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Biomedical subjects

Bruce Dunn

Publications and source records attributed to Bruce Dunn.

8 recordsLinked to original sources
PubMed2005

Engineering of vault nanocapsules with enzymatic and fluorescent properties.

One of the central issues facing the emerging field of nanotechnology is cellular compatibility. Nanoparticles have been proposed for diagnostic and therapeutic applications, including drug delivery, gene therapy, biological sensors, and controlled catalysis. Viruses, liposomes, peptides, and synthetic and natural polymers have been engineered for these applications, yet significant limitations continue to prevent their use. Avoidance of the body's natural immune system, lack of targeting specificity, and the inability to control packaging and release are remaining obstacles. We have explored the use of a naturally occurring cellular nanoparticle known as the vault, which is named for its morphology with multiple arches reminiscent of cathedral ceilings. Vaults are 13-MDa ribonucleoprotein particles with an internal cavity large enough to sequester hundreds of proteins. Here, we report a strategy to target and sequester biologically active materials within the vault cavity. Attachment of a vault-targeting peptide to two proteins, luciferase and a variant of GFP, resulted in their sequestration within the vault cavity. The targeted proteins confer enzymatic and fluorescent properties on the recombinant vaults, both of which can be detected by their emission of light. The modified vaults are compatible with living cells. The ability to engineer vault particles with designed properties and functionalities represents an important step toward development of a biocompatible nanocapsule.

Biological Transport, Active↗
PubMed2005

Photo-induced proton gradients and ATP biosynthesis produced by vesicles encapsulated in a silica matrix.

Sol-gel immobilization of soluble proteins has proven to be a viable method for stabilizing a wide variety of proteins in transparent inorganic matrices. The encapsulation of membrane-bound proteins has received much less attention, although work in this area suggests potential opportunities in microarray technology and high-throughput drug screening. The present paper describes a liposome/sol-gel architecture in which the liposome provides membrane structure and protein orientation to two transmembrane proteins, bacteriorhodopsin (bR) and F(0)F(1)-ATP synthase; the sol-gel encapsulation converts the liposomal solution into a robust material without compromising the intrinsic activity of the incorporated proteins. Here we report on two different proteoliposome-doped gels (proteogels) whose properties are determined by the transmembrane proteins. Proteogels containing bR proteoliposomes exhibit a stable proton gradient when irradiated with visible light, whereas proteogels containing proteoliposomes with both bR and F(0)F(1)-ATP synthase couple the photo-induced proton gradient to the production of ATP. These results demonstrate that materials based on the liposome/sol-gel architecture are able to harness the properties of transmembrane proteins and enable a variety of applications, from power generation and energy storage to the powering of molecular motors, and represent a new technology for performing complex chemical synthesis in a solid-state matrix.

Adenosine Triphosphate↗
PubMed2005

Nanostructured systems for biological materials.

The sol-gel process is a chemical technique for immobilizing biomolecules in an inorganic, transparent matrix. The dopant biomolecules reside in an interconnected mesoporous network and become part of the nanostructured architecture of the entire material. In this chapter, we review the sol-gel immobilization approach and discuss how it leads to the stabilization of a number of proteins against aggressive chemical and thermal environments. We also review the sensor applications of this material that result from having analyte molecules diffuse through the matrix and reach the immobilized biomolecule.

Biosensing Techniques↗
PubMed2004

Regression of significant tricuspid regurgitation after mitral balloon valvotomy for severe mitral stenosis.

BACKGROUND: Significant tricuspid regurgitation (TR) is occasionally associated with severe mitral stenosis and has an adverse impact on morbidity and mortality in patients undergoing mitral valve surgery. However, the effect of successful mitral balloon valvotomy (MBV) on significant TR is not fully elucidated. The aim of this study was to investigate TR after MBV in patients with severe mitral stenosis. METHODS: We analyzed the data of 53 patients with significant TR (grade > or =2, on a 1 to 3 scale) from the mitral balloon valvotomy database at our hospital. Patients were evaluated by Doppler echocardiography before valvotomy and at follow-up 1 to 13 years after MBV. Patients were divided into group A (27 patients), in whom TR regressed by > or =1 scale, and group B (26 patients), in whom TR did not regress. RESULTS: The Doppler-determined pulmonary artery systolic pressure was initially higher and decreased at follow-up more in group A (from 70.7 +/- 23.8 to 36.5 +/- 8.3 mm Hg; P < .0001) than in group B (from 48.7 +/- 17.8 to 41.6 +/- 13.1 mm Hg; P = NS). Compared with patients in group B, patients in group A were younger (25 +/-10 vs 35 +/- 11 years; P < .005), had higher prevalence of functional TR (85% vs 8%; P < .0001), and had lower incidence of atrial fibrillation (7% vs 38%; P < .005). Significant decrease in right ventricular end-diastolic dimension after MBV was noted in group A but not in group B. The mitral valve area at late follow-up was larger in group A than in group B (1.8 +/- 0.3 vs 1.6 +/- 0.3 cm2; P < .05). CONCLUSIONS: Regression of significant TR after successful MBV in patients with severe mitral stenosis was observed in patients who had severe pulmonary hypertension. This improvement in TR occurred even in the presence of organic tricuspid valve disease.

