bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extreme chemical variation in complex diamonds from George Creek, Colorado: a SIMS study of carbon isotope composition and nitrogen abundance
Authors: Fitzsimons I. C. W. , Harte B. , Chinn I. L. , Gurney J. J. , Taylor W. R. 
Published: July 2002

AbstractDiamonds from George Creek, Colorado, preserve complex intergrowth textures between two major growth generations: homogeneous diamond with yellow-buff cathodoluminescence (CL); and diamond with blue-green CL and local growth zonation. Secondary-ion mass spectrometry (SIMS) has revealed large variations in N concentration and C isotope composition within these diamonds. Even within single stones, N contents and δ13C values can vary from 0 to 750 ppm and 0 to −20‰ respectively. These variations are similar to those recorded elsewhere for entire diamond suites. The CL characteristics correlate directly with N: diamond with yellow-buff CL has uniform N contents, whereas the zoned diamond has bright blue CL bands with high N (50–750 ppm) and dark blue or green CL bands with low N (0–20 ppm). These bands are too narrow (10–5 µm) for analysis by IR spectroscopy. δ13C also varies between the two growth generations in any one diamond plate, and to a lesser extent within these generations, but shows no consistent correlations with either CL or N. The George Creek stones preserve evidence of extreme temporal and/or spatial variations in both δ13C and N concentrations during the period of diamond growth, but the factors controlling N content during diamond growth did not control δ13C.
Synthesis and release of B-lymphocyte stimulator from myeloid cells
Authors: Nardelli Bernardetta , Belvedere Ornella , Roschke Viktor , Moore Paul A. , Olsen Henrik S. , Migone Thi Sau , Sosnovtseva Svetlana , Carrell Jeffrey A. , Feng Ping , Giri Judith G. , Hilbert David M. 
Published: July 2002

AbstractB-lymphocyte stimulator (BLyS) is a recently identified novel member of the tumor necrosis factor ligand superfamily shown to exist in a membrane-bound and soluble form. BLyS was found to be specifically expressed on cells of myeloid lineage and to selectively stimulate B-lymphocyte proliferation and immunoglobulin production. The expression of a cytokine involved in potentiation of humoral immune responses, such as BLyS, is expected to be strictly controlled. The goal of the present study was to examine regulation of BLyS levels in monocytic cells in response to cytokines and during their differentiation to macrophages and dendritic cells. The presence of BLyS on the cell surface and in the culture medium of both normal blood monocytes and on tumor cells of myelomonocytic origin was demonstrated. BLyS gene expression and levels of membrane-associated and soluble BLyS were found to be regulated by cytokines, in particular interferon (IFN)-γ and to a lesser extent interleukin-10 (IL-10). The expression of BLyS on monocyte membranes was retained following differentiation into macrophages, but detection on the surface of monocyte-derived dendritic cells required stimulation with IFN-γ. Both IFN-γ and IL-10 enhanced the release of soluble BLyS that was active in B-cell proliferation assays. Cells transfected with BLyS complementary DNA mutated in a predicted cleavage site failed to release BLyS into the culture medium, thereby suggesting that soluble BLyS was derived from the membrane form. These results provide further support for an important role for BLyS expressed in myeloid cells in B-cell expansion and antibody responses.
Multiple signaling pathways regulate NF-κB–dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells
Authors: Goebeler Matthias , Gillitzer Reinhard , Kilian Karin , Utzel Kathrin , Bröcker Eva-Bettina , Rapp Ulf R. , Ludwig Stephan 
Published: July 2002

