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Biomedical subjects

B Nelson

Publications and source records attributed to B Nelson.

At least 19 recordsLinked to original sources
PubMed2005

Isolation of gene sets affected specifically by polyglutamine expression: implication of the TOR signaling pathway in neurodegeneration.

Transcriptional dysregulation as a result of sequestration of essential transcription factors into protein aggregates formed by polyglutamine (polyQ) expansions can lead to late-onset progressive neurodegeneration. DNA microarray analysis of Drosophila expressing polyQ in the compound eye over time revealed large numbers of transcriptional changes at the earliest stages of the disease including repression of the transient receptor potential calcium channels in a polyQ-induced cell death specific manner. While significant differences in expression profiles were found between the Drosophila compound eye and polyQ-sensitive neural cells, a number of possible key overlapping regulators were extracted. Among these, PDK1 was shown to act as a mediator for polyQ-toxicity, suggesting the involvement of the TOR pathway in polyQ-induced neurodegeneration.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2001

Role of scaffolds in MAP kinase pathway specificity revealed by custom design of pathway-dedicated signaling proteins.

BACKGROUND: Signal transduction pathways with shared components must be insulated from each other to avoid the inappropriate activation of multiple pathways by a single stimulus. Scaffold proteins are thought to contribute to this specificity by binding select substrates. RESULTS: We have studied the ability of scaffold proteins to influence signaling by the yeast kinase Ste11, a MAPKKK molecule that participates in three distinct MAP kinase pathways: mating, filamentation, and HOG. We used protein fusions to force Ste11 to associate preferentially with a subset of its possible binding partners in vivo, including Ste5, Ste7, and Pbs2. Signaling became confined to a particular pathway when Ste11 was covalently attached to these scaffolds or substrates. This pathway bias was conferred upon both stimulus-activated and constitutively active forms of Ste11. We also used membrane-targeted derivatives of the mating pathway scaffold, Ste5, to show that stimulus-independent signaling initiated by this scaffold remained pathway specific. Finally, we demonstrate that loss of pathway insulation has a negative physiological consequence, as nonspecific activation of both the HOG and mating pathways interfered with proper execution of the mating pathway. CONCLUSIONS: The signaling properties of these kinase fusions support a model in which scaffold proteins dictate substrate choice and promote pathway specificity by presenting preferred substrates in high local concentration. Furthermore, insulation is inherent to scaffold-mediated signaling and does not require that signaling be initiated by pathway-specific stimuli or activator proteins. Our results give insight into the mechanisms and physiological importance of pathway insulation and provide a foundation for the design of customized signaling proteins.

MAP Kinase Kinase Kinases↗
PubMed2001

A randomized clinical trial of exercise and spinal manipulation for patients with chronic neck pain.

STUDY DESIGN: A randomized, parallel-group, single-blinded clinical trial was performed. After a 1-week baseline period, patients were randomized to 11 weeks of therapy, with posttreatment follow-up assessment 3, 6, and 12 months later. OBJECTIVES: To compare the relative efficacy of rehabilitative neck exercise and spinal manipulation for the management of patients with chronic neck pain. SUMMARY OF BACKGROUND DATA: Mechanical neck pain is a common condition associated with substantial morbidity and cost. Relatively little is known about the efficacy of spinal manipulation and exercise for chronic neck pain. Also, the combination of both therapies has yet to be explored. METHODS: Altogether, 191 patients with chronic mechanical neck pain were randomized to receive 20 sessions of spinal manipulation combined with rehabilitative neck exercise (spinal manipulation with exercise), MedX rehabilitative neck exercise, or spinal manipulation alone. The main outcome measures were patient-rated neck pain, neck disability, functional health status (as measured by Short Form-36 [SF-36]), global improvement, satisfaction with care, and medication use. Range of motion, muscle strength, and muscle endurance were assessed by examiners blinded to patients' treatment assignment. RESULTS: Clinical and demographic characteristics were similar among groups at baseline. A total of 93% of the patients completed the intervention phase. The response rate for the 12-month follow-up period was 84%. Except for patient satisfaction, where spinal manipulative therapy and exercise were superior to spinal manipulation with (P = 0.03), the group differences in patient-rated outcomes after 11 weeks of treatment were not statistically significant (P = 0.13). However, the spinal manipulative therapy and exercise group showed greater gains in all measures of strength, endurance, and range of motion than the spinal manipulation group (P < 0.05). The spinal manipulation with exercise group also demonstrated more improvement in flexion endurance and in flexion and rotation strength than the MedX group (P < 0.03). The MedX exercise group had larger gains in extension strength and flexion-extension range of motion than the spinal manipulation group (P < 0.05). During the follow-up year, a greater improvement in patient-rated outcomes were observed for spinal manipulation with exercise and for MedX exercise than for spinal manipulation alone (P = 0.01). Both exercise groups showed very similar levels of improvement in patient-rated outcomes, although the spinal manipulation and exercise group reported greater satisfaction with care (P < 0.01). CONCLUSIONS: For chronic neck pain, the use of strengthening exercise, whether in combination with spinal manipulation or in the form of a high-technology MedX program, appears to be more beneficial to patients with chronic neck pain than the use of spinal manipulation alone. The effect of low-technology exercise or spinal manipulative therapy alone, as compared with no treatment or placebo, and the optimal dose and relative cost effectiveness of these therapies, need to be evaluated in future studies.

