bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the complement sensitivity of calcium loaded human erythrocytes
Authors: Test ST , Butikofer P , Yee MC , Kuypers FA , Lubin B 
Published: October 2019

Abstract
A deficiency of membrane proteins having a glycosylphosphatidylinositol (GPI) anchor is characteristic of the erythrocytes of paroxysmal nocturnal hemoglobinuria (PNH) and is currently believed to be the basis for the enhanced susceptibility to lysis by activated complement observed in these cells. Our recent observation that GPI-anchored proteins are preferentially lost into membrane vesicles shed from normal erythrocytes after calcium loading led us to examine the hypothesis that the remnant erythrocytes might also have increased sensitivity to complement-mediated hemolysis. Indeed, red blood cells treated in such a manner became more sensitive to lysis by antibody and complement or to lysis initiated by activated cobra venom factor complexes (CoFBb). As a consequence of membrane vesiculation, the erythrocytes lost up to approximately 50% of their immunoreactive decay- accelerating factor and 25% to 30% of their immunoreactive membrane inhibitor of reactive lysis (MIRL). Closer examination of the defect responsible for the marked increase in sensitivity to CoFBb-initiated hemolysis seen in calcium-loaded erythrocytes showed that a complex combination of factors produced the defect. These included a decrease in both functional and immunoreactive MIRL and depletion of intracellular potassium and adenosine triphosphate (ATP). These results suggest the possibility that loss of DAF and MIRL via membrane vesiculation, as well as decreases in intracellular potassium and/or ATP, might contribute to the phenotype of PNH erythrocytes. Further, normal or pathologic red blood cells might develop a PNH-like defect after membrane vesiculation if sufficient decreases in potassium and ATP also occurred.
Hemoglobin Neapolis, beta 126(H4)Val----Gly: a novel beta-chain variant associated with a mild beta-thalassemia phenotype and displaying anomalous stability features
Authors: Pagano L , Lacerra G , Camardella L , De Angioletti M , Fioretti G , Maglione G , de Bonis C , Guarino E , Viola A , Cutolo R 
Published: October 2019

Abstract
A novel beta-chain, beta 126(H4)Val----Gly, electrophoretically silent, was detected by reverse-phase high performance liquid chromatography in three unrelated families from Naples (Southern Italy) and accounted for about 30% of the total beta-chains. The amino acid substitution was detected by HPLC fingerprint. The eight heterozygous patients showed hematologic and biosynthetic alterations of mild beta-thalassemia type. The hemoglobin variant showed abnormal stability features. It was unstable in the heat stability and isopropanol precipitation tests, but did not cause a hemolytic syndrome in vivo and was stable in a time- course experiment of biosynthesis in vitro. DNA polymerase chain reaction direct sequencing of the mutated gene from 135 nt upstream of the cap site to 106 nt downstream of the polyadenylation site showed only the beta 126 GTG----GGG mutation, which was confirmed in the other patients by allele-specific oligonucleotide hybridization. The mutation was found to be associated with a type II beta-globin framework and restriction fragment length polymorphism haplotype V. The novel variant was named hemoglobin Neapolis.
Lymphokine profile in bone marrow transplant recipients
Authors: Schneider LC , Antin JH , Weinstein H , Abrams JS , Pearce MK , Geha RS , Vercelli D 
Published: October 2019

Abstract
Immune reconstitution after bone marrow transplantation (BMT) recapitulates immune ontogeny. At birth there is an imbalance in lymphokine production, with decreased production of interferon-gamma (IFN-gamma) compared with interleukin-4 (IL-4) and IL-2. We investigated whether a similar imbalance in lymphokine production occurs in BMT recipients within 6 months after transplantation. Our results show that BMT recipients not treated with immunosuppressive drugs have a decrease in IFN-gamma production and IL-2, in comparison with IL-4. This imbalance was likely to result from impaired signal transduction through surface receptors, because it was detectable on stimulation with Concanavalin A (ConA), but was overcome completely or largely by stimulation with phorbol myristate acetate (PMA) + ionophore, which bypass surface receptors and mimic the effects of second messengers. In contrast, lymphokine production in patients treated with immunosuppressive drugs (cyclosporine A, corticosteroids) was abnormal after stimulation with PMA and ionophore, as well as ConA. Thus, treated BMT recipients exhibit an additional deficit, which affects the signaling cascade down-stream of second messenger generation and results in impaired lymphokine production.
Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages
Authors: McCachren SS , Diggs J , Weinberg JB , Dittman WA 
Published: October 2019

