PubMed Health⌕ Search

Biomedical subjects

D L Wilson

Publications and source records attributed to D L Wilson.

At least 19 recordsLinked to original sources
PubMed2006

C57BL/6 and congenic interleukin-10-deficient mice can serve as models of Campylobacter jejuni colonization and enteritis.

Campylobacter jejuni is a globally distributed cause of human food-borne enteritis and has been linked to chronic joint and neurological diseases. We hypothesized that C. jejuni 11168 colonizes the gastrointestinal tract of both C57BL/6 mice and congenic C57BL/6 interleukin-10-deficient (IL-10(-/-)) mice and that C57BL/6 IL-10(-/-) mice experience C. jejuni 11168-mediated clinical signs and pathology. Individually housed mice were challenged orally with C. jejuni 11168, and the course of infection was monitored by clinical examination, bacterial culture, C. jejuni-specific PCR, gross pathology, histopathology, immunohistochemistry, and anti-C. jejuni-specific serology. Ceca of C. jejuni 11168-infected mice were colonized at high rates: ceca of 50/50 wild-type mice and 168/170 IL-10(-/-) mice were colonized. In a range from 2 to 35 days after infection with C. jejuni 11168, C57BL/6 IL-10(-/-) mice developed severe typhlocolitis best evaluated at the ileocecocolic junction. Rates of colonization and enteritis did not differ between male and female mice. A dose-response experiment showed that as little as 10(6) CFU produced significant disease and pathological lesions similar to responses seen in humans. Immunohistochemical staining demonstrated C. jejuni antigens within gastrointestinal tissues of infected mice. Significant anti-C. jejuni plasma immunoglobulin levels developed by day 28 after infection in both wild-type and IL-10-deficient animals; antibodies were predominantly T-helper-cell 1 (Th1)-associated subtypes. These results indicate that the colonization of the mouse gastrointestinal tract by C. jejuni 11168 is necessary but not sufficient for the development of enteritis and that C57BL/6 IL-10(-/-) mice can serve as models for the study of C. jejuni enteritis in humans.

Animals↗
PubMed2003

New normalization methods for cDNA microarray data.

MOTIVATION: The focus of this paper is on two new normalization methods for cDNA microarrays. After the image analysis has been performed on a microarray and before differentially expressed genes can be detected, some form of normalization must be applied to the microarrays. Normalization removes biases towards one or other of the fluorescent dyes used to label each mRNA sample allowing for proper evaluation of differential gene expression. RESULTS: The two normalization methods that we present here build on previously described non-linear normalization techniques. We extend these techniques by firstly introducing a normalization method that deals with smooth spatial trends in intensity across microarrays, an important issue that must be dealt with. Secondly we deal with normalization of a new type of cDNA microarray experiment that is coming into prevalence, the small scale specialty or 'boutique' array, where large proportions of the genes on the microarrays are expected to be highly differentially expressed. AVAILABILITY: The normalization methods described in this paper are available via http://www.pi.csiro.au/gena/ in a software suite called tRMA: tools for R Microarray Analysis upon request of the authors. Images and data used in this paper are also available via the same link.

Algorithms↗
PubMed2003

IL-4 and interferon gamma regulate expression of inducible nitric oxide synthase in chronic lymphocytic leukemia cells.

Chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-lived non-dividing CD5(+) B cells. Nitric oxide (NO) is an important regulator of apoptosis, and the viability of cultured B-CLL cells may be dependent on the autocrine production of nitric oxide by inducible nitric oxide synthase (NOS2). We performed this study to determine whether cytokine factors that prevent spontaneous in vitroapoptosis of B-CLL cells induce B-CLL cell NOS2 enzyme activity. B-CLL cells expressed NOS enzyme activity and NOS2 protein and mRNA. IL-4 and IFN-gamma increased B-CLL cell NOS2 enzyme activity and protein expression during in vitro culture. IFN-gamma, but not IL-4, increased NOS2 mRNA expression in cultured B-CLL cells suggesting that IL-4-mediated changes of NOS2 protein expression occurred at the post-transcriptional level. We were unable to detect increased concentrations of nitrite or nitrate (NO(x)) as surrogate markers of NO production in B-CLL cell cultures treated with IL-4 or IFN-gamma. IL-4 and IFN-gamma diminished NOS inhibitor-induced B-CLL cell death. In summary, we found that B-CLL cells expressed NOS2 and that IL-4 and IFN-gamma increased B-CLL NOS2 expression. Cytokine-mediated expression of NOS2 by B-CLL cells may promote their survival, and therapeutic strategies that target NOS2 or quench NO may be beneficial in patients with B-CLL.