Adult↗
PubMed2001

A psychosocial approach to arson--a case controlled study of female offenders.

Few studies of arsonists have focused specifically on females, many of whom have historically avoided prosecution. This study examines demographic details, psychopathology and personality characteristics of female arsonists and violent offenders in custody and compares them with an age matched group of comparison females. A significantly greater number of arsonists admitted to a history of deliberate self-harm and to sexual abuse as a child. The results emphasize the degree of psychosocial disadvantage in female arsonists and fit the model of displaced aggression in that female arsonists in this study are found to be less assertive and may displace their aggression onto property due to their inability to confront people directly. This channelling of aggression may be seen as an attempt to influence their environment and improve their self-esteem where other means have failed. Many of the findings match those of a previous study of male Special Hospital arsonists and indicate the need for larger studies within prison and hospital settings. Based on the potential areas for clinical intervention, prospective treatment studies of arsonists offer exciting implications in terms of risk management and may begin to address the needs of this severely disadvantaged group.

Adolescent↗
PubMed2000

Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles.

Genome-wide transcript profiling was used to monitor signal transduction during yeast pheromone response. Genetic manipulations allowed analysis of changes in gene expression underlying pheromone signaling, cell cycle control, and polarized morphogenesis. A two-dimensional hierarchical clustered matrix, covering 383 of the most highly regulated genes, was constructed from 46 diverse experimental conditions. Diagnostic subsets of coexpressed genes reflected signaling activity, cross talk, and overlap of multiple mitogen-activated protein kinase (MAPK) pathways. Analysis of the profiles specified by two different MAPKs-Fus3p and Kss1p-revealed functional overlap of the filamentous growth and mating responses. Global transcript analysis reflects biological responses associated with the activation and perturbation of signal transduction pathways.

Cell Cycle Proteins↗
PubMed2000

Exhaled nitric oxide levels correlate with measures of disease control in asthma.

BACKGROUND: Asthma guidelines emphasize maintaining disease control. However, objective measures of asthma disease control are lacking. OBJECTIVE: We sought to examine the relationship between exhaled nitric oxide (NO) levels and measures of asthma disease control versus asthma disease severity. METHODS: We performed a cross-sectional study of 100 patients (age range, 7-80 years) with asthma. We administered a questionnaire to identify characteristics of asthma, performed spirometric testing before and after administration of a bronchodilator, and measured exhaled NO levels in all participants. RESULTS: Exhaled NO was significantly correlated with the following markers of asthma disease control: asthma symptoms within the past 2 weeks (P =.02), dyspnea score (P =. 02), daily use of rescue medications (P =.01), and reversibility of airflow obstruction (P =.02). Exhaled NO levels were not correlated with the following markers of asthma disease severity: history of respiratory failure (P =.20), health care use (P =.08), fixed airflow obstruction (P =.91), or a validated asthma severity score (P =.19). Markers with relevance to both disease control and severity showed either a weak correlation (FEV(1) and FEV(1) percent predicted) or no correlation (controller drug use) with exhaled NO. CONCLUSION: We conclude that exhaled NO levels are correlated predominantly with markers of asthma control rather than asthma severity. Monitoring of exhaled NO may be useful in outpatient asthma management.

