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Biomedical subjects

S Kirazli

Publications and source records attributed to S Kirazli.

At least 37 records · Page 2Linked to original sources

Serum L-selectin and P-selectin levels in lymphomas.

The migration of normal and malignant lymphoid cells is governed by specific adhesion molecules. Selectins comprise a family of adhesion receptors expressed by leukocytes, platelets and endothelial cells. In this study, the serum levels of soluble L-selectin and P-selectin were measured in patients with non-Hodgkin's lymphoma and Hodgkin's disease and found to be significantly elevated in both patient groups compared to healthy controls. This result provides evidence that alterations in the expression and function of adhesion molecules may play an important role in the progression of lymphomas. Further studies are awaited to establish the exact roles of these adhesion molecules in distinct patterns of growth and spread of lymphomas.

Adult↗

Increased plasminogen activator inhibitor-1 activity in offspring of type 2 diabetic patients: lack of association with plasma insulin levels.

OBJECTIVE: To determine whether a dysregulation of the fibrinolytic system exists in normal glucose tolerant offspring of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In this cross-sectional study, 32 offspring of type 2 diabetic patients and 26 subjects with no family history of diabetes were studied. With respect to the metabolic parameters, plasma fasting and 2-h postload (75 g glucose) glucose and insulin levels, total cholesterol, triglycerides, and HDL cholesterol concentrations were determined. To evaluate the status of hemostatic factors, fibrinogen, tissue plasminogen activator (tPA) antigen level, plasminogen activator inhibitor-1 (PAI-1) antigen level, and PAI-1 activity were assessed. The statistical analyses included the Mann-Whitney U test to check the significance of differences between variables in the two groups and Spearman's rank correlation tests to check the interrelationships between the hemostatic and metabolic parameters in the offspring group. RESULTS: All subjects had normal glucose tolerance according to the American Diabetes Association criteria. Plasma fasting and postload insulin concentrations were significantly higher in offspring compared with control group (P<0.00001 and P<0.01, respectively). Plasma fasting and postload glucose, fibrinogen, tPA antigen, total cholesterol, and BMI were comparable between the groups. The offspring had significantly higher waist-to-hip ratio (WHR) (P = 0.03), higher triglycerides (P = 0.01), and lower HDL cholesterol (P<0.01) compared with the control group. PAI-1 antigen level and PAI-1 activity were higher in the offspring (P = 0.05 and P = 0.04, respectively). In the offspring group, PAI-1 activity was correlated with plasma PAI-1 antigen level (r = 0.40, P = 0.02), fibrinogen (r = 0.45, P = 0.01), and HDL cholesterol (r = -0.36, P = 0.04). However, tPA antigen level, fasting and postload plasma glucose and insulin, total cholesterol, triglycerides, WHR, and BMI did not correlate with PAI-1 activity. CONCLUSIONS: These data suggest that normal glucose tolerant offspring of type 2 diabetic subjects have elevated PAI-1 activity indicating to hypofibrinolysis in this group. The elevated PAI-1 activity has no association with plasma insulin concentration.

Adult↗

CA 15-3, ceruloplasmin and tissue polypeptide specific antigen as a tumour marker panel in breast cancer.

BACKGROUND: Tumour markers along with other tests, may be useful in the assessment of the prognosis, monitoring response to treatment and early detection of metastases in breast cancer. The most commonly used breast cancer antigen is CA 15-3. OBJECTIVE: To examine the value of CA 15-3, ceruloplasmin and tissue polypeptide specific antigen (TPS) panel in the monitoring of breast cancer. SUBJECTS: Serum concentrations of CA 15-3, ceruloplasmin and TPS were measured in 90 women: Fifteen controls, sixteen patients with benign breast disease (BBD), thirty one patients in remission and twenty eight patients with active breast cancer. RESULTS: The results of CA 15-3, ceruloplasmin and TPS estimates were separated into four groups. The patients not in remission were found to have significantly higher levels of CA 15-3 (p<0.0001) and ceruloplasmin (p<0.0001) compared with the other three groups. The difference between the patients in remission, BBD and the control group was not statistically significant (p>0.05) for CA 15-3 and ceruloplasmin. The difference for TPS between the patients in remission and the patients with active breast cancer was not statistically significant (p>0.05). The sensitivities of CA 15-3, ceruloplasmin, and TPS for detecting active breast cancer were 75.0%, 75.0%, and 78.0%, respectively. CONCLUSION: The highest sensitivity for active breast cancer detection was obtained by the combined use of three tumour markers. We concluded that there may be an advantage in using panels in the follow up of breast cancer patients, although so far such tests have too low a specificity to be of practical value in screening.

