bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal in vitro proliferation and differentiation of T colony-forming cells in patients with lymphadenopathy syndrome
Authors: Lunardi-Iskandar Y , Georgoulias V , Rozenbaum W , Klatzmann D , Coll MC , Meyer P , Gentilini M , Gluckman JC , Jasmin C 
Published: October 2019

Abstract
Patients with acquired immunodeficiency syndrome (AIDS) present impaired colony growth and in vitro differentiation capacity of peripheral blood and bone marrow T colony-forming cells (T-CFC). We show that peripheral blood, bone marrow, and lymph node T-CFC from patients with persistent lymphadenopathy syndrome (LAS), a syndrome that can precede AIDS, displayed similar abnormalities. Indeed, peripheral blood T-CFC generated a low number of colonies in seven out of 12 patients, and almost no colonies were obtained from bone marrow cells of all patients. The simultaneous study of T-CFC from peripheral blood and lymph node mononuclear cells seems to provide a reliable indicator for the risk of developing AIDS. The six patients who developed AIDS displayed extremely low numbers of peripheral blood T- CFC (13 +/- 17 colonies per 5 X 10(4) cells), and in two of them, no colonies could be obtained from lymph node T-CFC. The remaining patients who had not developed AIDS displayed a higher number of peripheral blood T-CFC (141 +/- 113 per 5 X 10(4) cells) and lymph node T-CFC, which, in addition, preserved their clonogenic capacity. In some patients, peripheral blood and lymph node, but not bone marrow, T-CFC were capable of generating colonies in the absence of added growth factors or mitogens, whereas in others, colony formation was obtained with purified interleukin 2 (IL 2) alone. Both spontaneous and IL 2- induced colony formation was abrogated by a monoclonal antibody against the IL 2 receptor. Taken together, these findings suggest that at least some T-CFC expressed IL 2 receptors. Colonies generated either in the presence or in the absence of added growth factors were composed of T4+, T6+, and T8+ cells, indicating impaired in vitro T-CFC differentiation. These findings indicate that a dramatic quantitative and qualitative impairment of the proliferation and differentiation of peripheral blood and lymph node T-CFC precedes the clinical evolution from LAS to AIDS.
Restricted expression of a new acute myelogenous leukemia-associated antigen (NHL-30.5) on normal hemopoietic progenitor cells
Authors: Askew DS , Eaves AC , Eaves CJ , Takei F 
Published: October 2019

Abstract
We have previously reported the isolation of a monoclonal antibody (NHL- 30.5) that reacts with an antigen expressed on a substantial proportion of marrow and blood cells of most patients with newly diagnosed or relapsing acute myeloid leukemia. This antigen is also found on several cell lines derived from myeloid malignancies of human origin. It is not present on mature hemopoietic cells or on the majority of differentiating bone marrow cells. In order to determine whether the NHL-30.5 antigen may, nevertheless, be expressed on low-frequency primitive normal hemopoietic cells, not detected in standard antibody screening procedures, its expression was studied on clonogenic erythropoietic and granulopoietic cells. Light-density (less than 1.077 g/mL) suspensions of normal or chronic myelogenous leukemia bone marrow and peripheral blood cells were stained with NHL-30.5 and fluorescein isothiocyanate labeled second antibody and then sorted into two fractions using the fluorescence-activated cell sorter. The first contained the top 5% of cells with the highest fluorescence intensity. The remainder were collected in the second fraction. Colony assays of both fractions showed the first to be enriched in CFU-E, BFU-E, and CFU- C content (fourfold to 17-fold). The second fraction was correspondingly depleted of these progenitors. These findings reveal NHL-30.5 antigen expression to be a transient event during normal hemopoiesis that characterizes primitive hemopoietic cells on several pathways. Subsequent experiments showed that the presence of up to 10 micrograms/mL of purified NHL-30.5 antibody in colony assay cultures neither inhibited nor stimulated colony formation. Marrow fibroblasts (subcultured marrow adherent cells) were NHL-30.5 negative. Immunoprecipitation studies showed that the antigen detected by NHL- 30.5 is clearly distinct from that identified by My-10, another monoclonal antibody that has previously shown some similarities to NHL- 30.5. It thus appears that the NHL-30.5 antibody reacts with a new myeloid differentiation antigen of as yet unidentified function that is normally restricted in its expression to early stages of hemopoiesis.
TCA: a polymorphic genetic marker in leukemias and melanoma cell lines
Authors: van Leeuwen A , Schrier PI , Giphart MJ , Noordermeer IA , Ruiter DJ , Rubinstein P , van Rood JJ 
Published: October 2019

