bluuebunny/crossref_metadata_2025_split huggingface dataset:
Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression
Authors: Visvader J , Adams JM 
Published: October 2019

Abstract
The GATA ‘zinc-finger’ transcription factors are thought to have important roles in the control of hematopoiesis. GATA-1 and GATA-2 are found in the erythroid, mast cell, and megakaryocytic lineages, and GATA-3 in T lymphocytes. GATA-1 is required for erythroid development and has recently been shown by gene transfer to direct megakaryocytic differentiation of the primitive myeloid cell line 416B. Here we show that enforced expression in 416B cells of either the GATA-2 or GATA-3 gene also induces megakaryocytic differentiation, as assessed by cellular morphology, acetylcholinesterase activity, polyploid DNA content, and loss of Mac-1 expression. No erythroid or mast cell differentiation was found. Unexpectedly, the level of endogenous GATA-1 mRNA had increased 20- to 30-fold among the transfectants, whereas that of GATA-2 mRNA was unaltered and endogenous GATA-3 transcripts remained undetectable. This finding suggests that GATA-2 and GATA-3 lie upstream of GATA-1 in a regulatory hierarchy and that, in 416B cells, GATA-1 may mediate the phenotypic changes induced by GATA-2 or GATA-3. Furthermore, 416B cells treated with the DNA demethylating agent 5- azacytidine underwent megakaryocytic differentiation accompanied by a marked increase in the level of GATA-1 mRNA but not that of GATA-2 or GATA-3. These results strongly implicate GATA factors in megakaryocytic differentiation and suggest that, at least for 416B cells, GATA-1 is a dominant regulator of maturation along this lineage.
T-cell-rich B-cell lymphoma
Authors: Rodriguez J , Pugh WC , Cabanillas F 
Published: October 2019

Abstract
We analyzed 23 cases of T-cell-rich B-cell lymphomas (BCL) to determine if the clinical features are characteristic of a discrete entity. Cases encoded as T-cell-rich BCL in the hematopathology archives of the University of Texas M.D. Anderson Cancer Center between 1988 and 1991 formed the basis of this study. At least 50% of the total population of cells were required to be of T-cell phenotype. Actually, all but one patient had more than 70% T cells in the total population. Sixty-five percent of all cases were referred with other diagnosis such as Hodgkin's mixed cellularity, peripheral T-cell lymphoma (PTCL), or diffuse mixed lymphoma, and had received therapy accordingly. With the exception of splenomegaly, which occurred in 35% of cases, the other clinical characteristics and the response to therapy did not indicate that this entity represents a distinct type of lymphoma. Ann Arbor stage I-II presentations were seen in 10 of 23 (43%) T-cell-rich BCLs. Serum lactate dehydrogenase (LDH) was elevated in eight of 19 patients. Age, sex, and beta 2-microglobulin were not significantly different from classical B-cell large cell lymphoma. The clinical presentation and clinical outcome of T-cell-rich BCL did not differ from that of common B-cell large cell lymphoma, except for the higher proportion of splenomegaly seen in patients with T-cell-rich BCL. The presence of the T-cell-rich infiltrate varied: it frequently was not seen at relapse or at other sites of disease at presentation. It was thus considered an unstable parameter. The major importance of identifying this entity is to distinguish it pathologically from other disorders such as Hodgkin's disease and PTCL, which would be treated in a different manner.
CDw60 glycolipid antigens of human leukocytes: structural characterization and cellular distribution
Authors: Kniep B , Flegel WA , Northoff H , Rieber EP 
Published: October 2019

Abstract
Monoclonal CDw60 antibodies recognize glycolipid antigens with restricted surface expression on human leukocytes. They allow us to define new functional subpopulations of T lymphocytes and are able to induce costimulatory signals. In this report, we describe the molecular composition of CDw60 glycolipid antigens derived from different human leukocyte subpopulations. The glycolipids were isolated and their structures were identified by immunochemical methods. All molecules containing the CDw60 determinant were found in the disialoganglioside fraction. They were O-acetylated derivatives of the gangliosides II3 (Neu5Ac)2-LacCer (GD3), IV3 (Neu5Ac)2-nLc4Cer (DSPG), and VI3 (Neu5Ac)2- nLc6Cer (DSnHC), respectively. The most common CDw60 glycolipid antigen in human leukocytes was 9-O-acetyl GD3. In a comparison of various cell types, the highest concentration of 9-O-acetyl GD3 on a per cell basis was determined in granulocytes and in blood T lymphocytes, whereas B lymphocytes, thymus cells, and monocytes contained considerably smaller amounts of this molecule. Polar CDw60 antigens such as 9-O-acetyl DSPG and 9-O-acetyl DSnHC were only detected in granulocytes.
Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells
Authors: Mandanas RA , Leibowitz DS , Gharehbaghi K , Tauchi T , Burgess GS , Miyazawa K , Jayaram HN , Boswell HS 
Published: October 2019

