bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for a novel in vivo control mechanism of granulopoiesis: mature cell-related control of a regulatory growth factor
Authors: Layton JE , Hockman H , Sheridan WP , Morstyn G 
Published: October 2019

Abstract
As part of phase I/II clinical trials of granulocyte colony-stimulating factor (G-CSF), the pharmacokinetics was studied. To determine the optimal way of abrogating the neutropenia caused by melphalan, patients received G-CSF and melphalan on several schedules. The half-life (t 1/2) of elimination of G-CSF was in the range 1.3 to 4.2 hours and was prolonged at higher doses, suggesting that one clearance mechanism becomes saturated at doses greater than 10 micrograms/kg, When a continuous subcutaneous (SC) infusion was administered for five days, a rapid reduction in serum G-CSF levels occurred during the last two days of the infusion, indicating that an additional clearance mechanism was induced. When a continuous infusion of G-CSF was administered after melphalan, serum G-CSF levels remained constant for a longer period of time but did decrease during the second phase of a biphasic neutrophil response. In another clinical trial, G-CSF was administered after high- dose chemotherapy and autologous bone marrow transplantation (ABMT). In these patients, the G-CSF levels did not decrease while the patients were neutropenic. These results show that increased neutrophil levels are associated with increased clearance of G-CSF. This may be one of the negative feedback mechanisms involved in maintaining neutrophil homeostasis in normal and disease states.
Human embryonic zeta-globin chains in fetal and newborn blood
Authors: Chui DH , Mentzer WC , Patterson M , Iarocci TA , Embury SH , Perrine SP , Mibashan RS , Higgs DR 
Published: October 2019

Abstract
A sensitive and specific radioimmunoassay (RIA) for human embryonic zeta-globin chains was used to study normal fetal blood and newborn cord blood as well as cord blood from newborns with alpha-thalassemias. From 17 weeks until 37 weeks of gestation, zeta-globin chains were present in almost all fetal and cord blood samples (0.27% +/- 0.15% in samples of weeks 17 through 30; 0.14% +/- 0.11% in samples of weeks 31 through 37). zeta-Globin chains were present in greater than 80% of cord blood hemolysates from normal, full-term newborns (0.15% +/- 0.11%) as well as from 16 near-term newborns of diabetic mothers (0.13% +/- 0.13%). zeta-Globin chains were not detected in normal infants aged 3 months to 2 years. In cord blood hemolysates from alpha-thalassemic newborns, the levels of zeta-globin chain content varied from very high to undetectable levels. Gene mapping of the zeta-alpha-globin gene cluster was performed in 12 newborns in whom cord blood zeta-globin chains had been determined. Newborns who were carriers of alpha- thalassemia-1 due to the (--SEA/) deletion had very high levels of zeta- globin chains (greater than 1.5%).
Interleukin-6 and granulocyte-macrophage colony-stimulating factor are candidate growth factors for chronic myelomonocytic leukemia cells
Authors: Everson MP , Brown CB , Lilly MB 
Published: October 2019

Abstract
Previous studies suggest that malignant cells from some patients with myeloid leukemias produce colony-stimulating factors (CSFs) that can function as autocrine growth factors in vitro. We have examined the roles of interleukin-6 (IL-6) and granulocyte-macrophage CSF (GM-CSF) in the proliferation of myeloid leukemia cells. IL-6 activity was assessed in conditioned medium (CM) from myeloid leukemia cell cultures or cell lysates using IL-6-dependent KD83 and 7TD1 murine cell lines. Media conditioned by cells from patients with chronic myelomonocytic leukemia (CMMoL), but not by normal monocytes, chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML) cells, contained substantial levels (50 to 1,000 U/10(6) cells) of IL-6. The IL-6 content of CM correlated directly with donor peripheral blood WBC count. CM from two of five CMMoL samples also contained greater than 350 pg/mL GM-CSF. Moreover, CMMoL cells spontaneously formed colonies in semisolid medium. CMMoL colony formation could be partially inhibited by antibodies to IL-6 or GM-CSF, whereas combination of these antibodies gave additive, and nearly complete (greater than 93%), inhibition of spontaneous colony formation. Cell lysates from uncultured CMMoL cells from one patient contained abundant GM-CSF protein but no detectable IL-6. These data suggest that IL-6 and GM-CSF act in vitro as autocrine growth factors for CMMoL cells, and that CMMoL cells in vivo may represent a GM-CSF-dependent autocrine growth system.
Use of scid mice to identify and quantitate lymphoid-restricted stem cells in long-term bone marrow cultures
Authors: Fulop GM , Phillips RA 
Published: October 2019