B-Lymphocytes↗
PubMed2001

Surface organization and nanopatterning of collagen by dip-pen nanolithography.

Collagen is a key fibrous protein in biological systems, characterized by a complex structural hierarchy as well as the ability to self-assemble into liquid crystalline mesophases. The structural features of collagen influence cellular responses and material properties, with importance for a wide range of biomaterials and tissue architectures. The mechanism by which fibrillar collagen structures form from liquid crystalline mesophases is not well characterized. We report positive printing of collagen and a collagen-like peptide down to 30-50-nm line widths, using the atomic force microscopy technique of dip-pen nanolithography. The method preserved the triple-helical structure and biological activity of collagen and even fostered the formation of characteristic higher levels of structural organization. The "direct-write" capability of biologically relevant molecules, while preserving their structure and functionality, provides tremendous flexibility in future biological device applications and in proteomics arrays, as well as a new strategy to study the important hierarchical assembly processes of biological systems.

Collagen↗
PubMed2001

Hearing-aid outcome measured following one month of hearing aid use by the elderly.

This study reports the results of a large number of hearing-aid outcome measures obtained from 173 elderly hearing-aid wearers following one month of hearing-aid use. All participants in this study were fit binaurally with identical full-concha in-the-ear (ITE) hearing aids having linear Class-D amplifiers with output-limiting compression. Outcome measures included several measures of speech recognition, as well as several self-report measures of hearing-aid performance, benefit, satisfaction, and use. Comparison of mean data from this sample of hearing-aid wearers to other larger sets of data, obtained previously for several of these measures of hearing-aid outcome evaluated in isolation, indicated that the participants in this study were representative of the participants in other larger-scale studies. Subsequent principal-components factor analysis of the data from this study indicated that there were seven distinct dimensions of hearing-aid outcome. Attempts to document the effectiveness and efficacy of hearing aids for elderly persons with impaired hearing will be most complete when assessing performance along all seven dimensions of hearing-aid outcome. Clinically efficient procedures for doing so are discussed.

Aged↗
PubMed2001

Comparison of algorithms for combining X-ray angiography images.

Using a one-dimensional convective-dispersive model of contrast agent flow in a blood vessel, we optimized and compared algorithms for combining a temporal sequence of X-ray angiography images, each with incomplete arterial filling, into a single-output image with fully opacified arteries. The four algorithms were: maximum opacity (MO) with a maximum over time at each spatial location; matched filtering (MAT); recursive filtering (REC) with a maximum opacity; and an approximate matched filter (AMF) consisting of a correlation with a kernel that approximates the matched filter kernel followed by a maximum opacity operation. Based on the contrast-to-noise ratio (CNR), MAT is theoretically the best algorithm. However, with spatially varying clinical images, a poorly matched MAT kernel greatly degraded CNR to the point of even inverting artery contrast. The practical AMF method maintained uniform CNR values over the entire field of view and gave >90% of the theoretical limit set by MAT. REC and MO created fully opacified arteries, but provided little CNR enhancement. By holding CNR at a nominal reference value, simulations predicted that AMF could be used with a contrast agent volume reduced by as much as 66%. Alternatively, X-ray exposure rate could be lowered. Although MO and REC are more easily implemented, the contrast enhancement with AMF makes it attractive for processing diagnostic angiography images acquired with a reduced contrast agent dose.

