bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute leukemia in idiopathic sideroblastic anemia: response to combination chemotherapy
Authors: Hussein KK , Salem Z , Bottomley SS , Livingston RB 
Published: October 2019

Abstract
Three patients with idiopathic sideroblastic anemia of variable duration developed acute leukemia. In two the leukemia was morphologically and histochemically myeloblastic, in one lymphoblastic. With combination chemotherapy remission was achieved in all three. The remission inductions were complicated by long periods of bone marrow suppression and the duration of remissions was brief (3, 2 and 3 months). Survival after diagnosis was 13, 10 and 9 mo, respectively. The ring sideroblast abnormality persisted during the leukemic and remission phases and transfusion requirements remained unaltered in the two patients with transfusion dependent anemia throughout their courses.
Preparation of factor IX deficient human plasma by immunoaffinity chromatography using a monoclonal antibody
Authors: Goodall AH , Kemble G , O'Brien DP , Rawlings E , Rotblat F , Russell GC , Janossy G , Tuddenham EG 
Published: October 2019

Abstract
A murine hybridoma clone is described that grows continuously in culture and produces a monoclonal antibody we have called Royal Free Monoclonal Antibody to factor IX No. 1 (RFF-IX/1). This has high affinity for a coagulation site on factor IX. RFF-IX/1 immobilised on sepharose can be used to deplete factor IX from normal human plasma. This immunoaffinity depleted plasma is indistinguishable from severe Christmas disease plasma and can be used as the substrate in a one stage coagulation assay for factor IX. The affinity column has high capacity and can be regenerated so that large scale production from normal plasma of factor IX deficient plasma as a diagnostic reagent is now feasible.
Immunologic evaluation of T chronic lymphocyte leukemia cells: correlations among phenotype, functional activities, and morphology
Authors: Pandolfi F , De Rossi G , Semenzato G , Quinti I , Ranucci A , De Sanctis G , Lopez M , Gasparotto G , Aiuti F 
Published: October 2019

Abstract
Chronic lymphocytic leukemia of T-cell origin (T-CLL), a rare variant of CLL, appears to be a clonal proliferation of mature T cells of one of several subsets. In the cells of 7 T-CLL patients, surface markers (including those reacting with a panel of monoclonal antibodies), functional activities, and electron microscopic morphology were evaluated. The phenotypic patterns of circulating T-CLL cells correspond to those of normal mature T-cell subsets. The cells of three patients demonstrated at least one marker reported to be expressed by suppressor/cytotoxic T cells: those of three patients expressed markers apparently linked with T-helper activity. Cells from one patient appeared to be a heterogeneous proliferation of more than one T-cell subset. These T-CLL cells may also retain some of the functional activity of the normal T subpopulations. Our data indicate that a combination of several tests should be used to characterize the proliferating cells in T-CLL.
Immunologic characterization of a helper T-cell lymphoma
Authors: Gramatzki M , Dolan MF , Fauci AS , Maples JA , Bonnard GD , Strong DM 
Published: October 2019

Abstract
The lymphocytes of a patient with a T-cell non-Hodgkin's lymphoma with peripheral blood involvement and polyclonal hypergammaglobulinemia were characterized in terms of surface markers and immunologic functions. Using the fluorescence-activated cell sorter and employing various monoclonal antibodies against T-cell surface antigens, it was shown that almost all of the patient's peripheral blood lymphocytes were positive for OKT4 and 9.3, antibodies that recognize helper T-cell subset. The circulating lymphoma cells had typical characteristics for T cells; they formed spontaneous rosettes with sheep erythrocytes and stained with the pan-T-cell antibodies 9.6 and 10.2, but did not react with other anti-T-cell monoclonal reagents such as OKT3, UCHT-1, and 3A1. The cells appeared to be mature by the fact that they did not stain with OKT6, and terminal deoxynucleotidyl transferase was undetectable. Functionally, they were able to provide “help” for antibody production, and they could be stimulated to produce moderate amounts of interleukin-2, while unable to proliferate in response to mitogens. Morphologically, some of the lymphocytes showed a deeply cleaved nucleus.
The biochemical and genetic basis for the microheterogeneity of human R- type vitamin B12 binding proteins
Authors: Yang SY , Coleman PS , Dupont B 
Published: October 2019

