bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunologic classification of lymphocytic leukemias based on monoclonal antibody-defined cell surface antigens
Authors: Schroff RW , Foon KA , Billing RJ , Fahey JL 
Published: October 2019

Abstract
A panel of monoclonal antibodies reactive with normal lymphocyte subsets was used to classify cases of lymphocytic leukemia on the basis of cell surface antigen expression. The antibodies employed were commercially available and included a common framework HLA-DR antibody, two pan-T antibodies (Leu-1 and OKT-3), and antibodies defining cytotoxic/suppressor (Leu-2 and OKT-8) and helper/inducer (Leu-3 and OKT-4) subpopulations of normal T lymphocytes. Cases of ALL could be subgrouped into non-T non-B, pre-T and T-ALL on the basis of reactivity with HLA-DR, Leu-1, and OKT-3 antibodies. Leukemic cells from patients with T-cell CLL could be divided into Leu-2/OKT-8 reactive and Leu- 3/OKT-4 reactive subpopulations, as well as a subgroup in which the majority of cells were unreactive with either of these antibodies. With the exception of one individual, all Sezary cell leukemias expressed a phenotypic pattern similar to that of the Leu-3 subgroup of T-CLL. Malignancies of B-cell lineage (B-CLL, prolymphocytic leukemia, and lymphosarcoma) that were examined were reactive with both the HLA-DR and Leu-1 antibodies. On the contrary, normal B lymphocytes and lymphoid cell lines of B-cell origin did not express surface antigens recognized by the Leu-1 antibody.
Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients
Authors: Storb R , Doney KC , Thomas ED , Appelbaum F , Buckner CD , Clift RA , Deeg HJ , Goodell BW , Hackman R , Hansen JA , Sanders J , Sullivan K , Weiden PL , Witherspoon RP 
Published: October 2019

Abstract
Sixty-five multiply transfused patients with severe aplastic anemia were given cyclophosphamide followed by grafts anemia were given cyclophosphamide followed by grafts from HLA-identical siblings. The effect of the administration of viable donor buffy coat cells following the marrow inoculum was evaluated with regard to graft rejection and survival. Results in 43 patients so treated are presented along with those in 22 concurrent patients given marrow alone. Most patients given buffy coat had positive in vitro tests of sensitization indicating a high risk for graft rejection, while all but one of the patients given marrow alone had negative tests. Thirty of the 43 (70%) patients given marrow and buffy coat are alive between 10 and 61 mo (median 36) after grafting; 4 died after graft rejection and 6 with acute or chronic graft-versus-host disease (GVHD). Eleven of the 22 (50%) patients given marrow alone are alive between 29 and 65 mo (median 52); 7 died after graft rejection and 3 with GVHD. The addition of buffy coat cell infusions to the marrow inoculum reduced the risk of rejection and increased survival in the currently reported transfused patients when compared to patients grafted before 1976. However, there was an increased risk of chronic GVHD. Recipients of marrow from female donors survived slightly better (73%) than recipients of male marrow (58%).
Determination of ultrastructural peroxidases and immunologic membrane markers in the diagnosis of acute leukemias
Authors: Marie JP , Perrot JY , Boucheix C , Zittoun J , Martyre MC , Kayibanda M , Rosenfeld C , Mishal Z , Zittoun R 
Published: October 2019

Abstract
Detection of membrane markers and ultrastructural peroxidase activity was carried out on the blasts of 16 apparently nonmyeloid adult acute leukemias. These patients were selected from 73 adult leukemic patients by the negativity of their routine cytochemical myeloid markers: i.e., myeloperoxidase, chloresterase activity, and Sudan Black B staining. B and T acute lymphoid leukemias (ALL) were excluded from the study. After concurrent testing from human T lymphocyte antigen (HuTLA), common ALL antigen (cALL), la-like antigens, and peroxidase activity at the electron microscopic level (POEM), only two patients remained undifferentiated (cALL-, POEM-). The other cases were classified as following : 6 common ALL (cALL+, POEM-), 1 pre-T-ALL (cALL+, HuTLA+, POEM-), 5 very poorly differentiated acute myelogenous leukemia (AML) (cALL-, POEM+), and 2 mixed leukemias (cALL+, POEM+). Terminal deoxynucleotidyl transferase activity (TdT) was measured in 7 cases and was found to be present at high levels in 4 cases of cALL and in the 2 cases of acute undifferentiated leukemias (AUL): it was absent in two cases of AML. Cytogenetic analysis had showed that 2 of the cALLs, 3 of the AMLs, and the 2 mixed leukemias were PH1+. We conclude that POEM detection is useful in apparently nonmyeloid leukemias with negative immunologic lymphoid markers, and that the existence of a Ph1 chromosome should be investigated, particularly in the unusual case of mixed (lymphoid-myeloid) acute leukemia.
Expression of Ia-antigens on normal and chronic myeloid leukemic human granulocyte-macrophage colony-forming cells (CFU-GM) is associated with the regulation of cell proliferation by prostaglandin E
Authors: Pelus LM , Saletan S , Silver RT , Moore MA 
Published: October 2019

