PubMed Health⌕ Search

Biomedical subjects

T Akoğlu

Publications and source records attributed to T Akoğlu.

At least 19 recordsLinked to original sources

Effect of interferon-alpha(2a) on neutrophil adhesion and phagocytosis in chronic myeloid leukemia and Behçet's disease.

Alpha-interferon (alpha-IFN) is implicated in a Behçet's disease (BD)-like syndrome observed in a small number of chronic myeloid leukemia (CML) patients. The effect of alpha-IFN on neutrophil adhesion and phagocytosis in CML patients, BD patients and healthy volunteers was investigated to clarify the reason for this observation. Ten subjects were studied for each group by incubating neutrophils with various doses of alpha-IFN. Basal neutrophil adhesions for CML patients, BD patients and healthy volunteers were similar. However, BD patients had greater basal phagocytosis than CML patients, and both groups had greater basal phagocytosis than healthy volunteers. Neutrophil adhesion and phagocytosis of CML patients increased following incubation with higher doses of alpha-IFN, and phagocytosis approached the high levels observed with BD neutrophils. This study provides evidence that alpha-IFN activates neutrophils in CML patients in a dose-dependent manner, and leads to a neutrophil function profile that resembles BD.

Adult↗

HSP 60 expression in mucocutaneous lesions of Behçet's disease.

BACKGROUND: Heat shock protein (60 kd HSP) has been implicated in the etiology of Behçet's disease, but its expression at sites of inflammation is unknown. OBJECTIVE: Our aim was to investigate local HSP 60 expression and to quantify T-cell receptor (TCR) gamma delta-positive cells, which are known to respond to HSP peptides. METHODS: Patients with active Behçet's disease (n = 21) and controls (n = 18) were included. Flow cytometric analysis was performed on peripheral blood to investigate TCR gamma delta-positive cell counts. Biopsies were performed on active skin lesions, and immunohistochemical analysis was performed by a streptavidin-biotin method using the monoclonal ML-30 antibody; HSP staining intensity and distribution were evaluated in a blinded fashion. Immunohistochemical studies were performed to quantify TCR gamma delta-positive cells at lesional sites. RESULTS: Mucocutaneous lesions of patients with Behçet's disease had statistically significantly increased expression of HSP 60/65. Peripheral blood TCR gamma delta-positive cell counts were similar in both groups. However, lesional skin of patients with Behçet's disease had significantly increased gamma delta-positive T-cell counts. CONCLUSION: Up-regulation of HSP expression was found at lesional skin sites in Behçet's disease. The increased number of TCR gamma delta-positive cells, which are known to respond to HSP peptides, may support the function of HSPs in the etiology of Behçet's disease. However, these findings may also be an epiphenomenon that needs to be further investigated.

Adult↗

Remitting seronegative symmetrical synovitis with pitting oedema associated with chronic lymphocytic leukaemia.

We describe a case of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE syndrome) in a 67-year-old man. Immunophenotyping studies and histology of biopsy specimens revealed chronic lymphocytic leukaemia (CLL). Polyarthritis and oedema were revealed by small doses of corticosteroids. The association of RS3PE syndrome with rheumatological and malign disorders are discussed.

Edema↗

Morphological and functional characteristics of short-term and long-term bone marrow cultures in chronic myelogenous leukemia.

Clonogenic capacity of bone marrow progenitors and stromal layers established from bone marrow of 12 patients with CML and 13 healthy controls were evaluated. The initial BFU-E and CFU-GM contents were slightly higher in the CML patients (p > 0.05) in contrast to CFU-GEMM. CFU-GEMM was lower in the patients compared to healthy controls (p < 0.001). In long-term cultures, the number of non-adherent cell population and total clonogenic progenitor cell content decreased gradually in both groups. Weekly evaluation of stromal confluency of adherent cells revealed that establishment of adherent stromal layer was slower in CML patients than in control samples (p < 0.05). At the end of fourth week, the number of samples presenting confluency was 41.7% in the CML group compared with 92.3% in the controls. The initial CD34 positive cell content of the bone marrow samples was similar in both groups. Although CD34 positive cell number in the adherent stromal layer was well preserved in the control group at the end of 4 weeks, this figure decreased significantly in the CML group. The numbers of total adherent cells as well as the total clonogenic progenitor content of adherent layer were also lower in the CML group (3.03% vs 98.2%). When normal CD34+ cells were cultured on IFN-alpha-treated stromal layer followed by the assessment of the long-term culture initiating cells, a reduced capacity to support hemopoietic growth was observed with IFN-alpha-treated normal stroma. This reduction was even higher when CML stroma was treated with IFN-alpha followed by the seeding of the normal CD34+ cells on this stromal layer (26.9% vs 42.8%). These findings show that stromal cells are abnormal in CML patients as well as the progenitor cells, and IFN-alpha treatment causes further defects of the stromal cells.

