bluuebunny/crossref_metadata_2025_split huggingface dataset:
A variant of erythrocyte membrane skeletal protein band 4.1 associated with hereditary elliptocytosis
Authors: Garbarz M , Dhermy D , Lecomte MC , Feo C , Chaveroche I , Galand C , Bournier O , Bertrand O , Boivin P 
Published: October 2019

Abstract
A family comprising three patients (a mother and two children) with mild hereditary elliptocytosis was studied. Each patient had prominent elliptocytosis, reduced red cell deformability, and normal erythrocyte thermal sensitivity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the erythrocyte membranes in each patient showed decreased levels of band 4.1 (approximately half of the normal value) and the presence of an additional band migrating below protein band 4.2. This additional band was shown to derive from protein 4.1. Comparative partial proteolytic mapping of protein 4.1 and the additional band revealed a number of common peptides. Enzyme-linked immunoelectrotransfer blots of the patients' erythrocyte membranes using a monoclonal antibody to protein 4.1 revealed that, in addition to protein 4.1, two other bands below protein 4.2 were stained; one of these bands migrated in the same position as the additional band detected in the Coomassie Blue-stained gels. Immunoblotting of the patients' whole cells using the antibody to protein 4.1 revealed that this altered band 4.1 occurred as such in the intact red cell. SDS-PAGE of protein 4.1 purified from one patient showed the presence of two lower molecular weight bands below protein 4.1; the lower band migrated in the same position as the additional band found on SDS-PAGE of the patients' erythrocyte membranes. The patient's purified protein 4.1 displayed a decrease of about 40% in the binding activity with crude spectrin extracted from normal controls. Spectrin-spectrin interactions were normal in the three patients. The additional band present in the patients' red cell membranes probably represents a proteolytic degradation product. This alteration, present both in whole cells and isolated membranes, might affect the intact cells in vivo. We suggest that the patients' erythrocyte membrane instability may be related to the presence of an abnormal protein 4.1 whose modulatory influence on the spectrin-actin interaction in the skeleton is defective.
A method for simultaneous study of the karyotype, morphology, and immunologic phenotype of mitotic cells in hematologic malignancies
Authors: Teerenhovi L , Knuutila S , Ekblom M , Rossi L , Borgstrom GH , Tallman JK , Andersson L , de la Chapelle A 
Published: October 2019

Abstract
A major problem in the cytogenetic analysis of hematologic neoplasms has been an inability to identify the cell from which the chromosomes were obtained. We describe a procedure that allows simultaneous analysis of karyotype and cell cytology in mitotic cells. The method differs from conventional cytogenetic analysis in that after mild hypotonic treatment, the cells are cytocentrifuged onto glass slides. In mitotic cells, this procedure often results in adequate spread of the chromosomes within the intact cell membrane. The cytoplasmic structure also remains intact, so that cytologic preparations are of good quality. Morphologic and immunologic identification of mitotic cells can be done using routine hematologic stains, such as Giemsa or Sudan black B, and various antisera using immunofluorescence techniques. The chromosomes can be simultaneously analyzed either without banding on slides stained with Giemsa or with Q-banding on slides stained with immunofluorescence techniques. Identification of numerical and structural karyotype aberrations thus is possible in morphologically identified cells.
Platelet-derived growth factor promotes polymorphonuclear leukocyte activation
Authors: Tzeng DY , Deuel TF , Huang JS , Senior RM , Boxer LA , Baehner RL 
Published: October 2019

Abstract
The platelet-derived growth factor (PDGF) has several well defined important biologic activities. Platelet-derived growth factor is the major mitogen in human serum for cells of mesenchymal origins; it is a potent chemoattractant protein for human monocytes, neutrophils, fibroblasts, and smooth muscle cells; and has been implicated in transformation by simian sarcoma virus and perhaps in transformation by other agents as well. In this article, PDGF has been shown to stimulate activation of human peripheral blood neutrophils defined by loss of membrane associated calcium as reflected by loss of chlortetracycline fluorescence, release of superoxide anion and specific granule enzymes, and enhanced neutrophil adherence and aggregation. These responses occurred in a dose-dependent fashion at concentrations of PDGF between 10 ng/mL (0.4 nmol/L) and 40 ng/mL (1.5 nmol/L) and were comparable to effects obtained with optimal concentrations of fMLP and C5a. Degranulation induced by PDGF was selective for secondary (specific) granules and not primary (azurophil) granules. Platelet-derived growth factor thus is ideally suited for a pivotal role in attracting inflammatory cells locally and initiating neutrophil activation at sites of blood vessel injury. Platelet-derived growth factor or a closely related protein also may play an important role in attracting and activating neutrophils in association with inflammatory tumors.
Stimulation of prostacyclin synthesis in vascular cells by mononuclear cell products
Authors: Dejana E , Breviario F , Balconi G , Rossi V , Remuzzi G , de Gaetano G , Mantovani A 
Published: October 2019

