important variable in a successful training program. Although other methods are available for measuring power output, there is no frame that is available that uses strain to quantify power output. Using a frame may prove superior to currently available products. Additionally, strain may prove useful for cycling technique analysis, another critical factor for success. In this study, a cyclocross bicycle frame was instrumented with six strain gages to determine if strain energy in the frame correlates with power output. For pilot data, an 85 kg subject rode the bike on rollers with a fork stand at 250 watts and a cadence of 90 rpm. Although more data needs to be collected and analyzed to find a correlation with power output, initial pilot data shows that the strain in the frame is cyclic in nature when pedaling and has a corresponding frequency with the pedaling cadence. It is hypothesized that the strain in the frame will have a high correlation with power output. While this application is specific to cycling, correlating strain to power output may prove useful in other applications.

Bicycling↗

PubMed2002

Influence of hip orientation on Wingate power output and cycling technique.

The effect of altered hip orientation angle ([HOA] angle of hip joint center to bottom bracket relative to horizontal) on Wingate anaerobic test results and cycling technique while maintaining a constant body configuration angle (included angle between torso, hip, and bottom bracket) and maximum hip-to-pedal distance was examined. Nineteen recreational cyclists, all men, with no recent recumbent cycling experience completed 30-second Wingate tests in 3 recumbent positions (HOA = -20 degrees, -10 degrees, and 0 degrees ) and the standard cycling position (SCP) (HOA = 75 degrees ). Peak, average, and minimum power output, as well as fatigue index, were not significantly different across all positions (p < 0.01). Average hip and knee extension angles increased slightly, and ankle angle did not change as HOA increased. These findings indicate that although HOA does have a small effect on cycling kinematics, these effects are not large enough to alter short-term power output. Therefore, anaerobic power output may be evaluated and compared in the recumbent positions and the SCP.

Adult↗

PubMed2001

Vaccine-induced antibodies to the native, oligomeric envelope glycoproteins of primary HIV-1 isolates.

A simple and sensitive method for measuring antibodies to primary human immunodeficiency virus type 1 (HIV-1) isolates has been developed. The flow cytometric immuno-fluorescence assay detects antibodies that bind to the native, oligomeric form of the envelope glycoprotein (gp120) expressed on the surface of PM-1 cells infected with primary isolates of HIV-1. Sera from people infected with HIV-1 or those immunized with recombinant gp120 vaccines were tested. Significant correlation was observed between neutralizing activity and oligomeric gp120 binding activity. Thirteen to 100% of individuals immunized with the subtype B bivalent vaccine AIDSVAX B/B developed oligomeric gp120 binding antibodies against a variety of subtype B primary isolates. For several isolates, AIDSVAX B/B sera reacted better than monovalent AIDSVAX B sera, suggesting that addition of the second immunogen improved the breadth of the antibody response. Cross-subtype binding activities, induced by AIDSVAX B/B, were lower than activities to subtype B isolates, suggesting that additional immunogen(s) may be desirable in vaccine(s) formulated for geographic regions where non-B subtypes are dominant.

AIDS Vaccines↗

PubMed2001

Multiple features contribute to efficient constitutive splicing of an unusually large exon.

Vertebrate internal exons are usually between 50 and 400 nt long; exons outside this size range may require additional exonic and/or intronic sequences to be spliced into the mature mRNA. The mouse polymeric immunoglobulin receptor gene has a 654 nt exon that is efficiently spliced into the mRNA. We have examined this exon to identify features that contribute to its efficient splicing despite its large size; a large constitutive exon has not been studied previously. We found that a strong 5' splice site is necessary for this exon to be spliced intact, but the splice sites alone were not sufficient to efficiently splice a large exon. At least two exonic sequences and one evolutionarily conserved intronic sequence also contribute to recognition of this exon. However, these elements have redundant activities as they could only be detected in conjunction with other mutations that reduced splicing efficiency. Several mutations activated cryptic 5' splice sites that created smaller exons. Thus, the balance between use of these potential sites and the authentic 5' splice site must be modulated by sequences that repress or enhance use of these sites, respectively. Also, sequences that enhance cryptic splice site use must be absent from this large exon.

Alternative Splicing↗

PubMed2001

Fluoroquinolone resistance in anaerobic bacteria following exposure to levofloxacin, trovafloxacin, and sparfloxacin in an in vitro pharmacodynamic model.

