bluuebunny/crossref_metadata_2025_split huggingface dataset:
Busulfan-induced chronic bone marrow failure: changes in cortical bone, marrow stromal cells, and adherent cell colonies
Authors: McManus PM , Weiss L 
Published: October 2019

Abstract
This study represented an effort to determine if there were quantitative or morphological changes in marrow stromal cells in busulfan-induced marrow failure and to relate these changes to other disturbances in blood and bone marrow. Mice received four busulfan (BU) injections at two-week intervals and were killed at various time points up to 40 weeks after the first injection. Evaluation techniques included complete blood counts, in vitro assay of short-term adherent cell colonies per femur (STACC per femur) and colony-forming unit- culture (CFU-C) per femur, light microscopy of sternebral marrow and spleen, and electron microscopy (EM) of sternebral marrow taken at 40 weeks. STACC per femur were acutely reduced to 25% of control, but recovered to 76% by 40 weeks. CFU-C per femur dropped to below 10% of control and never recovered. Histologically, we found that hypoplasia of acutely affected marrow was associated with heightened endosteum and cortical bone thickening. In the chronic phase of BU injury, bones became osteoporotic, and the frequency of adipocytes and mast cells rose. BU-affected spleens generally had enhanced erythropoiesis. No stromal cell changes in 40-week marrow were discernible by EM. We concluded that there were morphological changes in BU marrow stroma specifically involving endosteum, bone, adipocytes, and mast cells. Also, there was quantitative depression in stromal cells measured by the STACC assay, but this improved substantially with time, unlike damage to hematopoietic stem cells measured by the CFU-C.
A mono-sited transferrin from a representative deuterostome: the ascidian Pyura stolonifera (subphylum Urochordata)
Authors: Martin AW , Huebers E , Huebers H , Webb J , Finch CA 
Published: October 2019

Abstract
An iron-binding protein has been found in the plasma of Pyura stolonifera. This protein has a molecular weight of about 41,000 +/- 2,000 and binds 1 mol iron/mol protein. The absorption maxima are lambda = 280 and lambda = 429 nm (E429/E280 = 0.044). Bicarbonate is bound concomitantly with high affinity and is necessary for optimal color formation at lambda = 429 nm. The protein showed a negligible exchange of iron with human apotransferrin under physiologic conditions over two hours. Upon incubation with rat reticulocytes, the protein reacts with membrane receptors for transferrins, and the protein, with its iron, is transported intracellularly where the iron is incorporated into heme. The 59Fe protein, after intravenous injection, disappears rapidly from the plasma and is excreted largely in the urine, with a substantial fraction present in the kidney and another large fraction present in the gut. These findings established the protein as a “transferrin” and support the concept that the larger transferrin molecule in vertebrates, with two iron-binding sites, resulted from a gene duplication.
Lineage infidelity of a human myelogenous leukemia cell line
Authors: Palumbo A , Minowada J , Erikson J , Croce CM , Rovera G 
Published: October 2019

Abstract
We have analyzed the organization and expression of the immunoglobulin heavy and light chain gene in the human myeloblastic leukemic sublines, ML1, ML2, and ML3, and in the human myeloid leukemic cell lines, HL-60, U937, THP1, and K562. ML1, ML2, and ML3 cells, despite a predominant granulocytic phenotype, express a rearrangement of the immunoglobulin heavy chain gene that typically occurs during the early stages of the B cell differentiation pathway. No rearrangement was found in any of the other cell lines tested. These findings strongly support the notion that, at least in some cases, acute myeloid leukemia (AML) cells represent highly atypical cells with profoundly altered gene expression, rather than cells arrested at a well-defined stage of the myeloid lineage.
Nonhuman primates express human leukemia-associated antigens
Authors: Pesando JM , Conrad TA 
Published: October 2019

Abstract
Serologic studies using four murine monoclonal antibodies specific for the common acute lymphoblastic leukemia antigen (CALLA) and five monoclonal antibodies specific for the gp24 surface antigen indicate that these leukemia-associated antigens are present on cells of comparable tissues in man and in four nonhuman primates. As in man, adherent cell populations obtained from skin, lung, and bone marrow of Macaca fascicularis, M mulatta, M nemestrina, and Papio cynocephalus react with these antibodies. Similarly, granulocytes from both man and these nonhuman primates bind CALLA- and gp24-specific antibodies. Radioimmune precipitation experiments confirm the identity of these antigens. Our studies suggest that nonhuman primates can be used to screen serologic reagents to leukemia-associated antigens for potential toxic effects on normal tissues prior to their use in man. Similarly, nonhuman primates could be employed to assess the possible role of antigen-positive stromal cells in the reconstitution of bone marrow following transplantation.
Neutrophils mediate lipid peroxidation in human red cells
Authors: Claster S , Chiu DT , Quintanilha A , Lubin B 
Published: October 2019

