bluuebunny/crossref_metadata_2025_split huggingface dataset:
New approaches to the detection of myeloperoxidase deficiency
Authors: Dri P , Cramer R , Soranzo MR , Comin A , Miotti V , Patriarca P 
Published: October 2019

Abstract
Family studies on myeloperoxidase (MPO) deficiency have been carried out by quantitating the peroxidase activity of granulocyte preparations with three methods, namely guaiacol peroxidation, alanine decarboxylation, and spectroscopic analysis. The guaiacol assay failed to show a definite pattern of inheritance in two families with MPO- deficient subjects. Surprisingly, the granulocytes of three histochemically MPO-negative subjects had a peroxidase activity either half or even higher than that of control subjects. The peroxidase activity of these granulocyte preparations in these three subjects showed a positive correlation to the number of eosinophils. The possibility then considered was that eosinophils may have obscured the true pattern of inheritance in this assay. Two other methods of MPO assay, which are not influenced by the presence of eosinophil peroxidase (EPO), were therefore devised. One is based on the ability of MPO, but not EPO, to catalyze decarboxylation of L-alanine in the presence of Triton X-100, and the other relies on the different spectral properties of the two peroxidases. The results obtained with these two methods (1) were strictly comparable, (2) allowed detection of both totally and partially MPO-deficient subjects, (3) differed profoundly from those obtained with the guaiacol method when eosinophil- containing granulocyte preparations were used, and (4) revealed a pattern of autosomal recessive inheritance in the two families studied. The results of the three methods were comparable when eosinophil-free granulocyte preparations were assayed. It is concluded that failure to show a pattern of inheritance in some instances of primary MPO deficiency, or deviations from the autosomal recessive mode of transmission of this defect, may be attributed to interference by EPO. It is proposed that peroxidase assay methods not subject to EPO interference, such as the two described in this article, may be used, particularly in the detection of heterozygote subjects for MPO deficiency in the presence of high eosinophil counts.
Role of membrane lipids in cold agglutination of human erythrocytes
Authors: Flamm M , Basu MK , Schachter D , Bertles JF , Maniatis A 
Published: October 2019

Abstract
The membrane lipid fluidity of normal human erythrocytes was modified by enrichment and depletion in cholesterol, and the expression of I and SP1 antigens was assayed by quantitative hemagglutination from 4 degrees to 24 degrees C by use of a continuous flow system. Below 16 degrees--18 degrees C, cholesterol enrichment increased and cholesterol depletion decreased percent agglutination. As temperatures approached approximately 18 degrees--20 degrees C, differences in agglutination between modified and unmodified erythrocytes became insignificant despite marked differences in lipid fluidity at that temperature. Thus, fluidity changes alone cannot be responsible for the effect of membrane cholesterol on cold agglutination. In an additional study, the temperature dependence of a relative equilibrium association constant, estimated by probit analysis of percent agglutination at various antisera concentrations, was biphasic with a sharp break at 16 degrees C. Our studies are consistent with the hypothesis that I and Sp1 antigens preferentially partition into a lipid domain that forms during lateral phase separation of membrane lipid developing at low temperature. A resulting increase in antigen density would then become responsible for augmented agglutination by specific antibody.
Clonal assay of mouse mast cell colonies in methylcellulose culture
Authors: Nakahata T , Spicer SS , Cantey JR , Ogawa M 
Published: October 2019

Abstract
When mouse marrow and spleen cells were cultured for over 12 days in methylcellulose containing media conditioned by pokeweed-mitogen- stimulated spleen cells, colonies containing mast cells and blast cells were observed. The characteristic morphology of the colonies and the time course of their development allowed in situ identification of the mast cell colonies. Identification of the mast cells was confirmed by metachromatic staining with toluidine blue and alcian blue, transmission electron microscopy, and by demonstration of the membrane receptors for IgE. Coculture studies with male and female marrow cells strongly indicated the single cell origin of individual colonies. Detailed cytologic analyses of mixed hemopoietic colonies and replating experiments of individual mixed hemopoietic and mast cell colonies clearly established the hemopoietic origin of mast cells. In replating experiments of individual mast cell colonies, those without blast cells did not yield secondary mast cell colonies. This result strongly indicated that morphologically recognizable mast cells have lost their self-renewing capabilities. The quantitative nature of the mast cell colony assay was supported by linearity studies and provides a method for studies of the progenitors of mouse mast cells.
Human T-lymphocyte products stimulate human hemopoietic progenitor cell proliferation in diffusion chambers in vivo
Authors: Niskanen E , Oki A , Cline MJ , Golde DW 
Published: October 2019

