bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADP-induced platelet aggregation depends on the conformation or availability of the terminal gamma chain sequence of fibrinogen. Study of the reactivity of fibrinogen Paris 1
Authors: Denninger MH , Jandrot-Perrus M , Elion J , Bertrand O , Homandberg GA , Mosesson MW , Guillin MC 
Published: October 2019

Abstract
Fibrinogen Paris I contains a mutant gamma chain that is longer than the normal chain, resulting in altered fibrin polymerization and cross- linking. Because these functions involve the carboxy-terminal region of the gamma chain, we decided to determine whether fibrinogen Paris I or the isolated Paris I gamma chain supports normal ADP-induced platelet aggregation, a function that requires the ultimate 12 residues of the normal gamma chain (400 through 411). Aggregation of ADP-stimulated normal platelets was defective with fibrinogen Paris I and markedly depressed with the gamma Paris I chain. These findings prompted us to characterize the carboxy-terminal structure of the region of the gamma Paris I chain responsible for this activity. The carboxy-terminal cyanogen bromide (CNBr) peptide of the normal gamma chain (385 through 411) or that from gamma Paris I was isolated by differential adsorption to triethylene-tetramine resin or by reverse-phase high-performance liquid chromatography (HPLC). The CNBr peptide from the Paris I gamma chain was identical to that of the normal gamma chain in its retention time on HPLC, its amino acid composition, and its sequence. Thus, the primary structure of the gamma Paris I chain from residue 384 through 411 is normal, indicating that a peptide insertion has occurred upstream from residue 384, resulting in an impairment of those physiologic functions attributable to the carboxy-terminal end of the gamma chain from position 384 (ie, cross-linking, ADP-induced platelet aggregation, and at least a portion of the gamma chain polymerization site). These observations demonstrate that the gamma chain platelet recognition site in the fibrinogen molecule is necessary but not alone sufficient to support normal ADP-induced platelet aggregation. There appears to be an additional requirement for normal conformation of the gamma chain or availability of its terminal sequence during the interaction of fibrinogen with platelets.
An approximately 300 bp deletion involving part of the 5' beta-globin gene region is observed in members of a Turkish family with beta- thalassemia
Authors: Diaz-Chico JC , Yang KG , Kutlar A , Reese AL , Aksoy M , Huisman TH 
Published: October 2019

Abstract
Detailed gene mapping analyses of genomic DNA from two Turkish subjects with a beta-thalassemia trait demonstrated an approximately 300 bp deletion, which is located between the Rsa I restriction site 128 bp 5′ to the Cap site and the Acc I restriction site 284 bp 3′ to the same Cap site; it includes the 5′ beta promoter region, the first exon, and (part of) the IVS-I. Heterozygotes for this and two other beta- thalassemia types, which are also caused by deletions involving 5′ beta promoter sequences, appear to have higher hemoglobin (Hb) A2 levels, perhaps because the loss of this promoter results in an increased transcription of the delta globin gene, as delta and beta promoters may be influenced by the same enhancing sequences 3′ to the beta globin gene.
Immunologic reconstitution after haploidentical bone marrow transplantation for immune deficiency disorders: treatment of bone marrow cells with monoclonal antibody CT-2 and complement
Authors: Moen RC , Horowitz SD , Sondel PM , Borcherding WR , Trigg ME , Billing R , Hong R 
Published: October 2019

Abstract
Patients with congenital T lymphocyte deficiency disorders received transplants with parental bone marrow depleted of mature T cells by the use of an anti-T cell monoclonal antibody (CT-2) and complement. Our results with 16 consecutive patients (20 transplants) showed rapid engraftment of donor cells; cytoreduction (busulfan, cytosine arabinoside [ara-C], cyclophosphamide) was used in six transplants, and marrow ablation was used in six (ara-C, cyclophosphamide, 1,365-cGy total body irradiation). No patient received prophylactic anti-graft-v- host disease (GVHD) therapy posttransplant, and only one patient developed significant GVHD, which involved the skin, liver, and gastrointestinal tract. Seven others showed some manifestations of GVHD, but these were of minimal clinical significance and required only occasional steroid therapy. Overall, eight patients are alive and well; eight did not survive. Polyclonal immunoglobulin synthesis by donor memory B cells was seen shortly after transplantation, with peak donor- derived serum levels seen approximately 2 months after transplantation. After this initial immunoglobulin synthesis waned, another wave of B cell responses developed. This immunoglobulin response appears to be permanent. T cell functions appeared as soon as 3 weeks after transplantation. This experience in a variety of patients with combined immunodeficiency who received transplants with monoclonal antibody T cell-depleted marrow shows gratifying results with a consistent T and B cell benefit.
Induction of proliferation of B prolymphocytic leukemia cells by phorbol ester and native or recombinant interferon-gamma
Authors: Sauerwein RW , van der Meer WG , Aarden LA 
Published: October 2019

