bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti- CD19 immunotoxins
Authors: Uckun FM , Jaszcz W , Ambrus JL , Fauci AS , Gajl-Peczalska K , Song CW , Wick MR , Myers DE , Waddick K , Ledbetter JA 
Published: October 2019

Abstract
Extensive immunologic surface marker analyses and binding competition assays demonstrated that B43 monoclonal antibody (MoAb) is a new member of the CD19 cluster that recognizes the same surface epitope as several other anti-CD19 MoAbs. We used B43 MoAb to test for CD19 expression on neoplastic cells from 340 leukemia and 151 malignant lymphoma patients and on nonneoplastic cells in normal lymphohematopoietic and nonlymphohematopoietic tissues. Our study more than doubles the total number of cases with classified hematologic malignancies that have been examined for CD19 antigen expression. The data presented confirm that CD19 is the most reliable B lineage surface marker and support our view that this B lineage-restricted surface determinant may be an important functional receptor. Our findings provide unique and direct evidence that (a) CD19 is expressed on leukemic B lineage lymphoid progenitor cells freshly obtained from B lineage acute lymphoblastic leukemia patients but not on normal myeloid, erythroid, megakaryocytic, or multilineage bone marrow progenitor cells; (b) ligation of CD19 with B43 MoAb induces sustained increases in [Ca2+]i when crosslinked and inhibits high-molecular weight B cell growth factor (HMW-BCGF)-induced proliferation of activated B cells without affecting their low- molecular weight B cell growth factor (LMW-BCGF) response; therefore CD19 may be a unique signal receptor; (c) HMW-BCGF and LMW-BCGF augment expression of CD19, which suggests that CD19 and BCGF receptors may be under coordinate regulatory control; (d) approximately two million B43 MoAb molecules per cell can be bound to target B lineage lymphoma cells with a Ka of 1.9 x 10(8)/mol/L; (e) CD19 can undergo B43 MoAb-induced internalization; and (f) the opportunity is thus provided for using anti-CD19 MoAb to deliver toxins to B lineage neoplastic cells for more effective treatment of high-risk leukemia/lymphoma patients.
Tumor necrosis factor is the major monocyte product that increases complement receptor expression on mature human neutrophils
Authors: Berger M , Wetzler EM , Wallis RS 
Published: October 2019

Abstract
Interleukin-1 (IL-1) and other monocyte products have several important effects on the systemic response to infection in addition to their roles in lymphocyte stimulation. The present studies were carried out to determine whether products of stimulated monocytes activated circulating neutrophils (PMN) to increase expression of receptors for C3b (CR1) and C3bi (CR3), which are necessary for optimal margination, migration, and phagocytosis. Supernatants of human mononuclear cells that had been stimulated with lipopolysaccharide (LPS) or purified protein derivative (PPD) contained both tumor necrosis factor (TNF) and IL-1 and increased CR1 and CR3 expression on isolated PMNs. Supernatants of unstimulated cultures, media alone, or LPS or PPD alone had little or no effect. Supernatant effects were detectable at 1:3,000 final dilution and appeared to have a characteristic slow time course. These supernatants also caused dose- and time-dependent secretion of PMN granular constituents, but maximal receptor expression was accompanied by secretion of less than 10% of the cells' content of lysozyme and less than 16% of the B12 binding protein. Immunoadsorption studies showed that the supernatant's activity could be removed by anti- TNF but not by anti-IL-1. Recombinant IL-1 had no effect on receptor expression, but recombinant TNF increased CR1 and CR3 expression with kinetics similar to the supernatants. These results thus indicate that TNF is the major monocyte product that increases CR1 and CR3 expression on mature blood neutrophils. This would result in increased margination and phagocytic activity and may be an important systemic effect that would help the host eradicate infection.
An established CD4+ T lymphoma cell line derived from a patient with so- called Lennert's lymphoma: possible roles of cytokines in histopathogenesis
Authors: Shimizu S , Takiguchi T , Sugai S , Matsuoka M , Konda S 
Published: October 2019

