bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation
Authors: Rosmarin AG , Weil SC , Rosner GL , Griffin JD , Arnaout MA , Tenen DG 
Published: October 2019

Abstract
During the course of differentiation of early human myeloid cells toward monocytes and granulocytes, cell surface expression of the cell adhesion molecule, CD11b/CD18 (Mo1) increases dramatically and expression of myeloperoxidase (MPO), a bacteriocidal enzyme, decreases markedly. Using the inducible promyelocytic cell line HL-60 as a model, we studied the mRNA expression of these genes. Differentiation of these cells along both a monocytic and a granulocytic pathway demonstrated that the mRNA levels of the two subunits of CD11b/CD18 increased in a pattern temporally and quantitatively similar to the increase in cell surface expression of this heterodimer. In contrast, the expression of MPO mRNA decreased in a temporal and quantitative pattern similar to the known decrease in MPO protein during differentiation, suggesting that regulation of these myeloid-specific proteins may occur at the level of mRNA expression. These findings have important implications with regard to the nature of the block in differentiation in acute nonlymphocytic leukemia and the regulation of myeloid gene expression.
Vitamin D metabolite-mediated hypercalcemia and hypercalciuria patients with AIDS- and non-AIDS-associated lymphoma
Authors: Adams JS , Fernandez M , Gacad MA , Gill PS , Endres DB , Rasheed S , Singer FR 
Published: October 2019

Abstract
Fifteen patients with lymphoma and hypercalcemia (greater than or equal to 11.0 mg/dL) were identified by screening the serum chemistry profile obtained from patients upon admission to the Los Angeles County/USC Medical Center. Seven of the 15 (47%) possessed a frankly elevated serum concentration of 1,25-dihydroxyvitamin D [1,25-(OH)2-D]. An additional patient with severe hypercalcemia (16.2 mg/dL) had a serum 1,25-(OH)2-D concentration in the midnormal range, not a suppressed value. To examine the potential existence of hypercalciuria in absence of overt hypercalcemia, prospective screening of 23 normocalcemic patients with lymphoma was undertaken. Four of the 23 patients (17%) had increased fractional urinary calcium excretion rates (0.35 +/- 0.3 mg calcium/100 mL glomerular filtrate [GF], mean +/- SE; normal, less than 0.16 mg/100 mL GF); two of the hypercalciuric patients had a frankly elevated serum 1,25-(OH)2-D concentration. Of the 19 hypercalcemic/hypercalciuric lymphoma patients identified, none had an elevated serum immunoreactive parathyroid hormone concentration. Fourteen of the 19 hypercalcemic/hypercalciuric patients (74%) suffered from B-cell neoplasms, three had Hodgkin's lymphoma, and two had adult T-cell leukemia/lymphoma. All hypercalcemic/hypercalciuric patients had widespread disease (stage III or IV). Six patients, four with hypercalcemia and two with hypercalciuria, had acquired immunodeficiency syndrome (AIDS). These data suggest that the deregulated synthesis of a 1,25-(OH)2-D-like metabolite is a common cause of hypercalcemia and hypercalciuria in patients with lymphoma including patients with AIDS-associated tumors.
Granulocyte-macrophage colony-stimulating factor (CSF) and multilineage CSF recruit human monocytes to express granulocyte CSF
Authors: Oster W , Lindemann A , Mertelsmann R , Herrmann F 
Published: October 2019

Abstract
We assessed the capacity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and multilineage (Multi)-CSF to induce release of granulocyte-CSF (G-CSF) by highly purified peripheral blood monocyte (Mo) preparations. Our results reveal that GM-CSF and Multi-CSF, either alone or in a synergistic concert, activate Mo to transcribe G-CSF messenger (m) RNA and release biologically active G- CSF protein into their culture supernatants. G-CSF had no regulatory effect on Mo expression of cytoplasmic G-CSF mRNA levels and G-CSF protein secretion by itself. These differential actions of CSFs provide further insight into self-regulatory mechanisms within the growth factor hierarchy system.
Demonstration of a blood-bone marrow barrier to macrophage colony- stimulating factor
Authors: Shadduck RK , Waheed A , Wing EJ 
Published: October 2019

