bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia
Authors: Sokal JE , Gomez GA , Baccarani M , Tura S , Clarkson BD , Cervantes F , Rozman C , Carbonell F , Anger B , Heimpel H 
Published: October 2019

Abstract
Of 661 patients with Philadelphia chromosome (Ph)-positive, nonblastic chronic granulocytic leukemia, 58 had cytogenetic abnormalities in addition to the Ph at the time of diagnosis. Twenty patients had reduplication of the Ph in one or more metaphases. Twenty-one patients with a single Ph exhibited hyperdiploidy in one or more metaphases. Eleven patients had two or more hypodiploid metaphases as their only numerical abnormality. The remaining six patients had a variety of abnormalities. Many patients had more than one type of abnormality. Survival of patients in the different subgroups was similar, but these 58 patients had a shorter course than the 603 patients without additional cytogenetic abnormalities (P less than .02). Survival curves for the two populations did not diverge until the 2-year point, after which the annual death rate among patients with additional cytogenetic abnormalities was approximately 40% higher than that of patients without such abnormalities. The two populations had similar relative risk values according to a hazard ratio formula previously described by the International CGL Prognosis Study Group. Thus, they would have been expected to have essentially identical survival curves. We conclude that the presence of additional cytogenetic abnormalities at the time of diagnosis constitutes an independently significant prognostic feature with an unusually delayed influence on survival.
Molecular genetic analysis of porcine von Willebrand disease: tight linkage to the von Willebrand factor locus
Authors: Bahou WF , Bowie EJ , Fass DN , Ginsburg D 
Published: October 2019

Abstract
von Willebrand disease (vWD), one of the most common bleeding disorders in humans, is manifested as a quantitative or qualitative defect in von Willebrand factor (vWF), an adhesive glycoprotein (GP) with critical hemostatic functions. Except for the rare severely affected patient with a gene deletion as etiology of the disease, the molecular basis for vWD is not known. We studied the molecular basis for vWD in a breeding colony of pigs with a disease closely resembling the human disorder. The porcine vWF gene is similar in size and complexity to its human counterpart, and no gross gene deletion or rearrangement was evident as the pathogenesis of porcine vWD. A restriction fragment- length polymorphism (RFLP) within the porcine vWF gene was identified with the restriction endonuclease HindIII, and 22/35 members of the pedigree were analyzed for the polymorphic site. Linkage between the vWF locus and the vWD phenotype was established with a calculated LOD score of 5.3 (1/200,000 probability by chance alone), with no crossovers identified. These findings indicate that porcine vWD is due to a molecular defect within (or near) the vWF locus, most likely representing a point mutation or small insertion/deletion within the vWF gene.
Molecular cloning, expression, and chromosomal localization of a human gene encoding the CD33 myeloid differentiation antigen
Authors: Peiper SC , Ashmun RA , Look AT 
Published: October 2019

Abstract
Monoclonal antibodies of the CD33 cluster group recognize a 67- kilodalton (Kd) protein, designated p67, expressed on the surface of normal human myeloid progenitors and leukemic cells from most patients with acute myelogenous leukemia. The human gene encoding p67 was isolated in a mouse genetic background after DNA-mediated gene transfer and fluorescence-activated cell sorting (FACS) for transformants that bound the monoclonal antibody MY9. After three serial rounds of gene transfer and cell sorting, multiple independently derived tertiary mouse cell transformants were obtained that expressed p67. Southern blot analysis revealed that these transformants shared restriction fragments containing highly reiterated human DNA sequences. Two shared EcoRI fragments of 3.3-kilobase (kb) and 9.5-kb pairs were molecularly cloned into bacteriophage vectors. A subsegment of the 3.3-kb fragment lacking repeated sequences was then used as a unique sequence probe to isolate two independent cosmid clones. Cells transfected with DNA from both cosmid clones bound MY9, and the human p67 protein was demonstrated by immunoprecipitation. NFS mice inoculated with a mouse cell transformant coexpressing p67 and the v-fms oncogene product produced antisera that specifically immunoprecipitated p67 from human leukemic cell lines, mouse cell transformants, and mouse cells transfected with the biologically active cosmid clones. The human p67 locus was previously assigned to chromosome 19 by screening a panel of rodent X human somatic cell hybrids with the unique sequence probe. The gene was sublocalized to the q13.3 region of chromosome 19 by in situ hybridization. RNA transcripts of approximately 1.6 kb and 1.4 kb were identified in polyadenylated RNA from human myeloid leukemia cell lines using a probe from the genomic locus. Manipulation of the cloned p67 gene may provide insight into the function of its product and mechanisms regulating its expression.
Molecular cloning of the cDNA for human erythrocyte beta-spectrin
Authors: Winkelmann JC , Leto TL , Watkins PC , Eddy R , Shows TB , Linnenbach AJ , Sahr KE , Kathuria N , Marchesi VT , Forget BG 
Published: October 2019