Abstract
The presence of la-antigens and their relationship to the inhibitory effect of prostaglandin E on the proliferation of human CFU-GM was studied in animals and patients with chronic myeloid leukemia. Consistent reduction of normal colony formation to approximately 50% of baseline levels was observed using a monoclonal anti-human la antibody in a complement-dependent cytotoxicity assay titrated over serial dilutions. ELimination of the la-antigen-bearing CFU-GM population was associated with virtually a complete loss of responsiveness to the inhibitory effects of prostaglandin E. Maintenance of bone marrow cells in short-term suspension culture at 37 degrees C prior to agar culture resulted in the loss of detectable la-antigen on the CFU-GM and, similarly, loss of response to prostaglandin. In contrast, most patients with chronic myeloid leukemia showed greatly reduced levels of la-antigens on their CFU-GM in fresh marrow together with lack of prostaglandin sensitivity, suggesting a correlation with the abnormal growth regulation observed in these patients. In two chronic myeloid leukemia patients, levels of la-antigen higher than that observed in the majority of patients could be detected and correlated with a residual response to prostaglandin E. These results suggest a relationship in normals between the expression of la-antigens on CFU-GM and the physiologic response to regulation by prostaglandin E, and a possible mechanism for the aberrant regulatory response in patients with chronic myeloid leukemia.
Reticulocytosis, hypochromia, and microcytosis: an unusual presentation of the preleukemic syndrome
Authors: Tulliez M , Testa U , Rochant H , Henri A , Vainchenker W , Touboul J , Breton- Gorius J , Dreyfus B 
Published: October 2019

Abstract
Two patients exhibiting a highly unusual preleukemic syndrome with marked reticulocytosis, hypochromia, and microcytosis are reported. This red cell phenotype has been investigated by means of HbF, HbA2, and i-antigen activity dosages, immunofluorescence labeling of F cells, reticulocyte survival, globin chain synthesis, and electron microscopy study. The marked reticulocytosis is explained by a delayed disappearance of the reticulum. Serum iron is normal, and a thalassemic syndrome is excluded because of a balanced alpha/non-alpha globin chain synthesis. Electron microscopy studies are consistent with a defect in iron uptake by erythroid cells. All the hematologic data and investigations are similar to those observed for the Belgrade laboratory rat. It is hypothesized that the low expression of HbF and i- Ag associated with microcytosis are related to a prolongation of erythroid maturation as reflected by abnormal reticulocyte survival.
Malignant lymphoma of small cleaved lymphocytes of the follicular mantle zone
Authors: Palutke M , Eisenberg L , Mirchandani I , Tabaczka P , Husain M 
Published: October 2019

Abstract
We describe a highly unusual lymphocytic lymphoma. It appeared to originate in the mantle zones of hyperplastic follicles that had large reactive centers. The tumor cells in the mantle zone were small lymphocytes with cleaved or very irregular nuclei. They had coarse and abundant IgM, kappa surface immunoglobulin markers, and receptors for complement. The tumor involvement was generalized at the time of discovery. The diagnosis of a malignant lymphoma was initially made with difficulty because of the presence of reactive follicular centers as well as a polyclonal hypergammaglobulinemia and large numbers of interfollicular plasma cells and plasmacytoid lymphocytes containing all classes of immunoglobulin. However, 2 yr later, the follicular centers were replaced by tumor nodules composed of lymphocytes identical in appearance and immunologic type to those seen originally. This case illustrates that not all nodular lymphomas are follicular center cell (FCC) neoplasms and that morphological transformation from small round to small cleaved lymphocytes and a corresponding increase in surface immunoglobulins may take place in the follicular mantle zone. The patient had a high titer of antibody to Epstein-Barr virus (EBV) and a poor lymphocyte response to concanavalin A, but neither the tumor cells nor the plasmacytoid lymphocytes contained EBV DNA.
Effect of transfused reticulocytes on iron exchange
Authors: Finch CA , Huebers H , Eng M , Miller L 
Published: October 2019