Abstract
Phorbol ester phorbol myristate acetate (PMA) induces proliferation in nonmalignant human B cells and B cells from a patient with B prolymphocytic leukemia (B-PLL). Mitogen-free T cell-derived conditioned medium acts synergistically with PMA in inducing proliferation of B-PLL cells but does not enhance the PMA-stimulated outgrowth of nonmalignant B cells. Interleukin 2 (IL-2) has no effect on the outgrowth of B-PLL cells, and monoclonal antibodies against the IL-2 receptor do not influence the response to PMA and conditioned medium. Recombinant interferon-gamma (IFN-gamma), in contrast, is a potent enhancer of PMA-induced proliferation of B-PLL cells. With gel filtration techniques and with the use of anti-IFN-gamma antibodies, it is shown that IFN-gamma in the conditioned medium is responsible for the observed increase in B-PLL cell proliferation. Preincubation of B- PLL cells with IFN-gamma induces responsiveness to PMA, whereas IFN- gamma alone had no effect on these cells when pretreated with PMA. The combined data show that, in the presence of PMA, native and recombinant IFN-gamma are growth factors for B cells from a B-PLL patient and that IL-2 is not involved in this process.
Inhibition of hemopoietic growth factor-induced proliferation by adenosine diphosphate-ribosylation inhibitors
Authors: Colon-Otero G , Sando JJ , Sims JL , McGrath E , Jensen DE , Quesenberry PJ 
Published: October 2019

Abstract
The effects of adenosine diphosphate (ADP) ribosylation inhibitors on hematopoietic growth factor-induced proliferation were examined. Significant inhibition of interleukin-3 (IL-3), colony-stimulating factor 1, and lung conditioned media-induced clonal agar growth of normal murine hematopoietic cells by 10 mmol/L nicotinamide (NAM), 10 mmol/L 3-aminobenzamide (3AB), and 5 mmol/L N1-methylnicotinamide (1MN) was noted. Nicotinic acid, a related compound that does not inhibit ADP ribosylation, failed to inhibit the growth factor-mediated proliferation. NAM (10 mmol/L), 3AB (10 mmol/L), and 1MN (5 mmol/L) also prevented IL-3 and phorbol ester-stimulated 3H-thymidine incorporation into the IL-3-responsive FDC-P1 cell line. Exposure of FDC-P1 cells to 10 mmol/L NAM led to a significant decrease in nuclear poly-(ADP-ribose) levels. Exposure of FDC-P1 cells to 5 mmol/L 1MN did not affect the interaction of the phorbol ester receptor, protein kinase-C (PK-C), with the cell membrane as determined by assay of phorbol ester binding in cytosol and membrane preparations. Nor did it affect the catalytic activity of PK-C as determined by assaying the in vitro phosphorylation of histone H1 by cytosolic kinase preparations from FDC-P1 as well as EL4 thymoma cells. 1MN markedly enhanced the inhibitory effects of phorbol esters on DNA synthesis of EL4 cells even at concentrations (1.25 mmol/L) that had no effects on DNA synthesis in the absence of phorbol esters. Our findings demonstrate that (a) active ADP ribosylation inhibitors interfere with growth factor-induced proliferation of murine hematopoietic cells and (b) the inhibition occurs at a step that follows the activation and translocation of PK-C and is more closely linked to DNA synthesis.
Exposure to gamma-irradiation increases phorbol myristate acetate- induced H2O2 production in human macrophages
Authors: Gallin EK , Green SW 
Published: October 2019

Abstract
Cell number, protein, and phorbol myristate acetate (PMA)-induced H2O2 production were measured in cultured human peripheral blood monocytes for six days after exposure to varying doses of gamma-radiation. Both the number of adherent cells and the protein per dish decreased with increasing radiation doses. The dose of radiation decreasing the number of adherent cells by 37% on days 4 and 6 postirradiation was 29 Gy. Four hours postirradiation there was a small decrease in PMA-induced H2O2 production for doses of 7.5 Gy or greater; levels returned to normal by eight hours and increased at 24 hours postirradiation. By day 4 postirradiation significant increases in PMA-induced H2O2 production were noted at all radiation doses (2.5 to 50 Gy). This increase was not due to a shift in the PMA dose-response curve, a change in the time course of the PMA response, or an effect of decreased cell density on the assay system. Superoxide levels were not significantly changed in cells exposed to 20 Gy. Catalase, glutathione peroxidase, and superoxide dismutase levels also were unchanged. Culturing irradiated cells with gamma-interferon increased PMA-induced H2O2 release, which indicated that irradiated cells retained their capacity to respond to gamma-interferon. These data demonstrate that irradiation affects the PMA-induced H2O2 production of human monocytes in a time- and dose- dependent manner. An increase in the release of reactive oxygen intermediates by the macrophage may play a role in enhancing the deleterious effects of radiation in vivo.
1986 update of HIV seroprevalence, seroconversion, AIDS incidence, and immunologic correlates of HIV infection in patients with hemophilia A and B
Authors: Ragni MV , Winkelstein A , Kingsley L , Spero JA , Lewis JH 
Published: October 2019