Abstract
Supernatants were obtained from human peripheral blood mononuclear cells stimulated with phytohemagglutinin or in a mixed lymphocyte reaction. The effect of mononuclear cell products on vascular prostacyclin (PGI2) production was measured using cultured rat aortic smooth muscle cells (SMC) or aortic rings. PGI2 was measured by radioimmunoassay of its metabolite, 6-keto-PGF1 alpha. Supernatants containing mononuclear cell products induced PGI2 production in vascular tissue. Supernatant-induced PGI2 production of SMC was relatively slow, requiring more than six hours of incubation with supernatants, and was completely prevented by aspirin, a cyclooxygenase inhibitor. The regulation of arachidonic acid metabolism by products of stimulated mononuclear cells, which is critical to the physiology and pathology of blood vessels, may be an important aspect of the interaction between immunocompetent cells and vascular tissue.
Immunologic selection of hemopoietic precursor cells utilizing antibody- mediated plate binding ("panning")
Authors: Greenberg PL , Baker S , Link M , Minowada J 
Published: October 2019

Abstract
We utilized the property of antibody adherence to plastic to separate and obtain enriched fractions of human myeloid (CFU-GM), erythroid (BFU- E) and pluripotent (CFU-GEMM) hemopoietic precursor cells. Nonadherent buoyant human marrow cells coated with mouse anti-human HLA-DR monoclonal antibody (Mc ab), an anti-pan T lymphocyte Mc ab (Leu 1/17F12) or a granulocyte--monocyte-specific Mc ab (MCS2) were incubated on polystyrene Petri plates coated with affinity purified goat anti-mouse immunoglobulin G (IgG). Cells bound to the coated plates and nonbound cells were separately recovered (“panned”) by differential elution. Analysis of the nonadherent buoyant marrow cells demonstrated 12% to possess HLA-DR, 6% T, 40% MCS2 antigens on their surface by indirect immunofluorescence (IMF). After panning, 15% +/- 8%, 14% +/- 4% and 8% +/- 6% cells were plate-bound by their respective antibodies, demonstrating differing binding efficiencies. A substantial degree of purity of the recovered cell fractions was shown for bound 74% +/- 6% and 75% +/- 5% IMF positive cells) and nonbound cells (3% +/- 1% and 0.1% +/- 0.8% positive cells) coated with anti-HLA-DR or anti-T Mc ab respectively, with lesser purity for MCS2 panned cells. Seventy- three percent to 126% CFU recovery was noted, with a sevenfold enrichment of the HLA-DR bound cells for CFU-GM and CFU-GEMM, and 3.5- fold enrichment for BFU-E. Sequential panning, obtaining T nonbound-DR bound-surface immunoglobulin nonbound fractions, resulted in tenfold CFU-GM enrichment (107/10(4) cells, approximately equal to 1/100). Anti- MCS2 antibody was ineffective for panning, but use of this antibody in fluorescence-activated cell sorting (FACS) indicated the absence of the MCS2 antigen on the vast majority of CFU-GM. This study describes a relatively rapid and inexpensive method for obtaining enriched antigenically defined hemopoietic precursors in high yield. These techniques should prove useful for more clearly evaluating cellular and humoral interactions with hemopoietic precursor cells.
The effect of interleukin 3 and GM-CSA-2 on megakaryocyte and myeloid clonal colony formation
Authors: Quesenberry PJ , Ihle JN , McGrath E 
Published: October 2019