Abstract
TCA (T Cell system A) is a di-allelic system of HLA-like antigens encoded by genes located about 15 cM telomeric to HLA-A. In normal individuals, TCA antigens are only expressed on a subpopulation of T cells, the TG lymphocytes. We now report on the expression of TCA on leukemias and other malignancies. An increased proportion of cells carrying the TCA phenotype was encountered in testing peripheral blood lymphocytes from patients with acute lymphoblastic T-cell leukemia (T- ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). In contrast, patients with B-cell malignancies such as chronic lymphatic leukemia (CLL) and hairy cell leukemia (HCL) or non-T/non-B common acute lymphoblastic leukemia (common ALL) had normal proportions of TCA-positive lymphocytes. Quantitatively different levels of TCA expression are found on some melanoma cell lines and others are TCA negative. These variations are independent of the expression of HLA Class I antigens by the same cells. The expression of TCA antigens by malignant nonlymphoid cells suggests that this system may code for differentiation markers, important in the biology of neoplastic transformation.
Controlled trial of desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time
Authors: Mannucci PM , Vicente V , Vianello L , Cattaneo M , Alberca I , Coccato MP , Faioni E , Mari D 
Published: October 2019

Abstract
The synthetic vasopressin derivative desmopressin (DDAVP) shortens a prolonged bleeding time (BT) in patients with uremia, congenital platelet dysfunction, and von Willebrand disease. To establish the limits of the clinical usefulness of DDAVP, a controlled randomized study was carried out in 53 patients and ten volunteers with different conditions that have in common a prolonged BT. DDAVP significantly shortened the BT in 21 cirrhotics (P less than .01), in eight patients with unclassified prolonged BT (P less than .05) and in ten volunteers taking the antiplatelet drugs aspirin (P less than .05) and ticlopidine. The BT changes were not statistically significant in 15 patients with severe thrombocytopenia nor in nine with congenital platelet dysfunction, even though a few patients with storage pool deficiency responded with a marked BT shortening. Our findings indicate that DDAVP might be given when biopsies or other surgical procedures must be carried out in patients with prolonged BT. However, the compound is often ineffective in patients with thrombocytopenia or congenital platelet dysfunction.
Responses of hemopoietic precursors to 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 in the myelodysplastic syndromes
Authors: Swanson G , Picozzi V , Morgan R , Hecht F , Greenberg P 
Published: October 2019

Abstract
To determine the effects of the “maturation-inducing” agents 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 on marrow cells from normal individuals and patients with myelodysplastic syndromes (MDS), we assessed marrow hemopoietic clonogenicity and differentiation response patterns to these agents. These vitamins caused increased proliferation in vitro of normal clonogenic marrow myeloid precursor cells (CFU-GM), decreased erythroid precursors (BFU-E), and no change in multipotent stem cells (CFU-GEMM). Marrow hemopoietic colony-forming cell incidence was generally subnormal in the 22 MDS patients evaluated. In vitro exposure to both agents caused various patterns of alteration of MDS hemopoietic colony and cluster formation, with similar but more pronounced effects evoked by retinoic acid. In the vast majority of MDS patients, enhanced marrow clonal granulocyte-monocyte differentiation and decreased BFU-E growth were noted after in vitro exposure to these vitamins. Correlation of biological effects was demonstrated between in vivo changes of peripheral neutrophil counts and in vitro responses of myeloid precursors for ten MDS patients treated with an eight-week therapeutic course of retinoic acid. Cytogenetic analyses indicated persisting aneuploidy or coexisting normal and aneuploid karyotypes in the cultured MDS myeloid cells and (with one exception) in native marrow cells from the treated patients. The varying responses of the MDS cells may monitor differing proportions of normal versus leukemic marrow cells susceptible to proliferative and differentiative expression on exposure to these agents.
Myeloperoxidase biosynthesis by a human promyelocytic leukemia cell line: insight into myeloperoxidase deficiency
Authors: Nauseef WM 
Published: October 2019