Abstract
Human myeloid colony formation in diffusion chambers in mice (CFU-DG) was enhanced following administration of a human T-cell-line-derived conditioned medium (Mo). The Mo cell line also elaborates activities stimulating human myeloid colony formation in vitro in agar (CSF) and potentiating erythroid colony formation in vitro in methylcellulose (EPA). Depletion of CSF from Mo conditioned medium by heat inactivation or gel exclusion chromatography did not affect CFU-DG formation. EPA and CFU-DG stimulating activities are heat stable and have approximately the same molecular weight. Culture of human bone marrow cells in diffusion chambers in mice for 4 days under the influence of Mo conditioned medium resulted in significant increment of BFU-E and CFU-DG as judged by subculture of diffusion chamber contents. No effect on CFU-C could be detected.
Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study
Authors: Yates J , Glidewell O , Wiernik P , Cooper MR , Steinberg D , Dosik H , Levy R , Hoagland C , Henry P , Gottlieb A , Cornell C , Berenberg J , Hutchison JL , Raich P , Nissen N , Ellison RR , Frelick R , James GW , Falkson G , Silver RT , Haurani F , Green M , Henderson E , Leone L , Holland JF 
Published: October 2019

Abstract
A randomized comparison of the relative efficacy and toxicity of daunorubicin (DNR) at 30 or 45 mg/sq m or adriamycin (ADM) at 30 mg/sq m, given on the first 3 days of a 7-day continuous infusion of cytosine arabinoside (ara-C) at 100 mg/sq m/day, shows the outcome to be dependent on anthracycline, dose, and patient age. DNR 45 is significantly better than DNR 30 or ADM 30 for inducing complete remissions (CR) in patients younger than 60 yr, (72%, 59%, 58% CRs, respectively). DNR 30 is better than DNR 45 or ADM 30 for inducing CR in patients older than 60 yr (47%, 31%, 35%, respectively). There was a corresponding shift in the induction mortality for the age, dose, and anthracycline groups. Adriamycin was significantly more toxic to the gastrointestinal tract than daunorubicin. The duration of complete remission, with cyclic courses of maintenance therapy, was independent of the patient's age, the dose, or choice of anthracycline used in induction, and of whether the maintenance courses were given every 4 wk or every 8 wk.
The heterogeneity of the gamma-chain of fetal hemoglobin in HbS heterozygotes
Authors: Gardiner MB , Reese AL , Headlee ME , Huisman TH 
Published: October 2019

Abstract
The relative quantities of the three types of gamma chain (G gamma, A gamma I, A gamma T) were determined in 18 AS parents of selected SS patients, in 15 additional HbS heterozygotes, as well as in additional SS patients, and in 35 SS and 24 AS newborn babies. The low amount of HbF in all AS adults (less than 1%) made it necessary to further improve the isolation procedure of HbF, which was accomplished by introducing an HPL chromatographic method. The additional data for older SS patients confirmed the existence of two groups characterized by either low G gamma (40%) or high G gamma (60%) values in their HbF. A distinction into “high G gamma” and “low G gamma” producers could also be made for HbS heterozygotes. Family studies, however, make it unlikely that the “high G gamma” condition is inherited in a simple mendelian fashion assuming a change in a regulatory mechanism. The presence of the A gamma T mutation, occurring either in cis or in trans to the beta S mutation, has been used to evaluate the possible contribution by specific gamma-chain genes to the gamma-chain composition of the HbF of adult AS persons. No clear pattern because evident, suggesting that most of the gamma-chain of this small amount of HbF could originate from gamma-chain genes in cis or in trans to the beta S gene or from both sets of genes. It is speculated that heterogeneity among “F-cells” may be a primary cause of the observed differences in gamma-chain composition of HbF in HbS heterozygotes.
Analysis of T lymphocytes after bone marrow transplantation using monoclonal antibodies
Authors: Fox R , McMillan R , Spruce W , Tani P , Mason D 
Published: October 2019