Adult↗
PubMed2000

Class II correction in patients treated with class II elastics and with fixed functional appliances: a comparative study.

The aim of the present study was to evaluate quantitatively the skeletal and dental changes contributing to Class II corrections in subjects treated with Class II elastics (Begg technique) compared with subjects treated with fixed functional appliances (Herbst appliance). Thirty-six male patients with Class II, Division 1 malocclusions whose treatment had not included extraction were investigated. Eighteen were treated with the Begg technique, and eighteen were treated with Herbst appliance for an average period of 1.3 and 0.5 years, respectively. Lateral radiographs in habitual occlusion were taken at the start of treatment and 12 months afterwards. In the Begg group, the maxilla moved forward 1 mm more than in the Herbst group, and the mandible moved 1 mm more in the Herbst group than in the Begg group. The skeletal improvement in the Herbst group exceeded the changes in the Begg group by, on average, 2.0 mm (P <.01). The overjet reduction in the Begg group was larger (2.1 mm; P <.01) than in the Herbst group, mostly because of dental movements. The skeletal part of the overjet reduction was 4% in the Begg group compared with 51% in the Herbst group. The molar correction was similar in both groups, but in the Begg group, the skeletal improvement was 10%, compared with 66% in the Herbst group. The overbite correction and the increase in the anterior lower facial height and in the NSL/ML angle were larger in the Begg group (P <.05). The conclusions of this study were that the changes contributing to the Class II corrections in Begg and Herbst therapy were skeletal and dental. The skeletal changes were, however, larger in the Herbst-treated group. On the other hand, favorable and unfavorable vertical changes were more pronounced in the group treated with Class II elastics.

Adolescent↗
PubMed2000

Asg7p-Ste3p inhibition of pheromone signaling: regulation of the zygotic transition to vegetative growth.

The inappropriate expression of the a-factor pheromone receptor (Ste3p) in the MATa cell leads to a striking inhibition of the yeast pheromone response, the result of a functional interaction between Ste3p and some MATa-specific protein. The present work identifies this protein as Asg7p. Normally, expression of Ste3p and Asg7p is limited to distinct haploid mating types, Ste3p to MATalpha cells and Asg7p to MATa cells. Artificial coexpression of the two in the same cell, either a or alpha, leads to dramatic inhibition of the pheromone response. Ste3p-Asg7p coexpression also perturbs the membrane trafficking of Ste3p: Ste3p turnover is slowed, a result of an Asg7p-mediated retardation of the secretory delivery of the newly synthesized receptor to the plasma membrane. However, in the absence of ectopic Ste3p expression, the asg7Delta mutation is without consequence either for pheromone signaling or overall mating efficiency of a cells. Indeed, the sole phenotype that can be assigned to MATa asg7Delta cells is observed following zygotic fusion to its alpha mating partner. Though formed at wild-type efficiency, zygotes from these pairings are morphologically abnormal. The pattern of growth is deranged: emergence of the first mitotic bud is delayed, and, in its place, growth is apparently diverted into a novel structure superficially resembling the polarized mating projection characteristic of haploid cells responding to pheromone. Together these results suggest a mechanism in which, following the zygotic fusion event, Ste3p and Asg7p gain access to one another and together act to repress the pheromone response, promoting the transition of the new diploid cell to vegetative growth.

Cell Compartmentation↗
PubMed2000

Achieving a credible health and safety approach to increasing seat belt use among African Americans.

