bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal antibodies to discrete regions in alpha 2-plasmin inhibitor
Authors: Mimuro J , Koike Y , Sumi Y , Aoki N 
Published: October 2019

Abstract
Three monoclonal antibodies to alpha 2-plasmin inhibitor (alpha 2PI) were characterized. The first, JTPI-1, was directed against the reative site of alpha 2PI and inhibited antiplasmin activity by interfering with the formation of alpha 2PI-plasmin complexes. The avidity of JTPI- 1 to the preformed alpha 2PI-plasmin complex was markedly lower than that to free alpha 2PI, which made this antibody useful for measuring the free alpha 2PI in plasma. The second, JTPI-2, recognized an epitope in the C-terminal fragment of alpha 2PI (11,000 daltons [11 K]) that was cleaved from alpha 2PI by plasmin upon complex formation but remained noncovalently attached to the complex. However, binding of JTPI-2 to alpha 2PI was not inhibited by the C-terminal 26-residue peptide containing the plasminogen-binding site and had no effect on the function of alpha 2PI. These data suggested that JTPI-2 recognized an epitope between the C-terminal 26-residue peptide and the reactive site. The third, JTPI-3, bound the alpha 2PI-plasmin complex (150 K) as well as alpha 2PI. Binding was inhibited by the N-terminal 12-residue peptide of alpha 2PI, but factor XIII-catalyzed cross-linking of alpha 2PI to fibrin was not inhibited by JTPI-3. These results suggested that the antibody recognized an epitope near the N terminus. These three monoclonal antibodies were useful for analyzing the mechanism of interaction between alpha 2PI and plasmin.
Interrelationship between mitosis and endomitosis in cultures of human megakaryocyte progenitor cells [published erratum appears in Blood 1987 May;69(5):1547]
Authors: Arriaga M , South K , Cohen JL , Mazur EM 
Published: October 2019

Abstract
Sera from dogs rendered aplastic by total-body irradiation stimulate human bone marrow megakaryocyte progenitors to form megakaryocyte colonies in plasma clot cultures. In this investigation, we evaluated the effects of varying concentrations of such sera on both the mitotic and endomitotic phases of human megakaryocyte development in vitro. When low concentrations of aplastic canine sera (2.5% to 5.0% [vol/vol]) were added to cultures of human peripheral blood mononuclear cells in place of normal AB serum, megakaryocyte colony formation was augmented fivefold, cell numbers per colony increased approximately 2.5- fold, and the geometric mean megakaryocyte ploidy almost doubled. Further increasing the aplastic canine serum concentration from 10% to 30% (vol/vol) stimulated no additional colony formation. However, there was a further augmentation of cell numbers per colony associated with a progressive decrease in the mean megakaryocyte ploidy. Megakaryocyte cultures were harvested after 7, 12, 15, and 19 days of incubation, and these demonstrated that the lower mean ploidy values found at the higher concentrations of aplastic canine serum did not result from delayed endoreduplication. At all aplastic serum concentrations evaluated, there existed a strong correlation between nuclear ploidy and cell diameter. We conclude that both the mitotic and endomitotic events in human megakaryocytopoiesis may be influenced by a factor or factors present in aplastic canine serum. At lower in vitro concentrations, such sera stimulate both mitosis and endomitosis, which promotes the development of megakaryocyte colonies composed of larger cells with a higher mean ploidy. With increasing aplastic serum concentrations, colony formation plateaus and mitosis is favored over endomitosis. This results in colonies composed of more numerous but smaller megakaryocytes with a lower mean ploidy. Our data suggest that the size and extent of polyploidization that can be achieved by a developing megakaryocyte may be influenced by the mitotic prior history of its immediate precursor cell.
Hematologic engraftment and immune reconstitution posttransplantation with anti-B1 purged autologous bone marrow
Authors: Anderson KC , Ritz J , Takvorian T , Coral F , Daley H , Gorgone BC , Freedman AS , Canellos GP , Schlossman SF , Nadler LM 
Published: October 2019

