bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graded responses of human neutrophils induced by serum-treated zymosan
Authors: Whitin JC , Ryan DH , Cohen HJ 
Published: October 2019

Abstract
A modified zymosan preparation was used to probe the interaction of particulate stimuli with human neutrophils (PMNs). After extraction with alkali and detergent, the zymosan particles retained their ability to be opsonized in serum and to stimulate PMNs. Serum-treated zymosan (STZ) induced dose-dependent superoxide (O2-) production and membrane potential depolarization in the range of 1 to 10 mg/mL of STZ. The rate and extent of secretion of lysozyme and beta-glucuronidase were also dose-dependent in the range of 1 to 10 mg/mL of STZ. Cytochemical studies using nitroblue tetrazolium, however, showed that 92% of PMNs were stimulated to produce O2- at 0.1 mg/mL of STZ. The dose response of O2- production induced by STZ is therefore due to increasing O2- production by individual PMNs and not to the stimulation of more PMNs to produce O2-. Evidence for O2- production was found only in the area of PMN-zymosan contact, suggesting a mechanism for the graded responses of PMNs treated with particulate stimuli. In order to determine the nature of the dose dependence of depolarization (a measure of PMN activation), PMNs equilibrated with the fluorescent probe 3,3′- dipentyloxacarbocyanine were analyzed by flow cytometry. The results demonstrate that STZ induces a dose-dependent depolarization of the membrane potential of individual PMNs. These results also demonstrate that increasing concentrations of STZ can induce increasing PMN responses even when all of the PMNs have been activated. These results are consistent with the hypothesis that receptor-mediated particulate stimulation of PMNs is a phenomenon that results in graded PMN responses.
The kinetics of inhibition of thrombin by antithrombin in the presence of components of the hemostatic system
Authors: Jesty J 
Published: October 2019

Abstract
The inhibition of human thrombin by antithrombin has been measured in pure systems in the presence of other components of the hemostatic system that might affect the kinetics of the reaction. These included fibrinogen, calcium ions, phospholipid, prothrombin, platelets (both adenosine diphosphate [ADP]-stimulated and -unstimulated), and platelet extracts. Inhibition rates were measured in each case by a discontinuous amidolytic assay over a range of antithrombin concentrations, from 0 to 4.5 mumol/L. Under all conditions, rates of inhibition were proportional to antithrombin concentration. Calcium ions at 5 mmol/L caused a small (20%) reduction in rate, but phospholipid and prothrombin had no additional effect. In contrast, both fibrinogen and platelets significantly changed the rate of inhibition. In the presence of calcium, fibrinogen at concentrations from 0 to 12 mumol/L reduced the rate of inhibition in a competitive manner, giving an apparent Kd for fibrinogen of 6.0 mumol/L. As the plasma fibrinogen level is about 8 mumol/L, one may therefore predict that variations in fibrinogen level will have a significant effect on the rate of thrombin inhibition in plasma. More unexpected was the observation that platelets increase the rate of inhibition: unstimulated platelets increased the rate constant by 40%, and ADP- stimulated platelets increased it by 55%. However, this acceleratory effect could not be mimicked with either a KCI extract or a Triton extract of platelets, and its cause remains unknown. In sum, it has been shown that the rate of inhibition of thrombin can be modulated in at least three ways-antithrombin concentration, fibrinogen concentration, and platelets; each of which can vary independently in vivo. It is well known that defects of the first lead to an increased risk of thrombosis, and it is proposed that this may be substantially caused by changes in the kinetics of inhibition such as those described. Additionally, it is suggested that changes in inhibition rate caused by other components may also be significant, for the same reason, in modulating the clotting system in vivo.
Correction of symptoms of platelet storage pool deficiency in animal models for Chediak-Higashi syndrome and Hermansky-Pudlak syndrome
Authors: Novak EK , McGarry MP , Swank RT 
Published: October 2019