AbstractThe cytokine-induced C-C chemokine monocyte chemoattractant protein-1 (MCP-1) is an important regulator of leukocyte recruitment to sites of inflammatory challenge. Here, it is demonstrated that the widely distributed contact hapten NiCl2, like tumor necrosis factor α (TNFα), induces monocyte-chemoattractant activity in primary human endothelial cells via induction of MCP-1. NiCl2 rapidly activated mitogen-activated protein (MAP) kinase p38, and inhibition of p38 partially blocked NiCl2-induced MCP-1 messenger RNA and protein expression. Both NiCl2- and TNFα-induced MCP-1 synthesis was sensitive to D609, an inhibitor of phosphatidylcholine-dependent phospholipase C (PC-PLC). NiCl2-induced MCP-1 synthesis required activation of NF-κB since mutation of NF-κB–binding sites in the promoter resulted in complete loss of inducible promoter activity. Consistent with that finding, stimulation with NiCl2 or TNFα activated IκB kinase-β (IKKβ), and transient transfection of dominant-negative IKKβ strongly inhibited NiCl2- and TNFα-induced MCP-1 expression. However, D609 and the specific p38 inhibitor SB202190 did not affect NiCl2- and TNFα-induced IKKβ activation, NF-κB DNA-binding activity, or transcriptional activity of a Gal4p65 fusion protein. This indicates that p38- and PC-PLC–dependent pathways directly regulate the transcriptional activity of NF-κB factors in the transcriptional complex. Consistent with that, inhibition of p38 blocked enhanced transcriptional activity induced by the transcriptional coactivator p300. Thus, it was concluded that at least 3 independent pathways regulate MCP-1 expression in endothelial cells. Its induction requires activation of the IKKβ/IκBα/NF-κB signaling pathway, resulting in nuclear accumulation of p65 and subsequent recruitment of cofactors. Proper assembly and activity of this transcriptional complex is further modulated by the p38 MAP kinase cascade and a PC-PLC–dependent pathway.
Functional requirements for phenotypic correction of murine β-thalassemia: implications for human gene therapy
Authors: Persons Derek A. , Allay Esther R. , Sabatino Denise E. , Kelly Patrick , Bodine David M. , Nienhuis Arthur W. 
Published: July 2002

Abstract
As initial human gene therapy trials for β-thalassemia are contemplated, 2 critical questions important to trial design and planning have emerged. First, what proportion of genetically corrected hematopoietic stem cells (HSCs) will be needed to achieve a therapeutic benefit? Second, what level of expression of a transferred globin gene will be required to improve β-thalassemic erythropoiesis? These questions were directly addressed by means of a murine model of severe β-thalassemia. Generation of β-thalassemic mice chimeric for a minority proportion of genetically normal HSCs demonstrated that normal HSC chimerism levels as low as 10% to 20% resulted in significant increases in hemoglobin (Hb) level and diminished extramedullary erythropoiesis. A large majority of the peripheral red cells in these mice were derived from the small minority of normal HSCs. In a separate set of independent experiments, β-thalassemic mice were bred with transgenic mice that expressed different levels of human globins. Human γ-globin messenger RNA (mRNA) expression at 7% of the level of total endogenous α-globin mRNA in thalassemic erythroid cells resulted in improved red cell morphology, a greater than 2-g/dL increase in Hb, and diminished reticulocytosis and extramedullary erythropoiesis. Furthermore, γ-globin mRNA expression at 13% resulted in a 3-g/dL increase in Hb and nearly complete correction of red cell morphology and other indices of inefficient erythropoiesis. These data indicate that a significant therapeutic benefit could be achieved with expression of a transferred globin gene at about 15% of the level of total α-globin mRNA in patients with severe β-thalassemia in whom 20% of erythroid precursors express the vector genome.
Molecular genetic basis of porcine histo-blood group AO system
Authors: Yamamoto Fumiichiro , Yamamoto Miyako 
Published: July 2002

AbstractHisto-blood group A and B antigens are oligosaccharide antigens important in transfusion and transplantation medicine. The final steps in the synthesis of these antigens are catalyzed by glycosyltransferases encoded by the functional alleles at the ABO locus. Humans have 3 major alleles (A, B, and O), whereas pigs are known to have only A and O alleles. This paper reports the molecular genetic basis of the porcine AO system. The porcine A gene is homologous to the ABO genes in humans and other species. It encodes an α1 → 3N-acetyl-D-galactosaminyltransferase that synthesizes A antigens. Southern hybridization experiments using a porcine A gene coding-sequence probe failed to identify a corresponding homologous sequence in genomic DNA from group O pigs, thus suggesting a major deletion in the O gene. Therefore, inadvertent activation of a silent O gene seems unlikely in porcine organs xenotransplanted into humans.
Raised blast glutathione levels are associated with an increased risk of relapse in childhood acute lymphocytic leukemia
Authors: Kearns Pamela R. , Pieters Rob , Rottier M. M. Antoinette , Pearson Andrew D. J. , Hall Andrew G. 
Published: July 2002

