Biomedical subjects

Mark E Whipple

Publications and source records attributed to Mark E Whipple.

9 recordsLinked to original sources

PubMed2006

A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies.

Over the last decade, gene expression microarrays have had a profound impact on biomedical research. The diversity of platforms and analytical methods available to researchers have made the comparison of data from multiple platforms challenging. In this study, we describe a framework for comparisons across platforms and laboratories. We have attempted to include nearly all the available commercial and 'in-house' platforms. Using probe sequences matched at the exon level improved consistency of measurements across the different microarray platforms compared to annotation-based matches. Generally, consistency was good for highly expressed genes, and variable for genes with lower expression values as confirmed by quantitative real-time (QRT)-PCR. Concordance of measurements was higher between laboratories on the same platform than across platforms. We demonstrate that, after stringent preprocessing, commercial arrays were more consistent than in-house arrays, and by most measures, one-dye platforms were more consistent than two-dye platforms.

Chromosome Mapping↗

PubMed2006

Early introduction of clinical skills improves medical student comfort at the start of third-year clerkships.

BACKGROUND: To determine whether introducing clinical skills during the second year of medical school, via a competency-based College system approach, improves comfort level for medical students entering third-year clinical rotations. METHOD: From 2003-2005, two cohorts of third-year medical students at the University of Washington were surveyed on their comfort level in the categories of history taking, physical examination, communication, and patient care. RESULTS: The cohort of students exposed to the College system reported a statistically significant greater comfort level in half of the measured areas, and in at least one area within each general category. No area of study showed a statistically significant decline. CONCLUSION: A competency-based College system improves medical student comfort in core clinical skills at the start of the third year curriculum.

Clinical Clerkship↗

PubMed2005

Porous high-density polyethylene for orbital reconstruction.

OBJECTIVE: To determine the safety and efficacy of using porous high-density polyethylene (PHDPE) in the repair of orbital defects. DESIGN: Retrospective case series. SETTING: Academic tertiary care trauma center. Patients One hundred seventy patients with orbital defects requiring surgical repair. Intervention Orbital defect repair with PHDPE. Main Outcome Measure Our review documents surgical results and complications associated with the use of PHDPE. RESULTS: There was a 6.4% complication rate associated with the use of PHDPE. The infection rate was 1.8%. The persistent orbital malposition rate was 3.5%. The extrusion rate was 0%. CONCLUSIONS: This report represents the largest case series in the literature using PHDPE for orbital reconstructions. The use of PHDPE resulted in a low complication rate and excellent functional and cosmetic reconstructive results. Because of our success with the use of PHDPE, we have changed our clinical practice to minimize the use of autologous graft material, thereby eliminating donor site morbidity in cases involving orbital reconstruction.

Biocompatible Materials↗

PubMed2004

Deciphering gene expression profiles generated from DNA microarrays and their applications in oral medicine.

Genome-wide monitoring of gene expression profiles using DNA microarrays provides a unique approach to exploring the biological processes underlying oral diseases and disorders by providing a comprehensive survey of a cell's or tissue's transcriptional mapping. This revolutionary technology allows for the simultaneous assessment of the transcription levels of tens of thousands of genes, and of their relative expression between normal and diseased cells. As microarray data analysis evolves, there is a widespread hope that microarrays will significantly impact our ability to explore the genetic changes associated with disease etiology and development, ultimately leading to the discovery of new biomarkers for disease diagnosis and prognosis prediction as well as new therapeutic tools. The goal of this manuscript is to review 2 of the most commonly used microarray technologies, provide an overview of data analyses involved in a typical microarray experiment, and comment upon the application of microarrays to oral medicine.

Biomarkers↗

PubMed2004

A genomic predictor of oral squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: The objective was to identify a genomic profile that predicts the likelihood of oral squamous cell carcinoma compared with normal oral mucosa in unknown tissue samples. STUDY DESIGN: Using a training set of tissue samples that were histologically classified as oral squamous cell carcinoma or normal mucosa, the authors used principal component analysis to develop a genomic predictor for oral squamous cell carcinoma. On a separate test set of unclassified samples, the authors used the predictor to classify the samples, then evaluated the performance of the predictor using histological diagnosis. METHODS: The authors used a data set consisting of messenger RNA extracted from 29 oral squamous cell carcinoma and 19 normal oral mucosa tissue samples and hybridized to Affymetrix oligonucleotide microarrays containing probe sets for 7070 genes and expressed sequence tags. The samples were divided into a training set of 15 oral squamous cell carcinoma and 10 normal samples and a test set consisting of the remaining samples. Using principal component analysis on the training set, the authors found a composite gene expression vector (principal component vector), which they used to compute likelihood ratios for oral squamous cell carcinoma on the test set. By calculating the contribution of each gene to the principal component vector, the authors identified genes with the greatest predictive value. RESULTS: Using the likelihood ratio, the authors correctly classified all 23 samples in the test set as either oral squamous cell carcinoma or normal. The authors found that many of the most predictive genes are known to be markers of squamous cell carcinoma or normal mucosa. CONCLUSION: Principal component analysis can be used with genomic microarray data to correctly predict the presence of oral squamous cell carcinoma in unknown tissue samples.