Adult↗

Double G0/G1 peak in the DNA histogram of aberrant marker positive acute leukemia patients is associated with a poor clinical outcome.

In order to investigate the relationship between aberrant marker expression and DNA ploidy, 61 adult patients with acute leukemia (39 AML and 22 ALL) were studied. Aberrant marker expression was observed in 20 patients (16/39 of AML and 4/22 of ALL patients). In flow cytometric DNA analysis aneuploidy was observed in 18 patients (9/39 of AML and 9/22 of ALL patients). The incidence of aneuploidy in patients with aberrant marker expression was 35% whereas this was 26.8% in patients without aberrant marker expression. Furthermore, 7 patients with aberrant marker expression showed an aneuploid, double G0/G1 peaks appearance whereas the remaining 11 patients with aberrant marker expression had euploid DNA content. Double G0/G1 appearance was not observed in patients without aberrant marker expression. Further analyses revealed that this did not correlate with apoptosis. All 7 patients, who had both aberrant marker expression and double G0/G1 peak had a poor clinical outcome with a short survival and all died within three months whereas three-months survival was 67% for AML, 69% for ALL patients and 81% for patients with aberrant marker expression respectively (p<0.01). Our data indicate that the evaluation of the DNA ploidy in patients with aberrant marker expression may be of prognostic importance.

Acute Disease↗

Phagocytosis and oxidative burst by neutrophils in patients with recurrent furunculosis.

Neutrophil phagocytosis of fluorescently labelled Staphylococcus aureus and oxidative burst by the neutrophils were assessed by flow cytometry in 22 patients with recurrent furunculosis and in 17 controls. Phagocytosis and oxidative burst were not found to be significantly different between the patients and controls. Low serum iron concentrations were demonstrated in six patients (27%). In these patients with hypoferraemia, oxidative burst was significantly lower than in the patients without hypoferraemia and in the controls. These data suggest that hypoferraemia may be an important predisposing factor in a subgroup of patients with recurrent furunculosis in impairing oxidative killing by neutrophils.

Adult↗

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↗

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↗

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↗

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↗

Variable expression of CD49d antigen in B cell chronic lymphocytic leukemia is related to disease stages.

We have investigated the expression of the dual specific adhesion molecule, VLA-4 (CD49d/CD29) on lymphocytes obtained from 62 patients with B-CLL and compared it with normal controls, patients with other hematological malignancies, and umbilical cord blood. The mean CD49d expression in patients with CLL was lower than the other group of leukemia and the CD19+, CD5+ cells of normal peripheral blood and umbilical cord blood (P < 0.001). The patients in RAI stage 0, I and II (early stage) had even lower CD49d expression, whereas patients in RAI stage III and IV (advanced stage) had relatively higher CD49d levels. In vitro adhesion of lymphocytes to fibronectin, being the extracellular matrix ligand of CD49d, was also investigated. Lymphocytes obtained from B-CLL were found to have lower adhesion to fibronectin than that from controls (P < 0.03). Furthermore, CD49d(low) B-CLL cells had lower adhesion to fibronectin, whereas CD49d(high) B-CLL cells showed normal adhesion ratios (P < 0.002). Further phenotypic analyses revealed the presence of myeloid markers (CD13 and CD33) in most of the advanced stage patients, although these were negative in early stage cases. Expressions of CD11a and sIgM were also low but CD11b was relatively higher in the early stages of the disease. On the basis of these results, we concluded that early stages of CLL are correlated with the expression of CD49d(low), CD11a(low), CD11b(high), CD13-, CD33-, sIgM(low) and also had lower fibronectin adhesion, whereas advanced stages of CLL are associated with CD49d(high), CD11a(high), CD11b(low), CD13+, CD33+, SIgM(high) and show normal fibronectin adhesion.

Antibodies, Monoclonal↗

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↗

Human leukocyte antigen subtype analysis in patients with advanced adenocarcinoma of the prostate.

Human leukocyte antigens (HLA) are cell surface glycoproteins that have a significant role in the immune system. In some cancers, changes in major histocompatibility complex (MHC) class I and II expression, usually a reduction or loss of these molecules, appear to provide a mechanism whereby tumor cells may escape host immunity. HLA analysis in patients with advanced adenocarcinoma of the prostate revealed the antigens with the highest relative risk factors as DRw52, DRw53, Bw73, DR2, and B5(51). As a result, determination of HLA haplotypes may prove to be useful in determining the men with a higher risk of developing prostate cancer.

Adenocarcinoma↗

Serum and urine levels of tumour necrosis factor in patients with genitourinary cancer and their relevance to disease status.

Serum and urine levels of tumour necrosis factor (TNF) which is a lymphokine was measured in patients with genitourinary cancer (either prostatic, bladder or testicular carcinoma) in order to find out whether there were elevated levels of TNF in those patients and if it was related to disease status. Although the preliminary results are not conclusive, further research on TNF may prove this immunoprotein to be a potential diagnostic and therapeutic agent.

Biomarkers, Tumor↗