PubMed Health⌕ Search

Biomedical subjects

H A Messner

Publications and source records attributed to H A Messner.

At least 109 records · Page 6Linked to original sources
PubMed1986

The structure of the T cell gamma chain gene in lymphoproliferative disorders and lymphoma cell lines.

During the development of B and T cells, a number of genes undergo rearrangement. In this paper we have studied the structure of the T cell gamma-chain gene in primary lymphomas and cell lines derived from patients with lymphoma. Samples derived from patients with angioimmunoblastic lymphadenopathy (AIL), Lennert's lymphoma, and Hodgkin's disease were also examined. TcR gamma was rearranged in all T cell lymphomas and in some B cell lymphomas and B cell lymphoma cell lines. Rearrangement of the gamma-chain gene was also found in AIL, Lennert's lymphoma, and four of eight cases of Hodgkin's disease. These studies indicate that rearrangement of TcR gamma is a useful clonal marker but does not aid in the identification of cell lineage.

Cell Line↗
PubMed1986

Interferon alfa-2b in the treatment of chronic granulocytic leukemia.

Studies of the effect of interferon on the growth of colonies of myeloid leukemic blast cells, myeloma colony-forming cells, and normal hemopoietic precursor cells have demonstrated that interferon shows no specificity in inhibiting the growth of these cells in culture (ie, growth of the malignant and normal precursor cells is equally inhibited). However, interferon markedly reduces the self-renewal capacity of acute myeloid leukemic blast cells and myeloma cells. This observation suggested that interferon's ability to prolong rather than induce remissions should be tested. We have studied the ability of interferon alfa-2b (Intron A) to prolong remissions induced by busulfan (Myleran) in patients with chronic granulocytic leukemia (CGL). The leukocyte doubling time and remission duration among patients receiving no therapy was compared with the values observed during interferon alfa-2b maintenance therapy. Nine patients have begun the study; five have completed 3 months of interferon alfa-2b therapy. In four (80%) of the five patients, there has been a significant slowing of the leukocyte doubling time and prolongation of the remission duration. A larger study, with longer follow-up, will be required to determine whether interferon alfa-2b therapy will slow progression of CGL to the blast phase and prolong survival.

Adult↗
PubMed1986

Biology of acute myeloid leukaemia.

The assessment of clonogenic leukaemic precursors in cell culture has demonstrated considerable heterogeneity of patients with respect to their ability to give rise to leukaemic blast cell colonies. Specific growth patterns rather than the frequency of blast colonies, appear to be of prognostic value for the clinical outcome. In particular, blast cells with high self-renewal ability were associated with poor prognosis. A similar degree of heterogeneity among leukaemic blast cell populations can be identified by studies with monoclonal antibodies directed against various cell surface cytoplasmic determinants that are associated with haematopoietic precursors. Some of these reflect properties of pluripotent normal counterparts while others display patterns that are associated with precursors restricted to a single myeloid lineage. Blast cells examined after culture may differ in their marker expression from the original blast cell population. Usually, properties of more mature cells are acquired during the culture period. These changes reflect events of aberrant differentiation without leading to the full development of a morphologically normal phenotype and functional capability. The use of both technologies has provided considerable insight into the biology of leukaemic blast cell populations and it is anticipated that their future use will provide further information about the control mechanisms involved in their proliferation and their potential to differentiate normally.

Antigens, Surface↗
PubMed1986

Human leukemia: cell culture.

A number of culture systems are now in use to explore control mechanisms in normal and abnormal hemopoiesis. The combined use of these culture techniques with monoclonal antibodies, molecular probes, and growth-promoting activities have the potential to provide some insight into the mystery of leukemic proliferation.

Antibodies, Monoclonal↗
PubMed1985

Characterization of human megakaryocytic colony formation in human plasma.

We have analysed the contribution to megakaryocyte colony formation in methylcellulose made by human plasma, serum, media conditioned by phytohemagglutinin (PHA) stimulated leukocytes (PHA-LCM), erythropoietin (EPO) preparations, and platelets. The culture system was used as a bioassay for megakaryocyte colony stimulating activity (Meg-CSA) in plasma samples of patients with perturbed megakaryocytopoiesis. Preparations of heparinized platelet-poor plasma yielded the most consistent results. Platelet-poor plasma of normal subjects will at best facilitate the occasional growth of small megakaryocyte colonies. Colony frequency and size are reproducibly enhanced in the presence of PHA-LCM as a source of exogenous Meg-CSA. Commercially available EPO preparations may vary in their content of activities that influence megakaryocyte colony formation. Addition of these preparations to cultures that contain plasma and PHA-LCM usually does not enhance colony formation. In contrast to platelet-poor plasma, platelet rich plasma and serum are less supportive of megakaryocyte colony growth. It is suggested that this loss of activity may be related to the release of inhibitors by activated platelets or alternatively caused by absorption of activities by platelets. Plasma samples from patients with megakaryocytopoietic dysfunction may contain components that promote colony formation without addition of PHA-LCM or EPO. This phenomenon is consistently observed for patients with severe aplastic anemia and bone marrow transplant recipients after completion of their ablative preparative regimen.