AbstractA preliminary study has linked raised blast glutathione levels with chemoresistance in acute myeloid and lymphoblastic leukemia in adults and children. In this study, therefore, the relationship between leukemic blast glutathione levels and prognosis in childhood acute lymphoblastic leukemia (ALL) was investigated. A total of 77 childhood ALL samples were analyzed, 62 at initial presentation and 15 at relapse. A 20-fold interindividual variation in glutathione levels at presentation (median, 6.54 nmol/mg protein; range, 1.37 to 27.9) was demonstrated. The median level in T-lineage ALL was 2.3-fold higher than in B-lineage ALL (Mann-Whitney test,P &lt; .0001). There was a significant correlation between presenting white cell count (WBC) and glutathione level (Spearman rank correlation coefficient, ρ = 0.45, P = .001). A high DNA index correlated with low glutathione levels (Mann-Whitney test,P = .013). There was no significant relationship between glutathione levels and in vitro drug sensitivity. Patients with glutathione levels above the median had a significantly greater risk of relapse (log-rank test statistic, 5.55; P = .018), and the overall survival rate was significantly reduced (log-rank test statistic, 4.38; P = .04). Multivariate analysis demonstrated that glutathione concentration was of independent prognostic value when assessed in conjunction with age, gender, WBC, and immunophenotype. The association of elevated blast glutathione levels with an increased risk of relapse suggests that glutathione-depleting agents may be of therapeutic value in patients who present with a high WBC.
Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease
Authors: Teofili Luciana , Di Febo Anna Laura , Pierconti Francesco , Maggiano Nicola , Bendandi Maurizio , Rutella Sergio , Cingolani Antonella , Di Renzo Nicola , Musto Pellegrino , Pileri Stefano , Leone Giuseppe , Larocca Luigi Maria 
Published: July 2002

AbstractThe receptor for hepatocyte growth factor (HGF) is a transmembrane tyrosine kinase that is encoded by the proto-oncogene c-met. Recently, c-MET was detected in Reed-Sternberg (RS) cells from Epstein-Barr virus–positive (EBV+) Hodgkin disease (HD). The c-MET, EBER-1, and LMP-1 expression in 45 lymph node biopsies and 12 bone marrow biopsies obtained from patients with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individuals and 135 HD patients in different phases of disease. In all 45 lymph node and 12 bone marrow samples examined, RS cells expressed c-MET but not HGF+. These results were independent of the EBV infection. Interestingly, several HGF+ dendritic-reticulum cells were found scattered around c-MET+ RS cells. The mean ± SEM serum HGF levels in HD patients at diagnosis and at the time of relapse were 1403 ± 91 (95% confidence interval [CI], 1221-1585) and 1497 ± 242 pg/mL (95% CI, 977-2017), respectively. HGF values were significantly higher than those of healthy individuals (665 ± 28 pg/mL; 95% CI, 600-721; and P &lt; .001 for both groups of patients) and of HD patients in remission (616 ± 49 pg/mL; 95% CI, 517-714; andP &lt; .001 for both groups of patients). A significant correlation was found between serum HGF levels and B symptoms at diagnosis (P = .014). In conclusion, this study indicates that HGF and c-MET constitute an additional signaling pathway between RS cells and the reactive cellular background, thereby affecting adhesion, proliferation, and survival of RS cells. Furthermore, the serum concentration of HGF in HD patients may be a useful tool in monitoring the status of disease.
Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib
Authors: Dörmann Dagmar , Clemetson Jeannine M. , Navdaev Alexei , Kehrel Beate E. , Clemetson Kenneth J. 
Published: July 2002

Abstract
The snake venom C-type lectin alboaggregin A (or 50-kd alboaggregin) from Trimeresurus albolabris was previously shown to be a platelet glycoprotein (GP) Ib agonist. However, investigations of the signal transduction induced in platelets showed patterns of tyrosine phosphorylation that were different from those of other GPIb agonists and suggested the presence of an additional receptor. In this study, the binding of biotinylated alboaggregin A to platelet lysates, as well as affinity chromatography evaluations of platelet lysates on an alboaggregin A–coated column, indicated that this other receptor is GPVI. Additional experiments with reagents that inhibit either GPIb or GPVI specifically supported this finding. These experiments also showed that both GPIb and GPVI have a role in the combined signaling and that the overall direction this takes can be influenced by inhibitors of one or the other receptor pathway.
Identification of a blood-derived chemoattractant for neutrophils and lymphocytes as a novel CC chemokine, Regakine-1
Authors: Struyf Sofie , Proost Paul , Lenaerts Jean-Pierre , Stoops Griet , Wuyts Anja , Van Damme Jo 
Published: July 2002

