bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of HLA-DR antigens in subsets of human CFU-GM
Authors: Griffin JD , Sabbath KD , Herrmann F , Larcom P , Nichols K , Kornacki M , Levine H , Cannistra SA 
Published: October 2019

Abstract
Expression of HLA-DR surface antigens by granulocyte/monocyte colony- forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. “Early” (day 14) CFU-GM express higher levels of HLA- DR than do “late” (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high- level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.
Acetylcholinesterase in human thymus cells
Authors: Topilko A , Caillou B 
Published: October 2019

Abstract
Acetylcholinesterase (AChE) was long thought to be an enzyme found specifically at the sites of nerve synapses and neuromuscular junctions. It has also been found to occur, however, in cells that are not involved with neurotransmission. This study presents the ultrastructural localization of AChE activity in human thymus cells, using the indirect thiocholine method. Cytochemical demonstration of the enzyme was based on the coupling of acetylthiocholine iodide hydrolysis to the precipitation of heavy metal salts. AChE activity was selectively revealed in the perinuclear cisternae, within the endoplasmic reticulum, and in the Golgi complex of thymic lymphocytes and epithelial cells. Evidence of the presence of reaction product in the latter cells was also found in vesicles that opened into the extracellular space. This is the first demonstration of AChE in human thymus cells. Its possible physiologic role in the thymus gland is discussed.
Evidence for clonal development of childhood acute lymphoblastic leukemia
Authors: Dow LW , Martin P , Moohr J , Greenberg M , Macdougall LG , Najfeld V , Fialkow PJ 
Published: October 2019

Abstract
To determine whether acute lymphoblastic leukemia (ALL) is a clonal disease and to define the pattern of differentiation shown by the involved progenitor cells, we studied the glucose-6-phosphate dehydrogenase (G6PD) types in the cells of 19 girls heterozygous for this X chromosome-linked enzyme. Lymphoblast immunophenotypes were those of HLA-DR+, CALLA+ ALL (six patients); HLA-DR+, CALLA- ALL (four patients); pre-B cell ALL (two patients); T cell ALL (four patients); and undefined ALL (three patients). Malignant blast cells at diagnosis from ten patients displayed a single G6PD type, indicative of clonal disease. In contrast, both A and B G6PD in ratios similar to those found in skin were observed in morphologically normal blood cells from the same patients. The leukemic cells of three patients were examined at both diagnosis and relapse; in each instance the same G6PD type was found, consistent with regrowth of the original leukemic clone at relapse. Results of studies of cells from nine additional patients tested only at relapse were similar. Our results indicate that childhood ALL is a clonally derived disease involving progenitor cells with differentiation expression detected only in the lymphoid lineage.
Platelet membrane topography: colocalization of thrombospondin and fibrinogen with the glycoprotein IIb-IIIa complex
Authors: Asch AS , Leung LL , Polley MJ , Nachman RL 
Published: October 2019

Abstract
The distribution of platelet thrombospondin (TSP), fibrinogen, and glycoproteins IIb-IIIa (GPIIb-IIIa) and GPIb were studied in resting and activated human platelets using frozen thin-section immunoelectron microscopy. In resting platelets, TSP and fibrinogen were found within alpha granules and not on the platelet surface. In unstimulated platelets, GPIIb-IIIa and GPIb were distributed diffusely over the platelet membrane as well as within the body of the platelets. Upon thrombin or A23187 stimulation, TSP, fibrinogen, and GPIIb-IIIa colocalized on the platelet membrane and the canalicular system as well as on pseudopodia and between adherent platelets. GPIb distribution was unchanged by platelet activation. The findings support the hypothesis that a macromolecular complex of TSP-fibrinogen and GPIIb-IIIa forms on the activated platelet membrane.
A longitudinal study of patients with hemophilia: immunologic correlates of infection with HTLV-III/LAV and other viruses
Authors: Stein SF , Evatt BL , McDougal JS , Lawrence DN , Holman RC , Ramsey RB , Spira TJ 
Published: October 2019

