Biomedical subjects

H Direskeneli

Publications and source records attributed to H Direskeneli.

60 records · Page 4Linked to original sources

PubMedDate not supplied

The role of heat shock proteins in Behçet's disease.

Heat shock proteins (HSP) are highly conserved molecules with scavenger activity that are involved in the correct folding of newly synthesized proteins. Increased T and B cell activity against 60/65 kD HSP is observed in different ethnic populations in Behçet's disease (BD) with both alpha beta and gamma delta T cell responses. Although the specificity of these responses is not clear, animal models of uveitis treated with either subcutaneous and oral HSP-derived peptides suggest a significant role of HSPs in the immunopathogenesis of BD. Recent developments in the innate immune system with the description of toll-like receptors (TLR) and HSP60 as a ligand for TLR-2 and TLR-4 suggest also the role of HSP60 as an endogenous "danger" signal to the immune system with rapid inflammatory cytokine release and the enhancement of adaptive Th1-type responses. Activation of both innate and adaptive responses with HSPs also fit well into the clinical spectrum of BD with both early, limited responses (recurrent ulcers, pathergy, etc.) and chronic lesions (posterior uveitis, thrombosis, neuro-BD, etc.).

Animals↗

PubMedDate not supplied

T and NK cell subset changes with microbial extracts and human HSP60-derived peptides in Behçet's disease.

OBJECTIVE: Microorganisms such as streptococcus and autoantigens such as 60 kD heat-shock protein (HSP60) are implicated in the etiopathogenesis of Behçet's disease (BD). METHODS: Peripheral blood mononuclear cells from patients with BD (n = 16) and healthy controls (HC) (n = 11) were cultured for 5 days with extracts of S. sanguis-KTH-1 (SS), E. coli (EC) and a mixed peptide combination from human HSP60 (aa 136-50, 179-97, 224-58 and 336-51) reported to be associated with BD. T and NK cell subset changes were determined by flow cytometry. RESULTS: In unstimulated 5-day cultures gammadelta+ (both CD4+gammadelta+ and CD8+gammadelta+), CD8+alphabeta+, CD4+CD56+ and CD8+CD11b+ cells were increased in BD compared to HC. In antigen-stimulated cultures of BD patients CD3+ and alphabeta+ T cells responded to HSP60 peptides whereas EC stimulated only CD16/ CD56+ NK cells. In the control group, similar to BD, alphabeta+ and CD4+ T cells responded to HSP60 peptides, however SS and EC mainly activated cytotoxic T cell subsets (CD8+CD11b and CD4+CD56+ T cells). CONCLUSION: Significant increases in unstimulated T cell subsets suggest the presence of an in vivo T cell activation in BD. In both patients and controls similar patterns of responses were observed against different microorganisms, however the role of human HSP60 peptides as immunodominant, crossreactive antigens could not be demonstrated.

Adult↗

PubMedDate not supplied

Oxidative burst response to monosodium urate crystals in patients with Behçet's syndrome.

OBJECTIVE: An erythematous response to intradermal injection of monosodium urate crystals (MSU) has been demonstrated in Behçet's syndrome (BS). To further elucidate the pathogenesis of this response, the effects of MSU on in vitro oxidative burst reaction of neutrophils and monocytes were investigated. METHODS: Peripheral blood mononuclear cells from patients with Behçet's syndrome (BS), rheumatoid arthritis (RA), familial Mediterranean fever (FMF) and healthy controls (HC) were incubated with 100 ng/ml phorbol myristate acetate (PMA) and MSU at different dosages (25-500 microg/ml). Oxidative burst reaction was evaluated in neutrophils and monocytes by flow cytometry. RESULTS: In patients with BS, oxidative burst of neutrophils was significantly increased compared to HC at 125 microg/ml and 250 microg/ml dosages of MSU (p < or = 0.001 and 0.004 respectively). In patients with FMF; there was also an increased oxidative burst reaction at 75 microg/ml, 250 g/ml and 500 microg/ml (p < or = 0.007; 0.001 and 0.004 respectively). In patients with BS, oxidative burst of monocytes was increased only at 125 g/ml dosage of MSU (p < or = 0.002). However, in patients with FMF monocyte burst response was increased at 25 microg/ml, 75 microg/ml and 125 g/ml (p < or = 0.004; < 0.0001; < 0.0001 and 0.002 respectively). In RA group, stimulation with PMA resulted in a higher oxidative burst reaction than FMF and BS (p < or = 0.000 and p < or = 0.008). No correlation was observed between oxidative burst of neutrophils or monocytes and intradermal responses to MSU crystals. CONCLUSION: Oxidative burst reaction with MSU is augmented in neutrophils and monocytes of BS. However, the response is not specific and is unassociated with skin dermal test which has a high specificity for BS.

Adult↗

PubMedDate not supplied

The effects of TNF alpha inhibition on plasma fibrinolytic balance in patients with chronic inflammatory rheumatical disorders.