Abstract
The biosynthesis and processing of myeloperoxidase (MPO), a cationic enzyme present in the azurophilic granules of human polymorphonuclear leukocytes (PMNs), were studied in the human promyelocytic leukemia cell line, HL-60. HL-60 cells produce large quantities of enzymatically active MPO that has the same electrophoretic behavior as MPO isolated from normal PMNs. Mature MPO is a glycoprotein of approximately 150,000 molecular weight (mol wt) composed of two heavy-light protomers (alpha 2 beta 2) with subunits of 59,000 and 13,500 mol wt, respectively, under reducing conditions. The primary translation product of MPO messenger RNA (mRNA) isolated from HL-60 cells was a single polypeptide of mol wt 80,000. In HL-60 cells labeled with [35S]-methionine, the labeled MPO isolated by immunoprecipitation had a mol wt of 89,000. Treatment of this 89-kilodalton (kDa) species with endoglycosidase H produced a 79-kDa peptide, suggesting that the 89-kDa protein contained high-mannose side chains. The 89-kDa species had no detectable peroxidase activity. During chase experiments some of the 89-kDa peptide was processed to smaller species of mol wt 39,000, 59,000, and 13,500, although a fraction of the 89-kDa peptide remained unprocessed after a chase of 100 hours. In addition, a small amount of the 89-kDa peptide appeared in the medium without any of the processed smaller peptides. These studies suggest that the primary translation product in MPO biosynthesis is an 80-kDa peptide that undergoes cotranslational cleavage of the signal peptide and glycosylation to produce an 89-kDa pro-MPO, that pro-MPO is a single polypeptide containing the alpha and beta subunits of MPO and contains endoglycosidase H-susceptible high- mannose side chains, and that posttranslational modification of pro-MPO results in targeting to the lysosome and proteolytic maturation of pro- MPO to active enzyme. In light of the previous observation that MPO- deficient and normal PMNs contain an 89-kDa protein immunochemically related to MPO, these studies on MPO biosynthesis indirectly support the hypothesis that defective posttranslation processing by pro-MPO may underlie hereditary MPO deficiency.
On the interaction of rabbit antithrombin III with the luminal surface of the normal and deendothelialized rabbit thoracic aorta in vitro
Authors: Hatton MW , Moar SL , Richardson M 
Published: October 2019

Abstract
Pure rabbit antithrombin III was isotope labeled (with 125I or 3H) by two different methods; neither procedure caused a loss of antithrombin activity although both methods affected the affinity of the protein for Sepharose-heparin. From segments from freshly excised rabbit aorta, the uptake of isotope-labeled antithrombin III by the endothelium was rapid and saturable, although relatively small compared to the uptake of thrombin; binding of 3H-antithrombin III to the endothelium resembled that of 125I-antithrombin III. Transendothelial passage of antithrombin III into the subendothelial layers (intima-media) was slow and progressive. Endothelium binding was not affected by pretreating the vessel with either heparin, thrombin, or glycosaminoglycan-specific enzymes. Endothelium-bound antithrombin III was not selectively displaced by either heparin or thrombin. In contrast, endothelium-bound thrombin was rapidly dislodged by antithrombin III as a thrombin- antithrombin III complex. The surface of the deendothelialized aorta (ie, subjected to a balloon catheter) bound antithrombin III avidly. Pretreatment of the deendothelialized vessel with glycosaminoglycan- specific enzymes, particularly heparitinase, decreased intima-media binding by up to 80%. 125I-antithrombin III, when bound to the deendothelialized vessel surface, was actively displaced by either heparin, thrombin, or by unlabeled antithrombin III. The relatively poor binding of antithrombin III compared with that of thrombin by the endothelium in vitro supports an earlier proposal (Lollar P, Owen WG: J Clin Invest 66:1222–1230, 1980) that thrombin bound to high-affinity sites, possibly pericellular proteoglycan, of the endothelium is inactivated by plasma antithrombin III in vivo. Such a situation probably holds for large arteries at least.
Analysis of leukocyte differentiation antigens in blood and bone marrow from preleukemia (refractory anemia) patients using monoclonal antibodies
Authors: Hokland P , Kerndrup G , Griffin JD , Ellegaard J 
Published: October 2019

