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William Thompson

Publications and source records attributed to William Thompson.

13 recordsLinked to original sources
PubMed2004

Validation of the anthrax lethal toxin neutralization assay.

A validation of the performance characteristics of a toxin neutralization assay is presented. This in vitro assay measures the functional ability of antisera, containing antibodies to anthrax lethal toxin, to specifically protect J774A.1 cells against Bacillus anthracis lethal toxin cytotoxicity. This colormetric assay is based upon the reduction of MTT by living cells. Human and rabbit antisera produced against anthrax vaccine absorbed (AVA) were used to validate the assay. Results showed a high level of repeatability and reproducibility, particularly for a bio-assay. Inter-assay variability in absorbance values was the most prominent negative finding however, an acceptable level was demonstrated with a ratio [neutralization ratio (NR)] of the test serum 50% effective dose (ED(50)) to the reference standard ED(50). Accuracy was maintained, even in samples with minimal neutralizing capacity, and linearity was noted when sample dilutions resulted in accurate prediction of the Y(max)and Y(min). Specificity tests demonstrated that normal sera did not have an observable effect on the ability of the reference standard to neutralize toxin. The assay remained stable against time, temperature, and freeze/thaw effects on the reference standards, but not on the toxin. The assay also remained stable against media and solution storage effects. Cell passage number and cell plating density were two critical parameters identified during the robustness studies that may be responsible for inter-assay variability in absorbance values. The work was performed in accordance with the FDA's Bioanalytical Method Validation Guidance for Industry and the FDA's Good Laboratory Practice for Nonclinical Laboratory Studies (21 CFR Part 58).

Animals↗
PubMed2004

HIV-1/AIDS neuropathology in a Canadian teaching centre.

BACKGROUND: The nervous system is a major target of HIV-1 infection and site of many complications of AIDS. Most of our knowledge pertaining to the range and frequency of neuropathology in HIV-1/AIDS is from large centres outside Canada in different social and health care settings. The goal of the present study was to describe HIV-1/AIDS-associated neuropathology before and during the era of highly active antiretroviral therapy at a Canadian teaching centre. METHODS: The records of the Department of Pathology, London Health Sciences Centre were electronically searched for cases of HIV-1/AIDS that came to postmortem examination since 1985. The clinical records and pathological materials were reviewed. RESULTS: Sixteen autopsies of HIV-1/AIDS were identified. All patients were male. Fourteen contracted HIV-1 through high risk homosexual activity, one through the transfusion of blood products and one through intravenous drug use. Three patients (19%) had pre-mortem evidence of HIV-1 associated dementia. At autopsy, 12 of the 16 cases had neuropathological findings and the most common diagnoses were HIV-1 encephalitis, progressive multifocal leukoencephalopathy, toxoplasmosis, and primary CNS lymphoma. CONCLUSIONS: High risk homosexual activity was a more prominent factor in acquiring AIDS in cases coming to postmortem examination compared with previous reports from most larger urban centres outside Canada where injection drug use and high risk heterosexual activity factored prominently. The incidence of HIV-1 associated dementia was similar to that reported previously. This study confirms the heavy burden and wide spectrum of disease experienced by the nervous system in HIV-1/AIDS.

AIDS Dementia Complex↗
PubMed2004

Developing employment services for criminal justice clients enrolled in drug user treatment programs.

Approximately 80% of parolees have a history of substance abuse and nearly all are unemployed following release from prison. Common stipulations of parole require offenders to obtain employment and to not use mood-altering substances. This article explores a series of strategies implemented from 1999 to 2001 to help offenders paroled to substance user treatment to gain employment. A total of 245 paroled offenders enrolled in an outpatient substance abuse treatment program voluntarily agreed to participate in one of four different vocational intervention programs (Job Skill Development and Supported Work, Life Skill Development, Job Training, and Welfare to Work). Programmatic data (e.g., attendance, completion, job acquisition, and wage) were collected and reported for each of the vocational programs. Additionally, a 12-month pilot study examined criminal justice, substance use, and employment outcomes of 36 offenders referred to the job skill development and supported work project. Overall, 78% of the offenders enrolled in the vocational services completed the program and 134/245 (55%) were able to obtain employment. The data showed that completion of vocational services was strongly associated with obtaining employment 12 months postenrollment. Offenders identified the employment services as an integral part of their improved overall functioning. A series of practice recommendations and policy suggestions is offered to develop and manage vocational services for substance-using offenders. Employment services for parolees require considerable coordination of activities with parole officers, vocational programs, substance abuse treatment professionals, and funding systems.

Crime↗
PubMed2004

Decoding human regulatory circuits.

