Papers by Lionel G Filion
Canadian journal of comparative medicine, Apr 1, 1985
Clinical and diagnostic laboratory immunology, 1994
In blood, the CD4+ T cells of patients with human immunodeficiency virus type 1 (HIV-1) harbor HI... more In blood, the CD4+ T cells of patients with human immunodeficiency virus type 1 (HIV-1) harbor HIV-1; however, whether the CD4+ blood monocytes carry the virus is controversial. Tissue macrophages are known to be infected. To determine in blood monocytes from HIV-1-seropositive patients contain HIV-1, we separated monocytes and T-cell subsets by using monoclonal antibodies bound to magnetic beads and by monocyte adherence to glass. Monocytes were cultured with macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and interleukin-3. After 14 days in culture, cells were analyzed for the presence of HIV-1 antigen and multinucleated giant cells (MGCs). Freshly isolated cell subsets were analyzed for HIV-1 proviral DNA by PCR with modified env (SK68i and SK69i2) and gag (SK145i and SK150) primers. We found that (i) monocytes cultured without depletion of CD4+ T cells (11 of 11 patients) were HIV-1 antigen positive and showed dramatically increased sponta...
Circulation, 2009
As a part of the NASA sponsored program on the application of communication satellites to educati... more As a part of the NASA sponsored program on the application of communication satellites to educational development, a study was made of the utilization of telecommunications by academic and school libraries in the United states and the potential for future utilization by these institutions. The five basic functions performed by all libraries-acquisition, cataloging, storage, I retrieval, and circulation control-are identified, and an overview of library cooperation of a general nature not restricted to communication is presented. Applications of telecommunications are then described with respect to interlibrary information interchange and with respect to new uses. School and academic library budgets are discussed, together with the important role played by federal legislation and financial assistance. Current interlibrary communication utilization is described, noting that data communication is potentially an area of considerable value to libraries, but is currently used by only a few. The future of interlibrary communication utilization is projected; medical school libraries are seen as most likely to increase their utilization of data communication in the near future. cno
Mycobacterial Diseases, 2013
Tuberculosis is a significant threat to human health, infecting nearly one third of the world's p... more Tuberculosis is a significant threat to human health, infecting nearly one third of the world's population and causing over a million deaths per year. The need for an effective vaccine against tuberculosis is apparent however, the current vaccine has not been successful neither in the prevention nor recovery from infection. The pathogenesis of the causative agent, Mycobacterium tuberculosis has been extensively studied. The mechanisms of immune evasion and modulation that enable persistence of infection through subclinical latency and eventually active tuberculosis have been partially described. Many of these mechanisms are directly antagonistic to the intended benefit of vaccines, leaving a conundrum that has yet to be resolved. This review will first examine the nature of tuberculosis pathogenesis in the context of the immune response and outline the varied processes utilized by the bacterium to cause modulation. The review will also investigate other vaccination options that may overwhelm these microbial mechanisms or avert them entirely, allowing for the engagement of the immune response and clearance of the bacterium.
Clinical and experimental immunology, 1988
The production in vitro of antibody to hepatitis B surface antigen by peripheral blood mononuclea... more The production in vitro of antibody to hepatitis B surface antigen by peripheral blood mononuclear cells of healthy volunteers was studied after each of the three doses of hepatitis B vaccine. An in vitro hepatitis B surface antigen antibody response was successfully induced in 12% of the specimens taken over a 7 month period. The response to this antigen was induced in additional samples if cells had been treated previously with anti-CD4 and complement or anti-CD8 and complement prior to culture initiation. The addition of interleukin 2 could also induce the formation of antibodies to hepatitis B surface antigen. The results suggest that the antibody response to hepatitis B surface antigen is complex and varies depending on the individual and time of sampling.
