bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer of specific immunity to B-cell lymphoma with syngeneic bone marrow in mice: a strategy for using autologous marrow as an anti-tumor therapy
Authors: Kwak LW , Campbell MJ , Zelenetz AD , Levy R 
Published: October 2019

Abstract
Persistence of the underlying malignancy remains the major obstacle limiting the success of high-dose chemoradiotherapy with autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphomas. We used the 38C13 murine B-cell lymphoma model to explore the approach of transferring tumor antigen-specific immunity with syngeneic BM as a protective element. Mice serving as syngeneic marrow donors were twice immunized with tumor-derived surface Ig protein, the idiotype of which serves as a tumor-specific antigen, or with a control Ig of matched isotype. Naive lethally irradiated recipients reconstituted with marrow from immune donors showed serologic tumor idiotype-specific immunity, as well as protection against lethal tumor challenge. The immunoprotective effect of immune marrow was also shown in lethally irradiated recipients partially protected by specific immunization post- BMT. Combined donor and recipient immunization also replaced the requirement for the booster immunization of the donor. These results provide the rationale for active immunization with purified surface Ig from autologous tumor as an adjunct to autologous BMT in humans.
Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report
Authors: Linker CA , Levitt LJ , O'Donnell M , Forman SJ , Ries CA 
Published: October 2019

Abstract
We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.
Role of the glycoprotein IIb-IIIa complex in plasma membrane Ca2+ transport: a comparison of results obtained with platelets and human erythroleukemia cells
Authors: Suldan Z , Brass LF 
Published: October 2019

Abstract
Several studies have suggested that the glycoprotein (GP) IIb-IIIa complex, which serves as the platelet fibrinogen receptor, also plays a role in the regulation of Ca2+ influx across the platelet plasma membrane. To examine this possibility further, we have compared Ca2+ transport in platelets and human erythroleukemia (HEL) cells, a megakaryoblastic cell line which synthesizes GP IIb-IIIa complexes that appear to be identical to those found on platelets. As with platelets, the results show the presence in unstimulated HEL cells of a rapidly exchangeable cytosolic Ca2+ pool that is in equilibrium with an intracellular sequestered Ca2+ pool and with extracellular Ca2+. Allowing for differences in cell size, the rate constants for Ca2+ exchange in HEL cells were similar to those in platelets. As in platelets, thrombin caused an increase in cytosolic Ca2+ that was due partly to enhanced Ca2+ influx and partly to the mobilization of internal Ca2+ stores. Incubation of the HEL cells with EDTA at 37 degrees C irreversibly altered the GP IIb-IIIa complex as evidenced by decreased binding of a complex-specific monoclonal antibody. In platelets this was accompanied by a 40% decrease in the rate of Ca2+ influx. However, in HEL cells there was neither a diminution in Ca2+ influx nor a reduction in the magnitude of the increase in cytosolic Ca2+ caused by thrombin. These results show that the parameters of Ca2+ distribution and movement are similar in HEL cells and platelets and that in HEL cells, as in platelets, the GP IIb-IIIa complex can be altered by removing Ca2+. However, unlike platelets, dissociation of the HEL cell IIb-IIIa complex has no discernible effect on plasma membrane Ca2+ transport. This suggests that earlier observations in platelets correlating changes in the rate of Ca2+ influx with changes in the number of intact IIb-IIIa complexes reflect an indirect, rather than a direct, role of these proteins in Ca2+ transport.
Imbalance of thromboxane/prostacyclin biosynthesis in patients with lupus anticoagulant
Authors: Lellouche F , Martinuzzo M , Said P , Maclouf J , Carreras LO 
Published: October 2019