Abstract
Several previous studies suggested that murine macrophage colony- stimulating factor (CSF-1) might have impaired access to hematopoietic cells in the marrow. The apparent lack of hematopoietic responses to exogenous CSF and the finding of available or unoccupied CSF receptors despite saturating CSF levels in the serum led to studies of a potential blood-bone marrow barrier for this factor. Groups of mice were injected with pure unlabeled CSF-1 by either intravenous (IV) or intraperitoneal (IP) routes. Marrow and spleen cells were obtained at intervals after injection, held at 0 degree C, and assessed for changes in binding of 125I-CSF. Saturation of all available CSF receptors is achieved in vitro with 100 to 150 U CSF/mL. Despite achieving serum levels of 5,000 to 7,000 U/mL after IV injection of 25,000 units of CSF, less than 50% of the marrow receptors and less than 85% of the splenic receptors were saturated or downregulated. The decline in receptor availability was transient, with return of receptor sites in two to four hours. Increasing the IV dose to 125,000 units increased serum CSF values to approximately 20,000 U/mL and led to a virtual disappearance of available receptors for two to three hours. When administered IP, only approximately 40% of marrow and 80% of splenic receptors were affected for two hours. It was necessary to increase the dose of CSF to 250,000 units IP to saturate or downregulate receptors for three to four hours after injection. These observations indicate a marked blood-bone marrow barrier and lesser blood-spleen barrier for the transfer of serum CSF to responsive hematopoietic cells in vivo.
Rearrangement of the T-cell receptor delta genes in human T-cell leukemias
Authors: Foroni L , Laffan M , Boehm T , Rabbitts TH , Catovsky D , Luzzatto L 
Published: October 2019

Abstract
Two distinct types of T-cell receptors (TCR), designated alpha beta and gamma delta, have been identified on the surface of T cells. In the adult, T cells bearing the gamma delta TCR are a minority and they have the phenotype CD3+, CD4-, CD8-/+. By using appropriate probes, rearrangements of the TCR alpha, beta, and gamma genes have been extensively investigated in a variety of lymphoproliferative disorders. Because the TCR delta gene has been cloned only recently, no comparable information exists with respect to this in human leukemias. We report the analysis of the TCR delta gene configuration in 21 T-cell acute and chronic leukemias, 40 B-cell leukemias, 4 acute myeloid leukemias of difficult classification, and 12 normal controls. The TCR delta genes were structurally modified in all T-cell disorders and in germ-line configuration in all controls and all but one case of non-T-cell leukemias tested. In one case of T-chronic lymphocytic leukemia (CD3+, CD4-, CD8+) we found rearrangement and expression of TCR gamma and delta (but not alpha and beta), suggesting that leukemic transformation took place in a cell bearing a TCR gamma delta rather than a TCR alpha beta. In two cases of pre-T-acute lymphoblastic leukemia, only delta was rearranged out of the three TCR genes tested. This finding is in keeping with the suggestion that the TCR delta gene might be the first to rearrange in T cell ontogeny, and that its mode of rearrangement may play a role in the subsequent choice of the cell between production of a TCR alpha beta or gamma delta. Thus, TCR delta chain gene analysis can provide novel information of the clonal nature of T-cell disorders, particularly if the analysis of the beta and gamma genes has not been helpful.
Alternating v repeated postremission treatment in adult acute myelogenous leukemia: a randomized phase III study (AML6) of the EORTC Leukemia Cooperative Group
Authors: Zittoun R , Jehn U , Fiere D , Haanen C , Lowenberg B , Willemze R , Abels J , Bury J , Peetermans M , Hayat M 
Published: October 2019

Abstract
The value of a postremission treatment in acute myelogenous leukemia (AML), with alternating combinations of non-cross-resistant drugs, has been prospectively assessed. Of 515 evaluable patients, 347 (67.4%) entered into complete remission (CR), following induction treatment with daunorubicin (DNR), vincristine (VCR), and cytosine arabinoside (ara-C). After one consolidation course, 248 patients were randomized for six courses of intensive maintenance: either repeated treatment with DNR-VCR-ara-C, or alternating treatment where amsacrine (AMSA) was combined with high dose ara-C on cycle 1,3, and 5 and with 5- azacytidine on cycle 2, 4, and 6. Ninety-nine patients were not randomized: 57 were introduced in a bone marrow transplantation (BMT) program, and 42 went off study, mainly for treatment toxicity or refusal. The main prognostic factors for achievement of CR were performance status, cytogenetics, and age, and for the disease-free survival (DFS): age and number of courses to CR. The rate of second remission was fairly high (64%) for patients relapsing off therapy. The DFS appeared identical (median, 53 weeks), in the two randomized arms, the alternating treatment not showing superiority to the repeated one, in spite of an increased toxicity. The median overall survival for patients achieving a CR was 90 weeks. The reason for the failure of alternating maintenance treatment to improve the DFS is probably related to an insufficient dose intensity: five patients who relapsed during maintenance arm B achieved a second CR with a more intensive combination of high-dose ara-C and AMSA. In addition, 60 patients underwent a BMT (43 allogeneic and 17 autologous). The DFS of patients treated with allogeneic BMT tended to be superior to the one obtained with the chemotherapy program. However the overall survival, as well as the event-free survival, seemed equivalent, including patients who relapsed before the planned BMT. Comparisons between allogeneic BMT, autologous BMT, and intensive consolidation during first CR deserve further prospective studies in AML.
Inhibition against CFU-C and CFU-E colony formation by soluble factor(s) derived from hairy cells
Authors: Taniguchi N , Kuratsune H , Kanamaru A , Tokumine Y , Tagawa S , Machii T , Kitani T 
Published: October 2019

