bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of hepatic dysfunction on oral cyclosporin pharmacokinetics in marrow transplant patients
Authors: Yee GC , Kennedy MS , Storb R , Thomas ED 
Published: October 2019

Abstract
The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporin (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v- host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (less than 1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P less than .05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.
Prognostic information from cytogenetic analysis in chronic B- lymphocytic leukemia and leukemic immunocytoma
Authors: Juliusson G , Robert KH , Ost A , Friberg K , Biberfeld P , Nilsson B , Zech L , Gahrton G 
Published: October 2019

Abstract
Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic lymphocytic leukemia (CLL), 29 had immunocytoma (IC), two had prolymphocytic leukemia, and one had centrocytic lymphoma; one was not subclassified. Cytogenetic studies after B cell mitogen stimulation showed that six patients had an extra chromosome 12 as the sole abnormality. Another ten patients had an extra chromosome 12 together with other abnormalities. One patient had dup(12). Fifteen patients showed clonal aberrations without +12. Eleven patients showed only normal metaphases, and 12 patients were not evaluated cytogenetically. The cytogenetic subgroup pattern did not distinguish between CLL and IC patients. There was no significant difference between the CLL and IC groups as regards clinical findings and prognosis. However, the cytogenetic typing proved to be of prognostic significance. Increasing numbers of chromosomal aberrations within the cell clone were significantly associated with a poorer prognosis, ie, with impairment of survival (P = .04) and therapy-free survival (P less than 10(-4]. Patients with complex karyotypes (at least clonal aberrations) showed the poorest survival (P = .007). Patients with +12 required treatment earlier than patients with a normal karyotype (P = .01) and patients with karyotypic changes other than +12 (P = .006). These latter differences were even more pronounced when only IC patients were considered (P = .005 and P = .002, respectively). A multivariate analysis revealed that +12 was as strong an indicator of poor survival as advanced Rai or Binet stages and a stronger predictor of therapy-demanding disease.
Simultaneous or sequential expression of lymphoid and myeloid phenotypes in acute leukemia
Authors: Neame PB , Soamboonsrup P , Browman G , Barr RD , Saeed N , Chan B , Pai M , Benger A , Wilson WE , Walker IR 
Published: October 2019

Abstract
Acute mixed myeloid-lymphoid leukemia is uncommon. We report four cases in which myeloid and lymphoid cell markers were observed simultaneously or sequentially when 94 patients with acute leukemia were phenotyped according to the French-American-British (FAB) classification system, with cytochemical stains, and with immunologically defined differentiation markers (identified by monoclonal antibodies and antiterminal deoxynucleotidyl transferase [TdT]). In one case, conversion from acute lymphoblastic leukemia to acute myeloid leukemia was noted (FAB L1, TdT+ to FAB M4, Auer rods, TdT-). In another patient, two distinct populations of myeloid and lymphoid blast cells were observed simultaneously (TdT-, LeuM1+/TdT+, LeuM1-). In two additional patients, acute leukemia was characterized by the expression of both lymphoid and myeloid markers on the same cell (TdT+/Leu M1+, B4+/Leu M1+ and greater than or equal to 70% TdT+, T11+, My9+). The Philadelphia (Ph1) chromosome was negative in all cases, though other chromosomal abnormalities were noted in three out of four cases. Malignant transformation of a pluripotential stem cell for both lymphoid and myeloid lineages, with or without the Ph1 chromosome marker, could explain the coexistence of distinct populations of lymphoblasts and myeloblasts in acute leukemia. Acute leukemia with a biphenotypic profile may reflect genome depression accompanying neoplasia.
Increased binding of fibrinogen to platelets in diabetes: the role of prostaglandins and thromboxane
Authors: DiMinno G , Silver MJ , Cerbone AM , Riccardi G , Rivellese A , Mancini M , Thiagarajan P 
Published: October 2019

