The soluble interleukin-2 receptor: a new humoral marker in hematological malignancies.
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Biomedical subjects
Publications and source records attributed to I Frydecka.
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The binding of five fluorescein-labelled lectins: peanut agglutinin (PNA), lentil agglutinin (LEN), soybean agglutinin (SBA), wheat germ agglutinin (WGA) and asparagus pea agglutinin (ASP) to human B-cell chronic lymphocytic leukaemia (B-CLL) and B lymphocytes of normal donors was studied. The specificity of the fluorescence was demonstrated by inhibition with appropriate saccharides. The proportion of B cells was estimated using anti-B cell monoclonal antibody. Both leukaemic and normal B cells showed the binding ability of all except of one (ASP) studied lectins. We have found the differences in surface carbohydrate patterns between B-CLL and normal B lymphocytes. B-CLL cells showed the considerably lower ability to bind SBA and slightly higher expression of PNA and LEN receptors in comparison to normal B cells. The analysis of WGA binding allowed for recognizing two groups of CLL patients: one with high and the second one with low WGA receptor expression. The double marker studies revealed that B cells could simultaneously react with anti-B cell monoclonal antibody and fluorochrome labelled lectins.
Natural killer (NK) cell activity was investigated in 108 patients with Hodgkin's disease (HD) during the course of the disease and in 50 healthy volunteers. NK activity of peripheral blood lymphocytes was evaluated against 51Cr labeled K562 cell line in 4 hr Cr release assay. The mean NK activity was highly significantly lower in patients before treatment and in patients in the active phase of the disease during treatment compared with controls, whereas in patients in complete clinical remission was significantly higher. However, in patients responding to treatment NK activity was increasing, reaching normal rate in remission and was exceeding further during remission duration. Nonresponders to treatment showed considerable decrease of NK activity to undetectable values. The pretreatment level of NK activity was not related to subsequent prognosis of the individual patient.
In 20 patients with non-Hodgkin lymphoma as the first treatment and in 10 patients with the same diagnosis as the second treatment (group II) has been applied the therapeutical protocol proposed by I. Koza et al., composed of 4 monthly cycles of cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone and in the other 4 cycles of doxorubicin, vincristine bleomycin, prednisone. The diagnosis in the I group was: immunoblastic lymphoma in 13 cases, other high grade lymphomas in 5 and low grade lymphoma in 2 cases. In the group II half of the patients showed low or intermediate grade lymphoma but with maximal clinical advancement and resistance to previous therapy. Complete remission (CR) has been obtained in 12 patients of the I group, partial remission (PR) in 7, 1 patient did not respond to therapy. In 3 cases relapse of the disease has been noted, including 2 patients in whom relapse occurred before finishing therapy: the patients remained resistant to alternative one. In the group II the PR and CR has been obtained in 5 and 3 cases respectively: 2 patients with immunoblastic lymphoma resistant to previous therapy did not respond either. Among undesirable effects myelosuppression, mainly granulocytopenia has been mostly noted: infection and septic shock was a cause of death in 1 patient. In 2 patients severe polyneuropathy and in 2 other mucositis of the digestive tract was noted. The treatment used gives beneficial results as induction therapy in cases of immunoblastic lymphoma and enables obtaining remission in therapy resistant cases of low grade lymphoma.
The effect of LD Ara-C (10(-8) mol/l) (Ara-C), TPA (1.6 x 10(-7) mol/l) and 13-cis-retinoic acid (RA) (10(-6) mol/l) on the differentiation in liquid culture of bone marrow cells from 5 patients with acute lymphoblastic, 17 patients with acute myelogenous leukemia, 1 patient in myeloid and 1 in lymphoid crisis of chronic granulocytic leukemia was studied. Ara-C induced morphological and cytochemical differentiation into monocytic cells in 2 cases (M1, M5 type). TPA induced convincing morphological and cytochemical features of maturation into monocytic cells in 4 cases (two M1, one M2, and one M5 type) and into differentiated myeloid cells in 2 cases (M1, M4 type). RA in one case (M2 type) out of three AML studied induced cytochemical and immunocytochemical features of maturation. The results of the study indicate that although TPA is a better inducer of blast cell differentiation than Ara-C, however, neither is a potent differentiation agent of leukemic blasts in liquid culture. The heterogeneity of leukemic blasts within the same type of leukemia was confirmed by their different response to differentiating agents.
