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H Direskeneli

Publications and source records attributed to H Direskeneli.

At least 55 records · Page 3Linked to original sources
PubMed1998

Skin hyperreactivity of Behçet's patients (pathergy reaction) is also positive in interferon alpha-treated chronic myeloid leukaemia patients, indicating similarly altered neutrophil functions in both disorders.

Typical manifestations of Behcet's disease (BD) and a positive pathergy reaction were observed in a few patients with chronic myeloid leukaemia (CML) on interferon alpha (IFN-alpha) therapy and the significance of this observation was assessed in a prospective study. The skin pathergy test was applied to 15 patients with CML prior to IFN-alpha therapy, 29 patients with CML following IFN-alpha therapy and 30 patients with BD. Twenty-five patients with inflammatory arthropathies (IA), 20 patients with recurrent oral ulcers (ROU), 23 patients treated with IFN-alpha for various disorders and 20 normal individuals were also studied as control groups. The pathergy reaction was positive in nearly a quarter of IFN-alpha-treated CML cases (24%) as well as one-half of the patients with BD (50%). All CML patients prior to IFN-alpha treatment and all patients using IFN-alpha for other diseases were negative for the pathergy reaction. These results may indicate a similarly altered neutrophil function in both BD and IFN-alpha-treated CML patients.

Adolescent↗
PubMed1997

Behçet's disease in patients with chronic myelogenous leukemia: possible role of interferon-alpha treatment in the occurrence of Behçet's symptoms.

Two patients with chronic myelogenous leukemia (CML) who developed characteristic features of Behçet's disease (BD) during alpha-interferon (IFN-alpha) treatment and another patient who had a diagnosis of BD preceding CML are presented. In the first two patients, features of BD appeared 6 months after the initiation of IFN-alpha treatment: they included recurrent oral aphthae, genital ulceration, arthritis, folliculitis, and a positive skin pathergy test. The third patient, however, had a diagnosis of Behçet's disease 4 years before diagnosis of Philadelphia-positive CML. We prospectively examined the skin pathergy reaction in a group of patients with CML, multiple myeloma, and hairy cell leukemia both before and after IFN-alpha treatment and found two additional patients with CML who developed a positive skin pathergy test following IFN-alpha treatment.

Adult↗
PubMed1996

Recognition of B-cell epitopes of the 65 kDa HSP in Behçet's disease.

B-cell epitopes of the mycobacterial 65 kDa heat shock protein (HSP) were mapped in sera from patients with Behçet's Disease (BD). A series of 47 overlapping synthetic peptides (15ers) derived from the sequence of the Mycobacterium tuberculosis 65 kDa HSP was used in ELISA. Significant increases in IgA and IgG antibody levels were observed with peptides 111-125, 154-172 and 311-326 in sera from BD, compared with those from controls. Homologous peptides derived from the sequence of the human mitochondrial 60 kDa HSP were then examined. Peptides 136-150 and 336-351 showed comparable results to the homologous mycobacterial peptides 111-125 and 311-326, respectively. The B-cell epitopes defined in this investigation overlap with the T-cell epitopes the authors have previously reported in BD. Inhibition studies are consistent with the view that antibodies to each of the three B-cell epitope peptides represent a small proportion of the total B-cell epitope repertoire elicited by the 65 or 60 kD HSP. Sequential antibody studies suggest that IgA and IgG antibody titres to one or all three peptides tested may increase during exacerbation of ocular disease. The functional role of these antibodies needs to be determined, but the peptides may be involved in the immunopathogenesis of BD as they can induce experimental uveitis in Lewis rats, which is a principal manifestation of BD.

Adolescent↗
PubMed1996

Monocyte activity in Behçet's disease.

Monocytes obtained from patients with Behçet's disease (BD) were examined for differentiation markers (expression of CD14 and antigens reacting with monoclonal antibodies 25F9 and G16/1) and for expression of selected adhesion molecules. There was significantly raised expression of the CD14 molecule, and increased staining with 25F9 and G16/1 antibodies in monocytes obtained from patients with BD. A monocyte activation marker, soluble CD14, was also found to be raised in patients' serum compared with normal serum (8.1 +/- 9.2 vs 1.4 +/- 0.7 micrograms/ml). Furthermore, BD patients' monocyte culture supernatants caused significantly increased adhesion of normal neutrophils to endothelial cell monolayers in vitro. All these findings show that BD patients' monocytes are active in vivo and produce a number of pro-inflammatory cytokines which may play a role in the chronic inflammation found in these patients.