Abstract
Thrombomodulin is an essential cofactor for the activation of the anticoagulant protein C by thrombin. We have identified the expression of thrombomodulin messenger RNA (mRNA) and protein in peripheral blood monocytes. While untreated monocytes expressed thrombomodulin mRNA by Northern blot analysis, lipopolysaccharide-treated cells had decreased mRNA expression. Thrombomodulin antigen was shown in the cytoplasm and on the surface of monocytes by immunohistochemical staining, and thrombomodulin activity was shown on the surface of intact monocytes. One population of synovial lining cells that normally expressed mononuclear phagocyte antigens also expressed thrombomodulin in both noninflamed osteoarthritic synovium and in inflamed rheumatoid arthritis synovium. However, these cells did not express another endothelial protein, von Willebrand factor. We conclude that both circulating and tissue mononuclear phagocytes are capable of expressing thrombomodulin.
A randomized comparison of two doses of human lymphoblastoid interferon- alpha in hairy cell leukemia. Wellcome HCL Study Group
Authors: Smalley RV , Anderson SA , Tuttle RL , Connors J , Thurmond LM , Huang A , Castle K , Magers C , Whisnant JK 
Published: October 2019

Abstract
One hundred thirty-eight patients with hairy cell leukemia were randomized to receive either a dose of 2.0 megaunits (MU)/m2 or a 10- fold lower dose of 0.2 MU/m2 of a highly purified natural alpha- interferon, administered daily for 28 days followed by a three times a week schedule. Ninety-seven of these patients had previously undergone splenectomy, but otherwise none of the patients had received prior therapy for their leukemia. The two doses were comparable in their effect on improving the neutrophil and platelet count, whereas the higher dose had a greater beneficial effect on the hemoglobin level and a greater antileukemic effect on the marrow. Acute toxicity in the form of a flu-like syndrome, neurologic side effects, neutropenia, and the need for platelet transfusions was observed less frequently in the low- dose group, as was the chronic fatigue syndrome. No neutralizing antibody activity was seen in the sera from 61 patients examined. Because of its beneficial effect on the neutrophil and platelet count and a lower degree of toxicity (ie, a superior therapeutic/toxicity ratio), the low dose is recommended as initial therapy in patients with hairy cell leukemia. This therapy may be followed by dose escalation once clinical improvement is observed.
Modulation of cell proliferation and cytokine production in acute myeloblastic leukemia by interleukin-1 receptor antagonist and lack of its expression by leukemic cells
Authors: Rambaldi A , Torcia M , Bettoni S , Vannier E , Barbui T , Shaw AR , Dinarello CA , Cozzolino F 
Published: October 2019

Abstract
Interleukin-1 (IL-1) is spontaneously produced by acute myeloblastic leukemia (AML) cells. IL-1 also induces synthesis of colony-stimulating factors (CSFs) and sustains leukemic growth. An IL-1-specific inhibitor has been recently purified and cloned; this molecule binds to IL-1 receptors but has no IL-1 activity, fulfilling the characteristics of an IL-1 receptor antagonist (IL-1ra). Because high-affinity binding sites for IL-1ra were shown on AML cells by radioligand binding studies, we studied the effect of IL-1ra on the proliferative activity of blast cells isolated from 16 cases of AML. In each case, spontaneous proliferation was inhibited by addition of the IL-1ra in a dose- dependent manner (1 to 100 ng/mL). Culture supernatants of unstimulated leukemic cells contained IL-1 beta and granulocyte-macrophage CSF (GM- CSF), but when incubated with the IL-1ra, a reduction or disappearance of GM-CSF was observed in 8 of 10 cases, whereas spontaneous IL-1 production was reduced in four of seven cases. By Northern hybridization, IL-1 beta gene transcripts were shown in 20 of 23 AML cases, whereas IL-1ra-specific messenger RNA was present in only two of the patients studied. These data show a role for IL-1 in the spontaneous proliferation and cytokine production of AML cells and suggest that an imbalanced synthesis of IL-1 and of its natural receptor antagonist may contribute to the unrestricted growth of AML cells.
Prognostic correlation of plasma cell acid phosphatase and beta- glucuronidase in multiple myeloma: a Southwest Oncology Group study [see comments]
Authors: Saeed SM , Stock-Novack D , Pohlod R , Crowley J , Salmon SE 
Published: October 2019