Abstract
Two human diseases of platelet storage pool deficiency (SPD), Hermansky- Pudlak syndrome and Chediak-Higashi syndrome, are recessively inherited disorders characterized by hypopigmentation, prolonged bleeding, and normal platelet counts accompanied by a reduction in dense granule number. We have recently described seven independent recessive mutations in the mouse regulated by separate genes which are likely animal models for human SPD. Reciprocal bone marrow transplants were carried out between normal C57BL/6J mice and two of these mutants, beige and pallid, in order to test whether the platelet defects are due to a defect in platelet progenitor cells or to humoral factors. Normal and congenic mutant mice were transplanted with marrow after 950 rad whole body radiation. The long bleeding times and low serotonin concentrations of the two mutants were converted to normal values after transplantation with normal marrow. Likewise, normal mice displayed symptoms of SPD when transplanted with mutant marrow. These studies demonstrate that with each of the two mutations, platelet SPD results from a defect in bone marrow precursor cells. Also, the studies suggest that in severe cases, platelet SPD may be successfully treated by bone marrow transplantation.
Autosomal dominant polycythemia
Authors: Prchal JT , Crist WM , Goldwasser E , Perrine G , Prchal JF 
Published: October 2019

Abstract
Two families with polycythemia inherited as an autosomal dominant trait are described. Serial hemoglobin determinations in multiple family members and RBC volume measurements in selected affected subjects documented their polycythemia. Measurements of arterial p02s, p50s, and blood oxygen affinity were normal in all affected individuals from each family who were tested. Erythropoietin (EPO) levels were low in affected individuals from family 1 and normal in affected members of family 2. Stimulation of in vitro CFU-E colony growth by low levels of EPO was significantly increased in subjects from family 1, but normal in those affected from family 2. We conclude that although the inheritance pattern for the polycythemia in both of these families appeared to be the same, the biologic defect leading to the disorder in each of these unique families was different. The precise mechanism of the increased EPO sensitivity noted in affected subjects from family 1 awaits elucidation.
Further results in understanding the subpopulation structure of AML: clonogenic cells and their progeny identified by differentiation markers
Authors: Lowenberg B , Bauman JG 
Published: October 2019

Abstract
We performed a subpopulation analysis in acute myelocytic leukemia (AML) with the objective of relating the phenotypic diversity to the clonogenic properties of the cells. AML-CFUs considered as representatives of the leukemia precursor cell compartment were phenotyped for cell surface markers by use of eight monoclonal antibodies directed against myeloid differentiation antigens and the Ia antigen. Thus, specifically depleted (in complement-dependent lysis) or selected (in fluorescence-activated cell sorting), cells were inoculated into colony culture. We report here that AML-CFU surface phenotypes showed considerable variability among the seven patients with AML studied. The clonogenic cells were heterogeneous with regard to the antigen density on the cell surface and represented a distinct population among the leukemias. The immunophenotypes of AML-CFU did not differ as a consequence of variations of colony techniques, ie, the use of different stimulatory materials. The marrow and blood, as shown in four subjects, contained AML-CFU of identical maturation stages. In addition, the direct cellular offspring of AML-CFUs were phenotyped. This was done by analyzing the colonies produced in culture, and it was apparent that their antigenic markers were compatible with later stages of differentiation. For example, AML-CFUs in all patients were granulocytic antigen B4.3-negative, whereas their colony progeny contained significant numbers of B4.3-positive cells. This direct evidence indicating that progenitors and descendant cells in AML are identified by distinct maturation features corroborates the concept that the heterogeneous cellular structure of human AML is a reflection of the apparent differentiation capabilities of the precursors. The fact that the differentiation markers of the leukemia are variably expressed or even lacking on AML-CFUs has clinical importance in the immunodiagnosis of residual leukemia and in immunoseparation of leukemia from autologous bone marrow grafts.
Establishment and characterization of a new human eosinophilic leukemia cell line
Authors: Saito H , Bourinbaiar A , Ginsburg M , Minato K , Ceresi E , Yamada K , Machover D , Breard J , Mathe G 
Published: October 2019

Abstract
A human eosinophilic leukemia cell line, designated as EoL, was established from the peripheral blood of a patient with Philadelphia chromosome-negative eosinophilic leukemia (EL). The EoL cell line grows in single cell suspension with a doubling time of 48 hours for about one year. The reactivity of these cells was tested with a panel of monoclonal antibodies; they were found to express surface IA antigen, myeloid antigen (IF10, MY9) and membrane receptors for interleukin 2 (IL-2, Tac antigen). Under standard culture conditions, a small percentage of cells having more typical eosinophilic characteristics was present. These cells had cytoplasmic granules and were positive for Luxol-fast-blue and eosinophil peroxidase. Under culture conditions to induce the maturation of myeloid cells, such as alkaline medium or addition of dimethyl sulfoxide (DMSO), the frequency of cells with typical eosinophilic features increased to about 40%. In addition, cytogenetic studies showed that cultured cells and original leukemic blasts presented similar chromosome abnormalities. EoL seems to be a unique leukemic line committed to the eosinophilic lineage and can provide a useful in vitro model for the study of malignant eosinophilic properties.
Bone marrow transplantation for paroxysmal nocturnal hemoglobinuria: eradication of the PNH clone and documentation of complete lymphohematopoietic engraftment
Authors: Antin JH , Ginsburg D , Smith BR , Nathan DG , Orkin SH , Rappeport JM 
Published: October 2019