Abstract
Hematologic engraftment and immune reconstitution were examined in patients who received cyclophosphamide and total body irradiation therapy followed by infusion of autologous bone marrow purged with anti- B1 monoclonal antibody (MoAb) and complement as therapy for non- Hodgkin's lymphoma. Hematologic engraftment was prompt with return of greater than or equal to 0.5 X 10(3)/microL granulocytes and greater than or equal to 2 X 10(4)/microL platelets at a median of 26 and 29 days posttransplant, respectively. Immunologic reconstitution, in contrast, was prolonged. Normal numbers of circulating B cells were consistently noted by five months posttransplant, whereas return of normal immunoglobulin levels in some patients did not occur for one year. Normal numbers of T cells were evident within the first month posttransplant, but a reversed T4:T8 ratio persisted in some patients up to three years. In vitro responses of either B cells to triggers of activation or of T cells to mitogens and antigens were not normal for at least three months posttransplant. Natural killer (NK) cells predominated early after transplant and may demonstrate cytotoxicity against tumor cells. Our studies demonstrate that transplantation with anti-B1 purged autologous bone marrow results in complete hematologic and delayed immunologic engraftment. No significant acute or chronic clinical toxicities have been observed.
Gamma-interferon in aplastic anemia: inability to detect significant levels in sera or demonstrate hematopoietic suppressing activity
Authors: Torok-Storb B , Johnson GG , Bowden R , Storb R 
Published: October 2019

Abstract
A radioimmunoassay (RIA) was used to quantitate biologically active gamma interferon (INF-gamma) in sera and in supernatants of cultured mononuclear cells obtained from 50 patients with aplastic anemia. Only five of the 50 serum samples had INF-gamma levels above background (greater than 0 less than 0.5 units per mL). Detectable levels of spontaneous INF-gamma (0.3 to 868 U/mL) were found in 18 of the 50 mononuclear cell supernatants tested. The addition of patient sera or INF-gamma positive supernatants to cultures of normal hematopoietic colonies did not result in reduced colony growth. Flow cytofluorimetric analysis of mononuclear cells failed to establish a correlation between the presence of INF-gamma in supernatants and the number of activated T cells or natural killer (NK) cells in the mononuclear cell population. However, a significant correlation did exist between the presence of monocytes and the production of INF-gamma. Contrary to previous reports, our data suggest that patients with aplastic anemia do not have high circulating levels of INF-gamma. Unstimulated mononuclear cells from some patients will produce significant levels of INF-gamma, but this does not result in decreased in vitro hematopoiesis.
Inactivation of single-chain urokinase (pro-urokinase) by thrombin and thrombin-like enzymes: relevance of the findings to the interpretation of fibrin-binding experiments
Authors: Gurewich V , Pannell R 
Published: October 2019

Abstract
Whereas crude bovine thrombin activated single-chain urokinase-type plasminogen activator (scu-PA), otherwise called pro-urokinase (pro- UK), purified human thrombin converted pro-UK (scu-PA) to a two-chain form that had no amidolytic activity. The two chains (Mr approximately 33,000 and 22,000) were disulfide linked and resistant to subsequent activation by plasmin. By contrast, thrombin did not inactivate tissue plasminogen activator or two-chain urokinase. The enzyme from snake venom Agkistrodon contortrix, relatively specific for fibrinopeptide B, had an effect similar to thrombin, whereas the enzyme from Agkistrodon rhodostoma (ancrod), specific for fibrinopeptide A, did not. When pro- UK (scu-PA) was present during thrombin clotting of fibrinogen, degradation of 125I-pro-UK (scu-PA) in the clot supernatant was seen, whereas virtually full recovery (95%) of radioactivity was found. A loss of latent amidolytic activity in the clot supernatant was also found, the extent of which could be correlated with the degree of degradation of the radiolabeled probe. It was concluded that thrombin inactivation of pro-UK (scu-PA) accounts for the loss of amidolytic activity in the clot supernatant, which has been attributed to fibrin binding. Further confirmation was obtained from experiments in which ancrod was used as the clotting agent. Full recovery of both radioactivity and latent amidolytic activity of pro-UK (scu-PA) in the supernatant was obtained under these conditions. These findings indicate that thrombin may introduce an artifact in the results of certain experiments designed to study the fibrin affinity or fibrinolytic effect of pro-UK (scu-PA).
Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin deposition in rabbits
Authors: Krishnamurti C , Barr CF , Hassett MA , Young GD , Alving BM 
Published: October 2019