Behcet Syndrome↗
PubMed1996

Antibodies against endothelial cells in patients with multiple sclerosis.

OBJECTIVES: The humoral immune response seems to play a role in the pathogenesis of multiple sclerosis (MS). The blood-brain-barrier (BBB) and particularly the endothelial cell may be a possible target for this immune response. MATERIAL & METHODS: using an ELISA technique, we have investigated the prevalence of antibodies directed against human vein endothelial cells in the sera of 84 patients with MS, 35 stroke patients, 50 systemic lupus erythematosus (SLE) and 76 normal controls. The measurements in MS patients were tested a second time after cytokine stimulation with gamma and beta-interferon at different doses. Seven MS patients (two positive and five negative) had three or more clinical assessments including the Expanded Disability Status Scale (EDSS) over a three-month period, and at least three AECA determinations were carried out. Gadolinium MRI examinations were performed monthly during these three months. RESULTS: Anti-endothelial cell antibodies (AECA) have been identified in 9 of 84 patients suffering from MS (10.71%), in 3 of 35 stroke patients (8.57%) and in 20 of 50 SLE patients (40%). None of 76 normal controls had a positive titre of AECA. Cytokine stimulations did not modify the detection of these antibodies. No correlation between AECA and different clinical parameters such as onset age, clinical symptoms at onset and at sampling, clinical course and score measured by the EDSS was found in MS patients. No relationship was found between MRI activity and the presence of AECA. CONCLUSION: AECA do not seem to be a marker for a specific subset of MS patients.

Adolescent↗
PubMed1996

Neutrophil adhesion to endothelial cells and factors affecting adhesion in patients with Behçet's disease.

OBJECTIVES: To study the in vitro adhesion of polymorphonuclear leucocytes (PMNLs) to endothelial cells in patients with Behçet's disease (BD), and the humoral and cellular factors which may contribute to adhesion. METHODS: A total of 118 patients with BD and 60 healthy controls were studied. In vitro adhesion of chromium-51 labelled normal neutrophils to human umbilical vascular endothelial cell (HUVEC) monolayers were studied in the presence of normal serum or serum obtained from patients with BD. Adhesion of neutrophils from patients with BD to HUVEC stimulated with tumour necrosis factor (TNF), interleukin-1 (IL-1), and lipopolysaccharide (LPS) and adhesion molecule (CD11a, CD11b, CD18 and L-selectin) expression on the patient's neutrophils and lymphocytes were determined, and the serum concentration of IL-8 was measured. RESULTS: Sera from patients with BD were found to enhance the adherence of normal PMNLs to HUVEC monolayers in vitro. Patients' sera induced an increase in surface expression of CD11a and CD18 on normal neutrophils and intercellular adhesion molecule-1 (ICAM-1) expression on HUVECs. The number of CD11a positive neutrophils was greater in the blood of patients with BD than in that of healthy controls (89.4% v 71%; p < 0.001). Pretreatment of HUVECs with IL-1 alpha, TNF alpha or LPS resulted in an increased adhesion of patients' PMNLs greater than that observed for normal PMNLs. Monoclonal antibodies to CD11a, CD11b, CD18, and ICAM-1 caused varying degrees of inhibition of neutrophil adhesion. The concentration of IL-8 was also found to be significantly increased in sera of patients with BD (490 (SD 470) pg/ml) compared with normal controls (97.5 (56.3) pg/ml). CONCLUSION: Abnormalities of neutrophils, endothelial cells, or both, have been suggested to be responsible for many of the clinical manifestations of BD. Our findings may explain the underlying mechanism of neutrophil accumulation in Behçet's lesions.

Antibodies, Monoclonal↗
PubMed1995

Anti-endothelial cell antibodies, endothelial proliferation and von Willebrand factor antigen in Behçet's disease.

