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Biomedical subjects

E Januszewicz

Publications and source records attributed to E Januszewicz.

15 recordsLinked to original sources

Post-splenectomy lymphocytosis.

We describe post-splenectomy lymphocytosis (PSL) in 23 patients, a majority (20/23) of whom have undergone splenectomy as a staging procedure for Hodgkin's disease. The absolute lymphocyte count ranged from 4.0 to 8.7 x 10(9)/l. The lymphocytosis was noted 4-242 (median 70) months after splenectomy and persisted almost unchanged in most patients on prolonged follow up (median 50 months). Immunophenotyping of the lymphocytes revealed no monoclonal B cell population.

Adult↗

Secondary myelodysplastic syndrome following bone marrow transplantation: report of two cases.

We report two cases of secondary myelodysplastic syndrome (SMDS) which followed successful treatment of a primary malignancy with high-dose chemotherapy supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24 months and 40 months, respectively, following autografting. Both patients lived for 7 months after the diagnosis of SMDS. Our cases support the view that there is an increased risk of SMDS/acute leukemia following autologous marrow transplantation.

Adult↗

Butyric acid: inhibition of non-leukemic and chronic myeloid leukemia granulocyte macrophage clonal growth.

Butyric acid has been shown to inhibit the growth of several established tumor cell lines and to induce either granulocytic or erythroid differentiation in different human and murine leukemic cell lines. The dose-dependent effect of butyric acid was tested in vitro on the clonal growth of granulocyte macrophage progenitors in 13 patients with chronic myeloid leukemia (CML) and compared with control bone marrow and peripheral blood responses. The growth of myeloid progenitors from both healthy donors and non-leukemic and leukemic patients was almost completely inhibited by 1.0 mM butyric acid. At 0.5 mM butyric acid, inhibition of CML progenitors, both from chronic phase and blastic phase patients, was significantly greater (P less than 0.01) than bone marrow from non-leukemic patients and peripheral blood controls. Butyric acid, a 4-carbon compound, was the most potent inhibitor of six short chain fatty acids tested on CML myeloid progenitors.

Adult↗

Inhibition by retinoic acid of myeloid progenitors in chronic myeloid leukemia and myeloproliferative disease: increased sensitivity in blastic phase of chronic myeloid leukemia.

The effects of all-trans retinoic acid (RA) were tested on the growth in vitro of myeloid progenitors from peripheral blood or bone marrow, in 25 patients with chronic myeloid leukemia (CML), ten of whom were either in accelerated or blastic phase, and in nine patients with myeloproliferative disease (MPD). The responses were compared with 12 normal bone marrow controls obtained from patients with lymphoma. Clonal growth in CML blastic and accelerated phase was inhibited to the greatest degree (mean 49 +/- 9% (SEM) of control at 0.3 microM RA). The responses in CML chronic phase and MPD were more heterogeneous, but significant inhibition was seen at higher concentrations of RA (50 +/- 12% CML chronic phase, 58 +/- 26% MPD at 3.0 microM RA). At 0.3 microM and 1.0 microM RA there were significant differences between the CML chronic phase and the CML blastic phase patients (p less than 0.02 and p less than 0.05 respectively). At these concentrations there was no significant inhibition on normal bone marrow myeloid progenitors. Inhibition was independent of the proportions of progenitors in S phase, as assessed by tritiated thymidine suicide. Preincubation of cells from selected patients with RA for 48 hours before culture in agar resulted in a significant degree of inhibition (48 +/- 8% of control). Inhibition was prevented by delaying the addition of RA from 24 to 48 hours from the beginning of the culture, indicating that RA exerts an early direct effect on myeloid progenitors.

Blast Crisis↗

Hybrid biphenotypic acute leukemia with extreme hypodiploidy.

A patient diagnosed as having acute lymphoblastic leukemia (L2) relapsed 4 months later and was found to have morphologic and immunologic evidence of a biphenotypic hybrid acute leukemia. Chromosome analysis at relapse showed two abnormal clones, one with marked hypodiploidy and the other with exactly double the hypodiploid clone. It is considered that this is an example of a hybrid lymphoblastic/nonlymphoblastic leukemia with unique karyotype.

Adult↗

A therapeutic trial with low-dose cytarabine in myelodysplastic syndromes and acute leukemia.

The myelodysplastic syndromes are a group of bone marrow stem cell disorders which were considered refractory to chemotherapy until recently. Low-dose cytarabine was given to 6 patients with symptomatic myelodysplastic syndromes and 2 patients with acute leukemia. 5 patients responded to therapy, 3 of whom with refractory anemia achieved normalization of peripheral blood counts. Therapy was well tolerated, myelosuppression was the predominant side effect. This preliminary trial demonstrates that patients with symptomatic myelodysplastic syndromes, particularly patients with refractory anemia may be benefited by low-dose cytarabine therapy.

Acute Disease↗

Altered transcription of an oncogene in chronic myeloid leukaemia.

The oncogene abl, which resides on chromosome 9, is translocated to chromosome 22 as part of the Philadelphia (Ph1) chromosome. Leukaemic cells from 5 of 6 patients with chronic myelogenous leukaemia (CML) and the Ph1 chromosome were found to contain a new 8 kb abl RNA transcript. This finding raises the possibility that the abl oncogene is directly involved in the development of CML. It is suggested that the abl gene's expression is altered by the DNA rearrangement in the translocation.

