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Biomedical subjects

H A Messner

Publications and source records attributed to H A Messner.

At least 127 records · Page 7Linked to original sources
PubMed1983

Magna-field irradiation: work in progress in bone marrow transplantation at The Princess Margaret Hospital, Toronto.

Our work with total body irradiation (TBI) for acute leukemia in relapse dates from 1959. Following reports of the Seattle experience, we treated a small number of patients in remission--lowering the dose to 500 rad given at 50 rad/min, based in part on our experience with radiation pneumonitis complicating upper HBI. We have treated 51 patients since July 1979, with an actuarial survival of 65% overall, and 85% for patients 35 years-old or less. A specially designed cobalt-60 unit is used, which allows very large fields and high exposure rates. Dose is calculated at midplane and a homogeneity of +/- 5% obtained.

Acute Disease↗
PubMed1983

Fetal hemoglobin analysis of erythroid bursts in patients with chronic myelogenous leukemia (CML).

Early erythroid progenitors (BFUE) form colonies of mature progeny in culture. The development of hemoglobinized red cells within multilineage colonies (CFUGEMM) and erythroid bursts is dependent upon exogenously added erythropoietin and molecules released by hemopoietic subpopulations. Mixed colonies and erythroid bursts were grown from 3 patients with Ph' chronic myelogenous leukemia (CML). It was found that some mixed hemopoietic colonies and erythroid bursts did not require exogenously added erythropoietin. An increase of the plating efficiency of BFUE could be observed when erythropoietin was added. Erythroid bursts grown without added Ep from samples of the patients with chronic myelogenous leukemia have a higher probability to contain HbF than clones grown in the presence of Ep. The data support the view of a phenotypical heterogeneity among clonal descendents of a common ancestor as previously postulated for CML.

Adult↗
PubMed1983

Lineage infidelity in acute leukemia.

Blast cells from 20 patients with acute leukemia (13 diagnosed myeloblastic and 7 as lymphoblastic, using the FAB classification) were studied using antibodies to lineage-specific differentiation markers. The phenotypic findings were usually consistent with the clinical diagnosis. However, examples were encountered where individual blast cells had a cytoplasmic marker of one lineage and a surface marker of a different lineage (lineage infidelity). Six examples of intramyeloid (two different myeloid lineages in the same cell) and three examples of interlineage infidelity (myeloid and lymphoid markers in the same blast cell) were encountered. No doubly marked cells were found in control material consisting of normal marrow cells, marrow regenerating after transplantation, or multilineage colonies derived from marrow in culture. A significant trend was observed relating the presence of lineage infidelity and failure of remission-induction. The data are interpreted as support for abnormal gene expression in leukemia.

Acute Disease↗
PubMed1982

Bone marrow transplantation for leukemia and aplastic anemia: management of ABO incompatibility.

Between February 1971 and October 1980, 34 patients with leukemia or aplastic anemia received bone marrow transplants from HLA-identical siblings whose lymphocytes did not react in a mixed leukocyte culture. The donors of 10 patients were ABO-incompatible, and for five pairs the ABO incompatibility was major. Plasma exchanges followed by a red blood cell exchange transfusion reduced the anti-A titres to 1:4 or less in these patients. The ABO incompatibility had no adverse effect on the results of marrow transplantation. Twenty-two patients, including 16 of the 20 who received their transplant after Jan. 1, 1980, are still living. Seven of the 15 patients with acute leukemia have survived 89 to 466 days, and 4 of the 6 with chronic myelogenous leukemia (CML) have survived 117 to 545 days. Of the 13 patients with aplastic anemia, 11 are alive up to 8 years after transplantation. Marrow transplantation, when possible, is the treatment of choice for young patients with acute leukemia in remission and for patients with aplastic anemia. Marrow transplantation may also prove to be effective in patients with CML.

ABO Blood-Group System↗
PubMed1982

The growth of large megakaryocyte colonies from human bone marrow.

The growth of large, compact megakaryocyte colonies in cultures of human bone marrow is promoted by fresh human plasma and medium conditioned by phyto-hemagglutinin stimulated leukocytes (PHA-LCM). These colonies are typically composed of large cells with translucent cytoplasma, surrounded by a highly refractile border. In addition, they may also contain smaller cells of similar morphology. Independent of their size, all cells react positively with antibodies directed against human factor VIII antigen. The frequency of megakaryocyte colonies may vary for different individuals from 1-35 colonies per 10(5) mononuclear bone marrow cells. The observed linear relationships between the number of cultured cells and the frequency of colonies suggests a single cell origin. The described culture conditions also support the development of a larger megakaryocyte component within multilineage mixed colonies, so that it will now be feasible to investigate the mechanisms involved in directing pluripotent cells towards megakaryocytopoiesis.