Abstract
A comprehensive study was initiated to examine the immunologic status of a sample (n = 47) of the asymptomatic hemophilia A and B populations of metropolitan Atlanta and to determine if any of the abnormalities changed with time or correlated with infection by human T cell leukemia virus type III and lymphadenopathy-associated virus (HTLV-III/LAV) or other viruses either alone or in combination. Patients with hemophilia A (Hem-A) showed a defect in cellular immunity evidenced by a depressed T cell helper/suppressor ratio (P less than .0001), an increased absolute T suppressor cell number (P less than .0001), and a diminished number of T helper cells (P = .003) when compared with health professionals. Lymphocytes from these patients also showed a reduced ability to transform in response to phytohemagglutinin and pokeweed mitogen. No deterioration in immune status was seen during a median ten- month period of follow-up. Sixty-four percent of Hem-A patients had antibodies to HTLV-III/LAV and those who were seropositive had a significantly decreased helper/suppressor cell ratio (P = .018) and a diminished T helper cell number (P = .002); they were also more likely to have had exposure to cytomegalovirus than HTLV-III/LAV-negative Hem- A patients (P = .016). Heavy use of factor VIII concentrate was associated with a decreased number of T helper cells (P = .037) and seropositivity for HTLV-III/LAV (P = .011 in 1982). Hemophilia patients had higher IgG, immune complex, and beta 2-microglobulin levels than health professionals (P less than .0001). Although the most prominent abnormality observed in T cell subsets of patients with hemophilia is an increase in T suppressor cells, a finding likely to be associated with immune augmentation in response to multiple stimuli, the T cell abnormality that was predictive of exposure to HTLV-III/LAV, the putative acquired immunodeficiency syndrome agent, was a diminished number of T helper cells.
Suppressed expression of blood group B antigen and blood group galactosyltransferase in a preleukemic subject
Authors: Yoshida A , Kumazaki T , Dave V , Blank J , Dzik WH 
Published: October 2019

Abstract
The B antigen activity was severely diminished in a patient's RBCs at the preleukemic stage prior to chemo- or radiotherapy. The amount of H sites of the patient's RBC membranes was found to be comparable to that of O RBC membranes. The activity of alpha (1----2) fucosyltransferase (H enzyme) was not severely decreased in the patient's plasma and bone marrow. However, the activity of alpha (1----3) galactosyltransferase (B enzyme), which converts H substance to B substance, was drastically reduced in the patient's bone marrow. Thus, the diminished B antigen in the patient's RBCs was caused mainly by the blockage of conversion of the H substance to B substance. It is suggested that the viral oncogene linked to the ABO locus at q34 of chromosome No. 9 would occasionally suppress the expression of blood group A and B enzymes and A and B antigens.
Regulation of plasma factor XIII binding to fibrin in vitro
Authors: Greenberg CS , Dobson JV , Miraglia CC 
Published: October 2019

Abstract
The binding of plasma factor XIII to fibrinogen or fibrin that has been chemically or enzymatically induced to polymerize was studied. Factor XIII binding was assayed using a 3H-putrescine incorporation assay and an 125I-plasma factor XIII binding assay. More than 80% of the native and radiolabeled plasma factor XIII was bound to fibrin I formed by reptilase in EDTA, citrate, or heparin anticoagulated plasma. Plasma factor XIII and 125I-factor XIII was bound (89.6% to 92.5%) to fibrin II formed by thrombin in either citrate or EDTA anticoagulated plasma. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of 125I-plasma factor XIII bound to fibrin I or fibrin II formed by reptilase or thrombin in the presence of EDTA demonstrated the b2- subunit remained bound to the a-chains or thrombin-cleaved a-chains. In the presence of calcium chloride and thrombin, the b2-subunit dissociated and factor XIIIa was bound. Protamine sulfate caused fibrinogen polymerization in the absence of divalent cations and reduced both plasma factor XIII and immunologic fibrinogen levels. Fibrinogen polymerized by protamine sulfate bound plasma factor XIII and the a2-subunit of 125I-platelet factor XIII. Plasma factor XIII was also bound to sonicated non-cross-linked fibrin II in either normal plasma or afibrinogenemic plasma. Plasma levels of several coagulation proteins were unchanged after the addition of reptilase, protamine sulfate, or sonicated fibrin to plasma. These results demonstrate that a specific binding site for the a2-subunit of plasma factor XIII is present on polymerized fibrinogen, fibrin I, and fibrin II. Furthermore, the presence of divalent cations, thrombin-cleavage of plasma factor XIII, and release of fibrinopeptides A or B are not required for plasma factor XIII binding to polymerized fibrinogen and fibrin.
Phorbol ester induces abnormal chronic lymphocytic leukemia cells to express features of hairy cell leukemia
Authors: Caligaris-Cappio F , Pizzolo G , Chilosi M , Bergui L , Semenzato G , Tesio L , Morittu L , Malavasi F , Gobbi M , Schwarting R 
Published: October 2019

