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Biomedical subjects

L Sen

Publications and source records attributed to L Sen.

At least 91 records · Page 5Linked to original sources

Defective function of peripheral blood monocytes in patients with Hodgkin's and non-Hodgkin's lymphomas.

Phagocytosis and lysis of C. pseudotropicalis by peripheral blood monocytes from Hodgkin's and non-Hodgkin's lymphoma were analysed. In Hodgkin's disease, there was a decrease in the phagocytic activity of blood monocytes; moreover, the candidacidal activity was significantly decreased as compared with normal controls. Although monocytes from non-Hodgkin's patients presented normal phagocytic function, the ability to kill C. pseudotropicalis was impaired. In both groups of lymphomas, the data showed that the abnormal findings were not related to treatment. These results indicate that monocytes from Hodgkin's and non-Hodgkin's lymphoma posses a deficiency in killing C. pseudotropicalis, which could be due to an intrinsic macrophage defect in the myeloperoxidase-independent mechanisms and which may be responsible for the predisposition of the se patients to candida infections.

Adolescent↗

Defective blood mononuclear phagocyte function in patients with leprosy.

Patients with lepromatous leprosy possess a defective lymphocyte function in vivo and in vitro that is less evident in the tuberculoid form. Data concerning their macrophage ability to digest Mycobacterium leprae are controversial. The purpose of this study was to determine whether monocytes from patients with either tuberculoid or lepromatous leprosy were altered in their enzyme systems, that is myeloperoxidase-dependent and myeloperoxidase-independent systems. The ability of adherent blood monocytes to ingest and kill Candida pseudotropicalis after 30 and 60 min of incubation with yeast cells was tested. Mononuclear phagocytic cells from patients with either principal form of leprosy functioned similarly to normal monocytes in phagocytosis while their fungicidal activity for C. pseudotropicalis was statistically significantly altered and was more evident in the lepromatous than in the tuberculoid type. The results indicate that peripheral blood monocytes from patients with leprosy possess an impaired enzymatic candidacidal activity.

Adult↗

Initial prognostic factors and lymphoblast-erythrocyte rosette formation in 109 children with acute lymphoblastic leukemia.

Bone marrow lymphoblasts from 109 children admitted with untreated acute lymphoblastic leukemia (ALL) were tested for spontaneous rosette formation with sheep erythrocytes. Twenty-six children (24%) had lymphoblasts that formed rosettes (E+). Of 13 initial clinical characteristics, 8 were significantly associated with E+ lymphoblasts: mediastinal enlargement (86% of patients E+), leukocyte counts over 100 X 10(9)/liter (65% E+), nodes greater than 2 cm in any diameter (65% E+), age over 5 yr (46% E+), hemoglobin over 8 g/dl (44% E+), hepatomegaly greater than 5 cm (38% E+), boys (35% E+), and lymph node enlargement outside of the cervical area (28% E+). Spleen size, initial platelet counts, and periodic acid-Schiff scores did not distinguish E+ from E- patients. Since few patients were black and few presented with central nervous system leukemia, the association of these two characteristics with E+ blasts could not be determined. A hierarchical classification scheme and a linear logistic regression model were used to define the patterns of characteristics associated with E+ lymphoblasts. The initial clinical characteristics and the poorer course of E+ patients suggest that ALL comprises at least two biologically and clinically distinct types. The E+ ALL may result from a leukemic transformation of a non-Hodgkin lymphoma.

Adolescent↗

Acute lymphoblastic leukemia (ALL) antigens detected with antisera to E rosette-froming and non-E rosette-forming ALL blasts.

