bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin's lymphoma
Authors: Lo Coco F , Ye BH , Lista F , Corradini P , Offit K , Knowles DM , Chaganti RS , Dalla-Favera R 
Published: October 2019

Abstract
The pathogenesis of non-Hodgkin's lymphoma (NHL) with a large cell component (DLLC, including diffuse large cell, DLCL; diffuse mixed cell, MX-D; and immunoblastic, IMB) is unknown. A novel candidate proto- oncogene, BCL6, that is involved in chromosome band 3q27 aberrations in NHL has been recently identified. We have investigated the incidence and disease-specificity of BCL6 rearrangements in a large panel of lymphoid tumors, including acute and chronic lymphoid leukemias (96 cases), various NHL types (125 cases), and multiple myelomas (23 cases). BCL6 rearrangements were found in 16/45 (35.5%) DLLC, more frequently in DLCL (15/33, 45%) than in MX-D (1/10, 10%), in 2/31 (6.4%) follicular NHL, and in no other tumor types. BCL6 rearrangements represent the first genetic lesion specifically and recurrently associated with DLLC and should prove useful for understanding the pathogenesis as well as for the clinical monitoring of these tumors.
Dissociation between p93B-myb and p75c-myb expression during the proliferation and differentiation of human myeloid cell lines
Authors: Arsura M , Luchetti MM , Erba E , Golay J , Rambaldi A , Introna M 
Published: October 2019

Abstract
Direct and indirect evidence strongly indicates that the proto-oncogene c-myb plays an important role in the regulation of both the proliferation and differentiation of hematopoietic cells. In addition, recent data suggest that the structurally related B-myb gene is also necessary for the proliferation of these cells. To help understand the relationship between these two related gene products during proliferation and differentiation of myeloid cells, we have studied in parallel the regulated expression of c-myb and B-myb RNAs and proteins in human myeloid cells that were either growth-arrested or induced to differentiate along different pathways. For this purpose, we have produced a polyclonal antibody directed against a fragment of the recombinant B-myb protein. We have thus been able to detect the B-myb protein in human cell lines and have found it to be a 93-kD protein localized in the nucleus. We have chosen two models to study the expression of both c-myb and B-myb mRNAs and proteins during myeloid proliferation and differentiation. One of the models was the HL-60 cell line, which can be induced to differentiate towards the monocytic pathway with either phorbol ester (phorbol myristate acetate) or vitamin D3 and towards the granulocytic pathway with either dimethyl sulfoxide or retinoic acid. In addition, we have studied another recently established human leukemic cell line, called GF-D8, which is strictly dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF) for proliferation. The results show that the expression of B- myb RNA and protein closely correlates with proliferation in all experimental setups studied, whereas the c-myb protein levels do not always do so. We observed that the c-myb protein levels decreased well before the decrease of B-myb protein and of proliferation itself during differentiation toward monocytes. Such a difference was not present during granulocytic differentiation, in which c-myb levels decreased, if anything, later than those of B-myb and proliferation. Most striking was the finding that high levels of c-myb RNA and protein, but not of B- myb, were present in the GF-D8 cell line, even after growth arrest by GM-CSF deprivation. These data suggest that B-myb may function solely in the regulation of cellular proliferation, whereas c-myb has additional functions, for example, in the maintenance of an undifferentiated state.
Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia
Authors: Bedi A , Zehnbauer BA , Barber JP , Sharkis SJ , Jones RJ 
Published: October 2019

