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V Najfeld

Publications and source records attributed to V Najfeld.

At least 55 records · Page 3Linked to original sources
PubMed1992

The gene for human erythrocyte protein 4.2 maps to chromosome 15q15.

Protein 4.2 (P4.2), one of the major components of the red-blood-cell membrane, is located on the interior surface, where it binds with high affinity to the cytoplasmic domain of band 3. Individuals whose red blood cells are deficient in P4.2 have osmotically fragile, abnormally shaped cells and moderate hemolytic anemia. cDNA clones from both the 5' and the 3' coding regions of the P4.2 gene were used to map its chromosomal location by fluorescence in situ hybridization. The probes, individually or in combination, gave specific hybridization signals on chromosome 15. The hybridization locus was identified by combining fluorescence images of the probe signals with fluorescence banding patterns generated by Alu-PCR (R-like) probe and by DAPI staining (G-like). Our results demonstrate that the locus of the P4.2 gene is located within 15q15.

Biotin↗
PubMed1990

Identification of subpopulations of human macrophages through the generation of human macrophage hybridomas.

We have generated a series of human macrophage hybridomas by fusing an HGPRT-deficient promonocytic cell line, U937, with macrophages obtained by allowing monocytes to mature into macrophages in teflon bags. The fusions were documented as true hybrids by the acquisition of donor class I molecules, as well as donor derived macrophage surface antigens. The hybridomas represent clonal expansion of individual macrophages, retaining the surface antigen expression and functional capacity of the normal donor cells including cytokine production and stimulation in a mixed lymphocyte reaction. These cell lines differentially express Vmax antigens found on normal macrophages, potentially identifying subpopulations of macrophages. These lines may be useful not only to study normal macrophage function but may be relevant to a variety of disease states where expansion of subpopulations of macrophages identified by Vmax antigens may be important in disease pathogenesis.

Antibodies, Monoclonal↗
PubMed1990

del(2)(p23): a new recurrent abnormality in acute myeloid leukemia.

In two patients with acute myeloid leukemia, we found a new chromosome abnormality: del(2)(p23) which was detected in 13% and 50% of studied bone marrow cells, respectively. In patient one, del(2p) was an additional abnormality to t(8;21), while patient two had del(2p) as the sole abnormality. Based on our observation and a review of the literature we propose that del(2p) is a new recurrent chromosome abnormality for acute myeloid leukemia.

Adult↗
PubMed1989

A new variant translocation 11;17 in a patient with acute promyelocytic leukemia together with t(7;12).

Bone marrow cells from the majority of patients with acute promyelocytic leukemia (APL) are characterized by t(15;17)(q22;q11-12). At least 12 variant translocations have both also reported, and in each case, either abnormal chromosome 15 or del(17q) or both were involved in complex rearrangements. We report a patient with APL showing two translocations without apparent involvement of chromosome 15 and without del(17q). The karyotype was 46,XY,t(7;12)(p15;p13),t(11;17)(q13;q12). Rearrangement involving t(11;17) is probably associated with APL, while t(7;12) appears to be therapy related.

Aged↗
PubMed1989

P185BCR-ABL in two patients with late appearing Philadelphia chromosome-positive acute nonlymphocytic leukemia.

Two patients with acute nonlymphocytic leukemia (ANLL) who had normal karyotypes at diagnosis and developed the Philadelphia (Ph) translocation during leukemia relapse are described in this report. Patient 1 relapsed with Ph-positive acute leukemia, FAB classification M1. The Ig heavy chain locus and T cell receptor gamma and beta genes of relapse cells from this patient were all found to be germline configuration confirming the diagnosis of M1 acute leukemia. Patient 2 displayed a complex karyotypic evolution leading to Ph-positive M4 relapse. Ph-positive relapse specimens from both patients expressed P185BCR-ABL protein and RNA gene products that were identified serologically and by polymerase chain amplification of the BCR-ABL RNA junction. In vitro derived myeloid cell lines from relapse M1 leukemia cells of patient 1 also expressed the P185BCR-ABL protein. In two described patients, late appearance of the Ph translocation that encodes P185BCR-ABL coincided with relapse of acute leukemia. We conclude that P185BCR-ABL may be a strong indicator of Ph-positive acute leukemias.

Female↗
PubMed1988

Transformation of polycythemia vera to acute nonlymphocytic leukemia accompanied by t(1;3)(p36;q21) karyotype.

The case of a patient with a history of polycythemia vera and 46,XX karyotype who transformed into acute nonlymphocytic leukemia with 46,XX,t(1;3)(p36;q21) rearrangement is reported. Significant percentages of the circulating blasts in the peripheral blood were positive on immunocytochemical stains for megakaryocyte markers, anti-Factor VIII, and antiglycoprotein IIb/IIIa. On the basis of our studies and published reports, trilineage hematopoietic abnormalities and a poor response to therapy may represent typical features of patients with t(1;3).

