bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells
Authors: Lotem J , Sachs L 
Published: October 2019

Abstract
Transforming growth factor-beta 1 (TGF-beta 1) induces cell death in myeloid leukemia by apoptosis. In the M1 myeloid leukemia, this induction of apoptosis was inhibited by granulocyte colony-stimulating factor (G-CSF) or interleukin-6 (IL-6) and to a lesser extent by IL-1 alpha. IL-3 and stem cell factor/mast cell growth factor (SCF) showed only a marginal effect, and granulocyte-macrophage and macrophage CSFs (GM-CSF and M-CSF, respectively) were inactive. The induction of apoptosis by TGF-beta 1 in a different myeloid leukemia (7-M12) was inhibited by GM-CSF and IL-3 but not by the other cytokines. In the absence of TGF-beta 1, both M1 and 7-M12 leukemic cells were independent of hematopoietic cytokines for cell viability and growth. The cytotoxic compounds vincristine, vinblastine, adriamycin, cytosine arabinoside, cycloheximide, and sodium azide, some of which are used in cancer chemotherapy, induced cell death by apoptosis in both leukemias. As with TGF-beta 1, apoptosis induced by these cytotoxic compounds was inhibited by GM-CSF (7-M12 leukemia) and by G-CSF or IL-6 (M1 leukemia). Cyclosporine A decreased cell multiplication in M1 cells without inducing apoptosis, and G-CSF and IL-6 inhibited the cytostatic effect of cyclosporine A. It is suggested that the clinical use of cytokines to correct therapy-associated myelosuppression should be carefully timed to avoid protection of malignant cells from the cytotoxic action of the therapeutic compounds.
Heterogeneous immunophenotype of granular lymphocyte expansions: differential expression of the CD8 alpha and CD8 beta chains [see comments]
Authors: de Totero D , Tazzari PL , DiSanto JP , di Celle PF , Raspadori D , Conte R , Gobbi M , Ferrara GB , Flomenberg N , Lauria F 
Published: October 2019

Abstract
In this study, we have evaluated 14 large granular lymphocyte (LGL) expansions, 11 of which were CD8+. Analysis of the membrane expression of the alpha and beta chains of the CD8 antigen, using specific monoclonal antibodies (MoAbs), has shown that LGL expansions with the CD3+, CD4+, CD8+, CD57+ T-cell receptor (TcR) alpha beta phenotype bear the CD8 alpha/alpha isoform, while the CD3+, CD4-, CD8+, CD57+ TcR alpha beta samples were positive for both the CD8 alpha and CD8 beta chains. These data were confirmed also by messenger RNA analysis. One additional case, with a peculiar phenotype (CD3-, CD2-, CD4-, CD8+, CD57-) and a germline configuration of the TcR beta and gamma chain genes, expressed only the CD8 alpha chain. After additional phenotypic analysis with a wider panel of MoAbs, it was found that the beta chain of the interleukin-2 receptor was constitutively expressed on the majority of the samples tested, and that most of the monoclonal samples coexpressed CD45RA/R0 antigens. Using MoAbs directed against the variable regions of the TcR beta chain, we could show a preferential V beta region restriction in the CD8+ monoclonal cases. This more extensive characterization of CD8+ LGL expansions has further documented the marked heterogeneity within this rare condition and allowed a better phenotypic dissection between the monoclonal and polyclonal cases.
CD10/NEP is expressed on Thy-1low B220+ murine B-cell progenitors and functions to regulate stromal cell-dependent lymphopoiesis
Authors: Salles G , Chen CY , Reinherz EL , Shipp MA 
Published: October 2019