Abstract
We have investigated the relationship between chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and different normal B cell subsets: Mrbc+, T1+ and slgM+ tonsil cells; germinal center; mantle zone; and peripheral blood B lymphocytes. Both malignant and normal cells were incubated in vitro with the phorbol ester 12-O-tetradecanoyl- phorbol-13-acetate (TPA) for 72 hours and the morphology, cytochemical profile, and surface markers were evaluated. The results show that CLL cells TPA-induced become indistinguishable from HCL by four independent criteria: the morphology; the cytoplasmic tartrate resistant acid phosphatase (TRAP) enzyme activity; the membrane positivity with anti- Leu M5 (SHCL3); and anti-Tac monoclonal antibodies which, in the uninduced state, react only with HCL. The features of TRAP and Tac positivity are also expressed (though in variable degree) by different normal B cell populations activated with TPA or pokeweed mitogen (PWM). It is concluded that HCL might represent an aberrantly activated variant of CLL (or of a CLL-related disorder).
Modulation of in vitro eosinophil progenitors by hydrocortisone: role of accessory cells and interleukins
Authors: Slovick FT , Abboud CN , Brennan JK , Lichtman MA 
Published: October 2019

Abstract
The growth of human eosinophil progenitors (CFU-Eo) and the modulation of growth by hydrocortisone were studied as functions of the presence of lymphocytes and monocytes in marrow cells under study; and the source of colony-stimulating factors, specifically, media conditioned by macrophage-like cell line, GCT; phytohemagglutinin-stimulated mononuclear cells (PHA-LCM); or the T cell line, MO. CFU-Eo growth was greatest in marrow containing accessory cells as compared to marrow depleted of accessory cells; and in marrow treated with phytohemagglutinin-stimulated leukocyte conditioned media (PHA-LCM) or MO (T cell line)-conditioned medium (MO-CM) as compared with GCT cell- conditioned medium (GCT-CM). Hydrocortisone reproducibly inhibited eosinophil progenitor growth in unfractionated marrow stimulated by GCT- CM. This effect was abrogated by admixing irradiated mononuclear cells or T lymphocytes with the target marrow or by adding interleukin 1 or interleukin 2 (IL-1, IL-2). Inhibition by hydrocortisone did not occur when monocyte and T lymphocyte depleted marrow was studied. Unlike GCT- CM, MO-CM and PHA-LCM stimulated equal proportions of eosinophil progenitors in nondepleted and accessory cell-depleted marrow and demonstrated less hydrocortisone inhibition. However, both GCT-CM and PHA-LCM produced in the presence of hydrocortisone stimulated significantly fewer CFU-Eos in both unfractionated and accessory cell- depleted marrow target populations. These results indicate that the growth of CFU-Eo and inhibition of growth by hydrocortisone is a direct function of a monocyte-T cell interaction and probably is mediated through effects on the production/release of eosinophil colony stimulating factor (Eo-CSF).
Erythrocyte vitamin E is oxidized at a lower peroxide concentration in neonates than in adults
Authors: Vanderpas J , Vertongen F 
Published: October 2019