Abstract
The inhibitory effect by hairy cell conditioned medium (HCCM) on the growth of granulocyte and erythrocyte colony forming cells was studied in vitro. The percent inhibition of CFU-C formation by HCCM from four hairy cell leukemia (HCL) patients ranged from 36% to 76%, while no inhibition was observed with conditioned medium (CM) obtained from three B-cell chronic lymphocytic leukemia (B-CLL) patients nor from two normal controls. HCCM inhibited specially the growth of rG-CSF responding stem cells. The hairy cell-derived colony inhibitory factor from HCCM was nondialyzable, fairly stable to heat treatment, and trypsin sensitive. Its maximal inhibitory activity against granulopoiesis was observed in the fractions of 5,000 to 6,000 daltons. Moreover HCCM inhibited CFU-E colony formation but not BFU-E. These results indicate that hairy cells produce a factor that inhibits granulopoiesis and erythropoiesis in vitro. This factor may play a role in neutropenia and anemia observed in HCL.
Expression in Escherichia coli of the human fibrinogen B beta chain and its cleavage by thrombin
Authors: Bolyard MG , Lord ST 
Published: October 2019

Abstract
The human fibrinogen B beta chain was expressed in Escherichia coli to study the functions of fibrinogen associated with this subunit. Recombinant B beta chains were expressed at 100 ng/mL in an IPTG- dependent manner. A first cistron sequence, inserted into the expression vector 5′ to the B beta chain cDNA, was required to express the protein. Recombinant B beta chains were expressed within five minutes after induction with IPTG and were soluble in physiologic buffers. The recombinant B beta chains migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at a rate identical to B beta chains from fibrinogen treated with N-glycanase. Recombinant B beta chains were cleaved by thrombin, as demonstrated by the loss of cross-reactivity with a monoclonal antibody (MoAb) specific for the undigested B beta 1–42 fragment. The levels of expression of the B beta chain were much lower than those reported previously for the gamma chain of fibrinogen expressed in a similar vector in E coli. However, these levels are sufficient to allow further characterization of this fibrinogen subunit.
Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts
Authors: Keever CA , Small TN , Flomenberg N , Heller G , Pekle K , Black P , Pecora A , Gillio A , Kernan NA , O'Reilly RJ 
Published: October 2019

Abstract
The reconstitution of hematopoietic cells and in vitro assays of immunologic function have been followed in leukemic patients after conventional bone marrow transplantation (BMT) (N = 34) and T-cell depleted BMT (N = 52) from human leukocyte antigen (HLA)-identical sibling donors. No effects of the T-cell depletion could be seen on the recovery of myeloid or lymphoid cells as measured by the day to engraftment or by the absolute number of cells through day 100. Normal numbers of lytically active natural killer cells returned the earliest and were rapidly followed in both groups of patients by the appearance of circulating B cells and normalization of the responses to B-cell mitogens. However, the recovery of normal T-cell proliferative responses were more delayed in recipients of T-cell depleted grafts. Significant quantitative differences were seen only during the first 3 months after transplantation. Neither the number of CD3+ T cells nor the ratio of CD4:CD8 positive cells differed markedly between the two transplant groups. Mitogen-induced immunoglobulin production by peripheral blood lymphocytes (PBL) from patients following T-cell depleted BMT was quantitatively less than that of conventional marrow recipients through the first year, with low normal IgM production reached by 4 to 6 months in both groups. IgG production reached low normal 7 to 9 months after conventional BMT but did not remain at this level until 1 year following either type of transplant. Assessment of the incidence of infections from the day the absolute neutrophil count reached 500 until day 180 after transplant revealed no significant differences between the two groups; indeed, the overall nonleukemic mortality was higher in the recipients of conventional bone marrow. Thus, in our series, the removal of mature cells from the marrow graft did not affect the rate or degree of recovery of myeloid and lymphoid cells but did affect the regeneration of in vitro T-cell dependent functions. We noted early quantitative differences and a delay in the normalization of the T-cell functions measured rather than prolonged absolute deficiencies. The in vitro deficiencies did not result in significant clinically apparent differences between the two groups.
Deleterious effects of irradiation and bone marrow transplantation therapy in the genetically anemic an/an mouse
Authors: Eppig JT , Barker JE 
Published: October 2019