Abstract
The p21 RAS product has been implicated as part of the downstream signaling of certain nonreceptor tyrosine kinase oncogenes and several growth factor receptor-ligand interactions. We have reported that the chronic myelogenous leukemia oncogene p210 bcr-abl transforms a growth- factor-dependent myeloid cell line NFS/N1.H7 to interleukin-3 (IL-3) independence. In these p210 bcr-abl-transformed cells (H7 bcr-abl.A54) and in two other murine myeloid cell lines transformed to IL-3 independence by p210 bcr-abl, endogenous p21 RAS is activated as determined by an elevated ratio of associated guanosine triphosphate (GTP)/guanosine diphosphate (GDP), assayed by thin-layer chromatography of the nucleotides eluted from p21 RAS after immunoprecipitation with the Y13–259 antibody. Treatment of p210 bcr-abl-transformed cells with a specific tyrosine kinase inhibitor herbimycin A resulted in diminished tyrosine phosphorylation of p210 bcr-abl and associated proteins, without major reduction in expression of the p210 bcr-abl protein itself. Inhibition of p210 bcr-abl-dependent tyrosine phosphorylation resulted in a reduction of active p21RAS-GTP complexes in the transformed cells, in diminished expression of the nuclear early response genes c-jun and c-fos, and in lower cellular proliferation rate. To further implicate p21 RAS in these functional events downstream of p210 bcr-abl tyrosine phosphorylation, we targeted G- protein function directly by limiting the availability of GTP with the inosine monophosphate dehydrogenase inhibitor, tiazofurin (TR). In p210 bcr-abl-transformed cells treated for 4 hours with TR, in which the levels of GTP were reduced by 50%, but GDP, guanosine monophosphate, and adenosine triphosphate (ATP) were unaffected, p210 bcr-abl tyrosine phosphorylation was at control levels. However, expression of c-fos and c-jun nuclear proto-oncogenes were strongly inhibited and p21 RAS activity was downregulated. These findings show that p210 bcr-abl transduces proliferative signals, in part, through downstream activation of p21 RAS. Furthermore, p21 RAS activity is linked to pathways that regulate c-jun and c-fos expression.
Purification and functional characterization of homodimeric gamma B- gamma B fibrinogen from rat plasma
Authors: Lawrence SO , Wright TW , Francis CW , Fay PJ , Haidaris PJ 
Published: October 2019

Abstract
Heterogeneity in the human and rat plasma fibrinogen (FBG) gamma chains is due to differential splicing of the primary gamma chain mRNA transcript. The subunit composition of FBG containing the predominant form of the gamma chain is homodimeric (human: A alpha 2, B beta 2, gamma 50-gamma 50; rat: A alpha 2, B beta 2, gamma A-gamma A). The subunit composition of FBG containing the longer, minor form of the gamma chain is heterodimeric (human: A alpha 2, B beta 2, gamma 50- gamma 57.5; rat: A alpha 2, B beta 2, gamma A-gamma B). The variant gamma chain-FBGs comprise about 10% of the total plasma FBG in the human and 30% in the rat. Although the presence of homodimeric gamma B- gamma B FBG has been speculated, proof of its existence has been difficult to obtain experimentally. We now show that 5% to 6% of rat plasma FBG is found as homodimeric FBG with a subunit composition of A alpha 2, B beta 2, gamma B-gamma B. Commercially purified rat FBG was further purified by diethylaminoethyl-Sephacel chromatography with a combined pH and ionic strength gradient. The enriched gamma B-gamma B FBG fraction eluted at the lowest pH (6.3) and highest ionic strength (4.5 mmho) due to its increased net negative charge. To further purify gamma B-gamma B FBG, a Mono Q column with an NaCl gradient was used. The subunit composition of the purified gamma B-gamma B FBG was confirmed by its electrophoretic mobility under reducing and denaturing conditions both as FBG, and clotted and cross-linked fibrin. Homodimeric gamma B-gamma B FBG was unable to support adenosine diphosphate (ADP)-induced platelet aggregation, whereas heterodimeric gamma A-gamma B FBG was able to support ADP-induced platelet aggregation at 40% of that achieved with homodimeric gamma A-gamma A FBG, similar to previous observations with human FBGs. Taken together, these results support the hypothesis that the A alpha-RGD sites alone are not sufficient for dimeric FBG support of platelet aggregation. Furthermore, the data suggest that at least one intact platelet recognition site at the carboxyterminus of the gamma A or gamma 50 chain is required.
Overexpression of mitogen-activated protein kinase (ERK1) enhances T- cell cytokine gene expression: role of AP1, NF-AT, and NF-KB
Authors: Park JH , Levitt L 
Published: October 2019

