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Biomedical subjects

Kenneth R Diller

Publications and source records attributed to Kenneth R Diller.

14 recordsLinked to original sources
PubMed2006

Stress protein expression kinetics.

In all organisms there is an elevated synthesis of a select family of "stress proteins" in response to a broad array of environmentally driven stress vectors including elevated or depressed temperature, changes in pH, treatment with many classes of chemicals, ischemia, desiccation, and UV irradiation. The presence of stress proteins, often termed heat shock proteins (HSPs), has been recognized for more than four decades, and there is an extensive literature that addresses the structure and properties of HSPs, their function in normal and injured cells and tissues, and the molecular mechanisms of HSP expression in response to stress. Owing to this substantial aggregate of research, there is a growing appreciation of the potential for manipulating the magnitude and timing of elevated HSP expression to achieve targeted therapeutic objectives. The successful realization of this potential requires an understanding of the kinetics of the HSP expression process in response to sublethal stress regimens along with the ability to model the governing events in the process to design practical protocols that could be applied in therapeutic settings. Significant progress has been made in recent years in defining and developing capabilities in these two areas.

Adaptation, Physiological↗
PubMed2005

Transport processes in biomedical systems: a roadmap for future research directions.

A workshop was convened at Bethesda, Maryland on May 5 and 6, 2004 under the sponsorship of the NSF and NIH with the objectives of identifying emerging intellectual opportunities and applications in biotransport sciences and of guiding future research in the field. Approximately 50 leading researchers in the fields of fluid, heat, and mass biotransport were presented forward-looking perspectives and discussed how to synthesize broad cross-disciplinary areas: this defined guidelines for a roadmap document. Applications were presented in the context of disease analysis and diagnosis, therapy and prevention, and for physiologic and engineered living systems. The roadmap prioritizes specific research thrusts that reflect projected impacts on intellectuals, medical, and biological advances. Several overarching themes emerged. Most central is the expanded integration of fundamental transport sciences into the understanding of living systems and the great potential of patient specific modeling in designing a broad array of medical procedures.

Biological Transport↗
PubMed2005

Teaching for adaptive expertise in biomedical engineering ethics.

This paper considers an approach to teaching ethics in bioengineering based on the How People Learn (HPL) framework. Curricula based on this framework have been effective in mathematics and science instruction from the kindergarten to the college levels. This framework is well suited to teaching bioengineering ethics because it helps learners develop "adaptive expertise". Adaptive expertise refers to the ability to use knowledge and experience in a domain to learn in unanticipated situations. It differs from routine expertise, which requires using knowledge appropriately to solve routine problems. Adaptive expertise is an important educational objective for bioengineers because the regulations and knowledge base in the discipline are likely to change significantly over the course of their careers. This study compares the performance of undergraduate bioengineering students who learned about ethics for stem cell research using the HPL method of instruction to the performance of students who learned following a standard lecture sequence. Both groups learned the factual material equally well, but the HPL group was more prepared to act adaptively when presented with a novel situation.

Adult↗
PubMed2005

Correlation of HSP70 expression and cell viability following thermal stimulation of bovine aortic endothelial cells.

Thermal preconditioning protocols for cardiac cells were identified which produce elevated HSP70 levels while maintaining high cell viability. Bovine aortic endothelial cells were heated with a water bath at temperatures ranging from 44 to 50 degrees C for periods of 1-30 min. Thermal stimulation protocols were determined which induce HSP70 expression levels ranging from 2.3 to 3.6 times the control while maintaining cell viabilities greater than 90%. An Arrhenius injury model fit to the cell damage data yielded values of A = 1.4 X 10(66) s(-1) and Ea = 4.1 X 10(5) J/mol. Knowledge of the injury parameters and HSP70 kinetics will enhance dosimetry guideline development for thermal stimulation of heat shock proteins expression in cardiac tissue.

Adaptation, Physiological↗
PubMed2005

Thermally induced injury and heat-shock protein expression in cells and tissues.