Abstract
In 1982 a randomized trial of either alternating or syncopated VMCP/VBAP regimens for the treatment of active multiple myeloma was begun (Southwest Oncology Group Study 8229/30). A concurrent investigation was undertaken to evaluate the clinical importance and significance of cytochemically stainable plasma cell acid phosphatase (AP) and beta-glucuronidase enzymes (BG). Pretreatment bone marrow aspirates were available for analysis from 399 patients for AP and 398 patients for BG. The AP scores ranged between 42 and 395, and the BG scores ranged between 1 and 346. There was a significant increase of AP (P = .001) and BG (P = .002) in multiple myeloma as compared with a set of patients with benign plasmacytosis. The enzyme scores did not significantly relate to Ig idiotype of myeloma or other prognostic variables except that the BG scores varied significantly with the level of albumin (P = .03) and hemoglobin (P = .01). Analysis of patient groups with different levels of enzyme scores showed that 61 of 398 patients with an AP score of less than 130 had a poorer median survival of 1.7 versus 2.8 years for patients with higher scores (P = .001). In the multivariate analysis of survival, low AP score was an important prognostic factor (P = .006), but BG did not contribute significantly. It is suggested that the subset of patients presenting with low AP should be considered for specialized or more aggressive therapy.
Biochemical studies on red blood cells from a patient with the Inab phenotype (decay-accelerating factor deficiency)
Authors: Reid ME , Mallinson G , Sim RB , Poole J , Pausch V , Merry AH , Liew YW , Tanner MJ 
Published: October 2019

Abstract
A 38-year-old Russian woman (KZ) has been identified as the fourth proposita with the Inab blood group phenotype. Like the first two propositi, she has a chronic intestinal disorder and, as shown for the third proposita, her Inab phenotype is demonstrably inherited. KZ's serum contained anti-IFC, which reacted with a red blood cell (RBC) membrane component with an Mr of 70,000, which is decay accelerating factor (DAF). Her RBCs lacked all Cromer-related blood group antigens and DAF. Her RBCs were no more susceptible than normal control RBCs to lysis in acid lysis or in rabbit or human antibody-initiated complement lysis tests. Northern blots of total RNA isolated from KZ's Epstein- Barr virus-transformed lymphoblasts showed a marked reduction of DAF mRNA when compared with normal. Polymerase chain reaction (PCR) amplification of cDNA confirmed this reduced level of DAF mRNA. Sequencing of the PCR product showed a 44-nucleotide deletion in the mRNA close to the short consensus repeats IIIa/IIIb intron/exon boundary. This deletion results in a change in the reading frame that places a termination codon six amino acids after the deletion. The putative translation product would lack a glycosyl phosphatidyl- inositol linkage site and, therefore, would not be membrane-bound in the RBC.
Identification of four novel delta-globin gene mutations in Greek Cypriots using polymerase chain reaction and automated fluorescence- based DNA sequence analysis
Authors: Trifillis P , Ioannou P , Schwartz E , Surrey S 
Published: October 2019

Abstract
The molecular basis of most beta-thalassemia syndromes has been defined, while the spectrum of mutations causing delta-thalassemia is not well characterized. In an attempt to identify such mutations, the region encompassing the delta-globin gene from three Greek Cypriot families suspected of having delta-thalassemia was amplified by polymerase chain reaction (PCR), and DNA sequence determined using an automated fluorescence-based sequencer. Four novel mutations were identified: a G----T change at codon 27 that results in an alanine to serine change; a C----T change at codon 116 converting arginine to cysteine; a T----C change at codon 141 converting leucine to proline; and an AG----GG change at the consensus 3′-acceptor site in IVS-2. While the latter is clearly a thalassemic mutation, the low hemoglobin A2 in the first three may be due to either decreased production or instability of the altered delta-globin chain. All four mutations may be detected by PCR amplification of genomic DNA followed by restriction enzyme digestion. Two mutations abolish restriction sites while two create new cleavage sites. Screening for molecular defects that cause delta-thalassemia or unstable delta-globin by PCR amplification and restriction enzyme digestion will lead to correct diagnosis of beta/delta-thalassemia compound heterozygotes and improved genetic counseling.
Increased incidence of solid malignant tumors after bone marrow transplantation for severe aplastic anemia [see comments]
Authors: Socie G , Henry-Amar M , Cosset JM , Devergie A , Girinsky T , Gluckman E 
Published: October 2019