Abstract
Erythrocytes of neonates and adults were incubated with increasing concentrations of H2O2 in the presence of a catalase inhibitor and in the absence of glucose; the pattern of oxidation of vitamin E was analyzed in relationship to that of glutathione, hemoglobin, and polyunsaturated fatty acids (PUFA), and in relationship to hemolysis. The changes of these various parameters were analyzed in function of H2O2 concentration and in relation to incubation time, and were compared in erythrocytes from neonates and adults. In the absence of H2O2, erythrocyte glutathione and tocopherol levels were similar in neonates and adults, despite fourfold lower serum vitamin E level in neonates; alpha-tocopherolquinone, methemoglobin, and malonyldialdehyde (MDA) were not detectable. At 0.375 mmol/L of H2O2, glutathione was completely oxidized. Erythrocyte alpha-tocopherol remained unchanged up to 0.75 mmol/L of H2O2, then decreased linearly, with increasing H2O2 concentrations to 10% of its initial value at 1.5 mmol/L of H2O2 in erythrocytes from neonates, whereas those from adults required 2.0 mmol/L of H2O2 (P less than .05) for the same level of oxidation. The formation of alpha-tocopherolquinone appeared inversely related to the decrease of alpha-tocopherol. The incubation time did not influence the level of vitamin E oxidation. MDA was generated autocatalytically and resulted in hemolysis at 1.5 mmol/L of H2O2 in erythrocytes from neonates and at 3.5 mmol/L of H2O2 in erythrocytes from adults (P less than .001). After four hours of incubation, MDA reached a plateau at a greater level (365 +/- 46 nmol/L) in cells of neonates than in those of adults (208 +/- 37 nmol/L/mL) (P less than .001). Hemoglobin was oxidized in the same pattern in erythrocytes of neonates and adults, and 90% of it was oxidized at 0.625 mmol/L of H2O2. In conclusion, in the experimental conditions used, oxidation of glutathione precedes that of vitamin E, and tocopherol is the last antioxidant to be consumed before the autocatalytic generation of MDA. Differences in the pattern of vitamin E oxidation, MDA generation, and hemolysis in erythrocytes from neonates and adults may be due to a lower erythrocyte vitamin E-PUFA ratio in neonates.
Gray platelet syndrome: immunoelectron microscopic localization of fibrinogen and von Willebrand factor in platelets and megakaryocytes
Authors: Cramer EM , Vainchenker W , Vinci G , Guichard J , Breton-Gorius J 
Published: October 2019

Abstract
An immunogold method was used for investigating the subcellular localization of von Willebrand factor (vWF) and fibrinogen (Fg) in platelets and cultured megakaryocytes from normal subjects and from three patients with the gray platelet syndrome (GPS), a rare congenital disorder characterized by the absence of alpha-granules. In normal platelets at rest, vWF was detected exclusively in alpha-granules, with a characteristic distribution: gold particles were localized at one pole of each labeled granule, outlining the inner face of its membrane. vWF was distributed similarly in the alpha-granules of megakaryocytes at day 12 of culture, where it was also found in small vesicles near the Golgi complex. In contrast, Fg was observed in the whole matrix of all platelet alpha-granules but not in the nucleoids. In platelets from three patients with GPS, vWF and Fg were distributed homogeneously in the rare normal alpha-granules, which could be recognized by their size, and also in small granules identified as abnormal alpha-granules, which were similar in size to the small, possibly immature granules present in normal megakaryocytes. In addition, in some unstimulated platelets, Fg labeling was associated with dense material in the lumen of the surface-connected canalicular system (SCCS). At day 12 of culture, megakaryocytes from the patients with GPS contained some small alpha-granules labeled for Fg and vWF identical to those found in mature platelets. The majority of alpha-granules of normal size appeared partially or completely empty. Thus, we conclude that vWF is distributed differently from Fg in normal alpha-granules, and that unstimulated platelets from patients with GPS contain Fg and vWF in a population of small granules identifiable as abnormal alpha-granules only by immunoelectron microscopy. In addition, the presence of Fg in the SCCS of gray platelets suggests a spontaneous release of the alpha- granule content.
Separation of lymphoid and myeloid blasts in the mixed blast crisis of chronic myelogenous leukemia: no evidence for Ig gene rearrangement in CALLA-positive blasts
Authors: Ha K , Freedman MH , Hrincu A , Petsche D , Poon A , Gelfand EW 
Published: October 2019