Abstract
BCR-ABL expression is presumed to effect clonal expansion in chronic myeloid leukemia (CML) by deregulation of cell proliferation. However, most studies have found that relative rates of cell proliferation are not increased in CML. Moreover, we found that CML progenitors display a normal proliferative response to growth factors and do not manifest greater proliferative potential than normal progenitors. Growth of malignancies depends on an imbalance between the rate of cell production and the rate of cell death. We found that BCR-ABL expression inappropriately prolongs the growth factor-independent survival of CML myeloid progenitors and granulocytes by inhibiting apoptosis, a genetically programmed process of active cell death; inhibition of BCR- ABL expression by antisense oligonucleotides reversed the suppression of apoptosis as well as the enhancement of survival. The decreased rate of programmed cell death appears to be the primary mechanism by which BCR-ABL effects expansion of the leukemic clone in CML.
Rescue from anti-MHC class II antibody-mediated marrow graft failure by c-kit ligand
Authors: Deeg HJ , Beckham C , Huss R , Myerson D , Greinix H , Appelbaum FR , Graham T , Schuening F , Storb R 
Published: October 2019

Abstract
Dogs given 920 cGy of total body irradiation (TBI) followed by autologous marrow infusion uniformly achieve sustained hematopoietic reconstitution. We have previously shown that administration of the anti-MHC class II monoclonal antibody (MoAb) H81.98.21 (IgG2a) at 0.6 mg/kg/d immediately after transplantation results in delayed graft failure. A second noncrossblocking anti-MHC class II MoAb, B1F6, of the same isotype, at the same dose, did not interfere with sustained engraftment, suggesting that the observed effect was epitope dependent. Although higher concentrations of B1F6 were required, in the present study both MoAbs interfered with the propagation of long-term marrow cultures. When MoAb B1F6 was given in vivo at 1.2 mg/kg/d, ie, twice the dose used previously, dogs so treated also developed delayed marrow graft failure. Marrow failure with either MoAb involved myeloid, erythroid, and megakaryocytic lineages. Administration of recombinant canine c-kit ligand/stem cell factor (SCF) for 7 or 21 days posttransplant resulted in reversal of graft failure. Although the short course did induce a broad transient early peak of granulocytes, the longer course of SCF was accompanied by earlier sustained recovery than the short course. In conclusion, therefore, marrow graft failure induced by anti-MHC class II MoAb does not appear to be epitope dependent, involves all hematopoietic lineages, and is overcome by the administration of c-kit ligand.
Engraftment of human peripheral blood lymphocytes in normal strains of mice
Authors: Lubin I , Segall H , Marcus H , David M , Kulova L , Steinitz M , Erlich P , Gan J , Reisner Y 
Published: October 2019

Abstract
Transplantation of bone marrow from SCID mice into lethally irradiated normal mice can potentially endow the normal recipients with characteristics typical of the immune-deficient SCID mouse. In the present study, we investigated whether intraperitoneal grafting of human peripheral blood lymphocytes (PBLs), which has been documented in the SCID mouse, can also be achieved in irradiated BALB/c mice radioprotected with SCID bone marrow. Evaluation of different radiation protocols suggested that, considering the quality of engraftment and rate of survival, optimal results were obtained with split dose total body irradiation (TBI; 4 Gy followed 3 days later by 10 Gy). Monitoring of mouse T cells in peripheral blood indicated an inverse correlation between the presence of such cells and the engraftment of human CD45+ cells in the peritoneum. Also, engraftment of human PBLs in nude BALB/c mice, conditioned with the same radiation protocol, was significantly higher than that achieved in their normal counterparts. Further improvement of human PBL engraftment was found when the mice were thymectomized 2 weeks before conditioning with split TBI. After transplantation of 80 x 10(6) human PBLs in such recipients, a marked engraftment of human T cells and B cells in the peritoneum cavity could be detected for at least 2 months, whereas significant amounts of human Ig could be detected for more than 3 months. Migration of human PBLs into internal organs such as spleen, liver, kidney, and lungs (and into thymus in nonthymectomized mice) was found within a few days of grafting and also persisted for 2 to 3 months. The majority of the engrafted lymphocytes were single-positive CD4+ and CD8+ T lymphocytes, about 50% of which were activated, as judged by their expression of HLA- DR. Staining with anti-CD25 antibody was lower compared with that found with anti-HLA-DR. CD20+ B cells were detected in all of the above- mentioned internal organs, but were mainly concentrated in the spleen. CD14+ monocytes could be detected only during the first week posttransplant of PBLs. Total human Ig in peripheral blood reached an average of 2.8 mg/mL 14 days posttransplant, and continued to be significant for several months. In vitro transformation by Epstein-Barr virus of human B cells from different tissues could be established 30 days after transplantation and led to outgrowth of two IgG+ cell lines, two IgM+ cell lines, and one IgA+ cell line producing 0.6 to 4.2 micrograms/mL human Ig in the supernatant.
Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein
Authors: Meszaros K , Aberle S , Dedrick R , Machovich R , Horwitz A , Birr C , Theofan G , Parent JB 
Published: October 2019

