bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyclonal B-Cell Lymphocytosis With Features Resembling Hairy Cell Leukemia-Japanese Variant
Authors: Machii Takashi , Yamaguchi Mitsuhiro , Inoue Ryoichi , Tokumine Yukihiro , Kuratsune Hirohiko , Nagai Hiroshi , Fukuda Shunichi , Furuyama Kazumichi , Yamada Osamu , Yahata Yoshito , Kitani Teruo 
Published: October 2019

Abstract
Polyclonal B lymphocytosis was found in four patients having clinical and hematologic features resembling those of hairy cell leukemia (HCL). All four patients were women between 37 and 67 years of age. Three patients had splenomegaly. Lymphadenopthy was absent or slight. Persistent lymphocytosis was seen in all the patients, and anemia and/or thrombopenia was observed in three of the patients. Abnormal lymphocytes have long microvilli and prominent membranous ruffles on their surfaces. Bone marrow aspirates and biopsy specimens showed increased numbers of abnormal lymphocytes with round nuclei and abundant pale cytoplasm. Although these findings were similar to those of HCL, studies of Ig gene rearrangements and expression showed the polyclonal proliferation of B cells. We called this new disease hairy B-cell lymphoproliferative disorder (HBLD). All four patients exhibited a polyclonal increase in serum IgG. The morphology of the cells in HBLD was more similar to that of leukemia cells of a variant form of HCL (HCL-Japanese variant) than to typical HCL cells. The surface IgG+, CD5−, CD11c+, CD22+, CD24−, CD25− phenotype and the weak tartrate-resistant acid phosphatase activity in the cells were identical to those of HCL cells of the Japanese variant. Our findings suggest that the B cells in HBLD are the nonmalignant counterpart of leukemic B cells in HCL-Japanese variant.
Epstein-Barr Virus Modulates 5-Lipoxygenase Product Synthesis in Human Peripheral Blood Mononuclear Cells
Authors: Gosselin Jean , Borgeat Pierre 
Published: October 2019

AbstractThe effect of short-term coincubations of Epstein-Barr virus (EBV) with mononuclear cells on the synthesis of leukotrienes (LT) by monocytes was investigated. Although treatment of mononuclear cells with EBV alone had no significant effect on LT synthesis by monocytes, the preincubation of mononuclear cells with EBV before the further stimulation of the cells with either the ionophore A23187, the chemoattractant formyl-Met-Leu-Phe, or the phagocytic particles zymosan strikingly enhanced the formation of both LTB4 and LTC4 above the levels of synthesis observed with the stimuli alone. Such priming effect of EBV on LT synthesis was maximal after 15 minutes of preincubation of mononuclear cells with EBV and slowly declined at longer preincubation times; the priming effect of EBV was observed both in Hank's Balanced Salt Solution and plasma. The effect of EBV was abolished by prior treatment of viral particles by heat or by antibody raised against the glycoprotein gp350 of the viral envelope, but not by UV irradiation of the viral particles. Exposure of mononuclear cells to EBV was shown to strongly enhance the activation of the 5-lipoxygenase and the release of arachidonic acid induced upon cell stimulation with a second agonist. The release of arachidonic acid by the EBV-treated mononuclear cells was inhibitable by arachidonyl trifluoromethyl ketone, an inhibitor of the 80-kD cytosolic phospholipase A2 . Furthermore, EBV was shown to rapidly increase (maximum effect within 15 minutes) the levels of phosphorylated form of the cytosolic phospholipase A2 (as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis), a process related to the activation of this enzyme. These data show that the interaction of EBV with monocytes upregulates the formation of important lipid mediators of inflammation.
Ceramide Inhibits IgG-Dependent Phagocytosis in Human Polymorphonuclear Leukocytes
Authors: Suchard Suzanne J. , Hinkovska-Galcheva Vania , Mansfield Pamela J. , Boxer Laurence A. , Shayman James A. 
Published: October 2019

