bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological and immunological characterization of ATG and ALG
Authors: Raefsky EL , Gascon P , Gratwohl A , Speck B , Young NS 
Published: October 2019

Abstract
Antithymocyte globulin (ATG) and antilymphocyte globulin (ALG) are effective therapies in aplastic anemia; their mechanism of action is undefined. We assayed multiple properties of ATG and ALG to address the biological and immunological bases for differences between ATG and ALG and lot variation. In addition, we studied a lot reported to be inactive in an American clinical trial; however in retrospect, this lot appeared to be active in patients treated in Europe. Immunoprecipitation of thymocyte and lymphocyte membrane proteins with ATG and ALG showed between 14 and 18 major bands on SDS-PAGE, but the patterns for ATG and ALG were not identical. The ability of ATG and ALG to block binding of labeled monoclonal antibodies was assessed using flow cytometry and a radioimmunoassay. In general, there was more lot variation among ALGs than ATGs; however, all ALG lots were more potent blockers of binding of anti-HLA-DR and anti-Leu 1 antibodies than was ATG. Both ALG and ATG effectively blocked binding of anti-Leu 2a, anti- Leu 3a, anti-Leu 4, anti-Leu 5b, and anti-IL 2 receptor abs; neither blocked binding of anti-Leu 7. All preparations were capable of inducing T-cell blastogenesis, although there was considerable lot variation. All lots lysed 60% to 75% T cells in a rabbit complement- mediated cytotoxicity assay, with most having a plateau of activity at 5 to 10 ug/mL. Two lots of ALG, including the lot reported to be clinically inactive, showed less toxicity at suboptimal concentrations and did not plateau even at 80 ug/mL. In total, these results indicate important differences between ATG and ALG in general, more lot variation among ALGs than ATGs and only differences in cytotoxicity between an “inactive” lot of ALG and most, but not all, other active ATG and ALG preparations.
Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation
Authors: Bertram JH , Gill PS , Levine AM , Boquiren D , Hoffman FM , Meyer P , Mitchell MS 
Published: October 2019

Abstract
Eight patients with cutaneous T cell lymphomas (CTCL) and five with various other T cell malignancies were treated with mouse monoclonal antibody (MoAb) T101. Doses of 1 to 500 mg were administered weekly over a two-hour period and resulted in one complete remission (convoluted T cell lymphoma) and one partial remission (CTCL). Remission duration was 6 weeks and 3 months, respectively. Frequent toxicities were pruritus, hives, flushing, and shortness of breath. Supraventricular arrhythmias and blood pressure instability were also observed. Complete targeting of peripheral blood T cells was achieved with 1 mg of MoAb in the nonleukemic patients (WBC less than 10,000/microL), and free, bioavailable antibody was present at the next (10-mg) dose level. Even higher doses resulted in substantial antibody excess that persisted for as long as 6 weeks. Serum concentrations of MoAb decreased with increasing number of peripheral blood T cells, and 25 to 35 mg of T101 were required for induction of antibody excess in leukemic patients. Excess antibody induced antigenic modulation, which was of consequence only if MoAb excess persisted to the next treatment. In the original treatment, the rapidly administered MoAb was able to target and remove peripheral blood T cells before the development of antigenic modulation. Antimouse antibodies developed in three patients. Their presence rendered further therapy ineffective and was associated with an anaphylactic reaction in one patient. Development of these antibodies could not be predicted by lymphoproliferative assays. In these assays, however, the T101 protein strongly stimulated the mononuclear cells of the patient who reached the only complete remission of this trial. Immunologic stimulation by the MoAb thus might have played a role in this patient's antitumor response. In summary, therapy with MoAb T101 was specific but only modestly efficacious. Rapid infusion of nonmodulating doses of antibody provided excellent targeting and removal of peripheral blood T cells and might be a valid approach in future trials with immunoconjugated T101.
Expression of antigens of the platelet glycoprotein IIb/IIIa complex on human hematopoietic stem cells
Authors: Fraser JK , Leahy MF , Berridge MV 
Published: October 2019

