bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors with high-dose melphalan for refractory multiple myeloma [see comments]
Authors: Barlogie B , Alexanian R , Smallwood L , Cheson B , Dixon D , Dicke K , Cabanillas F 
Published: October 2019

Abstract
High doses of melphalan (HDM) and dexamethasone were administered to 43 patients with advanced multiple myeloma, 36 of whom were refractory to both standard melphalan-prednisone and vincristine-adriamycin- dexamethasone (VAD). Forty-four percent responded with greater than 75% reduction in calculated tumor mass, including three patients who achieved a complete remission. The response rate to HDM was 56% in 18 relapsing patients and 50% in 12 patients with less than 12 months of primary drug resistance, but it was only 23% among the remaining 13 unresponsive patients. A high early mortality rate of 30% was confined to 26 patients with either poor performance (Zubrod greater than 1) or impaired renal function (creatinine greater than 1.4 mg%). When this toxic treatment was given to the 21 patients with good performance (Zubrod less than 2) whose disease lacked high serum lactic dehydrogenase (less than or equal to 500 U/L) as a recently recognized feature of high-grade myeloma, a superior median survival of 18 months was obtained as opposed to only 3 months for the 22 remaining patients (P less than .001). Thus, when employed in a timely fashion, HDM overcomes resistance to standard chemotherapy and VAD and benefits selected patients with advanced myeloma.
Characterization of a new non-Hodgkin's lymphoma cell line (NCEB-1) with a chromosomal (11:14) translocation [t(11:14)(q13;q32)]
Authors: Saltman DL , Cachia PG , Dewar AE , Ross FM , Krajewski AS , Ludlam C , Steel CM 
Published: October 2019

Abstract
A new cell line, NCEB-1, was established by Epstein-Barr virus (EBV) transformation of peripheral blood mononuclear cells from a patient with centroblastic-centrocytic diffuse lymphoma expressing IgM lambda. The transformed cells were lymphoblastoid, with many cells showing a plasmacytoid morphology. The NCEB-1 cells had cytoplasmic Ig (CyIg), with loss of the surface Ig (SIg) expression. Cytogenetic analysis of the cell line demonstrated two clones with variations: a hypodiploid clone, with a complex karyotype including a t(11;14)(q13;q32) similar to the original tumor cells, and a near tetraploid clone with the same markers. Southern blot analysis of DNA from the patient's neoplastic cells and NCEB-1 demonstrated identical Ig heavy chain gene rearrangement, confirming the origin of the cell line. The cell line was not tumorigenic when tested in an in vitro assay using immunosuppressed mice. NCEB-1 has been in continuous culture for 9 months and will be valuable for the in vivo study of non-Hodgkin's lymphoma and EBV transformation.
The incidence of painful crisis in homozygous sickle cell disease: correlation with red cell deformability
Authors: Lande WM , Andrews DL , Clark MR , Braham NV , Black DM , Embury SH , Mentzer WC 
Published: October 2019

Abstract
To determine whether the vasoocclusive severity of homozygous sickle cell (SS) disease is influenced by cellular dehydration, we correlated the incidence of painful crisis with steady-state measurements of red cell hydration. Sixteen children with SS disease were followed for 3.3 to 8 years (mean, 6.8 years), and a single crisis rate was calculated for each patient. At the time of well visits, cellular hydration was assessed by measuring cell deformability, the percentage of red cells with a density greater than or equal to 1.1056 g/mL, and the percentage of irreversibly sickled cells (ISC). The incidence of painful crisis showed a strong positive correlation with Omax, a deformability measurement reflecting cellular hydration (r = .84, P less than .002), and with hemoglobin concentration (r = .59, P = .04). That is, higher crisis rates were observed in patients with less dehydrated, more deformable red cells and also in patients with higher hemoglobin concentrations. Furthermore, cell deformability and hemoglobin concentration were independent predictors of the incidence of painful crisis, which is consistent with separate effects of these two red cells parameters on vasoocclusive severity.
Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients
Authors: Duhrsen U , Villeval JL , Boyd J , Kannourakis G , Morstyn G , Metcalf D 
Published: October 2019