Abstract
Using monoclonal antibodies to cell surface antigens and fluorescent cell sorter analysis, we studied peripheral blood lymphocyte subsets after bone marrow transplantation (BMT). In 13 patients studied 3 mo or more after BMT, the ratio of T-cell subsets defined by antibodies OKT4 and OKT8 was reversed (OKT4/OK%8 = 0.7 +/- 0.3) in comparison to normal volunteers or bone marrow donors (ratio OKT4/OKT8 = 1.7 +/- 0.4) (p less than 0.001). This reversed ratio persisted for up to 3 yr after BMT. In contrast to a previous report, presence of an abnormal ratio of T-cell subsets did not correlate with clinically significant graft- versus-host disease (GVHD). In agreement with a previous study, (26% +/- 8%; less than 4% in normals (p less than 0.001) and antibody OKT10 reactive cells (39% +/- 20% versus 10% +/- 4%) (p less than 0.01), suggesting in vivo activation. However, their PBL did not react with antibody B3/25 (antitransferrin receptor), a marker found on normal PBL after in vitro activation by mitogens (BMT patients less than 5%; normal PBL T cells plus PHA 45% +/- 11%). These results demonstrate that BMT patients have: (A) an abnormal ratio of T-cell subsets in the presence or absence of clinically significant GVDH disease so that these measurements were not useful in monitoring patients; (B) an increased number of T cells with cell surface phenotype (OKT8+, Ia+, OKT10+, B3/25-) that is distinct from normals but similar to patients with infectious mononucleosis or acquired hypogammaglobulinemia.
Cellular and extracellular myeloperoxidase in pyogenic inflammation
Authors: Bradley PP , Christensen RD , Rothstein G 
Published: October 2019

Abstract
We explored the effect of in vitro phagocytosis and in vivo inflammation on the MPO content of functioning neutrophils and on the ability of these cells to export active MPO into the extracellular environment. After ingestion of staphylococci, neutrophils retained 52% of their MPO and released 8% into the medium in active form; the remaining 40% of their MPO could no longer be detected. During bacterial infection induced by intradermally injecting staphylococci, neutrophils harvested from minced infected lesions contained 52% of the MPO of circulating neutrophils that had not reached the lesions. Extracellular fluid from the lesions contained active MPO secreted by the neutrophils, and concentrations of 10–45 U/ml were detected. These data demonstrate that functioning neutrophils can lose approximately half of their MPO. In vitro, 4%-8% of neutrophilic MPO appears in the extracellular space and 40% is inactivated. In vivo, the MPO content of inflammatory neutrophils also decreases, and MPO appears in the extracellular fluid in active form where it is available to participate in a variety of physiologic processes.
Electron microscopic localization of factor-VIII-related antigen in adult human blood vessels
Authors: Rand JH , Gordon RE , Sussman II , Chu SV , Solomon V 
Published: October 2019

Abstract
We have localized factor-VIII-related antigen, using immunofluorescence and electron microscopy, in adult human blood vessels. In addition to its presence in endothelial cells, the antigen was localized within subendothelium and the layers of elastic lamina closest to the lumen. Also, we provide the first morphological evidence that factor-VIII- related antigen is associated with collagen fibrils within the vessel wall. These studies suggest that this subendothelial factor-VIII- related antigen may play a role in the adhesion of platelets to subendothelial components following endothelial injury.
Fibrinopeptide A, platelet factor 4, and beta-thromboglobulin levels in coronary heart disease
Authors: Nichols AB , Owen J , Kaplan KL , Sciacca RR , Cannon PJ , Nossel HL 
Published: October 2019