Abstract
Peripheral blood and bone marrow mononuclear cells from patients with refractory anemia (RA) or RA with sideroblasts (defined according to the revised French-American-British classification with less than 5% blast cells in the bone marrow) were analyzed using a panel of monoclonal antibodies directed against leukocyte antigens on B lymphocytes, T lymphocytes, monocytes, and myeloid cells. In the peripheral blood an increased proportion of T lymphocytes (and correspondingly a decreased proportion of B cells) could be demonstrated. However, when expressed in terms of absolute numbers, the T cell component was depressed because of severely decreased numbers of T4+ helper cells. In contrast, the absolute numbers of T8+ suppressor cells were either normal or increased in the majority of the patients. This resulted in markedly decreased ratios of T4+/T8+ cells, which were closely correlated to the number of transfusions given to the patients because of their refractory anemia. Finally, nearly all of the patients exhibited decreased numbers of cells reactive with the N901 natural killer (NK) antibody, thus explaining our earlier finding of decreased NK activity in these patients. In the bone marrow increased proportions of myeloid cells reactive with monoclonal antibodies present on immature myeloid cells (My7 and My9) were found, suggesting the presence of malignant clones. Indeed, when the numbers of My7+ cells and the morphologic evaluations of bone marrow smears at the time of diagnosis were compared to the progression of the disease, a group of patients with high numbers of My7+ cells and normal morphology could be identified that had a high probability of progression to refractory anemia with an excess of blasts or to overt acute myeloid leukemia. Thus, the use of antibodies defining leukocyte differentiation antigens might be of significant value in the diagnosis and prognostication of the myelodysplastic syndromes. These findings are discussed in relation to the pathogenesis of this potentially premalignant condition with special emphasis on possible defects in the immunologic defense mechanisms against early neoplasias.
Leukopenic chronic T cell leukemia mimicking hairy cell leukemia: association with human retroviruses
Authors: Sohn CC , Blayney DW , Misset JL , Mathe G , Flandrin G , Moran EM , Jensen FC , Winberg CD , Rappaport H 
Published: October 2019

Abstract
We report two cases of a T cell lymphoproliferative disease not previously described, with cytologic and clinical features similar to those associated with Galton's “prolymphocytic” leukemia (PL). Our patients, like those with Galton's PL, had massive splenomegaly and minimal or absent hepatomegaly and lymphadenopathy. In contrast, however, our patients had leukopenia, as well as low percentages of leukemic cells in the peripheral blood and in the bone marrow. In splenic imprints, the nuclear chromatin pattern of most of the leukemic cells was intermediate between those of mature lymphocytes and those of lymphoblasts, and the nuclei contained single, centrally located, conspicuous nucleoli. In sections of the spleen, the leukemic cells diffusely infiltrated the red pulp in a pattern strikingly similar to that of hairy cell leukemia; however, when the leukemic cells were studied cytochemically, the cytoplasmic acid phosphatase positivity was punctate and tartrate-sensitive. The leukemic cells were sheep erythrocyte rosette-positive and expressed T cell-associated antigens. Initially, both patients responded well to therapeutic splenectomy. One patient received combination chemotherapy after splenectomy and is alive and well 24 months after diagnosis. The other patient was in complete clinical remission for one year after splenectomy and received chemotherapy at relapse. He died, however, 23 months after splenectomy, with disseminated disease. IgG antibody titers against human T lymphotropic virus type I (HTLV-I) were detected in one patient and against HTLV-II in the other. The leukemia in these patients represents a distinct clinicopathologic entity within the spectrum of peripheral T cell lymphoproliferative diseases that includes Galton's PL of T cell derivation, T cell chronic lymphocytic leukemia, T cell hairy cell leukemia, and adult T cell leukemia/lymphoma.
Mechanisms of adenosine 5'-monophosphate catabolism in human erythrocytes
Authors: Paglia DE , Valentine WN , Nakatani M , Brockway RA 
Published: October 2019

Abstract
Uncertainties regarding the role of pyrimidine nucleotidase (PyrNase) in AMP catabolism were resolved by studies of erythrocytes from normal controls, controls with young mean cell ages, and patients with hereditary hemolytic anemia due to severe deficiency of PyrNase. Hemolysates from the latter exhibited undiminished capacity to dephosphorylate AMP over a broad range of pH, indicating that PyrNase was not directly involved. In each subject group, the rates of AMP dephosphorylation between pH 5.1 and 8.3 were indistinguishable from those of IMP, suggesting a potential role for AMP-deaminase, an erythrocyte enzyme that was stimulated by coformycin at pH 7.2. Quantitative analysis of catabolites in incubated hemolysates confirmed that AMP degradation preferentially occurred via deamination to IMP with subsequent dephosphorylation by another erythrocyte nucleotidase isozyme, deoxyribonucleotidase. Both AMP-deaminase and deoxyribonucleotidase have acidic pH optima with minimal activities at physiologic pH, suggesting that this pathway of AMP catabolism could accelerate depletion of the adenine nucleotide pool and thereby mediate the demise of senescent erythrocytes sequestered in the spleen.
Deformability and intrinsic material properties of neonatal red blood cells
Authors: Linderkamp O , Nash GB , Wu PY , Meiselman HJ 
Published: October 2019

