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Biomedical subjects

R Mertelsmann

Publications and source records attributed to R Mertelsmann.

At least 343 records · Page 19Linked to original sources
PubMed1981

Ultrastructural demonstration of terminal deoxynucleotidyl transferase (TdT).

Using an electronmicroscopic peroxidase-antiperoxidase technique in combination with a three-step fixation procedure according to Willingham, the ultrastructural site of terminal deoxynucleotidyl transferase (TdT) could be shown in cells of a human lymphoblastic leukemia cell line (MOLT 4). TdT appeared in the cytoplasm of the cells associated with large membrane bound granules from 150 to 600 nm in diameter usually arranged in aggregates. TdT-positive spaces were completely segregated form the rest of the cytoplasm and seemed to be interconnected by a tubular system. No TdT was detected in the nuclei.

Cell Compartmentation↗
PubMed1980

Analysis of multiple cell markers in acute leukemia complicating Hodgkin's disease.

A multidisciplinary methodology was applied to study 6 patients with acute leukemia (AL) following treatment for Hodgkin's disease. All 6 patients developed acute monocytic leukemia according to cytochemical criteria; morphologically, 3 cases were undifferentiated monoblastic leukemia; 3 cases were partially differentiated monocytic leukemia. In 3 of the 6 cases, cell suspensions from peripheral blood and/or bone marrow bore predominantly surface receptors for the Fc fragment of IgG and/or C-3 fraction of complement and exhibited variable degrees of phagocytosis. Two cases lacked any recognizable membrane markers or phagocytic activity. Terminal transferase enzymatic activity was not diagnostically elevated. Soft agar bone marrow culture studies revealed no growth or a characteristic leukemic cluster pattern. Chromosome analysis done in 1 of the 2 patients studied revealed hypodiploidy and structural rearrangement. Prospective studies, done serially, will help determine whether development of AL in patients with Hodgkin's disease results from the influence of intensive and potentially oncogenic therapy or represents progression from a preleukemic stage inherent to the original tumor.

Adult↗
PubMed1980

Subpopulations of human T lymphocytes. VI. Analysis of cell markers in acute lymphoblastic leukemia with special reference to Fc receptor expression on E-rosette-forming blasts.

A variety of surface markers, terminal deoxynucleotidyl transferase (TdT) activity, morphologic appearance, and cytochemical composition were studied in a group of 16 patients (13 children, 3 adults) with acute lymphoblastic leukemia (ALL). In 9 children, no surface markers were detected on lymphoblasts (null-type ALL). Leukemic blasts of 4 children formed E-rosettes. These E-rosette-forming blasts from 3 adult patients with ALL, were studied for the presence of Fc receptors. Of the leukemic blasts from these 7 patients, 2--76% expressed receptors for IgG Fc. Only 3 of 7 patients showed 9--42% receptors for IgM Fc. In addition, complement receptors were investigated in 6 of those 7 patients with T-cell ALL. Complement receptors were detected on 9--70% of the E rosette forming blasts from all 6 patients. TdT activity was elevated in T-cell ALL and in children with null-type ALL. The heterogeneity of Fc receptor expression on leukemic blasts in these patients demonstrates a malignant proliferation of T cells in different stages of differentiation or maturation. This observation might be helpful in subclassifying T-cell leukemias with regard to prognosis and the response to therapy.

Adult↗
PubMed1980

Childhood CML in blastic stage: an analysis of cell markers and cell kinetics.

The clinical course of Ph+CML and their terminal blastic stage is described in the following case histories. During blastic phase, cell surface markers, terminal deoxynucleotidyl transferase (TdT) activity, and flow cytometric measurements were used or determination of the blast cell phenotype which was undifferentiated by morphological and cytochemical criteria. A high proportion of blast cells expressed Fc receptors for IgG, TdT activity was normal in both children and RNA measurements of single cells flow cytometry showed a high RNA content in the majority of blasts. These findings are compatible with the phenotype seen in the myelomonocytic leukemias. Flow cytometry appears to be a useful adjunct to immunological methods and TdT activity for the rapid characterization of CML in blastic phase.