Abstract
A T lymphoma cell line, KT-3, was established from the peripheral blood of a patient with so-called Lennert's lymphoma when the patient developed leukemic lymphoma. The KT-3 cells stain positively for alpha- naphthyl acetate esterase, PAS, and acid phosphatase. The surface phenotype is E rosette-positive, CD1-, CD2+, CD3-, CD4+, CD5+, CD8-, CD11-, CD20-, CD25 (anti-Tac)+, OKla-1+, HNK-1-, J-5-, and My9-, and the surface membrane immunoglobulin is negative, which is almost the same phenotype as the leukemic cells studied when the culture was started. Southern blot analysis showed rearrangement in both beta and gamma T cell receptor genes. Although KT-3 cells proliferate spontaneously and form clusters, they cease proliferating when they are cultured at low cell densities. They proliferate vigorously in response to macrophages, macrophage-derived factor, or recombinant interleukin 2 (rIL-2) added to the culture. Furthermore, they secrete interferon- gamma (IFN-gamma) spontaneously, and the secretion is augmented when they are stimulated with macrophage-derived factor. The macrophage- derived factor enhancing KT-3 cell growth is different from IL-1 alpha, IL-1 beta, IL-2, or IFN-gamma. To our knowledge, this is the first tumor cell line established from a patient with Lennert's lymphoma. The results conclusively confirmed that, at the least, Lennert's lymphoma included CD4+ T lymphoma and also suggested that cytokines or factors secreted by T lymphoma cells and epithelioid histiocytes play an important role in the histopathogenesis of Lennert's lymphoma.
Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay
Authors: Declerck PJ , Alessi MC , Verstreken M , Kruithof EK , Juhan-Vague I , Collen D 
Published: October 2019

Abstract
An enzyme-linked immunosorbent assay for plasminogen activator inhibitor-1 (PAI-1) in biologic fluids was developed on the basis of two murine monoclonal antibodies raised against PAI-1 purified from HT- 1080 fibrosarcoma cells. The lower limit of sensitivity of the assay in plasma is 2 ng/mL. The assay is 12 times less sensitive toward the PAI- 1/human tissue-type plasminogen activator (t-PA) complex as compared with free PAI-1. The intraassay, interassay, and interdilution coefficients of variation are 5.2%, 8.0%, and 7.1%, respectively. The level of PAI-1 in platelet-poor plasma of healthy subjects is 18 +/- 10 ng/mL (mean +/- SD, n = 45). In platelet-rich plasma after freezing and thawing, 92% of PAI-1 antigen is released from platelets, whereas only 8% is found in the corresponding platelet-poor plasma. In platelet-poor plasma from healthy subjects, a linear correlation (r = 0.80) was found between PAI activity and PAI-1 antigen. In plasma approximately two thirds of the PAI-1 antigen was functionally active, whereas only 5% of the PAI-1 antigen released from platelets was active. During pregnancy a progressive increase of PAI-1 antigen levels up to three- to sixfold the control value was observed. In plasma of patients with recurrent deep vein thrombosis, PAI-1 levels were 44 +/- 20 ng/mL (mean +/- SD, n = 7), during a clinically silent phase. Four of these patients had a level above 38 ng/mL (mean +/- 2 SD of normal). The present assay, based on stable and reproducible reagents, allows the specific determination of PAI-1 antigen in biologic fluids. It may facilitate interlaboratory comparisons and be useful for further investigations of the role of PAI-1 in clinical conditions associated with impaired fibrinolysis and/or a tendency to thrombosis and investigations of the role of PAI-1 in platelets.
Site-selective cAMP analogs at micromolar concentrations induce growth arrest and differentiation of acute promyelocytic, chronic myelocytic, and acute lymphocytic human leukemia cell lines
Authors: Tortora G , Tagliaferri P , Clair T , Colamonici O , Neckers LM , Robins RK , Cho- Chung YS 
Published: October 2019

Abstract
Cyclic AMP (cAMP)-dependent protein kinase may play a role in the functional and morphological differentiation of leukemic cells. In this study, we showed that the cAMP analogs, potent activators of protein kinase recently shown to be selective for either site 1 or site 2 cAMP binding sites of protein kinase, demonstrate potent growth inhibition of acute promyelocytic, chronic myelocytic, and acute lymphocytic leukemic cell lines with no sign of toxicity. The growth inhibition accompanied monocytic differentiation in HL-60 cells and a loss of nuclear terminal deoxynucleotidyl transferase activity in Molt-4 leukemic cells. The growth inhibition also paralleled a decrease in c- myc protein and RI cAMP receptor protein. Thus, cAMP analogs selective for either site 1 or site 2 of the protein kinase appear to restore a coupling of proliferation and maturation in leukemic cells.
HL-60 cell line was derived from a patient with FAB-M2 and not FAB-M3
Authors: Dalton WT Jr , Ahearn MJ , McCredie KB , Freireich EJ , Stass SA , Trujillo JM 
Published: October 2019