Abstract
R-type vitamin B12 binding proteins (R proteins) from human granulocytes, erythrocytes, plasma, and other body fluids were characterized by isoprotein banding patterns on autoradiograms after resolution via thin-layer polyacrylamide isoelectric focusing (IEF) gel electrophoresis. R proteins obtained from various tissue sources in a given individual show tissue-specific electrophoretic patterns. The desialated R proteins obtained following in vitro treatment with neuraminidase are, however, the same for any given individual and do not show tissue specificity. The differences seen in native R proteins (i.e., transcobalamin I, III, and others) obtained from different tissues are due to variations only in the sialic acid content. Granulocytes from patients with chronic myelogenous leukemia (CML) contain both TC I and TC III, and these R proteins can be released in vitro by lithium stimulation. Normal granulocytes contain only TC III. Differences in desialated R proteins from individual to individual are due to a genetic polymorphism controlled by a single genetic locus (designated TCR) with two alleles, 1 and 2, which are found to be codominantly expressed in heterozygous individuals. The allelic variants of the desialated R proteins found in different blood cells and body fluids are controlled by only one genetic locus.
Changes in surface antigens on malignant T cells from lymphoblastic lymphomas at relapse: an appraisal with monoclonal antibodies and microfluorometry
Authors: Bernard A , Raynal B , Lemerle J , Boumsell L 
Published: October 2019

Abstract
By using a panel of monoclonal antibodies reactive with lymphoid differentiation antigens and microfluorometry, we investigated the malignant cells from five patients with T-cell lymphoblastic lymphoma both at initial involvement and at relapse. We have observed changes in cell surface antigens densities in four of the five cases. These changes could be interpreted as a shift in the status of differentiation of the malignant cells. In two cases the malignant cells appeared to be arrested at an earlier stage at relapse than at initial involvement, while in the two other cases, cells at relapse appeared to be arrested at a later stage than at initial involvement. Interestingly, a parallelism was observed between regression of the differentiative status of the malignant T cells and “leukemic conversion.” These observations are also relevant to the understanding of the development of tumor resistance to chemotherapy.
Monoclonal antibody BA-1 does not bind to hematopoietic precursor cells
Authors: Jansen J , Ash RC , Zanjani ED , LeBien TW , Kersey JH 
Published: October 2019

Abstract
Monoclonal antibody BA-1 binds to B lymphocytes, to cells from most cases of non-T acute lymphoblastic leukemia (ALL), and weakly to neutrophils. To determine whether BA-1 also reacts with hematopoietic progenitor cells (HPC), we studied the effect of removal of BA-1+ cells from human bone marrow on the proliferation in vitro of the trilineage precursor cell CFU-GEMM, and on the committed progenitor cells of granulopoiesis (CFU-C) and erythropoiesis (BFU-E/CFU-E). Complement- mediated cytotoxicity using BA-1 at concentrations far beyond those required to lyse BA-1+ bone marrow cells and ALL cells did not result in inhibition of colony formation in any of the assays. A rosette separation method, using ox red blood cells coated with BA-1, resulted in enrichment of HPC in the BA-1-depleted interface, whereas very few HPC were found in the BA-1-enriched pellet. Both methods indicate that BA-1 does not bind to HPC, although binding of the antibody to the lymphohematopoietic stem cell cannot be excluded yet. The high cytotoxic capacity of the IgM antibody BA-1, and the lack of reactivity with HPC, make the antibody particularly suitable for use in autologous bone marrow transplantation for patients with ALL.
Studies of circulating hemopoietic progenitor cells in human fetal blood
Authors: Linch DC , Knott LJ , Rodeck CH , Huehns ER 
Published: October 2019

Abstract
High levels of committed erythroid and granulocytic/monocytic progenitor cells have been demonstrated in fresh blood obtained at fetoscopy. The fetal progenitor cells were more sensitive to appropriate stimuli (erythropoietin and colony-stimulating factor) than adult progenitor cells grown under the same conditions, and this was shown to be due to intrinsic differences in the progenitor cells at the different developmental stages.
Genetic differences in red cell osmotic fragility: analysis in allophenic mice
Authors: Dewey MJ , Brown JL , Nallaseth FS 
Published: October 2019