Abstract
Transfected Jurkat cells overexpressing extracellular signal-regulated kinase (ERK1), also referred to as mitogen-activated protein (MAP) kinase, were selected by Western blotting assay using anti-ERK1 and antiphosphotyrosine antibodies in combination with a functional MAP kinase assay. We then asked whether enhanced ERK1 expression had any effect on induction of T-cell cytokine genes. The results show that overexpression of ERK1 enhances expression of T-cell interleukin-2 (IL- 2), IL-3, and granulocyte-macrophage colony-stimulating factor mRNA; no change was seen in expression of the alpha-actin gene. DNA-binding activities of the transcription factors AP1, NF-AT, and NF-kB were specifically increased twofold to fourfold in ERK1-overexpressing clones relative to nontransformed or vector-transformed cells, whereas no enhancement of CK1-CK2 protein DNA binding activity was detected after ERK1 overexpression. Additionally, increased NF-AT DNA binding activity was associated with functional enhancement of NF-AT transactivating activity in ERK1-overexpressing cells. These results provide direct evidence for the role of MAP kinase in the regulation of cytokine gene expression and indicate that such regulation is likely mediated through the enhanced DNA binding activity of specific nuclear transcription factors.
Transfected leukocyte integrin CD11b/CD18 (Mac-1) mediates phorbol ester-activated, homotypic cell:cell adherence in the K562 cell line
Authors: Hickstein DD , Grunvald E , Shumaker G , Baker DM , Back AL , Embree LJ , Yee E , Gollahon KA 
Published: October 2019

Abstract
The CD11b/CD18 leukocyte integrin molecule mediates diverse neutrophil adherence-related functions, including cell:cell and cell:extracellular matrix attachments. To study the individual role of this leukocyte integrin in cell adherence in hematopoietic cells, we expressed the CD11b/CD18 complex on the surface of K562 cells, a cell line derived from an individual with chronic myelogenous leukemia in blast crisis. We used an amphotrophic retroviral vector designated LCD18SN, harboring the complete coding sequence for the CD18 subunit, to transfer the CD18 cDNA into K562 cells and select stable cell lines. The CD11b subunit in the expression plasmid pREP4 was transfected into these K562/CD18 cells by electroporation and stable cell clones were selected. These K562 cells possessed RNA and intracellular protein for each subunit, and they expressed the CD11b/CD18 heterodimer on the cell surface. When CD11b/CD18 expressing K562 cells were stimulated with phorbol myristate acetate (50 ng/mL) for 24 to 48 hours, these K562 cells formed dense cell:cell aggregates. This homotypic aggregation required both activation of the CD11b/CD18 complex and the induction of the counter- receptor for CD11b/CD18 on the conjugate cell. This cell line will (1) enable the structure-function relationships between cell activation and homotypic adherence to be assessed, (2) provide the opportunity to identify accessory molecules required for activation of the CD11b/CD18 complex, and (3) facilitate the identification of novel ligands for the CD11b/CD18 complex.
A comparison of the iron-clearing properties of parabactin and desferrioxamine
Authors: Bergeron R , Streiff RR , King W , Daniels RD Jr , Wiegand J 
Published: October 2019