Adolescent↗

Effects of interferon-alpha2a treatment on serum levels of tumor necrosis factor-alpha, tumor necrosis factor-alpha2 receptor, interleukin-2, interleukin-2 receptor, and E-selectin in Behçet's disease.

This study was performed to investigate serum levels of various cytokines and E-selectin in patients with Behçet's disease (BD) before and after treatment with interferon-alpha2a (IFN-alpha). The study population consisted of 22 patients with active BD; 15 age- and sex-matched healthy adults served as the control group. IFN-alpha (3 million units subcutaneously) was given to all patients twice a week for 3 months. Twenty of twenty-two patients experienced clinical improvement with this therapy. Pre- and post-treatment serum levels of tumor necrosis factor-alpha (TNF-alpha), TNF-alpha2-receptor (TNFalpha2R), interleukin-2 (IL-2), IL-2 receptor (IL-2R), and E-selectin were measured by sandwich-type enzyme immunoassay. Baseline E-selectin, TNF-alpha, and TNF-alpha2R levels of the patients were increased in comparison with the control group and post-treatment values. However, IL-2 and IL-2R levels did not change either with treatment or compared with the control group levels. In conclusion, these results confirm the previously described efficacy of IFN-alpha in the treatment of BD. Serum levels of TNF-alpha, TNF-alpha2R, and E-selectin are prominently increased during active stage of the disease, indicating presence of immune system activation and endothelial injury/activation. Improvement of the pathological cytokinemia and endothelial disturbance accompany interferon-alpha-induced disease remission.

Adult↗

Serum thrombopoietin levels in haemodialysis patients: involvement of arteriovenous fistula.

BACKGROUND: Thrombopoietin (Tpo) is a recently cloned growth factor which plays a critical role in the regulation of thrombopoiesis. Tpo has also been shown to stimulate in vitro and in vivo erythroid cell growth. Although Tpo transcripts were detected in hepatocytes, proximal tubules and endothelium, mechanisms regulating the level of circulating Tpo have not been fully delineated. Changes in the vessel wall and blood flow in arteriovenous fistula (AVF) might alter Tpo activity. METHODS: Serum thrombopoietin levels and serum erythropoietin levels in samples concurrently obtained from venous returns of AVF and contralateral peripheral veins in 31 haemodialysis patients were determined and compared with 12 healthy controls. Levels were also compared between 14 haemodialysis patients (group I) treated with recombinant human erythropoietin (rHu-Epo) and 17 haemodialysis patients (group II) not requiring rHu-Epo. RESULTS: Serum Tpo levels (44.8 +/- 23.9 pg/ml, vs 129.9 +/- 113.6 pg/ml, P<0.05) and platelet counts (194 +/- 55, 10(6)/ml vs 273 +/- 94. 10(6)/ml, P<0.05) of haemodialysis patients were lower than healthy controls. Serum Tpo levels were inversely correlated with platelet counts in the control group (R=-0.61, P<0.05), but not in haemodialysis patients. Tpo concentrations of AVF samples were lower than peripheral venous samples (31.6 +/- 17.7 pg/ml vs 44.8 +/- 23.9 pg/ml, P=0.001). No significant difference was present between the serum Tpo concentrations of haemodialysis patients in group I and group II. Serum Tpo levels were not correlated with haemoglobin levels or serum erythropoietin levels in haemodialysis patients. CONCLUSION: Decreased serum Tpo levels despite low platelet counts in haemodialysis patients suggest that the proposed feedback mechanism of platelet uptake of Tpo is not fully operative in these patients. Moreover, AVF might affect the local production and/or catabolism of this growth factor.

Adolescent↗

Increased systemic coagulation activity in patients with rheumatic mitral stenosis: assessment of the clinical and echocardiographic determinants.

In this study, we aimed to determine systemic coagulation activity in patients with rheumatic mitral stenosis and to define determinants of a possible prethrombotic state. Peripheral venous plasma level of thrombin-antithrombin III complex was measured in 84 consecutive patients with rheumatic mitral stenosis who had no left atrial thrombus by transesophageal echocardiography. The patients had significantly higher thrombin-antithrombin III complex values (mean +/- SD = 9.6+/-15.9 ng/ ml) compared with the healthy subjects (2.1+/-1.8 ng/ml) (P<0.001). Among many clinical and echocardiographic variables, severe mitral regurgitation (odds ratio = 6.7, P<0.001) and left atrial spontaneous echo contrast (odds ratio = 22.8, P<0.001) appeared as significant predictors of the increased systemic coagulation activity in multivariate logistic regression analysis. In conclusion, systemic coagulation activity is increased in the patients with rheumatic mitral stenosis, and coexistence of severe mitral regurgitation and presence of left atrial spontaneous echo contrast are determinants of this increment.