Heat-shock proteins (HSPs) are critical components of a cell's defense mechanism against injury associated with adverse stresses. Initiating insults, such as elevated or depressed temperature, diminished oxygen, and pressure, increase HSP expression and can protect cells against subsequent, otherwise lethal, insults. Although HSPs are very beneficial to the normal cell, cancer cells can also use HSPs in response to stresses associated with various therapies (hyperthermia, chemotherapy, radiation), mitigating injury incurred by these treatments. Hyperthermia is a common treatment option for prostate cancer. HSPs can be induced in regions of the tumor where temperatures are insufficient to cause lethal thermal necrosis. Elevated HSP expression can enhance tumor cell viability and impart increased resistance to subsequent chemotherapy and radiation treatments, thereby promoting tumor recurrence. An understanding of the structure, function, and thermally stimulated HSP kinetics and cell injury for prostate cancer cells is essential to designing effective hyperthermia protocols. Measured thermally induced cellular HSP expression and injury data can be employed to develop a treatment planning model for optimization of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

Amino Acid Sequence↗
PubMed2004

Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy.

We describe a method for en face phase-contrast imaging of cells with a fiber-based differential phase-contrast optical coherence microscopy system. Recorded en face images are quantitative phase-contrast maps of cells due to spatial variation of the refractive index and (or) thickness of various cellular components. Quantitative phase-contrast images of human epithelial cheek cells obtained with the fiber-based differential phase-contrast optical coherence microscopy system are presented.

Cheek↗
PubMed2004

Measurement and simulation of water and methanol transport in algal cells.

BACKGROUND: Experimental data and a complementary biophysical model are presented to describe the dynamic response of a unicellular microalga to osmotic processes encountered during cryopreservation. METHOD OF APPROACH: Chlorococcum texanum (C. texanum) were mounted on a cryoperfusion microscope stage and exposed sequentially to various solutions of sucrose and methanol. Transient volumetric excursions were determined by capturing images of cells in real time and utilizing image analysis software to calculate cell volumes. A biophysical model was applied to the data via inverse analysis in order to determine the plasma membrane permeability to water and to methanol. The data were also used to determine the elastic modulus of the cell wall and its effect on cell volume. A three-parameter (hydraulic conductivity (Lp), solute permeability; (omega), and reflection coefficient, (sigma)) membrane transport model was fit to data obtained during methanol perfusion to obtain constitutive property values. These results were compared with the property values obtained for a two coefficient (Lp and omega) model. RESULTS: The three-parameter model gave a value for sigma not consistent with practical physical interpretation. Thus, the two-coefficient model is the preferred approach for describing simultaneous water and methanol transport. The rate of both water and methanol transport were strongly dependent on temperature over the measured temperature range (25 degrees C to -5 degrees C) and cells were appreciably more permeable to methanol than to water at all measured temperatures. CONCLUSION: These results may explain in part why methanol is an effective cryoprotective agent for microalgae.

Biological Transport↗
PubMed2003

Comparison of thermal insulation performance of fibrous materials for the advanced space suit.

The current multi-layer insulation used in the extravehicular mobility unit (EMU) will not be effective in the atmosphere of Mars due to the presence of interstitial gases. Alternative thermal insulation means have been subjected to preliminary evaluation by NASA to attempt to identify a material that will meet the target conductivity of 0.005 W/m-K. This study analyzes numerically the thermal conductivity performance for three of these candidate insulating fiber materials in terms of various denier (size), interstitial void fractions, interstitial void media, and orientations to the applied temperature gradient to evaluate their applicability for the new Mars suit insulation. The results demonstrate that the best conductive insulation is achieved for a high-void-fraction configuration with a grooved fiber cross section, aerogel void medium, and the fibers oriented normal to the heat flux vector. However, this configuration still exceeds the target thermal conductivity by a factor of 1.5.

Computer Simulation↗
PubMed2003

Kinetics study of endogenous heat shock protein 70 expression.

The purpose of this study was to determine the kinetics of HSP70 expression in response to mild thermal stress. The rationale is to produce a basis for design of optimal heating methods to induce HSP70 expression for preconditioning in cardiac surgery. Bovine aortic endothelial cells were heated at 42 degrees C for 0.5 to 5 hours followed by 37 degrees C recovery for 1 to 48 hours. Quantitative analysis of western blot results showed HSP70 expression kinetics is a coupled function of heating temperature and time and of post-heating duration. Bimodal HSP70 expression kinetics were identified which may be an important cause of the "second window of protection" observed by other researchers.

