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Biomedical subjects

Michael G Alexandrakis

Publications and source records attributed to Michael G Alexandrakis.

27 records · Page 2Linked to original sources
PubMed2003

Hemopoietic progenitor cells and bone marrow stromal cells in patients with autoimmune hepatitis type 1 and primary biliary cirrhosis.

BACKGROUND/AIMS: Autologous hematopoietic stem cell transplantation has been used in severe cases of autoimmunity. We investigated whether hemopoietic progenitor cells and/or bone marrow (BM) microenvironment are affected in autoimmune hepatitis type-1 (AIH-1) and primary biliary cirrhosis (PBC). METHODS: We studied 13 AIH-1 patients, 13 PBC patients, 12 cirrhotic controls (CC) and ten healthy controls (HC). Flow cytometry, expansion cultures, long-term BM cultures and clonogenic progenitor cell assays were used. Stromal cell function was assessed in long-term BM cultures recharged with normal CD34+ cells. RESULTS: AIH-1 had increased CD34+, CD34+/CD38+ and CD34+/CD38- cells compared to all groups (P<0.001). PBC had lower progenitor cells compared to controls (P<0.005). No differences were found between CC and HC. Committed progenitor cells in non-adherent cell fraction were increased in AIH-1 (P<0.05) but decreased in PBC compared to controls (P<0.05). Granulocyte-macrophage colony forming units (CFU) and erythroid-burst CFU were increased in AIH-1 compared to all groups (P<0.001). PBC had these CFUs decreased compared to controls (P<0.005). Stromal cells failed to support normal hemopoiesis in PBC. CONCLUSIONS: We demonstrated for the first time that AIH-1 had increased hemopoietic progenitor cells and normal stromal function. In PBC, progenitor cells and BM microenvironment were defective. Further studies will determine the significance of these novel findings.

ADP-ribosyl Cyclase↗
PubMed2003

Levels of serum cytokines and acute phase proteins in patients with essential and cancer-related thrombocytosis.

Essential thrombocytosis (ET) is a myeloproliferative disorder resulting in an increased production of abnormal platelets. Reactive thrombocytosis (RT) is occasionally observed in clinical situations including chronic inflammation and malignancy. The aim of the present study was to evaluate the discriminatory efficiency of various laboratory tests in patients with ET and cancer-related RT. Forty-five patients with ET, 52 patients with RT, and 25 age-matched normal individuals comprised the study population. Plasma interleukin-1 alpha (IL-1a), IL-2, IL-6, tumor necrosis factor alpha (TNF-a), platelets, hematocrit, hemoglobin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin were determined. We found increased levels of ferritin, LDH, CRP, ESR, IL-1a, and IL-6 in RT compared with ET (p < 0.01 to p < 0.0005). Hemoglobin, hematocrit, and platelets were significantly lower in RT than in ET (p < 0.0005). Furthermore, ferritin and ESR were negatively correlated with Hct, hemoglobin, and TNF-a, whereas ferritin was positively correlated with ESR, IL-1a, IL-6, and CRP, and IL-1a was positively correlated with IL-6. We consider that the aforementioned parameters should be included in the investigation of unexplained thrombocytosis for the differentiation of essential from cancer related thrombocytosis.

Acute-Phase Proteins↗
PubMed2002

The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome.

BACKGROUND: The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS). METHODS: We measured prospectively tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C). RESULTS: All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 - P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) levels. In contrast to BALF, serum levels of IL-1 and adhesion molecules exhibited a good NPV (68 to 96%), sensitivity (60 to 88%) and survival specificity (74 to 96%) in all groups. All molecules in serum and BALF IL-1 were correlated with the APACHE II (P < 0.05 - P < 0.0001). Serum and BALF IL-1 as well as BALF TNF-alpha were negatively correlated to PaO2/FiO2 (all P < 0.05). CONCLUSIONS: The studied molecules have good NPV for ARDS development both in serum and BALF. Serum rather than BALF levels seem to be related to outcome.

