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Biomedical subjects

Karen Robinson

Publications and source records attributed to Karen Robinson.

10 recordsLinked to original sources
PubMed2006

T-cell stimulating protein A (TspA) of Neisseria meningitidis is required for optimal adhesion to human cells.

T-cell stimulating protein A (TspA) is an immunogenic, T-cell and B-cell stimulating protein of Neisseria meningitidis. Sequence similarity between TspA and FimV, a Pseudomonas aeruginosa protein involved in twitching motility, suggested a link between TspA and type IV pili (Tfp). To determine the role of TspA an isogenic deletion mutant was created. Loss of TspA did not affect twitching motility or piliation indicating that there are functional differences between TspA and FimV. Mutation of tspA led to a significant reduction in adhesion of meningococci to meningothelial and HEp-2 cells, which was not due to a lack of transcription of adjacent genes or pilC1. Other Tfp-mediated phenotypes (i.e. auto-aggregation and transformation competence) were not altered. Our results indicate that the role of TspA in adhesion is unlikely to be directly linked to the function of Tfp. TspA was expressed by all N. meningitidis and Neisseria polysaccharea strains examined but not by Neisseria gonorrhoeae or Neisseria lactamica, although sequences with homology to tspA were present in their genomes. In summary, TspA is a highly conserved antigen that is required for optimal adhesion of meningococci to human cells.

Antigens, Bacterial↗
PubMed2006

Improving health care quality for racial/ethnic minorities: a systematic review of the best evidence regarding provider and organization interventions.

BACKGROUND: Despite awareness of inequities in health care quality, little is known about strategies that could improve the quality of healthcare for ethnic minority populations. We conducted a systematic literature review and analysis to synthesize the findings of controlled studies evaluating interventions targeted at health care providers to improve health care quality or reduce disparities in care for racial/ethnic minorities. METHODS: We performed electronic and hand searches from 1980 through June 2003 to identify randomized controlled trials or concurrent controlled trials. Reviewers abstracted data from studies to determine study characteristics, results, and quality. We graded the strength of the evidence as excellent, good, fair or poor using predetermined criteria. The main outcome measures were evidence of effectiveness and cost of strategies to improve health care quality or reduce disparities in care for racial/ethnic minorities. RESULTS: Twenty-seven studies met criteria for review. Almost all (n = 26) took place in the primary care setting, and most (n = 19) focused on improving provision of preventive services. Only two studies were designed specifically to meet the needs of racial/ethnic minority patients. All 10 studies that used a provider reminder system for provision of standardized services (mostly preventive) reported favorable outcomes. The following quality improvement strategies demonstrated favorable results but were used in a small number of studies: bypassing the physician to offer preventive services directly to patients (2 of 2 studies favorable), provider education alone (2 of 2 studies favorable), use of a structured questionnaire to assess adolescent health behaviors (1 of 1 study favorable), and use of remote simultaneous translation (1 of 1 study favorable). Interventions employing more than one main strategy were used in 9 studies with inconsistent results. There were limited data on the costs of these strategies, as only one study reported cost data. CONCLUSION: There are several promising strategies that may improve health care quality for racial/ethnic minorities, but a lack of studies specifically targeting disease areas and processes of care for which disparities have been previously documented. Further research and funding is needed to evaluate strategies designed to reduce disparities in health care quality for racial/ethnic minorities.

Ethnicity↗
PubMed2005

Host adaptation and immune modulation are mediated by homologous recombination in Helicobacter pylori.

Rearrangement of genomic DNA via homologous recombination provides an alternative mechanism of gene regulation that is essential for successful colonization of the gastric mucosa by Helicobacter pylori. Inoculation of outbred mice with the H. pylori SS1 wild-type strain elicited a T helper (Th) 2 response and established a persistent infection. In contrast, inoculation with an isogenic H. pylori strain defective for homologous recombination elicited a Th1-mediated immune response and clearance of infection within 70 days. We, therefore, demonstrate that recombination is critical for mediating persistence of a microbial pathogen through the induction of ineffective immune responses.

Adaptation, Physiological↗
PubMed2005

T-cell-stimulating protein A elicits immune responses during meningococcal carriage and human disease.

In recognition of the need for immunological memory-inducing components for future Neisseria meningitidis group B vaccines, we previously searched the proteome of N. meningitidis and identified T-cell-stimulating protein A (TspA). This study was designed to confirm the immunogencity of TspA and to examine the subset of T-helper cell responses to the protein in patients and nasopharyngeal carriers. The tspA gene was reconstructed, cloned, and expressed in Escherichia coli, and the recombinant TspA (rTspA) protein was affinity purified. T-cell proliferative responses to rTspA were detected in the peripheral blood mononuclear cells (PBMCs) of convalescent patients and carriers, confirming that TspA-specific T-cell responses were stimulated by invasive disease and nasopharyngeal colonization. Following stimulation of PBMCs with meningococcal lysate, increased frequencies of both Th1 and Th2 cells were observed, indicating that, as during carriage, invasive meningococcal disease induced an unbiased T-helper subset response. A similar unbiased T-helper response was also detected against rTspA in the PBMCs of convalescent patients. The response of PBMCs from the carriers to TspA stimulation, however, was very weak, and the frequencies of cytokine-positive CD4 cells were not significantly greater than the frequencies in unstimulated control cultures. All of the patients and carriers responded with serum antimeningococcal immunoglobulin G (IgG) antibodies, while four of six samples from patients and 5 of 14 samples from carriers contained detectable anti-rTspA IgG antibodies. Taken together, the results of this study confirmed the immunogenicity of TspA in humans during natural meningococcal infection, and therefore, TspA is worthy of further investigation as a possible T-cell stimulating component of future vaccines.

