Biomedical subjects

W J Jordan

Publications and source records attributed to W J Jordan.

16 recordsLinked to original sources

PubMed2006

Modulation of the human cytokine response by interferon lambda-1 (IFN-lambda1/IL-29).

The interferon lambda family (IFN-lambda1/2/3) is a newly described group of cytokines that are related to both the type-1 interferons and IL-10 family members. These novel cytokines are induced during viral infection and, like type-1 interferons, display significant anti-viral activity. In order to understand their function in more depth, we have examined the ability of IFN-lambda1/IL-29 to regulate cytokine production by human immune cells. Whole peripheral blood mononuclear cells (PBMC) exposed to IFN-lambda1 specifically upregulated IL-6, -8 and -10 but there were no visible effects on TNF or IL-1. This response was produced in a dose-dependant fashion and was inhibited by IL-10. Examination of purified cell populations isolated from PBMC demonstrated that monocytes, rather than lymphocytes, were the major IFN-lambda1-responsive cellular subset, producing IL-6, -8 and -10 in response to IFN-lambda1. Monocyte responses induced by low-level LPS stimulation were also synergistically enhanced by the presence of IFN-lambda1. Human macrophages were also shown to react to IFN-lambda1 similarly to monocytes, by producing the cytokines IL-6, -8 and -10. In conclusion, we have shown that IFN-lambda1, a cytokine produced in response to viral infection, activates both monocytes and macrophages producing a restricted panel of cytokines and may therefore be important in activating innate immune responses at the site of viral infection.

B-Lymphocytes↗

PubMed2005

A non-conservative, coding single-nucleotide polymorphism in the N-terminal region of lactoferrin is associated with aggressive periodontitis in an African-American, but not a Caucasian population.

Lactoferrin is an antimicrobial protein which plays an important role in regulating bacteria that are associated with aggressive periodontitis. Lactoferrin kills directly (via its strongly cationic N-terminal region) and indirectly, through sequestering the iron that bacteria require for growth. As aggressive periodontitis has a strong heritable component, we hypothesized that genetic variation within the lactoferrin gene may play a role in susceptibility to this condition. We have identified and examined a novel, functional, single-point A/G nucleotide mutation causing a threonine/alanine substitution at position 11 (T11A) of the secreted lactoferrin protein. In a pilot case-controlled study of aggressive periodontitis, analysis of 46 African-American patients and 78 controls showed that patients were twice as likely to express the G nucleotide (alanine) allele over controls (60.3 vs 30.4%; P=0.0007, odds ratio=2.564, 95% CI=1.475-4.459). A Caucasian population of 77 patients and 131 controls showed no such association (P=0.5201, odds ratio=0.862, 95% CI=0.548-1.356). The data presented provide a new insight into the genetic susceptibility to aggressive periodontitis.

Black or African American↗

PubMed2005

Interferon-alpha2a is sufficient for promoting dendritic cell immunogenicity.

Type I interferons (IFNs) are widely used therapeutically. IFN-alpha2a in particular is used as an antiviral agent, but its immunomodulatory properties are poorly understood. Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive T cells and therefore play a crucial role in initiating the adaptive phase of the immune response. We studied the effects of IFN-alpha2a on DC maturation and its role in determining Th1/Th2 equilibrium. We found that IFN-alpha2a induced phenotypic maturation of DCs and increased their allostimulatory capacity. When dendritic cells were stimulated simultaneously by CD40 ligation and IFN-alpha2a, the production of interleukin (IL)-10 and IL-12 was increased. In contrast, lipopolysaccharide (LPS) stimulation in the presence of IFN-alpha2a mainly induced IL-10 release. The production of IFN-gamma and IL-5 by the responder naive T cells was also amplified in response to IFN-alpha2a-treated DCs. Furthermore, IL-12 production by IFN-alpha2a-treated DCs was enhanced further in the presence of anti-IL-10 antibody. Different results were obtained when DCs were treated simultaneously with IFN-alpha2a and other maturation factors, in particular LPS, and then stimulated by CD40 ligation 36 h later. Under these circumstances, IFN-alpha2a did not modify the DC phenotype, and the production of IL-10/IL-12 and IFN-gamma/IL-5 by DCs and by DC-stimulated naive T cells, respectively, was inhibited compared to the effects on DCs treated with maturation factors alone. Altogether, this work suggests that IFN-alpha2a in isolation is sufficient to promote DC activation, however, other concomitant events, such as exposure to LPS during a bacterial infection, can inhibit its effects. These results clarify some of the in vivo findings obtained with IFN-alpha2a and have direct implications for the design of IFN-alpha-based vaccines for immunotherapy.