This investigation explored pharmacodynamic characteristics of fluoroquinolones against Bacteroides thetaiotamicron and the potential for development of resistance. An in vitro model was used to generate kill curves with three fluoroquinolones at various area under the concentration-time curve (AUC)/MIC ratios. Concentration-independent killing was observed. Increases in MICs were noted following exposure to fluoroquinolones at AUC/MIC ratios of 6 to 14.

Anti-Infective Agents↗

PubMed2000

Application of fluoroquinolone pharmacodynamics.

Pharmacodynamics provides a rational basis for optimizing dosing regimens by describing the relationship between drug, host and antimicrobial effect. The successful identification of meaningful pharmacodynamic outcome parameters can, therefore, greatly assist clinicians in making objective prescribing decisions rather than relying on static in vitro MIC data. While pharmacodynamic outcome parameters have been proposed for select antimicrobial agents, their clinical application remains to be defined fully. Quinolone antibiotics are generally considered to have concentration-dependent bactericidal activity and peak/MIC and AUC/MIC ratios have been identified as possible pharmacodynamic predictors of clinical and microbiological outcome as well as the development of bacterial resistance. Investigators have suggested that AUC/MIC ratios of 100-125 or peak/MIC ratios of >10 are required to predict clinical and microbiological success and to limit the development of bacterial resistance. These conclusions are derived primarily from studies of Gram-negative bacteria, and recent data suggest that these ratios may not be applicable for Streptococcus pneumoniae, where an AUC/MIC ratio of <40 appears to be a more accurate predictor. There is considerable variation in pharmacodynamic calculations and outcome parameters appear to be quinolone- and pathogen-specific. Additional prospective clinical research is needed to characterize quinolone pharmacodynamic parameters and answer unresolved questions regarding optimal pharmacodynamic outcome predictors for Gram-positive bacteria, anaerobes and atypical respiratory pathogens.

Animals↗

PubMed2000

Inertial effects on mechanically braked Wingate power calculations.

PURPOSE: The standard procedure for determining subject power output from a 30-s Wingate test on a mechanically braked (friction-loaded) ergometer includes only the braking resistance and flywheel velocity in the computations. However, the inertial effects associated with accelerating and decelerating the crank and flywheel also require energy and, therefore, represent a component of the subject's power output. The present study was designed to determine the effects of drive-system inertia on power output calculations. METHODS: Twenty-eight male recreational cyclists completed Wingate tests on a Monark 324E mechanically braked ergometer (resistance: 8.5% body mass (BM), starting cadence: 60 rpm). Power outputs were then compared using both standard (without inertial contribution) and corrected methods (with inertial contribution) of calculating power output. RESULTS: Relative 5-s peak power and 30-s average power for the corrected method (14.8 +/- 1.2 W x kg(-1) BM; 9.9 +/- 0.7 W x kg(-1) BM) were 20.3% and 3.1% greater than that of the standard method (12.3 +/- 0.7 W x kg(-1) BM; 9.6 +/- 0.7 W x kg(-1) BM), respectively. Relative 5-s minimum power for the corrected method (6.8 +/- 0.7 W x kg(-1) BM) was 6.8% less than that of the standard method (7.3 +/- 0.8 W x kg(-1) BM). The combined differences in the peak power and minimum power produced a fatigue index for the corrected method (54 +/- 5%) that was 31.7% greater than that of the standard method (41 +/- 6%). All parameter differences were significant (P < 0.01). The inertial contribution to power output was dominated by the flywheel; however, the contribution from the crank was evident. CONCLUSIONS: These results indicate that the inertial components of the ergometer drive system influence the power output characteristics, requiring care when computing, interpreting, and comparing Wingate results, particularly among different ergometer designs and test protocols.

Adult↗

PubMed1999

Cryptic intron activation within the large exon of the mouse polymeric immunoglobulin receptor gene: cryptic splice sites correspond to protein domain boundaries.

The fourth exon of the mouse polymeric immuno-globulin receptor (pIgR) is 654 nt long and, despite being surrounded by large introns, is constitutively spliced into the mRNA. Deletion of an 84 nt sequence from this exon strongly activated both cryptic 5' and 3' splice sites surrounding a 78 nt cryptic intron. The 84 nt deletion is just upstream of the cryptic 3' splice site; the cryptic 3' splice site was likely activated because the deletion created a better 3' splice site. However, the cryptic 5' splice site was also required to activate the cryptic splice reaction; point mutations in either of the cryptic splice sites that decreased their match to the consensus splice site sequence inactivated the cryptic splice reaction. The activation and inactivation of these cryptic splice sites as a pair suggests that they are being co-recognized by the splicing machinery. Interestingly, the large fourth exon of the pIgR gene encodes two immunoglobulin-like extracellular protein domains; the cryptic 3' splice site coincides with the junction between these protein domains. The cryptic 5' splice site is located between protein subdomains where an intron is found in another gene of the immunoglobulin superfamily.