Abstract
In vivo platelet alpha-granule release and fibrin I formation were measured in 82 patients with ischemic heart disease by radioimmunoassay of platelet factor 4, beta-thromboglobulin, and fibrinopeptide A. The presence and extent of coronary artery disease were determined by coronary arteriography, and the extent of left ventricular regional dysfunction was assessed by contrast left ventriculography. In patients with abnormal coronary arteriograms without previous myocardial infarction, mean levels of platelet factor 4, beta-thromboglobulin, and fibrinopeptide A were not elevated. In patients in whom myocardial infarction had occurred more than 6 mo previously, platelet factor 4 (8.3 ng/ml; p less than 0.01) and beta-thromboglobulin (33.2 ng/ml; p less than 0.001) levels were significantly elevated, but fibrinopeptide A levels were normal. Levels of platelet factor 4 and beta- thromboglobulin were unrelated to the extent of coronary artery disease. In the patients with prior infarction, beta-thromboglobulin correlated directly with extent of left ventricular regional dysfunction (r = 0.53; p less than 0.01) and inversely with ejection fraction (r = -056; p less than 0.05). In a small group of patients with left ventricular aneurysm, mean fibrinopeptide A levels were also elevated. We interpret these findings as indicating that platelet release in patients with ischemic heart disease results from platelet reaction with previously infarcted myocardium rather than with the atherosclerotic coronary arteries.
Prognostic significance of terminal transferase and adenosine deaminase in acute and chronic myeloid leukemia
Authors: Bertazzoni U , Brusamolino E , Isernia P , Scovassi AI , Torsello S , Lazzarino M , Bernasconi C 
Published: October 2019

Abstract
We have analyzed the distribution and prognostic significance of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) in connection with conventional cytology, cytogenetics, response to therapy, and survival. The study population consisted of 78 patients with AML, 44 patients with Ph1 + CML in chronic phase, and 35 adult patients with Ph1 + CML in blastic phase, among which 5 cases presented as Ph1 + acute leukemia. Nine percent of the AML cases were positive for TdT and were characterized by a high percentage of blast cells in bone marrow, myeloid features by cytochemistry and absence of the Philadelphia chromosome. The median ADA values of the TdT+ AML cases were several times higher than those obtained for the TdT- cases. The survival calculated for the two groups of AML cases subdivided according to ADA levels was significantly longer (p less than 0.025) for the patients with low levels of ADA (less than 250 U/10(8) cells). In chronic phase of CML, TdT was absent and ADA values were increased over normal controls only in cases with early signs of transformation. In blastic phase, 31% of the 35 cases were positive for TdT, and ADA values were significantly higher (p less than 0.001) in TdT+ than TdT- cases. The survival calculated from the onset of transformation was significantly longer for the TdT+ acute phase (10.4 mo) compared to the TdT- patients (4.8 mo; p less than 0.025). Four cases presenting as Ph1 + acute leukemia were TdT+ and had elevated levels of ADA; 3 of them responded to ALL therapy, reverting to a stable phase of CML.
A canine model of hemophilic (factor VIII:C deficiency) bleeding
Authors: Giles AR , Tinlin S , Greenwood R 
Published: October 2019

Abstract
A model of bleeding due to clotting factor deficiency has been developed in dogs. Normal and hemophilic (factor VIII:C deficient) animals were used. Bleeding was induced in lightly anesthetized animals by severing the apex of the nail cuticle using a guillotine device. In normal animals, bleeding usually ceased spontaneously after 2–8 min. In contrast, in hemophilic animals, bleeding continued for up to 20 min and necessitated either cauterization or the application of topical thrombin to achieve hemostasis. Pretreatment of the hemophilic animals with canine cryoprecipitate corrected the cuticle bleeding time to within the range noted for normal animals. The method is simple and reproducible and has the advantage that a number of observations can be made sequentially on the same animal. Rebleeding of the cauterized cuticle of the hemophilic animals did not usually occur. This model has considerable potential for the preclinical testing of products considered to bypass or replace factor VIII:C in patients with acquired inhibitors of factor VIII:C and may be adapted to the study of other mechanisms involved in normal and abnormal hemostasis.
Cells with Fc gamma receptors from normal donors suppress granulocytic macrophage colony formation
Authors: Spitzer G , Verma DS 
Published: October 2019

