bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization and localization of Plasmodium falciparum surface antigens on infected erythrocytes from west African patients
Authors: van Schravendijk MR , Rock EP , Marsh K , Ito Y , Aikawa M , Neequaye J , Ofori- Adjei D , Rodriguez R , Patarroyo ME , Howard RJ 
Published: October 2019

Abstract
The malaria-induced surface antigens on Plasmodium falciparum-infected erythrocytes from West African patients were characterized by agglutination of infected cells by human sera, surface immunofluorescence of live infected cells, inhibition of cytoadherence to C32 melanoma cells by human sera, immunoelectron microscopy (immunoEM), and immunoprecipitation. In a nonimmune individual, serum antibody reactivity to surface antigens of infected cells was acquired during convalescence, as tested by all five methods, and was generally parasite isolate-specific. By contrast, adult hyperimmune West African sera reacted with many isolates, including isolates from geographically distinct regions. A quantitative correlation was established between agglutination and surface immunofluorescence assay titers, and between surface immunofluorescence assay and immunoEM reactivity, suggesting that a single antigen or a set of coexpressed antigens is being detected. Surface iodination of infected cells identified trypsin- sensitive high M, antigens in the sodium dodecyl sulfate extract. All sera tested that agglutinated infected cells also immunoprecipitated these antigens. The same surface antigens were immunoprecipitated by the homologous convalescent serum as by adult sera. By immunoEM these antigens were localized exclusively at the knob-like protrusions of infected cells, where they may participate in adherence to vascular endothelium.
Use of leukocyte-depleted platelets and cytomegalovirus-seronegative red blood cells for prevention of primary cytomegalovirus infection after marrow transplant
Authors: Bowden RA , Slichter SJ , Sayers MH , Mori M , Cays MJ , Meyers JD 
Published: October 2019

Abstract
Seventy-seven cytomegalovirus (CMV)-seronegative marrow transplant patients were randomized in a prospective controlled trial comparing the use of leukocyte-depleted platelets plus CMV-seronegative red blood cells with standard unscreened blood products for the prevention of primary CMV infection during the first 100 days after transplant. Eligible patients included CMV-seronegative patients undergoing autologous transplant or seronegative patients undergoing allogeneic transplant for aplastic anemia or non-hematologic malignancy who had seronegative marrow donors. Patients and marrow donors were serologically screened for CMV and randomized before conditioning for transplant and followed for CMV infection with weekly cultures of throat, urine, and blood and with weekly CMV serologies until day 100 after transplant. Leukocyte-depleted platelets were prepared by centrifugation, a procedure that removed greater than 99% of leukocytes. There were no CMV infections observed in 35 evaluable treatment patients compared with seven infections in 30 evaluable control patients (P = .0013). There was no statistically significant difference in the mean number of platelet concentrates in the treatment patients (164 concentrates) compared with the control patients (126 concentrates). Leukocyte-depleted platelets plus CMV-seronegative red blood cells are highly effective in preventing primary CMV infection after marrow transplant.
Development of a novel 1,25(OH)2-vitamin D3 analog with potent ability to induce HL-60 cell differentiation without modulating calcium metabolism
Authors: Zhou JY , Norman AW , Akashi M , Chen DL , Uskokovic MR , Aurrecoechea JM , Dauben WG , Okamura WH , Koeffler HP 
Published: October 2019

Abstract
We describe several novel analogs of the seco-steroid 1,25(OH)2-vitamin D3[1,25(OH)2D3] and their effects on differentiation and proliferation of HL-60 human myeloid leukemic cells in vitro as well as their effects on calcium metabolism in vivo. The 1 alpha-25(OH)2–16ene-23yne-26,27F6- vitamin D3 is the most potent analog reported to date, having about 80- fold more activity than the reference 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of HL-60 cells. Also, this analog decreased RNA expression of MYC oncogene in HL-60 by 90% at 5 x 10(-10) mol/L. Intriguingly, intestinal calcium absorption and bone calcium mobilization mediated in vivo by 1 alpha-25(OH)2–16ene-23yne- 26,27F6-D3 was found to be markedly (15-fold) less than that of 1,25(OH)2D3. In addition, 1 alpha-25(OH)2D3 bound to 1,25(OH)2D3 receptors of both HL-60 and intestine more avidly than did 1 alpha- 25(OH)2–16ene-23yne-26,27F6-D3. This novel analog may open up new therapeutic strategies for several hematopoietic, skin, and bone abnormalities and may provide a new tool to understand how vitamin D3 seco-steroids induce cellular differentiation.
Constitutive expression and role in growth regulation of interleukin-1 and multiple cytokine receptors in a biphenotypic leukemic cell line
Authors: Cohen A , Grunberger T , Vanek W , Dube ID , Doherty PJ , Letarte M , Roifman C , Freedman MH 
Published: October 2019