Abstract
To further characterize the function of the common acute lymphoblastic leukemia antigen (CALLA; CD10, neutral endopeptidase 24.11, NEP) in early lymphoid development, we have identified murine lymphoid progenitors expressing CD10/NEP and analyzed the effects of inhibiting the enzyme in in vitro assays of murine lymphoid differentiation. CD10/NEP transcripts and enzymatic activity were primarily restricted to the subpopulation of murine lymphoid progenitors, termed pro-B cells, which were isolated from bone marrow (BM) and modified Whitlock- Witte cultures and defined by coexpression of B220 and low levels of Thy-1. CD10/NEP transcripts and cell surface enzymatic activity were also detected in BM stromal cells known to support the development of B- lymphoid progenitors. In contrast, Abelson and H-ras transformed pre-B- cell lines were CD10/NEP- as were Thy-1-B220+ pre-B cells from BM and modified Whitlock-Witte cultures and Thy-1lowLin- (B220-Mac-1-GR-1-Ly- 2/3-) uncommitted hematopoietic progenitors from BM. The expression of CD10/NEP on murine pro-B cells and BM stromal cells suggests a role for the enzyme in early B-cell ontogeny. In modified Whitlock-Witte cultures in which Thy-1lowLin- progenitors plated on BM stromal cells differentiate into Thy-1lowB220+ pro-B and Thy-1-B220+ pre-B cells, the addition of specific CD10/NEP inhibitors increased the number of lymphoid colonies at days 5 through 7 by 34% (P < .001). The results suggest that CD10/NEP participates in the regulation of the earliest stages of stromal cell-dependent B lymphopoiesis.
Involvement of CD36 on erythrocytes as a rosetting receptor for Plasmodium falciparum-infected erythrocytes
Authors: Handunnetti SM , van Schravendijk MR , Hasler T , Barnwell JW , Greenwalt DE , Howard RJ 
Published: October 2019

Abstract
Plasmodium falciparum-infected erythrocytes (parasitized red blood cells [PRBCs]) can adhere to uninfected erythrocytes (RBCs) to form rosettes, and adhere to the endothelial cell (EC) surface antigen CD36. These adherence phenomena have previously been considered quite different. We show that anti-CD36 monoclonal antibodies (MoAbs) reverse rosetting of PRBCs from both a culture-adapted line (Malayan Camp [MC] strain) and a natural isolate, GAM425. Three MoAbs that block adherence of PRBCs to ECs or C32 melanoma cells also reversed rosetting by greater than 50% at levels of less than 1 microgram/mL (OKM5, OKM8, and 8A6). Two other MoAbs that react with purified CD36 (1D3 and 1B1), but do not react with the surface of C32 cells, failed to reverse rosetting. When rosettes were disrupted and the RBCs and PRBCs were pretreated separately with antibodies before mixing to allow rosette reformation, only pretreatment of RBCs had an effect. MoAb 8A6 pretreatment of RBCs blocked rosette reformation, while MoAb 1B1 pretreatment did not. Rosetting was also reversed by purified human platelet CD36. In conjunction with evidence that CD36 is expressed on normal human erythrocytes (van Schravendijk et al, Blood 80:2105, 1992), we conclude that this CD36 is able to act as a host receptor for rosetting in the MC strain and some natural isolates of P falciparum.
A new in situ hybridization technique for spliced RNA species documents the bone marrow origin of pulmonary macrophages in chronic myelogenous leukemia
Authors: Ely P , Haase A , Wietgrefe S , Zupancic M , Beneke J , Hertz M , Miller W 
Published: October 2019

Abstract
Tissue macrophages derive from monocytes of bone marrow origin. Because monocytes from patients with chronic myelogenous leukemia (CML) contain the Philadelphia chromosome (Ph), it seemed probable that tissue macrophages in CML would originate from the malignant clone. Using powerful molecular techniques, we studied pulmonary alveolar macrophages (PAM) from two patients with CML. PAM from Patient 1, a patient in chronic phase studied before bone marrow transplantation (BMT), contained the Ph by Southern blot analysis. Patient 2, an accelerated phase patient, was studied after post-BMT relapse. PAM from this patient not only contained the Ph, but also expressed the BCR/ABL message documented by a new splice junction in situ hybridization technique. This new technique allows detection of BCR/ABL mRNA and determination of splice useage in individual cells. These data confirm the continued replenishing of PAM from peripheral blood monocytes in non-BMT settings and represent the first direct evidence that tissue macrophages are derived from the malignant clone in patients with CML.
Enhancement of T-cell-depleted bone marrow allografts in the absence of graft-versus-host disease is mediated by CD8+ CD4- and not by CD8- CD4+ thymocytes
Authors: Lapidot T , Faktorowich Y , Lubin I , Reisner Y 
Published: October 2019