Animals↗

PubMed1999

Pyriform augmentation as an ancillary procedure in facial rejuvenation surgery.

A patient is presented in whom augmentation of the pyriform aperture of the maxilla was performed with porous hydroxyapatite in concert with a face and brow lift. Basic research has recently shown that remodeling of the facial skeleton continues throughout life and that this remodeling process leads to changes in the position of several key areas. The pyriform aperture was identified as one region that remodels in a posterior direction, leading to retrusion of the alar base in the older individual. This skeletal retrusion occurs in a very site-specific fashion, and its effects are reflected on the overlying soft tissues of the face. With aging, remodeling of the pyriform aperture posteriorly causes the alar base to appear recessed and decreases the nasolabial angle, changes that are noted on the profile of the older individual. Augmentation of the pyriform aperture can be achieved through a buccal sulcus incision and, when used in conjunction with standard facial rejuvenation procedures, can improve the overall result in facial cosmetic surgery.

Female↗

PubMed1999

Fluoroquinolone resistance in Bacteroides fragilis following sparfloxacin exposure.

In vitro pharmacodynamic studies investigating the antimicrobial properties of five fluoroquinolones, (trovafloxacin, sparfloxacin, clinafloxacin, levofloxacin, and ciprofloxacin) against Bacteroides fragilis ATCC 23745 were conducted. The times required to reduce the viable counts by 3 log units were as follows: clinafloxacin, 2.9 h; levofloxacin, 4.6 h; trovafloxacin, 6 h; and sparfloxacin, 10 h. Exposure to ciprofloxacin did not achieve a 3-log decrease in viable counts. The susceptibility of B. fragilis was determined both prior to exposure and following 24 h of exposure to each of the five fluoroquinolones tested. The MICs of clinafloxacin, levofloxacin, trovafloxacin, sparfloxacin, ciprofloxacin, metronidazole, cefoxitin, chloramphenicol, and clindamycin were determined by the broth microdilution method. The MICs for B. fragilis preexposure were as follows: clinafloxacin, 0.25 microg/ml; trovafloxacin, 0.5 microg/ml; sparfloxacin, 2 microg /ml; levofloxacin, 2 microg/ml; and ciprofloxacin, 8 microg/ml. Similar pre- and postexposure MICs were obtained for cultures exposed to trovafloxacin, clinafloxacin, levofloxacin, and ciprofloxacin. However, following 24 h of exposure to sparfloxacin, a fluoroquinolone-resistant strain emerged. The MICs for this strain were as follows: clinafloxacin, 1 microg/ml; trovafloxacin, 4 microg/ml; sparfloxacin, 16 microg/ml; levofloxacin, 16 microg/ml; and ciprofloxacin, 32 microg/ml. No changes in the susceptibility of B. fragilis pre- and postexposure to sparfloxacin were noted for metronidazole (MIC, 1 microg/ml), cefoxitin (MIC, 4 microg /ml), chloramphenicol (MIC, 4 microg/ml), and clindamycin (MIC, 0.06 microg/ml). Resistance remained stable as the organism was passaged on antibiotic-free agar for 10 consecutive days. Mutant B. fragilis strains with decreased susceptibility to clinafloxacin, trovafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin were selected on brucella blood agar containing 8x the MIC of levofloxacin at a frequencies of 6.4 x 10(-9), 4x the MICs of trovafloxacin and sparfloxacin at frequencies of 2.2 x 10(-9) and 3. 3 x 10(-10), respectively, and 2x the MIC of clinafloxacin at a frequency of 5.5 x 10(-11); no mutants were selected with ciprofloxacin. The susceptibilities of strains to trovafloxacin, levofloxacin, clinafloxacin, sparfloxacin, and ciprofloxacin before and after exposure to sparfloxacin were modestly affected by the presence of reserpine (20 microg/ml), an inhibitor of antibiotic efflux. The mechanism of fluoroquinolone resistance is being explored, but it is unlikely to be efflux due to a lack of cross-resistance to unrelated antimicrobial agents and to the fact that the MICs for strains before and after exposure to sparfloxacin are minimally affected by reserpine.

Anti-Infective Agents↗

PubMed1998

Deconvolution by omission libraries.