Abstract
Mice of strain DBA/2J were found to produce red cells considerably more resistant to osmotic lysis than cells from C57BL/6J or the F1 hybrid between the two strains. Such strain-specific differences in osmotic fragility could be the result of genetically determined humoral or other systemic differences that indirectly influence red cell properties. Alternatively, this phenotypic variation might be an inherent property of the erythrocyte themselves and be directly controlled by their genotype. Analysis of red cells from allophenic (mosaic) mice of the strain composition C57BL/6J in equilibrium DBA/2J demonstrated that the latter possibility is the case. In such mice, erythrocytes of the DBA/2J genotype are relatively more resistant to osmotic lysis than are those of the C57BL/6J genotype; partial lysis of allophenic blood at intermediate salt concentrations results in marked enrichment for DBA/2J cells among the survivors. Future experiments designed to determine the mechanism underlying this difference can now focus on the properties of the red blood cells per se with the certainty that this property is inherent to the genotype of each cell.
Macrophage differentiation of human precursor B-cell line by phorbol ester and colony-stimulating factor
Authors: Hiraoka A , Kubota K , Preisler HD , Minowada J 
Published: October 2019

Abstract
A human round cell line, KLM-2, is considered to be precursor B-cell by immunologic surface marker analysis and histochemical studies. The effect of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and/or colony- stimulating factor (CSF) on KLM-2 cells was investigated. KLM-2 cells became adherent to the bottom of the flask on day 2 after liquid culture with TPA, and the number of macrophage-like adherent cells (mAC) with pseudopodia showed a TPA dose-dependent increase to the peak level on day 3 or 4. The mAC had a phagocytic activity. The suspending cells were positive for alpha-naphthyl acetate esterase (NAE) up to about 50% in culture with TPA. A TPA concentration of 100 ng/ml was optimal to provide a maximum number of mAC and NAE-positive suspending cells. Particularly, such effects of TPA on KLM-2 cells were markedly accelerated in the presence of CSF. These findings indicate macrophage differentiation of KLM-2 cells in the presence of TPA and CSF. KLM-2 cells may be a bipotential stem cell line differentiating into B-cell and monocyte-macrophage lineages.
Geometric, osmotic, and membrane mechanical properties of density- separated human red cells
Authors: Linderkamp O , Meiselman HJ 
Published: October 2019

Abstract
Although there is evidence that the deformability of the entire red blood cell (RBC) decreases during aging, reports on changes in relevant specific properties associated with the aging process are limited and not in total agreement. The purpose of this study was to evaluate some of the factors that might contribute to this decreased deformability. Geometric, osmotic, and membrane mechanical properties of unfractionated, top (“young”) and bottom (“old”) RBC from 5 healthy adult donors were measured using micropipette techniques. Surface area, volume, and diameter of RBC were measured at osmolalities of 297, 254, 202, and 153 mosm/kg. Two membrane mechanical properties, surface shear modulus of elasticity (mu) and time constant (tc) of viscoelastic recovery, were studied only in isotonic media. At each of the osmolalities, volume and surface area of the bottom cells were about 25% lower than those of the top cells. Bottom cells showed smaller increases in volume with decreasing osmolality than top cells; the surface area remained constant with changing osmolality for all three groups. The surface area-to-volume ratio and the minimum cylindrical diameter of the bottom cells were essentially identical to the top cells. However, both the surface area index (actual are of RBC divided by area of a sphere of same volume) and the swelling index (maximal volume divided by actual volume) of the bottom cells were significantly lower than top RBC. The shear modules of elasticity (mu) was about 0.006 dyne/cm in all 3 RBC populations, indicating that the forces necessary to deform a portion of the membrane did not change with RBC aging. The viscoelastic time constant (tc) was 0.148 +/- 0.020 (SD) sec for the bottom RBC and 0.099 +/- 0.017 sec for the top cells. This difference indicates that shape recovery following membrane deformation is delayed in old RBC. The membrane surface viscosity (eta), calculated as the product of tc times mu was 0.95 +/- 0.22 x 10(-3) dyne-sec/cm for the bottom cells and 0.54 +/- 0.15 x 10(-3) for the top RBC. These data indicate that the relative deficit in membrane surface area and the increased membrane viscosity of old RBC may be important determinants for their decreased deformability and their eventual removal from the circulation.
The osmotic fragility of erythrocytes after prolonged liquid storage and after reinfusion
Authors: Beutler E , Kuhl W , West C 
Published: October 2019