Child↗
PubMed1980

A micromethod for determination of terminal deoxynucleotidyl transferase (TdT) in the diagnostic evaluation of acute leukemias.

A micromethod for the determination of TdT in peripheral leukocytes and bone marrow cells has been developed that allows unequivocal identification and quantitation of TdT in less than 1 X 10(6) leukocytes from ALL patients, i.e., in 1 ml of peripheral blood and/or 0.5 ml of bone marrow obtained during routine clinical sampling. The method involves disruption of cell pellet with high salt and detergent followed by centrifugation of extracts at 12,000 X g and partial purification on phosphocellulose matrix by a batch elution technique using a standard laboratory microcentrifuge. Using this microassay, TdT activities have been determined in 500 samples of peripheral blood and bone marrow of 240 adult patients with acute leukemias (86 ALL, 108 ANLL, 44 blastic CML, two acute leukemias following P. vera). From an analysis of our data based on TdT activity, cell surface markers and growth patterns in soft agar and observations published in the literature, it can be concluded that the frequencies of TdT + phenotypes in the various clinical-morphological diagnostic groups are approximately 95% in ALL, 10% in ANLL, 50% in AUL, and 35% in blastic CML. Since the presence of high TdT activity is clearly associated with clinical response to specific forms of chemotherapy in blastic CML and most probably, also in ANLL, the determination of TdT should be considered in all cases of acute leukemias to objectively define prognostically important subgroups which can not be diagnosed by conventional means.

Acute Disease↗
PubMed1980

The acute monocytic leukemias: multidisciplinary studies in 45 patients.

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Adolescent↗
PubMed1980

Heterogeneity of cell lineages in L3 leukemias.

Five cases of adult leukemia with L3 morphology in bone marrow were studied for the presence of immunologic, metabolic, and enzymatic markers. Among the five patients, there were four males and female. Median age was 66 with a range of 16-80 yr. Median survival was only 5 mo. Serum lactate dehydrogenase (LDH) levels, 3H-thymidine labeling indices, and DNA/RNA content of the L3 lymphoblasts were markedly elevated. B-cell markers were found in three cases, two exhibiting surface membrane IgM-lambda, and one IgG-K. Terminal deoxynucleotidyl transferase (TdT) enzymatic activity was consistently low in this group. In one case, the L3 lymphoblasts displayed only surface Fc receptors demonstrated by the binding of aggregated IgG. TdT activity was found to be significantly increased. In another instance, the lymphoblasts formed spontaneous rosettes with sheep erythrocytes and exhibited paranuclear staining with acid phosphatase. TdT activity was found to be low. Although most of the L3 leukemias are neoplasias of B lymphocytes, other lineages may also express this morphology.

Adult↗
PubMed1980

Morphological classification, response to therapy, and survival in 263 adult patients with acute nonlymphoblastic leukemia.

Bone marrow smears of 263 protocol patients with acute nonlymphoblastic leukemia (ANLL) and related disorders treated between 1970 and 1978 at MSKCC were reviewed blindly by two pairs of hematomorphologists and classified according to the FAB system. It was found necessary to add one category (MO) for acute undifferentiated leukemia and to define more precise quantitative criteria for the categories M1-M6 based on bone marrow differential counts. Using this modified FAB classification, agreement between the two observer groups based on morphology alone was 69%. Cytochemical stains were essential in establishing the diagnosis in 9%, led to a change of diagnosis by one observer team in 14%, and helped to confirm the diagnosis in 32% of cases. Complete remission rates, remission duration, and survival were not significantly different among diagnostic categories. Myelodysplastic syndromes (MDS: M6, RAEB, CMML; CR rate 48%) and ANLL without differentiation (M0, M1, M5a; CR rate 50%) appeared to do less well than ANLL with partial differentiation (M2, M3, M4, M5b; CR rate 59%) on all three protocols studied. Auer rods were present in 53% of all cases with 63% in the myeloid categories (M1-M4). Auer rods were found to be the single most important prognostic parameter in this study, with a complete remission (CR) rate of 68% in the Auer-rod-positive and of 40% in the Auer-rod-negative group (p < 0.0001). Survival was significantly longer for patients exhibiting Auer rods (p < 0.0002). Median survival for the total group was 13.5 mo and median remission duration for responders was 11.5 mo in the Auer-rod-positive group compared to 6.2 mo median survival and 9.2 mo median remission duration for the Auer-rod-negative group.