Abstract
A cohort of 181 patients with hemophilia A (149) and hemophilia B (32) cared for at the Hemophilia Center of Western Pennsylvania was followed to determine human immunodeficiency virus (HIV) seroprevalence, seroconversion rate, and clinical and immunologic correlates of HIV infection. By December 1986, 82 (45%) were HIV seropositive, and of these, ten (12%) had developed AIDS, 28 (34%) had symptomatic HIV infection (CDC class III, IV), of whom 14 (17%) had AIDS-related complex (ARC), and 44 (54%) had asymptomatic HIV infection (CDC class II). The HIV seropositive group included 82% of those treated with factor VIII concentrate (97% severe, 5% moderate), 48% of those treated with factor IX concentrate (92% severe, 8% moderate), 10% of those treated with cryoprecipitate (67% severe, 33% moderate), and none of those treated with fresh frozen plasma. Based on 77 serially sampled HIV seropositive hemophiliacs (1977 to 1986), peak seroconversion occurred in 1982, with 14% (11 of 77) occurring since 1984. With increasing time from seroconversion, both T4 lymphocyte number and function (the latter measured by growth in soft agar [T colony assay]) progressively declined; T4 number declined to 135 +/- 26/mm3 (SEM), and colony count declined 1193 +/- 537 (control 3851 +/- 387) by 5 years after seroconversion. In those developing AIDS, total T4 fell below 100/mm3 (33 +/- 8/mm3) at diagnosis. In this cohort, the overall AIDS incidence is 5.5% (12% among the HIV seropositive) and in those seropositive 5 or more years, the AIDS incidence approaches 32%.
A delta-globin gene derived from patients with homozygous delta zero- thalassemia functions normally on transient expression in heterologous cells
Authors: Nakamura T , Takihara Y , Ohta Y , Fujita S , Takagi Y , Fukumaki Y 
Published: October 2019

Abstract
Three Japanese individuals with homozygous delta zero-thalassemia from different families were the subjects of molecular genetic analysis. They were homozygous for seven polymorphic sites in the beta-globin gene cluster. Nucleotide sequence analysis of the delta-globin gene cloned from each patient revealed a single nucleotide substitution (T- C) 77 base pairs 5′ to the cap site, just upstream of the CCAAC box of the delta-globin gene. When introduced into COS cells, the gene was expressed at normal levels with proper processing of RNA. These results suggest that the complete suppression of delta-globin chain synthesis in these patients is not due to a defective promoter, a defective RNA processing or a chain terminator mutation, but rather to impaired regulation of gene expression specific to erythroid cells. The region around the CCAAC box may have a significant role in expression of the delta-globin gene in erythroid cells.
Studies with a monoclonal antibody against activated platelets: evidence that a secreted 53,000-molecular weight lysosome-like granule protein is exposed on the surface of activated platelets in the circulation
Authors: Nieuwenhuis HK , van Oosterhout JJ , Rozemuller E , van Iwaarden F , Sixma JJ 
Published: October 2019

Abstract
To define the role of activated platelets we have attempted to prepare monoclonal antibodies specific for activated platelets. The IgG2b antibody of one of the clones, designated 2.28, was studied in more detail. Native platelets from normal individuals bound 650 125I-2.28 molecules/platelet, whereas thrombin-activated platelets bound 12,600 molecules/platelet with high affinity (4.6 nmol/L). Immunoelectrophoretic analysis revealed that 2.28 reacted with a 53,000- mol wt protein. Immunocytochemistry showed that the antigen is located in a special subclass of platelet granules in unstimulated platelets and is exposed on the surface of thrombin-activated platelets. Double- labeling studies with immunogold labels disclosed simultaneous localization of 2.28 binding sites and cathepsin D in the same granules both in megakaryocytes and endothelial cells, thereby indicating that the antigen may be localized in lysosomes. By using flow cytofluorometry, in vivo platelet activation was studied in patients undergoing cardiac surgery with cardiopulmonary bypass. Increased numbers of platelets that expressed the 2.28 antigen on their surface were observed after extracorporeal perfusion. The percentage of 2.28- positive platelets in the circulation was 3.9% +/- 2.7% (SD) in controls (n = 20), 5.5% +/- 3.0% in patients (n = 10) before cardiopulmonary bypass surgery, 24.6% +/- 13.5% after the bypass, and 8.5% in two patients with acute deep venous thrombosis. These data indicate that 2.28 may serve as a useful probe of in vitro and in vivo platelet activation.
A monoclonal anti-human plasma prekallikrein antibody that inhibits activation of prekallikrein by factor XIIa on a surface
Authors: Veloso D , Silver LD , Hahn S , Colman RW 
Published: October 2019

