bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the peptide subunits of human neutrophil myeloperoxidase
Authors: Nauseef WM , Malech HL 
Published: October 2019

Abstract
Myeloperoxidase is a cationic protein present in the azurophilic granules of human neutrophils and constitutes 2% to 5% of neutrophil protein by weight. Despite extensive characterization of the functional importance of myeloperoxidase in the microbicidal activity of neutrophils, there is no consensus regarding the subunit composition of this enzyme or the presence of genetic polymorphism. Using isoelectric focussing and peptide mapping of chymotryptic digests of myeloperoxidase subunits under reducing and nonreducing conditions, we found two different heavy chain peptides that have overlapping but distinctive chymotryptic digest maps. One of these heavy chains has a reducible intrapeptide disulfide bond not found in the other. These results suggest that the model proposed for the structure of myeloperoxidase as a symmetric molecule with two identical heavy-light protomers may not be correct.
Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors
Authors: Mitchell GH , Hadley TJ , McGinniss MH , Klotz FW , Miller LH 
Published: October 2019

Abstract
Plasmodium falciparum malaria parasites with different capabilities of invading sialic acid-deficient erythrocytes were identified. Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase-treated and Tn erythrocytes twice as efficiently as Thai-2 parasites cultured in normal erythrocytes and seven to ten times more efficiently than a cloned line of Camp parasites cultured in normal erythrocytes. All three parasite lines required sialic acid for optimal invasion, but Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase- treated erythrocytes with 45% efficiency whereas Camp parasites invaded neuraminidase-treated erythrocytes with less than 10% efficiency. P falciparum malaria parasites probably possess two receptors: one that binds to a sialic acid-dependent ligand and another that binds to a sialic acid-independent ligand. Parasites may differ in the quantity or affinity of their receptors for the sialic acid-independent ligand.
Defective platelet-fibrinogen interaction in hereditary canine thrombopathia
Authors: Catalfamo JL , Raymond SL , White JG , Dodds WJ 
Published: October 2019

Abstract
A unique, intrinsic, hereditary canine platelet disorder attributable to abnormal fibrinogen receptor availability is described. Thrombopathic platelets from 13 severely affected basset hounds failed to aggregate in response to all agonists tested except thrombin. Normal platelet interaction with the various stimuli was inferred on the basis of their ability to elicit unimpaired shape change in thrombopathic platelets. No quantitative differences in major platelet membrane glycoproteins, intraplatelet fibrinogen, adenine nucleotides, or serotonin uptake were detected. Dense granule secretion was impaired. The ultrastructural appearance of thrombopathic platelets was normal. Fibrinogen-platelet interaction was evaluated by reacting platelet-rich plasma (PRP) with fibrinogen coupled to polymeric acrylonitrile beads and scoring the extent of stimulus-induced agglutination. The aggregatory responses of normal and thrombopathic platelets were closely correlated with fibrinogen receptor availability. In contrast to human platelets, epinephrine-stimulated canine platelets did not interact with immobilized fibrinogen, and arachidonate generally induced only weak agglutination. Thrombopathic platelets agglutinated fibrinogen beads at reduced rates when stimulated with physiologic doses of thrombin and high-dose calcium ionophore, A23187. Our data suggest that thrombin-mediated induction of canine platelet fibrinogen receptors may proceed by pathway(s) alternate to those shared by other platelet agonists, and/or that secreted granule constituents may act synergistically with thrombin to overcome inhibition of signal-response- coupled reactions mediating the interaction of fibrinogen with its receptor. This congenital platelet defect provides further evidence, in a species other than human, for the pivotal role of fibrinogen receptor induction in platelet aggregation.
Clinical and phenotypic diversity of T cell lymphomas
Authors: Horning SJ , Weiss LM , Crabtree GS , Warnke RA 
Published: October 2019