AbstractChemokines constitute a large family of chemotactic cytokines that selectively attract different blood cell types. Although most inflammatory chemoattractants are only induced and released in the circulation during acute infection, a restricted number of CXC and CC chemokines are constitutively present in normal plasma at high concentrations. Here, such a chemotactic protein was purified to homogeneity from serum and fully identified as a novel CC chemokine by mass spectrometry and amino acid sequence analysis. The protein, tentatively designated Regakine-1, shows less than 50% sequence identity with any known chemokine. This novel CC chemokine chemoattracts both neutrophils and lymphocytes but not monocytes or eosinophils. Its modest chemotactic potency but high blood concentration is similar to that of other chemokines present in the circulation, such as hemofiltrate CC chemokine-1, platelet factor-4, and β-thromboglobulin. Regakine-1 did not induce neutrophil chemokinesis. However, it synergized with the CXC chemokines interleukin-8 and granulocyte chemotactic protein-2, and the CC chemokine monocyte chemotactic protein-3, resulting in an at least a 2-fold increase of the neutrophil and lymphocyte chemotactic response, respectively. The biologic effects of homogeneous natural Regakine-1 were confirmed with chemically synthesized chemokine. Like other plasma chemokines, it is expected that Regakine-1 plays a unique role in the circulation during normal or pathologic conditions.
Effect of HLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the US National Marrow Donor Program Experience
Authors: Petersdorf Effie W. , Kollman Craig , Hurley Carolyn Katovich , Dupont Bo , Nademanee Auayporn , Begovich Ann B. , Weisdorf Daniel , McGlave Philip 
Published: July 2002

AbstractThe clinical importance of HLA class II gene disparity in unrelated stem cell transplantation is not entirely known. The impact was evaluated of matching donors and recipients for HLA-DR, HLA-DQ, and HLA-DP genes on clinical outcome after stem cell transplantation for chronic myeloid leukemia (CML) performed between 1988 and 1997. HLA-DRB1, -DQA1, -DQB1, -DPA1, and -DPB1 alleles were identified in 831 transplant pairs using a combination of sequence-specific oligonucleotide probes, sequence-specific priming, and sequencing methods. Among the 831 pairs, 696 (84%) were HLA-A and -B serologically matched; of these, 565 (81%) were also matched for HLA-DRB1. HLA-DRB1 matching correlated with significantly improved survival (relative risk [RR], 1.29 [95% confidence interval (CI), 1.02-1.64; P = .04]) independently of HLA-DQA1 or HLA-DQB1 (RR, 1.01 [95% CI, 0.81-1.26; P = .94]) and HLA-DPA1 or HLA-DPB1 (RR, 1.11 [95% CI, 0.84-1.48;P = .46]). Single-locus HLA-DQ or HLA-DP disparity was not associated with significantly poorer survival. For patients who underwent transplantation in the first chronic phase (CP) from HLA-A, B matched donors, the presence of DRB1 allele mismatching was independently associated with increased incidence of grades III-IV acute graft-versus-host disease (GVHD). No significant associations of class II allele mismatching with risk for delayed engraftment or chronic GVHD disease were detected. This study clearly demonstrates the importance of precise matching of HLA-DRB1 alleles for successful transplantation. Furthermore, a good-risk population of patients whose transplantations were performed in the first CP of disease from HLA-A, B, DRB1 matched unrelated donors can be shown to have superior survival.
Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART
Authors: Kulkosky Joseph , Culnan Derek M. , Roman Jeanette , Dornadula Geethanjali , Schnell Matthias , Boyd Michael R. , Pomerantz Roger J. 
Published: July 2002

AbstractProstratin is a unique phorbol ester that stimulates protein kinase C activity but is nontumor promoting. Remarkably, prostratin is also able to inhibit de novo human immunodeficiency virus type 1 (HIV-1) infection yet up-regulate viral expression from latent proviruses. Prostratin's lack of tumor promotion, coupled with its ability to block viral spread yet induce latent proviral expression, prompted studies to determine whether this compound could serve as an inductive adjuvant therapy for patients treated with highly active antiretroviral therapy (HAART). The current experiments indicate that prostratin is a potent mitogen for mononuclear phagocytes possessing many of the activities of phorbol myristate acetate (PMA) with notable functional differences. Prostratin, like PMA, accelerates differentiation of the myeloid cell-lines, HL-60 and THP-1, as well as mononuclear phagocytes from bone marrow and peripheral blood. Enzyme-linked immunosorbent assay and gene array analyses indicate significant changes in the expression of proteins and messenger RNA after treatment of cells with prostratin, consistent with phagocyte activation and differentiation. Prostratin blocks HIV-1 infection relating to down-regulation of CD4 receptor expression. The array analysis indicates a similar down-regulation of the HIV-1 coreceptors, CXCR4 and CCR5, and this may also reduce viral infectivity of treated host cells. Finally, prostratin is capable of up-regulating HIV-1 expression from CD8+ T lymphocyte–depleted peripheral blood mononuclear cells of patients undergoing HAART. This novel observation suggests the agent may be an excellent candidate to augment HAART by inducing expression of latent HIV-1 with the ultimate goal of eliminating persistent viral reservoirs in certain individuals infected with HIV-1.
Splenectomy of rats selectively reduces lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1 expression on B-cell subsets in blood and lymph nodes
Authors: Milićević Novica M. , Luettig Birgit , Trautwein Christian , Wüstefeld Torsten , Mähler Michael , Jecker Peter , Wonigeit Kurt , Westermann Jürgen 
Published: July 2002