Abstract
The mechanism involved in the association between antiphospholipid antibodies and thrombosis or fetal loss remains unclear. We assessed the biosynthesis of thromboxane A2 and prostacyclin in 31 samples from 25 patients with lupus anticoagulant and in 32 controls. The urinary excretion of the major thromboxane metabolite of platelet origin (11- dehydrothromboxane B2) was very significantly increased (P less than .0003) in the patients. In contrast, the urinary metabolite reflecting the vascular production of prostacyclin (2,3-dinor-6-keto-prostaglandin F1 alpha) was much less increased (P less than .02). We found no correlation between the levels of anticardiolipin antibodies and the urinary excretion of 11-dehydro-thromboxane B2. Six patients with elevated urinary 11-dehydrothromboxane B2 were treated with low-dose aspirin (20 mg/d during 7 days). In these patients, there was a close relationship between the extent of inhibition of the thromboxane urinary metabolite (72%) and serum thromboxane B2 (79%). In contrast, the urinary excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha was nearly unchanged (13% reduction). In addition, the F(ab')2 fragments isolated from six patients presenting increased urinary 11-dehydro- thromboxane B2 enhanced the generation of thromboxane B2 (P = .04) and the release of 14C serotonin (P = .009) by normal washed platelets, as compared with F(ab')2 from controls. In summary, our study shows that in patients with lupus anticoagulant, platelet activation may occur without a compensatory increment in the vascular biosynthesis of prostacyclin. This observation may be crucial to cause or reflect an increased risk for thrombosis. In addition, our results may suggest a rationale for antiplatelet agents for the prophylaxis of thrombosis in many patients with the antiphospholipid syndrome.
The promoter of human T-cell leukemia virus type-I is repressed by the immediate-early gene region of human cytomegalovirus in primary blood lymphocytes
Authors: Gartenhaus RB , Wong-Staal F , Klotman ME 
Published: October 2019

Abstract
Infection with human T-cell leukemia virus type-I (HTLV-1) is associated with a low incidence of morbidity in the form of adult T- cell leukemia as well as neurologic disease, including tropical spastic paraparesis/HTLV-I-associated myelopathy, suggesting that there are other important factors which determine outcome of infection. HTLV-I and the human herpesvirus, cytomegalovirus (HCMV), have both been shown to infect OKT4+ T lymphocytes in vitro as well as in vivo. We investigated the effects of expression of HCMV IE-2 protein(s) on the HTLV-I long terminal repeat (LTR) containing the promoter elements in T- cell lines and primary lymphocytes. A consistent repressive effect was observed on HTLV-I LTR-driven chloramphenicol acetyl transferase activity after cotransfection with the HCMV IE-2 gene region, both in HTLV-I-producing cell lines as well as in uninfected primary peripheral blood lymphocytes and cloned lymphocyte lines. This repressive effect on the HTLV-I LTR by the HCMV IE-2 gene product(s) represent a unique interaction between two viruses capable of infecting the same target cell in vivo. Such an interaction may have important implications for disease expression associated with HTLV-I infection.
Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children: correlation between chromosomal abnormalities and prior therapy
Authors: Rubin CM , Arthur DC , Woods WG , Lange BJ , Nowell PC , Rowley JD , Nachman J , Bostrom B , Baum ES , Suarez CR 
Published: October 2019

Abstract
We have studied 20 children with therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were 3 months to 16 years old at diagnosis of their primary neoplasm and 1 to 24 years old at diagnosis of their secondary neoplasm. The median interval from initial treatment for the first malignancy to diagnosis of therapy- related MDS or AML was 46 months (range, 12 to 116 months). Twelve patients had chromosomal abnormalities resulting in loss of material from the long arm of chromosomes 5 and/or 7, three patients had abnormalities of chromosome 11 band q23, one patient had both classes of abnormalities, three patients had other abnormalities, and one patient had a normal karyotype. Ten of 12 patients with chromosome 5 and/or 7 abnormalities had been exposed to an alkylating agent, and two of three patients with 11q23 abnormalities had been exposed to an epipodophyllotoxin. The patient with both classes of abnormalities had been exposed to both types of therapy. We conclude that abnormalities of chromosomes 5 and/or 7 are common in children with therapy-related MDS or AML. The proposed relationships between exposure to alkylating agents and abnormalities of chromosomes 5 and/or 7 and between exposure to epipodophyllotoxins and abnormalities of 11q23 are supported in this pediatric series.
A novel human homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10;14)
Authors: Dube ID , Kamel-Reid S , Yuan CC , Lu M , Wu X , Corpus G , Raimondi SC , Crist WM , Carroll AJ , Minowada J 
Published: October 2019

