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D Heumann

Publications and source records attributed to D Heumann.

At least 73 records · Page 4Linked to original sources
PubMed1985

[Clinical characteristics of immature T-type (negative E-rosette) acute lymphoblastic leukemia detected by LAU-A1 monoclonal antibody].

Immature T-ALL is a newly defined subgroup of ALL in which the blasts lack the receptor for sheep erythrocytes (ER) and the usual T-cell markers, but express the 40 kDa pan-T surface antigen recognized by our monoclonal antibody LAU-A1. Patients with immature T-ALL represent 10% of all cases of adult ALL. Leukocyte counts are lower and spleen, liver and lymph node enlargement is less prominent, but mediastinal enlargement is more frequent than in mature (ER-positive) T-ALL. 7 patients with immature T-ALL (median age 42 years, range 13-73) were treated with intensified chemotherapy regimens, and only one 47-year-old female entered a short-lived complete remission. The overall survival of our patients was poor (median 7.5 months, with only one patient surviving at 15 months) and seemed not to be influenced by age. Our study indicates that immature T-ALL can only be accurately identified by the use of monoclonal antibodies recognizing the 40 kDa pan-T antigen, and that immature T-ALL is a separate disease entity typified by a poor prognosis.

Adolescent↗
PubMed1985

Heterogeneity of Ia antigen expression on myeloblastic leukaemias: correlation with stage of maturation defined by cytochemical markers.

The expression of Ia-like antigen (Ia) has been studied in 55 cases of acute myeloid leukaemia (AML) in correlation with the expression of both Sudan Black (SB) and naphthol AS-D chloroacetate esterase (NCAE) stains. Operationally the AML cases were divided into three groups using only NCAE expression on the leukaemic cells: the first group with early maturation stage (MS1) consisted of 30 cases with less than 10% NCAE positive cells (SB: 15-100%): the MS2 group of 14 cases with 10-70% NCAE positive cells (SB: 65-100%) and the MS3 group of 11 cases with 70-100% NCAE positive cells (SB: 89-100%). Ia expression was determined by complement-dependent cytotoxicity, immunofluorescence and immunoperoxidase methods. A similar high percentage (80%) of patients from both group MS1 and MS2 expressed Ia on the surface of 32-100% of the cells. Furthermore, individual comparison of all cases from these two groups showed no correlation between Ia, NCAE and SB expression. Only in the 11 cases from the MS3 group, which included nine cases of promyelocytic leukaemias, was there a correlation between very low expression of Ia antigen with the high NCAE expression. Thus, for AML with a low degree of differentiation the expression of Ia seems to be independent of conventional cytochemical markers of cell maturation.

Antigens, Surface↗
PubMed1985

Characterization of acute undifferentiated leukemia by combined analysis of plasma membrane-associated gamma-glutamyltranspeptidase and soluble terminal transferase.

gamma-Glutamyltranspeptidase (gamma-GT) is a plasma membrane-associated enzyme present in blasts of certain acute leukemias. We analyzed 90 cases of undifferentiated and differentiated acute leukemias for gamma-GT, using a colorimetric assay. Blasts of all patients with common acute lymphoblastic leukemia (ALL) and T-ALL were negative for gamma-GT (less than 5 units). In contrast, gamma-GT was significantly elevated in acute myeloblastic or monoblastic leukemia blasts (P less than .001). In 16 cases of acute undifferentiated leukemia (AUL) studied, the levels of gamma-GT ranged from 0 to 93 units; in eight cases, gamma-GT was positive (greater than 5 units), and six of these had 2% to 5% Sudan black-positive leukemic cells in the blast-enriched suspension. Combined gamma-GT/TdT analysis revealed that both enzyme markers were mutually exclusive in 75% of AUL cases, suggesting that gamma-GT+/TdT-blasts are of nonlymphoid origin, and gamma-GT-/TdT+ blasts are of lymphoid origin. Two cases were devoid of both enzyme activities and could represent truly undifferentiated leukemia. Thus, combined gamma-GT/TdT analysis underlines the heterogeneity of AUL and appears to be useful in defining the lineage commitment of undifferentiated leukemic blasts.