Abstract
Hematopoietic progenitor cell levels were monitored in the peripheral blood and bone marrow of 30 cancer patients receiving recombinant human granulocyte-colony stimulating-factor (rG-CSF) in a phase I/II clinical trial. The absolute number of circulating progenitor cells of granulocyte-macrophage, erythroid, and megakaryocyte lineages showed a dose-related increase up to 100-fold after four days of treatment with rG-CSF and often remained elevated two days after the cessation of therapy. The relative frequency of different types of progenitor cells in peripheral blood remained unchanged. The frequency of progenitor cells in the marrow was variable after rG-CSF treatment but in most patients was slightly decreased. The responsiveness of bone marrow progenitor cells to stimulation in vitro by rG-CSF and granulocyte- macrophage colony-stimulating factor did not change significantly during rG-CSF treatment. In patients nine days after treatment with melphalan and then rG-CSF, progenitor cell levels were very low with doses of rG-CSF at or below 10 micrograms/kg/d, but equaled or exceeded pretreatment values when 30 or 60 micrograms/kg/d of rG-CSF was given.
The human interleukin-1 alpha gene is located on the long arm of chromosome 2 at band q13
Authors: Lafage M , Maroc N , Dubreuil P , de Waal Malefijt R , Pebusque MJ , Carcassonne Y , Mannoni P 
Published: October 2019

Abstract
Interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) are two biochemically distinct, but distantly related, polypeptidic cytokines that play a key role in inflammation, immunologic reactions, and tissue repair. Recently, it has been shown that IL-1 alpha is identical to hematopoietin 1, which was described as a hematopoietic growth factor acting on early progenitor cells in synergy with other hematopoietic growth factors. In this report we discuss our use of in situ hybridization on human prometaphase cells with a human IL-1 alpha cDNA probe to localize the human IL-1 alpha gene on the proximal part of the long arm of chromosome 2 at band q13, in the same chromosomal region as the IL-1 beta gene.
Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay
Authors: Watari K , Asano S , Shirafuji N , Kodo H , Ozawa K , Takaku F , Kamachi S 
Published: October 2019

Abstract
In order to better understand the patho-physiologic role of granulocyte colony-stimulating factor (G-CSF), we estimated its serum levels in healthy persons and patients with various disorders, using a newly developed enzyme immunoassay (Motojima et al). In 49 of 56 normal healthy persons (88%), the levels were beneath the sensitivity of the assay (less than 30 pg/mL), while in the remaining seven healthy persons, the levels ranged from 33 to 163 pg/mL. On the other hand, nine of 11 patients (82%) with idiopathic aplastic anemia (AA), one patient with Fanconi's anemia, six of 12 patients (50%) with myelodysplastic syndrome (MDS), five of 12 patients (42%) with acute leukemia without any blast cells in the blood (M4: one, M5: one, L1: one, and L2: two), six of 18 patients (33%) with chronic myeloid leukemia (CML), one of two patients with chronic lymphoid leukemia (CLL), two of four patients with lung cancer, one patient with cyclic neutropenia, two of seven patients with malignant lymphoma, and four patients with acute infection had G-CSF levels ranging from 46 pg/mL to greater than 2,000 pg/mL. Interestingly, a reverse correlation between blood neutrophil count and serum G-CSF level was clearly demonstrated for aplastic anemia (r = -.8169, P less than .01). Moreover, it was found that the G-CSF level rose during the neutropenic phase of cyclic neutropenia and after chemotherapy or bone marrow transplantation (BMT) in three patients with leukemia; also high G-CSF levels were positively correlated to blood neutrophil counts in some cases of infectious disorders and lung cancer. The cellular sources and the mechanisms for production and secretion of circulating G-CSF were not investigated in this study, but the data presented here strongly indicate that G-CSF plays an important role as a circulating neutrophilopoietin.
Epinephrine induces platelet fibrinogen receptor expression, fibrinogen binding, and aggregation in whole blood in the absence of other excitatory agonists
Authors: Shattil SJ , Budzynski A , Scrutton MC 
Published: October 2019