Abstract
The efficacy and outcome of bone marrow transplantation therapy following lethal irradiation were examined in syngeneic mice that had a hereditary macrocytic anemia (an/an) or were genotypically normal (+/+). Successful RBC and WBC replacement, based on blood cell parameters and donor genetic markers, were observed in all combinations of transplant therapy. Nevertheless, the an/an mice died prematurely several months after treatment, whether they received +/+ or an/an marrow cells. In contrast, the +/+ recipients of either +/+ or an/an marrow cells survived for at least 1 year after transplantation. Premature death of the an/an mice was associated with lymphopenia, anemia, kidney lesions, and severe pathogen-free pneumonitis. On the basis of our results, we hypothesize that the premature deaths of an/an mice are caused by a kind of chronic irradiation damage to which an/an mice are especially susceptible.
Calcium-dependent proteolysis of actin during storage of platelet concentrates
Authors: Snyder EL , Horne WC , Napychank P , Heinemann FS , Dunn B 
Published: October 2019

Abstract
In an ongoing study of the changes that occur in platelet concentrates during storage, we investigated two 28–26-Kd proteins designated SP–1 and SP–2, respectively, which increase markedly during blood-bank storage of platelet concentrates at room temperature. Formation of SP–1 and SP–2 was inhibited by storage at 4 degrees C as well as by treatment of the concentrates with leupeptin, N–ethylmaleimide, and EDTA; DFP and PPACK had no effect. The calcium ionophore A23187 markedly stimulated production of SP–1 and SP–2. After partial purification, the two proteins were found to be associated with platelet cytoskeletal protein. Two-dimensional peptide mapping and amino acid sequencing identified SP-1 and SP-2 as fragments of actin formed by cleavage on the N-terminal side of residues Thr–106 and Ala- 114, respectively. Generation of SP–1 and SP–2 during storage of platelet concentrate is likely attributable to calcium-dependent neutral protease degradation of actin and may have implications for development of the platelet storage lesion.
Platelet membrane glycoprotein IIb heavy chain forms a complex with glycoprotein IIIa that binds Arg-Gly-Asp peptides
Authors: Lam SC , Plow EF , Ginsberg MH 
Published: October 2019

Abstract
Platelet membrane GPIIb is comprised of a disulfide-linked heavy chain (GPIIb(H)) and light chain (GPIIb(L)). We have examined the role of the two chains of GPIIb in the maintenance of the GPIIb-IIIa heterodimer and Arg-Gly-Asp (RGD) peptide-binding function. Lysates of surface radioiodinated platelets were treated with 1% 2-mercaptoethanol for 18 hours at 4 degrees C. Reduction of the interchain disulfide in GPIIb was followed by immunoprecipitation with antipeptide antibodies specific for GPIIb(H) or GPIIb(L). In addition to the GPIIb-IIIa complex, a polypeptide of 120 Kd was precipitated by anti-GPIIb(H) and a polypeptide of 23 Kd was precipitated by anti-GPIIb(L) from reduced platelet lysates. To determine whether GPIIb(H) or GPIIb(L) remained complexed with GPIIIa, reduced platelet lysates were immunoprecipitated with AP3, a monoclonal anti-GPIIIa antibody, resulting in the coimmunoprecipitation of GPIIb(H) but not GPIIb(L). Conversely, the monoclonal anti-GPIIb(H) antibody PMI-1 immunoprecipitated GPIIIa with GPIIb(H). Thus GPIIb(H) maintains its association with GPIIIa. Furthermore, the GPIIb(H)-IIIa complex retains its reactivity with AP2, a monoclonal antibody (MoAb) specific for the nondissociated GPIIb-IIIa complex. Affinity chromatography of reduced platelet lysates on immobilized KYGRGDS resulted in binding and specific elution of the GPIIb(H)-IIIa complex. These findings indicate that GPIIb(H) contains sufficient information for maintenance of a complex with GPIIIa and support of the binding of the heterodimer to RGD peptides.
Radiation sensitivity of resting and activated nonspecific cytotoxic cells of T lineage and NK lineage
Authors: Zarcone D , Tilden AB , Lane VG , Grossi CE 
Published: October 2019