Endothelial cell dysfunction has previously been demonstrated in Behçet's disease which has vasculitic features. In this study we investigated anti-endothelial cell antibodies (AECA) and von Willebrand factor antigen (vWF) levels in patients with Behçet's disease. In vitro effects of patient sera on endothelial cell proliferation were also evaluated. AECAs were present in 29% of 70 Behçet's disease patients (Binding Index: 25 +/- 29% vs 9 +/- 7% in normal controls, p < 0.005). 95% of AECA positive patients were clinically active compared to 74% of AECA negative patients (p = 0.04). Among specific organ manifestations only active arthritis correlated with AECA positivity (6 of 7 patients vs 14 of 63, p = 0.002). AECA positive patients had a significantly higher mean ESR (37 +/- 24 mm/h vs 21 +/- 17 mm/h, p:0.006). Mean vWF levels were also significantly higher in patients compared to controls (166 +/- 75% vs 84 +/- 34%, p < 0.0001). No correlations were observed between AECA titres and vWF levels. No significant differences were observed between patients and controls when endothelial cell proliferation was studied (Proliferation Index: 1.25 +/- 0.28 vs 1.12 +/- 0.25, p = 0.5). Our results suggest that AECA may be related to disease activity in Behçet's disease. The presence of vWF, even in patients in complete remission, might be related to factors other than endothelial damage for vWF release from endothelial cells.

Adolescent↗
PubMed1994

Autoantibodies against endothelial cells, extracellular matrix, and human collagen type IV in patients with systemic vasculitis.

Endothelial cells and subendothelial matrix (ECM) are involved in the pathogenesis of vasculitis. Exposure of the ECM following vascular damage may promote further immune and inflammatory response. To investigate this, we studied the prevalence of antibodies against endothelial cells (AECA), ECM, and its major component collagen type IV in systemic vasculitis patients. Seventy-one percent of patients had AECA (binding index, means +/- SD: 64.8 +/- 48.1%; normal controls: 8.9 +/- 6.9%, P < 0.001). Anti-ECM and anti-collagen type IV antibodies were also significantly higher in patients compared to normals (anti-ECM: 28.6 +/- 29.6% vs 9.0 +/- 11.3%, P < 0.002; anti-collagen type IV: 23.5 +/- 20.3% vs 8.1 +/- 9.1%, P < 0.002). AECA correlated with anti-ECM (r = 0.75, P < 0.0001) but not with anti-collagen type IV. Anti-ECM correlated with anti-collagen type IV (r = 0.45, P < 0.01). Positivity of cytoplasmic anti-neutrophil cytoplasmic antibodies (cANCA) was significantly lower in patients positive for anti-ECM and/or anti-collagen type IV antibodies (58% vs 11%, P = 0.048). AECA binding was partially reduced with ECM incubation by 25.1%. The addition of heparin caused a dose-dependent inhibition of binding activity (19.2-30.6%) in the AECA ELISA. These results support the hypothesis that there is a humoral response against ECM components in addition to endothelial cells in systemic vasculitis patients which might have pathological significance in vascular damage.

Adult↗
PubMed1994

Soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of disease relapse in idiopathic uveoretinitis.

This study reports the results of a point prevalence study of markers of endothelial dysfunction in the serum of patients with idiopathic uveoretinitis. sICAM-1, soluble endothelial leucocyte adhesion molecule (sELAM), anti-endothelial cell antibodies (AECA) and von Willebrand factor (vWF) levels were measured in 32 patients with isolated idiopathic uveoretinitis and seven with uveitis in association with systemic disease, using commercial and in-house ELISAs. Raised levels of AECA were found in 31% of patients with isolated uveitis, vWF in 28%, sELAM in 15.6% and sICAM-1 in 31%. Further analysis revealed that raised sICAM-1 levels were closely associated with recent relapse of disease (P = 0.00003). Patients with accompanying systemic disease were found to have a similar prevalence of these serum abnormalities to those with isolated ocular disease. In conclusion, vascular endothelial dysfunction may contribute to pathogenesis in uveoretinitis, and in particular sICAM-1 may prove a marker of disease relapse in this condition.

Adolescent↗
PubMed1994

Systemic interferon alpha 2b treatment in Behçet's syndrome.

