bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of refractory aplastic anemia with recombinant human granulocyte-macrophage-colony-stimulating factor
Authors: Champlin RE , Nimer SD , Ireland P , Oette DH , Golde DW 
Published: October 2019

Abstract
Fifteen patients with refractory aplastic anemia or agranulocytosis received treatment with recombinant human granulocyte-macrophage-colony- stimulating factor (rhGM-CSF) in doses from 4 to 64 micrograms/kg/d by continuous intravenous (IV) infusion. Ten of 11 evaluable patients with aplastic anemia had substantial increments in granulocytes, monocytes, and eosinophils associated with myeloid and eosinophilic hyperplasia in the bone marrow. Patients with pretreatment granulocytes greater than 0.3 x 10(9)/L had greater increments in circulating myeloid cells than patients with more severe granulocytopenia. Only one patient had improvement in erythrocytes and platelets. Blood counts fell to baseline after rhGM-CSF treatment was discontinued. Doses up to 16 micrograms/kg/d were relatively well tolerated in the absence of extreme leukocytosis. Fatigue and myalgia were common. Three patients developed pulmonary infiltrates that resolved with discontinuation of treatment. Patients tended to have recurrent inflammation in previously diseased tissues. These data indicate that rhGM-CSF will increase circulating granulocytes, monocytes, and eosinophils in patients with refractory aplastic anemia. Further studies are necessary to determine if rhGM-CSF treatment will reduce morbidity or improve survival.
Effects of normal mouse serum on the IL-3-induced proliferation of bone marrow cells
Authors: Dahl CA , Lindqvist C 
Published: October 2019

Abstract
Normal mouse serum (NMS) devoid of colony-stimulating factor (CSF) was found to enhance the interleukin 3 (IL-3)-driven colony formation of bone marrow in vitro. Inclusion of NMS in bone marrow colony-forming assays resulted in greatly increased numbers of colonies and clusters following seven days incubation; however, incubation of bone marrow with NMS before the colony-forming assay had no effect on resultant colony number. The levels of serum-enhancing activity (SEA) did not appear to vary significantly with age and in part was species restricted, in that human and guinea pig serum did not enhance mouse bone marrow colony formation. Conversely, NMS had no effect on human bone marrow colony formation. Levels of SEA were found to vary between strains, as did the degree to which bone marrow from various strains was enhanced by the serum. Serum fractionation studies indicated three active fractions with molecular weights of 800–900 Kd, 60–70 Kd, and 20- 30 Kd. The fraction at 800–900 Kd inhibited colony formation at high concentrations and enhanced colony formation on dilution, whereas the two other active fractions contained enhancing activity at all concentrations tested. These results would indicate that normal serum can play a greater role in colony-forming assays than nutritional supplements. The relationship of the SEA factors to other factors that have been reported to modulate bone marrow colony formation is discussed.
The clinical spectrum of heterozygous protein C deficiency in a large New England kindred
Authors: Bovill EG , Bauer KA , Dickerman JD , Callas P , West B 
Published: October 2019

Abstract
A family with a high incidence of venous thromboembolism was investigated. We performed medical evaluations on 184 of the 411 surviving members of the pedigree, which allowed assignment of individuals into positive, equivocal, or negative categories with respect to their clinical histories of thrombosis. Subjects with antigenic levels of protein C less than 66% of a normal plasma pool were classified as having protein C deficiency. Positive thrombotic histories were found in 13 of the 46 family members determined to be protein-C deficient and in only five of their 138 biochemically unaffected relatives. Statistical analysis of the association between thromboembolic disease and protein-C deficiency was strongly positive chi 2 = 24.95, P less than .0001 with n = 184), indicating that heterozygous protein-C deficiency is an important independent risk factor for the development of thrombotic manifestations in this pedigree. However, the absence of thromboembolic manifestations in many of the protein-C deficient family members to date indicates that other, as yet undefined, factors must play an important role in the clinical expression of this disorder.
Myelomonocytic myeloma cell line (LB 84-1)
Authors: Durie BG , Grogan TM , Spier C , Vela E , Baum V , Rodriquez MA , Frutiger Y 
Published: October 2019