AbstractCeramide is a product of agonist-induced sphingolipid metabolism in several cell types, including polymorphonuclear leukocytes (PMNs). In adherent PMNs, the kinetics of ceramide production correspond with the termination of fMLP-stimulated H2O2 release. Furthermore, short chain ceramides inhibit fMLP-mediated H2O2 release in adherent PMNs. In the present study, we investigated the effects of short chain ceramides and sphingoid bases on phagocytosis of IgG-opsonized erythrocytes (EIgG) by suspended PMNs activated with fMLP. N-Acetylsphingosine, N-acetylphytosphingosine, phytosphingosine, sphingosine, and dihydrosphingosine, but not N-acetyldihydrosphingosine, inhibited phagocytosis of EIgG. In contrast, these same lipids did not inhibit fMLP-mediated chemotaxis. Endogenous ceramide levels increased within the first few minutes of phagocytosis, with a significant (P < .05) accumulation by 30 minutes, the time by which phagocytosis was terminated. Neutral sphingomyelinase activity paralleled the increase in ceramide, consistent with the generation of ceramide by the hydrolysis of sphingomyelin. The N-acetyl-conjugated sphingols (C2 ceramides) blocked phosphatidylethanol formation indicating that phospholipase D (PLD) is an intracellular target of ceramide action. These data suggest that ceramides, generated through activation of the sphingomyelin cycle, act as negative regulators of FcγR-mediated phagocytosis.
Traditional Beer Consumption and the Iron Status of Spouse Pairs From a Rural Community in Zimbabwe
Authors: Moyo Victor M. , Gangaidzo Innocent T. , Gomo Z.A.R. , Khumalo Hlosukwazi , Saungweme Thokozile , Kiire C.F. , Rouault Tracey , Gordeuk Victor R. 
Published: October 2019

AbstractTo examine the relationship between dietary iron exposure through the consumption of traditional beer and the presence of iron overload in black Africans not related by birth, we studied 28 husband and wife pairs from a rural Zimbabwean community. Lifetime traditional beer consumption was estimated by questioning subjects and iron status was assessed by repeated measurements of serum ferritin and transferrin saturation in subjects who were fasting and had received vitamin C supplementation. Each of the 56 study subjects had an estimated lifetime traditional beer consumption <1,000 L. The mean ± standard deviation (SD) concentration of iron in the supernatants of nine samples of traditional beer from the community was 46 ± 10 mg/L. Four of 28 men (14.3%) and no women had the combination of an elevated serum ferritin and a transferrin saturation <70%, suggestive of substantial iron overload. Significant correlations were not found between the iron status of the husbands and their wives or between dietary iron exposure and iron stores. Our findings suggest that dietary iron exposure may not fully explain the development of iron overload in Africans and are consistent with the hypothesis that an iron-loading gene may also be implicated in pathogenesis.
Engraftment of Embryonic Hematopoietic Cells in Conditioned Newborn Recipients
Authors: Yoder Mervin C. , Hiatt Kelly 
Published: October 2019