Abstract
Activated neutrophils (ANs) are known to release reactive oxygen species that may cause oxidative damage to surrounding tissues. We determined if ANs could induce lipid peroxidation (LP) in human red cells and investigated the mechanism involved in this interaction. We studied neonatal glucose-6-phosphate dehydrogenase (G6PD) deficient, and sickle red cells, since each of these are known to be susceptible to oxidant injury. Neutrophils were isolated from whole blood and activated by incubation with opsonized zymosan. Mixtures of such neutrophils and red cells at a ratio of 1:100 were incubated for two hours at 37 degrees C, after which the malonyldialdehyde content in red cells was measured as an index of LP. All red cells underwent LP after AN treatment, and the degree of LP was proportional to the amount of AN in the mixture. Superoxide dismutase and catalase partially inhibited LP. When compared to normal red cells, only sickle cells demonstrated a significant increase in AN-mediated LP. Conversion of hemoglobin to carboxy-hemoglobin increased AN-mediated LP, whereas conversion to met- hemoglobin decreased AN-mediated LP. The protective effect of met- hemoglobin on LP was less in sickle cells than in normal cells. We conclude that AN can induce LP in red cells in vitro and that sickle cells are more susceptible to this process than normal cells. Hemoglobin can serve as an electron trap and protect the cell against peroxidative damage, but this mechanism is impaired in sickle cells. We speculate that the pathogenesis of hemolysis associated with infectious disease may include AN-induced red cell LP.
Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia
Authors: Foon KA , Schroff RW , Bunn PA , Mayer D , Abrams PG , Fer M , Ochs J , Bottino GC , Sherwin SA , Carlo DJ 
Published: October 2019

Abstract
A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.
Efficient transformation of previously activated and dividing T lymphocytes by human T cell leukemia-lymphoma virus
Authors: Merl S , Kloster B , Moore J , Hubbell C , Tomar R , Davey F , Kalinowski D , Planas A , Ehrlich G , Clark D 
Published: October 2019

Abstract
Modifying previously reported techniques, we attempted to increase the efficiency of human T cell leukemia-lymphoma virus (HTLV) transformation of human T lymphocytes. Lethally irradiated donor cells (DCs) were cultured with target mononuclear cells (TMCs). DCs included ten HTLV+ T cell lines with varying degrees of virus expression or seven cell lines that do not express HTLV. TMCs were prepared from 20 cord and 16 adult peripheral blood samples, including eight patients with acquired immunodeficiency syndrome (AIDS). TMCs were either added directly to the DCs or were first stimulated with phytohemagglutinin (PHA) (5 micrograms/mL) and grown in T cell growth factor (TCGF) prior to exposure to DCs. The presence of integrated HTLV proviral DNA in the transformed cells was determined by dot blot hybridization, utilizing a cloned probe to the HTLV-I genome. HTLV production by transformed TMCs was assessed for HTLV p19, reverse transcriptase, and virus particles. No transformation occurred with T cell donor lines that do not express HTLV. Low virus expressor DCs could only, with rare exception, transform preactivated TMCs. High-titer virus-producing DCs could transform activated and nonactivated cord blood cells and activated adult TMCs. Only MT-2 could routinely transform nonactivated normal adult and activated AIDS TMCs. HUT 102 B2 could transform only one activated AIDS sample, the cells of which initially expressed HTLV-like proteins and virions. Transformed cell lines contained subsets of mature T lymphocytes with variable HTLV expression. Prior activation and culture of the T lymphocytes increases the probability and rate of transformation by HTLV, allowing for biologic detection of low HTLV- producing cells and for in vitro expansion of T lymphocyte subsets from selected patients.
Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: Multicentric Trial of the Cooperative Latin American group on Hemostasis and Thrombosis
Authors: Pizzuto J , Ambriz R 
Published: October 2019

Abstract
In order to analyze the usefulness of different types of treatment in relation to the interval since the onset of idiopathic thrombocytopenic purpura (ITP), a collaborative study of 934 adult patients was undertaken. Prednisone was administered to 818 patients, and 32% of them achieved prolonged complete remission (PCR). However, only 14% of patients who had ITP for more than six months achieved a prednisone- induced PCR (P less than .01). Splenectomy was done in 399 patients, and 65% of them achieved PCR; the remission rate did not vary with the interval since the onset of ITP. Of 120 patients with chronic ITP that was refractory to corticosteroids and splenectomy, 91 received either azathioprine or cyclophosphamide; 21% of them achieved PCR and 55% had a favorable response. None of 19 patients treated with vincristine and only one of ten patients treated with vinblastine-loaded platelets achieved PCR.
Interrelationships of polymorphonuclear neutrophil membrane-bound calcium, membrane potential, and chemiluminescence: studies in single living cells
Authors: Sullivan GW , Donowitz GR , Sullivan JA , Mandell GL 
Published: October 2019