Abstract
From May 1980 to December 1989, 107 consecutive patients with non- constitutional severe aplastic anemia underwent bone marrow transplantation at our institution using cyclophosphamide and thoraco- abdominal irradiation as conditioning regimen. During the same period, 40 patients with Fanconi anemia were also grafted after a similar conditioning, giving a total series of 147 patients. With a mean follow- up of 64 months, four male patients developed a solid malignant tumor, a number that leads to an 8-year cumulative incidence rate of 22% (eg, relative risk to general population = 41, P less than .001). These results should be considered as a warning to clinicians who follow these successfully grafted long-term patients.
CD63/Pltgp40: a platelet activation antigen identical to the stage- specific, melanoma-associated antigen ME491
Authors: Azorsa DO , Hyman JA , Hildreth JE 
Published: October 2019

Abstract
CD63 is a 53-Kd lysosomal membrane glycoprotein that has been identified as a platelet activation molecule. The current study presents evidence that CD63 and Pltgp40, a platelet membrane glycoprotein identified in this laboratory, are the same molecule and that CD63/Pltgp40 is identical to the well-characterized, stage- specific melanoma-associated antigen ME491. Identity of CD63 and Pltgp40 was demonstrated by immunoprecipitation and sequential immunodepletion studies, which showed that the anti-Pltgp40 monoclonal antibody (MoAb) H5C6 and an anti-CD63 MoAb CLB/Gran 12 recognized the same 40- to 55-Kd platelet glycoprotein. In addition, the anti-CD63 MoAb specifically recognized immunoaffinity-purified Pltgp40. Amino acid sequences obtained from NH2-terminal and tryptic fragment peptides of Pltgp40 were used to generate complementary DNA (cDNA) probes using the polymerase chain reaction (PCR) technique. A 386-bp cDNA probe partially encoding CD63/Pltgp40 and a full length cDNA probe were 100% identical to the corresponding sequence of ME491. Antibodies H5C6 and CLB/Gran12 immunoprecipitated a 30- to 60-Kd heterodisperse glycoprotein from G361 melanoma cells, as had previously been reported for antibodies recognizing ME491. These data, taken together with the extensive homology recently reported between ME491, the Schistosoma mansoni membrane antigen SM23, CD37, the tumor-associated antigen CO- 029, and the target of an antiproliferative antibody-1, suggest that CD63 is a member of a new family of related molecules.
Selective expression of two homeobox genes in CD34-positive cells from human bone marrow
Authors: Deguchi Y , Kehrl JH 
Published: October 2019

Abstract
Proteins coded by homeobox-containing genes are sequence-specific DNA- binding proteins that have been implicated in the control of gene expression both in developing as well as in adult tissues. Two recently characterized human homeobox genes, HB24 and HB9, were found to be highly expressed in bone marrow cells enriched for CD34-positive cells, present at low levels in unfractionated bone marrow cells, and essentially undetectable in bone marrow cells depleted of CD34 cells. Treatment of CD34-enriched cells with recombinant interleukin-3 (IL-3) and granulocyte macrophage-colony-stimulating factor for 24 hours increased expression of HB24 threefold and HB9 fourfold. Based on studies with actinomycin D, the HB24 and HB9 transcripts in human CD34- positive cells have short half-lives, estimated to be 30 to 45 minutes. Downregulation of HB24 and HB9 expression was found following the treatment of in vitro cultures of CD34-positive cells with IL-3. Thus, the differentiation of CD34-positive cells along a specific cell lineage likely requires downregulation of both HB24 and HB9.
Characterization of a receptor for interleukin-5 on human eosinophils and the myeloid leukemia line HL-60
Authors: Ingley E , Young IG 
Published: October 2019