Abstract
Forty-one cases of T cell lymphoma were identified on the basis of morphology and the expression of two or more T cell antigens with an absence of B cell markers. Mycosis fungoides and lymphoblastic lymphoma were excluded. Marked clinical, morphological, and immunologic diversity was observed. Cutaneous lymphoma was found in approximately 50% of the patient group, and 27% had a prior history of dermatologic or immunologic disease. No correlations among immunologic and morphologic phenotypes and clinical course were apparent. Survival data was comparable to that of a concurrent group of non-T cell lymphoma patients studied at this institution, suggesting that, contrary to previous reports, T cell lymphoma may not necessarily confer a more unfavorable prognosis. Prospective studies using uniform treatments are necessary to address the clinical significance of the T cell phenotype definitively, independent of established histologic and clinical features.
The regulatory role of interleukin 2-responsive T lymphocytes on early and mature erythroid progenitor proliferation
Authors: Estrov Z , Roifman C , Wang YP , Grunberger T , Gelfand EW , Freedman MH 
Published: October 2019

Abstract
To analyze the role of T lymphocytes in human erythropoiesis, we evaluated the effect of recombinant interleukin 2 (IL 2) on marrow CFU- E and BFU-E colony formation in vitro. IL 2 resulted in an increase in CFU-E and BFU-E colony numbers in a dose-dependent manner. This increase could be prevented by anti-Tac, a monoclonal antibody to the IL 2 receptor. Moreover, anti-Tac on its own resulted in an overall decrease in colony numbers. Depletion of marrow adherent cells did not alter the effect of either IL 2 or anti-Tac on colony growth. Following the removal of marrow T lymphocytes, CFU-E and BFU-E colony formation proceeded normally; however, the effects of IL 2 and anti-Tac were markedly diminished. Readdition of T lymphocytes to the cultures restored the IL 2 effect. Although T lymphocytes were not themselves essential for in vitro erythropoiesis, our studies suggest that IL 2 and IL 2-responsive T cells can regulate both early and mature stages of erythroid differentiation.
Lipoxygenase metabolites of arachidonic acid modulate hematopoiesis
Authors: Snyder DS , Desforges JF 
Published: October 2019

Abstract
Lipoxygenase (LPO) metabolites of arachidonic acid participate in the activation and/or proliferation of a variety of cell types. In this study, we examined the role of LPO metabolites in controlling myelopoiesis and erythropoiesis in vitro. Monocyte depleted cells (MDC) prepared from human whole blood or whole mononuclear cells from human bone marrow were cultured in methylcellulose in the presence of various growth factors. Conditioned media containing human colony stimulating factors (CSF) or the tumor-promoting phorbol ester, phorbol myristate acetate (PMA), were added to induce myelopoiesis. Semipurified human erythropoietin (EPO) was added along with an endogenous source of burst- promoting activity (BPA) to induce erythropoiesis. The LPO inhibitor BW755C blocked all types of colony formation in a dose-dependent manner, with ID50 of 20 and 5 micrograms/mL for myeloid and erythroid colonies, respectively. MDC depleted of T cells were similarly inhibited by BW755C. Similar results were seen with two other LPO inhibitors, 1-phenyl-3-pyrazolidone and butylated hydroxyanisole. A fourth LPO inhibitor, nordihydroguaiaretic acid, inhibited at higher concentrations. Indomethacin, at concentrations that inhibit cyclooxygenase, had no significant effect, either alone or in combination with the LPO inhibitors. These results suggest that certain LPO products may be important mediators of both CSF- and PMA-induced myelopoiesis, and of BPA/EPO-induced erythropoiesis.
Absence of oncogene amplifications and occasional activation of N-ras in lymphoblastic leukemia of childhood
Authors: Rodenhuis S , Bos JL , Slater RM , Behrendt H , van 't Veer M , Smets LA 
Published: October 2019

