10 research outputs found
Investigation of the pro-oxidative and pro-inflammatory interactions of cobalt, palladium, platinum and vanadium with human neutrophils in vitro
Please read the abstract in the section 00front of this documentThesis (PhD (Medical Immunology))--University of Pretoria, 2008.Immunologyunrestricte
HLA-DRB1 shared epitope genotyping using the revised classification and its association with circulating autoantibodies, acute phase reactants, cytokines and clinical indices of disease activity in a cohort of South African rheumatoid arthritis patients
INTRODUCTION: The revised shared epitope (SE) concept in rheumatoid arthritis (RA) is based on the presence (S) or
absence (X) of the SE RAA amino acid motif at positions 72 to 74 of the third hypervariable region of the various
human leucocyte antigen (HLA)-DRB1 alleles. The purpose of this study was to investigate SE subtypes on the basis
of the American College of Rheumatology 1987 revised criteria for the classification of RA in a cohort of South
African RA patients (n = 143) and their association with clinical and circulating biomarkers of disease activity
(autoantibodies, acute phase reactants and cytokines).
METHODS: Genomic DNA was analysed using high-resolution recombinant sequence-specific oligonucleotide PCR
typing of the HLA-DRB1 allele. Subtypes of the SE were classified according to the amino acids at positions 72 to
74 for the RAA sequence, and further sub-divided according to the amino acids at positions 70 and 71, which
either contribute to (S2, S3P), or negate (S1, S3D) RA susceptibility. Disease activity was assessed on the basis of (1)
Disease Activity Score in 28 joints using C-reactive protein (CRP), (2) rheumatoid factor (RF), (3) CRP and (4) serum
amyloid A by nephelometry, anticyclic citrullinated peptide antibodies (aCCP) by an immunofluorometric
procedure, and cytokines by multiplex bead array technology.
RESULTS: Of the 143 RA patients, 81 (57%) were homozygous (SS) and 50 (35%) were heterozygous (SX) for the SE
alleles with significant overexpression of S2 and S3P (respective odds ratios (ORs) 5.3 and 5.8; P < 0.0001), and 12
(8%) were classified as no SE allele (XX). Both the SS and SX groups showed a strong association with aCCP
positivity (OR = 10.2 and P = 0.0010, OR = 9.2 and P = 0.0028, respectively) relative to the XX group. Clinical scores
and concentrations of the other biomarkers of disease activity (RF, CRP and T helper cell type 1 (Th1), Th2,
macrophage and fibroblast cytokines) were also generally higher in the SS group than in the SX and XX groups.
CONCLUSIONS: RA susceptibility alleles investigated according to revised criteria for the classification of RA were
significantly increased in South African RA patients and strongly associated with aCCP in particular as well as with
circulating cytokines and disease severity.The Connective Tissue Diseases Research Fund, University of the
Witwatersrandhttp://arthritis-research.com/content/13/5/R16
Circulating Cytokine Profiles and Their Relationships with Autoantibodies, Acute Phase Reactants, and Disease Activity in Patients with Rheumatoid Arthritis
Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease activity in DMARDs-naïve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblast-derived cytokines. RF correlated significantly with IL-1β, IL-2, IL-4, IL-10, IL-12, G-CSF, GM-CSF, IFN-γ, and TNF (P < .0001), and aCCP and aMCV with IL-1β, IL-2, IL-4, and IL-10 (P < .0002), while IL-6 correlated best with the acute phase reactants, CRP, and SAA (P < .0001). In patients with a DAS28 score of ≥5.1, IFN-γ, IL-1β, IL-1Ra, TNF, GM-CSF, and VEGF were significantly correlated (P < .04–.001) with high disease activity (HDA). Circulating cytokines in RA reflect a multifaceted increase in immune reactivity encompassing Th1 and Th2 cells, monocytes/macrophages, and synovial fibroblasts, underscored by strong correlations between these cytokines, as well as their relationships with RF, aCCP, and aMCV, with some cytokines showing promise as biomarkers of HDA
