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Robert Anderson

Publications and source records attributed to Robert Anderson.

31 records · Page 2Linked to original sources
PubMed2003

Construction of adeno-associated virus packaging plasmids and cells that directly select for AAV helper functions.

Recombinant adeno-associated virus type 2 (rAAV) has promise for use as a gene therapy vector. Potential problems in the production of rAAV stocks are both the limited amount of recombinant virus that is produced by traditional methods and the possibility of wild-type replication competent adeno-associated virus (wtAAV) contamination. The presence of these contaminants is largely dependent upon the helper plasmid used. Whilst wtAAV is not a pathogen, the presence of these contaminants is undesirable as they may affect experiments concerning the biology of rAAV. Additionally as protocols using rAAV with altered tropism are becoming more prevalent, it is important that no recombination be permitted that may cause the creation of a replication competent AAV with modified (targeting) capsids. Many experimental protocols require the generation of large amounts of high titre rAAV stocks. We describe the production of several AAV helper plasmids and cell lines designed to achieve this goal. These plasmids possess split AAV rep and cap genes to eliminate the production of wtAAV and they possess a selection mechanism which is operatively linked to expression from the AAV cap gene. This allows positive selection of those cells expressing the highest level of the structural capsid proteins and therefore those cells which yield the highest amount of rAAV.

CD4 Antigens↗
PubMed2003

Activation of vascular endothelial cells by IL-1alpha released by epithelial cells infected with respiratory syncytial virus.

Although pulmonary inflammation is a serious, sometimes life-threatening, consequence of respiratory syncytial virus (RSV) infection, the mechanisms involved are not well understood. Since the process of inflammation is initiated by a complex series of events including the activation of specific adhesion molecules on vascular endothelium, we searched for endothelial cell-activating factors released from RSV-infected epithelial cells. We demonstrate here that vascular endothelial cells exposed to culture supernatants from RSV-infected pulmonary epithelial A549 cells are activated to express increased cell surface ICAM-1, and to a lesser extent, VCAM-1 and E-selectin. IL-1alpha was identified as the predominant endothelial cell-activating factor by pretreating epithelial cell supernatants with anti-IL-1alpha antibody. The preferential upregulation of endothelial ICAM-1 (relative to VCAM-1 and E-selectin) by RSV-infected epithelial cell supernatants was replicated by recombinant IL-1alpha thus confirming IL-1alpha as a major endothelial cell-activating cytokine released by RSV-infected epithelial cells. Il-1alpha mediated endothelial cell activation is thus a likely contributory event in the initiation of leukocyte inflammation associated with RSV infection.

Cell Line↗
PubMed2003

Manipulation of cell surface macromolecules by flaviviruses.

Cell surface macromolecules play a crucial role in the biology and pathobiology of flaviviruses, both as receptors for virus entry and as signaling molecules for cell-cell interactions in the processes of vascular permeability and inflammation. This review examines the cell tropism and pathogenesis of flaviviruses from the standpoint of cell surface molecules, which have been implicated as receptors in both virus-cell as well as cell-cell interactions. The emerging picture is one that encompasses extensive regulation and interplay among the invading virus, viral immune complexes, Fc receptors, major histocompatibility complex antigens, and adhesion molecules.

Animals↗
PubMed2003

Expression of co-stimulatory molecules on acute myeloid leukaemia blasts may effect duration of first remission.