Abstract
Several cell surface and cytoplasmic markers specific for the megakaryocyte-platelet lineage have been described. However, as yet, none of these has been shown to be expressed on cells earlier than the committed megakaryocyte progenitor, CFU-Meg. The present study was aimed at determining whether platelet lineage antigens could be detected on human pluripotential stem cells. Rabbit antiserum against human platelets (APS) was extensively absorbed with erythrocytes and either platelets, neutrophils, monocytes, or cells of the monocytic cell line U937. The anti-stem cell antibodies in each absorbed antiserum were determined using a complement-dependent cytotoxic assay for the pluripotential stem cell CFU-mix. Platelets alone removed anti- stem cell antibodies from APS. Absorption of APS with platelets from a patient with Glanzmann's thrombasthenia failed to remove the anti-stem cell activity, providing evidence for involvement of the platelet glycoprotein IIb/IIIa complex. Antiserum against purified glycoprotein IIb and against glycoprotein IIIa also recognized stem cells, resulting in reduced formation of mixed colonies. Absorption of these antisera with normal platelets removed the anti-stem cell activity, indicating that both IIb and IIIa are represented on stem cells. Hence, cell surface antigens specific for the stem cell-megakaryocyte-platelet pathway are expressed on the platelet glycoprotein IIb/IIIa complex.
Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease
Authors: Kernan NA , Collins NH , Juliano L , Cartagena T , Dupont B , O'Reilly RJ 
Published: October 2019

Abstract
Early clinical trials using T lymphocyte-depleted human marrow for transplantation have reported that such grafts reduce, to varying degrees, both the incidence and the severity of graft-v-host disease (GVHD). However, to date, no clear estimates have been made as to what degree of T cell depletion is necessary to prevent GVHD in every case. To address this problem, we used a limiting dilution assay (LDA) to quantitate residual clonable T lymphocytes in human T cell-depleted bone marrow in 31 HLA-identical transplants for leukemia. The number of phytohemagglutinin -interleukin 2-responsive T lymphocytes determined by LDA and expressed as T cell per kilogram recipient weight was found to correlate with the subsequent development of GVHD: no patients who received less than 1 X 10(5) T cell per kilogram developed GVHD (N = 24). Of the seven patients who received 1 X 10(5) to 4.4 X 10(5) T cell per kilogram, four patients developed grade I or II skin GVHD. This study thus provides a quantitative estimate of the number of T lymphocytes necessary to initiate clinically detectable GVHD in an HLA- identical host.
What should be the morphologic criteria for the subdivision of follicular lymphomas?
Authors: Nathwani BN , Metter GE , Miller TP , Burke JS , Mann RB , Barcos M , Kjeldsberg CR , Dixon DO , Winberg CD , Whitcomb CC 
Published: October 2019

Abstract
The members of the Pathology Panel for Lymphoma Clinical Studies undertook a collaborative study with the hope of resolving some of the controversies regarding the criteria and methods for the subclassification of follicular lymphomas (FLs). A group of 105 patients with FL were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes and Collins, and Working Formulation systems. In each of these systems, FLs are subclassified by estimation of the different cell populations, without actual counting of cells. In the second method, precise counts of different cells were made according to the standard and modified Berard methods. With this counting method, diagnoses were independently derived, based on counts provided by the seven pathologists, for large cleaved (LC), small noncleaved (SNC), and large noncleaved (LNC) cells. To ascertain what method and which criteria are most useful in predicting survival, we made clinicopathologic correlations. When the subjective (first method) diagnoses were rendered, and when the consensus diagnoses of the seven pathologists were used, there were no significant differences in survival among patients with the different subtypes. On the other hand, when we used the counting method of Berard (second method) and the cut- off points for the cell counts suggested by him for the subclassification, we were able to divide the patient population into prognostic subgroups. Because the cut-off points proposed by Berard are not derived objectively, we made statistical comparisons of survival curves to determine cut-off points (and thus to establish objective criteria). We found that the patient population could be separated into at least two prognostic groups, for SNC and/or LNC and for SNC + LNC + LC cells. The cut-off points which we derived differed with cell type, however. Until the usefulness of these new cut-off points is established, we recommend that the cut-off points and the counting method of Berard be used for the subclassification of FL. Because the choice of treatment for the different subtypes of FL is totally dependent on the histologic diagnosis, and because of the variability among the diagnoses of pathologists, treatment planning is difficult.
Leu 11+ T gamma cell chronic lymphocytic leukemia with partially activated natural killer function and its further activation by recombinant IL2 in vitro
Authors: Tagawa S , Tokumine Y , Ueda E , Waki K , Kanayama Y , Taniguchi N , Nakanishi T , Inoue R , Kitani T 
Published: October 2019