Acute Disease↗
PubMed1984

Monoclonal antibody against a "Pan-T-cell" antigen expressed by thymocytes, peripheral T-lymphocytes and T-cell leukemias.

A monoclonal antibody, LAU-A1, which selectively reacts with all cells of the T-lineage, was derived from a fusion between spleen cells of a mouse immunized with paediatric thymocytes and mouse myeloma P X 63/Ag8 cells. As shown by an antibody-binding radioimmunoassay and analysis by flow microfluorometry of cells labelled by indirect immunofluorescence, the LAU-A1 antibody reacted with all six T-cell lines but not with any of the B-cell lines or myeloid cell lines tested from a panel of 17 human hematopoietic cell lines. The LAU-A1 antibody was also shown to react with the majority of thymocytes and E-rosette-enriched peripheral blood lymphocytes. Among the malignant cell populations tested, the blasts from all 20 patients with acute T-cell lymphoblastic leukemia (T-ALL) were found to react with the LAU-A1 antibody, whereas blasts from 85 patients with common ALL and 63 patients with acute myeloid leukemias were entirely negative. Examination of frozen tissue sections from fetal and adult thymuses stained by an indirect immunoperoxidase method revealed that cells expressing the LAU-A1 antigen were localized in both the cortex and the medulla. From the very broad reactivity spectrum of LAU-A1 antibody, we conclude that this antibody is directed against a T-cell antigen expressed throughout the T-cell differentiation lineage. SDS-PAGE analysis of immunoprecipitates formed by LAU-A1 antibody with detergent lysates of radiolabeled T-cells showed that the LAU-A1 antigen had an apparent mol. wt of 76,000 under non-reducing conditions. Under reducing conditions a single band with an apparent mol. wt of 40,000 was observed. Two-dimensional SDS-PAGE analysis confirmed that the 76,000 mol. wt component consisted of an S-S-linked dimeric complex. The surface membrane expression of LAU-A1 antigen on HSB-2 T-cells was modulated when these cells were cultured in the presence of LAU-A1 antibody. Re-expression of LAU-A1 antigen occurred within 24 hr after transfer of the modulated cells into antibody-free medium.

Animals↗
PubMed1984

Detection of the common acute lymphoblastic leukemia antigen in the serum of leukemia patients.

The common acute lymphoblastic leukemia antigen (CALLA) has been detected in biological fluids using a radioimmunoassay based on the inhibition of binding of 125I-labeled monoclonal anti-CALLA antibody to glutaraldehyde-fixed NALM-1 cells. With this assay, we showed first that CALLA was released in culture fluids from NALM-1 and Daudi cell lines but was absent from culture fluids from CALLA negative cell lines. Then, we found that the sera of 34 out of 42 patients (81%) with untreated common acute lymphoblastic leukemia (c-ALL) contained higher CALLA levels than any of the 42 serum samples from healthy controls. The specificity of these results was further demonstrated by testing in parallel the sera from 48 patients with CALLA negative leukemias, including 26 acute myeloid leukemia (AML), 12 T-cell acute lymphoblastic leukemia (T-ALL), and 10 acute undifferentiated leukemia (AUL). All of these sera gave negative results, except for one patient with AUL, who had a significantly elevated circulating CALLA level, and one patient with AML, who had a borderline CALLA level, 3 SD over the mean of the normal sera. Preliminary results suggest that circulating CALLA is associated with membrane fragments or vesicles, since the total CALLA antigenic activity was recovered in the pellet of the serum samples centrifuged at 100,000 g. In addition, the CALLA-positive pellets contained an enzyme considered as a membrane marker, 5'-nucleotidase. Evaluation of the clinical importance of repeated serum CALLA determinations for the monitoring of c-ALL patients deserves further investigation.

Antigens, Neoplasm↗
PubMed1983

Identification by a monoclonal antibody of a glycolipid highly expressed by cells from the human myeloid lineage.