Abstract
We investigated the role of normal human marrow cells with Fc receptors for IgG (Fc gamma+) on autologous granulocyte-macrophage colony (GM- CFC) formation. It was found that Fc gamma+ normal human marrow cells, both with (E+) or without receptors for sheep erythrocytes suppressed GM-CFC at as low a concentration as 0.25 X 10(5) cells/ml of culture. A similar effect was observed with E- Fc gamma+ but not E+ Fc gamma+ peripheral blood cells. Suppression by Fc gamma+ cells did not require mitogen activation and was not inactivated by irradiation (2000 R). This report presents a new in vitro regulatory mechanism for GM-CFC growth in normal donors.
Human blood monocytes and platelets share a cell surface component
Authors: Burckhardt JJ , Anderson WH , Kearney JF , Cooper MD 
Published: October 2019

Abstract
We describe a surface determinant shared by human monocytes and cells of the megakaryocytic axis that has been identified using a mouse monoclonal antibody. This monocyte-platelet antigen (MPA) is expressed on all (greater than 99%) of peripheral blood monocytes, platelets, and megakaryocytes. It is also expressed weakly on the monocytic cell line U937 and the promyelocytic line HL60 and is present on cells from 3 of 4 AML patients examined. It is absent from polymorphonuclear leukocytes, T and B lymphocytes, erythrocytes, and a panel of hematopoietic cell lines. MPA is stripped from monocyte membranes with pronase and is reexpressed overnight. The determinant is carried on a noncovalently linked biomolecular complex with molecular weights of 93,000 and 135,000.
Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis
Authors: Goodman SR , Shiffer KA , Casoria LA , Eyster ME 
Published: October 2019

Abstract
We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena.
Pathologic effects of plasma from patients with thrombotic thrombocytopenic purpura on platelets and cultured vascular endothelial cells
Authors: Burns ER , Zucker-Franklin D 
Published: October 2019

Abstract
The pathologic hallmarks of thrombotic thrombocytopenic purpura (TTP) include endothelial cell proliferation and subendothelial hyalin deposits in the microvasculature leading to symptomatic thrombotic occlusions. Plasma or sera from three consecutive patients with TTP were subjected to multiple analyses to determine whether they induce endothelial injury and/or platelet activation, two pathogenic mechanisms that may account for this disorder. Sera were utilized in a microcytotoxicity assay against cultured human umbilical vein endothelial cells (EC). These cells were assessed ultrastructurally and with immunofluorescence techniques to ascertain the nature of inflicted cell damage. Control plasmas were obtained from healthy volunteers as well as patients with immune complex disease and the adult hemolytic uremic syndrome. In the presence of TTP serum, cell kill of 3H-proline- labeled EC averaged 42% versus 8.6% for control sera. Cytotoxicity induced by an IgG fraction of TTP sera averaged 70% versus 16.8% for control IgG. Removal of IgG by immune precipitation diminished cytotoxicity by 70%. Using indirect immunofluorescence, IgG was detected on EC incubated with TTP serum but not on EC treated with control serum. Ultrastructural changes became apparent within 30 min after exposure of cultured EC to TTP serum. Virtually every cell developed numerous cytoplasmic inclusions rarely seen in EC in the presence of normal serum. Prolonged incubation with the TTP serum led to progressive cytolysis, terminating with complete cytoplasmic and nuclear degeneration. Plasma from all three patients with TTP caused spontaneous aggregation of normal washed platelets as monitored by aggregometry. No spontaneous aggregation occurred in response to control plasmas. These results indicate that the sera of the three TTP patients studied were able to mediate time-dependent immune destruction of human cultured endothelial cells and that their plasmas were capable of causing spontaneous aggregation of normal human platelets in vitro. It would seem likely that these mechanisms are also operative in vivo to produce the endothelial destruction as well as the thrombotic vascular occlusions seen in this disorder.