生物化学技术

Despite two generations of vascular prosthetic research, the optimal arterial surgical replacement for aortocoronary, femoropopliteal, and femorodistal reconstruction remains autogenous saphenous vein. It has become apparent from numerous investigations that the m ...

Although the administration of insulin by injection is clearly a life-saving intervention for patients devoid of β-cells, this approach falls short of the remarkable titration of insulin delivery and consequent control of glucose levels achieved by normal, healthy individuals. In t ...

Recent advances in our ability to microfabricate tissue culture environments (1), and to store and retrieve microscopy data in a digital format, have made it increasingly possible to study fundamental aspects of neuronal migration and response to environmental cues. Neuronal migrat ...

Cell therapy involving the transplantation of cells or tissues with specific differentiated functions has potential in the treatment of human disease. However, the need for immunosuppressive drugs may lead to a variety of serious side effects. One approach to minimizing or eliminati ...

Cell-cell and cell-matrix contacts play an important role in immunological processes and tissue organization. It has been shown that in many cases, cell adhesion is mediated by specialized adhesion receptors that are typically anchored in the cell membrane with mol wt ranging from 50 to 200 kD ...

Cartilage functionality is defined, in part, in terms of the ability of the extracellular matrix to support a mechanical load. It has been shown that such mechanical loading can influence the biological response of the chondrocytes that are embedded in the extracellular matrix. Cultured ti ...

Leukocytes must bind to vascular endothelium under conditions of flow to perform their appropriate physiological functions, which require trafficking into and out of the tissue space surrounding blood vessels. Trafficking into tissues is required of neutrophils during the acute ...

When a leukocyte enters a blood vessel, it may continue to move with flowing blood, collide with the vessel wall, adhere transiently or stably, and finally extravasate (1). These interactions are governed by both local hydrodynamic and adhesive forces. The former are determined by the vessel di ...

Over the past 20 yr, great strides have been made toward understanding the role of fluid hemodynamic forces in the vascular wall homeostasis at the molecular level. In vivo studies have demonstrated that blood vessels are adaptive to physiological changes in blood flow, with vessels tending to ...

Transport of nutrients and metabolites in many bioartificial tissue constructs relies exclusively on diffusion, i.e., on the presence of a concentration gradient between the inside of the construct and the surrounding milieu. A quantitative evaluation of the rate of diffusional pro ...

Size-exclusion chromatography (gel filtration) is a widely used method to determine the molecular weight of a protein. Often, the elution volume of several standard proteins is plotted against their known molecular weight to generate a standard curve, which is then used to determine the mo ...

Owing to simplicity, speed, cost advantage, and a generally high product yield, expression in Escherichia coli is the method of choice for the production of large amounts of protein. However, because of the high expression level, proteins often accumulate within the cells as insoluble aggre ...

Selective inhibitors of cyclic nucleotide phosphodiesterases (PDEs) have been widely studied as therapeutic agents for the treatment of various human diseases. Three-dimensional structures are essential for the design of highly selective inhibitors, but their availabili ...

The development of gene-targeting techniques has ushered in a new era in mouse genetics. Two discoveries have been instrumental: the finding that an exogenous DNA introduced in mammalian cells can recombine with homologous chromosomal sequences, a process known as gene targeting, and t ...

A PDE2A2-associated protein kinase phosphorylates PDE2A2 in vivo and in vitro to inhibit its catalytic activity. Rat brain PDE2A2 may be solubilized using nona (ethylene glycol) mono dodecyl ether (Lubrol 12A9). PDE2A2 exists in a complex with a protein kinase regulating its activity in an a ...

Recently, it has been shown that enzymes of the cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) family 4 can be directly phosphorylated by extracellular signal-regulated kinase 2 (ERK2). Phosphorylation of PDE4s by ERK2 is dependent on two docking domains ...

Cyclic nucleotide phosphodiesterases (PDEs) have been investigated for years as targets for therapeutic intervention in a number of pathophysiological processes. Phosphodiesterase-5 (PDE5), which is highly specific for guanosine 3′-5′-cyclic-monophosphate (cGMP) at b ...

An absolute majority of cyclic nucleotide phosphodiesterases (PDEs) form catalytic dimers. The structural determinants and functional significance of PDE dimerization are poorly understood. Furthermore, all known dimeric PDEs with the exception of retinal rod guanosine 3′, ...

Cyclic adenosine monophosphate (cAMP) controls the physiological response to many diverse extracellular stimuli. To maintain signal specificity, cAMP-mediated signaling is finely tuned by means of a complex array of proteins that control the spatial and temporal dynamics of the s ...

Rod and cone photoreceptor guanosine 3′5′-cyclic-monophosphate phosphodiesterases (PDEs) are classified into the PDE6 family of cyclic nucleotide PDEs. A unique feature of the PDE6 enzymes is the presence of inhibitory γ-subunits (Pγ). The inhibitory interaction between Pγ and the ...