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Biomedical subjects

Joanne M Stevens

Publications and source records attributed to Joanne M Stevens.

7 recordsLinked to original sources
PubMed2006

Actin-dependent movement of bacterial pathogens.

Listeria, Rickettsia, Burkholderia, Shigella and Mycobacterium species subvert cellular actin dynamics to facilitate their movement within the host cytosol and to infect neighbouring cells while evading host immune surveillance and promoting their intracellular survival. 'Attaching and effacing' Escherichia coli do not enter host cells but attach intimately to the cell surface, inducing motile actin-rich pedestals, the function of which is currently unclear. The molecular basis of actin-based motility of these bacterial pathogens reveals novel insights about bacterial pathogenesis and fundamental host-cell pathways.

Actins↗
PubMed2005

Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei.

Burkholderia pseudomallei is a Gram-negative facultative intracellular pathogen that enters and escapes from eukaryotic cells using the power of actin polymerization. We have identified a bacterial protein (BimA) that is required for the ability of B. pseudomallei to induce the formation of actin tails. BimA contains proline-rich motifs and WH2-like domains and shares limited homology at the C-terminus with the Yersinia autosecreted adhesin YadA. BimA is located at the pole of the bacterial cell at which actin polymerization occurs and mutation of bimA abolished actin-based motility of the pathogen in J774.2 cells. Transient expression of BimA in HeLa cells resulted in F-actin clustering reminiscent of that seen on WASP overexpression. Antibody-mediated clustering of a CD32 chimera in which the cytoplasmic domain was replaced with BimA resulted in localization of the chimera to the tips of F-actin enriched membrane protrusions. We report that purified truncated BimA protein binds monomeric actin in a concentration-dependent manner in cosedimentation assays and that BimA stimulates actin polymerization in vitro in a manner independent of the cellular Arp2/3 complex.

Actins↗
PubMed2005

Actin-binding proteins from Burkholderia mallei and Burkholderia thailandensis can functionally compensate for the actin-based motility defect of a Burkholderia pseudomallei bimA mutant.

Recently we identified a bacterial factor (BimA) required for actin-based motility of Burkholderia pseudomallei. Here we report that Burkholderia mallei and Burkholderia thailandensis are capable of actin-based motility in J774.2 cells and that BimA homologs of these bacteria can restore the actin-based motility defect of a B. pseudomallei bimA mutant. While the BimA homologs differ in their amino-terminal sequence, they interact directly with actin in vitro and vary in their ability to bind Arp3.

Actin-Related Protein 3↗
PubMed2004

A role for the thiol isomerase protein ERP5 in platelet function.

Formation and rearrangement of disulfide bonds during the correct folding of nascent proteins is modulated by a family of enzymes known as thiol isomerases, which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5 (ERP5), and ERP57. Recent evidence supports an alternative role for this family of proteins on the surface of cells, where they are involved in receptor remodeling and recognition. In platelets, blocking PDI with inhibitory antibodies inhibits a number of platelet activation pathways, including aggregation, secretion, and fibrinogen binding. Analysis of human platelet membrane fractions identified the presence of the thiol isomerase protein ERP5. Further study showed that ERP5 is resident mainly on platelet intracellular membranes, although it is rapidly recruited to the cell surface in response to a range of platelet agonists. Blocking cell-surface ERP5 using inhibitory antibodies leads to a decrease in platelet aggregation in response to agonists, and a decrease in fibrinogen binding and P-selectin exposure. It is possible that this is based on the disruption of integrin function, as we observed that ERP5 becomes physically associated with the integrin beta(3) subunit during platelet stimulation. These results provide new insights into the involvement of thiol isomerases and regulation of platelet activation.

Amino Acid Sequence↗
PubMed2004

Informatics resources to support health care quality improvement in the veterans health administration.

Information systems are increasingly important for measuring and improving health care quality. A number of integrated health care delivery systems use advanced information systems and integrated decision support to carry out quality assurance activities, but none as large as the Veterans Health Administration (VHA). The VHA's Quality Enhancement Research Initiative (QUERI) is a large-scale, multidisciplinary quality improvement initiative designed to ensure excellence in all areas where VHA provides health care services, including inpatient, outpatient, and long-term care settings. In this paper, we describe the role of information systems in the VHA QUERI process, highlight the major information systems critical to this quality improvement process, and discuss issues associated with the use of these systems.

Benchmarking↗
PubMed2004

Tachykinins regulate the function of platelets.

Evidence has been mounting for peripheral functions for tachykinins, a family of neuropeptides including substance P (SP), neurokinin A, and neurokinin B, which are recognized for their roles in the central and peripheral nervous system. The recent discovery of 4 new members of this family, the endokinins (EKA, B, C, and D), which are distributed peripherally, adds support to the notion that tachykinins have physiologic/endocrine roles in the periphery. In the present study we report a fundamental new function for tachykinins in the regulation of platelet function. We show that SP stimulates platelet aggregation, and underlying this is the intracellular mobilization of calcium and degranulation. We demonstrate the presence of the tachykinin receptors NK1 and NK3 in platelets and present evidence for the involvement of NK1 in SP-mediated platelet aggregation. Platelets were found to contain SP-like immunoreactivity that is secreted upon activation implicating SP-like substances in the autocrine/paracrine regulation of these cells. Indeed, NK1-blocking antibodies inhibited aggregation in response to other agonists. Of particular note is the observation that EKA/B cross-react in the SP immunoassay and are also able to stimulate platelet activation. Together our data implicate tachykinins, specifically SP and EKA/B, in the regulation of platelet function.

Blood Platelets↗