bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic relevance of cellular morphology in multiple myeloma
Authors: Fritz E , Ludwig H , Kundi M 
Published: October 2019

Abstract
Morphological characteristics of tumor cells have been employed in the prognosis of lymphomas and solid tumors. This report documents an attempt to predict survival from the known cytologic heterogeneity in multiple myeloma. Myeloma cells in bone marrow smears from patients at diagnosis were evaluated by assigning them to morphologically defined categories. Cox's multivariate regression model for censored survival data was used to generate optimal weights, which served as coefficients in two regression equations to estimate death risk from cellular morphology. Step-wise procedures excluded redundant parameters. “Myeloma morphology score” (MMS) discriminates significantly (p less than 0.0001) among 3 stages, with median survival times of 42.5, 30.7, and 9.1 mo. For clinical routine application, “myeloma progression scorex201D; (MPS), the weight sum of the proportion of plasmablasts and the extent of bone marrow plasma cell infiltration, is suggested as a simple prognostic tool. Its discriminative power is very high [p less than 10(-9)]. Median survival times of greater than 71.5, 23.4, and 6.1 mo were found for good, moderate, and poor risk groups, respectively. However, staging is not confined to three subgroups, grouping is flexible, and pairs of data can be matched. This fact may prove to be valuable in designing prognosis-controlled clinical trials or theoretical studies on cellular differentiation. Preliminary results suggest changes in morphology due to disease progression and/or the effect of therapy on tumor kinetics. Most importantly, staging according to MPS or MMS may facilitate the adaption of therapy to the current state of the disease in patients with multiple myeloma.
Rigid membranes of Malayan ovalocytes: a likely genetic barrier against malaria
Authors: Mohandas N , Lie-Injo LE , Friedman M , Mak JW 
Published: October 2019

Abstract
A high frequency of nonhemolytic hereditary ovalocytosis in Malayan aborigines is thought to result from reduced susceptibility of affected individuals to malaria. Indeed, Kidson et al. recently showed that ovalocytes from Melanesians in Papua New Guinea are resistant to infection in culture by the malarial parasite Plasmodium falciparum. In order to determine if protection against parasitic invasion in these ovalocytes might be the result of some altered membrane material property in these unusual cells, we measured their membrane and cellular deformability characteristics using an ektacytometer . Ovalocytic red cells were found to be much less deformable in comparison to normal discoid red cells. Similar measurements on isolated membrane preparations revealed a marked reduction in ovalocytic membrane deformability. To produce equal deformation of ovalocytic and normal membranes, ovalocytes required an 8–10-fold increase in applied shear stress, indicating that their membrane was capable of deforming under sufficient stress. To test the possibility that this increased membrane rigidity might confer resistance to parasitic invasion, we performed an in vitro invasion assay using Plasmodium falciparum merozoites and Malayan ovalocytes of varying deformability from seven different donors. The level of infection of the ovalocytes ranged from 1% to 35% of that in control cells, and the extent of inhibition appeared to be closely related to the reduction in membrane deformability. Moreover, we were able to induce similar resistance to parasitic invasion in nonovalocytic normal red cells by increasing their membrane rigidity with graded exposure to a protein crosslinking agent. Our findings suggest that resistance to parasite invasion of Malayan ovalocytes is the result of a genetic mutation that causes increased membrane rigidity.
Identification of the hereditary pyropoikilocytosis carrier state
Authors: Mentzer WC , Turetsky T , Mohandas N , Schrier S , Wu CS , Koenig H 
Published: October 2019

Abstract
We evaluated the hematologic, rheologic, and biochemical features of erythrocytes obtained from 10 relatives of a 5-yr-old black female with hereditary pyropoikilocytosis (HPP) and severe hemolytic anemia. Erythrocyte morphology was normal in the father and five other relatives, but ghost mechanical fragility and drug-induced red cell endocytosis were increased, as was the percentage of spectrin dimers noted on 3.2% nondenaturing PAGE of spectrin extracts. Identical changes were also noted in the mother and her sister, whose erythrocytes were elliptocytic and exhibited morphological changes upon heating to 45 degrees-48 degrees C (normal 49 degrees). The two other family members were normal in every respect. SDS-PAGE analysis of membrane proteins demonstrated diminished amounts of spectrin in HPP erythrocytes, but was normal in other family members. A diffuse band (mol wt 575,000–665,000), composed entirely of spectrin, was apparent adjacent to the dimer region on nondenaturing PAGE of spectrin extracts from the propositus, mother, and aunt. In this family, HPP appears to have resulted from compound heterozygosity for two distinct genetic abnormalities (reflected by the differences between elliptocytic and nonelliptocytic carriers). Although the membrane abnormalities in carriers did not result in hemolytic anemia, they were of sufficient magnitude to allow the detection of the carrier state.
Synthesis of coagulation factor V by cultured aortic endothelium
Authors: Cerveny TJ , Fass DN , Mann KG 
Published: October 2019