AbstractYolk sac hematopoiesis is characterized by restricted hematopoietic cell differentiation. Although multipotent hematopoietic progenitor cells have been identified in the early yolk sac, long-term multilineage repopulating (LTMR) hematopoietic stem cell (HSC) activity has not been demonstrable before day 11 postcoitus (PC) using standard transplantation assays. In the present study, day-10 PC yolk sac hematopoietic cells were infused into myeloablated congenic newborn pups and donor cell engraftment and multilineage reconstitution of peripheral blood cells for at least 11 months in primary recipients was observed. In contrast, transplantation of day-10 PC yolk sac cells into congenic adult recipients did not result in engraftment despite pretransplant conditioning of the recipients or use of recipients that were genetically deficient in stem cells. Although fresh yolk sac cells were incapable of reconstitution when injected into adult recipient mice, yolk sac donor-derived cells residing in the bone marrow of primary newborn transplant recipients were capable of efficient reconstitution of conditioned secondary recipient adult mice. Primary newborn and secondary adult recipient animals engrafted with yolk sac cells were observed to have normal peripheral blood white blood cell counts. Lymphocyte subsets in peripheral blood, thymus, and spleen were also similar to control animals. The distribution and frequency of lineage-restricted progenitors derived from bone marrow of secondary transplant recipients were normal. These results indicate that day-10 PC yolk sac HSCs are capable of engrafting and reconstituting the hematopoietic system of conditioned newborn but not adult recipient animals. Furthermore, the ability of the yolk sac HSCs to differentiate into all hematopoietic lineages in these recipients strongly suggests that the local cellular microenvironment plays a prominent role in regulating yolk sac HSC differentiation.
Radiotherapy-Associated Neutropenia and Thrombocytopenia: Analysis of Risk Factors and Development of a Predictive Model
Authors: Mac Manus Michael , Lamborn Kathleen , Khan Waqqar , Varghese Anna , Graef Lorin , Knox Susan 
Published: October 2019

Abstract
Risk factors for unscheduled interruptions in radiotherapy courses completed between June 1989 and August 1995, lasting ≥2 days, and associated with World Health Organization grade III-IV neutropenia or thrombocytopenia were studied retrospectively. A group of controls was randomly selected. Potential risk factors for myelosuppression were analyzed using univariate and multivariate analyses. The most important risk factors for treatment interruption with thrombocytopenia were concurrent chemotherapy (odds ratio [OR], 45.5; P &lt; .001), increasing percentage of marrow irradiated (OR, 4.1 for each 20%; P &lt; .001), and brain metastases (OR, 7.3; P = .01). Other significant (P &lt; .05) factors were leukemia/lymphoma, bone or bone marrow metastases, and prior chemotherapy. The most important risk factors for treatment interruptions with neutropenia were concurrent chemotherapy (OR, 42.1; P &lt; .001) and increasing percentage of marrow irradiated (OR, 3.3 for each 20%; P &lt; .001). Similarly, the most important risk factors for treatment interruptions with both thrombocytopenia and neutropenia were concurrent chemotherapy (OR, 48.6; P &lt; .001) and increasing percentage of marrow irradiated (OR, 3.9 for each 20%; P &lt; .001). Other significant (P &lt; .05) factors in these groups were bone marrow or brain metastases and previous chemotherapy. These data were used to create a model, assigning patients to groups at high, intermediate, or low risk for treatment interruption with thrombocytopenia. High-risk patients may be candidates for clinical trials of a platelet growth factor.
Host Conditioning With 5-Fluorouracil and kit-Ligand to Provide for Long-Term Bone Marrow Engraftment
Authors: van Os Ronald , Dawes Donald , Mislow John M.K. , Witsell Alice , Mauch Peter M. 
Published: October 2019

