bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic antiproliferative effect of recombinant interferon-gamma with recombinant interferon-alpha on chronic myelogenous leukemia hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM)
Authors: Carlo-Stella C , Cazzola M , Ganser A , Bergamaschi G , Pedrazzoli P , Hoelzer D , Ascari E 
Published: October 2019

Abstract
Recombinant interferons, alpha (rIFN-alpha) and gamma (rIFN-gamma), have been demonstrated to have significant antitumor activity as single agents in the treatment of chronic myelogenous leukemia (CML). Due to their possible synergistic efficacy, a combination rIFN therapy in CML has been proposed. To establish a biologic basis for this, we have studied the suppressive effects of rIFN-alpha and rIFN-gamma on the in vitro growth of CML-derived progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, CFU-GM), the optimal conditions for rIFN synergism, and the possible role of hematopoietic accessory cells (T-lymphocytes and monocytes- macrophages) in mediating rIFN-induced growth inhibition. When added to unseparated bone marrow cells, rIFN-alpha and rIFN-gamma significantly reduced colony formation, with 50% inhibition occurring at 71 and 186 U/mL for CFU-GEMM, 40 and 152 U/mL for CFU-Mk, 222 and 1,458 U/mL for BFU-E, and 119 and 442 U/mL for CFU-GM, respectively. A small amount of rIFN-gamma (5 U/mL) acted synergistically with increasing doses of rIFN- alpha, and the values of 50% inhibitory concentrations fell outside the lower limit (10 U/mL) used in our experiments. This synergy was evident even when rIFN-gamma was added 72 hours after the initiation of cultures; however, it was completely lost when the target cells were depleted of accessory cells. When a low dose of rIFN-alpha (5 U/mL) was added to rIFN-gamma, the 50% inhibitory concentration values were decreased up to tenfold. These studies (1) confirm that CML-derived hematopoietic progenitors are responsive to the suppressive activity of both rIFN-alpha and rIFN-gamma in vitro, (2) demonstrate that different mechanisms are responsible for the suppressive activity of the two rIFNs, and (3) characterize their synergistic interaction, providing a basis for future clinical trials aimed at investigating combination rIFN therapy in CML.
Glucocorticosteroids induce DNA fragmentation in human lymphoid leukemia cells
Authors: Distelhorst CW 
Published: October 2019

Abstract
The present study was undertaken to investigate the potential role of glucocorticoid-induced DNA damage in the lysis of human lymphoid leukemia cells by glucocorticoids. Lymphoblasts were isolated from patients with acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia (CML) in blast crisis and cultured in vitro with or without dexamethasone. DNA was then purified from the cells and analyzed by agarose gel electrophoresis. Only high molecular weight (mol wt) DNA was present in cells cultured without dexamethasone, but a ladder of DNA fragments ranging in size from 180 to 200 base pairs (bp) to greater than 1,500 bp was present in cells cultured with dexamethasone. The DNA fragments were multiples of 180 to 200 bp, suggesting an internucleosomal site of DNA cleavage. The same pattern of DNA fragmentation was detected in normal thymocytes isolated from adrenalectomized rats following in vivo treatment with dexamethasone and in S49 mouse thymoma cells after in vitro incubation with dexamethasone. Dexamethasone-induced DNA fragmentation preceded overt loss of viability in glucocorticoid-sensitive cells but was not detected in two variants of the S49 cell line that are glucocorticoid resistant owing to glucocorticoid receptor defects. The results suggest that glucocorticoids kill human lymphoblastic leukemia cells and both normal and malignant murine thymocytes by a common mechanism that involves glucocorticoid induction of an endonucleolytic activity with cleavage of genomic DNA.
Enhanced expression of the granulocyte-macrophage colony stimulating factor gene in acute myelocytic leukemia cells following in vitro blast cell enrichment
Authors: Kaufman DC , Baer MR , Gao XZ , Wang ZQ , Preisler HD 
Published: October 2019