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The binding ability of peanut agglutinin (PNA), lentil agglutinin (LEN), soybean agglutinin (SBA), wheat germ agglutinin (WGA), and asparagus pea agglutinin (ASP) to human natural killer (NK) cells with the use of the double-marker immunofluorescence technique was studied. For identification of NK cells, VEP 13 (DC 16) monoclonal antibody was used. The receptor for PNA lectin was shown exclusively after neuraminidase treatment of cells, and VEP 13 antigen was neuraminidase resistant. The majority of VEP 13+ cells showed coexpression of lectin receptors for PNA, LEN, and WGA. Our results suggested that VEP 13 antigen and PNA receptor are two distinct membrane structures, whereas there is some competitive binding between LEN as well as WGA lectin and VEP 13 antibody. In double-marker experiments using PNA and LEN lectin, the small fraction of VEP 13+ cells lacking receptors for these lectins was found. In spite of neuraminidase treatment of the cells, no binding of SBA and ASP was shown. These results indicated apparent heterogeneity of NK cells with respect to lectin receptor expression. WGA lectin, which bound to all VEP 13+ cells, could probably be useful for isolation of NK cells.
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The effect of radium therapy on NK activity in patients with gynecological cancer is presented. Patients were tested before treatment, immediately after treatment and at 1 week intervals for 2 weeks. NK activity in patients before treatment was not statistically different from the normal controls. There was a statistically significant decrease of NK activity after treatment compared to pretreatment value (p less than 0.001). After 1 week NK activity reached pretreatment value and did not change a week later. Radium therapy does not result in a long lasting depression of NK activity, the important host defense mechanism.
Various immunological parameters were studied in 20 asymptomatic patients with hemophilia A, 3 patients with hemophilia B and 1 patient with von Willebrand disease. Patients were treated with cryoprecipitate or fresh frozen plasma. Significantly decreased mean percentage and absolute count (p less than 0.01) of peripheral blood E-rosette-forming cells compared to controls was found. There were normal mean percentages and absolute counts of lymphocytes, T-helper inducer, T-suppressor cytotoxic and natural killer cells. The proportion and absolute number of B cells was slightly increased. Significantly decreased natural killer cell activity (p = 0.02) of peripheral blood lymphocytes was observed. Our results indicate that asymptomatic patients with hemophilia may have early evidence of immunodeficiency.
Clinical and laboratory data were investigated in 80 patients diagnosed during the chronic phase of CGL. Comparison has been made between the group of 24 patients surviving longer than 5 years vs. a group of 56 patients surviving shorter than 5 years. Additionally, a group of 6 patients surviving longer than 10 years was analysed separately. According to our findings the most favourable prognostic factors at diagnosis are: young age, normal hemoglobin level, leukocytosis less than 60 X 10(9)/l, absence of splenomegaly indicating rather a small tumour mass in the body.
The authors reviewed the literature concerned with the action of low dose Ara-C on MDS and some forms of AL and demonstrated their own results in vitro and in vivo. In vitro bone marrow blast cells short-term liquid culture were performed with and without addition of low dose Ara-C. After 5 days culture morphological and also cytochemical changes could be observed often inconsistent with the original cellular type. In vivo 8 patients suffering from AL or MDS were treated with low dose Ara-C and among them marked improvement in 3 cases only was observed.
Natural killer (NK) activity was investigated in 61 patients with Stage III and IV Hodgkin's disease during the course of disease and in 30 healthy age- and sex-matched healthy volunteers. The mean NK activity was significantly lower (P less than 0.001) in untreated patients and in patients in the active phase of the disease during treatment, compared with controls. There was a similar mean value of NK activity in normal subjects, compared with patients in clinical remission. NK activity correlated with the response to therapy. In patients responding to treatment, NK activity was increasing, reaching normal range in remission. The patients not responding to therapy showed gradual decrease of NK activity during the course of disease. These results suggest that the study of NK function might offer a helpful tool in following the clinical course and the efficacy of therapy, as well as for monitoring cancer patients from an immunologic viewpoint.
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