Abstract
Mononuclear phagocytes, stimulated by bacterial lipopolysaccharide (LPS), have been implicated in the activation of coagulation in sepsis and endotoxemia. In monocytes LPS induces the synthesis of tissue factor (TF) which, assembled with factor VII, initiates the blood coagulation cascades. In this study we investigated the mechanism of LPS recognition by monocytes, and the consequent expression of TF mRNA and TF activity. We also studied the inhibition of these effects of LPS by rBPI23, a 23-kD recombinant fragment of bactericidal/permeability increasing protein, which has been shown to antagonize LPS in vitro and in vivo. Human peripheral blood mononuclear cells, or monocytes isolated by adherence, were stimulated with Escherichia coli O113 LPS at physiologically relevant concentrations (&gt; or = 10 pg/mL). The effect of LPS was dependent on the presence of the serum protein LBP (lipopolysaccharide-binding protein), as shown by the potentiating effect of human recombinant LBP or serum. Furthermore, recognition of low amounts of LPS by monocytes was also dependent on CD14 receptors, because monoclonal antibodies against CD14 greatly reduced the LPS sensitivity of monocytes in the presence of serum or rLBP. Induction of TF activity and mRNA expression by LPS were inhibited by rBPI23. The expression of tumor necrosis factor showed qualitatively similar changes. Considering the involvement of LPS-induced TF in the potentially lethal intravascular coagulation in sepsis, inhibition of TF induction by rBPI23 may be of therapeutic benefit.
Direct correlation between the load of Epstein-Barr virus-infected lymphocytes in the peripheral blood of pediatric transplant patients and risk of lymphoproliferative disease
Authors: Savoie A , Perpete C , Carpentier L , Joncas J , Alfieri C 
Published: October 2019

Abstract
The Epstein-Barr virus (EBV) is known to cause posttransplant lymphoproliferative disease (PTLD) in immunosuppressed transplant patients. The results of this pilot study showed that all EBV- patients pretransplant experienced primary EBV infection within the first 3 months after transplant surgery. Virtually all of these patients had a higher burden of EBV-infected cells in their peripheral blood (PB) after infection by EBV than did the EBV+ pretransplant group when tested at the same intervals posttransplant. Salivary EBV titers also increased in most patients, but the difference between the two groups was statistically significant only at 12 months, whereupon EBV+ patients showed higher titers compared with EBV- (alpha < 0.053). Also, polymerase chain reaction amplification followed by Southern blotting was performed to detect EBV sequences in PB mononuclear cells. This technique allowed confirmation of the blood culture results and constituted a faster alternative compared with the culture assay. The highest increase in the number of EBV-infected lymphocytes at 3 months posttransplant obtained from PB was seen in a patient who developed fatal PTLD and in another with protracted infectious mononucleosis. Thus, the number of EBV-infected cells in PB was found to correlate positively with risk of development of PTLD at 3 months posttransplant in our group of pediatric transplant patients. This study showed that quantitative lymphocyte culture of PB was an accurate index of immunosuppression and a reliable method for assessing the risk of PTLD development.
Transforming growth factor-beta 1, macrophage inflammatory protein-1 alpha, and interleukin-8 gene expression is lower in stimulated human neonatal compared with adult mononuclear cells
Authors: Chang M , Suen Y , Lee SM , Baly D , Buzby JS , Knoppel E , Wolpe S , Cairo MS 
Published: October 2019