Abstract
Overlapping cDNA clones, totaling 3.3 kilobases (kb) in length, which encode over 50% of the human erythrocyte beta-spectrin subunit, were isolated by antibody screening of a lambda gt11 expression library constructed from human fetal liver mRNA. The amino acid sequence of the C-terminus of beta-spectrin was derived. The size of beta-spectrin mRNA in human erythroleukemia cells was found to be 7.5 kb. Erythrocyte beta- spectrin is encoded by a gene located on human chromosome 14, as determined by cDNA hybridization to human X mouse somatic cell hybrids.
Enhancement of release from MHC class II antigen-positive monocytes of hematopoietic colony stimulating factors CSF-1 and G-CSF by recombinant human tumor necrosis factor-alpha: synergism with recombinant human interferon-gamma
Authors: Lu L , Walker D , Graham CD , Waheed A , Shadduck RK , Broxmeyer HE 
Published: October 2019

Abstract
The influence of purified recombinant human tumor necrosis factor-alpha (rhuTNF-alpha) was assessed alone and in combination with purified recombinant human interferon gamma (rhuIFN-gamma) for its effects on enhancing release from human monocytes of activities that stimulate colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. RhuTNF-alpha or rhuIFN- gamma enhanced release of colony stimulating factors (CSFs), which were determined by a combination of human and mouse colony assays, morphological assessment of colony types and neutralization studies with anti-human macrophage CSF (CSF-1) and anti-human granulocyte (G)- CSF to be CSF-1 and G-CSF. The activity in the uninduced and induced monocyte conditioned media (CM) for CFU-GM-type colonies and clusters was attributed to the presence of both CSF-1 and G-CSF, while the activity in the monocyte CM for BFU-E and CFU-GEMM colonies was attributed to the presence of G-CSF. Monocytes were separated by two- color fluorescence using a dye laser flow cytometry system with cells labeled with anti-leu M3 conjugated with fluorescein isothiocyanate and anti-HLA-DR conjugated with phycoerythrin. While “constitutive” release of CSFs from monocytes was apparent from both the leu M3+, HLA-DR+ and the leu M3+, HLA-DR- (low density or negative DR) fractions, enhanced release of CSFs in response to rhuTNF-alpha or rhuIFN-gamma was confined to the leu M3+, HLA-DR+ population of cells. RhuTNF-alpha and rhuIFN-gamma synergized to enhance release of CSFs such that low concentrations of each molecule, which were inactive when used alone, were active when the two molecules were used together. These studies suggest a role, at least in vitro, for TNF-alpha and IFN-gamma in the release of CSFs from cells of the mononuclear phagocytic lineage.
Platelet IgG, IgA, IgM, and albumin: correlation of platelet and plasma concentrations in normal subjects and in patients with ITP or dysproteinemia
Authors: George JN , Saucerman S 
Published: October 2019

Abstract
IgG, IgA, IgM, and albumin are primarily known as plasma proteins. Their presence in platelets is poorly understood. The total platelet content of IgG, IgA, and albumin, measured in solubilized platelets by an enzyme-linked immunosorbent-assay (ELISA) technique, was greater than 90% secreted after stimulation by thrombin, consistent with an alpha-granule location. The platelet concentrations of these proteins correlated with their plasma concentrations in normal subjects and over a wide range of abnormalities in patients with IgG or IgA myeloma or liver cirrhosis. IgM was not detectable in normal platelets but was measurable and related to the plasma IgM concentration in patients with macroglobulinemia. In patients with idiopathic thrombocytopenic purpura (ITP), the platelet concentrations of IgG, IgA, and albumin were all twofold to threefold higher than normal despite normal plasma concentrations. Platelet surface IgG, measured by 125I-monoclonal antibody binding, constituted less than 1% of the total platelet IgG, and it appeared to be a pool distinct from the alpha-granule IgG since its concentration in normal subjects and patients did not correlate with either plasma or total platelet IgG concentrations. These observations are consistent with hypotheses that megakaryocytes incorporate plasma proteins into developing alpha-granules by pinocytosis and that the increased ratio of platelet to plasma of IgG, IgA, and albumin in ITP may reflect a younger average age of these platelets.
A prospective long-term cytogenetic study in polycythemia vera in relation to treatment and clinical course
Authors: Swolin B , Weinfeld A , Westin J 
Published: October 2019