AbstractAdministration of kit-ligand (KL) before and after doses of 5-fluorouracil (5-FU) results in marrow failure in mice, presumably because of enhanced KL-induced cycling of stem cells, which makes them more susceptible to the effects of 5-FU. In attempt to capitalize on this effect on stem cells, we studied the ability of KL and 5-FU to allow stable donor engraftment of congenically marked marrow in a C57BL/6 (B6) mouse model. KL was administered subcutaneously at 50 μg/kg, 21 hours and 9 hours before and 3 hours after each of two doses of 5-FU (125 mg/kg) given 7 days apart to B6-recipients. Animals then received three injections of 107 congenic B6-Gpi-1a-donor bone marrow cells at 24, 48, and 72 hours after the second 5-FU dose. A separate group of animals received a single dose of either 1 × 107 or 3 × 107 donor marrow cells 24 hours after the last 5-FU dose. The level of engraftment was measured from Gpi-phenotyping at 1, 3, 6, and 8 months in red blood cells (RBCs) and at 8 months by phenotyping cells from the thymus, spleen, and marrow. Percent donor engraftment in RBCs appeared stable after 6 months. The percent donor engraftment in RBCs at 8 months was significantly higher in KL + 5-FU prepared recipients (33.0 ± 2.7), compared with 5-FU alone (18.5 ± 2.6, P &lt; .0005), or saline controls (17.8 ± 1.7, P &lt; .0001). In an additional experiment, granulocyte colony-stimulating factor (100 μg/dose) was added to a reduced dose of KL (12.5 μg/dose); engraftment was similar to KL alone. At 8 months after transplantation the levels of engraftment in other tissues such as bone marrow, spleen, and thymus correlated well with erythroid engraftment to suggest that multipotent long-term repopulating stem cells had engrafted in these animals. There are concerns for the toxicity of total body irradiation (TBI)- or busulfan-based regimens in young recipients of syngeneic or transduced autologous marrow who are transplanted for correction of genetic disease. In these recipients complete donor engraftment may not be needed. The results with KL and 5-FU are encouraging for the further refinement of non-TBI, nonbusulfan techniques to achieve stable mixed chimerism.
The Src Family Kinases, Fgr, Fyn, Lck, and Lyn, Colocalize With Coated Membranes in Platelets
Authors: Stenberg Paula E. , Pestina Tamara I. , Barrie Rosemary J. , Jackson Carl W. 
Published: October 2019

AbstractNonreceptor protein tyrosine kinases phosphorylate proteins, thereby activating many intracellular signaling pathways and mediating protein-protein interactions. Protein phosphorylation is regulated in large part by the subcellular localization of these kinases and their respective substrates. Src is the most studied of these kinases, although other members of the Src family have been shown to be important in the differentiation of specific cell types. Src and Src family members are reported to be membrane-associated, but detergent-extraction studies have demonstrated a major difference in the solubility of Src compared with other members of the Src family (Fgr, Fyn, Lck, Lyn, and Yes), suggesting that their subcellular distributions may be different. By immunoelectron microscopy, we demonstrate that, unlike Src, the Src-related kinases are associated with electron-dense cytoplasmic domains and plasma membrane domains that correspond in size and frequency to endocytotic vesicles and coated pits. Clusters of labeling for these kinases also were seen adjacent to granule membranes. These kinases colocalize with the coated vesicle protein, clathrin, confirming their association with this class of endocytotic vesicle. We hypothesize that this vesicular association of Src-related kinases indicates a role for them in the endocytotic vesicle–mediated uptake and trafficking of plasma proteins into platelet granules.
Upregulation of Intracellular Glutathione by Fibroblast-Derived Factor(s): Enhanced Survival of Activated T Cells in the Presence of Low Bcl-2
Authors: Hyde Helena , Borthwick Nicola J. , Janossy George , Salmon Michael , Akbar Arne N. 
Published: October 2019

AbstractActivated interleukin-2 (IL-2)–dependent T cells express high levels of Bcl-2 protein. On cytokine withdrawal, Bcl-2 expression decreases and the cells die rapidly by apoptosis. We have previously shown that the survival of IL-2–deprived T cells can be promoted by factor(s) secreted by fibroblasts. Here we report that reduced glutathione (GSH), but not its oxidized counterpart GSSG, also enhances the in vitro survival of these cells. Exogenous GSH mediates its effect intracellularly, as (1) endogenous glutathione concentrations are increased up to fivefold in the presence of GSH, and (2) acivicin, an inhibitor of transmembrane GSH transport, abrogates GSH-dependent survival. The GSH-rescued T cells do not proliferate and express only low levels of Bcl-2, resembling WI38 fibroblast-rescued T cells. We, therefore, investigated a role for GSH in fibroblast-promoted T-cell survival. We show that WI38-promoted survival results in elevated GSH levels in surviving T cells and is abrogated by buthionine sulfoximine (BSO), an inhibitor of GSH synthesis. Furthermore, both WI38-promoted T-cell survival and GSH upregulation are associated with large molecular weight molecules (&lt;30 kD). Thus, the upregulation of GSH by WI38 fibroblasts appears to be crucial in their ability to enhance the survival of cytokine-deprived activated T cells in vitro.
Human Non-Hodgkin's Lymphomas Overexpress a Wild-Type Form of p53 Which Is a Functional Transcriptional Activator of the Cyclin-Dependent Kinase Inhibitor p21
Authors: Maestro Roberta , Gloghini Annunziata , Doglioni Claudio , Piccinin Sara , Vukosavljevic Tamara , Gasparotto Daniela , Carbone Antonino , Boiocchi Mauro 
Published: October 2019