Abstract
The exposure of fibrinogen receptors is an early event in agonist- induced platelet activation. Previous measurements of fibrinogen binding or aggregation in platelet-rich plasma or washed platelets have failed to define whether the initial response to epinephrine results solely from a direct effect of this agonist. To address this problem, we have measured fibrinogen receptor exposure on platelets in whole blood by using flow cytometry and a fluorescein isothiocyanate-labeled monoclonal antibody specific for the activated fibrinogen receptor (FITC-PAC1). We also measured platelet-bound fibrinogen with an antifibrinogen monoclonal antibody (FITC-9F9) as well as platelet aggregation in whole blood. In blood anticoagulated with citrate and in the presence of a cyclooxygenase inhibitor, epinephrine (0.1 to 100 mumol/L) caused significant FITC-PAC1 binding (P less than .001) that was maximal at 10 mumol/L epinephrine. The maximal epinephrine response was one third of that observed with 10 mumol/L adenosine diphosphate (ADP) and was eliminated by yohimbine, an alpha 2-adrenergic antagonist. Incubation of the blood with apyrase or phosphoenolpyruvate plus pyruvate kinase to remove extracellular ADP resulted in a 40% to 50% reduction in the epinephrine response. Despite this, FITC-PAC1 binding was still significant at epinephrine greater than or equal to 1 mumol/L (P less than .05). No reduction in epinephrine-induced FITC- PAC1 binding was observed in the presence of ATP alpha S, an ADP receptor antagonist; cinanserin, a serotonin antagonist; or WEB-2086, a platelet activating factor antagonist. Furthermore, addition of the thrombin inhibitors hirudin or leupeptin to citrated blood had no effect on the extent of the epinephrine response. Blood anticoagulated with hirudin also demonstrated an epinephrine response, even in the presence of apyrase. Similar results were obtained when FITC-9F9 was used to detect fibrinogen binding or when aggregation was assessed by a decrease in the number of single platelets. We conclude that epinephrine itself can induce fibrinogen receptor exposure, fibrinogen binding, and aggregation. This primary response is independent of synergistic interaction of epinephrine with traces of ADP, serotonin, platelet activating factor, or thrombin. However, such synergistic interaction with ADP present in whole blood may enhance the responses induced by epinephrine.
Hepatitis B virus DNA in the serum of Sardinian blood donors negative for the hepatitis B surface antigen
Authors: Lai ME , Farci P , Figus A , Balestrieri A , Arnone M , Vyas GN 
Published: October 2019

Abstract
The high endemicity of hepatitis B virus (HBV) infection and liver disease in Sardinia led us to assess the occurrence of HBV DNA in 1,411 sera of two selected groups of hepatitis B surface antigen (HBsAg)- negative blood donors: 793 with abnormal serum alanine aminotransferase (ALT) and 618 with normal serum ALT values (determined during routine testing of their blood donation). HBV DNA sequences were detected by dot-blot hybridization in 68 of 793 subjects (9%) with abnormal ALT but only in three of 618 subjects (0.5%) with normal ALT. HBV-core antibody (anti-HBc) was detected in 338 of 793 subjects (43%) with abnormal ALT as well as in 125 of 618 subjects (20.2%) with normal ALT. Among the 71 subjects positive for serum HBV DNA, 22 (31%) were positive for anti- HBc, while 49 (69%) were negative for all serologic markers of HBV infection. Thus, a high frequency of anti-HBc in apparently healthy HBsAg-negative individuals and a high prevalence of serum HBV DNA in the absence of immunologic markers of HBV infection suggest the existence of genetic variants of HBV that may be responsible for some of the presumed NANB hepatitis encountered in Sardinia and possibly other areas of high endemicity for HBV.
Studies of in vitro activated CD5+ B cells
Authors: Freedman AS , Freeman G , Whitman J , Segil J , Daley J , Nadler LM 
Published: October 2019

Abstract
Human B lymphocytes undergo distinct phenotypic changes following activation with antigen and polyclonal mitogens. Increasing interest has focused on the unique subpopulation of B cells that expresses the CD5 antigen. In this study, we examined the signals that induce the expression of CD5 on normal splenic B cells. Only 12-O- tetradecanoylphorbol-13-acetate (TPA) induced CD5 expression on highly purified splenic B cells, whereas anti-immunoglobulin (anti-Ig), Epstein-Barr virus, anti-CD20, recombinant interleukin-1 (rIL-1), rIL- 2, rIL-4, recombinant interferon-gamma (rINF-gamma), and B-cell growth factor all failed to induce CD5 expression. The expression of CD5 was detected on the cell surface by 48 hours and decreased by 96 hours. Dual-fluorochrome analysis demonstrated that the CD5+ B cells coexpressed the B-cell activation antigens B5, IL-2 receptor, and CD23, thereby providing phenotypic evidence that this B-cell subpopulation is activated. In vitro studies of dual-fluorochrome-sorted, TPA-stimulated splenic B cells demonstrated significantly greater tritiated thymidine incorporation and Ig secretion by the CD20+ CD5- cells than by the CD20+ CD5+ subset. These phenotypic and functional studies are consistent with the notion that TPA-induced CD5+ B cells are a subset of in vitro activated B lymphocytes.
Characterization of a novel form of transferrin receptor preferentially expressed on normal erythroid progenitors and precursors
Authors: Cotner T , Gupta AD , Papayannopoulou T , Stamatoyannopoulos G 
Published: October 2019