Adult↗

Selectins and IL-6 during the clinical course of idiopathic thrombocytopenic purpura.

'Stress thrombocytes', i.e. large and presumably hyperfunctioning platelets, is a well-known characteristic of patients with idiopathic thrombocytopenic purpura (ITP). Therefore, despite what may be severe thrombocytopenia these patients generally do not suffer from severe life-threatening hemorrhage. The plasma level of soluble P-selectin (sP-selectin) is a valuable marker reflecting platelet activation. Available data suggest that interleukin-6 (IL-6) may contribute to the regulation of megakaryocytopoiesis and platelet activity. The purpose of this study is to investigate the status and kinetics of IL-6 and selectins, which are involved in the platelet function, production, and immunologic functions, during the clinical course of ITP, that may be helpful for understanding the biology of the disease. Twenty-two ITP patients were studied prospectively in the course of their disease. Sixteen, 8 and 6 patients were available after platelet recovery, relapse and splenectomy, respectively. Fifteen healthy persons served as a control group. Higher levels of both sP-selectin and IL-6 were observed in all clinical stages of disease compared to the control group. However, more prominent elevations were present during active stages of ITP, i.e. pretreatment (p < 0.001 vs. control group for both sP-selectin and IL-6) and relapse periods (p < 0.001 vs. control group for both sP-selectin and IL-6). Pretreatment soluble L-selectin and soluble E-selectin levels were not different from the controls. Both sP-selectin (r = -0.32, p = 0.019) and IL-6 (r = -0. 41, p = 0.002) levels inversely correlated with platelet count during disease course. There was a positive correlation between the sL-selectin level and leukocyte count (r = 0.60, p < 0.001). These results suggest that residual platelets are activated in ITP, which offers a relatively benign clinical course compared to other thrombocytopenias. High IL-6 concentration during thrombocytopenia may be involved in compensatory megakaryocytopoiesis and augmented 'residual platelet' functions in ITP.

Adult↗

Paget-Schroetter syndrome associated with FV:Q506 and prothrombin 20210A--a case report.

Effort thrombosis of the axillary-subclavian vein (Paget-Schroetter syndrome) develops usually secondary to heavy arm exertion. An underlying chronic venous compressive anomaly at the thoracic outlet or intimal damage of the axillary vein following forceful hyperabduction, external rotation of the shoulder joint has been proposed to explain the pathophysiology of this thrombosis. This condition is usually not attributed to an underlying hypercoagulability such as deficiency of natural coagulation inhibitors. Here, the authors present a case with thrombosis of the axillary-subclavian vein following an effort, with factor V Leiden and prothrombin 20210A mutations. Both factor V Leiden and the genetic variant in the prothrombin gene have been shown to confer an increased risk for venous thrombosis. Although rare, effort thrombosis may develop in a patient with hereditary thrombophilia, so laboratory evaluation should include the common causes of thrombosis.

Adult↗

Clinical significance of hemostatic markers and thrombomodulin in systemic lupus erythematosus: evidence for a prothrombotic state.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with overwhelming thrombotic states. The precise pathogenetic mechanisms underlying the prethrombotic state in SLE is not fully understood, but interactions between the antiphospholipid antibodies and antigen targets on the coagulation components have been incriminated to play fundamental roles. To evaluate this issue, 34 women with antiphospholipid antibody negative SLE were investigated for molecular markers of blood coagulation and fibrinolytic activity: prothrombin fragment1+2 (PF1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin inhibitor complex (PAP), and tissue factor pathway inhibitor (TFPI). We also analysed plasma soluble thrombomodulin (sTM) levels. SLE disease activity was determined using the SLE Disease Activity Index (SLEDAI). Concentrations of TAT, PAP, PF1+2 and sTM were significantly elevated (P<0.0001, P=0.0002, P<0.0001, and P<0.0001, respectively), while TFPI antigen levels were found to be reduced (P<0.0001) in patients with SLE compared to the control group. In patients with active SLE, anti-ds DNA levels were correlated positively with plasma TAT (P<0.05), PF1+2 (P<0.05), and sTM (P<0.01) concentrations and negatively with plasma TFPI levels (P<0.05). SLEDAI scores were correlated positively with plasma TAT (P<0.01), PF1+2 (<0.01), and sTM (P<0.01) levels. This study illustrates that both a prethrombotic state and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.