Abstract
Two separate helper T cell-derived lymphokines, interleukin 3 and granulocyte-macrophage colony-stimulating activity-2, were found to stimulate a broad and similar range of hemopoietic colonies in in vitro soft agar cultures including granulocyte, macrophage, granulocyte- macrophage, megakaryocyte, and mixed megakaryocyte colonies. Both lymphokines were potent stimulators of in vitro megakaryocyte colony formation. At plateau levels of IL-3, megakaryocyte colony formation was increased by biologic activity in pokeweed mitogen spleen- conditioned media.
Abnormal megakaryocytopoiesis in the Belgrade laboratory rat
Authors: Rolovic Z , Jovanovic T , Stankovic Z , Marinkovic N 
Published: October 2019

Abstract
The Belgrade laboratory rat (b/b rat) has hereditary, hypochromic, microcytic anemia with a variety of red cell abnormalities. Although this anemic syndrome has been recently ascribed to the defective delivery of iron to the developing red cell, the basic hematopoietic defect is still unknown. In this article we present evidence that the b/b rat has an additional hematologic defect. We have found that the megakaryocyte number in the marrow of the b/b rat is decreased to one half that of the normal rat, but the maturation rate of recognizable megakaryocytes is accelerated and the size is increased. The platelet count is moderately reduced. These findings indicate that megakaryocytopoiesis in the anemic b/b rat is abnormal and suggest that the genetic defect may involve the progenitors of the megakaryocyte cell lineage. Alternatively, the megakaryocytic abnormalities may be secondary to the severe anemia.
Abnormalities in myelopoietic regulatory interactions with acidic isoferritins and lactoferrin in mice infected with Friend virus complex: association with altered expression of Ia antigens on effector and responding cells
Authors: Lu L , Broxmeyer HE , Moore MA , Sheridan AP , Gentile P 
Published: October 2019

Abstract
The regulation of myelopoiesis was evaluated in B6D2F1 mice inoculated with Friend virus complex (spleen focus-forming virus plus helper virus) or helper virus alone by analyzing acidic isoferritin (AIF) and lactoferrin (LF) interactions with target cells. Under normal conditions, AIF suppresses colony and cluster formation by an Ia- antigen-positive cycling subpopulation of mouse granulocyte-macrophage progenitor cells (CFU-GM). Under the same conditions, the release of AIF-inhibitory activity and granulocyte-macrophage colony stimulatory factors (GM-CSF) from an Ia-antigen-positive subpopulation of monocytes and macrophages is suppressed by LF. Within one to two days after inoculation in vivo with Friend virus complex or helper virus, mouse CFU-GM become insensitive in vitro to suppression by purified human AIF as well as crude mouse AIF, and by four days, bone marrow, spleen, and thymus cells of these mice release much greater quantities of AIF- inhibitory activity than the cells from mice injected with control medium. The Friend virus complex itself has no influence in vitro on CFU-GM from normal mice. In addition, the release of AIF-inhibitory activity from bone marrow, spleen, and resident peritoneal cells and the release of GM-CSF from resident peritoneal cells of mice infected with Friend virus complex are not suppressed by LF. The inability of AIF to suppress colony formation by bone marrow and spleen CFU-GM from mice infected with Friend virus complex is associated with the loss of Ia (I-A subregion) antigens from CFU-GM, even though CFU-GM are in cycle. The nonresponsiveness of bone marrow, spleen, and peritoneal cells from these mice to LF suppression of AIF release and the inability of LF to influence GM-CSF release from peritoneal cells is associated with loss of Ia antigens from these cells. The above abnormalities are similar to the defects noted using cells from patients with leukemia. These results suggest that mice infected with Friend virus complex can serve as a model for investigating abnormalities in cell regulation and their relationships to disease progression.
Microrheologic investigation of erythrocyte deformability in diabetes mellitus
Authors: Williamson JR , Gardner RA , Boylan CW , Carroll GL , Chang K , Marvel JS , Gonen B , Kilo C , Tran-Son-Tay R , Sutera SP 
Published: October 2019