Acute Disease↗
PubMed2002

Evaluation of bone disease in multiple myeloma: a correlation between biochemical markers of bone metabolism and other clinical parameters in untreated multiple myeloma patients.

INTRODUCTION: Multiple myeloma (MM) is characterised by an uncoupled bone formation/resorption process resulting in osteolysis. Osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) are markers of osteoblastic activity, whereas pyridinoline products and the cross-linked aminoterminal of type I collagen (NTx) reflect bone destruction. In this study, these markers were studied in relation to bone disease severity and other clinical parameters of MM activity. METHODS: Serum calcium, creatinine, CRP, beta 2 microglobulin (b(2)M), M-component, OC, BAP and free urine pyridoline (Pyd) and deoxypyridinoline (Dpd), free urine Dpd and NTx were determined in 38 newly diagnosed MM patients. X-ray examination defined the degree of bone involvement. Patients were classified according to the Durie-Salmon staging system. RESULTS: NTx, free urine Pyd + Dpd, and free urine Dpd increased with increasing degree of bone involvement. NTx was significantly higher in stages II and III compared to stage I (mean values: 100.7, 163.5 and 208.3 nmol BCE/mM creat, respectively, p < 0.002). Free urine Pyd + Dpd correlated positively with b(2)M and CRP. OC was increased in stages I and II compared to III (p < 0.005) and was inversely correlated with NTx, free urine Pyd + Dpd, and free urine Dpd alone. CONCLUSIONS: The measurement of bone turnover markers in MM provides significant information regarding disease progression and should be included in the evaluation of MM patients.

Alkaline Phosphatase↗
PubMed2002

Acquired inhibitors to coagulation factors in patients with gastrointestinal diseases.

OBJECTIVES: To study the frequency and specificity of acquired coagulation inhibitors in inflammatory and malignant gastrointestinal diseases. METHODS: In a 10-year period, 511 patients from the island of Crete in Greece were studied, 302 with ulcerative colitis, 112 with Crohn's disease, 82 with gastrointestinal carcinoma and 15 with gastrointestinal lymphoma. Prothrombin time and activated partial thromboplastin time were measured by routine methods. When prothrombin time and/or activated partial thromboplastin time were found to be prolonged, mixture experiments with 25%, 50% and 75% pooled normal human plasma were performed. If clotting times were inadequately corrected, the presence of an acquired inhibitor against a coagulation factor was suggested. Specific coagulation factor assays were then performed with deficient plasmas. RESULTS: Fifteen patients acquired inhibitors to the following coagulation factors within the 10-year observation period: factor IX (four patients); factor X (three patients); factor XII (three patients); factor VIII (two patients); factor XI (two patients); and factor V (one patient). The activity of the above factors varied from < 1% to 10%. Five patients with ulcerative colitis, six with Crohn's disease, two with gastrointestinal lymphoma and two with gastrointestinal carcinoma developed an inhibitor. Only one patient with factor VIII inhibitor presented with severe bleeding and was treated with recombinant human activated factor VII, while the others had no complications. Remission was obtained in all patients after immunosuppressive therapy, chemotherapy or tumour resection. CONCLUSION: An increased incidence of coagulation factor inhibitors was found in patients with gastrointestinal inflammatory and malignant diseases compared to the healthy population. In addition, an increased incidence of these inhibitors was also found in the common population of Crete compared to that found in other areas.

Adolescent↗
PubMed2002

Pleural interleukin-1 beta in differentiating transudates and exudates: comparative analysis with other biochemical parameters.