Abstract
Previous studies suggested a role for prostaglandins or thromboxane A2, or both in the exposure of fibrinogen receptors on normal platelets in response to several aggregating agents. Platelets from diabetics are known to be more sensitive to aggregating agents and to produce more prostaglandins and thromboxane than platelets from normal subjects. We compared fibrinogen binding to platelets from diabetic subjects with binding to platelets from normal subjects and determined whether aspirin (which inhibits the formation of prostaglandins and thromboxane) would inhibit the binding of fibrinogen to platelets from diabetic subjects and whether this correlated with its effects on platelet aggregation. We found the following: Aspirin suppressed thromboxane formation and rendered the platelets less sensitive to the induction of aggregation by adenosine diphosphate (ADP) or collagen. The amount of U-46619 [( 15s]-hydroxy-11-alpha, 9-alpha [epoxy-methano]- prosta[5Z,13E]-dienoic acid, a stable analog of prostaglandin endoperoxide/thromboxane A2) necessary to induce aggregation, was similar in normal and diabetic subjects and was unchanged after ingestion of aspirin. Binding of 125I-fibrinogen following stimulation of platelets by ADP or collagen was greater in diabetic (because more binding sites were exposed) than in normal subjects. However, following stimulation by U-46619, binding was similar in diabetic and normal subjects. Aspirin caused a reduction in the exposure of binding sites on both platelets from diabetic and normal subjects, so that (in this respect) platelets from diabetic subjects became more like those from normal subjects. Effects of the monoclonal antibody B59.2, which is specific for the platelet glycoprotein IIb-IIIa complex (the presumed receptor for fibrinogen on the platelet surface) were also studied. The amount of this antibody that bound to platelets was the same for normal and diabetic subjects both before and after aspirin and with or without stimulation by ADP or collagen. In addition, B59.2 inhibited aggregation and fibrinogen binding in both platelets from diabetic and normal subjects. The combined data suggest that the glycoprotein IIb- IIIa complex of platelets from diabetic subjects is similar to that of platelets from normal subjects and that the increased fibrinogen binding and aggregation of platelets from diabetic subjects in response to ADP or collagen is mediated by increased formation of prostaglandin endoperoxide or thromboxane A2, or both.
Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics
Authors: Stong RC , Korsmeyer SJ , Parkin JL , Arthur DC , Kersey JH 
Published: October 2019

Abstract
A cell line, designated RS4;11, was established from the bone marrow of a patient in relapse with an acute leukemia that was characterized by the t(4;11) chromosomal abnormality. The cell line and the patient's fresh leukemic cells both had the t(4;11)(q21;q23) and an isochromosome for the long arm of No. 7. Morphologically, all cells were lymphoid in appearance. Ultrastructurally and cytochemically, approximately 30% of the cells possessed myeloid features. The cells were strongly positive for terminal deoxynucleotidyl transferase. They were HLA-DR positive and expressed surface antigens characteristic for B lineage cells, including those detected by anti-B4, BA-1, BA-2, and PI153/3. Immunoglobulin gene analysis revealed rearrangements of the heavy chain and kappa chain genes. The cells lacked the common acute lymphoblastic leukemia antigen and antigenic markers characteristic of T lineage cells. The cells reacted with the myeloid antibody 1G10 but not with other myeloid monoclonal antibodies. Treatment with 12-O-tetradecanoyl- phorbol-13-acetate induced a monocyte-like phenotype demonstrated by cytochemical, functional, immunologic, and electron microscopic studies. The expression of markers of both early lymphoid and early myeloid cells represents an unusual phenotype and suggests that RS4;11 represents a cell with dual lineage capabilities. To our knowledge, RS4;11 is the first cell line established from t(4;11)-associated acute leukemia.
Absence of a surface-connected canalicular system in bovine platelets
Authors: Zucker-Franklin D , Benson KA , Myers KM 
Published: October 2019