Abstract
A cell line (B1) was established from the bone marrow of a patient with a relapse of acute leukemia characterized by a 4;11 chromosomal translocation and biphenotypic features of early B and myeloid lineages. Analysis of the growth requirements of this cell line showed density-dependent growth and secretion of an autostimulatory growth factor, suggesting an autocrine mechanism. Several lines of evidence implicate the participation of interleukin-1 (IL-1) in the autocrine growth regulation of B1 cells. These cells constitutively express the messenger RNA (mRNA) for IL-1 and IL-1 receptor and secrete IL-1; recombinant IL-1 stimulated the growth of colonies when cells were seeded at low density, and anti-IL-1 antibodies inhibited the growth of colonies with cells seeded at higher density. B1 cells do not express detectable levels of mRNA for any of the other cytokines tested, and other cytokines failed to support the growth of B1 cells at low density. In addition, B1 cells express multiple cytokine receptor genes, including the receptors for IL-6, IL-7, tumor necrosis factor and gamma-interferon. Addition of the respective cytokines to the B1 cells resulted in inhibition of the growth of leukemic cells in vitro. The multiplicity of growth-inhibitory cytokine receptors on this leukemic cell line might be due to its biphenotypic lineage and may suggest new therapeutic possibilities in controlling leukemic cell proliferation.
Breakpoint clustering in t(4;11)(q21;q23) acute leukemia
Authors: Chen CS , Medberry PS , Arthur DC , Kersey JH 
Published: October 2019

Abstract
Chromosome 11 band q23 is commonly involved in nonrandom chromosomal translocations in hematopoietic malignancies, especially in infant acute leukemias. By using pulsed-field gel electrophoresis (PFGE) with restriction endonuclease digests of DNA from both a leukemia cell line (RS4;11) bearing the t(4;11)(q21;q23) and from human/hamster hybrid cells, we have been able to construct a detailed restriction map of the chromosome 11q23 region and have localized the t(4;11) chromosome 11 breakpoint to a region located approximately 200 to 230 kb telomeric to the CD3 gamma region and approximately 580 kb centromeric to the PBGD gene. PFGE analyses of DNA from clinical leukemia specimens and cell lines indicated a tight clustering of breakpoints in all eight t(4;11) acute leukemias studied. These data strongly suggest that discrete genetic loci are interrupted on both chromosomes 4 and 11 in a manner likely to be critically involved in the pathogenesis of t(4;11) acute leukemias. To our knowledge, these results represent the first evidence of breakpoint clustering in t(4;11) acute leukemias. In contrast to t(4;11), other 11q23 abnormalities studied to date have frequently shown evidence for alternative breakpoint sites in 11q23.
Retrovirus-mediated gene transduction into long-term repopulating marrow cells of dogs
Authors: Schuening FG , Kawahara K , Miller AD , To R , Goehle S , Stewart D , Mullally K , Fisher L , Graham TC , Appelbaum FR 
Published: October 2019

Abstract
Amphotropic helper-free retrovirus vectors containing the bacterial neomycin phosphotransferase gene (neo) and the human adenosine deaminase gene (adenosine aminohydrolase, EC 3.5.4.4; ADA) were used to transduce canine marrow cells. In one approach, dogs were treated for 7 days with recombinant human granulocyte colony-stimulating factor to stimulate hematopoietic cell division. Bone marrow cells were collected and transduced by 24 hours of cocultivation on vector-producing cells followed by incubation in a vector-containing long-term marrow culture system for 4 days. Transduced autologous marrow (0.4 to 1.0 x 10(8) cells/kg) was infused into dogs administered otherwise lethal total body irradiation (TBI) of 920 cGy. Two of four dogs engrafted, and their marrows showed intermittently between 1% and 11% G418-resistant colony-forming unit granulocyte-macrophage (CFU-GM) colonies for up to 2 years after transplantation. In a different experimental approach, autologous marrow, obtained at the time of the PB neutrophil nadir 7 days after a single cyclophosphamide injection (40 mg/kg intravenously), was cocultivated for 24 hours on vector-producing cells and infused at doses of 0.06 to 0.18 x 10(8) cells/kg into dogs administered 920 cGy TBI. One of three dogs engrafted, and the marrow showed intermittently 1% to 10% G418-resistant CFU-GM colonies for at least 2 years. Culture results were confirmed by polymerase chain reaction (PCR) showing the presence of the neo gene in marrow cells, peripheral blood (PB) granulocytes, and PB and lymph node lymphocytes. Dilution experiments indicated that up to 10% of marrow, lymph node, and PB cells contained the neo gene, consistent with the culture results. Samples harboring the neo gene also contained the gene for human ADA. However, repeated analyses of PB and marrow cells for human ADA gene expression by starch gel electrophoresis were negative. PB samples of all dogs were free of helper virus, and no long-term side effects from the transduction were observed.
Rickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies
Authors: Sporn LA , Shi RJ , Lawrence SO , Silverman DJ , Marder VJ 
Published: October 2019

