bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased serum CD8 antigen level in childhood Hodgkin's disease relates to advanced stage and poor treatment outcome
Authors: Pui CH , Ip SH , Thompson E , Dodge RK , Brown M , Wilimas J , Carrabis S , Kung P , Berard CW , Crist WM 
Published: October 2019

Abstract
Measurement of the soluble form of CD8 antigen, a surface membrane component of suppressor/cytotoxic T cells, has yielded useful information relevant to prognosis in the lymphoid malignancies of childhood. We therefore determined pretreatment levels of serum CD8 antigen in 90 children with newly diagnosed Hodgkin's disease. The findings ranged widely, from 220 to 2,585 U/mL (median, 556 U/mL). In patients with advanced disease (stage III or IV), the median serum CD8 level was significantly higher than in those with less disease extension (stage I or II): 675 v 477 U/mL, P = .003. It was also higher in children with B symptoms compared with all others: 622 v 494 U/mL, P = .005. Cases with a histologic classification of mixed cellularity had a significantly higher median level of the antigen than did those classified as nodular sclerosis: 847 v 509 U/mL, P = .005. Finally, higher serum CD8 levels (greater than 430 U/mL) were significantly associated with an increased probability of treatment failure (P = .02). In a multivariate analysis, serum CD8 level retained its impact on treatment outcome after adjustment for other potentially useful prognostic factors, including disease stage, presence of B symptoms, histology, erythrocyte sedimentation rate, sex, age, and race. The prognostic strength shown by soluble CD8 in this analysis suggests that the antigen has clinical value. We postulate that increased CD8 levels in serum indicate enhanced suppressor T-cell activity, which may compromise the host's antitumor immunity, leading to unusually aggressive disease.
Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin
Authors: Janssen JW , Buschle M , Layton M , Drexler HG , Lyons J , van den Berghe H , Heimpel H , Kubanek B , Kleihauer E , Mufti GJ 
Published: October 2019

Abstract
Restriction fragment length polymorphisms (RFLPs) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 34 female patients with primary myelodysplastic syndromes (MDS). Twelve patients (35%) were heterozygous at the HPRT or PGK loci for BamHI or BglI RFLPs, respectively. In eight patients showing PGK polymorphisms, clonality was determined by X-chromosome inactivation analysis. These included patients from different morphologic subtypes: four with refractory anemia (RA), two with RA and ring sideroblasts (RARS), one patient with RA with excess of blasts (RAEB), and one with chronic myelomonocytic leukemia (CMML). A monoclonal pattern of X-chromosome inactivation was observed in seven cases. In a further case characterized by bone marrow hypoplasia, peripheral blood (PB) leukocytes were polyclonal in origin. Following low-dose cytarabine therapy, reversion to polyclonal hematopoiesis was observed in a case of RAEB indicating the presence of residual normal hematopoietic stem cells with the capacity for marrow reconstitution. The clonal relation of lymphoid and granulocyte/monocyte lineages was studied directly in two cases of CMML exhibiting somatic mutations of N-ras or Ki-ras oncogenes. By selective oligonucleotide hybridization to ras gene sequences amplified in vitro by the polymerase chain reaction, a mutated ras allele was demonstrated in PB granulocytes, monocytes, and B and T lymphocytes of both patients. We conclude that MDS arise from a multipotent hematopoietic stem cell with the potential for myeloid and lymphoid differentiation.
Protooncogene expression and the clinical characteristics of acute nonlymphocytic leukemia: A Leukemia Intergroup pilot study
Authors: Preisler HD , Raza A , Larson R , LeBeau M , Browman G , Goldberg J , Grunwald H , Volger R , Verkh L , Singh P 
Published: October 2019

Abstract
Northern blot analysis was used to assess the level of expression of five protooncogenes and histone H3 in the bone marrow cells of patients with acute nonlymphocytic leukemia (ANLL). The relationship between the level of gene expression and the clinical characteristics of the disease and response to therapy was studied. The levels of expression of c-myc and c-myb are weakly correlated and are unrelated to French- American-British (FAB) type of ANLL. The levels of expression of c-fms, c-fes, and c-fos are highly correlated with each other and are highest in leukemia with a monocytic component (c-fms v FAB = .71, c-fes v FAB = .75). High levels of c-myc expression are associated with a high probability of not responding to remission induction therapy (P = .004). The converse is true for c-fms expression levels. High levels of expression of c-myc or c-myb are associated with short remissions (P = .059 and .065, respectively), perhaps because they are associated with a high capacity for leukemic cell self-renewal and/or an inability of leukemic cells to differentiate in response to chemotherapy.
Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy
Authors: Hussein KK , Dahlberg S , Head D , Waddell CC , Dabich L , Weick JK , Morrison F , Saiki JH , Metz E , Rivkin SE 
Published: October 2019