Abstract
Human platelets possess a surface-connected canalicular system (SCCS) which has been postulated to subserve endocytosis as well as secretion. Platelets of most animal species studied to date, including those of cattle, function similarly. However, ultrastructural analysis of freeze- fractured bovine platelets or thin sectioned bovine platelets treated with electron-dense tracers failed to delineate a SCCS. This observation may throw an entirely new light on the role of this organelle.
Plasmin effect on platelet glycoprotein Ib-von Willebrand factor interactions
Authors: Adelman B , Michelson AD , Loscalzo J , Greenberg J , Handin RI 
Published: October 2019

Abstract
We have studied the effect of streptokinase on platelets in platelet- rich plasma (PRP) and of plasmin on washed platelets. By three and one- half minutes after the addition of 50,000 IU/mL streptokinase to PRP, the maximum rate of ristocetin-induced platelet agglutination declined 40%, and by 60 minutes, it declined 70%. During the same time interval, the thrombin time increased from 20 seconds to over 120 seconds. At a concentration as low as 50 IU/mL, streptokinase reduced the maximum rate of ristocetin-induced platelet agglutination by 50% and prolonged the thrombin time to 1.5 times control value. Streptokinase added to PRP also caused inhibition of platelet aggregation following stimulation by 2.9 mumol/L adenosine diphosphate, 0.25 U/mL thrombin, and 0.025 mg/mL collagen. Plasmin, 0.05 to 1.0 CU/mL, reduced ristocetin-mediated agglutination of washed platelets in the presence of von Willebrand factor (vWF) from 66% of control to 2% of control, following a one-hour incubation. Autoradiograms produced following sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) of plasmin- treated 125I-surface-labeled platelets demonstrated progressive loss of a protein with a molecular weight (mol wt) of 180,000; simultaneously, a protein with mol wt 135,000 appeared on autoradiograms produced following SDS-PAGE of the surrounding platelet medium. These proteins are similar in molecular weight to glycoprotein (gp) Ib, a platelet surface receptor for vWF, and glycocalicin, a proteolytic fragment of gpIb. By use of an enzyme-linked immunosorbent assay (ELISA) based immunoinhibition assay for glycocalicin, we were able to demonstrate that plasmin treatment of washed platelets released a glycocalicin- related antigen into the surrounding medium and that appearance of this material corresponding to loss of vWF-dependent, ristocetin-induced agglutination.
Killer cell activity of human monoblastic leukemia cells as detected with a monocyte-specific target cell
Authors: Ziegler-Heitbrock HW , Munker R , Thiel E , Krebs I , Riethmuller G 
Published: October 2019

Abstract
Peripheral blood leukemia cells from patients with acute monoblastic leukemia (AMoL) were tested for killer cell activity against target cells that detected natural killer cell-mediated or monocyte-mediated spontaneous cytotoxicity. The fibrosarcoma cell line Wehi 164, pretreated with actinomycin D to induce susceptibility to lysis, specifically detects the activity of unstimulated human monocytes. In four of six cases of AMoL, high killer cell activity could be measured against this target. In three of these four cases, the killer cell activity could be assigned exclusively to the leukemic clone, based on the high leukocyte counts and the resultant dilution of normal cells, as evidenced by marker and by functional analysis. While leukemic cells with killer cell activity against Wehi 164 contained 34% to 45% cells that were positive for binding of the 63D3 monoclonal antibody, the two leukemic samples without killer cell activity contained only 1% and 12% 63D3-positive cells. Cell sorting of 63D3-positive and -negative cells from two leukemias with killer cell activity demonstrated that the killer cell activity was restricted to the 63D3-positive fraction of AMoL cells. These data demonstrate that monoblastic leukemia cells can be potent killer cells and that killing activity is linked to the 63D3- defined cell surface molecule.
Von Willebrand factor in the vessel wall mediates platelet adherence
Authors: Stel HV , Sakariassen KS , de Groot PG , van Mourik JA , Sixma JJ 
Published: October 2019