Abstract
Mice homozygous for an autosomal recessive scid (severe combined immune deficiency) mutation on chromosome 16 exhibit a defect that specifically impairs lymphoid differentiation but not myelopoiesis. Consequently such mice are deficient in both humoral and cell-mediated immune functions. Despite their defect, scid mice survive under pathogen-free conditions and are fertile. The mutation does not impair the hematopoietic microenvironment necessary for lymphoid differentiation, since these mice can be cured with grafts of normal bone marrow (BM) or cells from long-term BM cultures (LTBMC); however, reconstitution requires sublethal (400 cGy) irradiation of recipients. Engraftment with cells from LTBMC gave near-normal levels of colony- forming B cells (CFU-B) in spleen and BM of the recipients by 6 weeks postgrafting. Since LTBMC are devoid of all mature B and pre-B cells but contain stem cells that restore lymphoid function in scid mice, we used a limiting-dilution assay to characterize and enumerate the number of stem cells in LTBMC capable of restoring lymphoid function. Curing was determined by the CFU-B-cell assay, since CFU-B are not detectable in normal scid mice. The results indicate that fewer cells from LTBMC than from fresh BM are required to obtain lymphoid reconstitution. As few as 10(3) LTBMC cells can repopulate significant B- and T-cell function in scid recipients. From these results we conclude that scid mice can be used as recipients to quantify lymphoid-restricted stem cells and that there is a functional separation of lymphoid- and myeloid-restricted stem cells in LTBMC with an enrichment for lymphoid- restricted stem cells in these cultures.
Different repopulation profile between erythroid and nonerythroid progenitor cells in genetically anemic W/Wv mice after bone marrow transplantation
Authors: Nakano T , Waki N , Asai H , Kitamura Y 
Published: October 2019

Abstract
Repopulation kinetics of erythrocytes and neutrophils and replacement of hematopoietic progenitors were studied in genetically anemic (WB x C57BL/6)F1-W/Wv (WBB6F1-W/Wv) hosts after bone marrow transplantation from C57BL/6-bgJ/bgJ or C57BL/6-bgJ/bgJ;Pgk-1a/Y mice. Electrophoretic pattern of hemoglobin was used as a marker of donor-type erythrocytes, giant granules of bgJ/bgJ mice as a marker of donor-type neutrophils, and A-type phosphoglycerate kinase-1 (PGK-1) as a marker of hematopoietic colonies produced by donor-derived progenitor cells. Repopulation of donor-type erythrocytes was significantly faster than that of donor-type neutrophils. Moreover, the extent of replacement was greater for erythroid progenitor cells than for nonerythroid progenitor cells. When nonirradiated WBB6F1-W/Wv mice with B-type PGK-1 received 10(5) bone marrow cells from C57BL/6-bgJ/bgJ;Pgk-1a donors, only approximately 20% replacement of erythroid progenitor cells gave rise to total reconstitution of erythrocytes. The present result suggests that normal multipotential stem cells may preferentially differentiate into erythroid lineage cells in anemic WBB6F1-W/Wv hosts and that normal erythroid progenitor cells may suppress the differentiation of erythroid progenitors of WBB6F1-W/Wv hosts.
Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro
Authors: Sutherland HJ , Eaves CJ , Eaves AC , Dragowska W , Lansdorp PM 
Published: October 2019

Abstract
To develop a purification strategy for isolating the most primitive hematopoietic stem cells present in normal human marrow we have combined cell separation techniques with an assay for cells that initiate sustained hematopoiesis in vitro in the presence of irradiated human marrow adherent cells. These “feeders” were established by subculturing 2- to 6-week-old primary long-term marrow culture adherent layers at a density of 3 x 10(4) irradiated cells per square centimeter. Test “long-term culture (LTC)-initiating cells” were plated on top of the feeders and the cocultures then maintained as standard long-term marrow cultures with half-media changes and removal of half of the nonadherent cells each week. The total number of myeloid, erythroid, and multilineage clonogenic progenitors present after 5 weeks was used to provide a quantitative assessment of the number of LTC-initiating cells originally added. Using this assay, the density, light scatter, and two cell surface antigen properties of LTC- initiating cells have been defined and compared with cells capable of directly forming colonies in methylcellulose. While the majority of the clonogenic cells were found in the high forward light scatter (FLS) “blast” window, LTC-initiating cells had significantly lower FLS properties and in this respect were more similar to lymphocytes. LTC- initiating cells also expressed less HLA-DR antigen than clonogenic cells. The majority of LTC-initiating cells were found in the top 2% of the CD34 (My10) fluorescence profile, whereas clonogenic cells were found throughout the top 5% of the CD34 fluorescence profile. By combining low FLS, low orthogonal light scatter (OLS), low HLA-DR expression, and high CD34 expression, a population could be obtained that was enriched for LTC-initiating cells approximately 800-fold over unseparated marrow. This population contains only 0.06% of the marrow cells and 2% of the total clonogenic cells, but retains 50% to 60% of the LTC-initiating cells present in the original marrow. The ability to purify these two populations independently shows that the LTC and clonogenic assays identify distinct, although not necessarily nonoverlapping cell types in human marrow. Since clonogenic cells are derived from LTC-initiating cells, the LTC assay clearly detects a more primitive population. The availability of a simple approach that allows the purification of such cells by three orders of magnitude in high yield should be useful for the investigation of early events in hematopoiesis as well as for the definitive isolation of human hematopoietic stem cells with long-term in vivo repopulating potential.
New variant of von Willebrand disease with defective binding to factor VIII
Authors: Nishino M , Girma JP , Rothschild C , Fressinaud E , Meyer D 
Published: October 2019