Abstract
The clinical manifestations of Rocky Mountain spotted fever (RMSF) result from Rickettsia rickettsii (R rickettsii) infection of endothelial cells and are mediated by pathologic changes localized to the vessel, including in situ thrombosis and tissue ischemia. This study uses in vitro infection of cultured human umbilical vein endothelial cells with R rickettsii to test the hypothesis that such infection induces von Willebrand factor (vWF) release from Weibel- Palade bodies, a process that could contribute to thrombotic changes. At 24 hours postinfection, there was an increase in metabolically prelabeled large multimers of vWF in the culture medium, with a concomitant decrease of these forms in the cell lysate samples. This release reaction was specific for the large multimer pool of vWF, localized to Weibel-Palade bodies, because no change in the distribution of dimeric forms between cells and culture medium was detected. Double-label immunofluorescence staining showed an inverse correlation between the number of R rickettsii and the number of Weibel- Palade bodies in infected cells. Cell lysis was minimal at 24 hours postinfection, as no detectable intracellular precursor forms (molecular weight 260,000) of vWF were released into the culture medium, there was no decrease in cell viability as measured by trypan blue exclusion, and no increase in 51Cr-release into the culture medium was observed when compared with uninfected controls. Release was likely a direct effect of the intracellular presence of the organism, rather than due to a noxious soluble factor such as endotoxin, because culture medium conditioned by infected endothelial cells was ineffective at inducing release in uninfected endothelial cell cultures. In summary, in vitro infection of endothelial cells by R rickettsii induces release of Weibel-Palade body contents, a process that may contribute to the pathogenesis of RMSF.
Inactivation of endothelin by polymorphonuclear leukocyte-derived lytic enzymes
Authors: Patrignani P , Del Maschio A , Bazzoni G , Daffonchio L , Hernandez A , Modica R , Montesanti L , Volpi D , Patrono C , Dejana E 
Published: October 2019

Abstract
Cultured bovine aortic endothelial cells (BAEC) released endothelin-1 (ET-1) in the culture medium in a time-dependent fashion. Coincubation of fMLP-activated human polymorphonuclear leukocytes (PMN) with BAEC caused a fast (maximal activity was reached within 15 minutes) and cell number-dependent disappearance of ET-1 from the medium. This effect was direct to ET-1, because it was also present when PMN were incubated with the synthetic peptide in the absence of BAEC. PMN-dependent disappearance of ET-1 was associated with loss of constrictor activity on isolated rabbit aorta. PMN-released products were responsible for ET- 1 degrading activity, because supernatants of activated PMN were equally effective as the intact cells. Resting PMN, in the same time frame, were uneffective. Eglin C, a potent blocker of PMN-derived elastase and cathepsin G, reversed the ET-1 inhibitory activity of fMLP- stimulated PMN and of their supernatant. Direct addition of elastase and cathepsin G to synthetic ET-1 destroyed its immunoreactivity and this effect was blocked by eglin C. High-performance liquid chromatography (HPLC) analysis supported the hypothesis that ET-1 degradation by PMN was due to enzymatic proteolysis. These data provide evidence that activated PMN are able to degrade ET-1 through the release of proteases. Because physiologic concentrations of PMN can destroy high amounts (up to 100 nmol/L) of ET-1 within a few minutes, we propose that this mechanism of ET-1 inactivation has biologic relevance.
Interleukin-3-induced downregulation of the expression of interleukin-2 receptor beta chain in human T cells
Authors: Onishi R , Ishikawa T , Kodaka T , Okuma M , Uchiyama T 
Published: October 2019