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) involves the proliferation of an abnormal and possibly premalignant hematopoietic stem cell. Successful treatment of PNH by marrow grafting requires that the PNH clone be eradicated by the pretransplant conditioning regimen. Four patients with PNH-associated marrow aplasia were transplanted with marrow from their HLA-matched, MLR-nonreactive siblings. Three patients were conditioned with cyclophosphamide, procarbazine, and antithymocyte serum (CTX/PCZ/ATS), and one was conditioned with busulfan/CTX/PCZ/ATS. Persistent complete engraftment of myeloid, lymphoid, and erythroid cell lines was demonstrated in all four patients by DNA sequence polymorphism analysis or cytogenetics, and RBC typing. There was no recurrence of the abnormal clone of cells for up to five years after transplantation despite the use of a conditioning regimen in three of them, which is not usually associated with permanent marrow aplasia. Bone marrow transplantation is a curative therapy in patients whose illness is severe enough to warrant the risk.
Molecular characterization of quinine/quinidine drug-dependent antibody platelet interaction using monoclonal antibodies
Authors: Berndt MC , Chong BH , Bull HA , Zola H , Castaldi PA 
Published: October 2019

Abstract
Two murine monoclonal antibodies, FMC 25 and AN 51, directed against distinct epitopes on the glycoprotein Ib complex, have been used to further define the mechanism of quinine/quinidine drug-dependent antibody interaction with platelets. FMC 25, directed against an epitope on glycoprotein IX, had no effect on platelet aggregation induced by collagen or adenosine diphosphate and little, if any, effect on ristocetin-induced platelet agglutination. FMC 25 and its (Fab)2 fragment, however, were potent inhibitors of drug-dependent antibody- induced platelet aggregation and blocked binding of drug-dependent antibody to platelets as assessed by indirect platelet immunofluorescence. In contrast, AN 51, directed against an epitope on the alpha-subunit of glycoprotein Ib, blocked ristocetin-induced, factor VIII/von Willebrand factor (FVIII/vWF)-dependent platelet agglutination but not drug-dependent antibody-induced platelet aggregation or binding of drug-dependent antibody to platelets. Selective proteolytic removal of the majority of the alpha-subunit of glycoprotein Ib (glycocalicin) from platelets by treatment with calcium- dependent protease did not affect binding of drug-dependent antibody. In addition, a quinidine-dependent antiplatelet antibody immunoprecipitated glycoprotein Ib complex from normal platelets and the membrane-associated proteolytic remnant of the glycoprotein Ib complex from calcium-dependent protease-treated platelets. Preincubation of drug-dependent antibody with purified glycoprotein Ib complex inhibited subsequent binding of antibody to platelets, but the separated components, glycoprotein Ib and glycoprotein IX, were both ineffective, suggesting that the normal interaction between glycoprotein Ib and glycoprotein IX in the intact complex was necessary for drug-dependent antibody recognition. The functional response of platelets to drug-dependent antibody was not mediated by way of platelet Fc receptor, since aggregation of washed platelets by acetone- aggregated IgG was not inhibited by FMC 25 (Fab)2. FVIII/vWF was not required for drug-dependent antibody-induced platelet aggregation. The combined evidence is consistent with quinine/quinidine-dependent antibody-platelet interaction occurring by way of a FVIII/vWF- independent, Fc receptor-independent mechanism that probably involves binding of antibody to glycoprotein IX or the beta-subunit of glycoprotein Ib or both.
Long-term follow-up of hemophiliacs with lymphocytopenia or thrombocytopenia
Authors: Eyster ME , Whitehurst DA , Catalano PM , McMillan CW , Goodnight SH , Kasper CK , Gill JC , Aledort LM , Hilgartner MW , Levine PH 
Published: October 2019