PLoS ONE, 2012
In vitro and animal studies report that some persistent organic pollutants (POPs) trigger the sec... more In vitro and animal studies report that some persistent organic pollutants (POPs) trigger the secretion of proinflammatory cytokines. Whether POP exposure is associated with a dysregulation of cytokine response remains to be investigated in humans. We studied the strength of association between plasma POP levels and circulating cytokines as immune activation markers. Plasma levels of fourteen POPs and thirteen cytokines were measured in 39 Caucasians from a comparator sample in Québec City (Canada) and 72 First Nations individuals from two northern communities of Ontario (Canada). Caucasians showed significantly higher levels of organochlorine insecticides (b-HCH, p,p9-DDE and HCB) compared to First Nations. Conversely, First Nations showed higher levels of Mirex, Aroclor 1260, PCB 153, PCB 170, PCB 180 and PCB 187 compared to Caucasians. While there was no difference in cytokine levels of IL-4, IL-6, IL-10 and IL-22 between groups, First Nations had significantly greater average levels of IFNc, IL-1b, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFa and TNFb levels compared to Caucasians. Among candidate predictor variables (age, body mass index, insulin resistance and POP levels), high levels of PCBs were the only predictor accounting for a small but significant effect of observed variance (,7%) in cytokine levels. Overall, a weak but significant association is detected between persistent organochlorine pollutant exposure and elevated cytokine levels. This finding augments the already existing information that environmental pollution is related to inflammation, a common feature of several metabolic disorders that are known to be especially prevalent in Canada's remote First Nations communities.
Clinical and Experimental Immunology, 1999
SUMMARY T helper (Th) responses are mediated in part by immunoregulatory cytokines and the signal... more SUMMARY T helper (Th) responses are mediated in part by immunoregulatory cytokines and the signals delivered by the costimulatory CD28–B7 pathway. In this study, we have investigated the relationship between the regulation of B7 isoform expression on antigen-presenting cells from HIV+ individuals and the production of Th cytokines. The level of expression of both B7.1 and B7.2 isoforms as measured by mean channel fluorescence was significantly decreased on freshly isolated monocytes from HIV+ individuals compared with HIV− controls. However, the levels of expression of B7.1 and B7.2 on both B cells and monocytes increased significantly following culture in HIV+ individuals compared with HIV− controls. B7 expression is subject to regulation by immunoregulatory cytokines. Therefore, we analysed the regulation of B7 expression by cytokines, namely IL-10 and tumour necrosis factor-alpha (TNF-α), the production of which is enhanced in HIV infection and have similar inhibitory effects on ...
Canadian journal of comparative medicine. Revue canadienne de médecine comparée, 1985
Clinical and Diagnostic Laboratory Immunology, 1997
ALX40-4C is an antiretrovirus agent that has been found to have some inhibitory properties agains... more ALX40-4C is an antiretrovirus agent that has been found to have some inhibitory properties against human immunodeficiency virus (HIV) replication in vitro. The compound was designed as a competitor of the HIV Tat protein for TAR binding. In addition to its anti-HIV properties, it has demonstrated the ability to inhibit in vitro replication of herpes simplex virus types 1 and 2 as well as human cytomegalovirus. Subsequently, in vivo pharmacokinetic evaluation of ALX40-4C necessitated the establishment of a detection system for the measurement of ALX40-4C in subject serum. For this purpose, an indirect-competition enzyme-linked immunosorbent assay with generated rabbit anti-ALX40-4C antiserum was developed. The original assay took 12 h to complete and required many manipulations. Herein, we describe alterations to the system that resulted in the overall reduction in assay time and manipulation. We demonstrate that our alterations do not affect the specificity or sensitivity of the ass...
The down regulation of CD4 by cultured monocytes has been observed by our group and by other inve... more The down regulation of CD4 by cultured monocytes has been observed by our group and by other investigators. Flow cytometric experiments were done to examine which factors might influence this phenomenon. The addition of lipopolysaccharide, granulocyte-macrophage colony-stimulating factor, macrophage colonystimulating factor, or interleukin-10 to monocyte cultures failed to inhibit the decrease in monocyte CD4 expression routinely observed following overnight culture. The down regulation was an adherence-independent phenomenon and was not influenced by the type of anticoagulant into which the peripheral blood was collected or by the presence or absence of lymphocytes within the cultures. The avoidance of the use of Ficoll-Paque to isolate peripheral blood mononuclear cells did not prevent monocyte CD4 down regulation. Finally, by tagging monocyte CD4 with an anti-CD4 phycoerythrin-conjugated monoclonal antibody prior to culture, we were able to determine that the down regulation observed was the result of the internalization of the molecule. At this time, we conclude that the observed down regulation of monocyte CD4 is probably due to the differentiation of blood monocytes into tissue culture-derived macrophages rather than to some artifact of the isolation procedure.