Abstract
Plasma levels of a fast-acting plasminogen activator inhibitor (PAI), which neutralizes both tissue plasminogen activator (t-PA) and urokinase, are markedly increased in endotoxin-treated rabbits. The ability of this inhibitor to prevent the fibrinolysis that occurs after a thrombogenic stimulus was investigated in a rabbit model. Normal and endotoxin-treated male New Zealand rabbits were infused with ancrod, an enzyme that causes noncrosslinked fibrin formation in vivo. Ancrod stimulated t-PA activity by 90% in normal rabbits and caused hypofibrinogenemia but did not increase PAI levels or induce fibrin deposition in target organs. Rabbits injected with endotoxin (10 micrograms/kg) showed an increase in PAI from less than 1 to 32 U/mL 4 hours later. When ancrod was infused at this time, 90% of the rabbits developed renal fibrin thrombi. Fibrin deposition was recorded in 40% of the rabbits that received a lower dose of endotoxin (1.0 microgram/kg) and had a PAI level of 14 U/ml at the time of ancrod infusion 4 hours later. Fibrin deposition did not occur in the endotoxin-treated rabbits that received normal saline. These data suggest that high levels of PAI inhibit fibrinolysis in vivo, thereby promoting fibrin clot deposition following a thrombogenic stimulus.
Monoclonal anti-light chain idiotype as a tumor-specific probe for human neoplastic B lymphocytes
Authors: Wrightham M , Tutt AL , Glennie MJ , Hamblin TJ , Stevenson GT , Stevenson FK 
Published: October 2019

Abstract
Tumor cells from patients with B cell neoplasms often secrete small amounts of free monoclonal light chains that can be found in the urine. Such tumor-derived light chains of the lambda type from a patient with typical chronic lymphocytic leukemia have been used to raise mouse monoclonal antibodies (MoAbs). A hybridoma-secreting antibody that recognized the idiotypic lambda chain but not normal lambda chains by a preliminary screen but which also reacted with idiotypic IgM from the patient's tumor cells was selected. This MoAb in fact recognized 1 in 20 X 10(3) molecules of pooled normal lambda chains, thus establishing its specificity for a private idiotypic determinant. It failed to give a detectable reaction with normal IgM, normal serum, or a panel of IgM paraproteins. The antibody bound to the patient's neoplastic B cells but not to normal tonsillar cells. The site of binding of the antibody to idiotypic IgM is clearly separate from that of another MoAb specific for idiotypic determinants on heavy plus light chains, since the two showed additive binding curves. The determinant also appeared to be less available in dimeric lambda chains than in monomeric lambda chains or in idiotypic IgM. Antibodies to idiotypic determinants on light chains show some technical advantages and should be useful for monitoring and possibly treating B cell tumors, either alone or together with the more conventional anti-idiotypic antibodies that usually recognize the heavy and light chain combination.
Blast cell colony assay for umbilical cord blood and adult bone marrow progenitors
Authors: Leary AG , Ogawa M 
Published: October 2019