Cells, Cultured↗
PubMed1982

The contribution of blast cell properties to outcome variation in acute myeloblastic leukemia (AML).

The blast cell population in AML includes progenitors capable of colony formation in culture. Certain properties of these progenitors have been determined, including their capacity for self-renewal and their sensitivities to the chemotherapeutic drugs cytosine arabinoside (Ara-C) and adriamycin (Adria). Wide patient to patient variation was found in these properties, although they were stable during the course of the disease in each patient. We tested the properties, together with clinical risk factors, as attributes contributing to the variation in remission induction and survival. As univariate parameters, self-renewal and Ara-C sensitivity contributed to remission induction, but only self-renewal was related to survival. In multivariate analysis, self-renewal, age and percentage blasts in the marrow contributed to outcome variation; drug sensitivities were not significant. We conclude that self-renewal, a biological property of malignant AML clones, although measured in culture, plays a significant role in determining response to treatment and survival in AML.

Analysis of Variance↗
PubMed1982

Peripheral blood blast cell progenitors in human preleukemia.

Progenitors of blast cell colonies have been identified in acute leukemia. The peripheral blood of 18 of 25 patients with preleukemic states yielded low numbers of blast cell colonies, and the colony-forming cells were in an active proliferative state when assessed using short-term exposure to tritiated thymidine. The clinical significance of blast cell colonies is uncertain, but we suggest that further analysis of this cultural abnormality may lead to a better understanding of mechanisms and management in preleukemia.

Adolescent↗
PubMed1982

Characteristics of erythroid colonies formed by bovine marrow progenitor cells in methyl cellulose cultures.

Bovine erythroid colonies containing eight to 100 erythroid cells were successfully cultured in methyl cellulose. The colonies required four to five days to mature and a direct linear relationship (r = 0.99) between the number of nucleated marrow cells plated and the number of colonies formed was demonstrated. Their optimum erythropoietin requirement was observed to be 1 U/ml. No second population of erythroid colonies developed either as a function of time or erythropoietin concentration. However, 1 to 5 per cent of the bovine erythroid colonies contained megakaryocytes in addition to the erythroid cells. Marrow samples from different cattle showed a wide variation in their response to erythropoietin in culture, while some produced many erythroid colonies in the absence of erythropoietin, others were observed to be entirely erythropoietin dependent. Large mixed colonies occasionally grew in methyl cellulose but their optimum culture conditions have not yet been established. Medium conditioned by phytohaemagglutinin-stimulated bovine peripheral leucocytes enhanced bovine erythroid colony growth. Bovine erythroid progenitor cells were observed to possess a sedimentation velocity of 9 +/- 1 mm per hour.

Animals↗
PubMed1981

Stimulatory activity of PHA-LCM for normal human hemopoietic progenitors and leukemic blast cell precursors: separation by isoelectric focusing.

Medium conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM) promotes growth of human hemopoietic progenitors (CFU-GEMM, BFU-E, CFU-C) and precursors of leukemic blast cells. PHA-LCM was separated by isoelectric focusing and each fraction tested with nonadherent cells of normal individuals as well as blast cells from two patients with acute myelogenous leukemia. Activity profiles for CFU-GEMM, BFU-E and CFU-C ranged form pH 5.0-6.5. The profile for activity stimulatory for leukemic blast cells was broader and ranged from pH 5.5-7.5. Although some overlap was observed, the main peaks of stimulatory activity for normally differentiating progenitors and precursors of leukemic blast cells were separable with respect to their isoelectric point.

Bone Marrow↗
PubMed1981

The heritable nature of clonal characteristics in acute myeloblastic leukemia.

Marked patient-to-patient variation is observed when blood or marrow from AML patients is examined using colony methods in culture. Concentrations of the progenitors of colonies change with time during the course of the disease. We asked whether blast progenitor properties were more stable. We measured blast cell self-renewal and drug sensitivity (adriamycin and cytosine arabinoside) repeatedly in the courses of seven AML patients. These properties were found to be stable or slowly evolving. We conclude that capacity for renewal and sensitivities to certain chemotherapeutic drugs are heritable characteristics in leukemic clones.

Clone Cells↗
PubMed1981

Self-renewal capacity of leukemic blast progenitor cells.