Abstract
A new variant of von Willebrand disease (vWD) was identified by a new analytic method which characterizes the ability of plasma von Willebrand Factor (vWF) to bind to purified factor VIII (F.VIII). vWF was isolated from small amounts of plasma by immunoadsorption with a selected monoclonal antibody to vWF previously coated onto wells of microtitration plates. Plasma F.VIII was removed from immobilized vWF by washing with 0.4 mol/L CaCl2; purified F.VIII was then added to the well. The amount of bound F.VIII was estimated directly in the wells by a chromogenic assay and immobilized vWF was estimated by an immunologic a pool of normal plasma, ten control individuals, 13 with hemophilia A and five with type I vWD. In all cases, the dose-response curves were linear and the slopes of the regression lines were essentially the same. The method was then applied to investigate the binding of vWF to F.VIII in two vWD patients (sister and brother) who demonstrated significantly lower activity of F.VIII than of vWF. The first patient, with a long history of epistaxis, bruising, and hematomas, showed a slightly prolonged bleeding time (10 minutes); 15% VIII:C and 39% of vWF:Ag and vWFRCo. Her brother, who has a bleeding syndrome but no hematomas, showed similar data (bleeding time 9 minutes, 20% VIII:C, 53% vWF:Ag and vWFRCo). Similar levels of F.VIII were observed in the two propositi by four different methods (one- and two-stage clotting and chromogenic and immunologic assays). Sodium dodecyl sulfate (SDS) 1.4% agarose gel electrophoresis showed that all multimers of vWF were present in both patients. vWF binding to F.VIII was markedly decreased in the two propositi. The abnormal binding of vWF to F.VIII was not corrected during pregnancy or after infusion of 1-deamino (8-D- arginine) vasopressin despite an increase in vWF levels. The qualitative abnormality of vWF in both patients was associated with a subtle alteration of the multimeric structure by SDS 3% agarose gel electrophoresis in which the two central subbands of the quintuplet of individual oligomers were undetectable or poorly visible. SDS- polyacrylamide gel electrophoresis under reducing conditions demonstrated a single band of 275 Kd in the plasma of both patients, and there was no evidence of a second band corresponding to pro-vWF, the precursor of the mature vWF subunit, suggesting that proteolytic processing of vWF was normal.
Lymphokine production by T-cell clones after human bone marrow transplantation
Authors: Velardi A , Varese P , Terenzi A , Dembech C , Albi N , Grossi CE , Moretta L , Martelli MF , Grignani F , Mingari MC 
Published: October 2019