Abstract
A patient with T gamma cell chronic lymphocytic leukemia with the Leu 11+ phenotype and novel function of activated natural killer cells is reported. The peripheral blood mononuclear cells of this patient showed large granular lymphocytes by May-Giemsa staining and lamellipodia by scanning electron micrography. Tests on reactivity with monoclonal antibodies showed that most cells were Leu 11+, OKT3-/Leu 1-, OKT4-, OKT8-, Leu 7-, OKM1-, and Tac-. Freshly collected cells lysed not only K562, which is highly sensitive to natural killer cells, but also Raji cells and Daudi cells, which are not. Leu 11+ cells were triggered by recombinant interleukin 2 (rIL2) to proliferate, produce gamma- interferon (gamma IFN), and show enhanced HLA-DR antigen expression, and 30% of the Leu 11+ cells became positive for IL2 receptor antigen (Tac). The spectrum of cytotoxic activity of these cells against target cells was extended by rIL2; after treatment with rIL2, the cells also lysed HeLa cells and even fresh cancer cells. This stimulation also increased the activities of acid phosphatase and tartrate-resistant acid phosphatase of the cells and resulted in the appearance of nonspecific esterase activity. The expanded cell population may represent a neoplasm, but these findings provide information on a novel differentiation stage of activated NK cells.
Characterization of host cells involved in resistance to marrow grafts in dogs transplanted from unrelated DLA-nonidentical donors
Authors: Raff RF , Deeg HJ , Loughran TP Jr , Graham TC , Aprile JA , Sale GE , Storb R 
Published: October 2019

Abstract
A canine model of marrow transplantation was used to further define the host cells mediating resistance to marrow engraftment. Recipient dogs were given 9.2 Gy of total body irradiation followed by marrow infusion from unrelated DLA-nonidentical donors. No postgrafting immunosuppression was given. At three and ten days posttransplantation recipient marrow and peripheral blood cells were obtained and characterized by the following in vitro studies: morphologic analysis; phenotypic analysis with monoclonal antibodies; assays for natural killer cell (NK) activity; and cocultures with donor marrow to study the effect on donor CFU-GM growth. Daily differential cell counts revealed a proliferation of peripheral blood mononuclear cells approximately eight days posttransplant. By day 10 surviving host cells were uniformly large granular lymphocytes which were phenotypically of T cell lineage, had NK activity, and were capable of suppressing donor marrow CFU-GM growth. Mononuclear cells from dogs given total body irradiation only and no marrow infusion (radiation control group), did not suppress CFU-GM growth when cocultured with marrow from unrelated DLA-mismatched dogs. These results suggest that radioresistant host cells with the morphology of large granular lymphocytes and NK activity and which proliferate in response to the infused donor marrow cells mediate resistance to DLA-nonidentical marrow grafts. It remains to be determined, however, whether in vitro functional studies reflect the mechanisms involved in vivo.
Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase
Authors: Wiedmer T , Esmon CT , Sims PJ 
Published: October 2019

Abstract
The capacity of platelets treated with nonlytic concentrations of the C5b-9 proteins to catalyze prothrombin activation and thereby trigger clot formation has been investigated. When suspended in the presence of exogenous factors Xa and Va, gel-filtered platelets treated with purified C5b-9 proteins catalyzed prothrombin to thrombin conversion at rates up to tenfold above controls, and exceeded by up to fourfold the prothrombinase activity observed for thrombin-stimulated platelets. In the absence of added factor Va, C5b-9 assembly on the platelet surface significantly shortened the lag period before prothrombinase expression that was observed for untreated platelets and increased the maximum catalytic rate of thrombin formation. A comparison with other platelet stimuli revealed that the C5b-9-induced activation of platelet prothrombinase closely paralleled the effects mediated by calcium ionophore A23187. Our data suggest that the C5b-9 proteins promote the release of platelet factor V and the assembly of the prothrombinase complex, thereby potentiating the effects of thrombin on the activation of prothrombinase. Membrane assembly of the C5b-9 proteins was also observed to markedly accelerate the rate of platelet-catalyzed plasma clotting, suggesting a direct link between C5b-9-mediated prothrombinase activation and procoagulant activity accompanying immunologic damage to the platelet.
Trial of repeated low-dose aspirin in diabetic angiopathy
Authors: DiMinno G , Silver MJ , Cerbone AM , Murphy S 
Published: October 2019