A review is presented of experimental information pertaining to the characteristics of a procedure designed to quantitate the capacity for self-renewal in clonogenic cells of human acute myeloblastic leukemia. In a series of 44 previously untreated patients, a significant correlation (p less than 0.01) was seen between low capacity for self-renewal and successful remission induction. Three cytotoxic drugs (Adriamycin, 1-beta-D-arabinofuranosylcytosine, and N-[4-(19-acridinylamino)-3-methoxyphenyl]-methanesulfonamide) were tested for preferential effect against self-renewal events. Surviving clonogenic cells to these agents had, respectively, unchanged, lower, and higher capacity for self-renewal. The implications of such drug properties are discussed.

Aminoacridines↗
PubMed1981

Identification of T lymphocytes in human mixed hemopoietic colonies.

The addition of a T-cell growth-promoting medium (PHA-TCM) to culture conditions that support growth of multi-lineage hemopoietic colonies enhances the proliferation of cells with lymphoid morphology within these colonies. These cells were identified as T lymphocytes by their ability to form rosettes with SRBC and their reaction with monoclonal antibodies (OKT3, OKT4) directed against T-cell-specific surface components. They continue to proliferate extensively under the influence of PHA-TCM after transfer of mixed colonies into liquid suspension culture. Supportive evidence for a common progenitor of myeloid and lymphoid cells within single mixed colonies is provided by Y-chromatin body analysis of E-rosette positive and negative cells in colonies grown in cocultures of male and female bone marrow cells.

Cell Division↗
PubMed1981

Pluripotent hemopoietic progenitors (CFU-GEMM) in polycythemia vera: analysis of erythropoietin requirement and proliferative activity.

Pluripotent hemopoietic progenitors (CFU-GEMM) give rise to multilineage hemopoietic colonies in culture. We have examined the erythropoietin requirements of CFU-GEMM-derived erythroid progeny in patients with polycythemia vera (PV) and studied their proliferative activity by short-term exposure to 3HTdR. Mixed colonies with erythroid components were observed in all bone marrow and peripheral blood samples from patients with PV that were cultured without addition of exogenous erythropoietin. This response is consistent with previously reported growth patterns for CFU-E and BFU-E. The frequency of mixed colonies increased regularly when erythropoietin was added to the cultures. Short-term exposure of peripheral blood specimens to 3HTdR prior to plating yielded a reduction of the plating efficiency by 20%-70% when compared to cells that were not exposed to 3HTdR. The observation of cycling CFU-GEMM in PV contrasts with the usually quiescent behavior of CFU-GEMM in peripheral blood of normal individuals under steady-state conditions. These results support the view that the increased proliferative rate observed for CFU-GEMM may be responsible for the increased formation of blood cells in PV.

Bloodletting↗
PubMed1980

Single-cell immunofluorescence assay for terminal transferase: human leukaemic and non-leukaemic cells.

The characteristics of a single-cell immunofluorescence assay for terminal deoxynucleotidyl transferase (terminal transferase, TdT) is described. The data indicate that the single-cell immunofluorescence assay is highly efficient and specific for the detection of cells containing TdT. Using this assay, we have examined 124 marrow or peripheral-blood samples from 104 patients with or without haematological malignancies. Results indicate that TdT(+) cells from 6% to 100% were found in the following patients: 34/40 samples from patients with ALL at the time of diagnosis or during relapse; 2/3 patients with acute undifferentiated leukaemia; 2/3 patients with acute myelomonocytic leukaemia; 1/24 patients with acute myeloblastic leukaemia; 1/5 patients with chronic myelocytic leukaemia (CML) in blastic crisis; and 2/2 patients with diffuse lymphoblastic lymphoma. In contrast less than 1% of TdT(+) cells were found in 20 marrow or peripheral-blood samples from ALL patients in complete remission; 8 patients with CML in chronic phase; 2 patients with myeloma; 1 sample from a patient with Hodgkin's disease, peripheral-blood samples from 7 normal donors and marrow samples from 6 patients without haematological malignancies. TdT(+) cells were also found in association with cells with lymphoblast morphology. The TdT(+) cells in marrow were shown to be directly correlated with the percentage of morphological lymphoblasts, with a Spearman rank coefficient of 0·81, significant at a 0·001 level. In 2 longitudinal studies of 2 ALL patients with TdT(+) cells at diagnosis, the percentage TdT(+) cells also changed in parallel with the proportion of lymphoblasts. However, studies of 2 other patients with morphologically diagnosed ALL with < 1% TdT(+) cells at diagnosis also showed < 1% TdT(+) cells throughout the period studied, indicating a stable phenotype of blast cells in these patients. The single-cell immunofluorescence assay for TdT, which requires < 0·1% of the cells used in a conventional biochemical assay, is highly specific, and could provide a technically more efficient alternative for use in clinics as well as in experimental investigations of subpopulations of leukaemic and normal marrow cells.

Bone Marrow↗