Omission libraries, synthesized by omitting one amino acid in all coupling positions, are very efficient tools for the rapid identification of the amino acid components of bioactive peptides. Based on the determined amino acids, an occurrence library can be defined and prepared which is much less complex than the full one while still comprising the bioactive peptide.

Amino Acid Sequence↗

PubMed1998

A waveguide-based acoustic microscope.

A new instrument is presented which is capable of high resolution acoustic imaging at relatively low frequencies. This approach results in increased complexity of the signal processing required and reduced throughput of the instrument. However, these disadvantages are amply compensated by the ability to create velocity scan images of materials with either high attenuation or low material velocities. These measurements are not possible using traditional/acoustic microscopes. The initial performance of the new instrument is demonstrated using thin samples of shim materials to show that acceptable spatial resolution and highly accurate time delay measurements are possible. An application is then shown using the instrument to evaluate subchondral sclerosis in horse bones. It has been hypothesized that changes in the elastic modulus may be associated with fatigue-induced microdamage. The modulus change may further represent bone damage which precedes the development of microcracking. Thin samples are used to allow complementary microradiography to be performed on the bone slices. Because of the low material velocity, surface wave interference methods (so called V(z) curves) are not well suited for use in some bone samples. The thickness of the samples eliminates the potential for the samples to be evaluated using pulse-echo time delay measurements. The new instrument is thus unique in its ability to create velocity scans of these samples.

Animals↗

PubMed1998

A nonimmunoglobulin transgene and the endogenous immunoglobulin mu gene are coordinately regulated by alternative RNA processing during B-cell maturation.

The immunoglobulin (Ig) genes have been extensively studied as model systems for developmentally regulated alternative RNA processing. Transcripts from these genes are alternatively processed at their 3' ends to yield a transcript that is either cleaved and polyadenylated at a site within an intron or spliced to remove the poly(A) site and subsequently cleaved and polyadenylated at a downstream site. Results obtained from expressing modified genes in established tissue culture cell lines that represent different stages of B-lymphocyte maturation have suggested that the only requirement for regulation is that a pre-mRNA contain competing cleavage-polyadenylation and splice reactions whose efficiencies are balanced. Since several non-Ig genes modified to have an Ig gene-like structure are regulated in cell lines, Ig-specific sequences are not essential for this control. This strongly implies that changes in the amounts or activities of general RNA processing components mediate the processing regulation. Despite numerous studies in cell lines, this model of Ig gene regulation has never been tested in vivo during normal lymphocyte maturation. We have now introduced a non-Ig gene with an Ig gene-like structure into the mouse germ line and demonstrate that RNA from the transgene is alternatively processed and regulated in murine splenic B cells. This establishes that the balance and arrangement of competing cleavage-polyadenylation reactions are sufficient for RNA processing regulation during normal B-lymphocyte development. These experiments also validate the use of tissue culture cell lines for studies of Ig processing regulation. This is the first transgenic mouse produced to test a specific model for regulated mRNA processing.

Alternative Splicing↗

PubMed1997

Expression of the thyroid hormone receptor gene, erbAalpha, in B lymphocytes: alternative mRNA processing is independent of differentiation but correlates with antisense RNA levels.

The erbAalpha gene encodes two alpha-thyroid hormone receptor isoforms, TRalpha1 and TRalpha2, which arise from alternatively processed mRNAs, erbAalpha1 (alpha1) and erb alpha2 (alpha2). The splicing and alternative polyadenylation patterns of these mRNAs resemble that of mRNAs encoding different forms of immunoglobulin heavy chains, which are regulated at the level of alternative processing during B cell differentiation. This study examines the levels of erbAalpha mRNA in eight B cell lines representing four stages of differentiation in order to determine whether regulation of the alternatively processed alpha1 and alpha2 mRNAs parallels the processing of immunoglobulin heavy chain mRNAs. Results show that the pattern of alpha1 and alpha2 mRNA expression is clearly different from that observed for immunoglobulin heavy chain mRNAs. B cell lines display characteristic ratios of alpha1/alpha2 mRNA at distinct stages of differentiation. Furthermore, expression of an overlapping gene, Rev-ErbAalpha (RevErb), was found to correlate strongly with an increase in the ratio of alpha1/alpha2 mRNA. These results suggest that alternative processing of erbAalpha mRNAs is regulated by a mechanism which is distinct from that regulating immunoglobulin mRNA. The correlation between RevErb and erbAalpha mRNA is consistent with negative regulation of alpha2 via antisense interactions with the complementary RevErb mRNA.

Alternative Splicing↗