Abstract
Expression of the granulocyte-macrophage colony-stimulating factor (GM- CSF) gene in acute myelocytic leukemia (AML) was assayed by Northern blot analysis. GM-CSF messenger RNA (mRNA) was detected in the freshly obtained mononuclear cells of only one of 48 cases of AML, in contrast with recent reports that GM-CSF mRNA might be detected in half of the cases of AML when RNA is prepared from T-cell- and monocyte-depleted leukemic cells. We did find, however, that expression of the GM-CSF gene was detectable in five of ten cases after in vitro T-cell and monocyte depletion steps. Additional studies suggest that expression of GM-CSF in the bone marrow of the one positive case, rather than being autonomous, was under exogenous control, possibly by a paracrine factor secreted by marrow stromal cells. These studies emphasize the potential for altering in vivo patterns of gene expression by in vitro cell manipulation.
Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine
Authors: Larson RA , Wernli M , Le Beau MM , Daly KM , Pape LH , Rowley JD , Vardiman JW 
Published: October 2019

Abstract
Seventeen patients with therapy-related myelodysplastic syndrome (t- MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL) were treated with single-agent high-dose cytarabine (HDAC; 1 to 3 g/m2 every 12 hours for 12 doses). The initial neoplasm was still present in eight patients when t-MDS/t-ANLL developed. Fifteen of the 16 patients with chromosomal abnormalities in bone marrow cells had loss or rearrangement of chromosomes 5 and/or 7. One patient had a t(15;17), and one had inadequate material for cytogenetic analysis. Twelve patients had normal metaphase cells (3% to 71%). Indications for HDAC therapy were progressive pancytopenia in 13 patients or rising blast count in four. Five patients died of marrow hypoplasia following therapy. Four others had refractory t-ANLL and died within the subsequent 5 months. Only one of ten patients with a poor performance status (PS greater than or equal to 2 using the ECOG scale) achieved a complete remission, but all seven patients with a good performance status (PS less than or equal to 1) had a complete remission. Hematologic remissions were achieved in 8 patients (47%) after one (6 patients) or two (2 patients) induction courses and were confirmed by recovery of a 100% normal marrow karyotype in six of the seven patients who were retested. Patients in remission received one to four consolidation courses with HDAC alternating with cytarabine/doxorubicin, but seven relapsed within 8 months (median remission duration, 5 months). In every case, the original chromosomal abnormality reappeared at relapse. HDAC has a high response rate for good-performance patients with t-MDS/t-ANLL, but complete remissions are short even when confirmed cytogenetically and consolidated intensively.
Ricin binding and protein synthesis inhibition in human hematopoietic cell lines
Authors: Leonard JE , Grothaus CD , Taetle R 
Published: October 2019

Abstract
Previous studies showed that human blood cells exhibited varying sensitivities to ricin. To investigate the basis for these differences, ricin binding to human hematopoietic cell lines was assessed and correlated with in vitro ricin sensitivities. Resistant mutants were also isolated and characterized. Ricin binding to CEM cells was rapid, time-dependent, and blocked by unlabeled ricin, but not albumin; ricin binding approached saturation at 3 mumol/L. Scatchard analyses showed multiple classes of binding sites, with maximum and minimum Kd values estimated at 1.5 x 10(-8) mol/L and 2.5 x 10(-7) mol/L. At 4 degrees C, membrane-bound ricin dissociated slowly from the cell surface in the presence of unlabeled ricin, but greater than 95% of the surface-bound ricin was removed with 0.1 mol/L lactose. At 37 degrees C, ricin dissociated from the cell surface with biphasic kinetics. Ricin uptake at 37 degrees C increased linearly for 15 to 30 minutes and plateaued at levels representing 12% to 29% of the amount of ricin bound at 4 degrees C, depending on the cell line. Ricin binding at 4 degrees C varied two- to fivefold among hematopoietic cell lines and was reduced approximately tenfold by incubation with lactose. When compared with parent CEM cells, ricin-resistant CEM variants showed a greater than 95% reduction in ricin binding and showed no detectable binding with lactose added. However, these cells were as sensitive as parent CEM cells to an anti-T-cell ricin immunoconjugate. For all cells examined, there was a close correlation (r = +.9) between ricin bound per cell and in vitro ricin sensitivity. Human hematopoietic cells show widely varying ricin binding, indicating major differences in the carbohydrate content or structure of surface glycoproteins and glycolipids. These variations are probably the major determinant of nonspecific toxicity of ricin immunoconjugates.
Two-dimensional iodopeptide mapping demonstrates that erythrocyte Rh D, c, and E polypeptides are structurally homologous but nonidentical
Authors: Blanchard D , Bloy C , Hermand P , Cartron JP , Saboori AM , Smith BL , Agre P 
Published: October 2019