Abstract
T cells recovering after bone marrow transplantation (BMT) were analyzed for their phenotypic and functional features by two-color immunofluorescence and a high efficiency cloning technique. A predominance of cells co-expressing natural killer (NK)-related surface antigens, such as Leu 7 (CD57) and CD11b, was detected within both the CD4+ and CD8+ subsets from 5 months postgrafting onward. Such cells are virtually absent among normal circulating CD4+ cells and account for a minority (approximately 30%) of normal CD8+ cells. Postgrafting T cells representative of the whole range of NK-related antigen co-expression were selected from six patients for clonal analyses. In control subjects, 63% and 41% of the CD4+ and CD8+ clones, respectively, produced interleukin-2 (IL-2) whereas approximately 30% of either CD4+ or CD8+ control clones produced interferon (IFN)-gamma. At variance, and irrespective of their CD4+/CD8+ phenotype, lower proportions of BMT recipient-derived clones produced IL-2 (20% and 12%, respectively), whereas the majority of both CD4+ and CD8+ clones (75% and 71%, respectively) released high amounts of IFN-gamma. Purified populations of CD57+/CD11b+ v negative cells from two BMT recipients and two control subjects were cloned and subsequently evaluated for IL-2 and IFN-gamma production. CD57+/CD11b+ cell-derived clones were poor IL-2 producers in both normal subjects and BMT patients. In contrast, IL-2- producing clones were frequent (62% to 79%) among those derived from CD57-/CD11b- cells from normal subjects, whereas they were still represented at lower than normal proportions, ie, 25% to 41%, among clones generated from BMT recipients. CD57+/CD11b+ cells gave rise to comparably high proportions of IFN-gamma producing clones in both normal subjects and BMT recipients (approximately 80%). In contrast, IFN-gamma producing clones were approximately 25% to 50% of CD57-/CD11b- cell-derived clones in both normal subjects and BMT patients. Therefore, while the predominance of NK-related antigen-positive T cells may be predictive of poor IL-2 and high IFN-gamma production, the immune derangement in long-term BMT recipients is further enhanced by the finding that all T cells may be poor IL-2 producers. It is also suggested that IL-2 production is a preferential function of T cells that do not express CD57 and CD11b, whereas IFN-gamma production is attributable to T cells that express CD57 and CD11b.
Increased plasma levels of interleukin-6 in sepsis [see comments]
Authors: Hack CE , De Groot ER , Felt-Bersma RJ , Nuijens JH , Strack Van Schijndel RJ , Eerenberg-Belmer AJ , Thijs LG , Aarden LA 
Published: October 2019

Abstract
Interleukin-6 (IL-6) is likely to be an important mediator of the inflammatory response. We measured levels of this cytokine in plasma samples from 37 patients with sepsis or septic shock obtained at the time of admission to the intensive care unit and related these levels to hemodynamic and biochemical parameters as well as to clinical outcome. In 32 of the 37 patients, increased levels of IL-6 were found, occasionally up to 7,500 times the normal level. The highest IL-6 levels were encountered in patients who suffered from septic shock (P value of the difference between patients with and without shock less than .0001). In addition, IL-6 significantly correlated with plasma lactate (P less than .0001), heart rate (P = .05) and, inversely, with mean arterial pressure (P = .01) and platelet counts (P = .0002). Significant correlations of IL-6 with the anaphylatoxins C3a (P = .0001) and C4a (P = .0002) and with the main inhibitor of the classical pathway of complement, C1-inhibitor (inverse correlation, P = .05), were also observed. IL-6 on admission appeared to be of prognostic significance: levels were higher in septic patients who subsequently died than in those who survived (P = .0003), in particular when only patients with septic shock were considered (P less than .0001). All nine septic patients with levels of less than 40 U/mL on admission survived, whereas 89% of the nine patients with levels exceeding 7,500 U/mL died. These data provide evidence for a role of IL-6 in the pathophysiology of septic shock. Further studies are needed to reveal whether IL-6 in sepsis is directly involved in mediating lethal complications or whether it is to be considered as an “alarm hormone” that reflects endothelial cell injury probably mediated by the anaphylatoxines.
Effects of tumor necrosis factor on sensitive and multidrug resistant human leukemia and myeloma cell lines
Authors: Salmon SE , Soehnlen B , Dalton WS , Meltzer P , Scuderi P 
Published: October 2019

Abstract
Two human tumor cell lines exhibiting acquired multidrug resistance (MDR) with increased expression of a cell surface glycoprotein (GP-170) were tested for their sensitivity to human recombinant tumor necrosis factor (rTNF). The drug resistant mutant lines (CEM/V, a T-cell leukemia line resistant to vinblastine, and 8226/D, a multiple myeloma line resistant to doxorubicin), were markedly more sensitive to rTNF in clonogenic assay than were their drug-sensitive parental lines (CEM, 8226). As determined by radioreceptor assay, the number of cell surface receptors for rTNF did not differ on the parental and drug-resistant lines. During the first 24 hours after addition of rTNF, there was a decrease in intracellular ATP content in the CEM/V line but not in the CEM line. No differential effect of rTNF on ATP content was observed between 8226 and 8226/D. As determined by RNA dot-blot analysis, total cellular RNA for GP-170 was increased in the 8226/D cells. After rTNF exposure, expression of total cellular RNA for GP-170 was not altered. Accumulation of radiolabeled doxorubicin by 8226/D cells was not altered by previous or coincubation with rTNF. These findings suggest that the effects of rTNF on MDR cells is not related to TNF receptor number and is mediated at a step subsequent to rTNF binding and not by either inhibition of synthesis of GP-170 or by alteration in the function of the GP-170 efflux pump.
An additional breakpoint region in the BCL-1 locus associated with the t(11;14)(q13;q32) translocation of B-lymphocytic malignancy
Authors: Meeker TC , Grimaldi JC , O'Rourke R , Louie E , Juliusson G , Einhorn S 
Published: October 2019