Abstract
Transplantation of T-cell-depleted C57BL/6-Nu/Nu (“nude”) bone marrow (BM) into C3H/HeJ recipients, conditioned with 8 Gy total body irradiation plus chemotherapy with the myeloablative drug dimethyl myleran, resulted in poor hematopoietic reconstitution 14 days posttransplant, compared with transplantation with T-cell-depleted BM from normal C57BL/6 donors. Hematopoietic reconstitution of “nude” BM could be improved by the addition of (C57BL/6xC3H/HeJ)F1 thymocytes void of graft-versus-host activity. Enhancement of BM allografting by thymocytes is sensitive to low radiation doses (> or = 5.0 Gy) and can be achieved by transplanting the BM 24 hours before the administration of thymocytes. Fractionation of F1 thymocytes by differential agglutination with peanut agglutinin (PNA) and by fluorescence activated cell sorting showed that this hematopoietic enhancing activity is enriched in the unagglutinated (PNA-) thymocyte fraction and is mediated by PNA- CD8+ and not by PNA- CD4+ thymocytes.
Analysis of the expression of the hybrid gene bcl-2/IgH in follicular lymphomas
Authors: Soubeyran P , Cabanillas F , Lee MS 
Published: October 2019

Abstract
To investigate the clinical and biologic significance of the circulating t(14;18)-carrying cells in follicular lymphoma (FL) patients, we analyzed the mbr/JH junction of the hybrid bcl-2/IgH gene simultaneously at the DNA and RNA levels by polymerase chain reaction (PCR) in 37 peripheral blood samples from 37 patients in different remission status: 4 before treatment, 8 during treatment, and 25 in complete remission (CR). Of these 37 patients, 22 were positive either at the DNA or RNA level (8 with active disease and 14 in CR). Among these positive patients, RNA was more often negative for patients in CR (9 of 14 [64%]) than for patients with active disease (2 of 8 [25%]; Fisher's exact test, P = .09). Among the 14 patients in CR with residual disease, 2 of 5 with RNA positivity relapsed, whereas 1 of 9 with RNA negativity and DNA positivity relapsed with a median follow-up after sample collection of 8 months (range, 4 to 18 months). Simultaneous analysis of the bcl-2/IgH gene at the DNA and RNA level showed heterogeneous patterns of PCR positivity in regards to the evaluation of the biologic activity of the t(14;18)-carrying cells. A larger study and long-term follow-up will help in determining whether the expression patterns in turn reflect the functional status of disease activity in FL patients.
Multiple genetic lesions in acquired immunodeficiency syndrome-related non-Hodgkin‧s lymphoma
Authors: Ballerini P , Gaidano G , Gong JZ , Tassi V , Saglio G , Knowles DM , Dalla-Favera R 
Published: October 2019

Abstract
Non-Hodgkin's lymphoma (NHL) develops in about 5% to 10% of acquired immunodeficiency syndrome (AIDS) patients. The vast majority of AIDS- NHL are clinically aggressive B-cell NHL that are histologically classified as small noncleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large noncleaved cell lymphoma (LNCCL). In an attempt to understand the molecular pathogenesis of these tumors, we have investigated the involvement of dominantly acting oncogenes (c-myc, N-, K-, H-Ras), tumor suppressor genes (p53, RB1), and Epstein-Barr virus (EBV) infection in 27 AIDS-NHL samples (16 SNCCL, 5 LC-IBP, and 6 LNCCL). The following lesions were detected in AIDS-NHL: EBV infection (10/24; 41.6%), c-myc rearrangement (19/24; 79.1%), Ras mutation (4/27; 14.8%), and p53 loss/mutation (10/27; 37.0%). These lesions are not uniformly distributed, but, rather, cluster with specific types of AIDS-NHL: EBV infection is preferentially associated with LC-IBPL (4/4; 100%), while it is present in only a fraction of SNCCL (5/16; 31.2%) and LNCCL (1/4; 25%); c-myc oncogene activation clusters with SNCCL (16/16; 100%), whereas it is less frequent in LC-IBPL (1/4; 25%) and LNCCL (2/4; 50%); p53 inactivation is restricted to SNCCL (10/16; 62.5%) and consistently associated with c-myc activation. These data show that AIDS-NHL are associated with multiple genetic lesions that involve both proto- oncogenes and tumor suppressor genes and may accumulate in the relatively short period of time (4 to 6 years) between human immunodeficiency virus infection and AIDS-NHL development. These genetic lesions differ in the various AIDS-NHL subtypes, suggesting the involvement of distinct molecular pathway.
Release of elastase from monocytes adherent to a fibronectin-gelatin surface
Authors: Xie DL , Meyers R , Homandberg GA 
Published: October 2019

