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T Grunberger

Publications and source records attributed to T Grunberger.

28 records · Page 2Linked to original sources
PubMed1986

Detection of residual acute lymphoblastic leukemia cells in cultures of bone marrow obtained during remission.

We used a semisolid culture assay to quantitate leukemia cells in the bone marrow of patients with childhood acute lymphoblastic leukemia (ALL). In bone marrow cultures from 40 patients with newly diagnosed disease, the colonies that developed in vitro consisted of lymphoblasts with the same surface markers and abnormal karyotype as the original diagnostic marrow specimens. We also studied marrow cultures from 13 patients in chemotherapy-induced remission; 6 of these, including 1 obtained from a patient during successful engraftment after marrow transplantation, also yielded lymphoblast colonies in culture, with the same immunologic phenotype or abnormal karyotype as the original leukemic marrow. Four of these patients, including the one who underwent marrow transplantation, relapsed within 2 to 30 months of the abnormal cultures; the other two are still in remission, one of them 30 months after diagnosis. Bone marrow cultures from eight normal controls and from the other seven patients in remission did not yield lymphoblast colonies; all seven of the latter are still in remission. This assay appears to allow detection of small numbers of residual leukemic cells. We conclude that the technique will be valuable in monitoring the efficacy of chemotherapy and allogeneic bone marrow transplantation in acute lymphoblastic leukemia, as well as in evaluating the quality of purged marrow for autologous marrow transplantation.

Antigens, Surface↗
PubMed1986

Clinical utility of marrow cell tissue cultures in acute leukemia of childhood.

To determine the clinical value of tissue culture techniques in the study of acute leukemia, marrows from 50 children (40 acute lymphoblastic [ALL], 10 acute myeloblastic [AML]) were cultured by the use of an AML blast colony assay and the CFU-GEMM assay. In the AML assay, AML marrow gave rise to high numbers of blast colonies within 24 to 48 hr; in sharp contrast, 37 of 40 ALL marrows did not yield colonies in this assay. In the CFU-GEMM assay, AML marrow produced excessive numbers of monocyte-macrophage CFU-C colonies, an obvious background of individual macrophages and clusters, and occasional blast colonies. ALL marrow yielded very low numbers of granulocytic CFU-C colonies, no background of macrophage cells, and no blast colonies. These clear-cut differences in cellular growth kinetics in vitro between ALL and AML marrows should allow confirmation of the type of acute leukemia within 24 to 48 hr. The colony assays may also be valuable in differentiating ALL from AML in difficult diagnoses when conventional approaches are nondiagnostic.

Acute Disease↗
PubMed1986

Characterization of malignant peripheral blood cells of juvenile chronic myelogenous leukemia.

Characterization studies were performed on the malignant peripheral blood cells from three patients with juvenile chronic myelogenous leukemia (JCML) by allowing the cells to increase numerically in liquid cultures. JCML cells proliferated rapidly and excessively in the absence of an added humoral growth factor, whereas control peripheral blood cells declined in number when cultured under identical conditions. Clonality of JCML cells was proven by cytogenetic analysis of the proliferating population. JCML cells were exclusively of monocytic lineage as determined by morphology, staining characteristics, and monoclonal antibody identification of cell-specific surface antigens, but cytochemical and functional studies identified aberrant properties indicating defective differentiation. Striking differences from control cells in ultrastructure and topography were also observed by transmission and scanning electron microscopy. These data provide new information on the cellular origin of JCML and form the basis for further study of leukemic cell biology in this disease.

Child, Preschool↗
PubMed1986

Juvenile chronic myelogenous leukemia: characterization of the disease using cell cultures.

To characterize juvenile chronic myelogenous leukemia (JCML), the proliferative properties of bone marrow (BM) and peripheral blood (PB) cells from nine patients were studied using assays for CFU-C and CFU-GEMM and liquid cultures. All specimens showed two reproducible abnormalities: impaired growth of normal hematopoietic progenitors and excessive proliferation of monocyte-macrophage colonies in the absence of exogenous colony-stimulating activity (CSA). Cytogenetic studies in one patient indicated that the CFU-C were malignant because BM cells at diagnosis and monocyte-macrophage colonies showed an abnormal karyotype, whereas PB lymphocytes did not. In contrast to JCML, PB from six adults with Philadelphia (Ph1) chromosome-positive chronic myelogenous leukemia (Ph1 + CML) yielded CSA-dependent CFU-C colonies which were composed of granulocytes, macrophages, or both, as well as exuberant growth of BFU-E colonies. Co-cultures of JCML BM adherent or nonadherent cells with normal BM resulted in suppression of normal hematopoietic colony formation. Supernatant from JCML adherent cells in liquid culture or plasma from newly diagnosed untreated JCML patients also suppressed control BM colony growth in a dose-dependent manner. These findings confirm that JCML is a malignant disorder of monocytic lineage and suggest that the mechanism of hematopoietic failure in JCML is mediated by an inhibitory monokine secreted by malignant JCML cells.