Abstract
A monoclonal antibody directed against the von Willebrand factor moiety (vWF) of factor VIII-von Willebrand factor (FVIII-vWF), which blocks ristocetin-induced platelet aggregation as well as the binding of FVIII- vWF to platelets in the presence of ristocetin, inhibited platelet adherence to human artery subendothelium when present in normal flowing blood. This monoclonal antibody, CLB-RAg 35, inhibited platelet adherence as a function of the shear rate. At wall shear rates below 500 s-1, platelet adherence was not affected, but at higher shear rates platelet adherence was gradually inhibited, reaching an average of 11% of the normal value at 2,500 s-1. Indirect immunofluorescence established the reactivity of CLB-RAg 35 with vWF present in artery subendothelium. Pretreatment of normal vessel walls with this antibody inhibited adherence of platelets in blood from a patient with severe homozygous von Willebrand's disease and in blood from normal individuals. The inhibition was shear-rate dependent and significant at high shear rates (2,500 s-1). By adding increasing amounts of purified FVIII-vWF to normal blood, the inhibition was gradually overcome. These data indicate that vWF present in the vessel wall contributes appreciably to platelet adherence. At high wall shear rates, platelet adherence is mediated virtually completely by both plasma FVIII-vWF and vWF in the vessel wall. At low wall shear rates (below 500 s-1), platelet adherence occurs independent of FVIII-vWF in plasma and vWF in the vessel wall.
The role of activated human platelets in prothrombin and factor X activation
Authors: Rosing J , van Rijn JL , Bevers EM , van Dieijen G , Comfurius P , Zwaal RF 
Published: October 2019

Abstract
The effect of activated human platelets in intrinsic factor X activation was compared with their effect in prothrombin activation. Compared with unstimulated platelets, platelets triggered by the combined action of collagen plus thrombin showed a tenfold activity increase in prothrombin activation, and a 20-fold rate enhancement in factor X activation. Treatment of collagen plus thrombin-stimulated platelets with N.naja phospholipase A2 almost completely abolished their activity in prothrombin and factor X activation. Since no significant cell lysis occurs during phospholipase treatment, this indicates that platelet phospholipids, exposed at the membrane exterior, play an essential role in the interaction of platelets with the proteins of the prothrombin and factor X-activating complexes. The time course of generation of the procoagulant platelet surface was different when the amount of coagulation factors present in the assay systems was varied. At suboptimal concentrations of coagulation factors, maximum platelet activity was reached after a shorter time period than at saturating concentrations. When measured at suboptimal amounts of coagulation factors, the platelet activity in prothrombin and factor X activation is also more sensitive to phospholipase treatment. Experiments with synthetic phospholipid mixtures show that prothrombin and factor X activation are optimal at low mol% phosphatidylserine when high concentrations of factor Va and factor VIIIa are employed. The optimal mol% phosphatidylserine increases when the concentrations of nonenzymatic protein cofactors are lowered. These findings are discussed in relation to a model in which phosphatidylserine, exposed at the outer surface of activated platelets, plays an essential role in prothrombin and factor X activation. It is proposed that this phosphatidylserine is not homogeneously distributed in the platelet outer membrane, but that areas with different phosphatidylserine density participate in coagulation factor activation.
Inherited phosphofructokinase deficiency in dogs with hyperventilation- induced hemolysis: increased in vitro and in vivo alkaline fragility of erythrocytes
Authors: Giger U , Harvey JW , Yamaguchi RA , McNulty PK , Chiapella A , Beutler E 
Published: October 2019