Abstract
A comparative study of the iron-clearing properties of subcutaneously administered desferrioxamine and parabactin is presented. The evaluation was performed in both a non-iron-overloaded bile-duct cannulated rat and an iron-loaded Cebus monkey model. Parabactin was superior to desferrioxamine in both the rodent and the primate. Unlike desferrioxamine, nearly all of the parabactin-induced iron clearance occurred in the bile. This study represents an evaluation of the iron- clearing properties of parabactin, a hexacoordinate catecholamide siderophore.
Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice
Authors: Siefer AK , Longo DL , Harrison CL , Reynolds CW , Murphy WJ 
Published: October 2019

Abstract
Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.
T-cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived versus thymic-independent progeny
Authors: Mackall CL , Granger L , Sheard MA , Cepeda R , Gress RE 
Published: October 2019

Abstract
To study the source of regenerated T cells after bone marrow transplantation (BMT), lethally irradiated thymectomized and thymus- bearing C57BL/6 (Thy 1.2+) mice were injected with syngeneic T-cell depleted bone marrow (TCD BM) cells and graded numbers of congenic B6/Thy 1.1+ lymph node (LN) cells. LN cell expansion was the predominant source for T-cell regeneration in thymectomized hosts but was minimal in thymus-bearing hosts. Analysis of T-cell receptor (TCR) expression on LN progeny showed a diverse V beta repertoire. Therefore, peripheral T-cell progenitors exist within V beta families, but expansion of these progenitors after BMT is downregulated in the presence of a functional thymus. CD4+ cells derived from BM versus LN in thymus-bearing hosts displayed differential CD44 and CD45 isoform expression. BM-derived cells were primarily CD45RB+CD44lo and LN derived cells were nearly exclusively CD45RB- CD44hi. In thymectomized hosts, BM, host, and LN CD4+ progeny were CD45RB- CD44hi. We conclude that T-cell regeneration via peripheral T-cell progenitors predominates in hosts lacking thymic function and gives rise to T cells that display a “memory” phenotype. In contrast, the ability to generate sizable populations of “naive” type T cells after BMT appears limited to the prethymic progenitor pool and could serve as a marker for thymic regenerative capacity.
The human MDM-2 oncogene is overexpressed in leukemias
Authors: Bueso-Ramos CE , Yang Y , deLeon E , McCown P , Stass SA , Albitar M 
Published: October 2019

Abstract
The human homologue of the mouse double minute 2 (MDM-2) gene codes for a cellular protein that forms a complex with the mutant and wild-type p53 protein and modulates its trans-activation activity. Overexpression of the MDM-2 gene in cells increases their tumorigenic potential and overcomes the growth-suppressive activity of p53. Previous reports have shown that the MDM-2 gene is amplified in approximately one third of human sarcomas. To examine the role of MDM-2 in leukemia, we analyzed MDM-2 gene amplification and mRNA expression in various types of leukemias. We did not detect gene amplification in any of the 48 cases of leukemia that we examined. In contrast, we observed significant MDM- 2 mRNA overexpression in 34 of 64 cases (53%). The level of mRNA overexpression in some cases of leukemias was comparable to that observed in some cases of sarcomas, which demonstrate more than 50-fold MDM-2 gene amplification. Furthermore, we divided these cases into different prognostic groups according to their karyotypic abnormalities. MDM-2 overexpression seemed to be associated with unfavorable chromosomal abnormalities. These findings suggest that the expression of the MDM-2 gene is altered in a significant fraction of human leukemias and MDM-2 may play a significant role in leukemogenesis. In addition, these results suggest that mechanisms other than gene amplification may play a significant role in deregulating the MDM-2 expression.
Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians [see comments]
Authors: Sansoni P , Cossarizza A , Brianti V , Fagnoni F , Snelli G , Monti D , Marcato A , Passeri G , Ortolani C , Forti E 
Published: October 2019