Abstract
A large fraction of non-Hodgkin's lymphomas (NHLs) accumulate a wild-type form of the p53 tumor suppressor protein at the nuclear level. In normal cells, p53 induction is associated with a temporary cell growth arrest at the G1-S boundary of the cell cycle. This activity of p53 as a G1 checkpoint molecule is strictly dependent on its ability to induce the transcription of the inhibitor of the cyclin dependent kinase, p21. To verify the functionality of the wild-type p53 protein accumulated in NHL cells, 70 cases were comparatively analyzed for p53 and p21 expression and status of the respective genes. Overexpression of the wt p53 protein was associated with the accumulation of p21, indicating that p53 is functional with respect to p21 induction in these tumors. The coaccumulation of p53 with Ki-67 antigen indicates that wt p53-positive cells and p21-positive cells, as well, are actively proliferative elements, supporting the notion that p53-induced, p21-mediated growth arrest is somehow overridden in NHL cells. No p21 mutation or particular allele variant was shown to correlate with p21 protein accumulation, thus excluding a role for p21 structural abnormalities. Taken together, our data suggest the existence in NHL of a peculiar mechanism of functional inactivation of the p53 G1 checkpoint pathway occurring downstream of the CDK inhibitor p21.
Increased Circulating Colony-Stimulating Factor-1 (CSF-1) in SJL/J Mice With Radiation-Induced Acute Myeloid Leukemia (AML) Is Associated With Autocrine Regulation of AML Cells by CSF-1
Authors: Haran-Ghera Nechama , Krautghamer Rita , Lapidot Tsvee , Peled Alpha , Dominguez Melissa G. , Stanley E. Richard 
Published: October 2019

AbstractThe SJL/J mouse strain has a high spontaneous incidence of a B-cell neoplasm, reticulum cell neoplasm type B (RCN B). In addition, following irradiation, 10% to 30% of these mice develop acute myelomonocytic leukemia (radiation-induced acute myeloid leukemia [RI-AML]), an incidence that can be increased to 50% by treatment of the mice with corticosteroids after irradiation. The role played by the mononuclear phagocyte growth factor, colony-stimulating factor-1 (CSF-1), in the development of RI-AML in SJL/J mice was investigated. Mice dying of RI-AML, but not those dying of RCN B or without disease, possessed elevated concentrations of circulating CSF-1. In addition, in mice developing RI-AML with a more prolonged latency, circulating CSF-1 concentrations were increased before overt expression of RI-AML. First-passage tumors from 14 different RI-AMLs all contained high concentrations of CSF-1, and six of six different first- or second-passage tumors expressed the CSF-1 receptor (CSF-1R). Furthermore, in vitro colony formation by first- or second-passage tumor cells from 20 of 20 different RI-AMLs was blocked by neutralizing anti–CSF-1 antibody, and four of four of these tumors were inhibited by anti–CSF-1R antibody. The results of these antibody neutralization studies, coupled with the observation of elevated circulating CSF-1 in mice developing RI-AML, show an autocrine role for CSF-1 in RI-AML development in SJL/J mice. Southern blot analysis of tumor DNA from six of six of these tumors failed to reveal any rearrangements in the genes for CSF-1 or the CSF-1R. Studies in humans have shown that patients with AML possess elevated levels of circulating CSF-1 and that AML cells can express CSF-1 and the CSF-1R. Thus, RI-AML in the SJL/J mouse appears to be a useful model for human AML.
Inhibition of Sickle Erythrocyte Adhesion to Immobilized Thrombospondin by von Willebrand Factor Under Dynamic Flow Conditions
Authors: Barabino Gilda A. , Wise Robert J. , Woodbury Valerie A. , Zhang Beibing , Bridges Kenneth A. , Hebbel Robert P. , Lawler Jack , Ewenstein Bruce M. 
Published: October 2019