Algorithms↗
PubMed2001

Digital subtraction peripheral angiography using image stacking: initial clinical results.

Using clinically acquired x-ray angiography image sequences, we compared three algorithms for creating a single diagnostic quality image that combined input images containing flowing contrast agent. These image-stacking algorithms were: maximum opacity with the minimum gray-scale value across time recorded at each spatial location, (REC) recursive temporal filtering followed by a maximum opacity operation, and (AMF) an approximate matched filter consisting of a convolution with a kernel approximating the matched filter followed by a maximum opacity operation. Eighteen clinical exams of the peripheral arteries of the legs were evaluated. AMF gave 2.7 times greater contrast to noise ratio than the single best subtraction image and 1.3 times improvement over REC, the second best stacking algorithm. This is consistent with previous simulations showing that AMF performs nearly equal to the optimal result from matched filtering without the well-known limitations. For example, unlike matched filtering, AMF filter coefficients were obtained automatically using an image-processing algorithm. AMF effectively brought out small collateral arteries, otherwise difficult to see, without degrading artery sharpness or stenosis grading. Comparing results using reduced and full contrast agent volumes demonstrated that contrast agent load could be reduced to one-third of the conventional amount with AMF processing. By simulating reduced x-ray exposures on clinical exams, we determined that x-ray exposure could be reduced by 80% with AMF processing. We conclude that AMF is a promising, potential technique for reducing contrast agent load and for improving vessel visibility, both very important characteristics for vascular imaging.

Algorithms↗
PubMed2001

Commissioning of a mobile electron accelerator for intraoperative radiotherapy.

Radiation performance characteristics of a dedicated intraoperative accelerator were determined to prepare the unit for clinical use. The linear accelerator uses standing wave X-band technology (wavelength approximately 3 centimeters) in order to minimize the mass of the accelerator. The injector design, smaller accelerator components, and low electron beam currents minimize radiation leakage. The unit may be used in a standard operating room without additional shielding. The mass of the accelerator gantry is 1250 Kg (weight approximately 2750 lbs) and the unit is transportable between operating rooms. Nominal electron energies are 4, 6, 9, and 12 MeV, and operate at selectable dose rates of 2.5 or 10 Gray per minute. D(max) depths in water for a 10 cm applicator are 0.7, 1.3, 1.7, and 2.0 for these energies, respectively. The depths of 80% dose are 1.2, 2.1, 3.1, and 3.9 cm, respectively. Absolute calibration using the American Association of Physicists in Medicine TG-51 protocol was performed for all electron energies using the 10 cm applicator. Applicator sizes ranged from 3 to 10 cm diameter for flat applicators, and 3 to 6 cm diameter for 30 degrees beveled applicators. Output factors were determined for all energies relative to the 10 cm flat applicator. Central axis depth dose profiles and isodose plots were determined for every applicator and energy combination. A quality assurance protocol, performed each day before patient treatment, was developed for output and energy constancy.

Calibration↗
PubMed2001

Effect of inherent location uncertainty on detection of stationary targets in noisy image sequences.

The effect of inherent location uncertainty on the detection of stationary targets was determined in noisy image sequences. Targets were thick and thin projected cylinders mimicking arteries, catheters, and guide wires in medical imaging x-ray fluoroscopy. With the use of an adaptive forced-choice method, detection contrast sensitivity (the inverse of contrast) was measured both with and without marker cues that directed the attention of observers to the target location. With the probability correct clamped at 80%, contrast sensitivity increased an average of 77% when the marker was added to the thin-cylinder target. There was an insignificant effect on the thick cylinder. The large enhancement with the thin cylinder was obtained even though the target was located exactly in the center of a small panel, giving observers the impression that it was well localized. Psychometric functions consisting of d' plotted as a function of the square root of the signal-energy-to-noise-ratio gave a positive x intercept for the case of the thin cylinder without a marker. This x intercept, characteristic of uncertainty in other types of detection experiments, disappeared when the marker was added or when the thick cylinder was used. Inherent location uncertainty was further characterized by using four different markers with varying proximity to the target. Visual detection by human observers increased monotonically as the markers better localized the target. Human performance was modeled as a matched-filter detector with an uncertainty in the placement of the template. The removal of a location cue was modeled by introducing a location uncertainty of approximately equals 0.4 mm on the display device or only 7 microm on the retina, a size on the order of a single photoreceptor field. We conclude that detection is affected by target location uncertainty on the order of cellular dimensions, an observation with important implications for detection mechanisms in humans. In medical imaging, the results argue strongly for inclusion of high-contrast visualization markers on catheters and other interventional devices.