Abstract
Although it is recognized that red cells lose membrane during storage, estimation of the osmotic fragility of erythrocytes has not previously proven to be a useful measurement of the storage lesion. Erythrocytes from blood stored in CPD-A2 were found to have a markedly increased osmotic fragility. A major portion of this increase was found to be due to accumulation of lactate, which is only slowly transported from within erythrocytes and which therefore exerts a strong osmotic effect in the usual osmotic fragility test. After an hour's incubation in a large volume of iso-osmotic buffer, the osmotic fragility curve of stored erythrocytes was much more nearly normal. Such cells were found to have a volume 5%--8% greater than that of normal cells, indicating that even after removal of lactate more osmotically active material was present in the stored erythrocytes than in fresh cells. Most of this differences can be accounted for by substitution of chloride ion for 2,3-DPG, since chloride exerts approximately 3.7 times the osmotic effect of 2,3-DPG per unit charge. In addition to the shift in osmotic fragility produced by the increased intracellular osmotically active material, a “fragile tail” of red cells was also present. Stored erythrocytes were labeled with 51Cr and reinfused into the volunteer donors. The osmotic fragility of the reinfused cells was estimated using a technique of sequential osmotic hemolysis that permitted accurate estimation of osmotic fragility of transfused cells using very small amounts of 51Cr. The osmotic fragility of the reinfused cells became less than those of fresh cells after 24 hr and was exactly the same as those of fresh cells after 4 days. The fragile tail disappeared at a rate that approximated the rate of loss of nonviable erythrocytes from the circulation as measured by 51Cr. These findings are consistent with the preferential destruction of a subpopulation of red cells with a diminished surface area.
A familial hemorrhagic diathesis in a Dutch family: an inherited deficiency of alpha 2-antiplasmin
Authors: Kluft C , Vellenga E , Brommer EJ , Wijngaards G 
Published: October 2019

Abstract
This study concerns a case of congenital homozygous deficiency in alpha 2-antiplasmin associated with a severe hemorrhagic diathesis. Heterozygous family members also show a mild bleeding tendency. The propositus is a 17-yr-old male born of white parents and showing a severe hemorrhagic diathesis characterized by spontaneous bleeding in the joints since his early childhood. He was originally suspected of having factor XIII deficiency but was found to have normal functions of the coagulation system and the platelets. Except for alpha 2- antiplasmin, all protease inhibitors showed normal plasma values. With the immediate plasmin inhibition test (synthetic substrate), only 2% of normal functional inhibition was detected, while no reaction with monospecific antisera for alpha 2-antiplasmin was observed. Inhibition of activator-induced fibrinolysis in vitro was reduced. No enhanced spontaneous in vitro fibrinolysis was detected nor were there signs of increased in vivo fibrinolysis during an asymptomatic period. During recovery from a hemorrhagic episode, signs of previous consumption of antithrombin III, alpha 2-macroglobulin, factor XIII, and inter-alpha- trypsin inhibitor were noted. After the diagnosis was made, treatment with tranexamic acid (4 daily doses of 1 g) was effective for about 2 yr. Among the 37 family members studied, a separate group of 16 individuals (including the father and mother of the propositus) with approximately one-half normal plasma levels of alpha 2-antiplasmin both functionally (59% +/- 6%) and immunologically 48% +/- 8%) was discovered. The defect appeared to be inherited as an autosomal recessive gene; no ancestral consanguinity could be shown. The group of apparent heterozygotes as a whole showed increased levels of alpha 1- antitrypsin (142% +/- 39%; p less than 0.01), indicating systemic consequences of the deficiency and reduced binding (+/- 50%) of alpha 2- antiplasmin to fibrin. Six exhibited a mild hemorrhagic diathesis for which no explanation was provided by routine screening of coagulation and platelet functions; also, within the group of heterozygotes, the occurrence of the bleeding tendency did not correlate with differences in residual alpha 2-antiplasmin levels and functions. It is concluded that not only the absence of alpha 2-antiplasmin but also a reduction in its plasma level to +/- 60% of normal may predispose to a hemorrhagic diathesis.
A B-lymphoma cell line that forms rosettes with neuraminidase-treated sheep erythrocytes through monoclonal surface immunoglobulin
Authors: Tsutsumi Y , Suzuki S , Mikata A , Suzuki H , Kageyama K , Watanabe S , Minato K , Shimoyama M 
Published: October 2019