Adult↗

Inhibition of normal human macrophage progenitors by retinoic acid.

The effects of retinoic acid on the clonal growth in nutrient agar of neutrophil and macrophage progenitors from normal bone marrow and fetal liver were studied. The technique of whole plate fixation and staining with luxol fast blue and haematoxylin was employed to distinguish colonies and clusters into morphological groups. Retinoic acid at a concentration of 3 X 10(-7) M resulted in 97% inhibition of macrophage clonal growth and a mean increase in neutrophil clonal growth from bone marrow of 150 +/- 14%. These effects of retinoic acid were most obvious on bone marrow cluster forming cells. The inhibition of macrophage cluster growth was independent of exogenous colony stimulating factor. This dual action of retinoic acid is likely to be a direct effect on the progenitor cells since it is (1) independent of cell concentration, (2) not mediated by phagocytic cells or other bone marrow cells, and (3) was maximal in the first 2 d of incubation before the appearance of clusters.

Bone Marrow Cells↗

Requirements for growth of human erythroid progenitors in nutrient agar.

Human erythroid bursts and neutrophil colonies from fetal liver, term cord blood, and adult bone marrow were grown in nutrient agar, and the colonies were scored using a fixed whole plate method. Human placental conditioned medium was shown to contain burst promoting activity, and low oxygen tension markedly enhanced growth of erythroid bursts. Morphological analysis of colonies showed that eosinophil colonies were more numerous in bone marrow than fetal liver and conversely macrophage and neutrophil-macrophage colonies were more numerous in fetal liver. Erythroid bursts were more numerous and larger in fetal liver. Human fetal liver cells do not produce endogenous colony-stimulating factor.

Adult↗

Blastic transformation of chronic lymphocytic leukemia.

A case is described of a patient with chronic lymphocytic leukemia whose disease underwent blastic transformation. The transformed cells had the same immunoglobulin types (mu and kappa) as the original chronic lymphocytic leukemia cells. Immunoperoxidase staining technique demonstrated that, in the transformed cells of the bone marrow, much of the immunoglobulin was intracellular. In the peripheral blood the transformed cells had dense surface immunoglobulin and features of primitive T-cells. These findings suggest that transformation to an immunoblastic type of leukemia had occurred.

Antigens, Neoplasm↗

Retrospective analysis of 158 cases of adult acute leukaemia: factors influencing prognosis and treatment response.

Discriminant and regression analyses were employed to determine the influence of a large number of clinical and laboratory indices on outcome of treatment in a series of 158 adults presenting with acute leukaemia between 1970 and 1977. Induction therapy had been most commonly cytosine arabinoside plus daunorubicin, vincristine and prednisolone. This induced complete remission in 42% of non-lymphoblastic, and in 58% of lymphoblastic plus undifferentiated leukaemias. Some induction failures who had non-lymphoblastic leukaemia were treated with cytosine arabinoside plus 6-thioguanine, which induced remissions in 46%. Advanced age was the factor most strongly associated with failure either to achieve or to sustain complete remission. Thrombocytopenia, promyelocytic leukaemia, high percentage of marrow blasts, and absence of metaphases in marrow cytogenetic preparations were also associated with poor survival. A number of other factors which appeared to be associated with poor prognosis were found by the analysis to lack significance as independent variables.

Adult↗

Partial purification and characterization of a growth factor for macrophage progenitor cells with high proliferative potential in mouse bone marrow.

A population of macrophage progenitor cells, with high proliferative potential, has recently been demonstrated in postfluorouracil-treated and normal mouse bone marrow (BM) in vitro, when the newly discovered growth factor (synergistic activity, SA) is combined with a macrophage colony-stimulating factor (CSF) as a proliferative stimulus. SA, shown to be present in human spleen and placental conditioned media (HSCM and HPCM, respectively) have been studied and found to be unstable to trypsin digestion and to heating at 50 degrees C or above; stable between pH 4 and 9; nonadherent to Con-A-Sepharose; and to have an isoelectric point between pH 5 and 5.8 and a molecular weight of between 14,000 and 21,000 as indicated by gel filtration chromatography. SAs from both HSCM and HPCM have been purified 89- and 122-fold, respectively, by precipitation of extraneous proteins at pH 5 followed by chromatographing twice on Sephacryl S200. Neither of these partially purified SAs contain any CSF for mouse BM. These results indicate that the SAs from HSCM and HPCM may be closely related and that they are structurally different from CSFs derived from various murine sources that have been shown to be stable to proteolytic enzymes and heat.

Animals↗

Dual presentation of polycythaemia vera and lymphatic leukaemia.

A case is described in which polycythaemia vera was found to co-exist with chronic lymphatic leukaemia at the time of presentation. This case can be added to five other reported cases of an association between polycythaemia vera and well-differentiated lymphocytic neoplasia, and adds further emphasis to the tendency for dual presentation, which has now occurred in all but one of these cases. One explanation is that the association is due to chance, but the tendency for dual presentation raises the possibility that the overall picture reflects neoplastic involvement of stem cells with capacity to differentiate into the lymphoid as well as the erythroid, myeloid and megakaryocytic series.

Humans↗