Abstract
The leukemia from which the human cell line HL-60 was derived was classified in 1976 as acute progranulocytic leukemia (APL), although it was recognized to show a number of atypical features. In the ensuing 10 years, the concept of APL and its integral association with t(15;17) has evolved, and the concept of APL as a morphologically recognizable entity has become embodied in the term French-American-British classification M3 (FAB-M3). It is now recognized that not every case of leukemia with a high proportion of progranulocytes can be classified as FAB-M3. We reviewed the light and ultrastructural morphology of the original diagnostic material from this case, and we report that the leukemia from which HL-60 was derived does not conform to the currently recognized entity of FAB-M3 and is more appropriately classified as an acute myeloblastic leukemia with maturation, FAB-M2.
Alteration and abnormal expression of the c-myc oncogene in human multiple myeloma
Authors: Selvanayagam P , Blick M , Narni F , van Tuinen P , Ledbetter DH , Alexanian R , Saunders GF , Barlogie B 
Published: October 2019

Abstract
Structural alterations of the c-myc oncogene in human Burkitt's lymphoma and mouse plasmacytoma suggest that this oncogene is involved in several B cell neoplasms. The possibility of c-myc alterations in human myeloma has not been explored, probably because the low proliferative activity characteristic of this tumor impairs the propagation of representative cell lines for the performance of adequate cytogenetic studies. This report describes alterations in the c-myc locus with concomitant elevated expression of mRNA in the tumor cells of two of 37 patients with multiple myeloma. In one case, somatic cell hybrid studies revealed that the cloned rearranged DNA was entirely derived from chromosome 8, thus indicating a novel mechanism of c-myc activation different from that in Burkitt's lymphoma. Seven other patients exhibited five- to 12-fold overexpression of c-myc RNA when compared with normal marrow cells. Elevated mRNA expression in about one fourth of our patients suggests that the c-myc oncogene has a pathogenetic role in the evolution of multiple myeloma.
The effect of deoxygenation rate on the formation of irreversibly sickled cells
Authors: Horiuchi K , Ballas SK , Asakura T 
Published: October 2019

Abstract
The effects of the deoxygenation rate on the formation of irreversibly sickled cells (ISCs) were investigated by using metabolically replete sickle cells (SS cells). We found that the formation of ISCs required Ca2+ and that the amount formed depended on the rate of deoxygenation. When less dense SS discocytes were deoxygenated slowly by flushing with 95% N2 and 5% CO2 at a rate of 3 mL/min, the percentage of ISCs increased from 5% to 26.5% after 24 hours. In contrast, upon rapid deoxygenation (10, 35 mL/min) ISC formation was reduced significantly. The difference may be related to fact that more sickle-shaped cells were formed upon slow deoxygenation than upon the rapid deoxygenation that resulted in the formation of star-shaped and granulated cells. So- called ISCs were formed more easily from sickle-shaped cells. To express the shape of sickled cells numerically, we calculated the mean maximum cell length (MCL) after cells were incubated under various deoxygenation conditions. The MCL of slowly deoxygenated SS cells after 24 hours of incubation was about twice (20.0 +/- 7.0 micron) that of quickly deoxygenated (35 mL/min) SS cells (12.5 +/- 5.0 microns) (initial MCL, 8.0 +/- 1.0 micron). The decrease in potassium content was greater with slow deoxygenation than with rapid deoxygenation. Because the increase in sodium influx was less than that of potassium efflux under slow deoxygenation, SS cells became more dense than those rapidly deoxygenated. In the absence of Ca2+, morphological changes were the same as in the presence of Ca2+; however, under this condition there was no change in density, and no ISCs were formed regardless of the rate of deoxygenation. These results demonstrate that the number of ISCs formed correlates with the MCL. The length of fibers of sickle hemoglobin may be a determinant of the length of sickled cells. This suggests that membrane stretching plays an important role in cell density and irreversible membrane deformation.
von Willebrand disease "Vicenza" with larger-than-normal (supranormal) von Willebrand factor multimers
Authors: Mannucci PM , Lombardi R , Castaman G , Dent JA , Lattuada A , Rodeghiero F , Zimmerman TS 
Published: October 2019