Anemia, Aplastic↗
PubMed1985

Origin of leukemic relapse after bone marrow transplantation detected by restriction fragment length polymorphism.

Bone marrow transplantation has become an accepted modality in the treatment of acute leukemia. With this therapy, it is possible to obtain long-term disease-free survival. However, leukemia recurs occasionally. In most cases, leukemic relapse is of recipient origin. There have been several reports, though, of leukemia developing in donor cells. These cases have been limited to instances in which there is an easily identifiable chromosome difference or abnormality, usually a sex chromosome. In this paper we describe the use of restriction fragment-length polymorphism analysis to determine the origin of recurrent leukemia cells in which no identifying chromosome was present. We found that the leukemia had recurred in recipient cells. We also were able to demonstrate the presence of normal hemopoietic cells of donor origin.

Adult↗
PubMed1985

Colony growth and self renewal of plasma cell precursors in multiple myeloma.

Culture conditions that support the growth of multi-and single-lineage hemopoietic colonies are also able to give rise to large myeloma colonies from bone marrow and peripheral blood samples of some patients with multiple myeloma. The culture system was used to determine the frequency of hemopoietic precursors and clonogenic myeloma progenitors in 71 patients with multiple myeloma studied in various clinical phases of the disease. The frequency of normal hemopoietic precursors in patients with benign monoclonal gammopathy and smoldering myeloma were indistinguishable from normal controls. Myeloma colonies were not observed in these subgroups. In contrast, patients with active disease showed significantly reduced hemopoietic colony formation, even before the initiation of therapy. A further reduction was demonstrated for patients with acute phase disease. A correlation between the frequency of hemopoietic colonies and the concentration of plasma cells in the plated sample was not observed. Large myeloma colonies with recloning potential were identified in cultures of specimens derived from 14 of the studied patients. These colonies were most frequently (ten cases) obtained from patients who had entered the acute phase of the disease. These patients manifested marrow failure (pancytopenia) and their marrow had a limited capacity to generate normal hemopoietic colonies. Three of the patients that formed myeloma colonies were studied in chronic phase following chemotherapy and one patient was examined at diagnosis. The myeloma colonies were composed exclusively of cells characterized by the same M protein as the patient. Some of the cells within the colonies retained their ability to self renew extensively, as demonstrated by serial recloning studies. Colonies derived from six of the patients are now propagated in semisolid and liquid medium for as many as nine to 34 generations. Patients that form myeloma colonies under these culture conditions represent a high-risk group with significantly shorter survival than patients not able to give rise to myeloma colonies. A Cox proportional hazards model was fitted to the data to determine the prognostic role of myeloma colony growth in culture after accounting for the influence of other well established risk factors, such as concentration of plasma cells and disease status. The analysis indicated that myeloma colony growth in culture serves as a strong and independent predictive indicator of poor clinical prognosis.

Actuarial Analysis↗
PubMed1985

Human megakaryocytopoiesis in cell culture.

In conclusion, a culture system is now available that reproducibly facilitates the development of megakaryocyte colonies and the emergence of megakaryocytes within multilineage colonies. The assay is dependent upon the use of human plasma and a source of exogeneous MEG-CSA. Patients with perturbed hemopoiesis plasma may contain activities able to replace exogeneous MEG-CSA. This system can therefore be used to evaluate MEG-CSA activities. In addition it is now feasible to study blast populations of patients with leukemia characterized by a megakaryocyte phenotype.

Bone Marrow Transplantation↗
PubMed1984

Allogeneic bone-marrow transplantation for chronic myelogenous leukaemia.

In 117 patients with chronic myelogenous leukaemia (CML) treatment with a combination of high-dose chemoradiotherapy plus transplantation of allogeneic bone-marrow from HLA-identical, mixed-lymphocyte-culture-identical siblings resulted in an actuarial probability of 3-year survival of 63 +/- 16% (95% confidence interval) for 39 patients transplanted in chronic phases; 36 +/- 14% for 56 transplanted in accelerated phase; and 12 +/- 15% for 22 transplanted during blast crisis. Irrespective of disease status at the time of transplantation, and in contrast to chemotherapy, a plateau-effect was observed in the survival curves starting 14 to 19 months after transplantation. The actuarial probability of recurrent or persistent leukaemia at 3 years was 7 +/- 9% for patients transplanted in chronic phase, 41 +/- 19% for accelerated phase, and 41 +/- 39% for blastic phase. All relapses occurred within 18 months of transplantation. This study demonstrates that long-term disease-free survival in CML can be achieved with bone-marrow transplantation. Best results were obtained in patients transplanted during chronic phase of the disease.