Abstract
We examined the effect of interleukin-3 (IL-3) on human CD4+ cloned T cells, P607 and 1C2. By flow cytometric analysis, we found that IL-3 downregulated the surface expression of IL-2 receptor (R) beta chain in a dose-dependent manner but had little effect on that of IL-2R alpha chain. A simultaneous 125I-labeled IL-2 binding assay showed a decrease in the number of high-affinity, but not of low-affinity, IL-2Rs by IL- 3. The downregulation of the IL-2R beta chain began 3 hours after culture initiation, increased further thereafter, and was completely inhibited by anti-IL-3 antibodies. Expression of mRNA for either alpha or beta chain was not reduced by IL-3, and this suggests that the reduction of surface beta chain expression was not caused by the reduction of beta chain mRNA. IL-3-accelerating internalization of IL- 2R beta chain appeared to be one of the mechanisms for IL-3-induced downregulation of surface IL-2R beta chain expression. IL-3 alone increased the proliferation of T-cell clones but decreased the existing increment of their proliferation by IL-2. Accordingly, IL-3 may be one of the factors acting as a liaison between the hematopoietic and immune systems.
Unusual pattern of antibodies to human T-cell leukemia virus type-I in family members of adult T-cell leukemia patients
Authors: Okayama A , Korber B , Chen YM , Allan J , Lee TH , Shioiri S , Tachibana N , Tsuda K , Mueller N , McLane MF 
Published: October 2019

Abstract
Detection methods for the human T-cell leukemia virus type-I (HTLV-I) for blood screening and diagnosis generally rely on antibody tests that use the structural proteins of HTLV-I as antigen. We have found an unusual pattern of antibody reactivity among people who are at high risk of HTLV infection due to being a family member of an adult T-cell leukemia (ATL) patient: a specific antibody reaction exclusively directed to the HTLV regulatory protein tax, and not to the HTLV-I structural proteins. Sera from 7 of 82 (8.5%) structural antibody- undetectable family members of ATL patients had the anti-tax reactivity. Two seroconverters were observed. One seroconverter a healthy resident of Miyazaki, tested negative for structural antibody, but positive for tax antibody. Two years later she tested positive for both. The other seroconverter, an Israeli hemophiliac, tested negative for both antibodies, but converted to tax antibody-positive/structural antibody-negative. The HTLV-I tax-only antibody profile was also observed in sera sets from two other populations at risk for HTLV infection, human immunodeficiency virus-1-infected patients at the Bronx-Lebanon Hospital in New York and Israeli hemophiliacs. DNA samples from lymphocytes of four individuals with antibody reactivity only to HTLV-I tax were tested in polymerase chain reaction experiments; no HTLV-I or -II DNA was detected.
In vivo stem cell function of interleukin-3-induced blast cells
Authors: Tsunoda J , Okada S , Suda J , Nagayoshi K , Nakauchi H , Hatake K , Miura Y , Suda T 
Published: October 2019

Abstract
The treatment of mice with high doses of 5-fluorouracil (5-FU) results in an enrichment of primitive hematopoietic progenitors. Using this procedure, we obtained a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro and could differentiate into not only myeloid cells but also into lymphoid lineage cells. The phenotypes of interleukin-3 (IL-3) induced blast colony cells were Thy-1-positive and lineage-marker-negative. We examined whether these blast colony cells contained primitive hematopoietic stem cells in vivo and could reconstitute hematopoietic tissues in lethally irradiated mice. Blast colony cells could generate macroscopic visible spleen colonies on days 8 and 12, and 5 x 10(3) blast cells were sufficient to protect them from lethally irradiation. It was shown that 6 or 8 weeks after transplantation of 5 x 10(3) blast cells, donor male cells were detected in the spleen and thymus of the female recipients but not in the bone marrow by Southern blot analysis using Y-encoded DNA probe. After 10 weeks, bone marrow cells were partially repopulated from donor cells. In a congenic mouse system, donor-derived cells (Ly5.2) were detected in the thymus and spleen 6 weeks after transplantation. Fluorescence-activated cell sorter analyses showed that B cells and macrophages developed from donor cells in the spleen. In the thymus, donor-derived cells were found in CD4, CD8 double-positive, single-positive, and double-negative populations. Reconstitution of bone marrow was delayed and myeloid and lymphoid cells were detected 10 weeks after transplantation. These results indicate that IL-3-induced blast cells contain the primitive hematopoietic stem cells capable of reconstituting hematopoietic organs in lethally irradiated mice.
Rescue from programmed cell death in leukemic and normal myeloid cells
Authors: Lotem J , Cragoe EJ Jr , Sachs L 
Published: October 2019