Abstract
This paper reports the results of cytogenetic studies in a consecutive series of 64 patients with polycythemia vera, 57 of whom could be followed prospectively. The median length of the cytogenetic observation time was 93 months (range, 24 to 224 months) after diagnosis. Clonal chromosome abnormalities were observed initially in 11 patients (17%) and later during the course of the disease in another 20 patients. An abnormal karyotype was found in 71% to 80% of the patients who were examined after the development of myeloid metaplasia, myelofibrosis, or leukemia. Patients treated with myelosuppressive agents showed a significantly greater risk of chromosome abnormalities developing than did patients who had been phlebotomized. Acute leukemia developed in eight patients, all of whom had been treated with myelosuppressive agents. A chromosome abnormality preceded the leukemia in only two of the patients. The initial presence of an abnormal karyotype did not predict a greater risk of development of leukemia. No consistent relationship was demonstrated between the occurrence of chromosome abnormalities and the development of myeloid metaplasia and/or myelofibrosis, which was observed in 42% of the patients. The chromosome abnormalities followed a nonrandom pattern, and those most frequently observed were trisomies for 1 q, 8, 9, or 9p and deletion of 20q. Deletions seem to be common and were found in 14 patients.
Decrease in BSF-2/IL-6 response in advanced cases of multiple myeloma
Authors: Asaoku H , Kawano M , Iwato K , Tanabe O , Tanaka H , Hirano T , Kishimoto T , Kuramoto A 
Published: October 2019

Abstract
Human myeloma cells freshly isolated from 40 patients with IgG multiple myeloma (MM, 10 in stage I and 30 in stage III), were cultured for 48 hours with recombinant B cell stimulatory factor 2 (rBSF-2)/interleukin- 6 (IL-6), which is considered a major growth factor for myeloma cells. Uptake of 3H-thymidine by these purified myeloma cells was measured, and BSF-2 response was evaluated by stimulation index and delta cpm induced by rBSF-2. Myeloma cells from cases in stage I responded to rBSF-2 better than those in stage III. Moreover rBSF-2 responders also showed better response to chemotherapy. Therefore, these results suggest that in vitro response of myeloma cells to BSF-2 correlates with disease progression and clinical response in patients of MM.
Failure of W/Wv mouse-derived cultured mast cells to enter S phase upon contact with NIH/3T3 fibroblasts
Authors: Fujita J , Nakayama H , Onoue H , Ebi Y , Kanakura Y , Kuriu A , Kitamura Y 
Published: October 2019

Abstract
Although W/Wv mutant mice are profoundly deficient in tissue mast cells, these mice do have cells with similar features of mast cells that develop from their bone marrow cells as efficiently as those from congenic +/+ mice in pokeweed mitogen-stimulated spleen cell- conditioned medium (PWM-SCM). With cultured mast cells (CMCs), we analyzed the mechanism of mast-cell deficiency in tissues of W/Wv mice. CMCs were established from bone marrow cells of W/Wv and congenic +/+ mice with PWM-SCM, and then co-cultured with various mouse fibroblast cell lines without PWM-SCM. All the examined mouse embryo-derived fibroblast cell lines maintained CMCs derived from +/+ mice, but not CMCs from W/Wv mice, for greater than 2 weeks. Mast cells in S phase were observed only in CMCs derived from +/+ mice under these conditions. The poor survival of W/Wv CMCs as compared with +/+ CMCs was not owing to a differential death rate but to the inability of W/Wv CMCs to continue active proliferation on fibroblasts without PWM-SCM. By synchronizing CMCs at the G1 phase of the cell cycle, the defect in W/Wv CMCs was further characterized as a failure to transit G1 and enter the S phase upon contact with fibroblasts. This finding indicates the indispensable function of the W gene product(s) for this response.
Four categories of gamma-globin gene triplications: DNA sequence comparison of low G gamma and high G gamma triplications
Authors: Liu JZ , Gilman JG , Cao Q , Bakioglu I , Huisman TH 
Published: October 2019