Artifacts↗
PubMed2001

Hyperefficient detection of targets in noisy images.

We compared human detection of visual targets in noisy images with that of a theoretically optimum matched filter. Using a small thin target with vertically aligned markers, we obtained hyperefficient detection as high as 91% as compared with the theoretical optimum, a value far exceeding the 30-50% value typically reported. When the markers were removed, detection efficiencies degraded to an average of 27%, even though subjects were aware that the target was always placed in the center of a reasonably small panel. Using a nine-alternative forced-choice experiment, we compared detection by human observers with a matched-filter computational observer on a trial-by-trial basis. With the markers present, when humans missed the correct panel, they most often chose the panel with the second-highest decision variable output from the computational observer, suggesting that the template-matching model is a good one. To model results without the markers, we included location uncertainty and additional noise sources in the template matching of the computational observer. A location uncertainty of only 1 pixel, corresponding to a retinal distance of approximately 12 microm, a dimension of the order of the size of the receptive field of photoreceptors, explained the psychometric data. With the marker present, the model suggests that hyperefficient detection is obtained by limiting target location uncertainty to <6 microm. Together these results give important new insights into human visual detection mechanisms.

Artifacts↗
PubMed2001

Home healthcare nurses--why they leave and why they stay.

This is a second article in a series of two reports on the National Association for Home Care's (NAHC) study of nursing recruitment and retention. The first article presented the results of the quantitative analysis. This article presents results of the qualitative analysis.

Community Health Nursing↗
PubMed2000

Isolating aging mutants: a novel method yields three strains of the nematode Caenorhabditis elegans with extended life spans.

We designed a novel procedure for the isolation of mutant strains with significantly increased life spans in the nematode Caenorhabditis elegans. This procedure involves using heat-shock to screen a large number of animals and isolate a few which are more resistant to heat-shock stress. From the heat-shock-resistant animals, three mutant strains, HG25, HG96, and HG246, all exhibiting increased life span, were isolated. One mutant strain (HG246) develops more slowly than the wild-type strain, N2. Two mutant strains, HG96 and HG246, exhibit lower fertility than the wild-type. Each of the three mutant strains has a normal appearance. Their locomotive behavior also appears normal; only HG246 shows slightly slower movement. Their feeding behavior appears normal, and the males of HG25 and HG96 show normal mating behavior. However, the males of HG246, either are defective in their mating ability or their sperm are defective. The results indicate that heat-shock can be used as a means to facilitate the isolation of mutants which have longer life expectancy.

Aging↗
PubMed2000

Prescribed clinician-fit versus as-worn coupler gain in a group of elderly hearing-aid wearers.