Abstract
Two male English springer spaniel dogs with a chronic hemolytic anemia and sporadic hemolytic crises, historically related to “stress” situations, were studied. Although canine erythrocytes are in general known to be more alkaline fragile, erythrocytes from both patients began to lyse earlier, at significantly lower pH values (near pH 7.4 at 37 degrees C), than erythrocytes from control dogs. Hyperventilation induced by 30 minutes of exercise, placement in a 39 degrees C water bath, or intravenous doxapram increased venous blood pH in dog 1 and control dogs, but transient hemoglobinemia, hemoglobinuria, and severe bilirubinuria occurred only in the studied patient. The erythrocyte phosphofructokinase (PFK) activity was severely decreased in both dogs (10% of controls). The erythrocyte 2,3-diphosphoglycerate content was markedly reduced and the cell chloride content was consequently increased. This change in cell chloride content is related to an increase in the erythrocyte pH, which may partially explain the pathogenesis of hemolysis in canine PFK deficiency. Thus, these studies demonstrate a presumably inherited erythrocyte PFK deficiency in English springer spaniels, which causes an increased in vitro and in vivo erythrocyte alkaline fragility. Dogs with PFK deficiency and inducible hemolytic crises may become a valuable genetic animal model in which to study the pathophysiology of hemolysis.
The E rosette-associated antigen of T cells can be identified on blasts from patients with acute myeloblastic leukemia
Authors: Mirro J , Antoun GR , Zipf TF , Melvin S , Stass S 
Published: October 2019

Abstract
Monoclonal antibody T-11, considered specific for the sheep erythrocyte rosette-associated antigen of T cells, reacted with leukemic blasts from four of 23 patients with morphologic and cytochemical criteria for acute myeloblastic leukemia (AML). Although 83%, 87%, 88%, and 96% of the blasts from these patients reacted with T-11, only one patient demonstrated a small percentage of heat-stable E rosettes (5%). Antibody 9.6, which also reacts with the E rosette-associated antigen, was tested on blasts from two of the T-11-positive patients and was also strongly reactive (96% and 98%). Dual staining of blasts from these two patients demonstrated a small number of cells that simultaneously expressed the E rosette-associated antigen and myeloid- associated cytochemistries (myeloperoxidase [MPO] and Sudan black B). Additionally, leukemic blasts were identified that simultaneously expressed the E rosette-associated antigen and contained Auer rods. Antibody OKT-11 immunoprecipitated a 48,100-dalton glycoprotein from these leukemic blasts that is similar in molecular weight to that previously determined for the T cell surface protein (Tp50), thus providing strong evidence that this molecule can be found in some cases of AML. Because cells simultaneously expressing both the E rosette- associated antigen and MPO were identified, it would appear likely that leukemic blasts with only the E rosette-associated antigen or only MPO arose from the same progenitor. Our findings further demonstrate that the epitopes identified by antibodies OKT-11, T-11, and 9.6 are not always associated with, or sufficient for, 37 degrees C E rosette formation and can be found on blasts from patients with AML.
Neutrophils autoinactivate secretory products by myeloperoxidase- catalyzed oxidation
Authors: Clark RA , Borregaard N 
Published: October 2019

Abstract
The neutrophil response to inflammatory stimuli involves the formation of reactive oxygen species and secretion of granule enzymes. In studying secretion of vitamin B12 binding protein by human neutrophils, we noted a major decrease in total recoverable activity from the extracellular fluid plus the stimulated cells (54% of resting cells). Recovery of B12 binding protein from neutrophils exposed to phorbol myristate acetate or opsonized zymosan was significantly enhanced on addition of heme enzyme inhibitors (azide, cyanide) or catalase or when halide-free medium was used. The changes in B12 binding protein recovery were attributable entirely to increases in extracellular fluid levels, and cell pellet content was unaffected. These data indicate extracellular destruction of functional B12 binding protein by the halide-dependent heme enzyme myeloperoxidase and H2O2. Kinetic studies demonstrated rapid secretion of B12 binding protein in the first two to five minutes, followed by its inactivation over the next 20 to 30 minutes. A cell-free extract of vitamin B12 binding protein was readily inactivated on exposure to purified myeloperoxidase, H2O2, and a halide. These findings document a functional interaction among products of the neutrophil specific granules (B12 binding protein), azurophil granules (myeloperoxidase), and metabolic burst (H2O2). They provide an interesting model for the modulation of the inflammatory response by oxidation of secretory products of neutrophils.