Abstract
A animal model was developed whereby reticulocyte-rich blood was introduced into normal rats by exchange transfusion. Measurements of plasma iron turnover was made at similar plasma iron concentrations before and after exchange transfusions. High reticulocyte blood obtained from animals rendered iron deficient by diet or by treatment with phenylhydrazine resulted in a mean increase of 86% in internal iron exchange, while the plasma iron turnover was unaffected by exchange with normal red cells. Since iron input from reticuloendothelial cells could have increased due to breakdown of transfused cells, iron absorption was also measured. Within 1 hr and for a least 6 hr after exchange with high reticulocyte blood, mean absorption in six groups of animals was increased over control animals by 50%-130%. The increased plasma iron turnover and absorption was not mediated by a decrease in plasma iron or an increase in unsaturated iron-binding capacity. Indeed, a higher plasma iron and transferrin saturation augmented the movement of iron into the plasma from iron- donating tissues. It is proposed that the donation of iron by transferrin in some way immediately facilitates the procurement of more iron by transferrin.
The coagulant-active phospholipid content is a major determinant of in vivo thrombogenicity of prothrombin complex (Factor IX) concentrates in rabbits
Authors: Giles AR , Nesheim ME , Hoogendoorn H , Tracy PB , Mann KG 
Published: October 2019

Abstract
In vitro evaluation of prothrombin complex concentrates in a thrombin generation assay, using DAPA and purified components of the prothrombinase complex, demonstrated significant levels of coagulant- active “phospholipid replacing” activity. Quantification of this activity showed a significant correlation (r = 0.8747, p less than 0.01) with thrombogenicity measured in vivo in a stasis model in rabbits. Extracted lipid material retained full phospholipid replacing activity in the vitro assay. Thin-layer chromatographic characterization confirmed the presence of phospholipids with known coagulant activity in vitro. In vivo, the extracted material was nonthrombogenic but augmented the thrombogenicity of purified factor Xa. Substitution of a synthetic coagulant-active phospholipid (phosphatidylcholine-phosphatidylserine lipid vesicles) for the extracted phospholipid produced a similar augmentation of a factor-Xa- induced thrombogenicity in vivo. It is concluded that the coagulant- active phospholipid content of prothrombin complex concentrates is a major determinant of thrombogenicity but requires the presence of activated clotting factors for its expression in vivo.
Characterization of the defect of the factor VIII/von Willebrand factor protein in von Willebrand's disease
Authors: Gralnick HR , Cregger MC , Williams SB 
Published: October 2019

Abstract
The factor VIII/von Willebrand factor (f.VIII/vWf) protein was purified from the plasma of a patient with von Willebrand's disease (vWd). The patient had all of the classic laboratory findings of vWd except for the ristocetin-induced platelet aggregation of his own platelet-rich plasma. The disease has been documented in three generations. Comparison of the purified normal and vWd f.VIIi/vWf protein revealed several abnormalities, including decreased concentration of f.VIII/vWf antigen; decreased specific vWf activity; absence of the larger molecular forms of the f.VIII/vWf protein; carbohydrate deficiencies affecting the sialic acid, penultimate galactose and N- acetylglucosamine moieties; and decreased binding of the f.VIII/vWf protein to its platelet receptor. These studies indicate the multiplicity of biochemical and functional abnormalities associated with the f.VIII/vWf protein in vWd. f.VIII/vWf protein to normal f.VIII/vWf protein that had been treated with 2-mercaptoethanol (2-ME) to reduce the multimer size and then treated with specific exoglycosidases to remove the sialic acid and penultimate galactose residues revealed similar biologic properties.
Non-T, non-B lymphomas are rare in childhood and associated with cutaneous tumor
Authors: Bernard A , Murphy SB , Melvin S , Bowman WP , Caillaud J , Lemerle J , Boumsell L 
Published: October 2019