Abstract
The human fetal gamma chains are produced by closely linked G gamma and A gamma genes, and unequal crossing over between them leads to gamma gene deletions and triplications. Nine gamma gene triplications from seven ethnic groups were analyzed for G gamma and hemoglobin F (Hb F) values of heterozygotes and for the presence of polymorphic XmnI restriction sites 5′ to the gamma genes. Four categories of triplication were found: I had low G gamma and low Hb F values and lacked XmnI sites 5′ to the three gamma genes [---]. II had high G gamma and slightly elevated Hb F values but was also [---]. III was similar to II, except that XmnI was [+--]. IV had very high G gamma and slightly elevated Hb F values, and XmnI was [++-]. One case each of triplications I and IV were cloned into Charon 35. For both, the two 5′gamma gene code for G gamma chain, while the 3′ gamma gene codes for A gamma chain. DNA sequencing showed that the unequal crossover occurred between 472 and 398 base pairs (bp) 5′ to the gamma gene Cap sites (- 472 and -398) for the type IV triplication and between -271 and codon 136 for the type I triplication. In addition, type I had a 4-bp deletion of AGCA from -225 to -222. The high G gamma values of the type IV triplication are explained by its -G gamma-G gamma-A gamma-gene arrangement and the XmnI sites 5′ to the G gamma genes. We hypothesize that the low G gamma value of the type I triplication, which is also -G gamma-G gamma-A gamma-, is due to inactivation of the middle G gamma gene by the AGCA deletion at -225 to -222.
Different distribution of decay-accelerating factor on hematopoietic progenitors from normal individuals and patients with paroxysmal nocturnal hemoglobinuria
Authors: Kanamaru A , Okuda K , Ueda E , Kitani T , Kinoshita T , Nagai K 
Published: October 2019

Abstract
Deficiency of decay-accelerating factor (DAF) occurs in blood cells in paroxysmal nocturnal hemoglobinuria (PNH), characterized by an unusual susceptibility to hemolysis by complement activation. This study examined DAF expression on hematopoietic progenitors from normal individuals and PNH patients using a fluorescence-activated cell sorter (FACS) with monoclonal antibodies to DAF. Nonphagocytic mononuclear marrow cells expressing different density distributions of DAF were sorted into DAF-, DAF+/-, DAF+, and DAF++ fractions. The cells from each fraction were cultured in methylcellulose and assayed for CFU-E, BFU-E, CFU-GM, and CFU-Mix. The percentages of distribution of DAF- negative normal progenitors increased in the order of CFU-E, CFU-GM, BFU-E, and CFU-Mix, whereas those of DAF-positive cells inversely decreased in this order. These results indicate that DAF expression may accompany differentiation from CFU-Mix to CFU-E. On the other hand, most progenitors in PNH patients had little, if any, expression of DAF on their cell surfaces. These findings were supported by another approach using a complement-dependent cytotoxicity method with the anti- DAF monoclonal antibodies. Abnormal expression of DAF was found on the progenitors in the bone marrow as well as on mature cells circulating in the blood in PNH.
Anti-prothrombin antibodies and the lupus anticoagulant
Authors: Fleck RA , Rapaport SI , Rao LV 
Published: October 2019