Abstract
Recent studies suggest that lymphoid blast crisis cells of chronic myelogenous leukemia (CML) expressing the common acute lymphoblastic leukemia antigen (CALLA) are B precursor cells, based on the demonstration of immunoglobulin (Ig) gene rearrangement similar to common acute lymphocytic leukemia. There is little evidence to suggest whether the cells with similar lymphoid characteristics in the mixed blast crisis of CML are also committed to B cell lineage. A patient in “mixed” blast crisis of CML was studied. On the basis of morphology, cytochemistry, and immunological studies, the blasts were classified as having either lymphoid or myeloid characteristics. A proportion of the leukemic blasts expressed CALLA, whereas others expressed My7 antigen. In order to characterize both populations of cell further, CALLA+ blasts and My7+ (myeloid) blasts were isolated by fluorescence- activated cell sorting. The My7+ cells were highly proliferative in cell culture blast colony assays, retained the Ph1 chromosome, and were indistinguishable from acute myelogenous leukemia blasts. The CALLA+ cells were also Ph1-chromosome positive, but in contrast, were poorly proliferative in vitro. Of particular note was their retention of germline configuration of Ig genes, thus distinguishing them from blasts in the lymphoid crisis of CML. We conclude that the lymphoid component in mixed blast crisis may represent a stage of differentiation prior to commitment to B lineage.
The -158 site 5' to the G gamma gene and G gamma expression
Authors: Labie D , Dunda-Belkhodja O , Rouabhi F , Pagnier J , Ragusa A , Nagel RL 
Published: October 2019

Abstract
To test the hypothesis advanced by Gilman and Huisman that the -158 site 5′ to the G gamma gene determines the G gamma expression after the first 4 months of life, we have examined DNA from sickle cell anemia (SS) patients from Africa and beta-thalassemic homozygotes from Algeria. We find that the Xmnl site is strongly linked to the Senegal haplotype among SS patients, to haplotype IX (most probably identical to the Senegal haplotype), and to haplotype III among the Algerian thalassemics. Thalassemics with haplotypes I/I and V/V have no Xmnl site and low G gamma expression. In contrast, beta-thalassemia- associated haplotype II (also characterized by high G gamma expression) fails to exhibit the Xmnl site. We conclude that, although highly correlated, the -158 C----T substitution does not perfectly predict the presence of high G gamma expression. These findings also exclude the possibility that the Xmnl site is solely involved in the determination of high G gamma expression and suggest that either several different site substitutions in the area 5′ to the gamma gene might have the same effect or that, alternatively, the Xmnl site and its surrounding area is not involved in G gamma expression and may be only in linkage disequilibrium with a controlling sequence elsewhere.
Part of the activating cross-linked immunoglobulin G is internalized by human platelets to sites not accessible for enzymatic digestion
Authors: Spycher MO , Nydegger UE 
Published: October 2019

Abstract
The differential uptake of tritium-labeled immunoglobulin G (IgG) cross- linked with bisdiazonium-benzidine (BDB) (3H-BDB-IgG) by washed, pooled human platelets to sites inaccessible to pronase digestion was tested. Up to 52% of the 3H-BDB-IgG associated with platelets at 37 degrees C resisted pronase treatment, whereas only 23% of the cross-linked IgG associated with platelets at 4 degrees C, or at 37 degrees C but in the presence of deoxyglucose/antimycin A, remained refractory to pronase. This effect was not due to platelet agglutination. Pronase resistance reached a maximum after a 60-minute incubation period at 37 degrees C. With increasing 3H-BDB-IgG input, both the total cross-linked IgG associated with platelets and the fraction resistant to pronase digestion approached saturation at 4 degrees C, but not at 37 degrees C. The proportion of 3H-BDB-IgG bound to platelets at 4 degrees C that was resistant to pronase treatment increased by 13% within five minutes of warming the platelets to 37 degrees C. Pretreatment of platelets with 10 mmol/L acetylsalicylic acid (or 10 mumol/L prostaglandin E1) prior to the addition of 3H-BDB-IgG led to a 74% (95%) inhibition of the 3H-BDB-IgG-induced 14C-serotonin release, but to only a 44% (49%) inhibition of pronase-digestible bound ligand. In contrast, pretreatment with 10 mumol/L cytochalasin B led to a mere 17% reduction of 14C-serotonin release, whereas acquisition of resistance to pronase digestion by the bound 3H-BDB-IgG was inhibited by 90%. Incubation of platelets at 37 degrees C with 3H-BDB-IgG and removal of unbound material prior to the addition of prostaglandin E1 or deoxyglucose/antimycin A had little effect on the susceptibility of platelet-associated 3H-BDB-IgG to pronase, whereas the addition of cytochalasin B to 3H-BDB-IgG-treated platelets resulted in greatly increased susceptibility of the platelet-associated ligand to pronase. Thus, after binding, 3H-BDB-IgG becomes transferred in an energy- dependent process to pronase-resistant cellular sites, most likely to the open canalicular system.