Abstract
The 32,000 molecular weight (mol wt) erythrocyte Rh D, c, and E polypeptides were separately purified from cDE/cDE erythrocytes by monoclonal immunoprecipitations and compared by two-dimensional iodopeptide mapping. Digestions of the isolated Rh polypeptides with alpha-chymotrypsin revealed a high degree of structural homology between c and E (13/14 iodopeptides were identical) and less striking homology between D and c or E (8/19 identical). The iodopeptide maps of Rh proteins purified by a nonimmunologic protocol from cDE/cDE erythrocytes were virtually identical to the composite pattern (D + c + E) deduced from the individual maps of Rh D, c, and E iodopeptides. Digestions of the isolated Rh polypeptides with trypsin revealed an overall homology of approximately 50% between iodopeptides derived from D, c, and E. These data indicate that the erythrocyte Rh D, c, and E antigens are carried by homologous but distinct molecular species; c and E appear more closely related to each other than to D.
The basic study on kappa-lambda imaging by delta-curve for the detection of a monoclonal B-cell population in the peripheral blood
Authors: Nakano M , Kuge S , Kuwabara S , Yaguchi M , Kawanishi Y , Kodama K , Akiya T , Toyama K 
Published: October 2019

Abstract
Recently, kappa-lambda analysis with the “D” value was developed by Ault to detect a minor population of malignant B cells in peripheral blood. This analysis is based on the Kolmogorov-Smirnov test, and the D value is calculated by a flowcytometer and a computer. We have recently devised a more sensitive parameter for the kappa-lambda analysis than the D value called the delta-curve (delta c); the delta c applies the same principle as that of the D value. Mixing experiments with kappa- type and lambda-type chronic lymphocytic leukemia cells revealed that the delta c could not only detect a minor population of malignant kappa- B cells, but also that of malignant lambda-B cells using more sensitivity than the D value. A total of 49 blood samples obtained from 27 patients with various B-cell malignancies were investigated. D values were abnormal in 37% of all samples, while abnormal patterns of the delta c were recognized in 71%. On the other hand, 59% of samples obtained from the patients with B-cell lymphoma in aleukemic phase showed abnormal delta c, whereas D values exceeded the upper limit of the normal value in only 15% of the samples. It was suggested that the delta c could detect 3% to 7% of malignant B cells that were mixed with a population of normal lymphocytes.
Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro
Authors: Sing GK , Keller JR , Ellingsworth LR , Ruscetti FW 
Published: October 2019

Abstract
The effects of transforming growth factor beta 1 or beta 2 (TGF-beta 1 or -beta 2) on the in vitro proliferation and differentiation of normal and malignant human hematopoietic cells were studied. Both forms of TGF- beta suppressed both the normal cellular proliferation and colony formation induced by recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the presence of GM-CSF or IL-3, optimal concentrations of TGF-beta (400 pmol/L) inhibited colony formation by erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor cells by 90% to 100%, whereas granulocyte or monocyte cluster formation was not inhibited. In contrast, neither form of TGF-beta had any effect on G- CSF-induced hematopoiesis. The suppressive action appeared to be mediated directly by TGF-beta since antiproliferative responses were also observed in accessory cell-depleted bone marrow cells. In contrast to normal bone marrow cells, both GM- and G-CSF-induced proliferation of cells from patients with chronic myelogenous leukemia were suppressed in a dose-dependent manner by TGF-beta. Differential effects of TGF-beta on the proliferation of established leukemic lines were also observed since most cell lines of myelomonocytic nature studied were strongly inhibited where erythroid cell lines were either insensitive or poorly inhibited by TGF-beta. These results suggest that TGF-beta is an important modulator of human hematopoiesis that selectively regulates the growth of less mature hematopoietic cell populations with a high proliferative capacity as opposed to more differentiated cells, which are not affected by TGF-beta.
Inhibition of differentiation and affinity purification with a monoclonal antibody to a myeloid cell differentiation-inducing protein
Authors: Shabo Y , Sachs L 
Published: October 2019