Abstract
Tumor cells from a total of 116 children with non-Hodgkin's lymphoma were studied for their pattern of reactivity with a battery of cell markers, including their capacity for spontaneous formation of sheep erythrocyte rosettes (E-rosettes), demonstration of surface immunoglobulins (SIg), and positivity with antisera against T-cell antigens, the common acute-lymphoblastic-leukemia-associated antigen (cALLa), and Ia-like antigens. Fifty-eight children (50%) had T-cell lymphomas, including all those with mediastinal tumors. Fifty children (43%) had B-cell lymphomas, including 44 of the 45 with abdominal primaries. Eight children (7%) had non-T, non-B tumors, 4 of whom presented at a young age with cutaneous lymphoblastic tumors. These results demonstrate that the great majority of children with NHL, not leukemic at diagnosis, have tumors clearly committed to either T- or B- cell differentiation pathways and only rarely exhibit the common ALL phenotype (cALLa+, Ia+, E-, T-, SIg-), contrasting with the distribution of childhood lymphoblastic leukemias. The unusual association of these non-T, non-B cases with skin involvement has not previously been reported, raising speculation regarding patterns of lymphocyte traffic and origins of childhood lymphomas and leukemias.
The contribution of blast cell properties to outcome variation in acute myeloblastic leukemia (AML)
Authors: McCulloch EA , Curtis JE , Messner HA , Senn JS , Germanson TP 
Published: October 2019

Abstract
The blast cell population in AML includes progenitors capable of colony formation in culture. Certain properties of these progenitors have been determined, including their capacity for self-renewal and their sensitivities to the chemotherapeutic drugs cytosine arabinoside (Ara- C) and adriamycin (Adria). Wide patient to patient variation was found in these properties, although they were stable during the course of the disease in each patient. We tested the properties, together with clinical risk factors, as attributes contributing to the variation in remission induction and survival. As univariate parameters, self- renewal and Ara-C sensitivity contributed to remission induction, but only self-renewal was related to survival. In multivariate analysis, self-renewal, age and percentage blasts in the marrow contributed to outcome variation; drug sensitivities were not significant. We conclude that self-renewal, a biological property of malignant AML clones, although measured in culture, plays a significant role in determining response to treatment and survival in AML.
Sex related differences in platelet function: the effect of aspirin
Authors: Kelton JG , Carter CJ , Santos A , Hirsh J 
Published: October 2019

Abstract
There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromboxane B2 generation. Infusion of collagen into untreated animals resulted in a 38 +/- 4% (m +/- SE, n = 13) decrease in platelet count (assessed by whole blood radioactivity) in the male animals, and a 27 +/- 3% (m +/- SE, n = 13) in the female animals. Pretreatment with aspirin resulted in a significant inhibitory effect in the male but not the female animals (p less than 0.05). The male animals had significantly greater thromboxane B2 generation in vivo than did the female animals following an equal dose of collagen (males, 2.64 +/- 0.7 ng/ml thromboxane B2, n = 14; females, 1.67 +/- 0.4 ng/ml thromboxane B2, n = 15, p less than 0.05). In contrast no sex related difference in the inhibitory effect of aspirin on maximal collagen induced aggregation was found when platelets were studied in vitro. The greater reactivity of male patients in vivo may be accounted for by the observed increase in thromboxane B2 generation. This might also explain the greater thrombotic tendency of males, and the observed difference in the antithrombotic effect of aspirin in males and females.
Acute myeloid leukemia colony growth in vitro: differences of colony- forming cells in PHA-supplemented and standard leukocyte feeder cultures
Authors: Swart K , Hagemeijer A , Lowenberg B 
Published: October 2019

Abstract
Bone marrow or blood of patients with acute myeloid leukemia was subjected to cell separation and the cells investigated for in vitro colony growth. Discontinuous albumin density gradient centrifugation and depletion of E-rosette-forming cells resulted in purified fractions of acute myeloid leukemia cells. From these fractions, growth of large leukemic colonies was obtained in the PHA-leukocyte feeder (PHA-LF) colony technique in 12 of 14 patients. The standard double agar layer techniques with a leukocyte feeder for granulocyte-macrophage colony forming cells (GM-CFC) supported colony formation in only four cases. The PHA-LF leukemic colony-forming cells (CFC) were found to be of low buoyant density (always less than or equal to 1.062 g.ml-1) when compared to normal marrow GM-CFC (peak at 1.065 g.ml-1). The density profile of PHA-LF CFC paralleled the distribution of the nucleated cells in 8 cases, but in 4 patients, the cFC peak was found at a distinctly lower density; this suggested that a specific leukemic subpopulation had a colony-forming capacity. In three of the four patients with colony growth in the double layer agar technique, it was evident that these CFC had density properties different from those of PHA-LF CFC. These findings suggest that cells giving rise to large colonies in the PHA-LF and double layer agar assays represent distinct leukemic subpopulations.
Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia
Authors: Dillman RO , Shawler DL , Sobol RE , Collins HA , Beauregard JC , Wormsley SB , Royston I 
Published: October 2019