Based on the presence or absence of erythrocyte receptors(E) a T cell marker, acute lymphocytic leukemia (ALL), can be divided into E+ALL and E-ALL. We studied cell surface antigens on blasts from 12 children with untreated ALL: eight with E-ALL and four with E+ALL. Heterologous antisera were raised against thymus cells, E+ and E-ALL blasts, appropriately absorbed and tested by immunofluorescence and a radiolabeled antibody assay with normal and leukemic lymphoid cells. By both methods, anti-thymus and anti-E+ALL sera reacted with human thymocytes. Specific binding of anti-E+ALL serum to T antigens was indicated by the fact that a single absorption with thymocytes abolished its binding to allogenic thymocytes, and the reactivity of anti-E+ALL serum with thymus, blood and bone marrow lymphocytes was similar to that of anti-thymus serum. After exhaustive absorption with blood leukocytes, anti-E+ALL and E-ALL sera were negative against normal lymphocytes and bone marrow cells from children with ALL in remission. Anti-thymus and anti-E+ALL sera reacted with blasts from patients with E+ALL, but not with E-ALL. In contrast, anti-E+ALL serum reacted with 40 to 96% of blasts from all children with E-ALL, whereas of the four patients with E+ALL, two were negative and two had the lowest percentage of immunofluorescent cells (10 to 22%). These results were confirmed with the radiolabeled antibody assay. Patients with active E-ALL had cells bearing E-ALL antigen(s) in the peripheral blood and bone marrow, but the number of immunofluorescent cells was lower in blood. Cells reactive with anti-E-ALL serum did not react with thymus cells, blood lymphocytes, remission bone marrow cells, Raji cells, PWM and PHA-induced blasts and CLL cells bearing mIg (uk). These data suggest that the antigen detected on E-ALL blasts by anti-E-ALL serum is neither a HLA-related nor a cell differentiation antigen. Thus, by using antiserum to E+ALL blasts, we have confirmed the presence of a T cell-specific antigen(s) on E+ALL cells. This antiserum did not recognize other leukemia-associated antigens common to E+ and E-ALL. We have also demonstrated an antigen(s) which is regularly expressed on E-ALL blasts and is either not detectable or is present in a lower proportion of E+ALL blasts.

Age Factors↗

Reactivity of human brain antiserum with neuroblastoma cells and nonreactivity with thymocytes and lymphoblasts.

Brain-associated antigens have been detected on human and mouse thymocytes. Also, murine neuroblasts and brain cells have common antigens. In this study we compared the reactivity of rabbit anti-human brain (HB) serum with neoplastic neuroblasts and normal and neoplastic lymphoid cells. The binding of HB antiserum to viable cells was assessed by immunofluorescence and an indirect radiolabeled antibody assay. HB antiserum reacted with greater than 80% of neuroblasts derived from two human cell lines and five children with neuroblastoma, but with less than 1% of human thymocytes, bone marrow lymphoid cells, and lymphocytic leukemia cells. HB antiserum also reacted with 5 to 10% of peripheral blood lymphocytes. Absorption with neuroblasts did not alt-r this reactivity. Rabbit antisera raised against normal human thymocytes and leukemic T-cells specifically bound to thymocytes but did not bind to neuroblasts. The reactivity of anti-HB serum against SK-N-SH neuroblasts was removed by absorption with HB, but not with human kidney or liver, or mouse and guinea pig brain. We conclude that human neuroblastoma cells possess cell-surface antigens that are present on HB. These antigens appear to be species specific and are not present on normal or malignant thymic cells. Conversely, thymus-associated antigens are not expressed on neuroblasts.

Antibodies↗

Erythrocyte receptors and thymus-associated antigens on human thymocytes, mitogen-induced blasts, and acute leukemia blasts.

Human thymus cells and blasts from some patients with acute lymphoblastic leukemia (ALL) express similar cell surface properties. This suggests that this type of ALL originates in the thymus or alternatively that these properties of ALL blasts reflect changes occurring during blastogenesis. To test these possibilities, we determined whether mitogen-thymus antigens found on blasts from E+ALL and on normal human thymocytes. E-rosettes of blood T-lymphocytes dissociated at 37 degrees; in contrast, rosettes formed by E+ALL blasts, human thymocytes, and pokeweed mitogen-stimulated blasts were stable at this temperature. Blasts that formed stable rosettes did not have cytoplasmic Ig, indicating that they were T-lymphoblasts. By immunofluorescence and a radiolabeled antibody assay we demonstrated a thymus antigen(s) that was present on the membrane of E+ALL blasts and on normal thymocytes, but not on normal blood T-lymphocytes [TL-like antigen(s)]. This antigen was not expressed on blasts induced by mitogens. The finding that that mitogen-induced blasts form temperature-stable rosettes, but lack TL-like antigen(s), indicates that this antigen is not required for the expression of E-receptors stable at 37 degrees. The results support the concept that E+ALL results from the malignant transformation of thymus cells.

Antigens↗

Clinical importance of lymphoblasts with T markers in childhood acute leukemia.

Of 48 children with acute lymphocytic leukemia 11 had blast cells with receptors for sheep erythrocytes in their initial bone-marrow aspirates and 37 did not. A comparison of selected clinical features indicated striking differences between the two groups. Leukemia with the receptors was associated with a high proportion of older children, predominantly boys, a thymic mass, and a high white-cell count at diagnosis. In contrast, the 37 children with leukemia without the receptors were generally less than five years of age, with a nearly equal distribution of boys and girls; all but one had normal chest roentgenograms, and only one had a white-cell count greater than 100,000. Thus, the presence or absence of lymphoblasts with sheep erythrocyte receptors--a T-cell marker--distinguishes two forms of childhood acute lymphocytic leukemia, each with a distinct distribution of age and sex as well as other characteristic clinical features.