Abstract
Fibronectin (Fn) is a circulating and extracellular matrix glycoprotein that may serve to facilitate phagocytosis because of its ability to bind many inflammatory ligands and to a monocyte receptor. Fn fragments have been shown in many systems to have augmented properties over those of native Fn. We show in this report that although Fn fragments did not cause elastase release from monocytes in suspension, fragments did cause elastase release from monocytes that were first bound to Fn- gelatin surfaces. An amino-terminal 29-Kd and a 140-Kd integrin-binding fragment were half-maximally active at 100 nmol/L, whereas the Arg-Gly- Asp-Ser integrin-recognition peptide was half-maximally active at 100 mumol/L. Fluid-phase Fn was ineffective yet blocked the activity of the Fn fragments. Complexing of Fn with gelatin or with heparin partially removed the blocking effect of Fn. Similar results were obtained with U- 937 cells. Substitution of the Fn-gelatin surface with bovine articular cartilage also promoted elastase release. Therefore, in conditions in vivo in which monocytes bind to tissue surface, a high ratio of Fn fragments to native Fn may upregulate certain monocyte activities such as protease release.
Transient changes in erythrocyte membrane permeability are induced by sublytic amounts of the complement membrane attack complex (C5b-9)
Authors: Halperin JA , Taratuska A , Rynkiewicz M , Nicholson-Weller A 
Published: October 2019

Abstract
We have previously shown that sublytic heterologous complement induces large but transient increases in erythrocyte membrane permeability. We now report that when erythrocytes are bystanders in zymosan-activated autologous serum, they increase their Na+ permeability 10-fold, indicating that autologous complement can also induce transient membrane lesions. When we isolated the effect of the C5b-9 membrane attack complex of complement by using human C5b-9 assembled from purified components, we found there was minimal lysis but efficient Na+ uptake. Suspension of the sublytically damaged erythrocytes in K+ medium caused the cells to lyse, which is consistent with the cells recruiting a compensatory K+ efflux similar to that observed when human erythrocytes were exposed to heterologous complement. Sublytic C5b-9 exposure also became lytic when extracellular Ca2+ was limited and when the cells were exposed to charybdotoxin, an inhibitor of the Ca(2+)- activated K+ channel. This indicates that Ca2+ is required for the functional termination of the C5b-9 lesion. We also show that the membrane hyperpolarization resulting from activation of the Ca(2+)- dependent K+ efflux does not influence the termination of the C5b-9 lesion. Thus, the influx of Ca2+ through the complement lesion initiates at least two apparently independent adaptive responses: (1) a process that terminates the leak; and (2) a K+ efflux that has a volume regulatory function. Our data support the potential of the sublytic C5b- 9 lesion to act as a physiologic mediator for autologous erythrocytes.
Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria
Authors: Shear HL , Roth EF Jr , Fabry ME , Costantini FD , Pachnis A , Hood A , Nagel RL 
Published: October 2019

Abstract
The polymorphic frequency of the gene for beta s-globin involved in the generation of sickle trait and sickle cell anemia in the human population is caused by the enhanced resistance of sickle trait individuals to Plasmodium falciparum malaria, as supported by epidemiologic and in vitro studies. However, the mechanism for the protective effect of sickle hemoglobin in vivo has not been fully defined. The generation of transgenic mice expressing high levels of human beta s- and alpha-chains has allowed us to study this phenomenon in vivo in an experimental model. We infected the transgenic beta s mice with two species of rodent malaria and found a diminished and delayed increase in parasitemia as compared with controls. This is in contrast to our previous studies involving the introduction of a beta A transgene, which does not alter the infection. The use of this model allowed us to address the question of the mechanism of protection against malaria in mice expressing sickle hemoglobin. We find that splenectomy of transgenic mice completely reverses the protection against Plasmodium chabaudi adami infection. The results reported have shown a relationship between the presence of the beta s gene product and partial resistance to malaria in an experimental model in vivo and shows that the spleen plays an important role in this protection.
Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit
Authors: Kasugai T , Okada M , Morimoto M , Arizono N , Maeyama K , Yamada M , Tei H , Dohmae K , Onoue H , Newlands GF 
Published: October 2019