Abstract
The translocation t(10;14)(q24;q11) is an acquired change seen in 4% to 7% of T-cell acute lymphoblastic leukemias (T-ALL). We previously demonstrated that the translocation juxtaposes the T-cell receptor (TCR) delta-chain gene in chromosome 14q11 with a novel region in chromosome 10q24 and is likely catalyzed by recombinases normally involved in the generation of immunoglobulin and TCR diversity. We now present the sequence of a gene on chromosome 10 that lies immediately telomeric of the breakpoints in nine new ALL patients with acquired rearrangements in 10q24. The gene is a novel human homeobox gene and is expressed in leukemic cells from ALL patients with rearrangements in a defined chromosome 10 breakpoint cluster region, but not in other adult tissues or cell lines. This new gene has been designated HOX11. Our results strongly support a role for homeobox genes in oncogenesis and may represent the first example of a human cancer in which deregulated expression of an unaltered homeobox gene is involved in tumorigenesis.
Analysis of B-lymphoid malignancies using allele-specific polymerase chain reaction: a technique for sequential quantitation of residual disease
Authors: Billadeau D , Blackstadt M , Greipp P , Kyle RA , Oken MM , Kay N , Van Ness B 
Published: October 2019

Abstract
The junctional sequences corresponding to the complementarity determining region 3 (CDR3) of rearranged heavy chain Ig genes can provide allele-specific markers in the detection of B-lymphoid malignancies. Consensus oligonucleotide primers were used to amplify CDR3 regions of rearranged heavy chain alleles in clinical samples from myeloma, acute lymphocytic leukemia, and chronic lymphocytic leukemia patients. From the sequence of the amplified products, allele-specific primers were synthesized and used directly in polymerase chain reaction (PCR) amplification to detect the malignant clone. This method was both highly specific and sensitive to 1 malignant B-cell in a background of 10(5) normal cells. In addition, parameters that affect the linearity of PCR detection were determined and, by using titrations of malignant target cells to generate standard curves, quantitations of residual malignancies were determined. The application of this method is shown in an analysis of myeloma patients whose marrows were analyzed sequentially during therapy. Allele-specific oligonucleotide-PCR provided a rapid, highly specific and quantitative measure of residual disease, even in patients with clinical parameters indicating complete remission.
Reticulocyte rigidity and passage through endothelial-like pores
Authors: Waugh RE 
Published: October 2019

Abstract
The importance of cell rigidity in regulating the release of reticulocytes from the bone marrow has been investigated in a model system. Reticulocytes were obtained from phlebotomized rabbits and separated from whole blood by discontinuous density gradient centrifugation. The mechanical properties of the cells were tested. Using single-cell micromechanical techniques, the membrane elastic rigidity and the viscoelastic response of reticulocyte and mature cell populations were measured. The reticulocyte membranes were more rigid than the mature membranes, but the reticulocyte properties were heterogeneous, and some cells exhibited behavior indistinguishable from the mature cells. The mean time constant for viscoelastic recovery was the same for reticulocytes as for mature cells, but the variability within the reticulocyte population was greater. The possible influence of this increased rigidity on cell egress from the bone marrow was tested using an in vitro model of the thin endothelial pores found within the marrow. A silicon wafer approximately 0.1 microns in thickness and containing a small (1.2-microns diameter) pore in its center was cemented over the tip of a large (15.0-microns ID) micropipette. The passage of cells through the pore was observed as a function of the pressure across the pore. Consistent with the difference in mechanical properties, the reticulocytes required greater pressures (as great as 4.0 mm Hg compared with less than 1.0 mm Hg) and took longer to traverse the pore. These measurements support the postulate that deformability is important in the regulation of the release of cells from bone marrow.
In vitro myelopoiesis stimulated by rapid medium exchange and supplementation with hematopoietic growth factors
Authors: Schwartz RM , Emerson SG , Clarke MF , Palsson BO 
Published: October 2019

