Biomedical subjects

Deborah A Payne

Publications and source records attributed to Deborah A Payne.

10 recordsLinked to original sources

PubMed2005

Molecular diagnosis of infectious diseases in dermatology.

UNLABELLED: The molecular diagnosis of infectious disease has been growing considerably over the past decade. Nucleic acid amplification techniques, such as polymerase chain reaction, ligase chain reaction, transcription-mediated amplification, and nucleic acid sequence-based amplification, provide highly accurate diagnosis of numerous bacterial, viral, fungal, and parasitic infections involved in a variety of dermatologic diseases. In addition, signal amplification with hybrid capture, branched-DNA assays, and in situ hybridization have been used to detect numerous viral pathogens with high degrees of sensitivity and specificity. New technology that involves the use of DNA and protein microarrays has also enabled the detection of a variety of genes and gene mutations. With time, these diagnostic assays are decreasing in cost, gaining approval of the U.S. Food and Drug Administration, and becoming easier and more efficient to use. In the future, these assays will be able to deliver rapid and accurate diagnosis of infectious diseases within a single clinic visit. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be familiar with molecular diagnosis of infectious diseases in dermatology.

Bacteria↗

PubMed2005

Developing a sustainable process to provide quality control materials for genetic testing.

PURPOSE: To provide a summary of the outcomes of two working conferences organized by the Centers for Disease Control and Prevention (CDC), to develop recommendations for practical, sustainable mechanisms to make quality control (QC) materials available to the genetic testing community. METHODS: Participants were selected to include experts in genetic testing and molecular diagnostics from professional organizations, government agencies, industry, laboratories, academic institutions, cell repositories, and proficiency testing (PT)/external Quality Assessment (EQA) programs. Current efforts to develop QC materials for genetic tests were reviewed; key issues and areas of need were identified; and workgroups were formed to address each area of need and to formulate recommendations and next steps. RESULTS: Recommendations were developed toward establishing a sustainable process to improve the availability of appropriate QC materials for genetic testing, with an emphasis on molecular genetic testing as an initial step. CONCLUSIONS: Improving the availability of appropriate QC materials is of critical importance for assuring the quality of genetic testing, enhancing performance evaluation and PT/EQA programs, and facilitating new test development. To meet the needs of the rapidly expanding capacity of genetic testing in clinical and public health settings, a comprehensive, coordinated program should be developed. A Genetic Testing Quality Control Materials Program has therefore been established by CDC in March 2005 to serve these needs.

Centers for Disease Control and Prevention, U.S.↗

PubMed2004

Molecular markers of clonality and identity in Epstein-Barr virus-associated B-cell lymphoproliferative disease.

Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disease may be polyclonal, oligoclonal, or monoclonal. The degree of tumor clonality reflects the disease pathogenesis and may have implications for disease diagnosis, prognosis, and treatment. In this study, specimens of EBV-associated B-cell lymphoproliferative disease obtained from immunocompromised hosts were analyzed for molecular markers of cellular and virologic clonality and virologic identity. Each tumor specimen was assessed for immunoglobulin gene JH region rearrangement, the structure of the EBV genome termini, and the EBV genotype(s) present using a new EBV genotyping assay based upon LMP-1 gene sequence variation. The results of the JH rearrangement and EBV termini assays were generally concordant in their assessment of tumor specimen clonality, and both assays contributed to establishing clonal identity between different tumor specimens. The EBV genotyping assay did not significantly contribute to the assessment of tumor clonality but did established clear virologic identity between different tumor specimens obtained from the same individual. In one individual, these three assays together characterized a multi-focal, monoclonal tumor that may have arisen through clonal selection after sequential infections with two different EBV genotypes. In summary, the JH rearrangement and EBV termini assays each provided different but complementary information on tumor clonality, while the EBV genotyping assay proved most useful for establishing virologic identity among tumors. Utilization of these three assays together may provide new insight into the pathogenesis of EBV-associated B-cell lymphoproliferative disease.

Amino Acid Sequence↗

PubMed2004

Molecular characterization of mutations in patients with benign and aggressive recurrent respiratory papillomatosis: a preliminary study.