Abstract
All basophils, mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC) are derived from the multipotential hematopoietic stem cell. Mutations at the c-kit locus resulted in deficiency of MMC and CTMC in both mice and rats. To investigate the role of the c-kit receptor tyrosine kinase for production of basophils, we used white spotting/white spotting (Ws/Ws) mutant rats that have a small deletion at the tyrosine kinase domain of the c-kit gene. When Ws/Ws, nude athymic, and normal (+/+) rats were infected with Nippostrongylus brasiliensis (NB), the number of basophils increased greater than 50- fold in the peripheral blood of Ws/Ws and +/+ rats but did not increase in that of nude rats. Blood histamine concentration increased significantly in Ws/Ws and +/+ rats but did not increase in nude rats. Immature basophils increased greater than 10-fold in the bone marrow of Ws/Ws and +/+ rats but did not increase in that of nude rats. Mature and immature basophils that developed after the NB infection were identified by electron microscopy. The present result confirms that T- cell-derived cytokines are indispensable for the augmented production of basophils and suggests that stimulation via the c-kit receptor may not be necessary for the augmented production.
Mast cell number in the skin of heterozygotes reflects the molecular nature of c-kit mutation
Authors: Tsujimura T , Koshimizu U , Katoh H , Isozaki K , Kanakura Y , Tono T , Adachi S , Kasugai T , Tei H , Nishimune Y 
Published: October 2019

Abstract
The W locus of mice encodes the c-kit receptor tyrosine kinase. Heterozygous WJic/+ and Wn/+ mice and homozygous Wf/Wf mice were similar in appearance; all of them have large depigmented areas lacking any well-defined pattern. The WJic, Wn, and Wf mutant alleles were characterized and their molecular nature was correlated with the mast cell differentiation in the skin and the biologic features of cultured mast cell (CMC). All WJic, Wn, and Wf were point mutations at the tyrosine kinase domain, and c-kit mRNA was normally transcribed from all of them. The mature 145-Kd form of the c-kit protein was produced from the WJic and Wf alleles, but not from the Wn allele. c-kit proteins produced by the WJic or Wf allele were expressed on the surface of CMCs, but those of the Wn allele were not. When double heterozygous mice were produced between W and WJic and between W and Wn, both W/WJic and W/Wn mice lacked skin mast cells. W/WJic CMCs and W/Wn CMCs did not survive in the coculture with fibroblasts. W/WJic CMCs normally attached to fibroblasts, but W/Wn CMCs did not. The defect of W/Wn CMCs in the attachment was attributed to the deficient extracellular expression of the c-kit protein. The number of skin mast cells was compared among WJic/+, Wn/+, Wf/+, and Wf/Wf mice. Mast cells decreased in WJic/+ and Wf/Wf mice, but not in Wn/+ and Wf/+ mice. Although the Wn was a point mutation at the kinase domain, the biologic effect of the Wn was comparable with that of the W mutant allele, which produces truncated c-kit protein without the transmembrane domain. The weak phenotype of Wn/+ mice may be explained by the deficient extracellular expression of c-kit proteins produced by the Wn allele. When WJic/WJic, Wn/Wn, and Wf/Wf CMCs were stimulated by the recombinant c-kit ligand, autophosphorylation activity was observed only in Wf/Wf CMCs. This result was consistent with the weak biologic effect of the Wf mutant allele.
A bone marrow stromal cell line is a source and target for platelet- derived growth factor
Authors: Abboud SL 
Published: October 2019

Abstract
Platelet-derived growth factor (PDGF) stimulates multipotent and erythroid progenitors as well as stromal fibroblasts. Any of the three dimeric forms of PDGF (AA, AB, or BB) could potentially interact with these cells; however, the precise cellular origin of PDGF production in the bone marrow microenvironment is not known. In the present study, we found that medium conditioned by MBA-2, murine bone marrow-derived endothelial cells, contains PDGF activity that competes for [125I]PDGF binding to human foreskin fibroblasts and is mitogenic for these fibroblasts. Northern analysis of poly(A)+ RNA from MBA-2 shows the expression of both PDGF A-chain and B-chain mRNAs. Because cytokines such as transforming growth factor-beta (TGF-beta) regulate hematopoiesis and stimulate PDGF in certain mesenchymal cells, we determined whether TGF-beta influences PDGF secretion and gene expression in MBA-2. TGF-beta induced PDGF A-chain and B-chain mRNAs and the release of PDGF activity. Each of the three PDGF isoforms also stimulated DNA synthesis in MBA-2, but with different potency (BB = AB = AA). Ligand binding studies showed specific binding of labeled PDGF BB and, to a lesser extent, PDGF AA isoform, consistent with predominant expression of the PDGF-beta receptor in MBA-2. These data show that murine endothelial stromal cells release PDGF activity and respond to PDGF. Local production of PDGF in the marrow microenvironment may play an important role in regulating hematopoietic and stromal cell proliferation.