Acute Disease↗
PubMed1988

Translocation (3;21) in Philadelphia chromosome-positive chronic myelogenous leukemia prior to the onset of blast crisis.

Two female patients in the chronic phase of CML were found to have, in addition to t(9;22), a new karyotypic abnormality--t(3;21)(q26;q22)--present in bone marrow cells. At diagnosis, this abnormality was observed in a small number of marrow cells in both patients, and as the disease progressed in patient 1, the percentage of cells showing t(3;21) was increased, reaching 100% as the transformation to blast crisis occurred. These observations suggest that t(3;21) may represent a new and rare nonrandom rearrangement which may be identified prior to the onset of blast crisis.

Adolescent↗
PubMed1988

Influence on immunoreactive folate-binding proteins of extracellular folate concentration in cultured human cells.

The influence of extracellular folate concentration on cellular levels of the folate transport protein and its soluble product was studied directly in cultured human nasopharyngeal carcinoma (KB) cells. As determined by radioimmunoassay, levels of the folate transport protein and the soluble folate-binding protein were 58 +/- 17 (mean +/- SD) and 5 +/- 2 pmol/mg cell protein, respectively, in KB cells maintained in standard medium (containing 2,300 nM folic acid). These levels significantly increased to 182 +/- 34 and 26 +/- 6 pmol/mg cell protein, respectively, in KB cells serially passaged in low folate medium (containing 2-10 nM 5-methyltetrahydrofolate). Increases in folate-binding protein levels occurred more rapidly in KB cells serially passaged in very low folate medium containing less than 2 nM folate and were prevented by the addition of 100 nM 5-methyltetrahydrofolate or 0.1-1 microM 5-formyltetrahydrofolate to this medium. When KB cells which had been passaged in low folate medium were passaged back into either standard medium or low folate medium supplemented with reduced folates, the levels of both folate-binding proteins fell linearly towards the levels in KB cells continuously maintained in standard medium. The folate transport protein was identified in and underwent similar changes in human and mouse mammary tumor cells. These studies indicate that the folate transport system is probably regulated by the extracellular folate concentration through changes in intracellular metabolite levels.

Animals↗
PubMed1988

Evidence for clonal development and stem cell origin of M7 megakaryocytic leukemia.

Previous studies have shown that acute nonlymphocytic leukemias are clonal diseases in which there is heterogeneity in the pattern of stem cell differentiative expression. To determine whether M7 megakaryocytic leukemia is a clonal disease and to evaluate the differentiative expression of the cells involved by the leukemia we studied a patient with megakaryocytic leukemia who was heterozygous for the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). The diagnosis of megakaryocytic leukemia was based on results obtained with the immunogold method and ultrastructural studies with the monoclonal anti-Gplla/IIIb antibody, 10E5. Direct testing of blood and marrow mononuclear cells and blood platelets demonstrated only A-type G6PD, whereas skin exhibited both B and A enzymes. The results indicate that the megakaryocytic leukemia in this patient was clonal at the time of study. To determine the differentiative expression of the stem cells, granulocyte/macrophage colony forming units and erythroid burst forming units were cultured and the resultant colonies were tested for G6PD. The results indicate that the stem cells involved by the leukemia exhibited differentiative expression multipotent for the megakaryocytic and granulocytic pathways, but no definitive conclusion could be made regarding the erythroid lineage.

Clone Cells↗
PubMed1987

Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia.

To determine whether acute nonlymphocytic leukemia develops clonally, to study the pattern of differentiation of the involved stem cells, and to determine whether clinical remissions are true remissions, we studied 27 patients with acute nonlymphocytic leukemia who were heterozygous for the X-chromosome-linked glucose-6-phosphate dehydrogenase. In each case, leukemic blast cells manifested only one type of glucose-6-phosphate dehydrogenase, indicating that the malignant process had developed from a single cell. In six elderly patients, circulating erythrocytes, platelets, or both expressed only the glucose-6-phosphate dehydrogenase found in blast cells, indicating that these leukemias had arisen from stem cells with multipotent differentiative expression. In 16 younger adults and children, erythroid cells and platelets were predominantly derived from normal stem cells. In three other cases, the stem cell that gave rise to leukemic blasts apparently also gave rise to erythroid progenitors but not to mature erythrocytes. Heterogeneity was also found during remissions. In 8 of 13 patients, restoration of nonclonal hemopoiesis and repopulation of the marrow by normal stem cells was observed during remission. In the other five patients, marrow stem cells remained partially or completely clonal, even during remission. These data indicate that acute nonlymphocytic leukemia is a heterogeneous disease with respect to differentiation of the stem cells involved by leukemia and the nature of remissions.

Acute Disease↗
PubMed1987

A chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch.

Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control gamma-to-beta switching, we analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome-i.e., chromosome 11--sufficient for expression of human fetal globin and the subsequent gamma-to-beta switch. The results suggest that the gamma-to-beta switch is controlled either cis to the beta-globin locus or by a trans-acting mechanism, the genes of which reside on human chromosome 11.