OBJECTIVE: To test the efficacy of systemic interferon alpha 2b (IFN alpha 2b) treatment in the mucocutaneous and joint symptoms of Behçet's syndrome. METHODS: The 48-week open, self-controlled trial was conducted in 3 phases. After the pretreatment phase of 16 weeks, 20 patients (8 men, 12 women; mean age 37 +/- 7 years SD) were treated with IFN-alpha 2b at a dose of 5 million units 3 times a week for 6 weeks followed by 5 million units once a week for 10 weeks. The subsequent 16 weeks not taking the medication was the posttreatment phase. RESULTS: Treatment with IFN-alpha 2b significantly reduced the mean number of arthritis attacks (F = 3.48; p < 0.05), their mean duration (F = 3.77; p < 0.05), and the mean erythrocyte sedimentation rate (F = 6.66; p < 0.001). The mean number of mucocutaneous lesions also showed a decrease, but this was not statistically significant. Except for the duration of arthritis, the mean number and frequency of all symptoms tended to return to pretreatment levels in the posttreatment phase. CONCLUSION: This pilot study shows that systemic IFN may be effective in the treatment of arthritis of Behçet's syndrome.

Adult↗
PubMed1992

Anti-lymphocyte, anti-monocyte, and anti-endothelial cell antibodies in chronic haemodialysis patients.

Patients receiving chronic haemodialysis treatment are known to have a high prevalence of anti-panel antibodies (anti-lymphocyte, anti-monocyte, and anti-endothelial cell) originating from a number of different possible sensitizing events such as blood transfusions, multiparity, or renal transplantation. In this study the prevalence of these antibodies in 123 chronic haemodialysis patients was evaluated. Anti-lymphocyte antibodies and anti-monocyte antibodies were found in 27.6% and 21.9% of the patient group respectively. Following exclusion of twelve patients within the study population with a history of previous graft rejection, anti-monocyte antibodies were encountered more frequently in transfused patients than those never having been transfused (22.4% versus 0%, P less than 0.05), whilst the prevalence of anti-lymphocyte antibodies was similar in both groups (28.2% versus 19.2%). Multiparity, patient age, or duration of dialysis treatment could not be demonstrated to significantly alter the prevalence of either of these antibodies. Of 12 patients with an episode of previous graft rejection, eight were positive for anti-monocyte antibodies and five for anti-lymphocyte antibodies. Anti-endothelial cell antibodies were common in patients in this group, being present in seven of eight individuals investigated.

Adolescent↗
PubMedDate not supplied

IL-8 producing cells in patients with Behçet's disease.

OBJECTIVE: IL-8 is thought to be the principal chemokine responsible for neutrophil activation and tissue infiltration in patients with Behçet's disease (BD). In various studies serum levels of IL-8 were reported to be increased. METHODS: IL-8 mRNA was purified from both peripheral whole blood samples and separated lymphocytes, granulocytes and monocytes of patients with BD and compared to that from healthy (HC) and disease controls. IL-8 sequences were revealed by PCR amplification using appropriate sequence-specific primers. mRNA levels were determined semi-quantitatively using an image analyser in comparison with beta-actin. RESULTS: Although the differences did not reach statistical significance, BD patients tended to have higher IL-8 mRNA levels compared to HC in whole blood samples (2.0 +/- 1.4 vs 1.5 +/- 1.2) as well as in their lymphocytes (2.7 +/- 1.6 vs 1.5 +/- 0.9). No differences were observed between BD and HC in monocyte or granulocyte IL-8 mRNA levels. CONCLUSION: Our results suggest that the cellular source of IL-8 is diverse in BD with a possible major contribution by lymphocytes.

Actins↗
PubMedDate not supplied

Neutrophil activation in Behçet's disease.