Adaptation, Physiological↗
PubMedDate not supplied

Adapting adult scald safety standards to children.

Scald burns by domestic tap water constitute a painful, potentially debilitating, and sometimes-fatal form of thermal injury. In this setting, the very young and older members of the population are particularly susceptible, owing in part to having thinner skin, which renders them more susceptible to thermal insult. Various codes have set forth a safety standard for maximum delivery temperature of domestic tap water at 120 degrees F (48.9 degrees C), based on adult susceptibility to burns. This work addresses the issue of how the current safety standard for tap water temperature could be adjusted to provide a level of protection to children equivalent to that for an adult at 120 degrees F. A well-accepted mathematical model for predicting burn injury as a function of applied surface temperature and time is used to identify these equivalent conditions. Data from the literature of sonographic measurements indicate a representative ratio of child to adult skin thickness of 0.72. The mathematical model shows that the equivalent surface temperature for a threshold scald injury in children is dependent on the depth into the skin at which the injury is identified. For example, the injury produced by a 120 degrees F, 10-second exposure at a depth of 600 microm in an adult is matched in a child at 72% of the depth (432 microm) by an insult of 115.9 degrees F for the same duration. The recommendation is that existing hot water standards be reduced by 3 to 4 degrees F to provide an equivalent level of scald protection to children.

Accidents, Home↗
PubMedDate not supplied

A model for assessing ignition, flame spread, and burn hazard potential of a multilayered jacket.

An analysis is presented of ignition, flame spread, and skin burn associated with the ignition and burning of a multilayered jacket. The important physical processes can all be detailed based on simple thermophysical modeling. The ignition process associated with proximity to a radiant heat source is analyzed to see how a change in external (outer) fabric could have diminished the likelihood of ignition. Once the composite jacket has been ignited, the flame spread process is responsible for the heat transfer to the skin that causes the burn. We analyze the effects of the jacket innermost material on flame spread and on possible burn damage. We show how available thermophysical property data can be used to estimate the effect of inner layer material on burn event duration. Finally, given best-available data on the heat transfer rates between a burning inner layer and skin, we examine the kinetics of skin burn damage to determine the most likely injury that would result.

Back↗
PubMedDate not supplied

Optimizing heat shock protein expression induced by prostate cancer laser therapy through predictive computational models.

Thermal therapy efficacy can be diminished due to heat shock protein (HSP) induction in regions of a tumor where temperatures are insufficient to coagulate proteins. HSP expression enhances tumor cell viability and imparts resistance to chemotherapy and radiation treatments, which are generally employed in conjunction with hyperthermia. Therefore, an understanding of the thermally induced HSP expression within the targeted tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of the overall tissue response. A treatment planning computational model capable of predicting the temperature, HSP27 and HSP70 expression, and damage fraction distributions associated with laser heating in healthy prostate tissue and tumors is presented. Measured thermally induced HSP27 and HSP70 expression kinetics and injury data for normal and cancerous prostate cells and prostate tumors are employed to create the first HSP expression predictive model and formulate an Arrhenius damage model. The correlation coefficients between measured and model predicted temperature, HSP27, and HSP70 were 0.98, 0.99, and 0.99, respectively, confirming the accuracy of the model. Utilization of the treatment planning model in the design of prostate cancer thermal therapies can enable optimization of the treatment outcome by controlling HSP expression and injury.

Animals↗
PubMedDate not supplied

Dehydration mechanism of optical clearing in tissue.

Previous studies identified various mechanisms of light scattering reduction in tissue induced by chemical agents. Our results suggest that dehydration is an important mechanism of optical clearing in collagenous and cellular tissue. Photographic and optical coherence tomography images indicate that air-immersed skin and tendon specimens become similarly transparent to glycerol-immersed specimens. Transmission electron microscopy images reveal that dehydration causes individual scattering particles such as collagen fibrils and organelles to become more densely packed, but does not significantly alter size. A heuristic particle-interaction model predicts that the scattering particle volume fraction increase can contribute substantially to optical clearing in collagenous and cellular tissue.

Animals↗