Adult↗
PubMed2004

Insulin, macronutrient intake, and physical activity: are potential indicators of insulin resistance associated with mortality from breast cancer?

High levels of insulin have been associated with increased risk of breast cancer, and poorer survival after diagnosis. Data and sera were collected from 603 breast cancer patients, including information on diet and physical activity, medical history, family history, demographic, and reproductive risk factors. These data were analyzed to test the hypothesis that excess insulin and related factors are directly related to mortality after a diagnosis of breast cancer. The cohort was recruited from breast cancer patients treated at the British Columbia Cancer Agency between July 1991 and December 1992. Questionnaire and medical record data were collected at enrollment and outcomes were ascertained by linkage to the BC Cancer Registry after 10 years of follow-up. The primary outcome of interest was breast cancer-specific mortality (n = 112). Lifestyle data were analyzed using Cox proportional hazards regression models to relate risk factors to outcomes, controlling for potential confounders, such as age and stage at diagnosis. Data for biological variables were analyzed as a nested case-control study due to limited serum volumes, with at least one survivor from the same cohort as a control for each breast cancer death, matched on stage and length of follow-up. High levels of insulin were associated with poorer survival for postmenopausal women [odds ratio, 1.9; 95% confidence interval (CI), 0.7-6.6, comparing highest to lowest tertile, P trend = 0.10], while high dietary fat intake was associated with poorer survival for premenopausal women (relative risk, 4.8; 95% CI, 1.3-18.1, comparing highest to lowest quartile). Higher dietary protein intake was associated with better survival for all women (relative risk, 0.4; 95% CI, 0.2-0.8, comparing highest to lowest quartile).

Adult↗
PubMed2002

Placement and characterization of pairs of luminescent molecules in spatially separated regions of nanostructured thin films.

Methods of making mesostructured sol-gel silicate thin films containing two different molecules deliberately placed in two different spatially separated regions in a one-step, one-pot preparation are developed and demonstrated. When the structure-directing agent is the surfactant cetyltrimethylammonium bromide, the structure is 2-D hexagonal with lattice spacings between 31.6 and 42.1 angstroms depending on the dopant molecules and their concentrations. The three general strategies that are used to place the molecules are philicity (like dissolves like), bonding, and bifunctionality. These strategies take advantage of the different chemical and physical properties of the regions of the films. These regions are the inorganic silicate framework, the hydrophobic organic interior of the micelles, and the ionic interface between them. Luminescent molecules that possess the physical and chemical properties appropriate for the desired strategies are chosen. Lanthanide and ruthenium complexes with condensable trialkoxysilane groups are incorporated into the silicate framework. 1,4-Naphthoquinone, pyrene, rhodamine 6G and coumarin 540A, and lanthanides with no condensable trialkoxysilanes occupy the hydrophobic core of micelles by virtue of their hydrophobicity. The locations of the molecules are determined by luminescence spectroscopy and by luminescence lifetime measurements. In all cases, the long-range order templated into the thin film is verified by X-ray diffraction. The simultaneous placement of two molecules in the structured film and the maintenance of long-range order require a delicate balance among film preparation methodology, design of the molecules to be incorporated in specific regions, and concentrations of all of the species.

Cetrimonium↗
PubMed2000

An Evaluation of Plasma Antioxidant Levels and the Risk of Breast Cancer: A Pilot Case Control Study.

Antioxidant micronutrients found in fruits and vegetables have been shown in numerous studies to be protective against cancer. There is limited information on the relationship between blood antioxidant micronutrient levels and cancer among ethnic minorities. We conducted a pilot case-control study to evaluate the potential for accrual to a study of the association of plasma levels of beta-carotene, retinol, lycopene, alpha-tocopherol, and gamma-tocopherol with breast cancer risk among African American and Caucasian women seen at a large university medical center in Detroit. Cases included women with newly diagnosed invasive breast cancer who had not yet had any cancer-related therapy and who were age-matched to controls within 5 years. Plasma levels of micronutrients were analyzed by high-pressure liquid chromatography. Compared to the expected accrual based on cancer registry data, only 26% (11/42) of African American women with breast cancer enrolled, while 100% (16/16) of Caucasian cases enrolled. Control women were quickly accrued with only a 6% refusal rate. Among African American women, there was a weak inverse association between plasma lycopene levels and breast cancer risk, with a mean level of 0.17 &mgr;mol/L (SD = 0.18) among cases, and 0.24 &mgr;mol/L (SD = 0.18) among controls (p = 0.09). There was a weak direct association between plasma retinol levels and breast cancer risk among African American women, with a mean retinol level of 2.37 &mgr;mol/L (SD = 0.73) among cases and 1.98 &mgr;mol/L (SD = 0.49) among controls (p = 0.132). The interaction effect of race and lycopene was statistically significant (p = 0.048). Among the lowest lycopene tertile, the risk of breast cancer among Caucasian women was 0.76 and the risk of breast cancer among African American women was 2.29, although these odds ratios were not statistically significant. Our recruitment efforts were largely successful among Caucasian cases and controls, and African American controls, but were unsuccessful among African American cases. The results suggest a possible relationship between plasma lycopene level and breast cancer among African American women, but these results should be confirmed by a larger, more definitive study.

Journal Article↗