This study reports the prescribed, clinician-fit, coupler gain and the user-adjusted, as-worn coupler gain measured in 55 adults ranging in age from 60 to 83 years (M = 72.2 years). All participants were fit with linear, output-limiting compression, Class D circuits in full-concha, in-the-ear (ITE) shells. The NAL-R prescription rationale was used to generate target real-ear insertion gain (REIG) and coupler gain values. The clinician-fit gain was measured when the hearing aid was dispensed initially and was found to be a close match to the prescribed coupler gain. Both clinician-fit and as-worn gain were measured subsequently at approximately 2 weeks, 1 month, 6 months, and 1 year after the initial fitting. As-worn gain was measured as soon as the participant returned to the clinic for one of the follow-up visits by simply removing the hearing aids and placing them in the test chamber without any adjustments in volume control. At each follow-up session, the clinician then inspected the hearing aids, evaluated the instruments electroacoustically, readjusted the volume control to the setting used to match the prescribed gain in the initial fit, and measured the clinician-fit coupler gain once again. Results revealed that, despite the capability of the hearing aid to achieve coupler gain that is a close match to the prescribed gain, these users consistently selected as-worn gain that was generally 6-9 dB below that prescribed by the NAL-R formula. Of this 6-9 dB disparity, however, as much as 3-6 dB could be due to binaural summation effects not taken into consideration in the NAL-R prescriptive formula. In addition, 5.4% of the time, the hearing aids were found to be in less than ideal operating condition when removed for the as-worn gain measurements (e.g., weak or dead battery, cerumen occluding the sound bore, telecoil switch in the incorrect position).

Aged↗
PubMed2000

Semiautomatic 3-D image registration as applied to interventional MRI liver cancer treatment.

We evaluated semiautomatic, voxel-based registration methods for a new application, the assessment and optimization of interventional magnetic resonance imaging (I-MRI) guided thermal ablation of liver cancer. The abdominal images acquired on a low-field-strength, open I-MRI system contain noise, motion artifacts, and tissue deformation. Dissimilar images can be obtained as a result of different MRI acquisition techniques and/or changes induced by treatments. These features challenge a registration algorithm. We evaluated one manual and four automated methods on clinical images acquired before treatment, immediately following treatment, and during several follow-up studies. Images were T2-weighted, T1-weighted Gd-DTPA enhanced, T1-weighted, and short-inversion-time inversion recovery (STIR). Registration accuracy was estimated from distances between anatomical landmarks. Mutual information gave better results than entropy, correlation, and variance of gray-scale ratio. Preprocessing steps such as masking and an initialization method that used two-dimensional (2-D) registration to obtain initial transformation estimates were crucial. With proper preprocessing, automatic registration was successful with all image pairs having reasonable image quality. A registration accuracy of approximately equal to 3 mm was achieved with both manual and mutual information methods. Despite motion and deformation in the liver, mutual information registration is sufficiently accurate and robust for useful applications in I-MRI thermal ablation therapy.

Algorithms↗
PubMed2000

Identification of ciprofloxacin-resistant Campylobacter jejuni by use of a fluorogenic PCR assay.

Fluoroquinolones are one class of antimicrobial agents commonly used to treat severe Campylobacter jejuni infection. C. jejuni strains resistant to high levels of the fluoroquinolone ciprofloxacin (MIC >/=16 microg/ml) have been predominantly characterized with a C-->T transition in codon 86 of gyrA. The gyrA gene encodes one subunit of DNA gyrase, which is a primary target for fluoroquinolone antibiotics. This study establishes a rapid PCR-based TaqMan method for identifying ciprofloxacin-resistant C. jejuni strains that carry the C-->T transition in codon 86 of gyrA. The assay uses real-time detection, eliminating the need for gel electrophoresis. Optimization of the assay parameters using purified Campylobacter DNA resulted in the ability to detect femtogram levels of DNA. The method should be useful for monitoring the development of ciprofloxacin resistance in C. jejuni. Compiled nucleotide sequence data on the quinolone resistance-determining region of gyrA in Campylobacter indicate that sequence comparison of this region is a useful method for tentative identification of Campylobacter isolates at the species level.

Animals↗
PubMed2000

Arthrodesis as an early alternative to nonoperative management of charcot arthropathy of the diabetic foot.