Abstract
Bovine aortic endothelium has been examined with respect to the synthesis of coagulation factor V. After cultured cells reached confluency, samples of supernatant culture media and solubilized cells were analyzed for factor V in a two-stage bioassay and in a double- antibody radioimmunoassay. In addition, preconfluent cells were pulsed for 4 days with 35S-methionine in methionine-free media. After the 4- day pulse, supernatant media were chromatographed on a factor V monoclonal antibody-Sepharose resin to isolate 35S-labeled factor V. The isolated material and 125I-factor V standards were analyzed by electrophoresis and autoradiography. The bioassay indicated an increase, with time, of unactivated factor V in the culture supernatant, whereas solubilized cells were negative for factor V. The radioimmunoassay indicated an increase, with time, of factor V antigen in the culture supernatants, and the solubilized cells yielded a constant level of antigen per cell. Autoradiograms of electrophoretograms of immunoadsorbed 35S-culture supernatant with 125I- factor V/Va standards revealed labeled proteins with electrophoretic mobilities compatible with 125I-factor V/Va standards. The data obtained from three different sources-bioassay, radioimmunoassay, and 35S-methionine incorporation-all indicate that factor V is synthesized by cultured bovine aortic endothelium.
Characterization of the effect of influenza virus on polymorphonuclear leukocyte membrane responses
Authors: Abramson JS , Parce JW , Lewis JC , Lyles DS , Mills EL , Nelson RD , Bass DA 
Published: October 2019

Abstract
Depressed chemotactic activity of polymorphonuclear leukocytes (PMNL) infected with influenza virus could be due to changes occurring at the plasma membrane. The present study examined the effect of unopsonized influenza virus on chemotaxis, adherence, receptor binding, shape change, membrane fluidity, and release of specific granules from PMNL. Chemotactic activity of PMNL under-agarose to the chemoattractants, zymosan-activated serum ( ZAS ) and N-formyl-methionyl-leucyl- phenylalanine (fMLP), and adherence of PMNL to a plastic surface were markedly decreased in virus-treated cells as compared to control cells. The binding of fMLP to the PMNL was increased in virus-treated cells compared with control cells. Exposure of cells to virus, ZAS , or fMLP caused 35%-50% of the cells to become bipolar in shape, whereas less than 5% of the cells exposed to buffer became bipolar. Influenza virus did not alter membrane fluidity as measured by electron spin resonance spectroscopy with the probe 5-doxyl stearate. Virus-treated PMNL stimulated with FMLP or Staphylococcus aureus exhibited a marked decrease in the amount of lactoferrin released into phagosomes, onto the cells' outer membrane, and into the extracellular medium as compared to control cells. The possible relationship between inhibition of lysosomal enzyme degranulation and decreased chemotactic activity and adherence of PMNL is discussed.
A cell line secreting stimulating factors for CFU-GEMM culture
Authors: Myers CD , Katz FE , Joshi G , Millar JL 
Published: October 2019

Abstract
The multipotent hemopoietic stem cell has fastidious growth requirements in vitro. Traditionally, phytohemagglutinin-stimulated leukocyte conditioned medium has been used to supply the undefined growth factors required for culture of the human multipotent hemopoietic progenitor. We describe the use of medium conditioned by the bladder carcinoma cell line, 5637, to replace PHA-LCM in CFU-GEMM cultures and show that the properties of this conditioned medium closely mimic those of PHA-LCM in two separate CFU-GEMM culture systems.
APO therapy for malignant lymphoma of large cell "histiocytic" type of childhood: analysis of treatment results for 29 patients
Authors: Weinstein HJ , Lack EE , Cassady JR 
Published: October 2019

