Biomedical subjects

Roberta Lamb

Publications and source records attributed to Roberta Lamb.

4 recordsLinked to original sources

PubMed2007

Biochemical and functional analyses of the human Toll-like receptor 3 ectodomain.

The structure of the human Toll-like receptor 3 (TLR3) ectodomain (ECD) was recently solved by x-ray crystallography, leading to a number of models concerning TLR3 function (Choe, J., Kelker, M. S., and Wilson, I. A. (2005) Science 309, 581-585; Bell, J. K., Botos, I., Hall, P. R., Askins, J., Shiloach, J., Segal, D. M., and Davies, D. R. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 10976-10980) The structure revealed four pairs of cysteines that are putatively involved in disulfide bond formation, several residues that are predicted to be involved in dimerization between ECD subunits, and surfaces that could bind to poly(I:C). In addition, there are two loops that protrude from the central solenoid structure of the protein. We examined the recombinant TLR3 ECD for disulfide bond formation, poly(I:C) binding, and protein-protein interaction. We also made over 80 mutations in the residues that could affect these features in the full-length TLR3 and examined their effects in TLR3-mediated NF-kappaB activation. A number of mutations that affected TLR3 activity also affected the ability to act as dominant negative inhibitors of wild type TLR3. Loss of putative RNA binding did not necessarily affect dominant negative activity. All of the results support a model where a dimer of TLR3 is the form that binds RNA and activates signal transduction.

Amino Acid Sequence↗

PubMed2006

Healthcare practice ISOlation: articulating systems that drift toward higher quality.

Can higher quality healthcare practices emerge from the development and use of a loosely integrated set of intranets? This paper examines that question through a series of empirical examples that draw on data from one healthcare organization that was part of a multi-year, multi-industry study of intranets. Some of this organization's intranets link clinical practice guidelines to healthcare delivery, in ways that mimic manufacturing sector efforts to improve product quality and reliability. Others act as staging grounds and information repositories for coordinating responses to new rulings and changing interpretations of how to implement recently enacted healthcare legislation. This activity is reminiscent of coordinated responses, among firms and their legal counsel, to new legislation in other industries, like telecommunications; and to wide-reaching regulatory efforts, like environmental protection. Although the technologies have changed and the legislative objectives vary greatly, organizational approaches to such improvements are less varied. Ironically, these overarching similarities focus attention on the need for continued articulation of changes and local differences in information system use, and the ability of boundary-spanners to introduce ways of working that bridge these gaps and refine healthcare practices that drift toward higher quality.

Computer Communication Networks↗

PubMed2006

A rapid and efficient method for generating anti-variable region monoclonal antibodies using type-1 interferons as immune modulators.

The generation of anti-variable region monoclonal antibodies (mAbs) against therapeutic antibodies is essential in the pharmacokinetic/pharmacodynamic (PK/PD) assessments of the drugs in clinical study samples. Sandwich EIA and other methods are typically employed to achieve sensitivity and selectivity for the PK/PD analyses. These assays usually require generation of mAb reagents that bind specifically to the drug in non-competing pair combinations. Thus, large panels of anti-variable region mAbs must be generated in an expeditious manner to increase the probability of success. Herein we describe a novel immunization method that utilizes type 1 interferons (IFNs) as immunomodulators coupled with an agonistic anti-CD40 mAb as a B cell proliferative agent to drive immune responses. This novel protocol allows for rapid and robust mAb reagent generation without the use of conventional protein-denaturing adjuvants. The use of IFNs allowed for the generation of comparable and in some cases, increased numbers of anti-variable region mAbs in a dramatically shorter timeframe. This IFN based, immunostimulatory approach utilizing a non-denaturing adjuvant, likely presents conformational epitopes and may optimize the humoral response for the rapid generation of anti-variable region reagents to therapeutic mAb candidates.

Adjuvants, Immunologic↗

PubMed2002

Managing managed care: the enabling role of IS/IT.

In their conceptualization of the principal/agent relationship, Jensen and Meckling were not referring to a knowledge worker (KM) agent. Agency theory is extended to the context of a KW agent to identify a key role for IS/IT in facilitating the monitoring function. To test this, the dynamics of a critical principal-KW agent relationship in the health-care industry are investigated It is demonstrated that IS/IT goes beyond just alleviating the agency problem to enabling the KW agent to perform "self-monitoring". The results are significant for health care, agency relationships and the use of IS/IT with knowledge workers.

Faculty↗