Many solid tumours have been shown to lack expression of either of the immune co-stimulatory molecules CD80 (B7.1) or CD86 (B7.2), which is thought to be one of the ways in which tumours may escape immune recognition. We have examined the surface expression of CD80, CD86, human leucocyte antigen (HLA) class I and II, CD11a, CD54, and CD58 on the blast cells from patients with acute myeloid leukaemia (AML) at presentation. CD80 was only rarely expressed on AML blasts and, in those leukaemic cells expressing CD80, the level of expression was low. In contrast, expression of CD86 was detected on the AML blasts in more than half of the samples tested and, in some cases, the level of expression was equivalent to that of mature monocytes and activated B lymphocytes. The percentage of leukaemic blasts expressing CD86 was higher in the M4 and M5 French-American-British (FAB) types, and expression of CD11a and HLA class II was higher in the M4 FAB type. There was no difference in expression of CD80, CD54, CD58, or HLA Class I between different FAB subgroups. There was no significant difference in duration of first remission with expression of CD80, CD86, CD11a, CD54 or HLA class II. However, when expression of CD80 and CD86 were considered together, a significantly longer duration of remission was found. We suggest that these molecules may play a role in immunosurveillance, resulting in prolonged remission in some patients treated for AML.

Acute Disease↗
PubMed2003

Surgeon training and complications in total ankle arthroplasty.

BACKGROUND: This study assessed the problems with initial use of ankle arthroplasty by surgeons who were trained by observing the surgeon/inventor (group I), who have completed a structured, hands-on surgical training course (group II), or who were trained during a 1-year foot and ankle fellowship (group III). MATERIALS AND METHODS: The perioperative records of the first 10 cases of nine surgeons were reviewed. We evaluated the 6-month-postoperative standing mortise and lateral radiographs for evidence of syndesmosis union and accuracy of tibial component implantation. Three surgeons were each in group I, group II, and group III. Average patient age at time of surgery was similar. Ankle arthritis was classified as rheumatoid arthritis (RA) or osteoarthritis (OA) as follows: group I (7 RA, 23 OA), group II (7 RA, 23 OA), and group III (3 RA, 27 OA). RESULTS: In group I, there were nine intraoperative complications, four postoperative wound dehiscences, and three postoperative deep infections. Radiographic evaluation of the 26 cases with adequate postoperative roentgenograms revealed that 10/26 (38%) had a delayed union of the syndesmosis. In group II, there were six intraoperative complications and two postoperative wound problems: an early anterior wound problem and a delayed lateral wound breakdown. Radiographic evaluation of the 26 cases with adequate postoperative roentgenograms revealed that 13/26 (50%) had a delayed union of the syndesmosis. In group III, there were four intraoperative complications and four postoperative wound problems--all healed with local supportive care with one requiring lateral hardware removal. Radiographic evaluation of the 26 cases with adequate postoperative roentgenograms revealed that 5/30 (17%) had a delayed union of the syndesmosis. The initial series from these three groups are statistically indistinguishable with respect to rates of complications, revisions, or malalignment. CONCLUSION: No identified training method had a statistically demonstrable positive impact on preparing surgeons for performing total ankle replacement. Some of these findings are likely generic for total ankle replacements and not restricted to any class or design of implant. Surgeon initial use of total ankle replacement needs to be done with caution and serious consideration.

Adult↗
PubMed2002

Enhanced immune protection by a liposome-encapsulated recombinant respiratory syncytial virus (RSV) vaccine using immunogenic lipids from Deinococcus radiodurans.

The radiation-resistant bacterium, Deinococcus radiodurans contains a variety of phospho-, glyco- and phosphoglycolipids, the structures of which appear to be largely unique in nature. We show here that such lipids are immunogenic when administered as liposomes intranasally in mice, as evidenced by the induction of serum antibodies which recognize D. radiodurans lipids but not other lipids by thin layer chromatographic immunostaining. By modifying a liposomal vaccine against respiratory syncytial virus (RSV) we find that vaccine efficacy is markedly enhanced by the inclusion of lipids isolated from D. radiodurans. Using dioleoylphosphatidylcholine (DOPC) or D. radiodurans lipids, liposomes were prepared which encapsulated a soluble fragment of the RSV G protein (G(128-188)) fused with a portion of the bacterial thioredoxin (Trx) protein. Mice immunized intranasally with D. radiodurans liposomes showed markedly greater protection against RSV challenge over mice immunized with DOPC liposomes. Enhanced vaccine efficacy was achieved using liposomes prepared from either whole D. radiodurans lipids or from a single isolated phosphoglycolipid previously identified as alpha-galactosylphosphatidylglyceroylalkylamine (lipid 7). Mice immunized and protected against RSV challenge were free of pulmonary eosinophilic infiltration, an undesirable consequence of many RSV vaccines. The results provide further support for liposome-based vaccines for RSV and underline the importance of lipid composition in liposome formulations.