Abstract
Undifferentiated lymphoma from a 39-year-old female became serially xenotransplantable to preirradiated nude mice. The tumor cells (KT) possessed a monoclonal surface immunoglobulin (SIg mu, kappa) and formed rosettes with neuraminidase-treated sheep erythrocytes (SEn). Precise characterizations of the SEn rosette, however, revealed the following facts: (1) Neuraminidase-untreated or 2- aminoethylisothiuronium bromide (AET) treated sheep erythrocytes were not bound to the KT cells. (2) SEn rosettes on the KT cells did not show a temperature dependency. (3) Neuraminidase-treated erythrocytes from man, horse, mouse, and rabbit were not bound to the KT cells. (4) Preincubation of the KT cells with antipolyvalent immunoglobulin or anti-kappa-chain serum abolished the SEn rosette formation. (5) Trypsinization decreased both SEn rosettes and SIg on the KT cells. (6) SEn rosettes on the KT cells were too loose to be separated from nonrosetting cells by a Percoll gradient centrifugation method. Summarizing these results, the monoclonal SIg on the KT cells recognized sheep erythrocyte antigen(s) that were exposed only after the neuraminidase treatment. Therefore, this was considered to be a case with peculiar B-lymphoma cells that bound SEn through their SIg.
A bleeding disorder due to deficiency of alpha 2-antiplasmin
Authors: Miles LA , Plow EF , Donnelly KJ , Hougie C , Griffin JH 
Published: October 2019

Abstract
A deficiency of alpha 2-antiplasmin has been identified in a female patient with severe and frequent bleeding episodes. Routine coagulation and platelet assays of the patient's plasma were within normal limits. However, abnormally rapid whole blood or dilute plasma clot lysis times and an abnormal FXIII test in which clots were lysed in the presence of urea or saline suggested an abnormal fibrinolytic system. Analysis of alpha 2-antiplasmin levels by radioimmunoassay revealed less than 1.0 microgram/ml alpha 2-antiplasmin. Functional assays indicated an alpha 2-antiplasmin level less than or equal to 10% of normal. Addition of purified alpha 2-antiplasmin to the patient's plasma restored its ability to inhibit plasmin in in vitro assays, and mixtures of patient plasma with normal plasma did not interfere with the antiplasmin activity of the normal plasma. Whereas normal platelets contain 68 ng alpha 2-antiplasmin/10(9) platelets, platelets from the patient contained 30% of the normal level of antigen. Analysis of alpha 2- antiplasmin functional and antigenic levels in the plasma of both parents and four siblings of the propositus provided evidence consistent with an autosomal mechanism of inheritance of alpha 2- antiplasmin deficiency. One sibling appeared to be homozygous and three siblings and the parents were heterozygous for the deficiency. Two heterozygotes had positive bleeding histories. The association of a bleeding disorder with a deficiency of alpha 2-antiplasmin emphasizes that lack of regulation of the fibrinolytic system can result in a hemostatic dysfunction.
Interruption of tumor-associated platelet consumption with platelet enzyme inhibitors
Authors: Slichter SJ , Weiden PL , O'Donnell MR , Storb R 
Published: October 2019

Abstract
Twenty dogs with naturally occurring metastatic tumors were treated with anticoagulants (Warfarin) or platelet enzyme inhibitor drugs (dipyridamole, dipyridamole plus aspirin, RA233, sulfinpyrazone, or a combination of RA233 and sulfinpyrazone) to determine if tumor-related reductions in platelet survival and concentration could be reversed. Anticoagulation was ineffective, while platelet enzyme inhibitors were able to produce improvements in platelet survival. Of the 18 dogs with metastatic tumor treated with platelet enzyme inhibitors, only 5 (28%) showed a reduction in platelet survival during the first week of observation on therapy compared to their baseline survivals. This is significantly different than the decreases in platelet survivals observed in 8 of 10 untreated dogs (80%) with metastatic tumor observed for the same interval. Furthermore, 8 of the 18 treated dogs (44%) had platelet survivals within 2 standard deviations of normal, compared to only 1 of 10 untreated dogs. Of the 8 dogs with normal platelet survivals, 6 were treated with a combination of a phosphodiesterase inhibitor (RA233 or dipyridamole) and a cyclooxygenase inhibitor (sulfinpyrazone or aspirin). The combination of RA233 and sulfinpyrazone was the best drug program tested and resulted in normal platelet survivals in 63% and improved platelet counts in 75% of the animals treated. Thus, platelet enzyme inhibitors with different mechanisms of action may have a synergistic effect in reversing the abnormal platelet hemostasis found in a variety of spontaneously occurring canine neoplasms.