Abstract
We studied the effect of the combination of rapid culture medium exchange with the addition of the human hematopoietic growth factors interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (Epo) on the proliferation and differentiation of human long-term bone marrow cultures (LTBMCs). Individually and in combinations, IL-3, GM-CSF, and Epo were added to the culture medium of LTBMCs that were maintained with 50% medium volume exchange per day. The combination of IL-3 + GM-CSF + Epo generated the most prolific cultures with an order of magnitude increase in nonadherent cell production from weeks 2 through 8 in culture as compared with unsupplemented controls. Under these conditions, the cultures produced as many cells as were inoculated every 2 weeks and led to a greater than 2.5-fold expansion in terms of the number of nonadherent cells produced over a 6- to 8-week period. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. The rapid medium exchange combined with the addition of human hematopoietic CSFs significantly enhances the proliferation and differentiation of LTBMCs. These results indicate that addition of combinations of hematopoietic CSFs, together with a rapid medium exchange rate, can provide culture conditions that are suitable for the expansion of the progenitor cell pool and perhaps for the increased survival of hematopoietic stem cells in culture. Although these culture conditions still fall short of full reconstitution of functional human bone marrow, they provide an improved approach to hematopoietic cell culture that may permit the expansion and manipulation of progenitor cells in vitro.
Aphidicolin, an inhibitor of DNA replication, blocks the TPA-induced differentiation of a human megakaryoblastic cell line, MEG-O1
Authors: Murate T , Hotta T , Tsushita K , Suzuki M , Yoshida T , Saga S , Saito H , Yoshida S 
Published: October 2019

Abstract
The commitment process of a human megakaryoblastic cell line (MEG-O1) induced with phorbol ester, TPA, was investigated with special reference to glycoprotein (GP) IIb/IIIa expression, multinuclear formation, and DNA replication. TPA (10(-7) mol/L) completely inhibited cellular division in MEG-O1, but did not suppress de novo DNA synthesis. Two days' culture with 10(-7) mol/L TPA was sufficient for MEG-O1 cells to initiate an irreversible commitment process. These cells could not resume cell growth and expressed GP IIb/IIIa antigen; some of them showed multinuclear form and DNA polyploidy even after removal of TPA from the culture medium. DNA histogram analysis showed that, upon treatment with TPA, the percentage of cells whose DNA ploidy was more than 8N was 5 to 10 times higher than that of control cells. Precise analysis using cell size fractionation by centrifugal elutriation method showed that there was strong correlation between the percentage of multinuclear cells and DNA polyploidy in TPA-treated cells. The percentage and staining intensity of GP IIb/IIIa and other megakaryocytic phenotypes such as von Willebrand factor and PAS staining were highest in large multinuclear cell populations, suggesting that these cells are the most differentiated population in this system. In TPA-treated cells, the activity of DNA polymerase alpha, a marker for cell growth, remained at the same level as in control cells. Aphidicolin, a specific inhibitor of DNA polymerase alpha, completely inhibited the differentiation induction of MEG-O1 cells with TPA measured by either GP IIb/IIIa expression or multinuclear cell formation. Therefore, DNA replication appears to be involved in the process of phenotypic expression as well as endomitosis in megakaryocyte differentiation of MEG-O1 cells. Aphidicolin was also effective in inhibiting megakaryocytic differentiation of other leukemia cell lines such as human erythroleukemia (HEL) and K562 cell lines induced with TPA, suggesting the close interplay of DNA replication and phenotypic expression in megakaryopoiesis.
Differentiation-associated expression of prostaglandin H and thromboxane A synthases in monocytoid leukemia cell lines
Authors: Sanduja SK , Mehta K , Xu XM , Hsu SM , Sanduja R , Wu KK 
Published: October 2019