Animals↗
PubMed2002

The Fugelli tactic.

Explore the source record for details and available documents.

Clinical Competence↗
PubMed2002

Interleukin-1alpha released from epithelial cells after adenovirus type 37 infection activates intercellular adhesion molecule 1 expression on human vascular endothelial cells.

A key event in virus-induced inflammation (leukocyte extravasation through the endothelium) is the local activation of endothelial cells, as indicated by the expression of adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin. In order to identify triggers of inflammation in adenovirus infection, we inoculated respiratory and ocular epithelial cells with adenovirus type 37 (Ad37), a human pathogen associated with keratoconjunctivitis as well as urogenital and respiratory infections. Fluids from virus-infected epithelial cells activated ICAM-1 (and to a lesser extent, VCAM-1) expression on cultured human umbilical vein endothelial cells. Blocking studies with anticytokine antibodies implicated interleukin-1alpha (IL-1alpha) as the epithelial cell-derived factor which activated endothelial cell ICAM-1 expression. The results thus identify epithelial cell-derived IL-1alpha as a potentially important activator of endothelial cells in Ad37-induced inflammation.

Cells, Cultured↗
PubMed2002

Dengue virus selectively induces human mast cell chemokine production.

Severe dengue virus infections usually occur in individuals who have preexisting anti-dengue virus antibodies. Mast cells are known to play an important role in host defense against several pathogens, but their role in viral infection has not yet been elucidated. The effects of dengue virus infection on the production of chemokines by human mast cells were examined. Elevated levels of secreted RANTES, MIP-1alpha, and MIP-1beta, but not IL-8 or ENA-78, were observed following infection of KU812 or HMC-1 human mast cell-basophil lines. In some cases a >200-fold increase in RANTES production was observed. Cord blood-derived cultured human mast cells treated with dengue virus in the presence of subneutralizing concentrations of dengue virus-specific antibody also demonstrated significantly (P < 0.05) increased RANTES production, under conditions which did not induce significant degranulation. Chemokine responses were not observed when mast cells were treated with UV-inactivated dengue virus in the presence or absence of human dengue virus-specific antibody. Neither antibody-enhanced dengue virus infection of the highly permissive U937 monocytic cell line nor adenovirus infection of mast cells induced a RANTES, MIP-1alpha, or MIP-1beta response, demonstrating a selective mast cell response to dengue virus. These results suggest a role for mast cells in the initiation of chemokine-dependent host responses to dengue virus infection.

Antibodies, Viral↗
PubMedDate not supplied

Informal diabetes education: impact on self-management and blood glucose control.

PURPOSE: The purpose of this study was to determine if participation in screening clinics to detect and treat diabetes-related eye disease also led to informal patient learning that had an impact on self-management behavior and blood glucose control. METHODS: To evaluate the evidence for patient learning over time, the data of patients who returned as advised for 2 subsequent annual diabetes disease screenings were analyzed. Evaluation measures included medication use, self-management behavior, and hemoglobin A1c (A1C). RESULTS: During the 2-year study period, the use of insulin increased by 37% at the first exam, 43% at the second exam, and 42% at the third exam (P = .02). No significant changes were found in the use of oral medication. Glucose self-monitoring also increased by 61% at the first exam, 71% at the second exam, and 76% at the third exam (P < .01). Mean A1C values for returning participants declined by 9.2% at the first exam, 8.9% at the second exam, and 8.6% at the third exam (P = .03). CONCLUSIONS: The screening clinics had an educational impact associated with behavior change (improved self-management and glucose control) even though the clinics were not intended to produce such change. Therefore, caregivers should consider that patient learning can and should be part of every diabetes care encounter.

Black or African American↗