Abstract
Immunologic abnormalities resembling those seen in patients with the acquired immunodeficiency syndrome (AIDS) are frequently observed in multitransfused but otherwise healthy individuals with hemophilia. To determine whether there was clinical or laboratory evidence to suggest an abnormality of immunoregulation in persons with hemophilia before the recognition of AIDS, we examined data collected by the Hemophilia Study Group from 1975 to 1979 on 1,551 patients with factor VIII deficiency. The prevalence of lymphocytopenia and thrombocytopenia in patients over 5 years of age on entry was found to be 9.3% (94/1,013) and 5.0% (26/518), respectively. These rates were significantly different from a normal population (P less than .00001 and less than .0003). No cases meeting the definition of AIDS were noted during the study. However, on follow-up in 1984 of a cohort of 79 patients with thrombocytopenia or lymphocytopenia on two or more occasions during the study, eight patients (10%) with AIDS-related abnormalities, including idiopathic thrombocytopenic purpura, non-Hodgkin's lymphoma, generalized lymphadenopathy, and oral moniliasis without obvious cause were identified. Of the 79 patients, liver disease accounted for five of the ten deaths (12.6% mortality) observed during a minimum follow-up of five years after detection of cytopenia. Only one death was attributed to bleeding in the absence of liver disease. We conclude that (a) the frequency of lymphocytopenia and thrombocytopenia was increased in multitransfused factor VIII-deficient hemophiliacs before the advent of AIDS, and (b) persistent lymphocytopenia and thrombocytopenia appear to be strongly associated with liver disease, which was the leading cause of death in a cohort of hemophiliacs followed five or more years.
Hereditary persistence of fetal hemoglobin or (delta beta)o- thalassemia: three types observed in South-Chinese families
Authors: Zeng YT , Huang SZ , Chen B , Liang YC , Chang ZM , Harano T , Huisman TH 
Published: October 2019

Abstract
Hematological and hemoglobin composition data, and results from extensive gene mapping, using a battery of restriction enzymes and probes, have been used to distinguish different types of hereditary persistence of fetal hemoglobin (HPFH) (or delta beta-thal) among three Chinese families from the southern part of China. The first (Family Z) is an A gamma-(delta beta)+-HPFH without a detectable deletion and may be the same as, or similar to, that described by Farquhar et al (Am J Hum Genet 35:611, 1983). The second (Family C) resembles a G gamma(A gamma delta beta)o-thalassemia and is characterized by a large deletion of DNA originating 3′ to the G gamma globin gene and extending beyond sequences recognized by the pRK28 probe. Data from various digests indicate possible differences in the 3c′ end of the deletion when compared with data for some other types of G gamma(A gamma delta beta)o- thalassemia, described by Trent et al (Br J Haematol 57:279, 1984). The third (Family Zh) concerns a G gamma A gamma(delta beta)+-HPFH, which is characterized in heterozygotes by a fetal hemoglobin level of 20% to 25% with a G gamma value averaging 60% and by the absence of any DNA deletion detectable by extensive gene mapping analyses. The C----G mutation at position 202 5c′ to the G gamma globin gene [characteristic for the high G gamma-(delta beta)+-HPFH (Proc Natl Acad Sci USA 81:4894, 1984; Blood 64:1292, 1984)] was absent, but the Xmn I site at position 158 5c′ to the G gamma globin gene [characteristic for a modest increase in G gamma values and thus and increased G gamma to A gamma ratio (Blood)] was present. No indication has yet been obtained explaining the elevation in both G gamma and A gamma chains; haplotyping showed that the chromosome carrying this G gamma A gamma(delta beta)+ determinant is unusual among the Chinese population.
Restriction fragment length polymorphisms as markers of engraftment in allogeneic marrow transplantation
Authors: Blazar BR , Orr HT , Arthur DC , Kersey JH , Filipovich AH 
Published: October 2019