Abstract
A panel of monoclonal antibodies (MoAbs) against cell surface proteins of early BFUe progeny was characterized. Five of these antibodies (Abs) reacted with normal erythroid, but not myeloid, bone marrow cells. Each of the five antibodies, typified by Ab 69.20, immunoprecipitated a dimeric complex of 185,000, which is composed of two identical disulfide-bonded subunits. This antigen had affinity for transferrin, and was essentially identical in biochemical characteristics to transferrin receptors precipitated with the well-characterized MoAbs OKT9 and 5E9. However, this form of transferrin receptor lacked both the OKT9 and 5E9 antigenic determinants and, moreover, the 69.20 epitope was absent from the conventional transferrin receptor, as defined by Abs OKT9 and 5E9. Modulation experiments demonstrated that both 69.20 and OKT9 modulated large, virtually independent populations of transferrin receptors. Both forms of transferrin receptor appeared to be derived from the product of a single gene, but the form defined by MoAb 69.20 apparently predominates in cells of the erythroid lineage and some transformed cell types that manifest a special requirement for iron. These data suggest that cells with a high iron requirement synthesize two forms of transferrin receptor, possibly by means of differential mRNA splicing or by posttranslational modification of the transferrin receptor.
In vivo cell growth and pharmacologic determinants of clinical response in acute myelogenous leukemia
Authors: Karp JE , Donehower RC , Enterline JP , Dole GB , Fox MG , Burke PJ 
Published: October 2019

Abstract
A predictable increase in the proliferative rate of malignant cells remaining after initial cytoreduction in vivo forms the rationale for timed sequential therapy (TST) with 1-B-D-arabinofuranosylcytosine (ara- C) for adult acute myelogenous leukemia (AML). The relationship between in vivo leukemic cell growth, intracellular ara-C metabolism, and clinical response to ara-C-containing TST was evaluated by comparing AML marrow cell growth kinetic and biochemical pharmacologic determinants obtained before therapy (day 0) and at the predicted peak of in vivo postdrug residual tumor proliferation (day 8). Serial measurements of DNA synthesis and net intracellular ara-C metabolism demonstrated marked increases in both determinants in day 8 residual tumor when compared with the pretreatment cells for newly diagnosed adults achieving complete remission but not for TST-refractory patients. The interrelationship of AML cell proliferation and biochemical pharmacology together quantitate cytotoxicity measured by both achievement and duration of remission and serve to predict eventual clinical outcome in response to TST with ara-C where both growth and favorable pharmacokinetics are intrinsic to the success of the drug schedule.
Aberrant restriction endonuclease digests of DNA from subjects with hereditary myeloperoxidase deficiency
Authors: Nauseef WM 
Published: October 2019

Abstract
Myeloperoxidase (MPO) is a critical component in the oxygen-dependent microbicidal activity of neutrophils. Hereditary deficiency of MPO occurs commonly, but its genetic basis has not been determined. Previously we have reported the presence of an 89-kilodalton protein, likely pro-MPO, in normal and MPO-deficient neutrophils and hypothesized that the absence of peroxidase activity in neutrophils from affected subjects was the result of defective posttranslational processing of pro-MPO. In this study we analyzed nucleic acids from three completely and two partially MPO-deficient individuals by using a cDNA probe for MPO. The affected individuals studied are unrelated to one another. Neutrophils from all affected subjects lacked mature MPO subunits; however, a monospecific antibody for MPO identified in these cells a high-molecular weight protein that is the same size as pro-MPO. Northern blots demonstrated that the amount and size of RNA (3.3 kilobases [kb]) in a completely deficient subject was normal. BglII digests of genomic DNA from control individuals (n = 14) contained three fragments that hybridized with cDNA for MPO under very stringent conditions. In contrast, BglII digests of genomic DNA from completely MPO-deficient individuals contained an extra fragment of 2.1 kb that was not present in DNA from controls. In addition, two different endonuclease digest patterns were found in MPO-deficient subjects who were biochemically and phenotypically identical. We conclude from these studies that (a) hereditary MPO deficiency is not associated with a major deletion or rearrangement of the MPO gene; (b) myeloid precursors in an MPO-deficient individual contain normal amounts of an mRNA that is the same size as that for MPO in normal individuals; and (c) the genetic basis for MPO deficiency may be heterogeneous, with at least two genotypes generating the same phenotype. These findings are consistent with the hypothesis that the genetic defect in MPO deficiency results in synthesis of a modified pro-MPO that undergoes defective posttranslational processing.
Respiratory burst oxidase activation can be dissociated from phosphatidylinositol bisphosphate degradation in a cell-free system from human neutrophils
Authors: Traynor AE , Scott PJ , Harris AL , Badwey JA , Sklar LA , Babior BM , Curnutte JT 
Published: October 2019