Abstract
To examine whether determination of (1) the copynumber or restriction pattern of certain oncogenes or (2) the mutational activation of the N- ras gene might contribute to the risk classification of acute lymphoblastic leukemia of childhood (ALL), we investigated DNA isolated from lymphoblasts of untreated patients. Restriction enzyme analysis of cellular oncogenes was performed on DNA of 25 patients. No rearrangements could be demonstrated within or near the genes c-myc, c- myb, c-abl, bcr, c-Ki-ras, and N-ras. No amplifications of these genes nor of N-myc or c-Ha-ras were present. Eight of 21 patients were heterozygote for “rare” Ha-ras allelic restriction fragments that have been associated with an increased risk of developing a malignancy. These patients were clinically indistinguishable from patients lacking these fragments. The breakpoint cluster region (bcr) that is rearranged in all patients with Philadelphia chromosome positive chronic myeloid leukemia, was normal in all cases, including at least one patient with Philadelphia chromosome positive ALL. A 2.8 kb HindIII fragment of a hitherto unknown gene or pseudogene related to v-myb probably derives from the Y chromosome. Nineteen patients were examined for point mutations in the N-ras gene, using a novel synthetic oligonucleotide hybridization assay. In two patients activating point mutations were present, both in positions 1 of the 12th codon. Both patients were somewhat older than the others (16 and 11 years), had L2 morphology, and were shown to have high growth fractions of tumor in their bone marrow.
Immunoglobulin class switch from IgG to IgA in a patient with smoldering multiple myeloma
Authors: Takahashi M , Tsukada T , Kojima M , Koide T , Koike T , Takahashi H , Sakai C , Kashimura M , Shibata A 
Published: October 2019

Abstract
Serum of a 67-year-old male patient with smoldering multiple myeloma was shown to contain two monoclonal immunoglobulins, IgG and IgA. For the initial seven months, monoclonal IgG was predominantly elevated. During the next one year and eight months, however, serum concentration of the monoclonal IgA increased, with a concomitant decrease of IgG. N- terminal amino acid sequences of heavy and light chains separated from monoclonal IgG and IgA were analyzed. Both light chains were lambda- type and showed identical amino acid sequences of variable regions. The heavy chains also had the same N-terminal amino acid sequence between IgG and IgA. These results strongly suggest that two monoclonal proteins, IgG and IgA, in this patient were produced by B lymphocytes within a clone and that class switch from IgG to IgA in immunoglobulin production during B cell differentiation has taken place in the clinical course of this case.
Thrombin causes subsecond changes in protein phosphorylation of platelets
Authors: Carty DJ , Spielberg F , Gear AR 
Published: October 2019

Abstract
We have developed a general quenched-flow approach to study platelet function as early as 0.3 seconds after stimulation. Phosphorylation of 20- and 40-kd proteins has been analyzed during the first five seconds of platelet response to thrombin from 0.1 to 5.0 U/mL and compared with the progress of aggregation and serotonin secretion. The onset time for aggregation and phosphorylation of both proteins was less than one second, although with lowest (less than 0.5 U/mL) thrombin levels, a lag of up to 0.6 seconds occurred before 40K phosphorylation increased. The thrombin sensitivity of aggregation and 20K phosphorylation was approximately twice that of 40K phosphorylation, with Ka values of 0.51 and 0.53 v 1.10 U/mL, respectively. External calcium was necessary for maximal 20K phosphorylation, since EDTA inhibited this by 30%. The 40K phosphorylation was not affected by EDTA. Platelet activation by thrombin thus induced biochemical changes well before one second. The quenched-flow approach may help to reveal relationships between phospholipase activation, calcium fluxes, and protein phosphorylation during these early periods of platelet function.
Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium
Authors: Chesterman CN , Owe-Young R , Macpherson J , Krilis SA 
Published: October 2019

Abstract
Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.
Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes
Authors: Jacobs RH , Cornbleet MA , Vardiman JW , Larson RA , Le Beau MM , Rowley JD 
Published: October 2019