Abstract
Twenty-nine patients with biopsy-proven malignant lymphoma of large- cell “histiocytic” type were treated with the APO protocol (vincristine, adriamycin, and prednisone). Treatment consisted of two years of therapy with a modified adriamycin-containing acute lymphoblastic leukemia regimen with preventive cranial irradiation and regional radiotherapy (for patients with clinically localized lymphoma). The median age was 13 years (range, two to 20 years). Thirteen patients had localized disease (stage I, II), and 16 had disseminated disease (stage III, IV). The median follow-up is four years (range, seven months to nine years), and Kaplan-Meier estimates of overall and relapse-free survival are 83% and 76%, respectively. No recurrences have been observed in primary or bulk sites of lymphoma in the group of children treated with chemotherapy only. We conclude that the APO protocol, which was modeled after an acute lymphoblastic leukemia regimen, combined with regional radiotherapy can produce long- term remissions for children with malignant lymphoma of large cell “histiocytic” type.
Two independent genetic factors in the beta-globin gene cluster are associated with high G gamma-levels in the HbF of SS patients
Authors: Gilman JG , Huisman TH 
Published: October 2019

Abstract
The gamma-chains of fetal hemoglobin (HbF) of newborn babies are composed of about 70% G gamma and 30% A gamma. In most babies, the G gamma value declines postnatally to 40%, but in about 20% of black SS patients from Georgia, 5 years and older, the G gamma level remains high at 60%. Moreover, some 3% to 4% of black newborns have high G gamma values of 85%. PstI digestion of DNA of one such high G gamma baby and of one normal newborn showed the former to be heterozygous for the -G gamma-G gamma- and -G gamma-A gamma-chromosomes. Only about one fourth of high G gamma SS patients were such heterozygotes, while three fourths were -G gamma-A gamma-/-G gamma-A gamma-homozygotes. Analysis of DNA of 38 SS patients without the -G gamma-G gamma-chromosome showed a correlation of G gamma values with genotype at one polymorphic restriction site: at the HincII site in the psi beta gene, all -G gamma- A gamma-/-G gamma-A gamma-homozygotes with high G gamma were +/- or +/+, while low G gamma individuals were all -/-. Family studies, involving analyses at four polymorphic sites (HindIII sites in the G gamma and A gamma genes and HincII sites in the psi beta gene and 3′ to it), suggested the association of an unidentified high G gamma genetic determinant with haplotype + - + +. This indicates that a genetic factor causing high G gamma levels in SS patients is closely linked to the -G gamma-A gamma-psi beta region of the beta-globin gene cluster.
Acquired immune hemolytic anemia associated with IgA erythrocyte coating: investigation of hemolytic mechanisms
Authors: Clark DA , Dessypris EN , Jenkins DE Jr , Krantz SB 
Published: October 2019

Abstract
We have investigated the hemolytic mechanisms in a patient with acquired immune hemolytic anemia whose red cells appeared to be coated with IgA alone. The clinical course was similar to that of patients with hemolytic anemia mediated by warm-reacting IgG antibody. Splenic sequestration of red cells was demonstrated, and marked reduction of hemolysis occurred after corticosteroid therapy. Antibody was eluted from the patient's red cells and used to sensitize normal red cells in vitro. These sensitized red cells were not lysed by fresh autologous serum, nor did they fix detectable amounts of C3. However, red cells sensitized by eluted antibody were lysed by normal human peripheral blood monocytes in a system designed to demonstrate antibody-dependent cell-mediated cytotoxicity. Monocyte-mediated hemolysis of sensitized red cells was inhibited by the addition of low concentrations of normal serum IgA to the system, but not by IgG. The ability of the eluate to induce monocyte-mediated hemolysis was abolished by its adsorption on Sepharose-bound anti-IgA, but not by preincubation with Sepharose-bound anti-IgG. In addition, normal human monocytes were demonstrated to ingest eluate-sensitized red cells. These data demonstrate an in vitro interaction of IgA-sensitized red cells with leukocytes and suggest a possible mechanism for the patient's hemolysis.
Immunochemical characterization of the platelet-specific alloantigen Leka: a comparative study with the PlA1 alloantigen
Authors: Kieffer N , Boizard B , Didry D , Wautier JL , Nurden AT 
Published: October 2019