Abstract
We previously described candidate human blast cell colonies in culture of umbilical cord blood cells. However, their replating efficiencies were low, and we were unable to grow colonies from adult marrow cells. We report here a consistent method of growth and identification of human blast cell colonies that are supported by low serum culture and by delayed addition of medium conditioned by a T lymphoblast cell line, C5MJ. Nonadherent mononuclear cord blood and bone marrow cells were prepared by use of Ficoll-Paque and overnight adherence to plastic. Bone marrow cells were further enriched for progenitors by panning with monoclonal anti-My-10 antibody. Cells were plated in methylcellulose culture containing 2% fetal calf serum and supplemented with bovine serum albumin, lecithin, cholesterol, and transferrin. On day 14 of culture, concentrated C5MJ-conditioned medium was carefully added to each dish. Blast cell colonies consisting of 18 to 100 cells were detected on days 21 to 28. Forty percent to 75% of the blast cell colonies in individual samples yielded secondary colonies upon replating (positive colonies). The replating efficiency of the positive colonies ranged from 3% to 100%. The largest secondary colony contained 7,800 cells. In addition to single-lineage colonies, multilineage colonies revealing two to five lineage combinations were seen. These results suggest that human primitive progenitors are dormant in cell cycle and that they survive in the absence of colony-stimulating factors. Human blast cell colonies may provide a unique population of progenitors for studies of the early process of human hemopoiesis.
T cell gamma gene rearrangements in hematologic neoplasms
Authors: Asou N , Matsuoka M , Hattori T , Kawano F , Maeda S , Shimada K , Takatsuki K 
Published: October 2019

Abstract
Rearrangements of the T cell gamma (T gamma) gene were studied in primary neoplastic cells from 75 patients with leukemia or lymphoma. T gamma gene rearrangements were observed in 19 of 21 T cell neoplasms; 14 of 21 immature B cell leukemias, including 4 out of 5 patients with rearrangements of both immunoglobulin heavy-chain (JH) and T cell receptor beta chain (T beta) genes; none out of 16 nonlymphoid leukemias. Thus, T gamma gene rearrangement is frequently found in immature B cells and is not always found in T cells showing T beta gene rearrangement, but it is not detected in nonlymphoid cells. Furthermore, T gamma gene rearrangement in cells with the germline configuration of the JH and T beta genes was observed. These results indicate that the detection of T gamma gene rearrangement does not allow a clear assignment to a particular lineage. However, an analysis of T gamma gene rearrangement provides a further potential tool to establish the lymphoid cellular origin and clonality of hematologic neoplasms and identify the normal stages of lymphocyte differentiation.
Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies [published erratum appears in Blood 1987 Jun;69(6):1789]
Authors: Blume KG , Forman SJ , O'Donnell MR , Doroshow JH , Krance RA , Nademanee AP , Snyder DS , Schmidt GM , Fahey JL , Metter GE 
Published: October 2019

Abstract
In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16–213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.
Development of T3/T cell receptor gene expression in human pre-T neoplasms
Authors: Pittaluga S , Uppenkamp M , Cossman J 
Published: October 2019

Abstract
Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation. Rearrangements of the T cell receptor beta and gamma genes appear concurrently and are preceded by surface expression of the 3A1 (CD7) molecule. Subsequent transcription of the beta gene is coordinated with surface expression of T1 (CD5) and T11 (CD2), transcription of T3 delta mRNA, and the appearance of intracellular T3 (CD3) protein. As late events, T alpha gene transcripts appear and, finally, T3, the multichain complex linked to the T cell receptor, is presented on the cell surface. Findings reported here provide a model of the developmental orchestration of genes encoding antigen recognition in human T cells.
Early T cell differentiated chronic myeloid leukemia blast crisis with rearrangement of the breakpoint cluster region but not of the T cell receptor beta chain genes
Authors: Gramatzki M , Bartram CR , Muller D , Walter M , Tittelbach H , Kalden JR 
Published: October 2019