Abstract
Hematopoiesis is developmentally immature in the newborn compared with the adult. Diminished gene expression of several positive hematopoietic regulators has been observed in activated cord compared with adult peripheral blood mononuclear cells (MNC; Cairo et al. Pediatr Res, 30:362, 1991 and Cairo et al, Pediatr Res, 31:574, 1992). However, altered expression of negative hematopoietic regulators during states of increased demand may also contribute to the pathogenesis of newborn dyshematopoiesis. To test this hypothesis, we measured protein levels of transforming growth factor-beta 1 (TGF-beta 1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the conditioned media of human umbilical cord and adult MNC using specific enzyme-linked immunosorbent assays. There was significantly less TGF-beta 1 in culture supernatants of cord versus adult MNC after 24, 72, and 120 hours of stimulation (P < .05), and significantly less MIP-1 alpha in cord versus adult supernatants after 72 hours and 120 hours of stimulation (P < .01). We then examined the mRNA expression of the negative regulators TGF-beta 1, MIP-1 alpha, and interleukin-8 (IL-8) in cord and adult MNC using Northern blot hybridization followed by quantitative densitometry. Cord MNC expressed significantly less TGF- beta 1 mRNA than adult MNC 6 hours and 72 hours after stimulation (P < .001). Cord MNC expressed significantly less MIP-1 alpha mRNA than adult MNC 6 hours (P < .01), 24 hours (P < .001), and 72 hours after stimulation (P < .001). Cord MNC also expressed significantly less IL-8 mRNA than adult MNC 6 hours after stimulation (P < .001). Therefore, decreased mRNA accumulation appears to coincide with reduced cytokine expression in the activated cord MNC. There were no significant differences in the transcription rates determined by nuclear run-on assay of either the TGF-beta 1 or MIP-1 alpha gene in cord versus adult MNC after 6 hours of stimulation, suggesting that the reduced TGF-beta 1 and MIP-1 alpha mRNA in activated cord MNC may be secondary to alteration in posttranscriptional regulation. The present results, together with those of our previous studies, suggest that the altered expression of both positive and negative hematopoietic regulators may be involved in the immaturity of host defense in human neonates.
Characterization of cell phenotype by a novel cDNA library subtraction system: expression of CD8 alpha in a mast cell-derived interleukin-4- dependent cell line
Authors: Hara T , Harada N , Mitsui H , Miura T , Ishizaka T , Miyajima A 
Published: October 2019

Abstract
We have established a unique variant cell line, MC/9.IL-4, which continuously proliferates in the presence of interleukin-4 (IL-4), from a murine interleukin-3 (IL-3)-dependent mast cell line, MC/9 (referred to as MC/9.IL-3). Compared with MC/9.IL-3 cells, MC/9.IL-4 cells are smaller, lack cytoplasmic granules and metachromasia, carry a very small amount of histamine, and express fewer high-affinity IgE receptors (IgERs) and IL-3 receptors. To further characterize MC/9.IL- 4, we developed a novel method to enrich cell type-specific cDNAs by cDNA library subtraction and applied it for MC/9.IL-3 versus MC/9.IL-4. Sequence analysis of cDNA clones isolated by this technique showed that MC/9.IL-4 cells specifically express CD8 alpha and expression of mast cell-specific proteases and major histocompatibility complex class II (MHCII) is considerably decreased. It was also noted that responsiveness to the IL-3-agonistic antibody F9 and expression of the transcription factor GATA-2 is diminished in MC/9.IL-4, indicating that MC/9.IL-4 have lost major characteristics of the bone marrow-derived cultured mast cells. Because other T-cell marker antigens, CD8 beta, CD4, Thy-1, were not detected on MC/9.IL-4 cells, MC/9.IL-4 cells may represent an unknown class of hematopoietic cells that express CD8 alpha. This cell line will be useful in studies of IL-4-mediated signal transduction, as well as transcriptional regulation of mast cell characteristic genes. This study also demonstrates the effective use of the cDNA library subtraction strategy to characterize unknown types of hematopoietic cells at the molecular level.
Growth enhancement of established tumors by allogeneic blood transfusion in experimental animals and its amelioration by leukodepletion: the importance of the timing of the leukodepletion
Authors: Bordin JO , Bardossy L , Blajchman MA 
Published: October 2019