Abstract
This study was undertaken to determine whether diabetes alters the viscoelastic properties of erythrocytes. The oldest and youngest 10% fractions of circulating red cells were separated by centrifugation of freshly drawn blood obtained from ten diabetics with disease of one to 20 years' duration and from an equal number of age- and sex-matched control subjects. Cells from each fraction were suspended in phosphate- buffered saline, and their rheologic behavior was examined in a rheoscope. The elongation of cells, the percentage of cells that tank- treaded in response to shear stress, tank-treading frequency, and the rate of recovery of cell shape upon cessation of shear stress were determined in the oldest and youngest 10% of cells for diabetics as well as for controls. All four parameters were virtually identical for diabetics and controls. Additional aliquots of cells were taken for assessment of nonenzymatic glucosylation of hemoglobin and cell membrane protein. The absence of any measurable difference in rheologic behavior of cells from diabetic and control subjects, despite substantial differences in nonenzymatic glucosylation of hemoglobin and cell membrane proteins, suggests that the magnitude of glucosylation observed in these cellular constituents does not alter the viscoelastic properties of the cells. The implication of these observations is that microvascular complications of diabetes are not attributable to altered deformability of red cells.
Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78
Authors: Creutzig U , Ritter J , Riehm H , Langermann HJ , Henze G , Kabisch H , Niethammer D , Jurgens H , Stollmann B , Lasson U 
Published: October 2019

Abstract
One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by maintenance with thioguanine and cytosine arabinoside for two years and additional Adriamycin during the first year. One hundred nineteen (79%) patients achieved a complete remission. Thirteen (9%) children died of early hemorrhages. After a median follow-up time of 36 (12 to 57) months, 47 relapses have occurred, with CNS involvement in seven cases. The life table analysis revealed a probability for overall survival after almost five years of 45% (SD, 4%), for event-free survival 41% (SD, 4%), and for the event- free interval 52% (SD, 5%). Up to now, no relapse was seen after 2 1/2 years. Risk factor analysis showed that early fatal hemorrhages occurred predominantly in children with M5 FAB type and with initial leukocytosis. An initial high WBC count and liver enlargement were unfavorable parameters for achieving remission. No factors could be identified concerning the risk for relapse. These data indicate that the applied treatment strategy is successful in inducing complete remissions in about three fourths of children with AML and also in enhancing considerably the chances for long-term remission.
Prognostic significance of immunoglobulin phenotype in B cell chronic lymphocytic leukemia
Authors: Baldini L , Mozzana R , Cortelezzi A , Neri A , Radaelli F , Cesana B , Maiolo AT , Polli EE 
Published: October 2019

Abstract
Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance. In this series of persons, Binet staging confirmed its usefulness as a prognostic index (P less than .001). With regard to Smlg, they were mu-type in 41 cases (53.9%), mu- type plus delta-type in 29 cases (38.2%), alpha-type in one case, and not detectable in five cases. No correlations were found between clinical stage and immunoglobulin phenotype, although all but one patient in stage C showed mu-type Smlg alone. On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease.
Cleavage of human von Willebrand factor by platelet calcium-activated protease
Authors: Kunicki TJ , Montgomery RR , Schullek J 
Published: October 2019

Abstract
In human platelet lysates prepared by addition of nonionic detergent (Triton X-100) or by sonication, the multimer composition and electrophoretic mobility of platelet von Willebrand factor (vWF) were consistently modified under conditions that would favor activation of the endogenous calcium-activated, sulfhydryl-dependent neutral protease (CAP). By sodium dodecylsulfate-agarose gel electrophoresis, native platelet vWF contained some multimers that were larger than those characteristic of plasma vWF. Modified platelet vWF contained a multimer population equivalent to or smaller than that of plasma vWF plus an additional fast-migrating band. In crossed immunoelectrophoresis (CIE), modified platelet vWF was characterized by a more anodic distribution and the appearance of a distinct, cross- reactive, anodic component previously designated VIIIR:Ag fragment. In the presence of calcium, radiolabeled purified plasma vWF was also degraded by the protease in question, with a decrease in the apparent molecular weight of the reduced monomer from 230,000 to 205,000. The VIIR:Ag fragment isolated from the same degraded plasma vWF by preparative CIE was shown to be composed of an identical mol wt 205,000 subunit. Because cleavage of plasma or platelet vWF was inhibited by prior addition of leupeptin, EDTA, ethylene glycol bis (beta-aminoethyl ether)-N, N, N′, N′-tetraacetic acid (EGTA), or N-ethylmaleimide (agents known to inhibit platelet CAP) but was unaffected by numerous other protease inhibitors, including soybean trypsin inhibitor, benzamidine, hirudin, phenylmethylsulfonyl fluoride, aprotonin, or epsilon-aminocaproic acid (none of which inhibits platelet CAP), we conclude that proteolysis of vWF observed in this study is a direct effect of CAP and is not mediated by way of secondary proteases.
Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes
Authors: First LR , Smith BR , Lipton J , Nathan DG , Parkman R , Rappeport JM 
Published: October 2019