Clusters of transcription factor binding sites (TFBSs) which direct gene expression constitute cis-regulatory modules (CRMs). We present a novel algorithm, based on Gibbs sampling, which locates, de novo, the cis features of these CRMs, their component TFBSs, and the properties of their spatial distribution. The algorithm finds 69% of experimentally reported TFBSs and 85% of the CRMs in a reference data set of regions upstream of genes differentially expressed in skeletal muscle cells. A discriminant procedure based on the output of the model specifically discriminated regulatory sequences in muscle-specific genes in an independent test set. Application of the method to the analysis of 2710 10-kb fragments upstream of annotated human genes identified 17 novel candidate modules with a false discovery rate </=0.05, demonstrating the applicability of the method to genome-scale data.

Algorithms↗
PubMed2003

Gibbs Recursive Sampler: finding transcription factor binding sites.

The Gibbs Motif Sampler is a software package for locating common elements in collections of biopolymer sequences. In this paper we describe a new variation of the Gibbs Motif Sampler, the Gibbs Recursive Sampler, which has been developed specifically for locating multiple transcription factor binding sites for multiple transcription factors simultaneously in unaligned DNA sequences that may be heterogeneous in DNA composition. Here we describe the basic operation of the web-based version of this sampler. The sampler may be acces-sed at http://bayesweb.wadsworth.org/gibbs/gibbs.html and at http://www.bioinfo.rpi.edu/applications/bayesian/gibbs/gibbs.html. An online user guide is available at http://bayesweb.wadsworth.org/gibbs/bernoulli.html and at http://www.bioinfo.rpi.edu/applications/bayesian/gibbs/manual/bernoulli.html. Solaris, Solaris.x86 and Linux versions of the sampler are available as stand-alone programs for academic and not-for-profit users. Commercial licenses are also available. The Gibbs Recursive Sampler is distributed in accordance with the ISCB level 0 guidelines and a requirement for citation of use in scientific publications.

Algorithms↗
PubMed2003

Identification of co-regulated genes through Bayesian clustering of predicted regulatory binding sites.

The identification of co-regulated genes and their transcription-factor binding sites (TFBS) are key steps toward understanding transcription regulation. In addition to effective laboratory assays, various computational approaches for the detection of TFBS in promoter regions of coexpressed genes have been developed. The availability of complete genome sequences combined with the likelihood that transcription factors and their cognate sites are often conserved during evolution has led to the development of phylogenetic footprinting. The modus operandi of this technique is to search for conserved motifs upstream of orthologous genes from closely related species. The method can identify hundreds of TFBS without prior knowledge of co-regulation or coexpression. Because many of these predicted sites are likely to be bound by the same transcription factor, motifs with similar patterns can be put into clusters so as to infer the sets of co-regulated genes, that is, the regulons. This strategy utilizes only genome sequence information and is complementary to and confirmative of gene expression data generated by microarray experiments. However, the limited data available to characterize individual binding patterns, the variation in motif alignment, motif width, and base conservation, and the lack of knowledge of the number and sizes of regulons make this inference problem difficult. We have developed a Gibbs sampling-based Bayesian motif clustering (BMC) algorithm to address these challenges. Tests on simulated data sets show that BMC produces many fewer errors than hierarchical and K-means clustering methods. The application of BMC to hundreds of predicted gamma-proteobacterial motifs correctly identified many experimentally reported regulons, inferred the existence of previously unreported members of these regulons, and suggested novel regulons.

Algorithms↗
PubMed2003

The bioterrorism preparedness and response Early Aberration Reporting System (EARS).

Data from public health surveillance systems can provide meaningful measures of population risks for disease, disability, and death. Analysis and evaluation of these surveillance data help public health practitioners react to important health events in a timely manner both locally and nationally. Aberration detection methods allow the rapid assessment of changes in frequencies and rates of different health outcomes and the characterization of unusual trends or clusters. The Early Aberration Reporting System (EARS) of the Centers for Disease Control and Prevention allows the analysis of public health surveillance data using available aberration detection methods. The primary purpose of EARS is to provide national, state, and local health departments with several alternative aberration detection methods. EARS helps assist local and state health officials to focus limited resources on appropriate activities during epidemiological investigations of important public health events. Finally, EARS allows end users to select validated aberration detection methods and modify sensitivity and specificity thresholds to values considered to be of public health importance by local and state health departments.

Bioterrorism↗
PubMed2003

Endovascular repair of acute innominate artery injury due to blunt trauma.

The utility of endovascular techniques has expanded greatly over the past decade. Physicians now have choices regarding the treatment of many injuries that have traditionally required open surgical repair. Technological advances in materials as well as improved training and expertise among practitioners has led to increased availability of endovascular procedures that can often provide an effective and less invasive means of management. The following case report describes the successful treatment of a traumatic blunt injury to the innominate artery using endovascular techniques. Also provided is a review of the physical and radiographic findings associated with innominate artery rupture as well as a discussion on the diagnosis and treatment of such an injury. Isolated injuries of the innominate artery are exceedingly rare, and very little has been published about the endovascular repair of this specific injury. An extensive MEDLINE search was conducted to investigate whether or not endovascular repair of this particular injury had yet been described, and we found no published reports in the American medical literature. Although the technical aspects of this case are not particularly unique this case report demonstrates yet another successful application of endovascular intervention in the acute setting of blunt injury.