Adult↗

Changes of hemostatic factors in children with acute lymphoblastic leukemia receiving combined chemotherapy including high dose methylprednisolone and L-asparaginase.

In this study, protein C (PC), protein S (PS), heparin cofactor II (HCFII), prothrombin fragment 1+2 (PF 1,2), thrombin-antithrombin III complex (TAT), von Willebrand factor (vWF) and thrombomodulin (TM) were investigated in 19 patients with acute lymphoblastic leukemia, (ALL) receiving combined chemotherapy including L-asparaginase (L-ASP) and high dose methylprednisolone (HDMP). HDMP was administered in doses of 30 mg/kg/day for 7 days, and 20 mg/kg/day for another 7 days. In order to evaluate the effect of HDMP on the hemostatic system, the 8 patients studied here received HDMP (30 mg/kg/day) therapy for 4 days before the combined chemotherapy. These parameters were also studied in 12 healthy children as a control group. PC levels were normal in the patients while PS levels were decreased both before and after combined chemotherapies. Patients with ALL have laboratory signs of coagulation activation such as PF 1,2, TAT prior to initiation of chemotherapy. With combined chemotherapy, TAT levels were found to be normal while PF1,2 were not. TM levels were found to be increased both before and after therapies whereas HCFII and vWF levels were not different from those of the control group. The short course of HDMP therapy did not prominently influence these hemostatic parameters. These results indicate that both the malignant process and the drugs used in combined chemotherapy cause a decrease in natural inhibitors and an increase in procoagulant activity and endothelial injury. These hemostatic changes may contribute to a thrombotic tendency in the patients with ALL.

Adolescent↗

Circulating thrombomodulin, thrombospondin, and fibronectin in acute myeloblastic leukemias.

In this study, soluble thrombomodulin (TM) was measured as an indicator of endothelial injury in acute myelocytic leukemia (AML) together with fibronectin (FN) and thrombospondin (TS). The study group comprised of 17 (6 men, 11 women; aged 34 +/- 10 years; range 21-61 years) newly diagnosed AML patients. There was infection in 6 patients. Twelve (4 men, 8 women; aged 31 +/- 11 years; range 18-55 years) healthy subjects were studied as the control group. Plasma soluble TM levels were significantly higher in AML patients than in the healthy control group (116.6 +/- 13.7 vs 37.2 +/- 1.75 ng/ml, respectively (mean +/- SEM), p < 0.01). Plasma FN levels were found to be significantly higher in AML patients compared to the control group (15.9 +/- 2.69 vs 8.1 +/- 2.46 ng/ml, respectively (mean +/- SEM). p < 0.01 ). Plasma FN levels in infected patients were significantly lower than in non-infected patients (6.47 +/- 1.3 vs 21.0 +/- 3.1 ng/ml, respectively (mean +/- SD), p < 0.01). Plasma TS levels in the patient group were significantly lower than in the control group (20.6 +/- 1.45 vs 120.8 +/- 18.2 ng/ml, respectively (mean +/- SEM), p < 0.01). In one patient with M7 megakaryoblastic leukemia who also had a high platelet count, plasma TS levels were significantly higher than that in other patients.

Adult↗

Thrombopoietin and thrombospondin in renal allograft recipients.

Recipients of renal transplants appear to be at increased risk of thromboembolic events. Despite accumulating evidence for the hyperreactivity of platelets, the primary regulator of thrombopoiesis, thrombopoietin (TPO), has not yet been studied in renal transplant recipients. Thus, the aim of the present study was to quantify the levels of TPO and to assess its contribution to increased platelet reactivity in recipients of renal allografts. Serum concentrations of thrombospondin (TSP) were also determined in patients undergoing renal transplants in order to evaluate the role of this multifunctional protein in platelet hyperaggregability. Serum levels of TPO were significantly lower in renal transplant recipients (n = 27) than in healthy controls (30.8+/-20.6 pg/ml versus 129.9+/-113.6 pg/ml, P = 0.001). Serum concentrations of TPO were correlated neither with serum levels of creatinine nor duration of transplantation. However, levels of TPO were negatively correlated with platelet counts (r = -0.50, P = 0.007) in recipients of renal transplants. Plasma levels of TSP were higher in renal transplant patients than in the control group (104.5+/-54.7 ng/ml versus 63.4+/-41.5 ng/ml, P = 0.003). No significant correlation was found between levels of TPO and TSP. We conclude that, rather than the allograft function, the platelet mass determines the levels of TPO in recipients of renal transplants. Despite the low serum levels of TPO, and increased concentrations of TSP, TPO might still play a role in the hyperaggregability of platelets in patients undergoing renal transplants.