Evaluation of circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict risk profile, response to antimicrobial therapy, and development of complications in patients with chemotherapy-associated febrile neutropenia : a pilot
The soluble Triggering Receptor Expressed on Myeloid cells 1 (sTREM-1) is a useful
marker of infection in patients with sepsis, but has not been adequately evaluated in
patients with chemotherapy-associated febrile neutropenia (FN). The value of
sTREM-1 in this setting has been tested in a retrospective, pilot study using stored
serum from 48 cancer patients with documented FN. On presentation, patients were
categorized according to the Talcott risk-index clinical score. Circulating soluble
sTREM-1 was measured using an ELISA procedure, while procalcitonin (PCT) or
interleukins 6 (IL-6) and 8 (IL-8), included for comparison, were measured using an
immunoluminescence-based assay and Bio-Plex suspension bead array system,
respectively. Circulating concentrations of both sTREM-1 and PCT were significantly
(P < 0.05) elevated in patients at high risk for complications or death, as predicted by
the Talcott score and were significantly lower in patients who responded to empiric
antimicrobial agents. Neither IL-6 nor IL-8 accurately predicted serious complications
in patients with FN. These observations, albeit from a pilot study, demonstrate that
sTREM-1 is indeed elevated in high-risk patients with FN and is potentially useful to
predict their clinical course, either together with, or as an alternative to PCT.http://www.springerlink.com/content/0939-555
Palladium attenuates the pro-inflammatory interactions of C5a, interleukin-8 and pneumolysin with human neutrophils
Increased Oxidants and Reduced Antioxidants in Irradiated Parenteral Nutrition Solutions May Contribute to the Inflammatory Response
Introduction of the AmpliChip CYP450 Test to a South African cohort : a platform comparative prospective cohort study
The original publication is available at http://www.biomedcentral.com/1471-2350/14/20Abstract
Background
Adverse drug reactions and lack of therapeutic efficacy associated with currently prescribed pharmacotherapeutics may be attributed, in part, to inter-individual variability in drug metabolism. Studies on the pharmacogenetics of Cytochrome P450 (CYP) enzymes offer insight into this variability. The objective of this study was to compare the AmpliChip CYP450 Test® (AmpliChip) to alternative genotyping platforms for phenotype prediction of CYP2C19 and CYP2D6 in a representative cohort of the South African population.
Methods
AmpliChip was used to screen for thirty-three CYP2D6 and three CYP2C19 alleles in two different cohorts. As a comparison cohort 2 was then genotyped using a CYP2D6 specific long range PCR with sequencing (CYP2D6 XL-PCR + Sequencing) platform and a PCR-RFLP platform for seven CYP2C19 alleles.
Results
Even though there was a low success rate for the AmpliChip, allele frequencies for both CYP2D6 and CYP2C19 were very similar between the two different cohorts. The CYP2D6 XL-PCR + Sequencing platform detected CYP2D6*5 more reliably and could correctly distinguish between CYP2D6*2 and *41 in the Black African individuals. Alleles not covered by the AmpliChip were identified and four novel CYP2D6 alleles were also detected. CYP2C19 PCR-RFLP identified CYP2C19*9,*15, *17 and *27 in the Black African individuals, with *2, *17 and *27 being relatively frequent in the cohort. Eliminating mismatches and identifying additional alleles will contribute to improving phenotype prediction for both enzymes. Phenotype prediction differed between platforms for both genes.
Conclusion
Comprehensive genotyping of CYP2D6 and CYP2C19 with the platforms used in this study, would be more appropriate than AmpliChip for phenotypic prediction in the South African population. Pharmacogenetically important novel alleles may remain undiscovered when using assays that are designed according to Caucasian specific variation, unless alternate strategies are utilised.Publishers' Versio