African American youth are 60 percent less likely than children from other racial or ethnic backgrounds to be buckled up. Seat belt use among African American males has largely remained stagnant while that for other groups has increased. Overall, African Americans buckle up less often than other racial or ethnic populations. Seat belt use is a preventive health care action within public health. Clearly, a credible health and safety message is not being communicated effectively to African American communities. This paper proposes a number of possible solutions, including: recognition of the role that health care providers play in shaping patient or consumer attitudes and subsequent behavior in terms of prevention of disease and injury, educating physicians and health care providers to routinely recommend seat belt use especially for children, culturally appropriate educational safety programs, an improved relationship between law enforcement and communities, and zero tolerance for nonuse of seat belts.

Adolescent↗
PubMed2000

Sarcoidosis of the scalp: a case series and review of the literature.

Sarcoidosis of the scalp is a rare manifestation of cutaneous sarcoidosis. We report 4 cases, all in African-American women with systemic sarcoidosis. A review of the English-language literature reveals only 24 reported cases, most in African-American women with systemic involvement and other cutaneous lesions. Scalp sarcoidosis may exhibit variable morphologies and therefore must be kept in the differential diagnosis of plaques or nodules of the scalp as well as both cicatricial and noncicatricial alopecia.

Adult↗
PubMed2000

Data acquisition, data storage, and data presentation in a modern genetics laboratory.

Modern genetic analysis can be divided into three main areas of investigation. The first is data acquisition, in the form of genomic sequence and the cataloguing of polymorphism data of the single nucleotide polymorphism variety (so called SNPs). Once identified, such genetic information can be adapted into high throughput tests to examine genetic information in large populations, making the analysis of sufficiently large numbers both cost and time effective so that relatively low-penetrant genetic effects can be accurately detected. The third step is correlating variation with phenotype (e.g. disease susceptibility or resistance) for a variety of disorders is paramount in our motivation and indeed is a common goal of modern human genetic analysis. While the technology to acquire vast amounts of genetic data is now well established and continues to expand, the ability to deal with such data, from the process of acquisition, storage, and analysis depends fundamentally on a solid informatics infrastructure as an essential component. Indeed, most of the major gains in productivity in this field are to be realized on the informatics front, and involve automating data acquisition, defining and sorting data in databases for quality control and analysis and facilitating access to data for the large variety of data analyses. Informatics-related issues including those relating to data acquisition, database structure, and analysis tools are summarized here in an effort to define some of the issues relevant to establishing informatics infrastructure in a small genetics laboratory focused on resequencing human immune response genes. From inherited diseases to drug efficacy to the specific genetic changes occurring during tumor development, this new field of medical genetics promises a profound impact on the state of human health. Ultimately, any and all advances in this field will continue to depend on major investments in informatics.

Computational Biology↗
PubMed1999

Restorative exercise for clinical low back pain. A prospective two-center study with 1-year follow-up.

STUDY DESIGN: A comparison of treatment of 412 patients with chronic back pain at two separate centers using the same treatment protocols and outcome measures. Outcome was defined by specific strength testing; Short Form-36 scores at intake, discharge, and 1-year follow-up; self-appraisal of improvement at discharge and in a 1-year follow-up; and reuse of health care services after discharge. OBJECTIVES: To investigate the efficacy of standardized treatment methods using isolated lumbar strength testing and strengthening based on progressive protocols using specific equipment. Comparison of results should clarify the effect of the treatment center versus the efficacy of standardized protocols. SUMMARY OF BACKGROUND DATA: There has been little support in the scientific literature for exercise programs based on standardized protocols. The use of specialized equipment to achieve intense specific exercise also has been poorly supported. Overall health benefit has not often been related to specific improvement in strength. METHODS: More than 400 individuals with chronic back pain were evaluated at the initiation of treatment, discharge, and 1 year after discharge. Measures of efficacy were based on Short Form-36 scores, self-appraisal of improvement, and reuse of health care services after discharge. Study participants were patients with chronic back pain consecutively referred to each treatment site and underwritten by a variety of payers, including workers' compensation, Medicare, and private insurance. RESULTS: Overall response during the course of the program and at 1-year follow-up was similar between the two centers. Similar proportions of participants at each site demonstrated improvement in SF-36 scores, self-appraisal of improvement, and reuse of health care services. CONCLUSIONS: Standardized protocols using specific strength and measurement equipment can achieve similar benefits at different sites.