Accidents, Traffic↗
PubMed2002

Facilitation of recovery from acute blood loss with hyperbaric oxygen.

BACKGROUND: Hyperbaric oxygen (HBO) has been used for more than 25 years as therapy for extreme blood loss in cases where transfusion has been unavailable. The use of HBO for lesser amounts of blood loss to avoid the transfusion of blood products has not been investigated. HYPOTHESIS: Hyperbaric oxygen up-regulates hemoglobin synthesis after acute blood loss in an animal model of moderate (30%) blood loss. DESIGN: Twenty-four New Zealand white rabbits were bled to a calculated loss of 30% of the circulating blood volume. The rabbits received Ringer lactate infusions to correct hypovolemia and were divided into 2 groups: a control group and a treatment group receiving HBO. INTERVENTION: One group of 12 animals received no treatment other than Ringer lactate resuscitation, whereas the other group of 12 received 5 HBO treatments in the 4 days immediately following blood loss. Hemoglobin levels and reticulocyte counts were monitored for 14 days after the bleeding episode. RESULTS: The control group was more affected by the blood withdrawal than the HBO group, reaching a low of 37% hemoglobin loss compared with 29% hemoglobin loss at 48 hours (P<.001). The HBO group recovered faster, reaching the baseline level of hemoglobin in 11 days as opposed to 14 days for the control group (P<.001). Reticulocyte counts were not significantly affected by HBO treatment. CONCLUSIONS: Treatment with HBO favorably affected recovery from moderate (30%) acute blood loss, resulting in lessened effects at 48 hours and hastening recovery to baseline hemoglobin levels. Our results support the data gained from clinical experience treating extreme blood loss with HBO.

Animals↗
PubMed2002

Preclinical and clinical studies of docetaxel and exisulind in the treatment of human lung cancer.

Lung cancer is the leading cause of cancer death in the United States. The majority of patients with non-small cell lung cancers present with inoperable disease because of the presence of metastases to regional lymph nodes or other metastatic sites. About one third of patients have stage IV disease with metastases to distant organs at the time of diagnosis. The prognosis for these patients is very poor. With best supportive care the median survival is only 4 months and the 1-year survival rate is 10% to 15%. Current chemotherapy combinations improve the survival and quality of life for patients with advanced non-small cell lung cancer. With two-drug combinations, median survival is increased to 8 months or more and 1-year survival is increased to 35% to 40%. Still, complete response rates are low and more than 80% of patients die within 1 year of diagnosis. The improvements created by current therapies led to studies of chemotherapy in the second-line setting. Docetaxel has been shown to improve survival of patients who failed platinum-based chemotherapy and was approved by the U.S. Food and Drug Administration for therapy in this setting. However, response rates were very low and survival very short. Therefore, new therapies are urgently needed. Exisulind is a novel oral anticancer agent that holds promise for the treatment of patients with advanced non-small cell lung cancer. Exisulind was originally developed as a chemoprevention agent for colorectal cancer. Preclinical studies showed that exisulind could prevent polyp formation and inhibit the growth of colorectal cancers. Subsequent preclinical studies showed that exisulind also inhibited the growth of human breast, prostate, and lung cancers. Phase I clinical studies showed that twice-daily oral doses could be given safely and would provide peak concentrations that were equivalent to those required for in vitro effects. These observations lead to the studies of the combination of exisulind and docetaxel in preclinical and clinical studies in human lung cancer described in this article.

Administration, Oral↗
PubMed2002

Factors influencing the identification of transcription factor binding sites by cross-species comparison.

As the number of sequenced genomes has grown, the questions of which species are most useful and how many genomes are sufficient for comparison have become increasingly important for comparative genomics studies. We have systematically addressed these questions with respect to phylogenetic footprinting of transcription factor (TF) binding sites in the gamma-proteobacteria, and have evaluated the statistical significance of our motif predictions. We used a study set of 166 Escherichia coli genes that have experimentally identified TF binding sites upstream of the gene, with orthologous data from nine additional gamma-proteobacteria for phylogenetic footprinting. Just three species were sufficient for approximately 74.0% of the motif predictions to correspond to the experimentally reported E. coli sites, and important characteristics to consider when choosing species were phylogenetic distance, genome size, and natural habitat. We also performed simulations using randomized data to determine the critical maximum a posteriori probability (MAP) values for statistical significance of our motif predictions (P = 0.05). Approximately 60% of motif predictions containing sites from just three species had average MAP values above these critical MAP values. The inclusion of a species very closely related to E. coli increased the number of statistically significant motif predictions, despite substantially increasing the critical MAP value.

Binding Sites↗