Abstract
The Southwest Oncology Group conducted a study of acute lymphoblastic leukemia (ALL) in adults over a 5-year period, testing the utility of the L-10M regimen initially described by the group from Memorial Sloan- Kettering Cancer Center. One hundred sixty-eight eligible patients were treated with this intensive combination chemotherapy regimen. One hundred fifteen (68%) achieved complete remission. With the current median follow-up time of 34.5 months, the median durations of remission, relapse-free survival, and overall survival were 22.9, 20.9, and 17.7 months, respectively. Only 35% of the patients over 50 years of age achieved a complete remission. Age was a significant prognostic factor for complete response, survival, relapse-free survival, and remission duration. In addition, a low initial WBC count was found to have a statistically significant association with longer remission duration. Responders between the ages of 20 and 49 years with WBC counts of less than 15,000 appear to have an exceptionally good prognosis.
The in vivo metabolism of recombinant human erythropoietin in the rat
Authors: Spivak JL , Hogans BB 
Published: October 2019

Abstract
We compared the in vivo plasma clearance and organ accumulation in anesthetized rats of 125I-labeled, recombinant human erythropoietin and 125I-labeled, desialylated recombinant erythropoietin. The immediate volume of distribution of 125I-labeled, recombinant erythropoietin approximated that of the plasma volume. Its plasma clearance was multiexponential, with an initial rapid distribution phase (t1/2 = 53 minutes) and a slower elimination phase (t1/2 = 180 minutes). Organ accumulation of labeled recombinant erythropoietin, as compared with 125I-labeled human albumin, was negligible until 30 minutes after injection when small amounts appeared in the kidneys and bone marrow. Only 24% of the 125I-labeled, desialylated recombinant erythropoietin was recovered immediately after injection, and 96% of the hormone was cleared from the plasma with a t1/2 of 2.0 minutes. The bulk of the desialylated hormone accumulated in the liver where it was rapidly catabolized and its breakdown products released back into the plasma. Significantly, in contrast to unmodified erythropoietin, there was also early accumulation of desialylated hormone in the kidneys, marrow, and spleen. Desialylated orosomucoid but not orosomucoid, yeast mannan, or dextran sulfate 500 inhibited the rapid plasma clearance and hepatic accumulation of desialylated erythropoietin. Oxidation of the desialylated hormone restored its plasma recovery and clearance to normal but rendered it biologically inactive, and accumulation in organs other than the kidney was negligible.
Differential biologic effects resulting from bimodal binding of recombinant human tumor necrosis factor to myeloid leukemia cells
Authors: Ishikura H , Hori K , Bloch A 
Published: October 2019

Abstract
Human recombinant tumor necrosis factor (rTNF) bound to ML-1 and HL-60 human myeloid leukemia cells in a bimodal manner. Saturable high- affinity binding was maximal at approximately 3 nmol/L rTNF, whereas saturable low-affinity binding reached its maximum at approximately 30 nmol/L. As analyzed by computer program, the observed data fit a two- receptor site model, with p less than .05. High-affinity binding concentrations of rTNF caused the differentiation of both cell lines, whereas low-affinity binding concentrations abolished this effect in a concentration-dependent manner. Thus, the type of biologic response elicited with rTNF in these cells is a function of the concentration at which the factor is applied. If generally applicable, this bimodal effect may require consideration when rTNF is to be used therapeutically.
Interleukin-6 synergizes with M-CSF in the formation of macrophage colonies from purified human marrow progenitor cells
Authors: Bot FJ , van Eijk L , Broeders L , Aarden LA , Lowenberg B 
Published: October 2019

Abstract
We examined the in vitro stimulative effects of recombinant human interleukin-6 (IL-6, or interferon-beta 2) on purified human bone marrow progenitor cells. IL-6 alone or in combination with erythropoietin (Epo), IL-3, GM-CSF, or G-CSF did not induce colony formation. However, IL-6 strongly synergized with M-CSF in stimulating macrophage colony formation (colony numbers and size). The magnitude of IL-6 synergism with M-CSF was dose dependent; maximal potentiation of M- colony formation was evident at approximately 100 to 1,000 U/mL IL-6. When the addition of IL-6 to M-CSF-supplemented cultures was delayed for more than one day after the beginning of culture, enhancement of macrophage colony formation was lost. IL-6 stimulation of M-CSF- responsive colony formation was not apparent when nonpurified marrow cells were plated, most likely due to endogenous IL-6 release. These observations suggest that IL-6, in addition to playing a role in B- lymphocyte proliferation can potentiate the human immune defence mechanism by stimulating monocyte-macrophage development as well.
Inhibition and complexation of activated protein C by two major inhibitors in plasma
Authors: Heeb MJ , Espana F , Griffin JH 
Published: October 2019