Abstract
Stimulated neutrophils show ionic fluxes that may function as “transducers” between stimuli and effector functions. Using fluorescent probes, patterns of membrane-associated calcium (chlortetracycline, CTC) and membrane potential (3–3′-dipentyloxacarbocyanine, di-O-C5 (3)) in single living human neutrophils were observed with a fluorescence microscope fitted with an image intensifier and photometer. Fluorescence changes were related to chemiluminescence. In unstimulated neutrophils, CTC and di-O-C5 (3) fluorescence was brightest in the perinuclear region. Di-O-C5 (3) fluorescence was also seen in mitochondria. Neutrophil stimulation with zymosan, phorbol myristate acetate (PMA) or calcium ionophore (A23187) resulted in loss of di-O-C5 (3) and CTC fluorescence and chemiluminescence proportional to the strength of the stimulus. Experiments demonstrated the independence of these processes. (1) Digitonin stimulation caused chemiluminescence and di-O-C5 (3) darkening without loss of CTC fluorescence. (2) Depolarization of neutrophils did not induce CTC darkening or chemiluminescence. (3) Calcium ionophore (A23187) stimulation of neutrophils in calcium-free medium resulted in normal di-O-C5 (3) and CTC darkening, but a blunted chemiluminescence peak. (4) Calcium ionophore (A23187) stimulated the loss of di-O-C5 (3) and CTC fluorescence from chronic granulomatous disease neutrophils, but did not trigger an oxidative burst. Although neutrophil depolarization, calcium release from membranes, and oxidative activity are linked, these processes can clearly be separated.
Oncogene expression in human leukemia
Authors: Blick M , Westin E , Gutterman J , Wong-Staal F , Gallo R , McCredie K , Keating M , Murphy E 
Published: October 2019

Abstract
The transforming genes of retroviruses (v-onc) are derived from normal cellular genes referred to as proto-oncogenes. These cellular genes have the capacity for conversion to oncogenes (c-onc) that are capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in human leukemia, we have analyzed their expression in a variety of fresh samples. We found that a number of oncogenes are expressed in different leukemic types and that although the transcript size did not vary for each gene, the copy number did. The myc gene (2.4 kb transcript) and the rasHa gene (1.5 kb transcript) were universally expressed. But in contrast to rasHa, the myc signal intensity varied. Myb (4.5 kb transcript) was expressed in all samples except B cell diseases. We detected low levels of abl expression (multiple mRNA species) in all leukemic types analyzed. Sis gene (4.2 kb transcript) expression was restricted to one patient sample with chronic myelogenous leukemia in blast transformation.
The human platelet membrane glycoprotein complex GP IIb-IIIa expresses antigenic sites not exposed on the dissociated glycoproteins
Authors: Rosa JP , Kieffer N , Didry D , Pidard D , Kunicki TJ , Nurden AT 
Published: October 2019

Abstract
A number of recent reports have described murine monoclonal antibodies that react specifically with the complex formed by human platelet membrane glycoproteins (GP) IIb and IIIa. We show that the IgG L, a previously described human alloantibody isolated from a polytransfused thrombasthenia patient, has similar properties. When used in non- precipitating amounts in crossed immunoelectrophoresis (CIE), 125I-IgG L bound strongly to the IIb-IIIa complex. However, after dissociation of the complex with EDTA, only a weak binding to GP IIb and no binding to GP IIIa was detected. In further studies, increased amounts of IgG L were interacted with 125I-labeled membrane glycoproteins in (a) CIE and (b) classical indirect immunoprecipitation experiments. Although the antibody was able to quantitatively precipitate the IIb-IIIa complex from Triton X-100-soluble extracts of platelet membranes, no precipitation of GP IIb or GP IIIa was observed after divalent cation chelation. Addition of EDTA to immunoprecipitates containing GP IIb- IIIa resulted in dissociation and partial release of both glycoproteins. The interaction of the IgG L with electrophoretically separated GP IIb and GP IIIa was studied using a Western blot procedure in the presence of Ca2+, Mg2+, or EDTA. The presence of divalent cations did not increase the reactivity of the antibody with the individual glycoproteins. Overall, our results show that acquired antibodies to IIb-IIIa, such as the IgG L, may predominantly react with complex-dependent determinants.
Purging murine leukemic marrow with alkyl-lysophospholipids
Authors: Glasser L , Somberg LB , Vogler WR 
Published: October 2019