Adult↗
PubMed1999

Overjet reduction and molar correction in fixed appliance treatment of class II, division 1, malocclusions: sagittal and vertical components.

The purpose of this study was to quantitatively evaluate skeletal and dental changes contributing to Class II correction in patients treated with the Begg technique. The sample consisted of 18 male subjects with Class II, division 1, malocclusions treated with fixed appliances (Begg technique, nonextraction) for an average period of 1.3 years (standard deviation, 0.24 years). Lateral radiographs in habitual occlusion taken at 6 months before the start of treatment, at the start of treatment, and 6, 12, and 18 months after the start of treatment were analyzed. During the control period, normal sagittal and vertical growth changes occurred. In the initial treatment period (0 to 6 months), the overjet reduction (6.6 mm; P <. 001) and the molar correction (2.2 mm; P <.001) were obtained mainly by dental movements. The overbite was reduced by 4.1 mm (P <.001). The NSL/ML and NL/ML angles increased by 1.5 degrees (P <.05) and 1. 4 degrees (P <.01), respectively, and the anterior lower facial height increased by 3.1 mm (P <.001). During the second period of treatment (6 to 12 months), the molar correction continued to improve, and the anterior lower facial height continued to increase. During the third period (12 to 18 months), a small relapse in overjet and overbite was noted, but the anterior lower facial height continued to increase. During the total treatment period (0 to 18 months), the overjet reduction and molar correction were 5.8 mm (P <. 001) and 3.0 mm (P <.001), respectively. Mandibular growth exceeded maxillary growth by 1.1 mm (P <.01). The overbite correction and the increase in anterior lower facial height were 3.0 mm (P <.001) and 5. 0 mm (P <.001), respectively. The NSL/ML angle increased 1.0 degrees (P <.05). The conclusions were that the changes contributing to the Class II correction were mostly dental. Vertically, the net effects of treatment were an increase in the mandibular plane angle and in lower anterior facial height.

Adolescent↗
PubMed1998

Leadership in health: effecting change.

The following article is an edited version of a paper presented to the joint Australian Private Hospitals Association and Australian Healthcare Association Conference, 'Caring with Skill', held at Southport, Queensland, on 7-8 April 1998.

Australia↗
PubMed1998

The relationship between medical students' academic achievement and patterns of initial postgraduate placement.

PURPOSE: To explore the relationship between various levels of academic achievement and the spectrum of initial specialty placements for graduates. METHOD: The authors studied the initial specialty placements of all 1984-1994 graduates of the University of Kentucky College of Medicine. Statistical analyses were used to determine the nature and strength of the relationships between initial specialty selection and students' achievement indicators and changes in that relationship over time. RESULTS: Students tended to aggregate across time into discernible levels of achievement. The relationships between academic achievement levels and initial specialty placements were highly variable. CONCLUSION: Although students with higher levels of achievement had broader choices available to them, graduates at every level of achievement entered a wide variety of specialties. Thus, the authors believe that academic achievement should not be used to the exclusion of other performance characteristics in determining how students and residencies should be matched.

Career Choice↗
PubMed1998

Similar Müller-Lyer effects from operant and comparison response modes.

A one-sided (monopole) version of the Müller-Lyer was used to assess the effect of response mode on the metric distortion associated with the illusion. Two different response modes were tested for comparability. The Operant Mode required the judgment of stimulus span to be indicated by marking a dot on the test page. The Comparison Mode required judgment of equality of two adjoining prepositioned spans. The perceptual effects with the comparison procedure are known to consist of underestimation of spans which are bounded by concave fin-sets and over-estimation of spans which are bounded by convex fin-sets. The question is whether the motor demands of the operant task produce an additional source of metric bias. Analysis indicate a very high correlation of judgments for the two modes of testing. Also, data with either mode of responding closely fit a linear model of the effect, and the model provides comparable index values for the concave and convex versions. These results should mitigate concern about potential motor bias from the operant method and encourage its use as a more efficient procedure for assessing metric distortion.

Distance Perception↗