OBJECTIVE: Neutrophils are implicated in the pathogenesis of Behçet's disease (BD). Various functions of neutrophils are studied to clarify this role. METHODS: The oxidative burst and phagocytic functions of neutrophils and surface molecules associated with neutrophil activation (CD10, CD14 and CD16) were investigated in BD patients by flow cytometric methods. Patients with inflammatory arthropathies, sepsis and healthy controls were also studied. RESULTS: In the oxidative burst experiments, after fMLP and PMA stimulation, stimulation index was found to be significantly decreased in patients both with BD and sepsis compared to healthy controls and inflammatory arthropathies (p < 0.001 and p < 0.01, respectively). The phagocytosis of labelled E. coli particles in patients with BD was not different from that of the healthy controls, while it was decreased in diseased controls (p < 0.001). The surface density of neutral endopeptidase (CD10) and the mean percentage of LPS receptor (CD14) was found to be significantly higher in both BD patients and diseased controls (p < 0.001). The mean percentage of CD16 expression was only low in patients with sepsis (p < 0.001), whereas CD16 intensity on cells was found to be lower in patients with BD as well as in sepsis (p < 0.01). CONCLUSION: These findings indicate the presence of in vivo pre-activated neutrophils in BD. A similar activation was also a feature of severe inflammatory disorders.

Adult↗
PubMedDate not supplied

The effects of nitric oxide donors and inhibitors on neutrophil functions in Behçet's disease.

OBJECTIVE: The effects of nitric oxide donor SNAP and nitric oxide inhibitors L-NMMA and AG on the functions of neutrophils in patients with Behçet's Disease (BD) were investigated in vitro. METHODS: Oxidative burst and phagocytosis of neutrophils were evaluated by flow cytometry in patients with Behçet's disease (n = 32), inflammatory (n = 17) and healthy controls (n = 14), in the presence of L-NMMA, AG and SNAP. RESULTS: The stimulation index of oxidative burst was found to be significantly decreased following PMA stimulation in patients with active BD compared to inflammatory and healthy controls. Oxidative function of neutrophils were inhibited in all 3 groups in the presence of L-NMMA, AG and SNAP L-NMMA inhibited the oxidative burst of neutrophils obtained from healthy controls more than inflammatory controls and BD (80% vs 52% and 53% respectively, p = 0.001). No significant difference of phagocytosis inhibition was found with L-NMMA, AG and SNAP and there were also no differences between the groups (% 9-39). CONCLUSION: Nitric oxide donors and inhibitors may have a therapeutic role in Behçet's disease by suppresing neutrophil activity.

Adult↗
PubMedDate not supplied

Coronary stent implantation in Behçet's disease.

Behçet's disease (BD) is a systemic vasculitis that rarely involves the coronary arteries. Coronary arteritis may lead to myocardial infarction and death, and the management of coronary lesions due to BD has been described only in a small number of patients. The outcome of a young patient with BD is reported who was admitted with acute coronary syndrome and underwent balloon angioplasty and coronary stent implantation. Coronary stent implantation is an alternative treatment for coronary artery lesions of BD but careful monitoring is mandatory due to the progressive vasculities.

Adult↗
PubMedDate not supplied

MEFV mutations are increased in Behçet's disease (BD) and are associated with vascular involvement.

OBJECTIVE: A high prevalence of Behçet's disease (BD) among familial Mediterranean fever (FMF) patients has been described recently and a weak association of BD and certain MEFV gene mutations, originally linked to FMF, has been reported in an ethnically mixed population from France. We further investigated the presence of MEFV mutations in BD patients from Turkey, a country with a high prevalence of both disorders. METHODS: The frequencies of three FMF-related MEFV mutations (M694V, M680I and V726A) were investigated in BD patients (n = 57) by molecular genetic studies using a polymerase chain reaction with the ARMS method. All patients fulfilled the International Study Group Criteria for the diagnosis of BD and patients with FMF-like symptoms or a chronic inflammatory disease were excluded. RESULTS: Fifteen BD patients were found to carry one single MEFV mutation (26%), compared to 9.1% in the control group (p = 0.003, OR: 3.5, 95% CI: 1.6-7.6). Among 20 BD patients with vascular involvement, 11 (55%) had MEFV mutations compared to 4 patients (11%) in the non-vascular group (p = 0.001, OR: 10, 95% CI: 2.5-39.3). M694V was the dominant mutation in our study group (11 out of 15 patients with mutated alleles). Six out of 7 female patients with vascular involvement carried MEFV mutations in contrast to 5 out of 13 male patients (85.7% versus 38.4%, p = 0.07, OR: 0.1, 95% CI: 0.009-1.14). No association with other clinical manifestations was observed. CONCLUSION: MEFV mutations, originally linked to FMF, may act as a genetic susceptibility factor for other inflammatory disorders such as vascular BD.

Adult↗