This study was performed to determine whether genetic polymorphisms within the human papillomavirus (HPV) can predict the disease course in patients with recurrent respiratory papillomatosis. The HPV type and genomic variations were determined by comparing the sample sequence to a prototypical HPV in the database of the National Center for Biotechnology Information. The results were correlated with the clinical course. Seven children and 6 adults were studied. Six of the 7 children had aggressive disease associated with HPV type 11. The remaining child had HPV type 6. Five of the 6 adult patients had HPV type 6; 1 had a history of juvenile recurrent respiratory papillomatosis. The remaining adult had an aggressive disease course associated with HPV type 11. The HPV type and specific polymorphisms were conserved over time in serial isolates. The age of onset and medical therapy did not appear to affect the polymorphisms present. Future studies may find that the presence of certain polymorphisms is associated with different geographic locations and possibly with the disease course.

Adult↗

PubMed2004

HIV pharmacogenomics: closer to personalized therapy?

Pharmacogenomics classically focuses on host nuclear genetic polymorphisms that can be used to predict adverse drug reactions (ADRs). Because ADRs are defined as any noxious, unintended, and undesired drug effects, loss of efficacy due to the development of antiretroviral drug resistance and both acute and cumulative adverse effects of antiretroviral therapy can be considered ADRs. In order to address these types of antiretroviral-associated ADRs, pharmacogenomic testing methods have expanded to include molecular assays that characterize extranuclear genetic material (e.g. HIV and mitochondrial genomes), as well as the host nuclear genetic material. Recent molecular advances permit high resolution resistance testing that detects loss of therapeutic efficacy through the use of phenotypic, genotypic and/or virtual phenotypic resistance testing. These assays use complex technical and interpretative methods to improve the therapeutic efficacy of antiretroviral therapy. The resistance assays demonstrate the utility of pharmacogenomic testing for patients undergoing lifelong and complex antiretroviral therapies. Future applications of antiretroviral-directed pharmacogenomic tests range from quantitative detection of mitochondrial depletion as an early surrogate marker for drug toxicity, to qualitative analysis of host immune haplotypes, and metabolic/transporter genetic polymorphisms for predicting disease progression. In summary, pharmacogenomic testing for HIV-positive patients provides proof of principle that these tests can be used clinically to improve outcomes for patients undergoing complex and sustained drug regimens.

Anti-HIV Agents↗

PubMed2003

Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia.

Infection with high-risk human papillomavirus (HPV) plays a major role in the etiology of cervical cancer (CC). However, most infected women do not develop cancer. Therefore, exposure to other carcinogenic agents may be a contributing risk factor for CC. We investigated the hypothesis that environmental exposure to cigarette smoke and inheritance of polymorphic chemical metabolizing genes (CYP2E1, GSTM1, and mEH) significantly increase the risk for neoplasia. We selected 76 cases with high-grade cervical neoplasia or with invasive CC and 75 matched healthy controls. The collected data support the well-established observation that infection with high-risk HPV is the major risk factor for CC (OR = 75; 95% CI = 26-220). In addition, our data show that women who smoked more than 15 "pack-year" had a significant 6.9-fold increase in risk (95% CI = 1.2-40.3) after adjustment for HPV infection. The CYP2E1 variant genotype did not significantly increase the risk for neoplasia. A significant increase in risk for neoplasia was observed for the low-activity mEH 113 His allele after adjustment for smoking (OR = 3.0; 95% CI = 1.4-6.3). The GSTM1 null genotype was associated with a significant 3.3-fold increased risk for neoplasia (95% CI = 1.0-11.8) compared to women who were GSTM1-positive after adjustment for smoking and HPV infection. Our study suggests that genetic differences in the metabolism of cigarette smoke, particularly GSTM1, may confer susceptibility to CC. Further studies using larger populations will be needed to confirm our observations and to validate data for disease prevention.

Adolescent↗

PubMed2003

Capillary electrophoresis and its application in the clinical laboratory.