Abstract
To determine the major physiologic inhibitors of activated protein C (APC), plasma was incubated with APC or with Protac C and subjected to immunoblotting. APC:inhibitor complexes gave two major bands reacting with antiprotein C antibodies when immunoblotted on nondenaturing gels, and additional minor bands that varied between serum and plasma. Formation of one of the two major bands of APC:inhibitor complex, but not the other, was stimulated by heparin and only this band reacted with antibodies to the previously described APC inhibitor that is here designated PCI-1. Plasma immunodepleted of PCI-1 formed complexes with APC as visualized with antiprotein C but not anti-PCI-1 antibodies, and exhibited heparin-independent inhibition of APC activity, providing evidence for the existence of a second major physiologic APC inhibitor, PCI-2. Formation of APC:PCI-2 complexes in PCI-1-depleted plasma paralleled inhibition of APC amidolytic activity. PCI-2 was separated from PCI-1 and partially purified using column chromatography. PCI-2 formed inactive complexes of approximately 110,000 molecular weight (mol wt) with APC suggesting PCI-2 has an approximate mol wt of 50,000. Thus, inhibition of APC in plasma involves two major distinct 50,000 mol wt inhibitors, the heparin-dependent PCI-1 and the heparin- independent PCI-2.
Identification of a F.VIII epitope recognized by a human hemophilic inhibitor
Authors: Lubahn BC , Ware J , Stafford DW , Reisner HM 
Published: October 2019

Abstract
Hemophilia A, one of the most common of the inherited bleeding disorders, results from a deficiency or abnormality of factor VIII (F.VIII). In approximately 15% of persons with hemophilia, treatment with exogenous F.VIII is complicated by the development of anti-F.VIII antibodies which block F.VIII coagulant activity. These antibodies have been termed inhibitors. To localize epitopes recognized by inhibitors, we used a lambda gt11 library which expresses small random fragments of F.VIII as fusion proteins. One epitope has been mapped to the 25-amino acid sequence lys-338 through asp-362 of F.VIII (E338–362). Immunoaffinity-purified antibodies that react with this epitope neutralize F.VIII:C activity. E338–362 is adjacent to an enzymatic cleavage site at arg-372 which is important in F.VIII activation. Hence, an antibody binding to E338–362 would probably block this cleavage and thereby block activation of F.VIII.
Monocytoid B-cell lymphoma: its evolution and relationship to other low- grade B-cell neoplasms
Authors: Traweek ST , Sheibani K , Winberg CD , Mena RR , Wu AM , Rappaport H 
Published: October 2019

Abstract
Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.
Small lymphocytic lymphoma: a clinicopathologic analysis of 268 cases
Authors: Ben-Ezra J , Burke JS , Swartz WG , Brownell MD , Brynes RK , Hill LR , Nathwani BN , Oken MM , Wolf BC , Woodruff R 
Published: October 2019

Abstract
We analyzed specimens from 268 patients with small lymphocytic lymphoma (SL) to identify prognostic factors significant for survival. These patients were staged and treated according to the protocols of the Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Southeastern Cancer Study Group, and the Southwest Oncology Group. Univariate analysis showed that a large-cell grade greater than I, WBC greater than 10,000/microL, hemoglobin (Hgb) less than 11 g/dL, age greater than or equal to 55 years, and failure to respond to treatment were all poor prognostic factors. Multivariate analysis showed that large-cell grade, age, degree of capsular invasion, and symptom type were independently associated with survival. Separate analyses of cases with and without leukocytosis indicated differences in survival. In patients without leukocytosis, age, presence or absence of anemia, and treatment response were significant prognostic variables; in patients with leukocytosis, large-cell grade, presence or absence of anemia, symptom type, and treatment response were significantly related to survival. Multivariate analysis showed that age was the only significant independent prognostic variable in patients without leukocytosis; in patients with leukocytosis, symptom type, large-cell grade, and bone marrow involvement were independently associated with survival. We conclude that several parameters, both clinical and pathologic, should be assessed at the initial diagnosis of SL to predict prognosis better.
Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results
Authors: Champlin RE , Horowitz MM , van Bekkum DW , Camitta BM , Elfenbein GE , Gale RP , Gluckman E , Good RA , Rimm AA , Rozman C 
Published: October 2019