Abstract
We report the immunochemical characterization of a new platelet- specific alloantigen detected using an IgG antibody isolated from the serum of a patient with posttransfusion purpura (PTP). In indirect immunoprecipitation experiments, the antibody, termed anti-Leka, predominantly precipitated glycoprotein (GP) IIb from Triton X-100 lysates of normal human platelets. In an immunoblot procedure, which involved the transfer of platelet polypeptides separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to nitrocellulose membrane, anti-Leka bound exclusively to GP IIb. Under identical conditions, four anti-PlA1 antibodies each reacted with GP IIIa. No binding of anti-Leka IgG occurred to Leka (-) platelets or to their separated polypeptides although GP IIb was normally detected by Coomassie blue staining. After electrophoresis of reduced platelet proteins, the Leka determinant was localized to the IIb alpha chain. Thus, unlike the PlA1 antigen, the Leka determinant was not destroyed by disulfide reduction. Analysis of platelets from a patient with Glanzmann's thrombasthenia revealed little or no binding in the GP IIb position. Anti-Leka permitted the identification of 76,000 and 60,000 dalton fragments of GP IIb retained by the platelet following chymotrypsin treatment. Our results further highlight the immunogenicity of the GP IIb-IIIa complex. They also suggest that antibodies against GP IIb can cause the thrombocytopenia observed in PTP and that anti-PlA1 antibodies do not account exclusively for the pathophysiology of this immune disorder.
Identification of platelet proteins that bind alloantibodies and autoantibodies
Authors: Devine DV , Rosse WF 
Published: October 2019

Abstract
We have used the techniques of radioimmunoprecipitation (RIP) and Western blot to identify the membrane proteins that bind certain alloantibodies. Anti-PlA1 sera precipitated two bands, corresponding to platelet glycoproteins IIb and III, whether or not calcium was present during the procedure. By Western blot, this antibody bound only glycoprotein III. Anti-PlA1 serum does not precipitate proteins from the platelets of a patient with Glanzmann's thrombasthenia. Two monoclonal antibodies reacting with lymphocyte HLA antigens, as well as sera from highly allosensitized patients, precipitated bands of 38,500 and 13,500 daltons. These bands correspond to the molecular weights of the two subunits of the HLA antigen, as it has been described for other cell types. The patients' sera also precipitated a protein of 72,000 daltons from some platelets. The sera of two patients with quinidine- induced thrombocytopenia precipitated a 138,000-dalton band (glycoprotein Ib-alpha) in the presence of quinidine. The purified IgG antibody from one patient did not require other plasma factors to bind to platelets in the presence of quinidine, while purified antibody from a second patient required plasma factors other than, or in addition to von Willebrand factor. Although several sera from patients with idiopathic thrombocytopenic purpura (ITP) were tested, only one precipitated membrane proteins by the RIP method; this serum identified binding proteins corresponding to glycoproteins IIb and III.
Plasma protein S deficiency in familial thrombotic disease
Authors: Schwarz HP , Fischer M , Hopmeier P , Batard MA , Griffin JH 
Published: October 2019

Abstract
A family with a history of severe recurrent venous thromboembolic disease was studied to determine if a plasma protein deficiency could account for observed disease. Protein S levels in plasma were determined immunologically using the Laurell rocket technique. The propositus, his mother, his aunt, and his cousin who were clinically affected had 17% to 65% of the control levels of protein S antigen (normal range, 71% to 147%). Since three of these patients were receiving oral anticoagulant therapy, the ratios of protein S to prothrombin, factor X, and protein C in these patients were compared with values for a group of orally anticoagulated controls. These results suggested that protein S is half-normal in all family members with thrombotic disease. Other proteins known to be associated with familial thrombotic disease, including antithrombin III, plasminogen, fibrinogen, and protein C, were normal. Because plasma protein S serves as a cofactor for the anticoagulant activity of activated protein C and because protein C deficiency is associated with recurrent thrombotic disease, it is suggested that recurrent thrombotic disease in this family is the result of an inherited deficiency of protein S.
Chemistry of a human monocyte-derived cell line (U937): identification of the angiotensin I-converting activity as leukocyte cathepsin G
Authors: Snyder RA , Kaempfer CE , Wintroub BU 
Published: October 2019

