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At least 361 records · Page 20Linked to original sources
PubMed1991

Bioengineering in development of the hybrid artificial pancreas.

The hybrid artificial pancreas for treatment of diabetes consists of insulin-secreting pancreatic tissue which is surrounded by a membrane that protects the tissue from rejection by the immune system following implantation. In this paper, we review the alternative therapeutic approaches for diabetes under study and then discuss the technical requirements that must be met by a hybrid device useful to humans. Previous work on intravascular and extravascular immunoisolation devices is reviewed from the standpoint of these requirements, and three critical unresolved issues are discussed: biocompatibility, oxygen supply limitations, and prevention of immune rejection.

Animals↗
PubMed1982

Bioengineering studies of periodic external compression as prophylaxis against deep vein thrombosis-part I: numerical studies.

This paper presents the results of a numerical study of the technique of periodic external compression for the prevention of deep vein thrombosis. In the model the veins of the lower leg are portrayed as a continuous system rather than as discrete elements as in previous models. Consequently, we are able to explore the detailed effects of different modes of compression including (i) uniform compression, the simultaneous application of uniform pressure over the entire lower leg, (ii) graded compression, the application of nonuniform pressure, maximum at the ankle and minimum at the knee, and (iii) wavelike compression, a wave of compression proceeding from the ankle toward the knee. These numerical results indicate that the effectiveness of uniform compression is severely compromised by the formation of a flow-limiting throat at the proximal end of the compression cuff that reduces both the rate at which blood is discharged from the lower leg and the total blood volume removed. Both of these detrimental effects can be avoided by the use of either wavelike of graded compression. Both alternated methods are shown to produce more uniform augmentation of volume flow rate, flow velocity and shear stress, throughout the entire lower leg. In the companion paper, Part II [18] (see following article), these same compression modes are tested using a simple hydraulic model consisting of a single latex tube inside a foam cylinder as a highly simplified representation of a human leg.

Blood Flow Velocity↗
PubMed1982

Bioengineering studies of periodic external compression as prophylaxis against deep vein thrombosis-part II: experimental studies on a stimulated leg.

In this companion paper to "Part I: Numerical Simulations, " we report in vitro experimental studies performed on a simple model leg consisting of a "vein" of thin-walled latex tubing surrounded by "tissue" of open-pore foam rubber. Three modes of periodic external compression, were investigated: i) uniform compression; (ii) graded compression, decreasing from ankle to knee; and (iii) sequential compression, progressing from ankle to knee. The modes are compared on the basis of three hemodynamic criteria: degree of vessel collapse, level of fluid velocity, and level of shear stress. In uniform compression these measures of merit are distributed very nonuniformly along the length of the leg: they are high near the proximal end of the cuff but low elsewhere, a result due to the formation proximally of a partially occlusive throat. The latter does not form in either graded or sequential compression, with the consequence that favorable values of the three measures of merit occur more uniformly along the length of the pressurized region. It is concluded that either the graded or sequential mode of compression, or perhaps a combination of the two, would be more effective than uniform compression as a prophylaxis against deep vein thrombosis.

Gravity Suits↗
PubMed1999

Characterization of a bioengineered chimeric Na+-nucleoside transporter.

Na+-dependent nucleoside transporters mediate the intracellular uptake of purine and pyrimidine nucleosides. The N1, N2, and N3 Na+-nucleoside transporters differ in substrate selectivity. N1 is purine-selective, N2 is pyrimidine-selective, and N3 is broadly selective. Recently, we created a chimeric transporter, T8, from the cloned rat N1 and N2 transporters. Whereas most chimeric proteins exhibit the characteristics of one of the two parent proteins, limited studies suggested that T8 possesses either a combined substrate selectivity of N1 and N2 or the selectivity of N3. The purpose of this study was to determine the substrate profile, transport mechanisms, and Na+-coupling stoichiometry of T8 and to compare these measurements with those of wild-type N1, N2, and N3. In Xenopus laevis oocytes expressing T8, Na+-dependent uptake of 3H-labeled purine (adenosine, inosine, and guanosine) and pyrimidine nucleosides (uridine, thymidine, and cytidine) was significantly enhanced (3.5-18.6-fold), which suggests that T8 accepts both purine and pyrimidine nucleosides as permeants. T8-mediated uptake of [3H]thymidine was competitively inhibited by inosine, and T8-mediated uptake of [3H]inosine was competitively inhibited by thymidine, which suggests that purine and pyrimidine nucleosides share a common binding site. Base-modified ribo- and 2'-deoxyribonucleosides were potent inhibitors of T8. In contrast, 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, and 3'-azidothymidine, which are known inhibitors of N1 or N2, did not inhibit T8-mediated uptake. These data suggest that the substrate profile of T8 is not a combination of those of N1 and N2; rather, it is similar to that of N3. However, the Na+/nucleoside stoichiometric ratio of T8 was determined to be 1, consistent with both N1 and N2 but different from N3.

Animals↗
PubMed2006

Overproduction of wild-type and bioengineered derivatives of the lantibiotic lacticin 3147.

Lacticin 3147 is a broad-spectrum two-peptide lantibiotic whose genetic determinants are located on two divergent operons on the lactococcal plasmid pMRC01. Here we introduce each of 14 subclones, containing different combinations of lacticin 3147 genes, into MG1363 (pMRC01) and determine that a number of them can facilitate overproduction of the lantibiotic. Based on these studies it is apparent that while the provision of additional copies of genes encoding the biosynthetic/production machinery and the regulator LtnR is a requirement for high-level overproduction, the presence of additional copies of the structural genes (i.e., ltnA1A2) is not.

Bacterial Proteins↗
PubMed2000

Bioengineering models of cell signaling.

Strategies for rationally manipulating cell behavior in cell-based technologies and molecular therapeutics and understanding effects of environmental agents on physiological systems may be derived from a mechanistic understanding of underlying signaling mechanisms that regulate cell functions. Three crucial attributes of signal transduction necessitate modeling approaches for analyzing these systems: an ever-expanding plethora of signaling molecules and interactions, a highly interconnected biochemical scheme, and concurrent biophysical regulation. Because signal flow is tightly regulated with positive and negative feedbacks and is bidirectional with commands traveling both from outside-in and inside-out, dynamic models that couple biophysical and biochemical elements are required to consider information processing both during transient and steady-state conditions. Unique mathematical frameworks will be needed to obtain an integrated perspective on these complex systems, which operate over wide length and time scales. These may involve a two-level hierarchical approach wherein the overall signaling network is modeled in terms of effective "circuit" or "algorithm" modules, and then each module is correspondingly modeled with more detailed incorporation of its actual underlying biochemical/biophysical molecular interactions.

Algorithms↗