Abstract
When normal volunteers or patients with type I von Willebrand disease (VWD) are given desmopressin (DDAVP), a set of larger-than-normal (supranormal) von Willebrand factor (VWF) multimers, similar to those present in VWF-containing cells such as platelets megakaryocytes and endothelial cells, appear transiently in postinfusion plasma. In two kindreds with mild lifelong bleeding symptoms transmitted as an autosomal dominant trait, all ten symptomatic members (but none of the five asymptomatic members) had a supranormal multimeric structure for plasma VWF, apparently identical to that seen for postdesmopressin normal plasma. Plasma factor VIII coagulant activity (VIII:C), VWF antigen (VWF:Ag), ristocetin-induced platelet agglutination, and ristocetin cofactor (RiCof) activity were low. Platelet VWF:Ag and RiCof levels (tested for three patients only) were normal. Bleeding times were normal or slightly prolonged. The patients' platelet multimeric structure was the same as that for normal platelets. After desmopressin infusion the plasma VWF multimeric structure remained supranormal as for preinfusion plasma, with VIII:C VWF:Ag and RiCof increasing markedly over baseline values and disappearing at a normal rate. Examination of the VWF subunit composition from three of these patients indicated that proteolytic processing of their VWF did not differ from normal. This study describes the first variant of VWD with a supranormal multimeric structure.
Human mast cells synthesize new granules during recovery from degranulation. In vitro studies with mast cells purified from human lungs
Authors: Dvorak AM , Schleimer RP , Lichtenstein LM 
Published: October 2019

Abstract
Secretory cells undergoing release and recovery events related to constitutive and/or stimulus-initiated secretion might be expected to undergo distinctive changes in morphology as well. We studied the release and recovery events of human mast cell secretion stimulated by antibody to immunoglobulin E. We used enzymatically digested mast cells from human lung specimens further purified by countercurrent centrifugation elutriation. Release kinetics were like those reported for isolated human lung mast cells. In two complete kinetic experiments we restudied these early release patterns (0 to 30 minutes). Mast cells, either stimulated or controls, were then cultured and sampled for electronmicroscopic studies at periodic intervals (3 to 48 hours). We describe events of the late recovery period here, although some overlap with processes seen in early recovery samples occurred. Mast cells that released nearly all their cytoplasmic granules and exteriorized the containers, eg, granule-channel membranes, underwent progressive enlargement of Golgi structures and development of numerous small cytoplasmic vesicles and small, membrane-bound granules filled with particulate and dense content. Ultimately, new mature cytoplasmic granules of all substructural patterns occurred. Nuclear blast changes and expansion of cytoplasmic mass accompanied this period of new granule synthesis. Mixed recovery patterns were present in individual cells. These represented the morphological expression of a variety of recovery events. Thus, some cells showed a combination of channel recovery and remodeling to form new granule containers within which condensation of content produced crystalline patterns, as well as synthesis of new granules, as described here. This morphological versatility resulted in multiple mast cell morphological phenotypes during these release and recovery processes.
Restriction of cell lysis by homologous complement: II. Protection of erythrocytes against lysis by newly activated complement
Authors: Houle JJ , Hoffmann EM , Esser AF 
Published: October 2019