Abstract
We had reported previously (Blood 81:1880, 1993) that allogeneic blood transfusions (ABT) administered before the infusion of tumor cells in both inbred and outbred experimental animals promote tumor growth and that this effect can be ameliorated by leukodepletion. To better reproduce the human situation, we evaluated, in this present study, the effect of ABT in animals with established tumors using enumeration of pulmonary metastatic nodules as the end point. The role of allogeneic blood component transfusions in promoting tumor growth and the relative efficacy of prestorage versus poststorage leukodepletion of the ABT in preventing tumor growth enhancement were also evaluated. In an inbred murine animal model, C57Bl/6J mice were administered nonleukodepleted allogeneic (ABT), leukodepleted allogeneic (LD-ABT), or syngeneic (SBT) blood transfusions after the intravenous infusion of syngeneic methylcholanthrene-induced fibrosarcoma cells using two different protocols. A significant increase in the number of pulmonary nodules was observed in those mice that received ABT, in both protocols, compared to animals transfused with SBT or LD-ABT. Significantly higher numbers of pulmonary nodules were also seen in mice transfused with allogeneic buffy-coat leukocytes compared with mice that received either nonleukodepleted allogeneic plasma or LD-ABT. In an outbred animal (rabbit) model, recipient rabbits were administered either nonleukodepleted ABT, prestorage LD-ABT, poststorage LD-ABT, or SBT on days +4 and +9 after the infusion of syngeneic epithelial tumor cells. A significant increase in the number of pulmonary nodules was seen in rabbits that received nonleukodepleted ABT compared to animals transfused with SBT. Significantly lower numbers of pulmonary nodules were observed in rabbits that received prestorage LD-ABT compared to animals transfused with poststorage LD-ABT, but no significant difference was seen in rabbits that received poststorage LD-ABT compared with animals transfused with nonleukodepleted ABT. These studies show that ABT promote tumor growth of established animal tumors, that the ABT-induced tumor growth effect is related to the presence of donor allogeneic leukocytes, and that this effect can be ameliorated by prestorage leukodepletion. The present results also provide evidence for the lack of efficacy of poststorage leukodepletion in preventing ABT tumor growth promotion.(ABSTRACT TRUNCATED AT 400 WORDS).
Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases
Authors: Kobayashi H , Montgomery KT , Bohlander SK , Adra CN , Lim BL , Kucherlapati RS , Donis-Keller H , Holt MS , Le Beau MM , Rowley JD 
Published: October 2019

Abstract
Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12–13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown.
Stem cell factor enhances the survival but not the self-renewal of murine hematopoietic long-term repopulating cells
Authors: Li CL , Johnson GR 
Published: October 2019

Abstract
The effects of stem cell factor (SCF) have been tested on a murine bone marrow subpopulation (RH123lo, Lin-, Ly6A/E+) that is highly enriched for long-term hematopoietic repopulating cells. SCF maintained cells from this population with long-term repopulating ability for up to 10 days in vitro. However, compared with freshly isolated cells, the level of engraftment in vivo by the cultured cells declined during the in vitro culture period, suggesting that SCF alone was unable to stimulate the self-renewal of long-term repopulating cells. By direct visualization of cultures, only small numbers of cells survived and rarely underwent cell division. However, SCF did directly stimulate proliferation of a population (Rh123med/hi,Lin-,Ly6A/E+) enriched for short-term repopulating cells. These data suggest that stem cell differentiation is associated with the development of mitogenic activity by SCF at least in some progenitor cell populations.