AbstractSickle red blood cell (RBC) adhesion to the blood vessel wall is hypothesized to be the initiating event in the periodic vaso-occlusive episodes that characterize sickle cell disease (SCD). Thrombospondin-1 (TSP) and von Willebrand factor (vWF ) have each been implicated in the adhesion of sickle RBC to vascular endothelial cells (EC) and subendothelial matrices. To better understand the contributions of each of these adhesive glycoproteins, we examined the adhesion of sickle RBC to immobilized TSP and vWF using a parallel plate flow chamber. Under postcapillary venular shear stress (1 dyne/cm2), sickle RBC adhered preferentially to TSP. To explore potential interactive effects of vWF and TSP, we examined sickle RBC adhesion to mixtures of these proteins. Whether the proteins were first combined in solution or sequentially applied to the slide, the presence of vWF inhibited the binding of sickle RBC to TSP. The inhibition of adhesion by vWF was shown to be the result of specific and saturable binding of vWF to TSP. Furthermore, vWF in solution at normal plasma levels also inhibited RBC adhesion to immobilized TSP. These data indicate that sickle RBC adhesion in vivo may be significantly influenced by the relative concentrations of TSP and vWF in the vascular wall.
Evidence of Genetic Diversity Underlying Rh D−, Weak D (Du), and Partial D Phenotypes as Determined by Multiplex Polymerase Chain Reaction Analysis of the RHD Gene
Authors: Avent Neil D. , Martin Peter G. , Armstrong-Fisher Sylvia S. , Liu Wendy , Finning Kirstin M. , Maddocks Deborah , Urbaniak Stanislaw J. 
Published: October 2019

Abstract
The human blood group Rh antigens are expressed by proteins encoded by a pair of highly homologous genes located at chromosome 1p34-36. One of the genes (RHCE ) encodes Rh CcEe antigens, while the other (RHD) the D antigen. Point mutations in the RHCE gene generate the C/c and E/e polymorphisms, while it has been shown that an RHD gene deletion can generate the D-negative phenotype. We have analyzed intron 4 of the RHCE and RHD genes and have defined the site of an RHD-specific deletion located in this intron. Using a multiplex RHD typing assay, which combines a reverse polymerase chain reaction (PCR) primer, which straddles this RHD-specific sequence, and a pair of primers located in exon 10 of the RHD gene, we have analyzed 357 different genomic DNA samples derived from individuals expressing D+, D−, weak D, and partial D phenotypes. Of these, we have noted a significant discordance with our multiplex PCR assay in the D− phenotypes dCcee and dccEe (which have been previously described) and weak D phenotypes. Our results suggest that in five serologically D− individuals we have identified an apparently intact RHD gene. Sequence analysis of transcripts obtained from one of these individuals (of phenotype dCCee) illustrates the presence of full-length RHD transcripts, which have a point mutation at nucleotide 121 (C → T), which generates an in-frame stop codon (Gln41Stop). Thus, we describe a different molecular basis for generating the D− phenotype to the complete RHD gene deletion described previously. We also show that there are discordances with serotype and the multiplex assay in weak D and partial D phenotypes, indicating that the underlying molecular basis can be heterogeneous. Existing Rh D PCR assays assume the complete absence of the RHD gene in D− phenotypes. We describe a different molecular basis for generating the D− phenotype to the complete RHD gene deletion described previously.