Abstract
The normal myeloid hematopoietic regulatory proteins include four growth-inducing proteins called colony-stimulating factors (CSF), including interleukin-3 (IL-3), or macrophage and granulocyte inducers, type 1 (MGI-1), and another type of protein (MGI-2) with no myeloid cell growth-inducing activity that induces differentiation of normal myeloid precursor cells and certain clones of myeloid leukemic cells. An IgG2a monoclonal antibody was prepared and it neutralized two forms of MGI-2 (MGI-2A and MGI-2B) produced by mouse Krebs ascites tumor cells. The monoclonal antibody was used for affinity purification of MGI-2. This antibody also neutralized MGI-2 produced by normal mouse macrophages, normal myeloblasts incubated with IL-3, and MGI-2 produced by the lungs and found in the serum of mice injected with lipopolysaccharide (LPS). The anti-MGI-2 antibody did not inhibit the activity of any one of the four myeloid growth-inducing proteins (CSF or IL-3 = MGI-1), IL-1, tumor necrosis factor, or lymphotoxin. This antibody also inhibited induction of differentiation of myeloid leukemic cells by LPS, which is mediated by the endogenous production of MGI-2, but did not inhibit induction of differentiation in these leukemic cells by dexamethasone or cytosine arabinoside, which is not mediated by MGI-2. Anti-MGI-2 antibody thus inhibited differentiation when MGI-2 was added externally to cells or when it was mediated by endogenously produced MGI-2.
Interleukin-1 alpha enhances the in vitro survival of purified murine granulocyte-macrophage progenitor cells in the absence of colony- stimulating factors
Authors: Williams DE , Broxmeyer HE 
Published: October 2019

Abstract
Interleukin-1 (IL-1), recently identified as hemopoietin-1, affects hematopoiesis by presumably direct and indirect mechanisms. IL-1 stimulates primitive hematopoietic stem cells to express receptors for the granulocyte-macrophage colony-stimulating factors (GM-CSFs) and stimulates CSF release from accessory cells. We used highly purified murine granulocyte-macrophage progenitor cells (CFU-GM, up to 92% cloning efficiency) to assess the effects of IL-1 alpha on the proliferation, differentiation, and survival of these cells. The results demonstrated that IL-1 alpha does not directly influence the proliferation or differentiation of purified CFU-GM in the presence of plateau concentrations of purified natural or recombinant CSFs, and IL- 1 alpha lacks intrinsic CSF activity of its own. CSF deprivation studies showed that IL-1 alpha rapidly (within one hour) promoted CFU- GM survival in the absence of CSF. This enhanced survival stimulated by IL-1 alpha was observed with CFU-GM responding to purified recombinant GM-CSF, natural M-CSF, recombinant G-CSF, recombinant IL-3, or IL-3 in WEHI-conditioned medium, and no effect on the pattern of CFU-GM differentiation occurred in cultures incubated with IL-1 alpha in the absence of CSF. The IL-1 alpha effects on CFU-GM are probably due to a direct action on progenitor cells because the presence or absence of accessory cells did not alter the results and concentrations of the CSFs that were too low to stimulate the proliferation of CFU-GM could not mimic the IL-1 alpha effect on CFU-GM survival.
Antibody produced against isolated Rh(D) polypeptide reacts with other Rh-related antigens
Authors: Suyama K , Goldstein J 
Published: October 2019

Abstract
Rh(D) antigen-containing polypeptide was prepared by immune precipitation of intact cDE/cDE erythrocytes by using a high-titer preparation of polyclonal anti-D. when isolated Rh(D) polypeptide was administered to rabbits, antibody was produced that was unresponsive toward Rh-positive and -negative cells but reacted strongly with the immunogen in enzyme-linked immunosorbent assay-type immunobinding and Western blot immunostaining assays. Rabbit antibody also immunostains isolated Rh(c) polypeptide as well as the Rh antigen-containing components of sodium dodecyl sulfate-polyacrylamide gel electrophoresis- separated membrane proteins from Rh(D)-positive (cDE/cDE,CDe/CDe), Rh(D)-negative (cde/cde,Cde/Cde), and -D-/-D- cells. It does not react with any membrane protein from Rh-null regulator type cells, thus indicating a specificity for Rh-related proteins. We have also been able to demonstrate that polyclonal and monoclonal anti-D preparations that do not immunostain isolated Rh(D) polypeptide will react with it in our immunobinding assay.
Growth of clonogenic myeloblastic leukemic cells in the presence of human recombinant erythropoietin in addition to various human recombinant hematopoietic growth factors
Authors: Asano Y , Okamura S , Shibuya T , Harada M , Niho Y 
Published: October 2019