Animals↗
PubMed1987

Treatment of acute myeloid leukemia cells in vitro with a monoclonal antibody recognizing a myeloid differentiation antigen allows normal progenitor cells to be expressed.

Monoclonal antibody L4F3 reacts with most acute myeloid leukemia (AML) cells and virtually all normal granulocyte/monocyte colony-forming cells (CFU-GM). Our objective was to determine whether lysis of AML cells with L4F3 and complement allowed expression of normal myeloid progenitors. The five glucose-6-phosphate dehydrogenase (G6PD) heterozygous patients with AML studied manifested only a single G6PD type in blast cells and in most or all granulocyte colony-forming cells, indicating that the leukemias developed clonally. The cells remaining after L4F3 treatment from two of the patients gave rise to granulocytic colonies that expressed the G6PD type not seen in the leukemic clone, indicating that they were derived from normal progenitors (CFU-GM). L4F3-treated cells from these two patients cultured over an irradiated adherent cell layer from normal long-term marrow cultures also gave rise to CFU-GM, which were shown by G6PD analysis to be predominantly nonleukemic. In the other three patients, the progenitor cells remaining after L4F3 treatment were derived mainly from the leukemic clone. The data suggest that in vitro cytolytic treatment with L4F3 of cells from certain patients with AML can enable normal, presumably highly immature progenitors to be expressed.

Adolescent↗
PubMed1986

Trisomy 22--a new abnormality found in acute leukemia characterized by eosinophilia and monocytoid blasts expressing immature differentiation antigens.

Bone marrow cells from three patients with acute myeloid leukemia, with marrow eosinophilia and monocytoid blasts, showed a new nonrandom chromosomal abnormality, trisomy 22. In two patients the classification of leukemia was M4 and in the third patient M2 (FAB classification). Pretreatment bone marrows in these patients revealed 31%, 30%, and 4% eosinophils, respectively. Blast cells isolated from peripheral blood were Ia-positive and expressed immature monocyte lineage antigens (U26, U28, U48) in 26%-92% of cells. All three patients had a population of bone marrow cells characterized by an extra chromosome #22. One patient also had inversion of chromosome #16. Trisomy 22, bone marrow eosinophilia, and monocytoid blasts displaying early monocyte differentiation antigens may represent a new subgroup of patients with acute myeloid leukemia.

Adult↗
PubMed1985

Adult and fetal human globin genes are expressed following chromosomal transfer into MEL cells.

Somatic cell hybridization of mouse erythroleukemia (MEL) cells and HEL cells, a human erythroleukemia line that produces fetal (gamma) but fails to express adult (beta) globin, was used to test whether the expression of the two human globin genes is regulated cis or trans. An experimental approach using anti-human globin monoclonal antibodies for detection, efficient cloning, and monitoring of hybrids of interest was employed. Further characterization of hybrids used isoelectric focusing for detection of human globins and S1 nuclease mapping. In contrast to the parental HEL line, all chromosome 11-retaining HEL-MEL hybrids expressed human beta-globin, suggesting that the HEL beta-globin genes (i) are transcriptionally competent, (ii) become activated in response to a positive trans-acting element within the MEL environment, and (iii) fail to express into the HEL environment because of either the absence of a positive trans-acting element or the presence of a trans-acting inhibitor of beta-globin gene expression. In addition to beta-globin, the primary HEL-MEL hybrids co-expressed gamma-globin; however, gamma-globin expression segregated by subcloning so that secondary and tertiary clones either expressed only beta-globin or co-expressed gamma- and beta-globin. The results of subcloning can be explained by assuming that gamma-globin gene expression is controlled by a HEL cell-derived transacting element encoded by a gene not syntenic to chromosome 11 or by postulating that the HEL gamma-globin genes become randomly modified during the continuous proliferation of hybrids.

Animals↗
PubMed1985

Evidence for clonal development of childhood acute lymphoblastic leukemia.

To determine whether acute lymphoblastic leukemia (ALL) is a clonal disease and to define the pattern of differentiation shown by the involved progenitor cells, we studied the glucose-6-phosphate dehydrogenase (G6PD) types in the cells of 19 girls heterozygous for this X chromosome-linked enzyme. Lymphoblast immunophenotypes were those of HLA-DR+, CALLA+ ALL (six patients); HLA-DR+, CALLA- ALL (four patients); pre-B cell ALL (two patients); T cell ALL (four patients); and undefined ALL (three patients). Malignant blast cells at diagnosis from ten patients displayed a single G6PD type, indicative of clonal disease. In contrast, both A and B G6PD in ratios similar to those found in skin were observed in morphologically normal blood cells from the same patients. The leukemic cells of three patients were examined at both diagnosis and relapse; in each instance the same G6PD type was found, consistent with regrowth of the original leukemic clone at relapse. Results of studies of cells from nine additional patients tested only at relapse were similar. Our results indicate that childhood ALL is a clonally derived disease involving progenitor cells with differentiation expression detected only in the lymphoid lineage.

Adolescent↗