Abstract
A human cell line (LB 84–1) has been established from the bone marrow of a patient with Bence-Jones myeloma. Coexpression of plasma cell (Leu[CD38]) and myelomonocytic antigens (Leu MI[CD15], Leu M5 [CD11c], MY7 [CD13] plus butyrate and chloracetate esterase) proved to be an unusual but sustained feature of this cell line. The plasma cell phenotype with multinuclearity was retained. Shared major chromosomal abnormalities (del [5] [p14], t[5;?] [q35;?], del [6] [q21], and del 7[q32]) between the direct and cell line karyotypes affirmed the LB 84- 1 cell as being derived from the original patient myeloma clone. The mechanisms potentially responsible for the aberrant coexpressed phenotype are discussed. This myelomonocytic myeloma cell line will hopefully prove to be a valuable tool for the study of the genotypic and phenotypic evolution of human myeloma.
Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus
Authors: Knowles DM , Inghirami G , Ubriaco A , Dalla-Favera R 
Published: October 2019

Abstract
Each of three individuals with acquired immunodeficiency syndrome (AIDS) developed a pleomorphic malignant neoplasm in which a precise histopathologic diagnosis could not be rendered. In each case, the tumor cells expressed leukocyte common antigen and a variable constellation of antigens associated with B- and T-cell activation (HLA- DR, T9, T10, BL2, BL3, Ki-24, BLAST-2). They lacked all B cell, T cell, myeloid, and monocyte lineage-restricted antigens, resulting in their classification as hematopoietic neoplasms of uncertain lineage. However, antigen receptor gene rearrangement analysis demonstrated that each of these three neoplasms exhibited clonal immunoglobulin heavy chain and kappa light chain gene rearrangements and lacked T-cell receptor beta chain gene rearrangements and therefore were B cell- derived non-Hodgkin's lymphomas (NHL) representative of an equivalent, relatively mature stage of B-cell differentiation. In contrast with most AIDS-associated NHLs, each of these three neoplasms lacked c-myc gene rearrangements and contained Epstein-Barr virus (EBV) proteins and/or sequences. These studies demonstrate that these three AIDS- associated neoplasms of uncertain lineage exhibit a strikingly similar constellation of distinctly uncommon morphologic, immunophenotypic, and molecular genetic characteristics that distinguishes them substantially from the vast majority of NHLs that have been reported to occur in association with AIDS. The consistent presence of EBV proteins and/or DNA sequences suggests that the Epstein-Barr virus played a pathogenetic role in the development of these three AIDS-associated neoplasms. Finally, these studies further illustrate the utility of antigen receptor gene rearrangement analysis in the diagnosis and classification of hematopoietic neoplasms of uncertain lineage.
A PvuII polymorphism of the bcr region in patients with hematopoietic disorders and their families
Authors: Opalka B , Wandl U , Kloke O , Oberle C , Koppe J , Niederle N , Schmidt CG 
Published: October 2019

Abstract
The BCR gene on chromosome 22 has received increasing attention because of its involvement in the Philadelphia (Ph′) translocation. For most restriction enzymes, this locus has been found to be nonpolymorphic. Two alleles have only been found when Taql-digested DNA is hybridized to a 5′ bcr-specific probe. We describe another two-allele polymorphism detected by the same probe in PvuII-digested DNA. The polymorphism is characterized by an additional PvuII site in the bcr region: this causes the appearance of an additional band of about 2.3 kb or 2.5 kb besides a 4.8-kb fragment in hybridizations with the 5′ bcr or a 3′ bcr probe. The incidence of the second allele is very low. It has only been found in some patients with hematopoietic malignancies and in a group of volunteers having a leukemia patient in their families.
Monoclonal antibodies to the human CSF-1 receptor (c-fms proto-oncogene product) detect epitopes on normal mononuclear phagocytes and on human myeloid leukemic blast cells
Authors: Ashmun RA , Look AT , Roberts WM , Roussel MF , Seremetis S , Ohtsuka M , Sherr CJ 
Published: October 2019