Abstract
Whole cell and membrane deformability are essential for red blood cell (RBC) survival and for effective blood flow. Neonatal RBCs display several specific properties (eg, large size, high hemoglobin F) that could influence their deformation characteristics and contribute to their shortened life span. The present study was designed to compare selected rheologic properties (cellular deformability, pressure required to aspirate RBC into micropipettes, static and dynamic viscoelastic material properties) of neonatal and adult RBCs. RBC deformability, as studied by a rheoscope, was similar for neonates and adults over a shear stress range of 2.5 to 500 dyn/cm2. The pressure required to aspirate RBCs completely into 3.3-micron diameter pipettes was 129 +/- 87 dyn/cm2 for neonatal RBCs and 71 +/- 37 dyn/cm2 for adult RBCs. The aspiration pressure for neonatal and adult RBCs increased with increasing RBC volume, suggesting that the increased mean aspiration pressure for neonatal RBCs resulted from their larger volume. When RBCs with same volume and diameter were compared, the aspiration pressure tended to be smaller for neonatal RBCs than for adult cells. To characterize material properties determining RBC deformability, we measured membrane extensional (shear) and bending elastic moduli, the time constant for elastic recovery from extensional deformation and hemoglobin viscosity (ie, cytoplasmic viscosity) of neonatal and adult RBCs. Membrane surface viscosity and time constant for recovery from bending deformation were calculated. The extensional and bending moduli of neonatal RBCs were slightly smaller (10% and 16%, respectively) compared with adult cells. This suggests that the static resistance of neonatal RBC membrane to deformation and failure in response to a given force is slightly smaller. The time constant for recovery from extensional deformation of neonatal RBCs was larger by 14%, compared with adult cells. The time constant for bending deformation related to the RBC diameter and surface area was increased by 18% in the neonates. Membrane surface viscosity and hemoglobin viscosity were similar for both cell types. These results indicate that the deformability and viscoelastic properties of neonatal RBCs deviate only slightly from those of adult RBCs and that the increased aspiration pressure of neonatal RBCs is solely due to their large size. Some of the specific deformation characteristics observed in this study (increased aspiration pressure, decreased resistance to elastic deformation) may contribute to the shortened life span of neonatal RBCs.
A combination of a T cell-derived lymphokine differentiation-inducing activity and a physiologic concentration of retinoic acid induces HL-60 to differentiate to cells with functional chemotactic peptide receptors
Authors: Imaizumi M , Breitman TR 
Published: October 2019

Abstract
The human acute promyelocytic leukemia cell line HL-60 is induced by retinoic acid (RA) and N,N-dimethylformamide (DMF) to differentiate into cells having many of the functional and morphologic characteristics of mature granulocytes. With normal human phagocytic cells there is both superoxide anion (O2-) production and chemotaxis in response to chemoattractants such as N-formyl-methionyl-leucyl- phenylalanine (FMLP). We have now found that although HL-60 cells induced with RA alone produce O2- in response to 12–0-tetradecanoyl- phorbol-13-acetate (TPA) they are deficient in FMLP-stimulated O2- production and chemotaxis. In contrast, HL-60 induced either with DMF or with a combination of 10 nmol/L RA and a T cell-derived lymphokine, differentiation-inducing activity (DIA), produce O2- and exhibit chemotaxis in response to FMLP. The basis for these results appears to be the concentration of cell surface chemotactic peptide receptors. Thus, untreated HL-60 and HL-60 induced with either RA alone or DIA alone do not have measurable levels of FMLP receptors, whereas HL-60 induced with a combination of RA and DIA has 5,400 receptors per cell. HL-60 induced with RA and DIA plus 1 mumol/L dexamethasone have 25,000 receptors per cell and have greater chemotactic activity than HL-60 induced with the combination of RA and DIA. Thus, differentiation of HL- 60 to cells with many properties of normal phagocytes can be induced in vitro by physiologic substances.