Abstract
Growth factor-independent clones of myeloid leukemic cells can regain a growth factor-dependent state during differentiation. Loss of viability in these differentiating leukemic cells in the absence of growth factor was associated with DNA fragmentation and morphologic changes typical of programmed cell death (apoptosis). The differentiating leukemic cells could be rescued from apoptosis by a hematopoietic growth factor such as interleukin-3 (IL-3) and by the tumor-promoting phorbol ester 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), but not by the nonpromoting phorbol ester 4-alpha-TPA. IL-3 and TPA rescued differentiating myeloid leukemic cells by different pathways and also rescued normal myeloid precursor cells from apoptosis. The rescue of differentiating leukemic and normal myeloid cells by IL-3 or TPA was blocked by amiloride inhibitors of the Na+/H+ antiporter. We suggest that TPA may act as a tumor promoter by inhibiting programmed cell death.
Activation of Epstein-Barr virus replication in Hodgkin and Reed- Sternberg cells
Authors: Pallesen G , Sandvej K , Hamilton-Dutoit SJ , Rowe M , Young LS 
Published: October 2019

Abstract
Recent evidence has shown that Hodgkin's disease (HD) is associated with Epstein-Barr virus (EBV) in a substantial number of cases and that in these cases EBV DNA is localized exclusively to Hodgkin and Reed- Sternberg (RS) cells. The virus genome is not silent in RS cells because two EBV latent gene products, latent membrane protein (LMP) and EB early region (EBER) transcripts, have recently been reported to be expressed in RS cells. However, little information is available about the possible activation of EBV replicative genes in HD. This prompted us to investigate HD biopsies from 96 patients for expression of replicative gene products. Cryostat sections were immunostained with monoclonal antibodies to protein BZLF1, which controls the switch between EBV latency and replication, and also to LMP. LMP was demonstrated in RS cells in 47 cases (49%). Three of the LMP-positive cases (6%), but none of the LMP-negative cases, expressed the BZLF1 protein. BZLF1 positively was confined to rare RS cells. These three cases showed no detectable early, virus capsid, or membrane antigens. Our findings show that activation of EBV immediate early genes occurs only infrequently in RS cells, indicating that control of viral latency is not severely impaired in HD patients.
Recombinant human granulocyte-macrophage colony-stimulating factor after chemotherapy in patients with acute myeloid leukemia at higher age or after relapse
Authors: Buchner T , Hiddemann W , Koenigsmann M , Zuhlsdorf M , Wormann B , Boeckmann A , Freire EA , Innig G , Maschmeyer G , Ludwig WD 
Published: October 2019

Abstract
To reduce critical neutropenia after chemotherapy (CT) for acute myeloid leukemia (AML) we administered recombinant human granulocyte- macrophage colony-stimulating factor (GM-CSF) to patients over the age of 65 years with newly diagnosed AML and to patients with early or second relapse. CT was 9-day 6-thioguanine, ara-C, and daunorubicin (TAD9) in newly diagnosed AML and sequential high-dose ara-C and mitoxantrone (S-HAM) for relapse. In patients whose bone marrow was free from blasts a continuous intravenous infusion of GM-CSF 250 micrograms/m2/d started on day 4 after CT. Thirty-six patients entered the study and 30 of them did receive GM-CSF. For comparison, a historical control group of 56 patients was used. Complete remission rate was 50% (18 of 36) versus 32% in controls (P = .09), and early death rate was 14% versus 39% (P = .009). Treatment with GM-CSF was not associated with major adverse events. Two patients showed a marked leukemic regrowth that was completely reversible in one patient and appeared to be GM-CSF independent in the other patient. Remission duration does not seem to be reduced after GM-CSF. Under GM-CSF the blood neutrophils recovered 6 and 9 days earlier in the TAD9 (P = .009) and S-HAM (P = .043) groups associated with a rapid clearance of infections in most patients. We conclude that GM-CSF was of therapeutic benefit to our patients and this provides a basis for larger controlled trials.