Abstract
The first monoclonal antibodies (MoAbs) to epitopes in the extracellular domain of the human c-fms proto-oncogene product (receptor for the macrophage colony stimulating factor, CSF-1) were used with flow cytometric techniques to study receptor expression on normal human peripheral blood monocytes, bone marrow cells, and leukemic blasts. On normal cells CSF-1 receptors were restricted in their expression to cells of the mononuclear phagocyte lineage. CSF-1 receptors were detected on leukemic blasts from 15 (30%) of 50 children with acute myeloid leukemia, compared with four (15%) of 26 adults. By contrast, detectable CSF-1 receptors were uniformly absent on blasts from 19 children with acute lymphoblastic leukemia. CSF-1 receptors on normal monocytes and myeloid leukemia cells could be induced to downmodulate by incubation with either human recombinant CSF-1 or phorbol esters, confirming that the receptors had functional ligand- binding sites and responded to transmodulation by inducers of protein kinase C. The numbers of receptors per cell and the percentage of positive cases were highest for leukemic blasts with cytochemical and morphological features of monocytes. However, CSF-1 receptors were also detected on a subset of leukemic blast cells with features of granulocytic differentiation (FAB subtypes M1 through M3). Southern blotting analyses of DNA from 47 cases of acute myeloid leukemia demonstrated no rearrangements within the 32 kb of genomic sequences that contain CSF-1 receptor coding exons or in the 50 kb upstream of the first coding exon. Analysis of the upstream region of the c-fms locus revealed that sequences representing the terminal 112 untranslated nucleotides of c-fms mRNA map 26 kb 5′ to the first coding exon, suggesting that at least one c-fms promoter is separated from the receptor coding sequences by a very long intron. Whereas expression of the CSF-1 receptor in myeloid leukemic blasts is not restricted to cells with monocytic characteristics, the apparently aberrant pattern of receptor synthesis in a subset of cases with granulocytic features appears not to be due to chromosomal rearrangements within 50 kb upstream of sequences encoding the receptor.
The human myeloma cell line LP-1: a versatile model in which to study early plasma-cell differentiation and c-myc activation
Authors: Pegoraro L , Malavasi F , Bellone G , Massaia M , Boccadoro M , Saglio G , Guerrasio A , Benetton G , Lombardi L , Coda R 
Published: October 2019

Abstract
The characteristics of a human cell line (LP-1) derived from the peripheral blood of a patient with IgG-lambda myeloma in leukemic transformation are described. The cells resemble immature plasma cells in that they exhibit a membrane phenotype that is intermediate between late B lymphocytes and plasma cells, even though they secrete IgG- lambda chains. Treatment of LP-1 cells with 12–0 tetradecanoylphorbol- 13-acetate (TPA) or pokeweek mitogen (PWM) induces the appearance of surface markers and ultrastructural features typical of mature plasma cells but does not affect their proliferative activity. Molecular analysis of the cell line showed an increased expression of the c-myc protooncogene and the presence of abnormally sized transcripts. Conventional cytogenetics and pulsed-field gel electrophoresis showed no structural rearrangements of the c-myc gene, suggesting that the abnormal c-myc expression may be due to point mutations or small deletions within the gene. The LP-1 cell line is a useful model in which to study the process of B-cell maturation; such study may lead to the uncovering of unusual mechanisms of c-myc activation. Furthermore, the LP-1 cell is a potential partner in the generation of human hybridomas.
Cytogenetic and molecular analysis in Philadelphia negative CML
Authors: van der Plas DC , Hermans AB , Soekarman D , Smit EM , de Klein A , Smadja N , Alimena G , Goudsmit R , Grosveld G , Hagemeijer A 
Published: October 2019