Abstract
Forty-nine patients with primary myelodysplastic syndromes (MDS) were subclassified according to French-American-British (FAB) Cooperative Group criteria. Eight patients had acquired idiopathic sideroblastic anemia (AISA), ten had chronic myelomonocytic leukemia (CMMoL), 14 had refractory anemia (RA), nine had refractory anemia with excess blasts (RAEB), and five had refractory anemia with excess blasts in transformation (RAEB-T); three patients could not be subclassified. The actuarial median survival for patients with AISA or with RA had not been reached at 60 months of follow-up. The median survival times for patients with CMMoL, RAEB, and RAEB-T were 25, 21, and 16 months, respectively. The percentages of patients with each subtype who developed ANLL were none in AISA, 20% in CMMoL, 7% in RA, 56% in RAEB, and 40% in RAEB-T. Patients with CMMoL had a poor prognosis independent of transformation to acute nonlymphocytic leukemia (ANLL), whereas patients with RAEB and RAEB-T had a high incidence of transformation and short survival times. Clonal chromosomal abnormalities were present in bone marrow cells from 19 patients at the time of diagnosis, and two others developed an abnormal karyotype at the time of leukemic transformation. The most frequent abnormalities, including initial and evolutionary changes, were trisomy 8 (9 patients), deletion of 5q (4 patients), and deletion of 20q (4 patients). The median survival times were 32 months for patients with an abnormal karyotype, and 48 months for those with a normal karyotype (P = 0.2). Specific chromosomal abnormalities were not associated with particular histologic subtypes; however, a high percentage of patients with RAEB and RAEB-T had an abnormal clone (89% and 80%, respectively). The percentages of patients with clonal abnormalities were 13% for AISA, 20% for CMMoL, and 29% for RA. The MDS transformed to ANLL in 42% of patients with an abnormal karyotype, compared to 10% of those with an initially normal karyotype (P less than .01). Among patients with RA, RAEB, and RAEB-T, the risk of leukemic transformation was confined to those with an abnormal karyotype (P less than .01). Thus, in the present study, morphology and karyotype combined were the best indicators of outcome in patients with MDS.
Thrombocytopenia in venocclusive disease after bone marrow transplantation or chemotherapy
Authors: Rio B , Andreu G , Nicod A , Arrago JP , Dutrillaux F , Samama M , Zittoun R 
Published: October 2019

Abstract
Hepatic venocclusive disease (VOD) is a frequent complication of bone marrow transplantation (BMT). Analysis of 13 cases observed during a 3- year period in our BMT center shows that VOD is associated with a constant peripheral thrombocytopenia and refractoriness to platelet transfusion. These signs appear in the very early stage of VOD, five to ten days before the classical signs, painful hepatomegaly and sudden weight gain. Analysis of platelet consumption, frequency of platelet transfusion and platelet recovery, and examination of known causes of peripheral thrombocytopenia (mainly allo- and autoimmunization, disseminated intravascular coagulation [DIC] and splenomegaly) lead to the conclusions that this association is not coincidental. The exact mechanism of platelet consumption in VOD is unknown.
Chinese A gamma fetal hemoglobin: C to T substitution at position-196 of the A gamma gene promoter
Authors: Gelinas R , Bender M , Lotshaw C , Waber P , Kazazian H Jr , Stamatoyannopoulos G 
Published: October 2019

Abstract
The molecular basis for the hereditary persistence of fetal hemoglobin (HPFH) phenotype was studied in a Chinese individual who was heterozygous for a nondeletion form of A gamma-HPFH. Both allelic A gamma-globin genes were isolated by molecular cloning and subjected to nucleotide sequence analysis. One A gamma gene promoter showed a cytosine to thymine transition at position -196, whereas the other promoter was normal. This mutation at position -196 has now ben found in unrelated individuals with the A gamma-HPFH phenotype from Italy, Sardinia, and China, suggesting that it may have arisen independently. The implications of this mutation for models of fetal globin gene switching are discussed.
3A1 (CD7) expression precedes T beta gene rearrangements in precursor T (lymphoblastic) neoplasms
Authors: Pittaluga S , Raffeld M , Lipford EH , Cossman J 
Published: October 2019