Abstract
The investigators have evaluated the frequency and manifestations of anti-prothrombin antibodies in patients with the lupus anticoagulant. Thirty-one of 42 patients with lupus anticoagulants associated with a variety of underlying conditions (74%) had evidence on crossed immunoelectrophoresis of anti-prothrombin antibodies. Twenty-four of 25 patients with an activated partial thromboplastin time exceeding 50 seconds and 14 of 15 patients with a prothrombin time exceeding control by more than two seconds had demonstrable anti-prothrombin antibodies. Three of the 31 patients with anti-prothrombin antibodies had essentially no measurable plasma prothrombin, a presumed result of accelerated clearance of prothrombin/prothrombin antibody complexes. Each of these patients had bled abnormally. The remaining patients with anti-prothrombin antibodies had neither substantial hypoprothrombinemia nor hemorrhagic manifestations, which confirms the non-neutralizing property of anti-prothrombin antibodies associated with the lupus anticoagulant. Since lupus anticoagulant immunoglobulins are known to react with phospholipids, the high prevalence of antibodies binding prothrombin led us to test the hypothesis of antibody polyreactivity. Adsorption of three lupus anticoagulant plasmas with insolubilized prothrombin markedly diminished evidence of both prothrombin/prothrombin antibody complexes and anticoagulant activity. Eluates of the insolubilized prothrombin contained IgG that not only bound prothrombin but possessed lupus anticoagulant activity.
Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation
Authors: Sullivan KM , Witherspoon RP , Storb R , Weiden P , Flournoy N , Dahlberg S , Deeg HJ , Sanders JE , Doney KC , Appelbaum FR 
Published: October 2019

Abstract
We conducted a randomized, double-blind comparison of prednisone and placebo (group I) v prednisone and azathioprine (1.5 mg/kg/day) (group II) as early treatment of extensive chronic graft-v-host disease (GVHD). Patients with platelet counts less than 100,000/microL were placed into therapy with prednisone alone (group III). All three groups received identical doses of prednisone (1 mg/kg every other day) and one double-strength trimethoprim-sulfamethoxazole (TMP-SMX) tablet twice daily. Between January 1980 and December 1983, 179 previously untreated patients were enrolled and 164 were evaluable. Patients randomized to group I (n = 63) and group II (n = 63) were well matched for prognostic factors; those placed into group III (n = 38) had more frequent acute GVHD and progressive onset of chronic GVHD. Median duration of therapy was 2 years. Complications included diabetes (5%), aseptic necrosis (5%) and infection. For groups I, II, and III, the respective incidence of infection was disseminated varicella, 11%, 24%, 34%; bacteremia, 6%, 11%, 34%; and interstitial pneumonia, 5%, 14%, 18%. Recurrent malignancy was the most frequent cause of death and did not differ significantly across the groups. Nonrelapse mortality, however, did differ: 21% in group I, 40% in group II, and 58% in group III (I v II, P = .003; I v III, P = .001). Forty patients in group I, 30 in group II, and 10 in group III survive with a minimum follow-up of 3.8 years. Karnofsky performance scores for 68 survivors are 90% to 100%, scores for seven survivors are 70% to 89% and scores for five survivors are less than 70%. Actuarial survival at 5 years after transplant is 61% in group I, 47% in group II, and 26% in group III (I v II, P = .03; I v III, P = .0001). Treatment with prednisone alone results in fewer infections and better survival than prednisone and azathioprine in standard-risk chronic GVHD. Treatment with prednisone alone is less effective in high-risk patients with thrombocytopenia, and other strategies are required.
Granulocyte-macrophage colony-stimulating factor enhances selective effector functions of tissue-derived macrophages
Authors: Coleman DL , Chodakewitz JA , Bartiss AH , Mellors JW 
Published: October 2019

Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is produced by a variety of cells at sites of exposure to antigens. GM-CSF has a stimulatory effect on a number of neutrophil functions, but the effect on macrophage function is less clear. We investigated the effect of purified murine recombinant GM-CSF on murine peritoneal macrophage oxidative metabolism, Fc-dependent phagocytosis, anti-Toxoplasma activity, and expression of class II major histocompatibility antigen (Iad). GM-CSF significantly increased phorbol myristate acetate- and zymosan-elicited H2O2 release by resident and thioglycollate-elicited macrophages after 48 hours in vitro. The effect of recombinant GM-CSF was blocked by polyclonal anti-GM-CSF antibody and was not altered by lipopolysaccharide (0.01 to 1.0 microgram/mL). GM-CSF also stimulated Fc-dependent phagocytosis by peritoneal macrophages, although the stimulation of resident macrophages (1.4-fold) was less dramatic than that of thioglycollate-elicited cells (2.1-fold). GM-CSF (at doses up to 100 U/mL) had no effect on macrophage anti-Toxoplasma activity or on expression of Iad. In addition to stimulating macrophage growth, GM-CSF selectively promotes the functional capacity of tissue-derived macrophages.