Abstract
We compared the ability of aspirin to suppress platelet aggregation and thromboxane synthesis in ten normal subjects and ten patients with diabetic angiopathy and high rate of entry of new platelets into the circulation. When single doses of 100 to 1,000 mg aspirin were ingested daily for 1 month, there were time gaps between doses in which platelets from diabetics and normals aggregated and formed thromboxane ex vivo in response to the combination of arachidonic acid plus collagen. Similar gaps were also found for diabetics, but not for normals, following four daily doses (every six hours) of 25 or 100 mg. Our data show that dose schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation. We suggest that continual suppression of platelet thromboxane synthesis and aggregation by low-dose, “slow- release” preparations of aspirin would be an ideal long-term approach for the prevention of thrombosis in patients with a high rate of entry of new platelets into the circulation.
t(14;14)(q11;q32) in biphenotypic blastic phase of chronic myeloid leukemia
Authors: Dastugue N , Kuhlein E , Duchayne E , Roubinet F , Bourrouillou G , Attal M , Pris J , Colombies P 
Published: October 2019

Abstract
A blastic crisis of chronic myeloid leukemia without a detectable chronic phase is reported. At diagnosis, blast cells present t(9;22)(q34;q11),t(14;14)(q11;q32) translocations and early B cell phenotype (DR +, TdT +, B4 +, BA1 +, J5 +). At relapse, the malignant clone evolves to a biphenotypic expression, the initial markers remain unchanged, and two myeloid antigens (My 7, My 9) appear. The wide overlap in percentages of blast cells displaying lymphoid and myeloid markers shows that a single clone bears antigens of both lineages. Simultaneous occurrence of a t(14;14)(q11;q32) translocation, usually found in T cell malignancies, and of a B cell phenotype raises the question of the relationship between chromosomal changes and surface marker expression. The malignant cell is assumed to be a progenitor cell, already committed to lymphoid lineage and retaining the potential to switch to myeloid lineage.
Recipient immune-competent T lymphocytes can survive intensive conditioning for bone marrow transplantation
Authors: Butturini A , Seeger RC , Gale RP 
Published: October 2019

Abstract
Bone marrow transplantation is usually preceded by intensive chemotherapy and radiation therapy designed to completely eliminate recipient immune-competent cells that might reject the donor bone marrow. We show that seven of 14 bone marrow transplant recipients who received intensive conditioning retained circulating T lymphocytes that proliferate after incubation with interleukin 2 and phytohemagglutinin and function as effector cells in an in vitro model of graft rejection. These T cells may mediate graft rejection.
The L4F3 antigen is expressed by unipotent and multipotent colony- forming cells but not by their precursors
Authors: Andrews RG , Takahashi M , Segal GM , Powell JS , Bernstein ID , Singer JW 
Published: October 2019

Abstract
Antibody L4F3 is a murine monoclonal antibody that recognizes an antigen expressed on in vitro colony-forming cells, including virtually all CFU-GM, CFU-Meg, BFU-E, and CFU-Mix. In the present study we examined whether cells that do not express the L4F3 antigen include precursors of hematopoietic colony-forming cells. Colony-forming cells were depleted from marrow by treatment with L4F3 and complement. The remaining cells generated CFU-GM, BFU-E, and CFU-Mix when cultured in the presence of irradiated adherent cell layers from long-term marrow cultures. Marrow cells not expressing the L4F3 antigen, which were separated by cell-sorting techniques, were depleted of colony-forming cells but nevertheless generated CFU-GM when cultured over irradiated adherent cell layers. These data suggest that there are marrow precursors that do not express the L4F3 antigen and that give rise to colony-forming cells of multiple types. Negative selection techniques should allow the enrichment of these precursors of colony-forming cells, thereby enabling direct studies of these immature stem cells.
Production of granulocyte-macrophage colony-stimulating factor by Abelson virus-induced tumorigenic mast cell lines
Authors: Chung SW , Wong PM , Shen-Ong G , Ruscetti S , Ishizaka T , Eaves CJ 
Published: October 2019