Abstract
Of five IgGI/k murine monoclonal anti-human prekallikrein antibodies produced (MAbs), MAb 13G11 was selected for studying interaction of prekallikrein with factor XII and high-mol-wt kininogen (HMWK) during activation on a surface. Immunoblots from sodium dodecyl sulfate (SDS) gels showed that this MAb recognizes two variants (88 kd and 85 kd) of prekallikrein and kallikrein both in purified proteins and normal plasma. Under reducing conditions, kallikrein exhibits the epitope on the heavy chain but not on the light chains. Preincubation of MAb 13G11 with prekallikrein (added to prekallikrein-deficient plasma) or with normal plasma inhibited surface activation of prekallikrein 60% to 80%, as judged by amidolytic and coagulant assays. In normal plasma, inhibition by the Fab fragments was 87% of that with the entire MAb. Inhibition was not by competition between the MAb and HMWK, since neither binding of 13G11 to prekallikrein (coated on microtiter plates) was inhibited by an excess of HMWK, nor was hydrolysis of HMWK by kallikrein inhibited by 13G11. Using purified proteins in a system mimicking contact activation, inhibition by 13G11 of prekallikrein activation by factor XIIa, HMWK, and kaolin present was approximately 80%. Decreased inhibition (55% to 25%) occurred without HMWK or when kallikrein was used instead of prekallikrein. Kallikrein activity was not inhibited by 13G11 Fab fragments. These results indicate that the effect of 13G11 in plasma was neither dissociation of prekallikrein- HMWK complex nor a direct effect on kallikrein activity. Similar to the results in plasma, activation of prekallikrein, HMWK present, by factor XIIa bound to kaolin, was inhibited approximately 70% by 13G11. The results suggest a previously unrecognized site on the prekallikrein (heavy chain) required for its interaction with factor XIIa, either shared with the 13G11 epitope or located in very close proximity. The inhibition of kallikrein by intact 13G11 indicates that its binding site on the heavy chain is sterically related to the active site (light chain).
Establishment of an interleukin 2-dependent human T cell line from a patient with T cell chronic lymphocytic leukemia who is not infected with human T cell leukemia/lymphoma virus
Authors: Hori T , Uchiyama T , Tsudo M , Umadome H , Ohno H , Fukuhara S , Kita K , Uchino H 
Published: October 2019

Abstract
We established an interleukin 2 (IL-2)-dependent human T cell line, Kit 225, from a patient with T cell chronic lymphocytic leukemia (T-CLL) with OKT3+, -T4+, -T8- phenotype. Southern blot analysis showed that Kit 225 is not infected with human T cell leukemia/lymphoma virus (HTLV) type I or II, and is probably derived from the major clone in the fresh leukemic cells. Kit 225 cells express a large amount of IL 2 receptors constitutively and their growth is absolutely dependent on IL 2. No other stimuli, such as lectins or antigens, are required for maintaining the responsiveness to IL 2. As abnormal IL 2 receptor expression was also seen originally in the fresh leukemic cells, the establishment of this cell line with IL 2 suggests that IL 2-mediated T cell proliferation is involved in the leukemogenesis of some cases of HTLV-negative T-CLL.
Bone marrow matrix modulation of HL-60 phenotype
Authors: Luikart SD , Sackrison JL , Maniglia CA 
Published: October 2019

Abstract
The initiation and maintenance of cellular differentiation for a variety of cell types has been shown to be influenced by the microenvironment. To investigate the influence of bone marrow stroma on leukemic cell differentiation, HL-60 human promyelocytic leukemia cells were grown in the presence of Triton-treated extracellular matrix derived from normal human bone marrow stromal cells. This bone marrow matrix microenvironment had a dramatic impact on the phenotypic expression of this malignant line. HL-60 cellular proliferation, morphology, nonspecific esterase activity, formation of Fc rosettes, and sensitivity to induction by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were all influenced by the presence of matrix molecules. In contrast, stromal cell-conditioned media did not alter HL-60 phenotype. Thus, HL-60 cells appear to retain responsiveness to a human bone marrow stromal cell-derived matrix despite their ability to grow autonomously. Studies of the interaction of leukemic cells and marrow stroma in vitro may provide important information concerning the regulation of leukemic cell behavior.
Immunohistochemical characterization of a 183 KD myeloid-specific-DNA- binding protein in B5 fixed, paraffin-embedded tissues, and bone marrow aspirates by monoclonal antibody BM-1
Authors: Epstein AL , Samoszuk M , Stathopoulos E , Naeve GS , Clevenger CV , Weil S , Marder RJ 
Published: October 2019

Abstract
A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.