Over the past 10 years, capillary electrophoresis (CE) is an analytical tool that has shown great promise in replacing many conventional clinical laboratory methods, especially electrophoresis and high performance liquid chromatography (HPLC). The main attraction of CE was that it was fast, used small amounts of sample and reagents, and was extremely versatile, being able to separate large and small analytes, both neutral and charged. Because of this versatility, numerous methods for clinically relevant analytes have been developed. However, with the exception of the molecular diagnostic and forensic laboratories CE has not had a major impact. A possible reason is that CE is still perceived as requiring above-average technical expertise, precluding its use in a laboratory workforce that is less technically adept. With the introduction of multicapillary instruments that are more automated, less technique-dependent, in addition to the availability of commercial and cost effective test kit methods, CE may yet be accepted as a instrument routinely used in the clinical laboratories. Thus, this review will focus on the areas where CE shows the most potential to have the greatest impact on the clinical laboratory. These include analysis of proteins found in serum, urine, CSF and body fluids, immunosubstraction electrophoresis, hemoglobin variants, lipoproteins, carbohydrate-deficient transferrin (CDT), forensic and therapeutic drug screening, and molecular diagnostics.

Chemistry, Clinical↗

PubMed2003

Intraspecific diversity of Vibrio vulnificus in Galveston Bay water and oysters as determined by randomly amplified polymorphic DNA PCR.

Randomly amplified polymorphic DNA (RAPD) PCR was used to analyze the temporal and spatial intraspecific diversity of 208 Vibrio vulnificus strains isolated from Galveston Bay water and oysters at five different sites between June 2000 and June 2001. V. vulnificus was not detected during the winter months (December through February). The densities of V. vulnificus in water and oysters were positively correlated with water temperature. Cluster analysis of RAPD PCR profiles of the 208 V. vulnificus isolates revealed a high level of intraspecific diversity among the strains. No correlation was found between the intraspecific diversity among the isolates and sampling site or source of isolation. After not being detected during the winter months, the genetic diversity of V. vulnificus strains first isolated in March was 0.9167. Beginning in April, a higher level of intraspecific diversity (0.9933) and a major shift in population structure were observed among V. vulnificus isolates. These results suggest that a great genetic diversity of V. vulnificus strains exists in Galveston Bay water and oysters and that the population structure of this species is linked to changes in environmental conditions, especially temperature.

Animals↗

PubMed2002

Porphyria cutanea tarda: multiplicity of risk factors including HFE mutations, hepatitis C, and inherited uroporphyrinogen decarboxylase deficiency.

The coexistence of factors considered to contribute to development of porphyria cutanea tarda was studied in 39 consecutive patients. Highly prevalent factors were alcohol intake in 79%, smoking in 86%, hepatitis C virus infection in 74%, estrogen use in 73% of 11 females, and at least one mutation in the HFE (hereditary hemochromatosis) gene in 65%. The C282Y mutation was found in 29%, H63D in 47%, and S65C in 0%. HFE genotypes included C282Y/C282Y in 9%, H63D/H63D in 9%, C282Y/H63D in 12%, C282Y/wild type in 9%, and H63D/wild type in 26%. Less prevalent were HIV infection in 15% (or 25% of those tested, N = 24) and erythrocyte uroporphyrinogen decarboxylase deficiency, which distinguishes familial (type 2) from "sporadic" (type 1) porphyria cutanea tarda, in 19%. Multiple contributing factors coexisted in both types 1 and 2, with 92% of all patients having three or more factors. These observations indicate that this porphyria is multifactorial in the individual patient, and therefore is seldom attributable to a single identifiable cause. Profiling for all potentially contributing factors is important for individualizing management.

Alcohol Drinking↗

PubMedDate not supplied

Enabling proteomics discovery through visual analysis. The peptide permutation and protein prediction tool.

Proteins play a key role in cellular processes, making proteomics central to understanding systems biology. MS techniques provide a means to observe entire proteomes at a global level. Yet, high-throughput MS proteomics techniques generate data faster than it can currently be analyzed. The success of proteomics depends on high-throughput experimental techniques coupled with sophisticated visual analysis and data-mining methods. Visual analysis has been applied successfully in a number of fields plagued with huge, complex data sets and will likely be an important tool in proteomics discovery. PQuad, a novel visualization of MS proteomics data, provides powerful analysis capabilities that support a number of proteomic data applications. In particular, PQuad supports differential proteomics by simplifying the comparison of peptide sets from different experimental conditions as well as different protein identification or confidence scoring techniques. Finally, PQuad supports data validation and quality control by providing a variety of resolutions for huge amounts of data to reveal errors undetected by other methods.

Algorithms↗