A monoclonal antibody (MAb) HL-C5, which bound selectively to cells of the myeloid lineage tested, was derived from a fusion between P3/NS2/1-AG8 myeloma cells and splenocytes from a mouse immunized with cells of the promyelocytic leukemia line HL-60. Among a panel of 29 human cell lines derived from either hematopoietic or solid tumors, MAb HL-C5 was found to react exclusively with cells from the five differentiated acute myeloid leukemia lines, HL-60, ML1, ML2, ML3, KG-1B and not with the less differentiated myeloid lines. Fluorescence-activated cell sorter analysis of normal bone marrow samples confirmed that the reactivity of MAb HL-C5 was limited to myeloid cells, from the promyelocytic stage of differentiation to the mature granulocytes. Indirect immunoperoxidase staining of cytocentrifuge preparations of normal bone marrow and peripheral blood leukocytes confirmed these results and showed that MAb HL-C5 stained neutrophils but not eosinophils or basophils. The antigen recognized by HL-C5 was recovered in the upper phase of chloroform-methanol-water lipid extracts prepared from HL-60 cells. By competitive binding experiments, it was found that MAb HL-C5 recognizes the same antigenic determinant as MAb WGHS 29-1, which has been reported to react with glycolipids containing the sugar sequence lacto-N-fucopentaose 111. Autoradiographs of thin layer chromatograms of HL-60 glycolipid extracts which were revealed by incubation with MAb HL-C5 or WGHS 29-1 followed by the addition of 125I-labelled rabbit anti-mouse immunoglobulin antibody confirmed that the two MAbs reacted with the same or structurally very similar glycolipids.

Animals↗
PubMed1983

Characterization of a monoclonal antibody (A12) that defines a human acute lymphoblastic leukemia-associated differentiation antigen.

A human leukemia-associated differentiation antigen has been identified by a monoclonal antibody (A12) raised to the lymphoblastoid cell line NALM-1. The A12 antigen was expressed on the surface of leukemic cells from patients with common acute lymphoblastic leukemia (c-ALL) as well as on cells of the hematopoietic cell lines NALM-1, Reh-6, Raji, Daudi, CEM, and 8402 as determined by an antibody-binding radioimmunoassay, as well as by indirect immunofluorescence and FACS analysis. This antigen was not detected on normal blood lymphocytes, normal bone-marrow cells or leukemic cells from patients with acute myeloid leukemia (AML). The A12 antigen had an apparent molecular weight of 100 kD as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and appeared to be related to if not identical with the acute lymphoblastic leukemia antigen CALLA described by others. Cross-blocking experiments indicated that preincubation of NALM-1 cells with antibody A12 or J5 (anti-CALLA) could block subsequent binding of 125I-labeled A12 and J5 antibody. These results suggest that the two monoclonal antibodies recognize identical or closely located antigenic sites. The surface membrane expression of A12 antigen in NALM-1 cells was modulated when the cells were cultured in the presence of A12 antibody. Under these conditions, the expression of Ia antigens was unaffected. Re-expression of A12 antigen occurred within 24 h after transfer of the modulated cells into medium devoid of monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1983

Expression of common acute lymphoblastic leukemia antigen (CALLA) on human malignant melanoma cell lines.

Fifteen human melanoma cells lines were tested by an antibody-binding radioimmunoassay using a monoclonal antibody (A12) directed against the common acute lymphoblastic leukemia antigen (CALLA). Cells from six melanoma lines were found to react with this antibody. The level of antigen and the percentage of positive cells in these six melanoma lines showed wide variation, as demonstrated by analysis in the fluorescence-activated cell sorter (FACS). Immunoprecipitation of solubilized 125I-labeled membrane proteins from CALLA positive melanoma cells with A12 monoclonal antibody revealed a major polypeptide chain with an apparent m.w. of 100,000 daltons, characteristic for CALLA as determined on SDS-polyacrylamide gel electrophoresis. The expression of CALLA on MP-6 melanoma cells was modulated when the cells were cultured in the presence of A12 antibody. Reexpression of CALLA on these cells occurred within 5 days after transfer of the modulated cells into medium devoid of monoclonal antibody.