Abstract
Isolated thrombocytopenia after bone marrow transplantation was investigated in 65 fully engrafted patients surviving at least 60 days posttransplant. Twenty-four patients (37%) developed this complication, which occurred most frequently in patients receiving pretransplant preparation with total body irradiation or busulfan. Two distinct thrombocytopenic syndromes were identified: (1) transient thrombocytopenia (nine patients), in which a normal platelet count (greater than 100,000/microL) was initially established by day +40 but then diminished to less than 10,000 to 45,000/microL on day +40 to +70, with subsequent resolution of the thrombocytopenia by day +90; (2) chronic thrombocytopenia (15 patients), in which a platelet count greater than 100,000/microL was not achieved at any time during the first four months posttransplant, despite the simultaneous presence of normal granulocyte and reticulocyte counts. Although the transient syndrome did not adversely affect prognosis, the chronic syndrome carried a high mortality (21% actuarial survival at 1,000 days posttransplant compared with 67% survival for all patients, P less than .01) and had a high association with both severe (grades 3 to 4) acute graft-versus-host disease (GVHD) and chronic GVHD. In three of nine patients with transient thrombocytopenia, a temporal association with trimethoprim-sulfamethoxazole administration was observed, whereas in all other patients, no drug association could be found. Bone marrow biopsies in those patients with drug-associated thrombocytopenia showed decreased numbers of megakaryocytes, whereas biopsies in the remainder of the transiently thrombocytopenic patients demonstrated adequate numbers of platelet precursors, suggesting peripheral platelet destruction or ineffective thrombopoiesis. Biopsies in the chronic thrombocytopenic patients included those with and without adequate numbers of platelet precursors, although the association with chronic GVHD was strongest in patients demonstrating normal numbers of megakaryocytes. We conclude that isolated thrombocytopenia represents a significant complication of bone marrow transplantation, particularly in patients receiving hematopoietic ablative preparatory regimens, and that it is the chronic, not the transient, thrombocytopenic syndrome that is associated with an adverse patient prognosis.
A monoclonal anti-human platelet antibody: a new platelet aggregating substance
Authors: Higashihara M , Maeda H , Shibata Y , Kume S , Ohashi T 
Published: October 2019

Abstract
A monoclonal anti-human platelet antibody, TP82, is described, which caused irreversible aggregation of platelets in association with the release of adenosine triphosphate or [14C] serotonin, and which inhibited ristocetin-induced agglutination. Immunofluorescence assay showed that the antibody binds to platelets, megakaryocytes, and common acute lymphoblastic leukemia cells. The antibody (IgG1) immunoprecipitated a polypeptide of 23,000 daltons with an isoelectric point of about 7.0. The aggregation induced by the purified antibody and/or F(ab')2 fragments occurred in platelet-rich plasma and with washed platelets, but not with formalin-fixed washed platelets. TP82- induced aggregation was completely inhibited by disodium ethylendiaminotetraacetate, diltiazem, W-7, PGE1, and several metabolic inhibitors. At a concentration of apyrase or CP/CPK, which inhibited adenosine 5-diphosphate-induced aggregation. TP82-induced aggregation was only partially affected. Thrombin was not required for the antibody- mediated effects, since two thrombin inhibitors failed to block the reaction. The antibody, at least at a high concentration, induced platelet aggregation by a mechanism almost independent of thromboxane A2 formation, since cyclooxygenase inhibitors had little inhibitory effect on aggregation. TP82 monoclonal antibody is a new platelet- aggregating substance that interacts with a low-molecular-weight binding site on the platelet membrane.