Abstract
Our previous work revealed that homologous complement (C) was ineffective in lysing antibody-sensitized erythrocytes (EA) even at high concentrations. It was also shown that activation of complement on homologous EA resulted in the binding of C9 and the formation of EA bearing complement proteins C1 through C9 (EAC1–9), yet few hemolytic sites were formed. Instead, as shown here, the formation of homologous EAC1–9 caused the cells to become resistant to lysis even by heterologous complement during a second incubation. In contrast, when homologous EAC1–8 were produced by incubating EA with C9-depleted serum, such intermediates were not protected against lysis by heterologous complement during a second incubation. Furthermore, homologous C9 on EAC1–9 was able to reduce the hemolytic efficiency of heterologous complement without blocking C activation and the formation of new C5b-9 complexes. Protection was not modified when homologous EAC1–9 were produced in one step, by incubation of EA with serum, or sequentially by adding C9 to EAC1–8. The minimum number of 9-sites required to confer a protective effect on EAC1–9 was less than 200 per cell. Thus, in addition to its known effect in heterologous cell killing, homologous C9 is capable of protecting homologous cells against inadvertent complement lysis.
Platelet-agglutinating protein P37 from a thrombotic thrombocytopenic purpura plasma forms a complex with human immunoglobulin G
Authors: Siddiqui FA , Lian EC 
Published: October 2019

Abstract
We have previously reported the purification of a 37-kd platelet- agglutinating protein (PAP p37) from the plasma of a patient with thrombotic thrombocytopenic purpura (TTP) that was shown to be present in a subset of TTP patients. The platelet agglutination induced by PAP p37 has been shown to be inhibited by IgG from normal human adults and the same TTP patient after recovery. To elucidate the mechanism of inhibition of IgG, the interaction between PAP p37 and IgG was studied. The complex formation was demonstrated by the binding of fluid-phase IgG from normal adults and the same TTP patient after recovery to adsorbed PAP by using an enzyme-linked immunosorbent assay. The binding was specific, concentration dependent, and saturable. IgG purified from a 5-month-old baby and the same TTP patient during active disease did not form complex with PAP p37. The IgG covalently cross-linked to Sepharose 4B bound 125I-PAP p37 but not 125I-fibrinogen. Sucrose density gradient ultracentrifugation of a mixture of 125I-PAP p37 and IgG also revealed the fluid-phase complex formation with a sedimentation value of 19S. Complexes of molecular weight ranging from 180,000 to over 350,000 daltons were also detected by molecular sieve chromatography. The IgG that was bound to PAP p37 conjugated to Sepharose 4B inhibited the agglutination of washed platelets induced by TTP plasma containing PAP p37, whereas the IgG that was not bound to PAP p37 did not have a significant inhibitory effect. The complex formation between PAP p37 and specific IgG is likely to account for the in vitro inhibition of TTP plasma-induced agglutination and, at least partly, the in vivo successful treatment with specific IgG-containing normal plasma.
Natural history of idiopathic refractory sideroblastic anemia
Authors: Cazzola M , Barosi G , Gobbi PG , Invernizzi R , Riccardi A , Ascari E 
Published: October 2019

Abstract
We analyzed the natural history of idiopathic refractory sideroblastic anemia (IRSA) in 37 patients studied between 1969 and 1986. Although erythroid abnormalities were prominent in all, 12 patients also showed involvement of the granulocytic and/or megakaryocytic cell lines, and nonrandom chromosomal aberrations were observed in five of 23 patients studied for such defects. Measurements of erythroid marrow function showed in most cases erythroid expansion with ineffective erythropoiesis. In seven patients, however, the erythroid activity was found to be inappropriately low for the degree of anemia. Transfusion dependence occurred in 26 of 37 cases. Iron overload was a common feature at presentation but produced clinical manifestations of hemochromatosis only in those patients who subsequently had a regular need for blood transfusions. Five patients progressed to bone marrow failure, and another five patients (two of whom had monosomy 7) evolved into acute nonlymphocytic leukemia (ANLL). The median survival was 72 months, with a high transfusion requirement, multilineage defects, and inappropriately low erythroid proliferation being associated with a poor prognosis. The most common causes of death were complications of iron overload and evolution into ANLL. We conclude that (a) the natural history of IRSA is characterized by an initial phase of erythroid hyperplasia and ineffective erythropoiesis, which is usually stable for many years but in a subset of patients may be followed by a phase of marrow failure with or without the later emergence of leukemic blasts; (b) peripheral blood counts, measurement of erythroid marrow function, and chromosomal analysis are useful for identifying subjects at risk of evolution into marrow failure or ANLL; and (c) IRSA patients with no need for blood transfusions are very likely to be long survivors, whereas those who become transfusion dependent are at risk of death from the complications of secondary hemochromatosis.