Acute Disease↗
PubMed1980

Induction of differentiation in human marrow T cell precursors by the synthetic serum thymic factor, FTS.

The serum thymic factor, 'facteur thymique serique' (FTS), was analysed in vitro for its ability to induce differentiation of normal human marrow T cell precursors into cells with T lymphocyte characteristics. FTS has been isolated, characterized, sequenced and synthesized. In the mouse, natural and synthetic FTS have similar activities in vitro in the rosette inhibition assay. Both substances influence a variety of T cell differentiation markers and functions in vivo. In this study, we found that synthetic FTS induced appearance of two T cell surface markers, HTLA phenotypes and the ability to form E rosettes, on a selective population of normal human marrow cells sedimenting in layers II or III of a Ficoll discontinuous density gradient. In addition, a population of lymphoid cells also found in layer III, which bears receptors for peanut agglutinin (PNA), was decreased in number following exposure to FTS. In the same gradient layer, cells which expressed terminal deoxyribonucleotidyl transferase (TdT) activity showed decreased activity after treatment with FTS. Functional activities characteristic of T lymphocytes were also enhanced in marrow cells of gradient layer III after preincubation with FTS. These T cell functions were demonstrated in marrow cells by their ability to respond and to stimulate allogeneic peripheral blood lymphocytes (PBL) in mixed lymphocyte reactions and by responses to phytomitogens, PHA, Con A and pokeweed. These changes were not observed in marrow cells of gradient layers I, IV and V or after incubation with an FTS analogue that lacked biological and antigenic activity in the mouse system.

Antigens, Surface↗
PubMed1979

The coexistence of acute myeloblastic leukemia and diffuse histiocytic lymphoma in the same patient as demonstrated by multiparameter analysis.

Measurement of cellular DNA content by flow cytometry demonstrated presence of two distinct aneuploid neoplasms in a patient who developed acute myeloblastic leukemia (AML) 4 mo after diagnosis of a diffuse histiocytic lymphoma (DHL). A lymph node aspirate contained peroxidase-negative, "null," hyperdiploid (2.6C) DHL cells, while the bone marrow (BM) contained 84% primitive peroxidase-positive tetraploid AML cells (4.0C). Minor populations of hyperdiploid HDL and normal diploid cells could be detected by flow-cytometry in the BM, and all three populations were also seen in the peripheral blood.

Adult↗
PubMed1978

Evidence for distinct lymphocytic and monocytic populations in a patient with terminal transferase--positive acute leukemia.

Two distinct cell populations with lymphoblastic and monocytic characteristics were separated and characterized by multiple cell markers in a patient with terminal transferase-positive acute acute leukemia. The clinical course and sequential cell marker studies were consistent with the interpretation of a defect at the level of a common stem cell giving rise to a terminal transferase--positive lymphoblastic cell population at diagnosis and, following initial therapy, a terminal transferase--negative monocytic population.

Adult↗
PubMed1977

[False diagnosis of "osteoporosis" in diffuse multiple myeloma (author's transl)].

Multiple myeloma is very frequently diagnosed too late. In ten patients in whom the diagnosis was ultimately made in the course of one year, the early symptom of back or skeletal pain was at first most frequently misdiagnosed as osteoporosis and so treated. Such symptoms as loss of weight, increased sedimentation rate and increase in gamma-globulins should have led to further tests, for example sternal puncture, radiological survey of the entire skeleton, and immuno-electrophoresis.

Aged↗