BACKGROUND: This study was performed to evaluate the use of arthrodesis of the tarsal-metatarsal area for the treatment of Eichenholtz stage-I Charcot arthropathy in patients with diabetes. Currently, the standard treatment of stage-I Charcot arthropathy is the application of a non-weight-bearing total-contact cast. Although this treatment can be effective for allowing a patient to walk without undergoing an operation, a nonunion or malunion may still result. The subsequent deformities may lead to complications, including ulceration of the foot and the need for operative intervention. Recently, a group of patients who had had early operative intervention for a variety of reasons provided us with the opportunity to objectively evaluate the effects of such treatment. This analysis provided valuable information about whether this treatment is a reasonable alternative to current nonoperative approaches. METHODS: Between January 1991 and December 1996, fourteen patients had an operation because of Eichenholtz stage-I diabetic neuropathy. The classification of the disease as Eichenholtz stage I (the developmental stage) was based on radiographic evidence of varying degrees of articular-surface and subchondral-bone resorption and fragmentation as well as joint subluxation or dislocation without evidence of coalescence or callus formation. The operative procedure consisted of extensive debridement, open reduction, and internal fixation of the tarsal-metatarsal region with autologous bone graft. Postoperative treatment consisted of immobilization of the limb in a non-weight-bearing cast for a minimum of six weeks. All of the patients returned for a final follow-up visit at a mean of forty-one months (range, 25.3 to 77.3 months) postoperatively, at which time clinical and radiographic evaluations as well as gait analysis (with measurement of plantar pressures) were performed. The gait-analysis data was compared with similar data from a group of fourteen patients with diabetic neuropathy who had had a below-the-knee amputation and with that from a group of fourteen patients with diabetic neuropathy who had no history of plantar ulceration. RESULTS: All of the arthrodesis procedures were successful. Clinically, none of the patients had immediate or long-term complications postoperatively. No patient reported ulceration after the operation. The mean time to assisted weight-bearing was 10 +/- 3.3 weeks (range, six to fifteen weeks), the mean time to unassisted weight-bearing was 15 +/- 8.8 weeks (range, eight to thirty-four weeks), and the mean time to return to the use of regular shoes was 27 +/- 14.4 weeks (range, twelve to sixty weeks). All of the patients regained the level of walking ability that they had had prior to the arthropathy. The calculated confidence intervals revealed no differences between the arthrodesis group and either of the two comparison groups with regard to the time-distance gait parameters of velocity, cadence, and stride length or with regard to the minimum, maximum, and total range of motion of each of the joints. In contrast to able-bodied subjects, all three groups showed a reduction in sagittal-plane ankle motion that was primarily related to loss of plantar flexion. The first metatarsal, great toe, and heel showed the highest peak plantar pressures, with little difference among the groups. CONCLUSIONS: To our knowledge, the present study is the first to demonstrate the potential for early operative treatment to restore anatomical alignment and improve function of diabetic patients with stage-I Charcot arthropathy.

Adult↗
PubMed1999

Characterization of a life-extending mutation in age-2, a new aging gene in Caenorhabditis elegans.

We have generated a life-extending mutation, yw23, in Caenorhabditis elegans. The mutation is in what appears to be a new aging gene, which we have designated age-2. When homozygous, yw23 produces an increase of mean and maximum life span of about 20% over that of the wild-type strain, N2. Strain HG23 [age-2(yw23)] was obtained by screening for longer life spans among 430 lines of nematodes two generations after exposure to the mutagen ethylmethanesulfonate. Strain HG231 [age-2(yw23)] was obtained after a single out-crossing of HG23 to N2. When compared with N2, HG231 exhibits normal motility, slightly higher swimming rates, reduced fertility (especially at higher temperatures), somewhat longer development times, and a slightly larger size at the time of first egg laying. A Gompertz analysis suggests that HG231 extends life span by reducing the initial mortality rate. In genetic crosses, yw23 complements other known aging mutants in C. elegans genes-age-1, daf-2, spe-26, clk-1, clk-2, clk-3, and gro-1. A double-mutant strain, HG284, combining mutations in age-1 and age-2, lives longer than animals with individual mutations in either age-1 or age-2, and exhibits a longer life span at 25 degrees C than at 20 degrees C.

Aging↗