Abstract
Activation of the respiratory burst oxidase in cell-free preparations from 32P-labeled neutrophils was compared with changes in levels of radioactively labeled phosphoinositides in the same preparations. With membrane particles, treatment with sodium dodecyl sulfate (SDS) in the presence of cytosol led to activation of the oxidase without an alteration in levels of labeled phosphatidylinositol 4,5-bisphosphate (PIP2) or phosphatidylinositol 4-phosphate (PIP). Conversely, solubilization of the membrane particles with deoxycholate resulted in loss of nearly 98% of the radioactive PIP2 without activation of the oxidase. In this solubilized preparation, the oxidase could subsequently be fully activated by SDS in the presence of cytosol, even though the labeled PIP2 was almost totally depleted. Two PIP2-derived second messengers, diacylglycerol and inositol 1,4,5-trisphosphate, as well as the protein kinase C activator phorbol myristate acetate (PMA), failed to activate the oxidase. These results suggest that in a cell- free preparation from human neutrophils, detergent-mediated activation of the respiratory burst oxidase is independent of changes in the levels of phosphoinositides or phosphoinositide-derived second messengers.
Elevated glutathione accelerates oxidative damage to erythrocytes produced by aromatic disulfide
Authors: Maede Y , Kuwabara M , Sasaki A , Inaba M , Hiraoka W 
Published: October 2019

Abstract
It has been shown that certain dogs have erythrocytes characterized by an inherited high concentration of reduced glutathione (GSH), five to seven times the normal level (high-GSH RBCs). We examined whether increased GSH in dog erythrocytes leads to increased protection against oxidative damage induced by acetylphenylhydrazine (APH) and/or 4- aminophenyl disulfide (4-AD). When erythrocytes were incubated with 30 mmol/L APH, the Heinz body count was appreciably higher in normal RBCs than in high-GSH RBCs, while there was no difference in the increase of the methemoglobin (metHb) concentration in both RBCs. In contrast, both the Heinz body count and metHb production were much higher in high-GSH RBCs than in normal RBCs when erythrocytes were incubated with 4-AD. Furthermore, the generation of the superoxide in erythrocytes treated with 4-AD, which was measured by spin trapping combined with electron spin resonance (ESR), was obviously higher in high-GSH RBCs than in normal RBCs. These results clearly indicate that erythrocyte GSH is an important defense against oxidative damage induced by certain compounds such as APH, but that, in contrast, elevated GSH appears to accelerate oxidative damage to erythrocytes produced by aromatic disulfides, such as 4-AD, which generated a superoxide in erythrocytes via its redox reaction with GSH.
An A gamma type of nondeletional hereditary persistence of fetal hemoglobin with a T----C mutation at position -175 to the cap site of the A gamma globin gene
Authors: Stoming TA , Stoming GS , Lanclos KD , Fei YJ , Altay C , Kutlar F , Huisman TH 
Published: October 2019

Abstract
The nondeletional types of hereditary persistence of fetal hemoglobin (ndHPFH) concern the continued synthesis of hemoglobin (Hb) F with either G gamma or A gamma chains in amounts varying from 5% to 30%. Several mutations have been identified in either the A gamma or G gamma promoter which are considered causative to the continued production of one of the two gamma chains because the substitutions occur in sequence motifs essential for the expression characteristics of the gamma-globin gene in the 3′ position. We report the discovery of a T----C mutation at position -175 in the A gamma promoter which was associated with a greatly increased level of Hb F (with mainly A gamma) and a decreased level of Hb A in the one (Black) heterozygote who had a beta c gene in trans. The same mutation has been observed in the G gamma promoter of a Black heterozygote who had high levels of Hb F with G gamma chains only. A detailed comparison between these two individuals indicated significant differences in the levels of Hb F and Hb A which may result from an additional mutation at position -158 in the G gamma promoter.