Abstract
Angiotensin-converting enzyme, a dipeptidyl carboxypeptidase, catalyzes the conversion of angiotensin I to the vasoactive peptide angiotensin II. The finding of angiotensin-converting enzyme in dexamethasone- stimulated cultured monocytes and alveolar macrophages prompted the examination of a human monocyte-like cell line (U937) for angiotensin I- converting activity. Conversion of angiotensin I (5 X 10(-5) mol/L) to angiotensin II by U937 cell extracts (10(4) - 4 X 10(6) cells) was detected, and the pH optimum for the reaction was 7.0 to 8.0. The U937 cell angiotensin I-converting activity was purified to homogeneity by carboxymethylcellulose chromatography and trasylol affinity chromatography. The purified protein performed similarly to purified human neutrophil cathepsin G on sodium dodecyl sulfate-gradient polyacrylamide gel electrophoresis (SDS-gradient PAGE), elicited a reaction of complete identity with neutrophil cathepsin G when diffused against anti-cathepsin G antiserum, and had quantitatively similar angiotensin I-converting activity as neutrophil cathepsin G. Neutrophils and U937 cells had 143 and 52 times greater angiotensin I- converting capability than cultured monocytes or peripheral blood mononuclear cells, suggesting the relative importance of mobile cells containing cathepsin G in the local generation of angiotensin II. These data identify the angiotensin I-converting activity of the U937 cell as leukocyte cathepsin G and provide evidence that the U937 cell has neutrophil-like as well as monocyte-like characteristics.
Ultrastructural localization of lactoferrin and myeloperoxidase in human neutrophils by immunogold
Authors: Cramer E , Pryzwansky KB , Villeval JL , Testa U , Breton-Gorius J 
Published: October 2019

Abstract
Colloidal gold was used as a marker for immunoelectron microscopy to localize lactoferrin (LF) and myeloperoxidase (MPO) in human peripheral blood neutrophils. Cells were reacted with monospecific antibodies against LF or MPO and then with gold-labeled antiglobulin. MPO cytochemistry was also associated with immunologic detection of LF. Immunologic labeling of thin sections after embedding in glycol methacrylate gave good ultrastructural morphology and specific localization of both proteins. MPO was detected in the large azurophil granules, whereas LF was consistently localized in the matrix of another population of morphologically distinct granules, smaller and more numerous than azurophil granules. When cytochemical detection of MPO was coupled with immunologic detection of LF, LF was observed in the population of MPO-negative granules, which were identified as specific. This was confirmed on cells that were permeabilized with saponin and stained for LF and MPO before embedding. No other neutrophil organelles displayed labeling for LF; other blood cells also were unreactive for LF. In the bone marrow, myeloblast and promyelocyte granulations were not stained and LF-containing granules appeared at the myelocyte stage. In conclusion, we confirm previous biochemical and light microscopic studies by ultrastructural demonstration of LF and MPO in two categories of granules, the specific and azurophil granules, respectively. The method described in this article avoids disruption caused by cell fractionation procedures. In the future, other intragranular proteins can be localized by a similar approach.
Plasmodium falciparum in vitro: diminished growth in hemoglobin H disease erythrocytes
Authors: Ifediba TC , Stern A , Ibrahim A , Rieder RF 
Published: October 2019

Abstract
Studies of the ability of Plasmodium falciparum to grow in vitro in the red blood cells of subjects with certain beta-thalassemia syndromes are often difficult to interpret because of the known inhibitory effect of an elevated cellular content of human fetal hemoglobin (HbF). P falciparum therefore was cultured in vitro in the erythrocytes of subjects with hemoglobin H (HbH) disease and various other alpha- thalassemia genotypes that are unaccompanied by increased levels of HbF. Growth of the malaria parasite was markedly retarded in HbH red blood cells, when compared with growth in blood from normal control subjects. No consistent impairment of growth was seen in the erythrocytes of subjects having deletion of only one or two alpha- globin genes. These results indicate that erythrocytes with a severe thalassemia phenotype provide a less hospitable growth environment for P falciparum than normally hemoglobinized red blood cells, even in the absence of increased levels of HbF.
Recurrence of aplastic anemia following cyclophosphamide and syngeneic bone marrow transplantation: evidence for two mechanisms of graft failure
Authors: Appelbaum FR , Cheever MA , Fefer A , Storb R , Thomas ED 
Published: October 2019

Abstract
Two patients with aplastic anemia were treated with high-dose cyclophosphamide and marrow transplantation from their normal, genetically identical twin. Both patients rapidly recovered normal marrow function, but marrow failure recurred 13 and 18 months later. Because donor and host pairs were identical twins, these cases of graft failure could not have resulted from the usual cause of graft failure, ie, immunological reactivity of host cells against unshared minor histocompatibility antigens of the donor. These results imply that there are at least two mechanisms responsible for graft failure after marrow transplantation for severe aplastic anemia.