OBJECTIVE: Recent studies support an inflammatory basis for atherosclerosis. Patients with chronic inflammatory rheumatical disorders are at increased risk for cardiovascular events, and this can be partially attributed to the inhibition of fibrinolytic system. TNF a inhibitors such as infliximab are shown to retard the progression of inflammatory arthritides. In this study, we investigated the effects of infliximab on plasma fibrinolytic parameters. METHODS: Thirteen patients (7 female, 6 male; mean age: 44 +/- 11 years) with a clinical indication for infliximab (rheumatoid arthritis (RA) (n = 8), ankylosing spondylitis (AS) (n = 5)) were selected. Plasma plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA) antigens (Ag) and high sensitive C-reactive protein (hs-CRP) levels were measured during low salt intake at baseline. All patients received infliximab (Remicaide, i.v. infusion, 3 mg/kg). Plasma PAI-1 Ag, t-PA Ag and hs-CRP were measured during low salt intake at the end of 2 weeks. All samples were collected at 9 AM. Antigen levels were determined using a 2-site enzyme-linked immunosorbent assay. RESULTS: Patients experienced significant improvement in disease related activity scores after infliximab treatment. DAS score (for rheumatoid arthritis) and BASDAI index (for ankylosing spondylitis) decreased significantly after treatment (p = 0.01 and p = 0.04 respectively). Infliximab significantly reduced the marker of inflammation (hs-CRP) (8.3 +/- 3.9 vs. 4 +/- 4.1 mg/L, p < 0.01). Plasma PAI-1 antigen (64.7 +/- 26.9 vs. 40 +/- 31.1 ng/ml, p = 0.03) and PAI-1/t-PA ratio (10.8 +/- 5.9 vs. 6.6 +/- 3.8, p = 0.02) were significantly lower after the treatment. In contrast, plasma t-PA levels were unchanged (9.4 +/- 4.4 vs. 9.0 +/- 4.3 ng/ml, p = 0.73). CONCLUSION: This study provides evidence that TNF alpha inhibition with infliximab decreases PAI-1 Ag level and PAI-1/t-PA ratio, and hence activates fibrinolytic system in patients with chronic inflammatory disorders.

Adult↗

PubMedDate not supplied

Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1B gene polymorphisms in Turkish patients with rheumatoid arthritis.

OBJECTIVE: Interleukin 1 (IL-1) family is composed of two agonists, IL-1alpha and IL-1Beta and IL-1 receptor antagonist, IL-1Ra. The purpose of this study was to determine the relationship between polymorphisms of IL-1 receptor antagonist (IL-1RN), IL-1B promoter and IL-1B exon 5 genes and susceptibility to rheumatoid arthritis (RA) in Turkish population. METHODS: Polymerase chain reaction (PCR) was used to determine the genotype of the IL-1RN for 94 RA patients and 104 healthy controls. Genotyping of IL-1B polymorphisms at positions -511 (C/T) and +3953 (C/T) was detected by PCR followed restriction fragment length analysis. RESULTS: There was no significant difference in IL-1RN genotype and allele distributions between RA and the control groups. In addition, no significant association was observed in the allelic frequency (C or T) of IL-1B promoter (-511) between RA patients and the controls (P = 0,118), but the genotype distribution of 1/2 (C/T) at position -511 showed a significant difference (P = 0,038). Also, 2/2 genotype (T/T); (P = 0,028), and allele 2 (T) distribution (P = 0,011) of IL-1B (+3953) showed significant differences between RA patients and the control groups in the study population. CONCLUSION: These results imply that 2/2 (T/T) genotype or allele 2 (T) of IL-B (+3953) are susceptibility factors for RA in Turkey. Also, 1/2 genotype (C/T) of IL-1 -511 can play a protective role for RA.

Alleles↗

PubMedDate not supplied

Markers of vascular damage in lupus pregnancy.

OBJECTIVE: To study serum levels of von Willebrand factor antigen (vWF:Ag) and anti-endothelial cell antibodies (AECA) in pregnancies with systemic lupus erythematosus (SLE) compared to healthy pregnancies and to evaluate their correlation with disease activity and fetal outcome. METHODS: Twenty-four patients with SLE were compared with 26 healthy pregnancies. vWF:Ag and AECA levels were measured by ELISA. RESULTS: In lupus pregnancies vWF:Ag and AECA levels were significantly elevated compared to healthy pregnancies (vWF:Ag: 255 +/- 160%, 10/24 positive vs 135 +/- 59%, 1/26 positive, p = 0.006; AECA Binding Index: 36 +/- 29%, 5/24 positive vs 17 +/- 16%, 1/26 positive, p = 0.002). When samples taken during follow-up were evaluated, vWF:Ag was positive in 21/27 (78%) of the samples during exacerbations compared to 4/25 (16%) in remission. Only 5/27 (19%) of the samples during exacerbations and none during remission were positive for AECA. Samples during three pregnancy failures were positive for vWF:Ag, but not for AECA. Of the 13 samples taken from the mothers of 4 babies with neo-natal lupus, 10 were positive for vWF:Ag and three for AECA. No correlations of anti-cardiolipin antibodies (aCL) were seen either with vWF:Ag or AECA titres. CONCLUSION: Compared to healthy pregnancies, vWF:Ag and AECA levels are increased in lupus pregnancies. vWF:Ag levels also correlated with active disease.

Abortion, Spontaneous↗