Abstract
We studied the clinical, hematologic, cytogenetic and molecular biologic features in four patients with Philadelphia (Ph) negative chronic myeloid leukemia (CML). In all four cases the clinical and hematologic characteristics were indistinguishable from Ph positive CML. Cytogenetic analysis showed a normal karyotype in two patients and chromosomal translocations apparently not affecting chromosome 22 in the other two cases. Southern blot analysis using probes of the bcr region, demonstrated a bcr break-point in all four patients. In situ hybridization with bcr, c-abl, and c-sis probes showed unusual hybridization sites for 5′-bcr and c-abl indicating complex chromosomal rearrangements affecting three different chromosomes in the four patients investigated. Using polymerase chain reaction (PCR) followed by hybridization to oligonucleotide probes specific for the bcr-abl fusion region, the expression of a chimeric bcr-abl mRNA was detected. In these patients we demonstrated that (a) CML with a breakpoint in the bcr region without cytogenetically detectable Ph chromosome is characterized by the same genomic recombination of 5′-bcr and c-abl as CML with standard Ph translocation and (b) unusual localization of 5′- bcr and c-abl sequences caused by complex Ph translocation does not interfere with transcription of the bcr-abl fusion gene.
In utero gene transfer and expression: a sheep transplantation model
Authors: Kantoff PW , Flake AW , Eglitis MA , Scharf S , Bond S , Gilboa E , Erlich H , Harrison MR , Zanjani ED , Anderson WF 
Published: October 2019

Abstract
Retroviral-mediated gene transfer was used to insert a Neo R gene into fetal sheep hematopoietic cells obtained by exchange transfusion from lambs in utero. After gene transfer the cells were returned to the donor fetus. The lambs were examined after birth for the presence of a functioning Neo R gene. Of ten analyzable animals, six were positive for G418 resistant progenitor cells (CFU-Mix, CFU-C, BFU-E, CFU-E). Two animals were studied for extended periods of time: 8 and 24 months. Each has demonstrated a pattern wherein positive periods are interspersed with times when there were no detectable G418-resistant cells. We conclude that retroviral-mediated gene transfer can be used to insert genes into early progenitor cells of fetal sheep in utero and that the animals can continue to demonstrate blood cells expressing the gene for more than 2 years after birth. This is a US government work. There are no restrictions on its use.
Evidence for the presence of tissue factor activity on subendothelium
Authors: Weiss HJ , Turitto VT , Baumgartner HR , Nemerson Y , Hoffmann T 
Published: October 2019

Abstract
By a variety of methods, tissue factor activity was demonstrated in the subendothelium of rabbit aorta and human umbilical artery. In one method, everted segments of de-endothelialized vessels were mounted in an annular perfusion chamber and the subendothelial surface was exposed to nonanticoagulated human blood under controlled flow. Procoagulant activity was assessed by measuring fibrin deposition on subendothelium and fibrinopeptide A (FPA) levels in post chamber blood. Both fibrin deposition and FPA were decreased with rabbit vessel segments exposed (at a shear rate of 650 seconds-1) to blood from patients with factor VII deficiency and with umbilical artery segments (at shear rates of 90 to 180 seconds-1) that had been pretreated with a monoclonal antibody to human tissue factor. In a second method, everted umbilical artery segments were mounted on a stir bar and the subendothelial surface was exposed, with stirring, to plasma or purified coagulation factors. The capacity of the surface to clot plasma on addition of calcium was inhibited by the antibody to tissue factor. The surface also activated purified 3H-factor X in the presence of factor VIIa, but not in its absence, and this surface property was almost entirely eliminated by pretreating the vessel segments with antitissue factor. Tissue factor activity in subendothelium could play a role in both the arrest of bleeding and in promoting the formation of thrombi at sites of vascular injury.
Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor
Authors: Orstavik KH , Kornstad L , Reisner H , Berg K 
Published: October 2019

Abstract
A significant fraction (30%) of the genetically determined variance in plasma concentration of the von Willebrand factor antigen (vWf:Ag) has been shown to be related to ABH determinants. Individuals with blood group O, who have the highest amounts of blood group H substance, have the lowest concentration of vWf:Ag. The Lewis substances, Le(a) and Le(b), are biochemically closely related to the ABH substances as both can be produced from the same precursor substance. We studied the effect of the presence of the Lewis antigens on the plasma concentration of vWf:Ag and factor VIII antigen (VIII:Ag) in 323 individuals of different ABO groups from a series of twins and in 58 blood donors of blood group O. Among persons belonging to blood group O, those with the Le(a) antigen had a higher concentration of both vWf:Ag and VIII:Ag than individuals lacking Le(a). Le(a+b-) people are nonsecretors and Le(a-b+) people are secretors of ABH substance. Thus, the lowest concentration of vWf:Ag and VIII:Ag was found in group O secretors. The effect is most likely due to an effect of the secretor locus. This finding may be of importance for the detection of carriers of hemophilia A and for the diagnosis of type I von Willebrand disease.
Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes
Authors: Wieser M , Bonifer R , Oster W , Lindemann A , Mertelsmann R , Herrmann F 
Published: October 2019