BACKGROUND: The differential diagnosis of pleural effusion is a frequent clinical problem. The possible role of pleural fluid cytokines in discriminating transudates from exudates has not been studied adequately. OBJECTIVE: The aim of this study was to evaluate the serum and pleural fluid levels of interleukin-1 beta (IL-1 beta) and to compare it with common biochemical parameters such as cholesterol (CHOL), lactate dehydrogenase (LDH), total protein and albumin. METHODS: One hundred and six consecutive patients with pleural effusion were studied. IL-1 beta was measured simultaneously in blood and pleural fluid using a radioimmunoassay. Standard laboratory methods were employed for biochemical parameters. RESULTS: Using ROC analysis, a pleural IL-1 beta cutoff level 18.16 fmol/ml had a sensitivity of 76.8%, a specificity of 58.3% and a positive predictive value (PPV) 86.3% in the discrimination of transudates vs. all exudates. Serum IL-1 beta levels were higher in the nonmalignant group but without statistical difference compared with transudate patients. In addition, a significant difference was found between serum IL-1 beta in the malignant group in comparison with those of the transudate group (p < 0.01), also IL-1 beta levels were significantly increased in exudate effusion when compared with transudate (p < 0.001, p < 0.05, respectively). CHOL values of > or =65 mg/dl had 92.7% sensitivity, and 100% specificity and PPV for both. CONCLUSIONS: The results of this study suggest that although IL-1 beta could be a marker with relatively good sensitivity and PPV for the differentiation of pleural effusion, the cost and time needed do not support its use as a routine laboratory test.

Adult↗
PubMed2001

Reduced CD43 expression on the neutrophils of MDS patients correlates with an activated phenotype of these cells.

CD43 (also known as leukosialin and sialophorin) is a surface sialoglycoprotein expressed at high levels on most leukocytes implicated in adhesion, antiadhesion, and activation/proliferation mechanisms. We studied the expression of this molecule on the leukocytes of patients with myelodysplastic syndromes (MDSs) in an effort to detect acquired deficiencies of this molecule. We used immunofluorescence flow cytometry in analyzing whole blood and isolated neutrophils from 49 MDS patients, 33 men and 16 women aged 33 to 85 years (median, 75 years), and 18 healthy individuals aged 35 to 80 years (median, 72 years). According to French-American-British classification criteria, 13 patients had refractory anemia, 18 had refractory anemia with ringed sideroblasts, 9 had refractory anemia with excess of blasts, 4 had refractory anemia with excess of blasts in transformation to acute leukemia, and 5 had chronic myelomonocytic leukemia. We found decreased expression of CD43 on the neutrophils of these patients, and we correlated this finding with the activation status of these cells as it is defined by their phenotypes. We studied the expression of CD11b, CD18, CD35, CD67, CD69, CD44, and CD53 molecules known to be changed in the activated form of neutrophils. CD43 expression correlated positively with CD53 and CD44 expression and negatively with CD11b, CD18, CD35, CD67, and CD69 expression. Additionally, increased levels of soluble vascular cell adhesion molecules were detected in these patients, suggesting endothelial cell activation. In conclusion, we believe that the decreased expression of CD43 on the neutrophils of MDS patients is associated with activation of these cells and is probably due to cleavage of the molecule from the cell surface and that the same mechanism is possibly responsible for the parallel down-regulation of CD44 and CD53.

Adult↗
PubMedDate not supplied

The isoflavone genistein inhibits proliferation and increases histamine content in human leukemic mast cells.

Mast cells are involved in allergic inflammation and some rare disorders such as systemic mastocytosis and mast cell leukemia. Certain naturally occurring flavonoids have been shown to inhibit mast cell activation and promote maturation of secretory granules. Here, we report that the isoflavone genistein inhibited the growth of human leukemic mast cells (HMC-1) by 68.8, 51.6, and 30.2% at 10(-4), 10(-5), and 10(-6) M, respectively, at day 3 (p < 0.001). Genistein at 10(-4) M increased the histamine content per 2 x 10(5) cells at day 3 from 5.9 +/- 1.2 micrograms/mL to 11.1 +/- 1.3 micrograms/mL (n = 6; p < 0.0001). These results indicate that genistein can inhibit proliferation and induce maturation of HMC-1 cells.

Cell Culture Techniques↗