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, Jan 4, 2017
To assess blood levels of cortisol and cytokines (inflammatory and non-inflammatory) in members o... more To assess blood levels of cortisol and cytokines (inflammatory and non-inflammatory) in members of the regular Canadian Armed Forces (CAF), and examine the associations between sex, age and adiposity and circulating levels of cortisol as well as pro- and anti-inflammatory cytokines. As part of a larger ranging project, 331 blood samples were collected from a representative population of the total CAF, which included officers and non-commissioned women and men from the Air Force, Navy and Army. The blood samples were analyzed for levels of cortisol, C-Reactive Protein, adiponectin and 20 cytokines (that included interleukins, interferons and Tumor Necrosis Factors). Higher levels of adiponectin were found in women compared to men (median and IQR; 16.71 (7.68-25.32) vs 5.81 (3.52-13.19) µg/ml), and higher levels of IL-18 in men compared to women (89.25 (84.03-94.48) vs 75.91 (69.70-82.13) pg/ml). An association between age and levels of stress and inflammatory cytokines was observed, ...
Immunobiology, Nov 30, 1990
Experiments were performed to delineate the mechanism by which tetanus toxoid (TT) suppresses the... more Experiments were performed to delineate the mechanism by which tetanus toxoid (TT) suppresses the immune response. A CD4+ cell has been shown to suppress the PHA response (18). TT suppresses the phytohemagglutinin (PHA) blastogenic response and pokeweed mitogen (PWM) induction of IgM and IgG in a dose-dependent fashion. The suppression is partially reversed by indomethacin or interleukin-2. The tumor necrosis factor had no effect. TT induced the suppression within 36 h and the immunosuppressive activity induced could downregulate the response of fresh syngeneic cultures of peripheral blood leucocytes. We conclude that TT can induce nonspecific suppressor cells that can dampen mitogen responses which has important implications in the development and usage of vaccines.
J Neuroimmunol, 1998
γδ T cells may contribute to the pathogenesis of Multiple Sclerosis (MS) via cytotoxicity directe... more γδ T cells may contribute to the pathogenesis of Multiple Sclerosis (MS) via cytotoxicity directed at the myelin-oligodendrocyte unit. We have previously demonstrated that peripheral blood-derived γδ T cells lyse fresh human oligodendrocytes in vitro. The present work extends these observations to γδ T cells derived from both peripheral blood (PBL) and cerebrospinal fluid (CSF) of MS and non-MS neurological disease controls and addresses the mechanism of cellular cytotoxicity. We found that MS patients contained increased proportions of Vδ1+γδ T cells in both CSF and PBL samples compared to other neurological disease (OND) controls. Although γδ T cells from all patients were cytotoxic towards Daudi, RPMI 8226, U937, Jurkat, oligodendroglioma and fresh human oligodendrocyte targets, OND-derived, Vδ2+ rich, populations derived from the CSF exhibited greater cytotoxicity towards cell lines (Daudi, RPMI 8226) known to express high levels of heat shock proteins (hsp). To clarify the mechanism(s) of cytotoxicity used by γδ T cells, we first showed that cell-target contact was necessary by the use of physical barriers (transwells), which reduced target cell lysis by at least 75%. The use of Ca2+-free media reduced lysis by up to 50%, but fully blocking γδ T cell Perforin release and function by either Ca2+ chelation (Mg2EGTA) or the H+-ATPase inhibitor Concanamycin-A (CMA), completely abrogated the lysis of Fas−/hsp60high expressing targets (Daudi, U937). However, additional treatment with Brefeldin A was required for the complete inhibition of γδ T cell mediated killing of Fas+ expressing Jurkat targets and fresh human brain-derived oligodendrocytes. Inhibition of granzyme activity by an isocoumarin compound reduced cytolysis only slightly. The use of either Brefeldin A or an anti-Fas antibody alone did not significantly affect lysis. These findings suggest that in MS, γδ T cells may utilize either the Fas-mediated or Perforin-based cell cytotoxicity pathways in exerting oligodendrocyte damage, though the Perforin pathway is predominant.
The Journal of otolaryngology
The development of monoclonal antibodies (Mabs) represents a major contribution of immunology to ... more The development of monoclonal antibodies (Mabs) represents a major contribution of immunology to the study of head and neck cancer. The interest of the otolaryngologist in this new field is quite recent, but our knowledge of cancer and other immunoproliferative disorders will exponentially expand with the characterization of tumor-associated antigens of squamous cell carcinomas. The author reviews briefly the technique for producing monoclonal antibodies and presents an overview of the application of Mabs to clinical medicine, oncology and, more specifically, head and neck cancer. Very few contributions have been made in head and neck cancer, but the field of Mabs will significantly alter our diagnostic and therapeutic armamentarium.
Canadian journal of comparative medicine. Revue canadienne de medecine comparee
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Papers by Lionel G Filion