Abstract
To elucidate the differentiation-associated expression of enzymes catalyzing arachidonic acid metabolism, we measured arachidonate metabolites by reverse-phase high pressure liquid chromatography in monocytoid leukemia (ML-1, THP-1, and U937) and myeloid leukemia (KG-1) cell lines. Undifferentiated ML-1 or THP-1 cells produced trace amounts of eicosanoids via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Upon differentiation induced by phorbol ester (phorbol 12- myristate 13-acetate [PMA]), metabolites via the COX pathway were increased by 100-fold in ML-1 and THP-1 cells, while the LOX products remained barely detectable. All the COX metabolites were elevated, but thromboxane A2 (TXA2) formation was threefold higher in ML-1 cells than in THP-1 cells. Similar time-related increases in COX metabolites were observed in THP-1 cells induced to differentiate with retinoic acid. Undifferentiated U937 cells were capable of generating a much higher quantity of COX products than ML-1 or THP-1 cells, but, upon PMA- induced differentiation, COX products were increased by only two-fold to threefold over the undifferentiated cells and the total COX products in differentiated U937 cells were only one-seventh of those produced by differentiated ML-1 or THP-1 cells. KG-1 cells had an entirely different metabolic profile. They produced a large quantity of a metabolite coeluted with prostaglandin D2, and PMA had no effect on inducing changes in arachidonic acid (AA) metabolism. Increased COX metabolite formation in differentiated THP-1 and ML-1 cells was due to an enhanced level of prostaglandin H synthase enzyme mass, as measured by Western blot analysis. The TXA synthase activity was also increased by approximately 100-fold in PMA-induced ML-1 cells and 10-fold in THP- 1 cells. These findings indicate that increased expression of prostaglandin H and TXA synthase enzymes is a feature of differentiated monocytoid leukemia cell lines.
c-kit expression by CD34+ bone marrow progenitors and inhibition of response to recombinant human interleukin-3 following exposure to c-kit antisense oligonucleotides
Authors: Catlett JP , Leftwich JA , Westin EH , Grant S , Huff TF 
Published: October 2019

Abstract
The c-kit proto-oncogene encodes a receptor having tyrosine-specific kinase activity and has been mapped to chromosome 4 in the human and chromosome 5 in the mouse, at the dominant white spotting locus (W). Mutations at the W locus affect various aspects of murine hematopoiesis. The c-kit proto-oncogene has been shown to be expressed by leukemic myeloblasts, but not by normal unseparated human bone marrow cells. The role of this oncogene in differentiation and proliferation of human hematopoietic progenitors is presently undefined. To determine c-kit expression by normal hematopoietic progenitors, CD34+ cells were isolated from disease-free human bone marrow, and RNA-based polymerase chain reaction (PCR) techniques were used to assess expression. By this method, we have demonstrated c-kit expression by CD34+ bone marrow progenitors. To address the functional requirement for c-kit expression in normal human hematopoiesis, CD34+ cells were incubated in the presence of sense, antisense, or missense oligonucleotides to c-kit, and subsequently cultured in the presence of either recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or recombinant human interleukin-3 (rhIL-3). Exposure of CD34+ cells to c-kit antisense oligonucleotides significantly inhibited colony-forming ability of cells cultured in the presence of rhIL-3, but had no effect on colony formation of cells cultured in rhGM- CSF. Together, these data suggest a possible role for c-kit in hematopoietic proliferation and differentiation that may be linked to some, but not all, stimulatory factors.