Abstract
Interleukin-5 (IL-5) promotes the growth and differentiation of human eosinophils and may regulate the selective eosinophilia and eosinophil activation seen in certain diseases. Radiolabeled recombinant human IL- 5 (hIL-5) was used to characterize the IL-5 receptor present on normal human eosinophils and on the myeloid leukemia line HL-60, which can be induced to differentiate into eosinophilic cells. Binding studies with eosinophils and HL-60 cells grown under alkaline conditions demonstrated similar high-affinity binding sites for hIL-5 on both cell types with kd values of approximately 400 pmol/L. The binding observed was specific in that it was not inhibited by hIL-3, human granulocyte- macrophage colony-stimulating factor, or hIL-2. Binding studies with a number of other human cell lines, including a B-lymphoma line, and with lymphocyte and neutrophil preparations were also performed, but IL-5 receptors were not detectable on these cells. The number of hIL-5 receptors on HL-60 cells could be correlated with its propensity to differentiate towards an eosinophilic cell type. Expression of hIL-5 receptors on HL-60 cells was upregulated by butyric acid under alkaline conditions, downregulated by hIL-3, virtually eliminated by dimethyl sulfoxide and hIL-5, while hIL-2 had no detectable effect. One major 125I-hIL-5-crosslinked complex of 75 to 85 Kd in Mr was detected on HL- 60 cells using crosslinking agents giving a molecular mass of 55 to 60 Kd for the hIL-5 receptor itself. Studies using cellular autoradiography showed that IL-5 receptors were evenly distributed on eosinophils but that receptor distribution on HL-60 cells was noticeably heterogeneous. Eosinophils were the only cells in slides prepared from peripheral blood that had detectable levels of IL-5 receptors in agreement with the specific action of IL-5 on the human eosinophil lineage.
Changes of DNA methylation and chromatin structure in the human myeloperoxidase gene during myeloid differentiation
Authors: Lubbert M , Miller CW , Koeffler HP 
Published: October 2019

Abstract
Expression of the myeloperoxidase (MPO) gene is tightly regulated in a tissue- and development-specific manner. Accumulation of MPO messenger RNA (mRNA) occurs only at the late myeloblastic and promyelocytic stages of myeloid differentiation and is negligible at other stages of myeloid development and in other tissues. The goal of our studies was to begin to understand the events that occur to control MPO gene expression during normal granulocytopoiesis. Chromatin structure of the MPO gene was evaluated by DNase I treatment of isolated nuclei and Southern blot analysis. No detectable DNase I hypersensitive sites were found in the region of the MPO gene in non-myeloid cells. One site was present in the 5′ upstream region in myeloid cells that are developmentally too immature to transcribe MPO. Three sites of hypersensitivity in the regions of the putative MPO promoter and upstream region occurred in MPO-expressing promyelocytes. These sites were markedly reduced in terminally differentiated, non-expressing myeloid cells. Analysis of DNA methylation of the MPO gene using methylation-sensitive restriction enzymes showed that the gene was highly methylated in non-myeloid cells. Stepwise demethylation occurred in myeloid cells developmentally too immature to transcribe MPO. Maximal demethylation in the 5′ gene region occurred in MPO-expressing promyelocytes. This methylation pattern did not change in terminally differentiated, MPO non-expressing myeloid cells. A somatic hybrid cell formed by fusion of HL-60 (MPO-expressing cells) and PUT (MPO non- expressing lymphoid cells) extinguished expression of MPO and showed a chimeric pattern of MPO gene methylation, suggesting that demethylation is necessary but not sufficient for expression of the MPO gene. Our studies show that demethylation and DNase I hypersensitivity of the MPO gene were associated with a tissue-dependent potential for MPO gene expression that preceded the developmental ability to express MPO mRNA.
Effect of fibrinogen concentration on the velocity of platelet aggregation
Authors: Landolfi R , De Cristofaro R , De Candia E , Rocca B , Bizzi B 
Published: October 2019

Abstract
The relationship between fibrinogen binding to its receptor and platelet aggregation has been investigated by comparing 125I-fibrinogen binding and aggregation velocities of gel-filtered platelets in the presence of adenosine diphosphate (ADP). Aggregometric responses at various fibrinogen concentrations are found to be bell-shaped and show a maximum at fibrinogen concentrations (Fmax) similar to the 125I- fibrinogen hemisaturating doses. At higher and lower fibrinogen concentrations, platelet aggregation velocities decrease in a parallel manner. Lowering ADP concentration increases Fmax, in agreement with the modulatory effect of ADP on fibrinogen binding to platelets. Variations of fibrinogen in the range of physiopathologic plasma concentrations affect platelet aggregation induced by any ADP dose. These results clarify the relationship between the fibrinogen binding process and aggregation and demonstrate that plasma fibrinogen concentration has a major influence on the velocity of platelet aggregation.