Abstract
The contribution of the immune system to healthy aging and longevity is still an open question. For this reason, several immune parameters (T, B, and natural killer [NK] cell subsets; non-major histocompatibility complex [MHC]-restricted cytotoxic activities, ie, natural and redirected killing [RDK] activities) were studied in a total of 138 healthy subjects of different ages, from 4 to 106 years of age, including 26 centenarians. The major age-related modifications were the following: (1) a decrease in the absolute number of T lymphocytes (CD3+), involving both CD4+ and CD8+ subsets, accompanied by a marked concomitant increase in the number of activated T cells (CD3+, HLA- DR+); (2) a marked decrease in the number of B lymphocytes (CD19+); and (3) an increase in the number of cells with markers of NK activity and of T lymphocytes able to mediate non-MHC-restricted cytotoxicity. These modifications linearly progressed with age and centenarians followed the trend, suggesting that their immune system did not escape the aging process. However, other immunohematologic parameters (number of red blood cells, platelets, and leukocytes) and important immune functions, such as cytotoxic activities (NK and RDK cell activities), were well preserved throughout life until the last decades of life. Unexpectedly, in apparently healthy middle-aged subjects, a decrease of cytotoxic activities was observed in comparison with those of both young controls and centenarians. In conclusions, our data suggest that in centenarians some immune responses are kept at a high level of efficiency, likely contributing to their successful aging. However, this selected group of people does not escape the aging process, as shown by the progressive derangement of a variety of immune parameters.
Hematopoietic progenitor cells from patients with adult T-cell leukemia- lymphoma are not infected with human T-cell leukemia virus type 1
Authors: Nagafuji K , Harada M , Teshima T , Eto T , Takamatsu Y , Okamura T , Murakawa M , Akashi K , Niho Y 
Published: October 2019

Abstract
The in vivo host range of human T-cell leukemia virus type 1 (HTLV-1) has not been definitively established. To determine if hematopoietic stem cells from patients with adult T-cell leukemia-lymphoma (ATL) are infected with HTLV-1, we used a clonogenic progenitor assay followed by the polymerase chain reaction for the detection of HTLV-1 DNA. In vitro growth characteristics of myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells among nonadherent T-cell-depleted bone marrow (BM) mononuclear cells (NA-T-MNCs) from 10 patients with ATL was not significantly different from those of HTLV-1-seronegative controls (P = .20); numbers of colonies per 1 x 10(5) NA-T-MNCs were 34.9 +/- 7.6 for CFU-GM and 39.0 +/- 12.5 for BFU-E in patients with ATL, whereas those were 32.1 +/- 9.5 for CFU-GM and 41.4 +/- 12.7 for BFU-E in normal controls. HTLV-1 DNA was not detected in individual colonies formed by CD34+ cells from any of the patients. Similarly HTLV-1 DNA was not detected in 1 x 10(3) CD34+ cells sorted on a fluorescence-activated cell sorter (FACS) from six patients with ATL studied. In contrast, HTLV-1 DNA was detected in BM mononuclear cells from all patients. These observations clearly indicate that hematopoietic progenitor cells from patients with ATL are normal in their colony-forming capacity and that CD34+ cells from patients with ATL are not infected with HTLV-1 in vivo.
Aberrant regulation of complement by the erythrocytes of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS)
Authors: Tomita A , Parker CJ 
Published: October 2019

Abstract
Susceptibility to hemolysis in acidified serum is a pathognomonic feature of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS, congenital dyserythropoietic anemia type II). The purpose of the studies reported herein was to determine if aberrant regulation of complement contributes to the susceptibility of HEMPAS erythrocytes to acidified serum lysis. The results of these experiments have demonstrated that regulation of both the C3 convertase of the alternative pathway and the membrane attack complex of complement by HEMPAS erythrocytes is aberrant. However, these abnormalities are not a consequence of quantitative or functional deficiencies of the erythrocyte complement-regulatory proteins, decay accelerating factor (DAF, CD55), or membrane inhibitor of reactive lysis (MIRL, CD59). Our recent studies have shown that glycophorin A (GPA), the major erythrocyte sialoglycoprotein is a complement regulatory protein. Analysis by radioimmunoprecipitation suggested that GPA on HEMPAS erythrocytes is abnormally glycosylated. Further analysis indicated that the abnormality involves the O-linked oligosaccharide moiety. Together, these studies show that complement regulation by HEMPAS erythrocytes is abnormal and that constituents other than DAF and MIRL participate in controlling complement activation on the erythrocyte membrane. Additionally, these studies suggest that the glycosylation defect that is characteristic of HEMPAS involves GPA.