Animals↗
PubMed1982

Postnatal development of the visual cortex of the mouse after enucleation at birth.

Quantitative data in the neocortex up to the age of 180 days (neuronal densities, number of neurones, glial cells, dendritic intersections and spines) were compared in normal mice and mice enucleated at birth. Bilateral enucleation induced an increase of neuronal density in all cortical layers of areas 17, 18a, and 41, the supragranular layers II-III being more affected than layers IV-VI. This was noticed in layer II 10 days after the operation and was maximal in all layers between 30 and 60 days; at 180 days there was some return to normal of the neuronal density in all layers. The total number of neurones and glial cells were the same in the bilaterally enucleated mice as in the controls. No reaction in dendritic branching was evident for pyramids of layers III and V in areas 17 and 41 after bilateral enucleation. In contrast the number of spines was reduced on the apical dendrites of pyramids from layers II and V in area 17, but not in area 41. After unilateral enucleation the reaction was less severe and delayed compared with bilateral enucleation, the first signs of increase of neuronal density appearing 30 days after the lesion in the contralateral hemisphere. The contralateral areas 17 and 18a were more affected than the ipsilateral ones and area 41 showed no change compared to the control. As after bilateral enucleation, layers IV and V were least affected by unilateral enucleation in both ipsi- and contralateral cortices. These results suggest that deafferentation in an immature system affects the development of all cortical layers but with a greatest intensity in supragranular layers, which are not the main direct targets of thalamo-cortical input.

Aging↗
PubMed1981

[Classification of acute leukemias by surface markers and correlation with the morphological diagnosis. Results of 111 cases].

111 patients with acute leukemia, including 29 children, were classified according to the surface markers and cytochemistry of their blasts. The acute leukemias were separated into two majors groups (lymphoid and non-lymphoid) depending on the presence or absence of specific lymphoid markers. On the basis of these criteria a correlation of 94% with the hematological diagnosis was obtained. Acute lymphoblastic leukemia (ALL) was divisible into three sub-groups: 11 cases expressing T-cell specific markers were classified as T-ALL and 33 cases expressing the common ALL antigen (CALLA) as c-ALL. 18 of the latter expressed an additional marker, DSA (Daudi surface antigen), splitting c-ALL cases in two subgroups. Cytochemistry of the cases lacking specific surface markers (n = 67) served to diagnose 41 acute myeloid leukemia (AML) cases and 8 monoblastic leukemias. The remaining 18 cases could not be classified. The presence of absence of HLD-DR (Ia) antigens served to subdivide AML into two major subgroups. The prognostic significance of these new diagnostic splits is under active study.

Acute Disease↗
PubMed1981

Distribution and properties of Fc receptors for IgG on different leucocyte populations in man.

The distribution and some characteristics of Fc receptors for immunoglobulin (Fc gamma R) were analysed on different human leucocyte populations. Interaction of Fc gamma R present on T gamma cells with ox erythrocytes-IgG immune complexes (IgG-IC) provides a switch-off signal for the expression of the Fc gamma R themselves; in addition, these receptors are sensitive to the proteolytic activity of pronase. Since both of these phenomena could have important effects on certain functional activities of the cells, we have analysed the effect of the interaction between IgG-OxE and the Fc gamma R present on various leucocyte populations. The large majority of T gamma cells or of tonsil B cells lost their Rc gamma R after interaction with IC; IC, in turn, had no effect on the Fc gamma R of AC and PMN. Twelve to 22% of the non-T, non-AC fractions retained surface Fc gamma R. Enzymatic treatment of the cells showed that T cells, non-T, non-AC and B cells have Fc gamma R sensitive to pronase, whereas Fc gamma R present on AC and PMN are resistant even to very high concentrations of the enzyme.

Antigen-Antibody Complex↗
PubMed1980

Postnatal development of the dorsal lateral geniculate nucleus in the normal and enucleated albino mouse.