Biomarkers, Tumor↗

PubMed2004

A log likelihood predictor for genomic classification of oral cancer using principle component analysis for feature selection.

DNA microarrays are powerful tools for exploring gene expression and predicting disease state. However, since the number of variables (genes) typically exceeds the number of samples (tissue specimens), many potentially spurious genes may be selected for a predictor function. Principle component analysis (PCA) can greatly reduce the high-dimensional microarray data space while retaining most of the inherent variability. We propose a methodology that uses PCA to identify a predictor vector between two mutually exclusive and collectively exhaustive classes. By projecting the training set upon this vector a distribution of projections can be computed for each class. A log-likelihood ratio is then calculated for class membership. We used this methodology to classify 48 biopsy specimens as either oral squamous cell carcinoma or normal oral mucosa using oligonucleotide microarrays. The system was trained using a set of half the samples, and correctly predicted the membership of the other half. The three most highly positively and three most highly negative predictive genes were all keratins that are known markers of squamous cell carcinoma.

Biopsy↗

PubMed2003

Microarrays and clinical dentistry.

BACKGROUND: The Human Genome Project, or HGP, has inspired a great deal of exciting biology recently by enabling the development of new technologies that will be essential for understanding the different types of abnormalities in diseases related to the oral cavity. LITERATURE REVIEWED: The authors review current literature pertaining to the advanced microarray technologies arising from the HGP and how they can contribute to dentistry. This technology has become a standard tool for monitoring activities of genes at both academic and pharmaceutical research institutions. RESULTS: With the availability of the DNA sequences for the entire human genome, attention now is focused on understanding various diseases at the genome level. Deciphering the molecular behavior of genetically encoded proteins is crucial to obtaining a more comprehensive picture of disease processes. Important progress has been made using microarrays, which have been shown to be effective in identifying gene expression patterns and variations that correlate with cellular development, physiology and function. Arrays can be used to classify tissue samples accurately based on molecular profiles and to select candidate genes related to a number of cancers, including oral cancer. This type of oral genetic approach will aid in the understanding of disease progression, thus improving diagnosis and treatment for patients. CLINICAL IMPLICATIONS: Microarrays hold much promise for the analysis of diseases in the oral cavity. As the technology evolves, dentists may see these tools as screening tests for better managing patients' dental care.

Anti-Bacterial Agents↗

PubMed2003

Functional relationships between gene pairs in oral squamous cell carcinoma.

We developed a novel method for the discovery of functional relationships between pairs of genes based on gene expression profiles generated from microarrays. This approach examines all possible pairs of genes and identifies those in which the relationship between the two genes changes in different diseases or conditions. In contrast to previous methods that have focused on differentially expressed genes, this method attempts to find changes in the correlation between genes. These changes may be indicative of the functional relationships related to a disease mechanism. We demonstrate the utility of this approach by applying it to an oral squamous cell carcinoma (OSCC) microarray data set. Our results suggest new directions for future experimental investigations.

Carcinoma, Squamous Cell↗

PubMed2002

Gene expression profiling by DNA microarrays and its application to dental research.

UNLABELLED: DNA microarray technology has been used for genome-wide gene expression studies that incorporate molecular genetics and computer science skills on massive levels. The technology permits the simultaneous analysis of tens of thousands of genes for the purposes of gene discovery, disease diagnosis. improved drug development, and therapeutics tailored to specific disease processes. OBJECTIVE: In this review, the two most common microarray technologies and their potential application to dental research will be discussed. The authors review current articles pertaining to the technologies and analysis of mRNA expression using DNA micro-arrays and its application to dental research. Since many genes contribute to normal functioning, research efforts are moving from the search for a disease specific gene to the understanding of the biochemical and molecular functioning of a variety of genes and how complicated networks of interaction can lead to a disease state, such as oral cancer. With the incorporation of DNA micro-array based research, we can look forward to more accurate diagnosis and surgical treatment/drug-delivery therapy based on an individual patient's genetic profile.

Carcinoma, Squamous Cell↗