Abstract
Natural killer (NK) cell-mediated killing of tumor cells is a radiation- sensitive function that in most subjects is completely abrogated by treatment of the effector cells with 3,000 cGy. The radiation sensitivity of LAK (lymphokine-activated killer) cells and their precursors, the bulk of which are NK cells, is undetermined. In this study, functional cytotoxicity assays and electron microscopy were used to determine the effect of radiation on the cytotoxic function of NK cells, LAK cells (generated by three-day culture of peripheral blood lymphocytes with IL-2), and LAK cell precursors (lymphocytes irradiated prior to culture with IL-2). For comparison, we analyzed the radiation sensitivity of lectin-dependent cell-mediated cytotoxicity (LDCC), which is primarily a function of CD3+ CD8+ granular lymphocytes. We also analyzed the radiation sensitivity of nonspecific cytotoxicity mediated by mitogen-activated T cells (AK activity). Following 3,000 cGy irradiation, NK cells retained their ability to bind to tumor cell targets but, as shown by both morphologic and functional analyses, they did not undergo activation after conjugate formation, and were unable to release the content of their granules. In order to evaluate LDCC, lymphocytes were depleted of CD16+ cells and tested in a cytotoxicity assay in the presence of Con A. The radiation sensitivity curve was comparable to that of NK cell-mediated cytotoxicity. IL-2-treated lymphocytes (LAK cells) were relatively radioresistant as compared with untreated NK cells, and their cytotoxic function was not abrogated until treatment with greater than 10,000 cGy. Cells receiving such radiation doses displayed cytoplasmic blebbing and damage of their cytoskeletal structures, with disruption of centrioles and microtubules, and disarray of the intermediate filaments. As was shown with NK cells, irradiated LAK cells formed conjugates with tumor targets but failed to degranulate. The radiation sensitivity of nonspecific cytotoxicity mediated by mitogen-activated T cells was identical to that of LAK effector cells. Doses up to 2,000 cGy did not prevent generation of LAK cells from blood lymphocytes, but 3,000 cGy did so. Blast transformation similar to that observed in IL-2- stimulated controls occurred when lymphocytes irradiated with 3,000 cGy were cultured with IL-2. These transformed cells were not cytotoxic and displayed a normal cytoskeletal apparatus but did not bear electron- dense granules.(ABSTRACT TRUNCATED AT 400 WORDS)
Profiles of expression of activated cell antigens on peripheral blood and lymph node cells from different clinical stages of adult T-cell leukemia
Authors: Shirono K , Hattori T , Hata H , Nishimura H , Takatsuki K 
Published: October 2019

Abstract
The expression of activated cell antigens (Ags) on adult T cell leukemia (ATL) cells at different clinical stages (acute, chronic, and smoldering), and ATL cells from enlarged lymph nodes were studied using monoclonal antibodies (MoAbs). The expressions of CD25 (Tac), CD28, T9 (transferrin receptor), and Ki-67 (proliferating cell nuclear antigen) Ags were high, and that of CD7 Ag was low in both acute and chronic ATL cells compared with that in normal T cells. The expressions of T9 and Ki-67 Ags were higher in acute ATL cells than in chronic ATL cells. The expression of CD38 Ag was higher in acute ATL cells but not in chronic ATL cells compared with normal T cells. On the contrary, the expression of HLA-DR Ag on the cell surface and the transcript of the HLA-DR Ag gene were high in chronic ATL cells, but not in acute ATL cells. A high percentage of lymph node ATL cells expressed T9, CD38, and Ki-67 Ags, although the peripheral blood ATL cells of the same patients showed significantly lower levels of expression of the same Ags. Interestingly, CD7 and HLA-DR Ags were detected on the majority of lymph node ATL cells. Moderately high percentage of smoldering ATL cells expressed CD25, CD28, and HLA-DR Ags, though a few numbers of leukemic cells were present in the samples. These findings confirm that the modes of activation of ATL cells in different clinical stages differ, and suggest that the differences might be reflected in the clinical features. The low expression of HLA-DR Ag in acute ATL cells, despite high expression of the Ag in chronic ATL cells, suggests that successive events that suppress HLA-DR Ag expression are necessary for the transformation of chronic ATL cells into acute ATL cells. Moreover, the high expressions of T9, CD38, Ki-67, CD7, and HLA-DR Ags on lymph node ATL cells indicate that ATL cells preferentially proliferate in lymph nodes.