Abstract
Autologous bone marrow transplantation is potentially curative in the treatment of acute leukemia if residual leukemic cells in the marrow can be eliminated prior to transplantation. We studied the purging effects of a synthetic alkyl-lysophospholipid (ALP) on marrow containing leukemic cells from a transplantable myelomonocytic leukemia (WEHI-3B) in BALB/c mice. Simulated remission bone marrow containing 2% leukemic cells treated in vitro with 20 and 100 micrograms/mL of ET-18- OCH3 (1-octadecyl-2-methyl-sn-glycerol-3-phosphocholine) significantly prolonged survival of lethally irradiated transplanted recipients. At a dose of 100 micrograms/mL, 88% of the mice survived for the duration of the experiment (approximately five months). Autopsies showed that 25% of these survivors had microscopic evidence of leukemia. Thus, in vitro treatment of marrow eliminated leukemic blasts and spared sufficient normal stem cells to allow hematologic reconstitution. The effect of ET- 18-OCH3 is not entirely selective for leukemic cells. A spleen colony assay showed that ALP has some cytotoxic effect on normal hematopoietic stem cells.
Concordance of a point mutation 5' to the G gamma globin gene with G gamma beta +. Hereditary persistence of fetal hemoglobin in the black population
Authors: Collins FS , Boehm CD , Waber PG , Stoeckert CJ Jr , Weissman SM , Forget BG , Kazazian HH Jr 
Published: October 2019

Abstract
Hereditary persistence of fetal hemoglobin (HPFH) is a genetically heterogeneous and clinically benign condition characterized by persistent expression of fetal hemoglobin (Hb F) into adulthood. In the G gamma beta + type, no major deletions in the globin gene cluster occur; adult heterozygotes produce approximately 20% Hb F, which results from overproduction of G gamma chains, with no apparent increase in production from the adjacent A gamma gene. We have recently described a point mutation 202 base pairs 5′ to the cap site of the G gamma gene in an individual with G gamma beta + HPFH. This mutation abolishes a normal ApaI restriction endonuclease site, and thus can be detected by blotting of genomic DNA. We present here further data on the ApaI mutation: (1) It occurs in six of seven families with G gamma beta + HPFH. (2) In three families, detailed haplotype analysis using 11 polymorphic restriction sites in the beta globin cluster has been done. The two that carry the missing ApaI site are identical but the third, which has a normal ApaI pattern, differs from the other two in at least two sites, one of which is a new polymorphic Nco I site between the delta and beta globin genes. This suggests the possibility of a different HPFH mutation in the third family. (3) The haplotype of the G gamma beta + HPFH chromosome carrying the ApaI mutation is different from that of 108 beta A chromosomes of black individuals that have been tested. (4) The G gamma ApaI site is normal in 61 beta A and 109 beta S alleles from non-HPFH black individuals, including 22 who share the same haplotype for the intragenic G gamma, A gamma HindIII polymorphisms. These data add support to the possibility that the -202 mutation is actually causative of the G gamma beta + HPFH phenotype.
Loss of suppression of normal bone marrow colony formation by leukemic cell lines after differentiation is induced by chemical agents
Authors: Steinberg HN , Tsiftsoglou AS , Robinson SH 
Published: October 2019

Abstract
The human leukemic cell lines K562 and HL-60 were cocultured with normal bone marrow (BM) cells. Coculture with 10(4) K562 or HL-60 cells results in 50% inhibition of normal CFU-E and BFU-E colony formation. However, when the same number of K562 and HL-60 cells is first treated for two to five days with agents that induce their differentiation, a gradual loss in their capacity to inhibit CFU-E and BFU-E colony formation is observed. The inhibitory material in K562 cells is soluble and present in conditioned medium from cultures of these cells. The degree to which leukemic cell suppression of CFU-E and BFU-E growth is reversed is correlated with the time of exposure to the inducing agent. Suppression is no longer evident after five days of prior treatment with inducers. In fact, up to a 90% stimulation of CFU-E growth is observed in cocultures with K562 cells that have been pretreated with 30 to 70 mumol/L hemin for five days. K562 cells treated with concentrations of hemin as low as 30 mumol/L demonstrate increased hemoglobin synthesis and grow normally, but no longer have an inhibitory effect on CFU-E growth. Hence, reversal of normal BM growth inhibition must be caused by the more differentiated state of the K562 cells and not by a decrease in the number of these cells with treatment. Thus, induction of differentiation in cultured leukemic cells not only alters the malignant cell phenotype but also permits improved growth of accompanying normal marrow progenitor cells. Both are desired effects of chemotherapy.