Quantitative data (numbers of neurones and glial cells, total volumes, internuclear volumes) were obtained during normal development and after bilateral and unilateral enucleation at birth in the dorsal lateral geniculate nucleus (LGNd) of the mouse, at 5, 10, 30, 60, and 180 days postnatal. During normal development there is a neuronal loss of about 30% up to 30 days, at which age the total number of neurones stabilises at around 17,000. Glial proliferation and an increase in the volume of LGNd continues at least to 180 days. More severe degenerative effects were found after bilateral than after unilateral enucleation. At 180 days, bilateral enucleation leads to a neuronal loss of 27% compared to the controls, with a glial deficit of 53% and a decrease in the volume of LGNd of 57%. Degenerative effects were very different in LGNd contralateral or ipsilateral to enucleation in monocularly enucleated mice, due to the extensive crossing of the retinal fibres. At 180 days, we found a deficit of 10% in the numbers of neurones and glial cells, in the ipsilateral LGNd compared to normal: the volume of LGNd was slightly less (3%) than in controls. The contralateral LGNd after unilateral enucleation behaved like LGNd after bilateral enucleation until 60 days. At 180 days, some minor modifications were found, showing an additional neuropil decrease of 13% and an additional neuronal loss of 6% in the bilaterally enucleated LGNd compared to the unilaterally enucleated contralateral LGNd. The time-course of degeneration both after bilateral and unilateral enucleation was discussed.

Animals↗
PubMed1978

Postnatal development of the mouse cerebral neocortex. III. Some dynamical aspects.

In this paper we analyse our data from the quantitative cytoarchitectonic study of motor and sensory areas 10--4--3 and 2(Leuba and coll., 1977) and of visual and auditory area 5--17--18a--18--41 and 20 (Heumann and coll., 1977). The analysis of neuronal densities and cortical depths shows the following facts during the postnatal maturation: 1. Generally the sequence of maturation of the cortical layers is the same in the 9 studied areas: first layers I. and V, then VIb and VIa followed by III and IV and finally II. 2. This sequence is the same between 5 and 10 days as between 10 and 30 days. Still the maturation is much faster between 5 and 10 days. After 30 day differences between the layers are not very important. 3. For layers I, V and VI our 9 areas show an approximately similar degree of development from 5 days on. 4. Layers II, III and IV are in a faster period of development between 5 and 10 days. At this moment and for these layers, areas 17, 2, 3, 4 and 10 are less well developed than areas 41, 20, 18 and 18a. 5. One can thus consider that in mice the maturation of the areas seems to be more correlated with their localization than with their function. Effectively areas 41, 20 and 18a are in the vicinity of the rhinal fissure and a maturational gradient may start in this fissure. 6. In terms of neuronal densities and cortical depths an adult aspect of the layers and of the areas seems to be reached around 30 days. But some other phenomena of maturation exist after 30 days.

Aging↗
PubMed1978

Postnatal development of the mouse cerebral neocortex. IV. Evolution of the total cortical volume, of the population of neurons and glial cells.

The total neocortical volume delimited between precise anatomical features was measured. Serial frontal sections cresyl-violet stained were measured with plainimetric methods and the total volume evaluated at 5, 10, 30, 60 and 180 days. The total volume was used to obtain the total number of neurons and glial cells at each age using our quantitative data (published in our previous papers). The evolution of the cellular densities were studied in the sensory and motor areas 10--4--3 and 2 (Leuba and coll. 1977) and in the visual and auditory areas 17--18a--18--41 and 20 (Heumann anc coll. 1977) in the mouse cerebral neocortex. 1. The total neocortical volume increases rapidly between 5 and 10 days, less between 10 and 30 days, slightly decreases at 60 days and reincreases at 180 days. 2. Between 5 and 30 days, the loss of cortical neurons is of about 30% by neuronal death. 3. The total number of glial cells doubles between 5 and 180 days. The increase is progressive through the development.

Animals↗