Abstract
The effects of human recombinant erythropoietin (rEpo) in the presence of other stimulators on the growth of clonogenic leukemic blast cells from ten Japanese patients with acute myeloblastic leukemia were studied with an in vitro leukemic blast colony assay in methylcellulose culture. With the addition of rEpo alone, no leukemic blast colony formation was stimulated in any of the cases examined. However, when rEpo and phytohemagglutinin lymphocyte-conditioned medium (PHA-LCM) were added to the culture simultaneously, in contrast to results with PHA-LCM alone, the number of leukemic blast colonies formed was significantly increased in two of the ten cases (P less than .01). These two cases were classified as M1 according to the French-American- British (FAB) classification. This enhancing effect of rEpo was observed with human recombinant granulocyte/macrophage colony- stimulating factor (rGM-CSF) or human recombinant interleukin-3 (rIL-3) but was not observed with human recombinant granulocyte CSF (rGCSF).
Rearrangement of both immunoglobulin and T-cell receptor genes in a prolymphocytic variant of hairy cell leukemia patient resistant to interferon-alpha [published erratum appears in Blood 1989 Feb;73(2):624]
Authors: Giardina SL , Young HA , Faltynek CR , Jaffe ES , Clark JW , Steis RG , Urba WJ , Mathieson BJ , Gralnick H , Lawrence J 
Published: October 2019

Abstract
We describe a patient with the so-called “prolymphocytic variant” form of hairy cell leukemia (HCL) resistant to treatment with interferon- alpha (IFN-alpha). Analysis of immunoglobulin (Ig) and T-cell receptor- beta (TCR beta) gene rearrangements from serial peripheral blood mononuclear cell specimens (MNCs) confirmed not only the B-cell nature of the disease, but also the subsequent emergence of a morphologically indistinguishable population of cells with a clonal TCR beta rearrangement in addition to the original Ig gene rearrangement. With the exception of a transient increase in peripheral blood T cells during treatment with deoxycoformycin (DCF), the MNCs remained essentially constant throughout therapy with no evidence of a co- existing T-cell clone to account for the TCR beta rearrangement. Although MNCs from this patient bound significantly less IFN-alpha than did MNCs from other HCL patients, the binding was of high affinity with a kd similar to that of control cells. The number of IFN-gamma receptors on our patient's MNCs was four times higher than the number of IFN-alpha receptors and was similar to the number of IFN-alpha receptors on MNCs from HCL patients responsive to IFN-alpha. While various treatments including IFN-alpha, DCF, chlorambucil, splenectomy, leukopheresis, and IFN-gamma were not able to change the clinical progression of the disease, they may have provided an opportunity for the divergent TCR beta rearranged clone to expand and displace the initially dominant clone.
The response of platelets to epinephrine in storage pool deficiency-- evidence pertaining to the role of adenosine diphosphate in mediating primary and secondary aggregation
Authors: Weiss HJ , Lages B 
Published: October 2019

Abstract
Aggregation responses and thromboxane (Tx) formation in ten patients with storage pool deficiency (SPD) specific to the dense granules (delta-SPD) were studied to assess further the role of dense granule adenosine diphosphate (ADP) in mediating platelet aggregation by epinephrine. The ability of epinephrine to elicit secondary aggregation (SA) responses was highly variable in delta-SPD when tested at 5 mumol/L epinephrine, but was consistently abnormal when tested over a range of concentrations. The occurrence of SA in both delta-SPD patients and normal subjects was correlated with the magnitude of the rate of primary aggregation (PA). This PA rate was normal, on average, for the entire patient group but was greater in patients with more consistent SA responses. The PA findings were related to the Kd value obtained in binding studies with 3H-yohimbine, but not with the number of alpha 2-receptor sites. Studies on Tx production (assessed by radioimmunoassay of TxB2) showed that the ability to synthesize Tx from arachidonate was not impaired in delta-SPD, and that there was an absolute positive correlation between epinephrine-induced SA and Tx production. Aggregation in delta-SPD platelets in response to the Tx receptor agonist U44069 was consistently decreased, but could be corrected by addition of ADP. The results of the study suggest that dense granule-derived ADP is not required for PA by epinephrine, but mediates SA as a synergistic agonist with TxA2. This role of ADP in SA may be elucidated more precisely by further studies on platelet activation processes in delta-SPD.