Abstract
T cells are known to interact cooperatively with monocytes to produce Colony-Stimulating Factors (CSF), although T cell-mediated signals leading to CSF secretion by monocytes are not completely understood. We have made use of Northern blot hybridization and specific bioassays to study the effects of the T cell product interleukin-4 (IL-4) on monocyte CSF expression. The results suggest a previously unrecognized role of IL-4 as a CSF inducer since exposure of monocytes to IL-4 resulted in accumulation of transcripts for granulocyte-CSF (G-CSF) and macrophage-CSF (M-CSF). Consequently, IL-4-activated monocytes released factors in their culture supernatants biologically and antigenically indistinguishable from G- and M-CSF.
Differences in the expression of alkaline phosphatase mRNA in chronic myelogenous leukemia and paroxysmal nocturnal hemoglobinuria polymorphonuclear leukocytes
Authors: Rambaldi A , Terao M , Bettoni S , Bassan R , Battista R , Barbui T , Garattini E 
Published: October 2019

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) and the stable phase of chronic myelogenous leukemia (CML) are the two hematological conditions known to be associated with low levels of leukocyte alkaline phosphatase (LAP) activity in peripheral blood polymorphonuclear cells (PMN). LAP mRNA levels were determined in PMN from PNH and CML patients by RNA blotting analysis. In CML, LAP mRNA is undetectable, suggesting either decreased transcription or rapid degradation of the message. Contrarily, in PNH normal or high levels of LAP mRNA are present. This latter finding supports the concept of a deficit in the anchorage of the protein to the plasma membrane through the glycolipid pathway, even though other post-transcriptional mechanisms could be involved.
Interleukin-4 induces a substance in bone marrow stromal cells that reversibly inhibits factor-dependent and factor-independent cell proliferation
Authors: Peschel C , Green I , Paul WE 
Published: October 2019

Abstract
Bone marrow-derived stromal cell monolayers pretreated with recombinant interleukin-4 (IL-4) inhibit the growth of hematopoietic cells. This was demonstrated by inhibition of fresh bone marrow-derived, IL-3- induced soft agar colonies as well as by inhibition of proliferation of IL-3-dependent cell lines and of a Friend virus-transformed erythroleukemic cell line. Pretreatment of stromal cells with IL-4 for five to seven days induced the inhibitory activity. IL-4 could then be removed before “plating” the bone marrow cells in soft agar, indicating that the inhibitory activity did not depend on the action of IL-4 on the precursors of the soft agar colonies. The inhibitory activity appears to be mediated by a soluble factor since inhibition was achieved even if the stromal cell layer was separated from the colony forming cells by an “empty” agar layer. However, supernatants of IL-4- induced stromal cell layers had no detectable inhibitory activity. The inhibitory action of the IL-4-pretreated stromal cell lines was not the result of killing of the precursor cells since it could be reversed if the agar layer containing the colony-forming cells was removed from the stromal cell layer and cultured with IL-3. Hydrocortisone (HC) blocked the inhibitory effect if added either in the IL-4 preincubation phase or during the colony formation stage, implying that HC blocked both induction of the inhibitory activity and its release or its effector function. A homogenous long-term stromal cell line could not be induced to exert the inhibitory activity; partial inhibition could be achieved with pure macrophages stimulated with IL-4 and CSF-1, suggesting that the inhibitory activity induced by IL-4 in mixed stromal cell layers may depend on a complex mechanism involving more than one cell type. Northern analysis of RNA from IL-4-induced and uninduced stromal cells indicated that IL-4 did not upregulate expression of CSF-1 or transforming growth factor-beta (TGF-beta) and only modestly increased expression of tumor necrosis factor, suggesting that these cytokines were not responsible for the inhibitory activity. The capacity of IL-4 to induce inhibitory activity in stromal cell layers suggests that IL-4 may play a role in the regulation of hematopoiesis.