Abstract
We infused the murine monoclonal antibody T101 into two patients with advanced refractory chronic lymphocytic leukemia (CLL) after confirming its reactivity with their CLL cells. One patient received doses of 1, 3, and 12 mg; the second patient received 10 mg. Antibody was delivered over 10--15 min. The major observations were: (1) T101 murine monoclonal antibody did bind to cells with T65 surface antigen and saturated these cells in vivo; (2) cells that bound T101 disappeared from the circulation by 2 hr after treatment, as evidenced by a marked drop in lymphocyte counts; (3) T101 serotherapy resulted in some intravascular cell injury associated with sequestration and probably destruction in the liver and lung; (4) free serum T101 was demonstrable, but disappeared by 2--4 hr after infusion; (5) rapid infusion of T101 did not induce significant modulation of T65; (6) rapid infusion of greater than 10 mg of T101 was associated with significant systemic reactions. Monoclonal antibodies may someday have an application in leukemia therapy, but additional experimental trials are clearly indicated.
Human platelet activation in the absence of aggregation: a calcium- dependent phenomenon independent of thromboxane formation
Authors: Levy-Toledano S , Maclouf J , Bryon P , Savariau E , Hardisty RM , Caen JP 
Published: October 2019

Abstract
In response to ionophore A 23187, thrombasthenic and EDTA-treated control platelet-rich plasmas (PRP) undergo a change in light transmission (LT) accompanied by a normal 14C-serotonin (5HT) release and thromboxane (TX) synthesis in the absence of aggregation. Ultrastructural qualitative electron microscopy revealed central apposition of organelles and loosely packed platelets in both models, while a central gel mass appeared only in thrombasthenic patients. Quantitative analysis of this ultrastructural change showed an increase in the elongation and a decrease in the circularity coefficients of thrombasthenic platelets, indicating a shape change with pseudopod formation, while EDTA-treated platelets underwent a shape change in the absence of pseudopod formation. Morphometric analysis showed that the ionophore caused extensive degranulation in both types of platelets (decrease of the granule volume), which occurred in the presence of contraction of thrombasthenic PRP (decrease of the SCS plus granule volume) but in its absence in EDTA-treated platelets. The change in LT was not inhibited by aspirin, suggesting a dissociation between release of 14C-5HT and TX formation. Moreover, it was not inhibited by creatine phosphate plus creatine phosphokinase, prostaglandin E1, or cytochalasin and/or colchicine. It was not dependent on ADP, cAMP, or the integrity of microfilaments and microtubules. However, chlorpromazine, TMB 8, and dibucaine, which interfere with intracellular membrane transport of Ca2+, inhibited this platelet activation (change in LT, 14C-5HT release and TX synthesis.
Subtypes of cutaneous T-cell lymphoma defined by expression of leu-1 and Ia
Authors: Wood GS , Deneau DG , Miller RA , Levy R , Hoppe RT , Warnke RA 
Published: October 2019

Abstract
Monoclonal antibodies were used to characterize immunohistologically the expression of cellular antigens in 25 patients with cutaneous T- cell lymphoma (CTCL). Although all cases expressed the Leu-2a-/Leu-3a+ immunophenotype characteristic of helper T cells, four subtypes were defined based on variable expression of Leu-1 and Ia. In individual patients, the immunophenotype was constant irrespective of body compartment sampled or interim therapy. Ia+ non T-cells typically constituted one-third of the cellular infiltrate. Along with neoplastic cells, Ia+/T6+ dendritic cells were observed within Pautrier microabscesses, dermis, and individually throughout the epidermis. It will be important to determine if different CTCL immunophenotypes represent different biologic subsets of disease or have prognostic relevance. Prospective studies will be facilitated by single- and double-label immunohistologic techniques that allow the simultaneous evaluation of cellular antigen expression and architectural detail.