Adult↗

Circulating thrombopoietin in systemic sclerosis.

OBJECTIVE: To investigate circulating thrombopoietin (TPO) concentrations in systemic sclerosis (SSc). METHODS: TPO concentrations were measured by ELISA in serum samples of 13 patients (11 female, 2 male) with diffuse SSc, 15 healthy controls (13 female, 2 male), and 15 patients (13 female, 2 male) with rheumatoid arthritis (RA). Thrombocyte counts of patients with SSc and RA and controls were recorded. RESULTS: Median TPO concentrations were 115 (164) in SSc, 76 (32) in RA, and 62 (34) pg/ml in controls. Median serum TPO concentration in the SSc group was significantly higher than other groups; there was no difference between controls and patients with RA (p<0.001 for both comparisons). Median platelet counts of SSc, RA, and controls were 224+/-58x10(9)/l, 238+/-44x10(9)/l, and 272+/-35x10(9)/l, respectively. There was no correlation between thrombocyte counts and TPO levels in any group. CONCLUSION: We show that patients with SSc have higher serum TPO concentrations compared to healthy controls and patients with RA. It can be hypothesized that TPO mediated release of particular growth factors may participate in the pathogenesis of the fibrotic process of SSc.

Adult↗

Determinants of soluble CD23 antigen levels in hemodialysis patients: effect of 1.25 dihydroxyvitamin D3 and recombinant human erythropoietin treatment.

BACKGROUND: The immunodeficiency of end-stage renal disease (ESRD) paradoxically coexists with T cell and monocyte activation. In spite of well known defective antibody responses in ESRD, the functional status of B cells in the immune system dysregulation of uremia is still controversial. Soluble CD23 (sCD23) antigen is a recently identified B cell activation marker and is also involved in T cell activation process. Effects of parathyroid hormone (PTH), red blood cells and ferritin on T and B cell functions have been shown both in vivo and in vitro. PATIENTS AND METHODS: In this study, serum levels of sCD23 in hemodialysis patients were determined to evaluate the functional status of B cells and possible linkages between this cytokine and PTH levels, ferritin levels, red blood cell counts were investigated. RESULTS: Serum sCD23 levels were significantly elevated in hemodialysis patients relative to healthy controls (12.5+/-8.4 micro/l vs. 2.4+/-1.1 micro/l, p<0.001). Serum sCD23 levels were negatively correlated with red blood cell count (r = -0.61, p = 0.009) and serum PTH levels (r = -0.62, p = 0.008), while positively correlated with serum ferritin levels (r = 0.63, p = 0.007) in hemodialysis patients. We also investigated the immunumodulator effects of 1.25 dihydroxyvitamin D3 (1.25OHD3) and recombinant human erythropoietin (rHu-Epo) treatment in hemodialysis patients. 1.25OHD3 treatment for eight weeks did not change serum sCD23 levels in hemodialysis patients (n = 8). On the other side, rHu-Epo administration for 16 weeks led to a decrease in serum sCD23 levels (17.7+/-8.6 microg/l vs. 9.8+/-3.5 microg/l, p = 0.007) in these patients (n = 9). CONCLUSION: These results suggests that similar to T cells, B cells are activated in uremia and the degree of this activation is correlated with red blood cell count, serum parathyroid hormone levels and iron status of the hemodialysis patients. Moreover, B cell activation could be altered by recombinant human erythropoietin therapy in hemodialysis patients.

Adult↗

Activation of blood coagulation in patients with mitral stenosis and sinus rhythm.

The aim of this study was to assess whether there is blood coagulation activation in patients with mitral stenosis (MS) and sinus rhythm (SR) and to investigate the value of left atrial spontaneous echo contrast (LASEC) as a predictive sign of increased coagulation activity. Using thrombin-antithrombin III complexes and prothrombin fragment 1+2 as in vivo hemostatic markers, we concluded that there is a hypercoagulable state in patients with MS and SR when LASEC is present.

Adult↗

Thrombomodulin levels in Behçet's disease with and without the factor V Leiden mutation.

The plasma levels of thrombomodulin (TM) in 34 patients with Behçet's disease and 79 healthy control subjects were studied. Eight patients had the factor V Leiden (FVL) mutation. The TM level was significantly lower in patients with the FVL mutation than in patients without the mutation and in the healthy controls (p < 0.05 and p < 0.01). However, there was no difference in overall mean plasma TM concentration between the patients without the mutation and the healthy controls.

Behcet Syndrome↗