Animals↗

PubMed2004

Toll-like receptor mRNA expression patterns in human dendritic cells and monocytes.

The innate immune system recognises a wide spectrum of pathogens without a need for prior exposure. The main cells responsible are monocytes, macrophages, dendritic cells (DC) and neutrophils phagocytose microbial pathogens triggering a cytokine network resulting in the development of inflammatory and specific immune responses. Findings in the Toll-like receptor (TLR) family, initially discovered in Drosophila, further elucidated these processes. Toll-like receptors induce activation of an innate immune response and at present ten TLRs have been identified, named TLRs 1-10. In addition to the ignition of the innate immune response, evidence implicates the TLR family in a spectrum of systemic disorders following bacterial infections including sepsis and multiple organ failure, and can be detrimental, leading to tissue injury. In this project, our main goal was to investigate the effects of a TLR4 ligand, lipolysaccharide (LPS) in human DC and monocytes. Our hypothesis is that different professional APCs, express different mRNA TLR transcripts. Our findings indicate that TLR expression patterns change in relation to the pathogen involved and in the case of DC, and the maturation stage the latter are upon challenging. Our results and interpretation showed significant alteration of transcript expression patterns upon LPS challenge in all cell subsets, with DC subsets expressing different TLR mRNA patterns as they go through different maturation stages.

Dendritic Cells↗

PubMed1993

Improved patient compliance with cleft palate team regimes.

A cleft palate team's prescribed regimen requires prompt and continued compliance to meet the objectives of the clinical management and to achieve the best clinical results for the patient. In a previous study (Paynter et al., 1990), we reported an overall compliance rate of 64% for patients seen by a cleft palate team during its first 8 years of operation. After the study, changes in the team's operational procedures were made in an attempt to provide better service, improve patient compliance, and improve the efficiency of the clinic. The purposes of the current clinical investigation were to determine the degree of compliance with recommendations made by the cleft palate team for the patients seen during the four years after the implementation of the changes and to identify variables that interfered with compliance. A subject was defined as the person(s) who could best respond to questions concerning the management of the team's patient. Each subject was interviewed using a questionnaire based on the Health Belief Model (Becker et al., 1977). The mean patient compliance rate was 82%. Using Jones and Caldwell's (1981) classification, 56.7% of the patients were classified as compliers, 40% as partial compliers, and 3.3% as noncompliers. Compliance with specific recommendations ranged from 58 to 100%. No specific variable was found to interfere with compliance.

Adolescent↗

PubMed1991

Accuracy of information reported by parents and children evaluated by a cleft palate team.

Children with palatal clefts and their parents were interviewed to determine what information they had about the cleft and its management. Their responses were compared with the standards of 17 team members from seven disciplines. Both parent and child were consistently provided information about clefts that they were expected to remember. The children's responses met the standards 67 percent of the time. Their parents' responses met the standards 80.6 percent of the time. Parents accurately predicted their children's responses 92 percent of the time.

Adolescent↗

PubMed1990

Patient compliance with cleft palate team regimens.

A cleft palate team's prescribed regimen requires prompt and continued compliance in order to meet the management objective and to justify the large investment of professional time. The purposes of this clinical investigation were to determine the rate of compliance with the recommendations made by a cleft palate team for its patients and to identify variables associated with compliance. A subject was defined as the person(s) who could best respond to questions concerning the management of the team's patient. Each subject was interviewed using a questionnaire. The mean patient compliance rate was 64.4%, and noncompliance with specific recommendations ranged from 12.5% to 100%. Using Jones and Caldwell's (1981) classification, 17.1% of the patients were classified as compliers, 78% as partial compliers, and 4.9% as noncompliers. The best predictor of compliance was a set of nine variables.

Cleft Palate↗

PubMed1985