Antigens, Bacterial↗
PubMed2004

Secreted proteins from Neisseria meningitidis mediate differential human gene expression and immune activation.

Meningococcal secreted proteins (MSPs) have been poorly characterized. We hypothesized that MSPs play essential roles in host--bacterial interactions and in the pathogenesis of disease. In order to test this, we examined differential host gene expression in human meningeal-derived cells, in response to endotoxin-depleted MSPs compared to live bacteria. Using expression arrays, upregulated expression of several pro-inflammatory and apoptosis-related genes was found to be induced by MSPs. The transcription and translation of representative genes was confirmed by using various methods. Increased interleukin 8 (IL-8) and cyclooxygenase 2 (COX-2) gene transcription was confirmed using real-time PCR. Upregulated IL-8, IL-6, ICAM-1 and COX-2 protein expression were confirmed by ELISA, flow cytometry or Western immunoblots. Furthermore, exposure of cells to MSPs or live meningococci induced a small significant resistance effect to staurosporine-induced apoptosis. Secreted meningococcal virulence factors are therefore important in inducing host inflammatory responses and resistance to apoptosis, and they are worthy of extensive investigation.

Apoptosis↗
PubMed2004

Neisseria meningitidis-induced death of cerebrovascular endothelium: mechanisms triggering transcriptional activation of inducible nitric oxide synthase.

The intense host response to meningococcus reflects marked functional and morphological alterations in blood-brain barriers. We showed previously that mouse-derived cerebrovascular endothelium responded to meningococcal lysates with a robust nitric oxide (NO) response, resulting in the loss of cell viability. To understand how the NO synthase-2 gene in endothelium is activated by meningococcus, we investigated upstream roles for specific protein kinases. Using known kinase inhibitors, and measuring both mRNA expression and nitrite release, we found MAPK/ERK kinase (MEK)2, p38 kinase and phosphoinositide 3-kinase (but not MEK1 or phospholipase C) to be implicated in the NO synthase-2 response. Recruitment of these kinases by meningococcus did not depend on the prior release of the proinflammatory cytokines tumour necrosis factor alpha or interleukin-1beta from endothelium. These endothelial cells were found to express toll-like receptors (TLR) 2, 4 and 9 and antibodies directed against TLR 2 and 4 (but not TLR 9) blocked the NO synthase-2 response to meningococcus. Both meningococcus-induced translocation of nuclear factor-kB (NF-kB) and endothelial cell death were blocked by a known inhibitor of p38 kinase. Calpain inhibitor-1 blocked the NO synthase-2 response to meningococcus, which is further evidence of a role for NF-kB.

Active Transport, Cell Nucleus↗
PubMed2003

The Vanderbilt Professional Nursing Practice Program: part 1: Growing and supporting professional nursing practice.

Professional practice programs are designed to attract, retain, and reward nurses. This three-part series will describe Vanderbilt's performance-based career advancement system, the Vanderbilt Professional Nursing Practice Program (VPNPP). Part 1 outlines the overall program's foundation, philosophical background, and basic structure. The VPNPP is built upon Benner's work, distinguishing among four levels of practice: novice, competent, proficient, and expert. Work by many in the organization identified the expected behaviors for nurses at each level, which were then used to develop clear process evaluation criteria. Part 2 will examine the performance measurement and evaluation system created to support the program. The process of advancing within the program will be described in part 3.

Academic Medical Centers↗
PubMedDate not supplied

Clinical nurse specialist practice within the Acute Care for Elders interdisciplinary team model.

As the complexity of care increases for hospitalized older adults, the clinical nurse specialist is essential for ongoing development of nursing practice and care standards. This article describes the Acute Care of the Elderly (ACE) model for interdisciplinary management of older adults and clinical specialist responsibilities within this interdisciplinary team. Within the model, clinical care specialists utilize clinical expertise and consultation skills reflecting three spheres of practice related to care of high-risk community-dwelling older adults admitted an acute medical unit. The goal for this patient group is to achieve medical stability while preserving maximum functioning. The Acute Care of the Elderly team members include primary nurses (staff nurses), physicians, clinical care specialists, therapies, social workers, dietitians, pharmacists, and a discharge planner. Under the leadership of the primarily nurse, the team develops a comprehensive care and discharge plan, implemented across a care continuum. Using protocols and working together, the team delivers cost-effective, coordinated care that promotes process improvement resulting in practice that is in alignment with current standards of care.

Activities of Daily Living↗
PubMedDate not supplied

Supervision as professional development for psychiatric mental health nurses.

Clinical supervision is an essential element in the professional development of advanced practice psychiatric mental health nurses, and many interpersonal approaches exist to facilitate this process. This article discusses the issues underlying supervision, the key elements of the supervision process, and the current literature focused on the development of best practices in the conduct of clinical supervision. Recommendations for the implementation of supervision are identified.

Benchmarking↗