Abstract
Early T cell differentiation is described in a case of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in blast crisis, supporting multi-lineage differentiation potential of CML precursor cells. In the absence of myeloid markers, strong positivity for terminal deoxynucleotidyl transferase (TdT) and reactivity with T cell antibody 3A1, but lack of more mature T cell antigens, provided evidence for immature T cell differentiation. Molecular analysis of the breakpoint cluster region (bcr) in chromosome 22 revealed a rearrangement and thus confirmed the CML origin of the early T cell blasts. T cell receptor beta chain sequences were found in germline configuration and therefore suggest a very immature stage of T cell differentiation in the CML blasts.
In vitro action of tumor necrosis factor on myeloid leukemia cells
Authors: Munker R , Koeffler P 
Published: October 2019

Abstract
We investigated the in vitro action of recombinant tumor necrosis factor alpha (TNF) on the clonal growth of normal and malignant myeloid cells. Clonogenic cells from six of nine myeloid leukemia cell lines were very sensitive to the effects of TNF with 50% of the colonies inhibited (ED50) by concentrations of TNF that ranged between 6 and 150 U/mL. A decrease in DNA, RNA, and protein synthesis and in cloning efficiency occurred within three hours of exposure of HL-60 promyelocytes to TNF. The TNF in combination with recombinant interferons produced an additive or synergistic inhibition of colony formation of HL-60 and THP-1 myelomonoblasts. Normal human CFU-GM are sensitive to TNF (ED50 between 100 and 50,000 U/mL), but their sensitivity to TNF depends on the source of colony stimulating factor (CSF) with T lymphocyte derived GM-CSF (recombinant or natural) partially protecting the CFU-GM from the suppression exerted by TNF (and interferons). In eight of 15 cases the clonogenic myeloid leukemia cells from patients with acute or chronic myeloid leukemia were more sensitive than normal CFU-GM using GM-CSF as a source of colony stimulating activity. Further studies showed that the action of TNF on myeloid leukemia cells probably can be only partially explained by differentiation. Our finding of a possible selective cytotoxicity to leukemic clonogenic cells by TNF suggests that TNF may have value in the therapy of some patients with myeloid leukemia.
Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro
Authors: Graziani G , Pasqualetti D , Lopez M , D'Onofrio C , Testi AM , Mandelli F , Gallo RC , Bonmassar E 
Published: October 2019

Abstract
Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord- blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity.
The syndrome of T8 hyperlymphocytosis: variation in phenotype and cytotoxic activities of granular cells and evaluation of their role in associated neutropenia
Authors: Grillot-Courvalin C , Vinci G , Tsapis A , Dokhelar MC , Vainchenker W , Brouet JC 
Published: October 2019

Abstract
We performed a longitudinal study of the phenotype and functions of granular lymphoid cells from seven patients with T8 hyperlymphocytosis and neutropenia. Whereas cells retained a T3+ T8+ (six cases) or T3- T8+ (one case) phenotype at different examinations, the expression of natural killer (NK)-related antigens (HNK1- and Leu11-defined antigens) exhibited striking variations, some of which were also observed after in vitro culture. Similarly, natural or antibody-mediated cytotoxic activities fluctuated in vivo and in vitro. Cells from the patient with T3- T8+ proliferation were able to inhibit directly the growth of early CFU-GM, CFU-E, and BFU-E and to a lesser extent of late CFU-GM, as shown by cultures of autologous blood or marrow progenitors after depletion (and subsequent addition) of granular cells. In the other six patients with T3+ T8+ cells, no such effect was found. However, after a 24-hour incubation of the progenitors with the granular cells, CFU-GM growth was clearly inhibited; this was not observed in all experiments, a finding which may be related to the spontaneous variations of cell killer functions. Finally, no correlation was noted between the clinical course or extent of lymphoid proliferation and cell function or phenotype or with the monoclonal (two cases), polyclonal (three cases) or germ-line (one case) patterns of T cell receptor beta gene configuration.