AbstractSplenectomy increases the number of B cells in the blood of humans and animals. It is unknown whether this is due to changes in migration, proliferation, or both. The numbers of naı̈ve (IgD+IgM+), memory (IgD−IgMhigh), newly formed (IgMhighCD90high), early recirculating follicular (IgMlowCD90high), recirculating follicular (IgMlowCD90−), and marginal zone (IgMhighCD90−) phenotype B cells were determined in control and splenectomized rats by flow cytometry. All subsets increased significantly in the blood after splenectomy. Because surface molecules are involved in the regulation of migration and proliferation, their expression (lymphocyte function-associated antigen 1 [LFA-1], intercellular adhesion molecule 1 (ICAM-1), L-selectin, α4-integrins, CD44, major histocompatability complex class II, interleukin 2 receptor-α chain) was determined on B- and T-cell subsets of both groups. B cells, but not T cells, showed a significantly reduced LFA-1 and ICAM-1 expression in blood and lymph nodes, whereas the expression of the other surface molecules analyzed remained unchanged. The down-regulation of these molecules did not influence the adherence of B cells to high endothelial venules in vitro. In vivo, however, ICAM-1low–expressing B cells migrated significantly faster through lymph nodes (ICAM-1low 41 ± 5 hours versus ICAM-1high58 ± 3 hours), whereas proliferation of B cells in bone marrow, lymph node, and blood remained unchanged. Thus, the presence of one organ is necessary for appropriate expression of LFA-1 and ICAM-1 on B cells in other, distant organs. The more rapid transit of ICAM-1low B cells through lymph nodes may be responsible for the increased B-cell number in the blood after splenectomy.
CD34 cell dose in granulocyte colony-stimulating factor–mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen–identical sibling transplantation
Authors: Zaucha J. Maciej , Gooley Theodore , Bensinger William I. , Heimfeld Shelly , Chauncey Thomas R. , Zaucha Renata , Martin Paul J. , Flowers Mary E. D. , Storek Jan , Georges George , Storb Rainer , Torok-Storb Beverly 
Published: July 2002

AbstractA retrospective analysis of granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood mononuclear cell (G-PBMC) products harvested from healthy donors indicates significant variability in both the absolute number and relative proportion of CD34, CD3, and CD14 cells obtained. This report examined whether variations in the cellular composition of G-PBMC products correlated with clinical outcomes after myeloablative allogeneic transplantation. The numbers of CD34, CD3, and CD14 cells infused into 181 human leukocyte antigen (HLA)–identical sibling recipients were analyzed with respect to tempo of engraftment, acute graft-versus-host-disease (GVHD), clinical extensive chronic GVHD, overall survival, and disease relapse. Neither acute GVHD, overall survival, nor disease relapse was statistically significantly associated with CD34, CD3, or CD14 cell doses or the CD14 to CD3 ratio. CD3 and CD14 cell doses and CD14 to CD3 ratios did not correlate with the tempo of neutrophil and platelet engraftment. However, increasing CD34 cell numbers were significantly associated with accelerated neutrophil (P = .03) and platelet (P = .01) engraftment. Higher doses of CD34 cells (&gt; 8.0 × 106/kg) were also associated with a significantly increased hazard of clinical extensive chronic GVHD (HR = 2.3, 95% confidence interval [CI] 1.4-3.7,P = .001), but neither CD3 nor CD14 doses were statistically significantly associated with chronic GVHD. It was concluded that CD34 cell dose in G-PBMC grafts appears to affect both the engraftment kinetics and the development of clinical extensive chronic GVHD in HLA-identical sibling recipients but without a demonstrable impact on survival, relapse, and acute GVHD. Given the morbidity associated with extensive chronic GVHD, efforts to further accelerate engraftment in HLA-matched sibling transplants by increasing CD34 cell number in G-PBMC products may be counterproductive.