Abstract
Graft failure was analyzed in 625 patients receiving allogeneic bone marrow transplants from HLA-identical sibling donors as treatment for severe aplastic anemia. Sixty-eight (11%) had no or only transient engraftment. Second bone marrow transplants were successful in achieving extended survival in 16 of 27 patients with transient initial engraftment but in none of ten patients with no sign of engraftment after the first transplant. The major factors associated with a reduced risk of graft failure were use of radiation for pretransplant immunosuppression and use of cyclosporine rather than methotrexate or T- cell depletion of the donor bone marrow for prophylaxis against graft-v- host disease (GVHD). Among 266 patients prepared for transplantation with cyclophosphamide alone, the risk of graft failure was increased in patients who received previous transfusions and reduced in those who received corticosteroids for previous therapy. Neither cell dose nor administration of donor buffy coat cells affected the probability of engraftment. Although use of radiation in conditioning reduced graft failure, survival was not improved. Posttransplant treatment with cyclosporine and avoidance of pretransplant blood transfusions were associated with improved survival.
The effect of recombinant human granulocyte macrophage colony- stimulating factor on neutrophil activation in patients with refractory carcinoma
Authors: Kaplan SS , Basford RE , Wing EJ , Shadduck RK 
Published: October 2019

Abstract
Patients with refractory carcinoma were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by intravenous (IV) infusion. During the period of treatment, studies of polymorphonuclear leukocyte superoxide (O2-) release in response to formylmethionylleucylphenylalanine (fMLP) and phorbol myristate acetate (PMA) and studies of chemotaxis in response to fMLP and C5a were performed. We observed that patients receiving rhGM-CSF in vivo exhibited primed O2- release after stimulation both with fMLP and PMA. Chemotaxis, however, was not enhanced by the treatment. These data suggest that host defenses may be enhanced by this treatment and that rhGM-CSF may be a useful therapeutic adjunct in compromised patients.
Interacting cytokines regulate in vitro human megakaryocytopoiesis
Authors: Bruno E , Miller ME , Hoffman R 
Published: October 2019

Abstract
The effects of hematopoietic growth factors on in vitro human megakaryocytopoiesis were studied using a serum-depleted culture system. Both recombinant interleukin-3 (r-IL-3) and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) increased megakaryocyte (MK) colony formation (P less than .01) above that observed in baseline cultures. Recombinant interleukin-4 (rIL-4) and interleukin 1 alpha (rIL-1 alpha) failed either to promote MK colony formation alone or to increase rIL-3 or rGM-CSF promoted colony formation. Recombinant erythropoietin (rEpo) and purified thrombocytopoiesis-stimulating factor (TSF) did not increase (P greater than .05) MK colony formation when added alone but synergized with rIL- 1 alpha, leading to a twofold increase in MK colony formation. Such a synergistic relationship was not observed between rIL-4 and rEpo. In addition, TSF enhanced the ability of rIL-3 but not rGM-CSF to promote MK colony formation. Addition of rEpo to optimal or suboptimal concentrations of rGM-CSF or suboptimal concentrations of rIL-3 resulted in a significant increase (P less than .05) in the total number of MK-containing colonies, due to the appearance of multilineage colonies containing MKs. The addition of rEpo to optimal concentrations of rIL-3 resulted in increased numbers of multilineage colonies containing MKs; however, the number of total MK-containing colonies was not significantly increased when compared to assays containing rIL-3 alone. By contrast, transforming growth factor-beta (TGF-beta) inhibited both rIL-3, and rGM-CSF promoted MK colony formation, with optimal inhibition resulting in a 35%-45% reduction of MK colony formation.
In vivo hematopoietic effects of recombinant interleukin-1 alpha in mice: stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin
Authors: Johnson CS , Keckler DJ , Topper MI , Braunschweiger PG , Furmanski P 
Published: October 2019

Abstract
Interleukin-1 alpha (IL-1 alpha) is a macrophage-derived, multifunctional cytokine that broadly potentiates myelopoiesis and induces the synthesis of hematopoietic colony-stimulating factors (CSF) in vitro and in vivo. To evaluate the possibility for use of IL-1 alpha in ameliorating in vivo bone marrow suppression induced by drugs or radiation, we examined the in vivo effects of the cytokine on erythropoietic and other hematopoietic progenitor cells. Normal mice were treated with a single intraperitoneal (IP) injection of recombinant human IL-1 alpha at varying doses and were assayed at various times post-treatment. By six hours postinjection, a significant suppression of mature erythroid progenitors (CFU-E) was observed in animals treated with IL-1 alpha (0.5 micrograms/mouse), with maximum suppression of CFU-E and peripheral blood reticulocyte counts occurring at 24 hours. Decreases in peripheral blood hematocrit did not occur after a single IL-1 alpha injection but were observed after multiple injections of the cytokine. The suppressive effects of IL-1 alpha on late-stage erythropoiesis were abrogated by simultaneous administration of erythropoietin (EPO). At 48 hours post-treatment, a marked stimulation was observed in the numbers of spleen and marrow immature erythroid (BFU-E), macrophage (CFU-M), granulocyte (CFU-G), granulocyte- macrophage (CFU-GM), and megakaryocyte (CFU-meg) progenitor cells. These results demonstrate the potential use of IL-1 alpha as a generalized stimulator of hematopoiesis and show that the cytokine- induced suppression of late-stage erythropoiesis can be prevented by EPO.