Adolescent↗

Lack of correlation of lymphoblast cell size with presence of T-cell markers or with outcome in childhood acute lymphoblastic leukaemia.

The proportion of pretreatment bone marrow macrolymphoblasts was determined in a total of 93 children with acute lymphoblastic leukaemia (ALL) in order to assess the validity of cell size as a prognostic indicator. A macrolymphoblast (MLb) was defined as having a diameter greater than 12 mum, and patient samples were divided simply on the basis of whether they had more or less than 10% MLb present at diagnosis. In a retrospective study of a sample of 47 children treated according to Total Therapy Study VII, the continuous complete remission duration, survival and incidence of CNS disease bore no relationship to the cell size distribution present at diagnosis. A second sample of 46 current patients with untreated ALL was examined both for the presence of surface markers for T- and B-cells and for cell size. Bone marrow blasts from 10 of these 46 children formed rosettes with sheep erythrocytes (E)-- a T-cell marker. E-rosette formation was associated with a constellation of adverse prognostic factors, including older age, very high initial WBC counts, organomegaly, and mediastinal enlargement; yet the presence of this T-cell marker was unrelated to cell size. We conclude that pretreatment lymphoblast cell size is not a reliable prognostic indicator in childhood ALL.

Adolescent↗

E receptors on blasts from untreated acute lymphocytic leukemia (ALL): comparison of temperature dependence of E rosettes formed by normal and leukemic lymphoid cells.

The presence of receptors for sheep erythrocytes (E) and sufrace Ig on the bone marrow blasts was investigated in 29 children with untreated acute lymphocytic leukemia (ALL). In 6 of them more than 50% of the bone marrow blasts formed E rosettes, while in none of the 29 were surface Ig detected. The six children with rosette-forming blasts had WBS greater than 5 times 10-4/mm-3 at admission and 4 of them presented with thymic enlargement. E-positive ALL blasts and normal human thymocytes formed rosettes after incubation for 1 hr at 4 degrees C or 37 degrees C. In contrast, normal human peripheral T lymphocytes from blood, spleen, and pleural fluid also formed rosettes at 4 degrees C but these rosettes dissociated at 37 degrees C. In two patients with E-positive ALL, the disappearance from blood of cells forming rosettes at 37 degrees C during the 1st week of treatments paralleled the reduction in circulating blasts. Conversely, after 6 days of therapy almost one-half of the remaining cells formed rosettes at 4 degrees C and had the morphologic features of normal lymphocytes. We conclude that, in contrast to peripheral T cells, normal thymic cells and E-positive blasts share the property of forming E rosettes after 1-hr incubation at 37 degrees C. In patients with E-positive ALL this property may be used to evaluate drug effects upon leukemic and normal T lymphocytes.

Animals↗

Reactivity of antihuman thymocyte serum with acute leukemic blasts.

The presence of receptors for sheep erythrocytes (E) on some leukemic lymphoblasts is suggestive but not conclusive evidence for a thymic origin of these lymphoid cells. Normal and leukemic lymphoid populations were therefore examined to determine if the formation of spontaneous E rosettes correlated with the presence of thymus-associated cell surface antigens. Lymphoblasts from four of 12 children with acute lymphoblastic leukemia (ALL) formed spontaneous E rosettes at 4 degrees C and 37 degrees C (E+) and bound rabbit antihuman thymocyte serum, as determined by indirect immunofluorescence and by an indirect radiolabeled antibody assay. The blasts from the other eight children did not form E rosettes at 4 or 37 degrees C (E-) and did not bind antithymocyte serum. Absorption of the antiserum with peripheral blood leukocytes removed all detectable reactivity with normal peripheral blood lymphocytes, normal bone marrow cells, and E- bone marrow cells, but did not remove all reactivity with thymus cells or E+ leukemic blasts. Absorption of the antiserum with thymus from one donor removed all reactivity against thymus cells from another donor. After absorption with normal peripheral blood leukocytes, the antithymocyte serum reacted with E+ leukemic blasts but not with remission lymphocytes from the same patients. Thus, there are at least two distinct thymus-associated antigens-one that is present on T lymphocytes from peripheral blood as well as thymus and another that is present only on normal thymus and on ALL blasts that are identified by their ability to form E rosettes at 37 degrees C.

Adult↗