Abstract
The t(11;14)(q13;q32) translocation is associated with human B- lymphocytic malignancy. This translocation divides the IgH locus on chromosome 14q32 and may activate a postulated proto-oncogene, bcl–1, located on chromosome 11q13. Two samples of chronic lymphocytic leukemia with the t(11;14)(q32;q13) translocation were studied. The break in one sample was shown to join Jh sequences with the previously described bcl–1 major translocation cluster. DNA blots of the second sample suggested that Jh sequences were joined to a different breakpoint region on chromosome 11. This translocation was cloned and found to link the human Jh3 region and a new breakpoint region 63 kb telomeric of the major translocation cluster. This translocation occurred in part as the result of an aberrant D-J recombination. Recurrent translocations human B-lymphocytic malignancy. The definition of a new breakpoint region may aid the identification of the postulated bcl–1 gene.
Expression of c-jun protooncogene in human myelomonocytic cells
Authors: Bertani A , Polentarutti N , Sica A , Rambaldi A , Mantovani A , Colotta F 
Published: October 2019

Abstract
A prototypic “immediate early” gene, c-fos, has been extensively investigated in relation to the differentiation and activation of myelomonocytic cells. The c-fos gene product is associated in transcriptional complexes with the c-jun product. These protooncogenes are part of the regulatory network of gene expression. The present study was designed to investigate expression of the c-jun protooncogene in human circulating myelomonocytic cells. We found that c-jun is constitutively expressed in normal monocytes and granulocytes, whereas low levels of transcripts are found in lymphocytes. Acute myelogenous leukemia (AML) samples of French-American-British Cooperative Group (FAB) subtypes 1 through 4 express appreciable levels of this protooncogene. Normal phytohemagglutinin (PHA)-activated lymphocytes express high levels of c-jun. Expression in normal myelomonocytic cells is detectable even after 18 hours of culture. The c-jun transcripts in myelomonocytic cells have a half-life of approximately 20 minutes and are superinduced by cycloheximide, which affects both the degradation rate of mRNA and the transcriptional activity of the c-jun gene. Functional activation of monocytes and granulocytes with phorbol esters, lipopolysaccharide, and tumor necrosis factor (TNF) increase c- jun expression. This induction is rapid, transient, and does not require intervening protein synthesis. Runoff experiments showed that in freshly isolated untreated monocytes, the c-jun gene is constitutively transcribed, and that induction by lipopolysaccharide is at least in part at the transcriptional level. Moreover, lipopolysaccharide (LPS) treatment reduced the degradation rate of c- jun transcripts, prolonging the half-life to approximately two hours. Expression of c-jun in resting and activated monocytes and granulocytes suggests that this protooncogene may play a role in the differentiation and activation of cells belonging to the myelomonocytic lineage.
t(3;22)(q27;q11): a novel translocation associated with diffuse non- Hodgkin's lymphoma [see comments]
Authors: Offit K , Jhanwar S , Ebrahim SA , Filippa D , Clarkson BD , Chaganti RS 
Published: October 2019

Abstract
Of 187 specimens of non-Hodgkin's lymphoma and four hyperplastic lymphoid proliferations with clonal chromosome abnormalities ascertained serially over a 4 1/2-year period, nine cases with t(3;22)(q27;q11) were identified. Seven of the lymphomas were diffuse tumors, predominantly large cell type. The eighth tumor, a follicular small cleaved cell lymphoma, exhibited a t(3;22) and a t(14;18)(q32;q21). The ninth case was a lymph node from a human immunodeficiency virus-positive patient which showed atypical hyperplasia. Overall survival of t(3;22) diffuse lymphoma patients was not different from that of patients with abnormal karyotypes without t(3;22). The t(3;22) diffuse tumors studied showed a disproportionate frequency of lambda light chain on their cell surfaces, a finding similar to that observed in t(8;22)(q24;q11) Burkitt's lymphomas. Our results indicate that the t(3;22)(q27;q11) is the third most common recurring translocation in diffuse non-Hodgkin's lymphoma.