Biomedical subjects

K Wayne Marshall

Publications and source records attributed to K Wayne Marshall.

5 recordsLinked to original sources

PubMed2006

Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects.

Plasma lipid levels have been known to be risk factors for atherosclerosis for decades, and in recent years it has become accepted that inflammation is a crucial event in the pathogenesis of atherosclerosis. In this study, we investigated the relationship between plasma lipids and leukocytes by profiling and analyzing leukocyte gene expression in response to plasma lipid levels. We discovered several interesting patterns of leukocyte gene expression: (1) the expression of a number of immune response- and inflammation-related genes are correlated with plasma lipid levels; (2) genes involved in lipid metabolism and in the electron transport chain were positively correlated with triglycerides and low-density lipoprotein cholesterol (LDL) levels, and negatively correlated with high-density lipoprotein cholesterol (HDL) levels; (3) genes involved in platelet activation were negatively correlated with HDL levels; (4) transcription factors regulating lipogenesis-related genes were correlated with plasma lipid levels; (5) a number of genes correlated with plasma lipid levels were found to be located in the regions of known quantitative trait loci (QTLs) associated with hyperlipemia. Our findings suggest that leukocytes respond to changing plasma lipid levels by regulating a network of genes, including genes involved in immune response, and lipid and fatty acid metabolism.

Adult↗

PubMed2006

Novel blood biomarkers of human urinary bladder cancer.

PURPOSE: Recent data indicate that cDNA microarray gene expression profile of blood cells can reflect disease states and thus have diagnostic value. We tested the hypothesis that blood cell gene expression can differentiate between bladder cancer and other genitourinary cancers as well as between bladder cancer and healthy controls. EXPERIMENTAL DESIGN: We used Affymetrix U133 Plus 2.0 GeneChip (Affymetrix, Santa Clara, CA) to profile circulating blood total RNA from 35 patients diagnosed with one of three types of genitourinary cancer [bladder cancer (n = 16), testicular cancer (n = 10), and renal cell carcinoma (n = 9)] and compared their cDNA profiles with those of 10 healthy subjects. We then verified the expression levels of selected genes from the Affymetrix results in a larger number of bladder cancer patients (n = 40) and healthy controls (n = 27). RESULTS: Blood gene expression profiles distinguished bladder cancer patients from healthy controls and from testicular and renal cancer patients. Differential expression of a combined set of seven gene transcripts (insulin-like growth factor-binding protein 7, sorting nexin 16, chondroitin sulfate proteoglycan 6, and cathepsin D, chromodomain helicase DNA-binding protein 2, nell-like 2, and tumor necrosis factor receptor superfamily member 7) was able to discriminate bladder cancer from control samples with a sensitivity of 83% (95% confidence interval, 67-93%) and a specificity of 93% (95% confidence interval, 76-99%). CONCLUSION: We have shown that the gene expression profile of circulating blood cells can distinguish bladder cancer from other types of genitourinary cancer and healthy controls and can be used to identify novel blood markers for bladder cancer.

Adult↗

PubMed2006

Chondrocyte genomics: implications for disease modification in osteoarthritis.

Advances in genomic technologies have made genome-wide-association and gene-expression studies a reality. Despite technical and analytical challenges, the application of genomic technologies to osteoarthritis research will lead to a better understanding of the disease at the molecular level. Functional genomics will identify genes involved in the chondrocyte response to cartilage injury and cartilage repair, and will help clarify the role of chondrocytes in arthritis onset, progression and outcome. Systems biology will enable researchers to develop a full portrait of osteoarthritis, a complex and multifactorial disease that involves not only articular cartilage but also synovium, synovial fluid, subchondral bone and peripheral blood. Ultimately such an approach will result in novel diagnostic and therapeutic targets and better disease management.

Chondrocytes↗

PubMed2005

Characterization of proteoglycan depletion in articular cartilage using two-dimensional time domain nuclear magnetic resonance.

In vitro proteoglycan (PG) depletion in the 20-40% range (enzymatic PG depletion of normal cartilage in the early osteoarthritis (OA) PG depletion range) was investigated in articular cartilage using 2D time domain NMR relaxation techniques. Spin-lattice relaxation times were measured at low fields (T(1rho)) and at high fields (T(1)) using nonselective and selective excitation pulse sequences. The short relaxation time magnetization components in T(1rho) ( approximately 8% signal) and nonselective T(1) ( approximately 5% signal) experiments were significantly altered with PG degradation. In addition, a magnetization component ( approximately 5% signal) with a "fast " T(1) approximately 7 ms was observed in the T(1) experiment involving selective excitation. This fast T(1) was at least 10 times shorter than the short T(1) in the nonselective experiment and was associated with a strong magnetization exchange mechanism between collagen and PG. The results suggest that T(1rho) and T(1) (nonselective and selective) relaxation based MRI techniques, which focus on the short relaxation time magnetization components, have the potential of detecting molecular abnormalities associated with early OA earlier than single, long relaxation time component approaches.

Algorithms↗

PubMed2003

Intra-articular hyaluronan therapy.

Viscosupplementation, in which hyaluronan derivatives are injected into the intra-articular space of osteoarthritic joints, is now widely used to treat knee osteoarthritis (OA). No viscosupplements have been approved for osteoarthritic joints other than the knee. To date, no clinical trials using viscosupplements to treat ankle or foot OA have been published. However, the mechanisms thought to be responsible for viscosupplementation's therapeutic effects would likely apply in any synovial joint. A goal of this article is to stimulate interest in research to assess the potential role of viscosupplementation in treating foot and ankle OA.

Animals↗