Abstract
The phenotypes of early stages of T cell maturation are reflected by precursor T (lymphoblastic) neoplasms. In the present study, a series of such neoplasms was analyzed to reveal the developmental association of the expression of stage-related cell surface markers and T cell receptor gene rearrangement. Rearrangements of the T cell receptor beta- chain (T beta) gene were found in most, but not all, cases (88%) of T cell lymphoblastic neoplasms. T beta gene rearrangement preceded surface expression of the T cell receptor-linked molecular complex T3. Of all monoclonal anti-T cell antibodies tested, only antibody 3A1 was capable of reacting with neoplastic cells from all cases irrespective of the occurrence of T cell receptor gene rearrangements. In contrast, markers T1 and T11, normally expressed by mature T cells, were absent from the neoplastic cells in many cases (73% and 60% positive cases, respectively). Thus, antibody 3A1 is a valuable probe for the identification of T lymphoblastic neoplasms since its target antigen is consistently expressed and does not require prior T beta gene rearrangement. Furthermore, expression of 3A1 prior to T beta gene rearrangement suggests that it may be a cell surface protein that participates in the triggering of T cell receptor gene rearrangement and expression. It is concluded that precursor T cell neoplasms display an early T cell development hierarchy that, in sequence, consists of 3A1 expression, T beta gene rearrangements, and surface T3 expression.
Nonrandom distribution of iron in circulating human transferrin
Authors: Zak O , Aisen P 
Published: October 2019

Abstract
By combining the urea gel electrophoresis technique of Makey and Seal with Western immunoblotting, a method has been developed for analyzing the distribution of iron between the two sites of circulating human transferrin. The new method avoids exposure of samples to a nonphysiologic pH that may promote removal or redistribution of iron from the protein; this facilitates examination of multiple samples at one time. Analysis of 21 freshly drawn specimens from normal human subjects confirms previous reports that iron is not randomly distributed in the specific sites of transferrin. Rather, there is a considerable range in the ratio of occupancies of N-terminal and C- terminal sites (N:C ratio), from 0.31 to 6.87 in the present study, with the N-terminal site predominantly occupied in most subjects. The N:C ratio correlates modestly with serum iron concentration (r = .54). Possible flaws in studies indicating a random occupancy of the specific sites of circulating transferrin may lie in the low pH to which samples may be exposed during procedures based on isoelectric focusing or in drawing inferences from data considering only total monoferric transferrin rather than the two distinguishable monoferric species.
Purified colony-stimulating factors enhance the survival of human neutrophils and eosinophils in vitro: a rapid and sensitive microassay for colony-stimulating factors
Authors: Begley CG , Lopez AF , Nicola NA , Warren DJ , Vadas MA , Sanderson CJ , Metcalf D 
Published: October 2019

Abstract
The survival of purified human blood neutrophils and eosinophils was monitored using microwell cultures. Survival was enhanced in cultures containing human or murine colony-stimulating factors (CSFs). The survival of both cell types was enhanced by purified recombinant human granulocyte-macrophage CSF and partially purified preparations of the native molecule, CSF alpha. Neutrophil but not eosinophil survival was enhanced by murine granulocyte-CSF and its human analogue CSF beta. Eosinophil but not neutrophil survival was enhanced by murine eosinophil differentiation factor (eosinophil CSF). The mature cell survival provided an assay system for CSF that was 10(2) to 10(3) more sensitive than the standard assay of stimulation of colony formation in agar cultures and could be completed within 48 hours. These results demonstrated that CSF induced and enhanced survival of mature human neutrophils and eosinophils in vitro. Furthermore, the lineage specificity of purified murine CSFs was retained in their action on human cells.