Abstract
We have used DNA hybridization techniques employing restriction fragment length polymorphisms (RFLPs) to quantitate the level of donor cell engraftment in bone marrow transplantation recipients. The genetic origin of the bone marrow cells and various peripheral blood populations was analyzed in 14 patients. We found at least one informative polymorphism for each donor-recipient pair. Additional markers of engraftment included cytogenetic analysis, HLA typing, and red cell typing. By DNA analysis, four patients had complete engraftment, five had partial engraftment, and five had no evidence of donor cell engraftment. In three cases, DNA analysis permitted detection of minor populations (5% to 10%) of donor or host cells. Eight of fourteen patients were evaluable for chimerism posttransplant by cytogenetic analysis. In five cases, cytogenetic results were completely concordant with DNA analyses. In two cases of apparent autologous recovery, as assessed using RFLPs, a small number of cells of donor karyotype was seen. In one other case, a small number of cells of host karyotype was not detected by RFLP studies. HLA typing in three partially engrafted patients was purely either of donor or host type. Red cell typing was discordant with DNA and/or cytogenetic results in four of eight cases. We conclude that DNA analysis at a limited number of informative genetic loci is useful for quantitating the degree of engraftment in multiple populations of nondividing cells following allogeneic bone marrow transplantation.
Quantitation of apo-, mono-, and diferric transferrin by polyacrylamide gradient gel electrophoresis in patients with disorders of iron metabolism
Authors: DiRusso SC , Check IJ , Hunter RL 
Published: October 2019

Abstract
We have developed a polyacrylamide gradient gel electrophoretic method to quantitate apo-, mono-, and diferric transferrin based upon differences in their molecular size. Purified transferrin saturated to different extents (3% to 98%) with iron showed proportions of the three forms as predicted from an approximately random distribution of iron between the two metal-binding sites. The iron distributions in sera of 14 normal individuals similarly correlated with the predicted values. In contrast, 22 of 43 patients with diseases associated with abnormalities in iron or transferrin metabolism had a disproportionate increase in monoferric transferrin. This abnormality occurred in seven of nine patients who had received bone marrow transplants, seven of 14 with chronic liver disease, and eight of nine menstruating women with probable iron deficiency anemia. Interestingly, 11 patients with malabsorption or chronic renal disease had normal iron distributions. The finding of abnormal distributions of iron on transferrin suggests that gradient gel analysis may be a useful tool for studying the physiologic mechanisms controlling iron utilization.
Inhibition of dog platelet function by in vivo infusion of F(ab')2 fragments of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor
Authors: Coller BS , Scudder LE 
Published: October 2019

Abstract
To assess the potential of monoclonal antibodies that inhibit platelet function in vitro as in vivo therapeutic agents, F(ab')2 fragments (0.17 to 0.81 mg/kg) of a murine monoclonal antibody (7E3) that binds to platelet glycoproteins IIb and/or IIIa and blocks platelet aggregation induced by ADP were infused into three dogs. Soon after infusion, platelets recovered from the dogs showed a decreased aggregation response to adenosine diphosphate, with the highest dose producing nearly total inhibition. These platelets also showed decreased ability to bind 125I-7E3, which was assumed to reflect occupancy of the sites by the unlabeled F(ab')2 fragments. At the highest dose, the binding decreased by 85%, reflecting the binding of approximately 44,000 molecules of 7E3 F(ab')2 per platelet. Platelet counts decreased after antibody infusion by less than 20%, and none of the dogs showed spontaneous bleeding. Both the aggregation and binding results reverted toward normal within one day. We conclude that it is possible to profoundly inhibit platelet function by in vivo infusion of F(ab')2 fragments of a monoclonal antiplatelet antibody without producing spontaneous hemorrhage or significant thrombocytopenia.
Antibodies to human T-cell leukemia virus type III in hemophiliacs from Spain
Authors: Kitchen L , Leal M , Wichmann I , Lissen E , Ollero M , Allan JS , McLane MF , Essex M 
Published: October 2019

Abstract
We tested serum samples from 50 hemophiliacs from Sevilla, Spain, for antibody to HTLV-III by indirect membrane immunofluorescence (IMI) and radioimmunoprecipitation with SDS polyacrylamide gel electrophoresis (RIP-SDS/PAGE). All had received commercial clotting factors from the United States with the exception of one hemophiliac who had never been transfused. Thirty-four (68%) reacted with HTLV-III-infected cells (H9/HTLV-III) by both methods, but not with the uninfected line (H9). Of 41 hemophilia-A patients tested, 28 (68%) were positive, and of nine hemophilia-B patients, six (66%) were positive. The nontransfused hemophilia-B patient was negative for antibody to HTLV-III by both methods. One patient with clinical AIDS tested positive as did six of seven with chronic unexplained lymphadenopathy. The eight individuals with AIDS or lymphadenopathy all had hemophilia A. We conclude that exposure to HTLV-III is widespread among asymptomatic hemophiliacs in Spain.