Bone Marrow Cells↗
PubMed1986

The regulatory role of interleukin 2-responsive T lymphocytes on early and mature erythroid progenitor proliferation.

To analyze the role of T lymphocytes in human erythropoiesis, we evaluated the effect of recombinant interleukin 2 (IL 2) on marrow CFU-E and BFU-E colony formation in vitro. IL 2 resulted in an increase in CFU-E and BFU-E colony numbers in a dose-dependent manner. This increase could be prevented by anti-Tac, a monoclonal antibody to the IL 2 receptor. Moreover, anti-Tac on its own resulted in an overall decrease in colony numbers. Depletion of marrow adherent cells did not alter the effect of either IL 2 or anti-Tac on colony growth. Following the removal of marrow T lymphocytes, CFU-E and BFU-E colony formation proceeded normally; however, the effects of IL 2 and anti-Tac were markedly diminished. Readdition of T lymphocytes to the cultures restored the IL 2 effect. Although T lymphocytes were not themselves essential for in vitro erythropoiesis, our studies suggest that IL 2 and IL 2-responsive T cells can regulate both early and mature stages of erythroid differentiation.

Animals↗
PubMed1985

Growth inhibitory effect of gene-cloned interferons on human myeloblast colonies.

The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulted in a sharp increase in the IFN-induced enzyme 2-5A synthetase, indicating the expression of IFN cell receptors as well as the ability of leukemia cells to respond metabolically. Dose-response studies showed a dose-dependent suppression of myeloblast colony formation in all experiments using concentrations of 10(2)-10(5) U/ml of the three IFN subtypes. In self-renewal assays derived from the primary cultures that initially contained IFN alpha 2, a "carryover" antiproliferative effect was observed with a dose-dependent decline in secondary growth. In comparison studies of IFN alpha-A and IFN alpha-C, the suppressive effect on primary myeloblast growth was much more pronounced with IFN alpha-C at concentrations of 10(3) U/ml and higher; in self-renewal assays, the antiproliferative effect of IFN alpha-C on secondary growth was no longer observed, whereas that of IFN alpha-A persisted. These three subtypes of gene-cloned IFN have antileukemic properties in vitro, with differences in degree of suppression of primary myeloblast growth and of self-renewal.

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Erythropoietic inhibitors in uremic serum.

The anemia of chronic renal failure was studied by assessing the inhibitory effect of uremic serum on the proliferation of normal human marrow erythroid progenitor cells (CFU-E and BFU-E) using an in vitro colony assay. Of 10 uremic patients studied, sera from 9 inhibited CFU-E colony growth by 29-100%, sera from 8 inhibited BFU-E colony growth by 23-94%, and sera from all inhibited either CFU-E or BFU-E. The sera were fractionated by Sephacryl gel filtration and the fractions were added to the marrow cultures. Almost all the suppressive activity against erythroid colony growth was detected in fractions with mol. wts of from 47,000 to greater than 150,000 daltons and this indicates the presence of several high mol. wt inhibitors. Serum fractionation by Sephacryl gel was useful in confirming the presence of uremic inhibitors of erythropoiesis, and in concentrating them to a degree that will allow detailed characterisation studies.

Adult↗
PubMed1975

Influence of albumin on rubella virus hemagglutination and the hemagglutination-inhibition test.

The HEPES-saline-albumin-gelatin (HSAG) diluent found optimal for agglutination of fowl erythrocytes by rubella virus antigen is also optimal for agglutination of trypsin-treated human group O cells. Albumins from different commercial sources, however, can have varying inhibitory effects on rubella hemagglutination titers. This can have a significant effect on the hemagglutination-inhibition test since antibody titers measured by this procedure are related to the amount of antigen used.

Animals↗
PubMed1975

A microplaque reduction assay for human and mouse interferon.

A microplaque reduction assay for human and mouse interferons is described, using plastic disposable multicompartmental plates with flat-bottomed wells of 6 mm in diameter. The procedure is rapid and reproducible and lends itself to a considerable degree of automation. Its potential application in other areas of virology, such as rapid screening of samples for virus content or assay of neutralizing antibodies, is also discussed.

Cell Line↗