Abstract
We have recently described a system that supports the development of continuously growing and tumorigenic cell lines after infection of individual multilineage hematopoietic colonies with Abelson murine leukemia virus (A-MuLV). We now provide definitive evidence that these transformed lines express features characteristic of mast cells. Although these lines have been maintained in some cases for more than a year in the absence of exogenous growth factors other than those present in fetal calf serum, colony formation could consistently after 2 months, and variably after 5 months, be shown to be increased several fold when pokeweed mitogen-stimulated spleen cell conditioned medium (CM) was added to the cultures. CM from the A-MuLV-transformed lines was then tested for its ability to stimulate hematopoietic colony formation by cells from both fetal and adult tissues. Four of four randomly selected cell lines produced factors that were active on erythropoietic, granulopoietic, and in some cases pluripotent progenitors. Removal of viral particles from the CM from one of the lines (27d1) by either heat inactivation or high-speed centrifugation did not alter the colony-stimulating activity detected. When CM from 27d1 cells was tested for its ability to stimulate the proliferation of interleukin 3 (IL3) granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent FDC-P1 cells, a positive result was obtained. This stimulatory activity was not reduced in the presence of neutralizing anti-IL 3 immunoglobulin (Ig), suggesting that the activity detected was GM-CSF and not IL 3. This was confirmed by the lack of expression of the IL 3 gene in 27d1 cells as determined by Northern analysis of 27d1 cell RNA. Furthermore, S1 analysis of mRNA from 27d1 cells as well as two other lines indicated that the GM-CSF gene in all three was transcriptionally active. Taken together, these data suggest that A- MuLV transformation of normal mast cells or their precursors under certain conditions commonly activates the production of GM-CSF.
Large granular lymphocytes from patients with expanded LGL populations acquire cytotoxic functions and release lymphokines upon in vitro activation
Authors: Pistoia V , Prasthofer EF , Tilden AB , Barton JC , Ferrarini M , Grossi CE , Zuckerman K 
Published: October 2019

Abstract
The phenotypic and functional features of purified large granular lymphocytes (LGL) from ten patients with LGL population expansions and cytopenias are described. The predominant LGL phenotypes were T3+, T8+, Leu-11+/-; however, in two patients, LGL expressed a T3-, Leu-11+ phenotype. Variable combinations of other LGL markers (OKM1, Leu-7), and HLA-DR were detected in individual cases. In nine of ten cases, freshly isolated LGL did not exert cytolytic activity for K562 target cells, but purified LGL cultured in the presence of recombinant interleukin 2 (rIL2) acquired potent cytotoxic activity in all cases tested. LGL did not proliferate in response to phytohemagglutinin (PHA). However, LGL released variable amounts of IL2 and gamma- interferon (gamma-IFN) after PHA stimulation. In some cases, stimulation of fresh LGL with recombinant IL2 induced production of gamma-IFN. No correlation was found between the functional capabilities and the original phenotype of the expanded LGL populations.
Phenotype of early erythroblastic leukemias
Authors: Villeval JL , Cramer P , Lemoine F , Henri A , Bettaieb A , Bernaudin F , Beuzard Y , Berger R , Flandrin G , Breton-Gorius J 
Published: October 2019

Abstract
Nine cases of early erythroblastic leukemia, unidentified by usual criteria, have been diagnosed using a panel of antibodies. Three cases arose in patients with Down's syndrome, one in a patient with therapy- related leukemia, and four patients were in blast crisis of chronic myeloid leukemia; only one case arose de novo. Blast cells could be assigned to two main stages of erythroid differentiation: presence of all erythroid-specific proteins in two patients, a phenotype corresponding to an immature erythroblast; absence of the erythroid markers such as glycophorin A and spectrin in the presence of carbonic anhydrase isoenzyme I, ABH group antigens, and the antigen defined by FA6 152 monoclonal antibody in six patients, a phenotype related to a late erythroid progenitor (CFU-E). One patient had an intermediate phenotype. All patients except one demonstrated a megakaryocytic component. In three patients, chromosomal abnormalities were present, detected both in blasts and in erythroid colonies. In conclusion, these findings indicate that most “cryptic erythroleukemias” are blocked at a “CFU-E-like” stage of differentiation, it may be a frequent event in Down's syndrome and chronic myeloid leukemia, and these erythroleukemias are phenotypically heterogeneous.