Adolescent↗
PubMed1984

Flexible association of hemopoietic differentiation programs in multilineage colonies.

Pluripotent hemopoietic progenitors lose potentialities during the process of differentiation. We have examined events that lead to lineage restriction by determining the cellular composition of 785 multilineage colonies grown from peripheral blood samples of glucose-6-phosphate-dehydrogenase (G-6-PD) heterozygous volunteers. Of these colonies, 762 contained only one isoenzyme type and were considered to be of clonal origin. A considerable heterogeneity was observed. Some colonies were composed of cells belonging to two different lineages, while other colonies contained three or more different cell types. A small number of colonies consisted--in addition to myeloid cells--of T-lymphocytes. The variable association within individual colonies of members belonging to different hemopoietic lineages suggests a flexible determination and expression of differentiation programs by early progenitors.

Bone Marrow Cells↗
PubMed1984

Contributions of host- and disease-related attributes to the outcome of patients with acute myelogenous leukemia.

Three sequential trials of treatment for acute myelogenous leukemia (AML) involving 173 patients were analyzed to identify clinical and myeloblast-cell progenitor properties in culture related to outcome. The latter, including self-renewal capacity expressed as plating efficiency (PE2) and drug sensitivity, were determined for a representative group of 45 patients. Despite increasingly intensive remission induction therapy, similar response rates were achieved in the three trials and no increase in the duration of survival was observed. Clinical attributes at presentation by multivariate analyses were not consistently predictable of outcome. Of the blast cell attributes, only PE2 was predictive of duration of survival (p less than 10(-6)). For patients in remission the relapse rate during the first year was 0.63 compared with 0.15 in subsequent years. The percentage marrow myeloblasts at presentation, a measure of disease activity, was significantly higher for the patients having remissions lasting less than one year. These studies demonstrate the importance of disease-related attributes on the outcome of patients with AML.

Actuarial Analysis↗
PubMed1984

G6PD isoenzyme analysis of myeloid and lymphoid cells in human multilineage colonies.

Some multilineage hemopoietic colonies contain, in addition to myeloid cells, T lymphocytes. These proliferate extensively in liquid suspension culture under the influence of a T cell growth factor provided by phytohemagglutinin-T cell-conditioned medium (PHA-TCM). The clonal origin of these myeloid and lymphoid components was investigated by determining the glucose-6-phosphate dehydrogenase (G6PD) isoenzyme types of multilineage colonies grown from peripheral blood of 4 G6PD heterozygous normal volunteers. The G6PD assay is sufficiently sensitive to detect enzyme concentrations contributed by as few as 30 granulocytes and erythroblasts, 4-6 megakaryocytes, 2-3 macrophages, and 50-100 T cells. T cell components can be detected even if myeloid cells are present in 10-20-fold excess. A small number of multilineage colonies with T cells produced a single G6PD isoenzyme on direct analysis and after expansion in liquid culture. This observation supports the view of a common progenitor for myeloid and lymphoid cells in the peripheral blood of normal adults.

Adult↗
PubMed1983

Pluripotent hemopoietic progenitors (CFU-GEMM) in chronic myelogenous leukemia.

Human hemopoietic pluripotent progenitors form multilineage colonies when cultured in methylcellulose with medium conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM) and erythropoietin (EPO). We have examined their frequency, culture requirements and proliferative activity in 20 peripheral blood and 29 bone marrow specimens from patients with CML in chronic phase. Multilineage colonies developed under regular culture conditions in approximately 50% of all samples. The frequency ranged from 1-36 per 2 X 10(5) mononuclear cells of density less than 1.077 gm/ml. The requirements for PHA-LCM and EPO varied for patients with CML when compared to normal individuals; i.e., cells from some patients gave rise to mixed colonies with substantial erythroid components in the absence of PHA-LCM or without addition of the usually required EPO concentrations. The proliferative activity of CFU-GEMM was assessed using a short-term exposure to tritiated thymidine (3HTdR) prior to plating. The plating efficiency in all bone marrow and peripheral blood samples was reduced to 40-70% of the unexposed controls. In contrast, the plating efficiency after exposure to 3HTdR in normal individuals usually ranged from 70-90% of controls for bone marrow samples and from 85-100% of controls for peripheral blood samples. Thus, an increased proliferative rate of pluripotent hemopoietic progenitors is a consistent feature of CML patients. In addition, at least in some patients, different requirements for erythropoietin or PHA-LCM were observed when compared to normal culture conditions.

Cell Division↗